Tumor cells from growing cancers are shed into the blood stream. The FDA has approved the use of circulating tumor cell numbers for prognostication in multiple cancers, but this approach is less than optimal. The numbers of circulating tumor cells are usually relatively small and often are difficult to capture from the circulation. If there are enough circulating tumor cells, one can conclude that the tumor is metastasizing and by that time the prognosis may not be very good. Currently there is no good panel of circulating tumor cell based biomarkers available to the clinician. (more...)

Novel effective treatments for cancer remain in high demand and targeting so called imunomodulators to enhance antitumor immunity has gained considerable interest. Particular cells of the innate and adaptive immune system can, in conjunction with secreted molecules, function as potent extrinsic suppressors of tumorigenesis and cancer progression. However, depending on the type of tumor-infiltrating immune cells and established cytokine network, the immune system can have an inhibitory or promoting effect on cancer growth. Extensive study of this dual role of immunity on tumorigenesis led to the development of the concept of cancer immuno-editing. One family of cytokines that has been associated with strong antitumor effects is the interferons (IFN). However, IFNs have been widely discarded in current cancer therapy of solid tumors due to their broad effect on many different cell types resulting in severe side effects. (more...)

Breast density is an important risk factor for breast cancer, second only to age and BRCA1 and BRCA2 mutations. Women with dense breasts have been shown to have significantly increased risk of developing breast cancer. Most cancers arise in dense ductal tissue. While mammography is the ”gold standard” for early breast cancer detection, early cancer detection rates are only in the range of 50% in women with dense breasts. Women with dense breasts thus may benefit from other screening and diagnostic imaging approaches (e.g. ultrasound and MRI). Therefore, determining the best strategy is dependent on characterizing the breast density. Therefore, improved breast density assessment and more cost-effective hardware are needed to improve breast cancer detection in women with dense breasts. (more...)

Acute Myelogenous Leukemia (AML) is a cancer that typically presents with rapid and uncontrolled growth of immature cells of the myeloid lineage and represents the most common form of acute leukemia in adults. The disease is fatal is left untreated. Current therapies are largely ineffective, leading to relapse and death in the majority of patients. Roughly 35% of patients less than 60 years of age survive longer than 5 years. In the case of elderly patients, the survival rate is less than 10%. Due to the aggressive nature of the disease and the lack of successful treatment options, AML remains a challenging disease. (more...)

This invention identifies a class of novel small molecule inhibitors of two interconnected cellular pathways: the integrated stress response (ISR) and the PERK branch of the unfolded protein response (UPR).   (more...)

Researchers at UC San Diego discovered a consensus motif derived through a combination of chemical and biological studies on FD-895 and related pladienolide polyetides. These studies not only demonstrate a a pharmacologically-advanced analog but also provide one of the most potent splicing inhibitors discovered to date, with a favorable therapeutic index and pharmacological properties. (more...)

Nuclear Magnetic Resonance (NMR) spectroscopy is a widely-utilized method for analyzing small molecule compositions. It is among the most sensitive techniques available and has great potential for studying metabolic profiles in living organisms. Since variations in the metabolite concentrations are indicative of many disease states, NMR can be a powerful diagnostic tool. In practice, however, this requires sensitivity still beyond the capabilities of current instruments. As a result, using NMR for diagnostic purposes has been limited to academic research. A key component responsible for the sensitivity is the NMR probe, which holds the sample as it is inserted into the magnetic field. Advancing the probe design is critical to enabling practical medical applications of NMR. (more...)

Focal therapy and needle-based procedures on the prostate are challenging due to the high potential for off-target side effects.  These side effects, which include severe pain, incontinence, and impotence, could be mitigated by more accurate visualization of the boundaries of prostate.  While CT and MRI provide anatomical information of the prostate, they cannot readily provide real-time imaging information during a procedure.  Transrectal ultrasound (TRUS) probes are the current gold standard for procedural real-time imaging of the prostate, however, this technique suffers from inherent imaging constraints due to its external positioning to the prostate, such as poor resolution of the anterior side of the prostate and susceptibility to artifacts due to the rectal wall. (more...)

Due to global concerns for monitoring radiation exposure on an individual scale, there is a need for a simple method to assess radiation risk that does not involve cumbersome radiation detectors or collecting biological samples to detect biomarkers. (more...)

Together, the specificity of engineered antibodies and the diagnostic power of in vivo imaging provide a tremendous opportunity for exploring disease pathogenesis. CD8 is expressed on a subtype of T cells, known as cytotoxic T cells as well as a subset of dendritic cells. CD8+ T cells are the subject of intense research efforts, including those for developing cellular immunotherapies and for understanding tumor oncology.  The present invention describes a functional CD8-imaging agent based on engineered antibodies.  The agents have clear use in a variety of preclinical disease and immuno-therapeutic models. The ability to monitor the migration, expansion, and longevity of therapeutically transferred cells using molecular imaging technologies is of critical importance for developing immunomodulating therapies.  (more...)

Breast cancer is the most common type of cancer that occurs in women in the US and ranks as the second leading cause of cancer death after lung cancer. Of the 230,480 invasive breast cancer cases diagnosed in the US in 2011, approximately 15-20% were "triple negative breast cancer" (TNBC), a subtype of breast cancer that lacks clinical expression of estrogen receptor-alpha (ERα), progesterone receptor, and HER-2 receptors. TNBC tends to occur often in younger and African American women, and it is associated with high proliferative rates, and poor survival. Despite initial responsiveness to some types of chemotherapy, TNBC often recurs early with distant metastases. Treatment of TNBC has also been hindered by its insensitivity to widely-used targeted therapies including trastuzumab, lapatinib, tamoxifen, and aromatase inhibitors. Due to the aggressive nature of TNBC, it accounts for nearly half of all breast cancer deaths. Therefore, there is an urgent need to develop new and more effective therapies for this deadly subtype of breast cancer. The use of novel metformin analogues detailed below may present a promising new treatment for TNBC. (more...)

Researchers at UCSD have synthesized a number of new nucleoside compounds that may have advantages in certain antiviral and anticancer indications. These compounds are new acyclic nucleoside phosphonates that may have less toxicity than traditional nucleoside compounds. (more...)

ImmunoPET is a powerful imaging tool that combines monoclonal antibodies (mAbs) with radiochemistry to illuminate biological processes in vivo.  Much like metabolic PET tracers, such as FDG, ImmunoPET tracers can distinguish areas of high and low expression or activity of a particular biological process.  By providing a snapshot of localization of a particular antigen within the body, ImmunoPET has vast utility as tool for diagnosing disease, monitoring treatment, and tailoring therapy.    CD20, a surface protein found on B cells, has been established as a biomarker for B cell lymphoid malignancies and a subset of autoimmune diseases.  CD20 is also widely used as a target for antibody therapies.  Anti-CD20 mAbs (Arzerra®, Rituxan®, Zevalin ®) have been developed for treating B cell neoplasms, autoimmune diseases, and have demonstrated some efficacy as anti-rejection therapies for transplant patients.  However, there is significant patient-to-patient variation in treatment responses to anti-CD20 therapy.  Given the large costs associated with antibody treatments and the genetic heterogeneity between patient tumors, there is need for reliable diagnostic imaging that can be used to personalize therapy.  Thus, new ImmunoPET tracers based on anti-CD20 antibodies have enormous potential as tools for diagnostics and therapy management. (more...)

Hydrogen peroxide (H2O2) is a toxic byproduct of many physiologic and pathological reactions, and elevated in a variety of conditions in which free radicals have been implicated, such as inflammation, infection, cancer, diabetes, aging, and cardiovascular disease. Most conventional methods for H2O2 detection are limited to in vitro use. Being able to detect and image elevated H2O2 levels in vivo and in situ provides accurate and real time diagnosis and monitoring of many pathologies and body’s response to perturbation. (more...)

Sulfatases are a family of enzymes that release sulfate from a range of substrates (steroids, glycoproteins, sulfolipids and proteoglycans). Heparin sulfate proteoglycans (HSPG’s) are present on the outside of most animal cells and are major elements of the extracellular matrix. With their ability to bind to protein ligands, including growth factors, growth factor receptors, cytokines, proteases, lipases, matrix proteins and cell adhesion molecules, HSPG’s are involved in a host of cell signaling and structural functions. Sulfatase-1 (Sulf-1) and sulfatase-2 (Sulf-2) are sulfatases that modify the sulfation status of HSPG’s and thereby regulate a number of critical cell signaling pathways. The dysregulation of sulfatases is observed in many cancers with Sulf-2 in particular being implicated as a driver of carcinogenesis in non small cell lung cancer (NSCLC), pancreatic cancer and hepatocellular carcinoma (HCC). Sulf-2 has been implicated as a cancer causing gene and could be a novel target for new therapeutic strategies. (more...)

T cells are adaptive immune cells essential for durable responses against infection and cancer. They are equipped to respond to these challenges with bursts of proliferation, cytokine production, and cytotoxicity. These responses allow direction of complementary innate immune responses, while the T cells directly attack virally-infected host cells and cancer cells alike. However, the consequences of dysregulated T cell function are dire: poor T cell responses (i.e. exhaustion and tolerance) in the cases of chronic viral infection and cancer enable viral persistence and tumor outgrowth, while unchecked responses result in immunopathology in response to certain viral infections or autoimmunity such as multiple sclerosis. Therefore, the capacity to therapeutically modulate T cell responses - augmenting or blunting where appropriate, would be of pivotal clinical relevance in treatments for cancer, chronic viral infection, and autoimmunity. (more...)

Inflammation has been found to drive metastasis by involving the migration of immune cells to the site of the tumor and disruption of the epithelial lining, thereby allowing tumor cells to metastasize. Therefore suppression of inflammation can potentially have therapeutic value in cancer treatment. (more...)

Cancer is one of the most expensive diseases in the U.S., incurring a direct cost over $100 billion and a loss of over 0.5 million lives annually. In particular, every year close to 150,000 Americans will be diagnosed with colorectal cancer and more than 50,000 will die of it. In order to optimize drug therapy for a patient, the physician not only needs to match drugs to the patient's genotype, but also needs to monitor the patient's response to drugs. There is a need for biomarkers and related diagnostic tests that enable effective companion diagnostics and prognostics. (more...)

Bone metastases are detected in 80-100% of men who die of prostate cancer and such metastasis leads to painfully debilitating fractures, spinal compression and rapid decline. In addition, metastases to bone tissue often become resistant to standard therapies including androgen deprivation, radiation and chemotherapy. The scarcity of primary human prostate cancer bone metastasis tissues has crippled direct analysis and options to better understand the disease. In addition, spontaneous bone metastasis of prostate cancer in murine models, even to implanted human bone, is an exceedingly rare event. The development of a patient-derived xenograft (PDX) model of bone metastatic prostate cancer presents new options for improving therapeutic options. (more...)

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer mortality in adult American men, with an estimated 217,730 new cases diagnosed in the U.S. in 2010.  Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer.  However, elevated serum PSA can be present in other non-malignant conditions, such as benign prostatic hyperplasia and, therefore, PSA screening has a high false positives rate.  Active surveillance (AS) of prostate cancer is a current strategy that is used to reduce overtreatment by monitoring of low-risk patients with physical exams, PSA assesssments and repeat biopsies, and offering treatment to those with signs of progression.  However, nomograms that utilize these predictors of disease progression demonstrate an accuracy of only 61-79% in the clinic.  Given the limitations of PSA and significant disease that can be used to categorize patients with localized prostate cancer and assist in treatment decision-making.  Several recent studies have shown that serum miRNA signatures have potential value as prognostic tools for prostate cancer. (more...)

The Hippo pathway is known to play a crucial role in controlling organ size and contributing to tumorigenesis but the signals regulating this pathway are only beginning to become clear. (more...)

ROR1, receptor tyrosine kinase like orphan receptor one, is a molecule expressed at high levels during embryogenesis that plays a major role in the development of the skeleton, lungs and nervous system. The actual functional roleof the ROR1 protein during embryogenesis is unknown, although it is believed to be a receptor for Wnt proteins that regulate cellular polarity and cell to cell interactions. ROR1 expression is greatly decreased in post-partum mammalian cells to levels that are barely detectable. (more...)

Liver cancer is among the most lethal cancers, the third and sixth most frequent cause of cancer death in men and women, respectively.  Amongst the several histologically different primary hepatic malignancies, hepatocellular carinoma (HCC) accounts for 70 to 85% of the cases.  Animal models that mimic features of liver tumor development in human are invaluable research tools for understanding the mechanism of liver carcinogenesis and developing new drugs for treatment of patients with HCC. (more...)

Compelling studies suggests that leukemia relapse occurs because standard chemotherapy fails to eradicate self-renewing leukemia stem cells (LSC), which may achieve therapeutic resistance via the cumulative effects of activating mutations in signaling pathways that promote self-renewal and survival within specific niches. One leukemia subtype, T cell acute lymphoblastic leukemia (T-ALL) is particularly prone to early systemic and isolated CNS relapse - often consequent to mutational activation of the NOTCH1 signaling pathway. These results suggested that identification and targeting of LSC within selective niches may abrogate the processes that culminate in the relapse of T-ALL. (more...)

Chronic Myeloid Leukemia (CML) is known to be associated with a chromosomal transposition that yields a constitutively active BCR-ABL "fusion" kinase and current therapies include kinase inhibitors (e.g., imatinib and dasatinib) that are designed to "turn off" the constitutive activation of the fusion kinase. However, these are marginally effective in the later, more aggressive stages of the disease. One cause of refractory disease appears to be the residence of cancer stem cells (CSC) in protected tumor niches where they exit the cell cycle and revert to a quiescent state, which does not respond to the standard line of care. Such cells are found to have an altered isoform expression profile, which may provide new means to attack stem cells that are refractory to first-line therapies. (more...)

The early (Chronic) form of Chronic Myeloid Leukemia (CML) is most commonly treated with Bcr-Abl tyrosine kinase inhibitors (e.g., imatinib and dasatinib). These drugs effectively counteract the constitutive activation of a BCR-ABL kinase, which derives from a chromosomal transposition of part of the BCR region of chromosome 22 to the ABL gene on chromosome 9. However, the Chronic phase of CML is followed by two progressively more aggressive phases and current therapies are marginally effective in the later Accelerated and Blast Crisis stages of the disease. To prevent and treat refractory forms of CML, there is a need for alternative means targeting molecular processes that fuel progression. (more...)

SIO scientists have mined their rare collection of marine organisms to identify, characterize and analog a proprietary, small molecule with anti-cancer properties. SAR studies have identified regions of the molecule that have yielded analogs of greatest interest. Compositions of matter and methods of use are claimed for the treatment of cancer and hyperproliferative disorders. (more...)

High affinity peptides that bind preferentially to acute myeloid leukemia stem cells (LSCs) have been identified.  Peptide-coated nanoparticles can be used for transporting a high-dose chemotherapeutic drug cargo specifically into LSCs to eradicate them in addition to killing leukemia cells throughout the body and decreasing chemotherapy-associated toxicity. (more...)

No pancreas-specific contrast materials are currently available to highlight normal pancreas and distinguish it from tumor at high resolution CT imaging.  Current state-of-the-art clinical imaging of pancreatic tumors by CT and MRI rely on nonspecific intravenous contrast materials that transiently highlight all of the abdominopelvic vasculature and end organ parnechyma, including tumors.  Further, current pancreatic CT requires precise timing of imaging, after rapid intravenous contrast material delivery, to optimally distinguish between the tumor and surrounding pancreas.  Early detection of pancreatic cancer is extremely difficult.  This invention solves this problem. (more...)

The Dixdc1 protein may play an important role in the pathogenesis of schizophrenia, major depressive disorder, bipolar disorder, autism and other major psychiatric disorders.  In addition, Dixdc1 may also contribute to cancer metastasis, invasiveness and planar cell polarity.  Molecular signaling pathways potentially involving Dixdc1 include the Wnt/b-catenin, Nde1/CDK5 and the TGF-b pathways.  Importantly, Dixdc1 protein is an establised partner of the Disc1 protein, the product of one of the best-established neuropsychiatric susceptibility genes (DISC1).  Previous studies have utilized RNA interference to knock down Dixdc1 protein.  However, a genetic knockout in mice, an important rsearch tool that would be very useful for studying Dixdc1 function in disease, has not been described in the scientific literature to date. (more...)

The Dact3 protein plays an important role in oncogenesis, metastasis, wound healing and stem cell biology.  Molecular signaling pathways potentiallly involving Dact3 include the Wnt/b-catenin pathway, the Wnt/PCP non-b-catenin-dependent pathway, regulation of small GTPase of the Rho family, and pathways involving the Dishevelled signal transduction molecule, such as p120-catenin signaling.  Dact3 may also be involved in the regulation of the TGF-b pathway.  In vitro and in vivo knockdown models would be very useful for studying Dact3 function in disease but have not been reported to date. (more...)

These novel, fully human antibodies are demonstrated to eliminate tumor burden in a xenograft mouse model of triple negative breast cancer (TNBC).  They competitively block urokinase plasminogen activator receptor (uPAR)-mediated signaling and are effective either as a monotherapy or in radioimmunotherapy.   uPAR expression is highly correlated with aggressive phenotypes of breast cancer and inversely correlated with efficacy of tamoxifen in treatment.  Anti-uPAR therapy promises to be effective in treating patients with TNBC, drug-resistant breast cancer and metastatic breast cancer.     (more...)

Although treatment of cancer through non-surgical methods such as chemotherapy and radiation has dramatically improved survival rates, these therapies are associated with a fair degree of toxicity. The deleterious effects are particularly due to inability of these treatment methods to target cancer cells specifically without affecting surrounding normal cells. The challenge therefore, has been to find methods of selectively protecting normal cells, while maintaining susceptibility of cancer cells to therapy. Apoptosis triggered by chemotherapy and radiation is the most common cause of destruction of normal cells and is due to activation of a fully functional p53 protein present in these cells. p53 protein-induced transactivation of several genes involved in the apoptosis pathway leads to elimination of normal cells when exposed to anti-cancer agents. Therefore, therapeutic suppression of p53 directly or of its pathways leading to apoptosis, are attractive targets to prevent damage to normal cells during anti-cancer therapy. Earlier efforts in this area led to the isolation of a chemoprotectant, pifithrin that protected normal cells against radiation and chemotherapy-induced damage. However, this agent was not potent, was unstable and was not a specific inhibitor of p53-related apoptotic pathways. Hence, there is a clear need for new chemical inhibitors that are more robust, stable and specific as chemoprotectants of normal cells during anti-cancer therapy. (more...)

Novel high affinity ligands that bind to the human membrane protein caveolin have been developed. Caveolin has been implicated in a number of diseases, and specific ligands that bind with high affinity to caveolin may provide new therapeutic approaches for the treatment of these diseases. (more...)

UCLA researchers have identified mutually exclusive mechanisms of acquired resistance to B-RAF inhibitors. By utilizing resistant melanoma sub-lines, patient-derived biopsies and short-term cultures they determined that a subset exhibit a mutation in N-RAS, a component of the MAPK signaling pathway. Another subset exhibits activation of PDGFRβ, a receptor tyrosine kinase involved in additional cell proliferation and survival pathways. Knockdown of N-RAS or PDGFRβ significantly reduced the growth of the resistant melanomas. Importantly, the acquired resistance develops not from secondary B-RAF mutations, but through reactivation of MAPK signaling or activation of alternate survival pathways. These findings offer assays to stratify patients for sequential treatment strategies. (more...)

Tumors have historically been removed through surgical intervention but recently many tumors are instead treated with needle tumor ablation. This is a procedure in which needles are inserted manually via a small skin incision, through the muscle and inner tissue layers, towards a tumor. The tumor is destroyed by applying energy through the needle (high frequency heat in the case of radiofrequency ablation and cold energy in the case of cryotherapy). The needle’s trajectory in relation to the patient’s body must be carefully monitored by CT or MRI scans to ensure that the needle does not damage collateral tissues such as blood vessels or other organs. Any displacement of the needle during the procedure may not only result in needle placement error, but could potentially lead to bleeding or rupture of the tumor and the in-situ release of tumor cells. Improvements in CT scan and MRI scan image resolution have advanced needle ablation therapy, allowing even small tumors to be easily detected. However, the need for continual imaging by CT scan results in the use of increased doses of radiation. Indeed, doses can be between 100 to 500 times greater than those used for conventional radiography. Furthermore, as small changes in needle positioning require repeat imaging, the operator must vacate the CT suite many times, adding a significant time delay to the procedure. (more...)

There has been much focus in recent years on the identification of so called "driver mutations" in cancer and their subsequent evaluation as potential prognostic markers and drug targets. Although such mutations may represent key genetic "hits" to drive transformation, the process of tumor progression is actually characterized by a variety of genetic and epigenetic abnormalities, which in combination contribute to malignant cell behavior. In lung cancer there is significant intratumoral heterogeneity, not only in the catalogue of genetic mutations and epigenetic dysregulations between cancer cells, but also in terms of the particular combinations active in each cancer cell. This makes the association between any particular mutation or epigenetic dysregulation with a specific aggressive (prognostic) behavior imprecise. Because the phenotypic effect of a driver mutation or epigenetic dyregulation is dependent on the developmental stage of the cell and the tumor microenvironment, Dr. Batra hypothesizes that the best way to get to the key combinations of genetic mutations and epigenetic dysregulations that control aggressive behavior is to approach the disease from a specific behavioral property down. In effect, Dr. Batra envisions a tumor as being comprised of subsets of functionally distinct cancer cells that are collectively responsible for the behavior of the tumor. Conventional cancer models severely underestimate intratumoral heterogeneity and are therefore inadequate for (a) evaluating the efficacy of novel therapeutic agents and (b) identifying markers to predict disease progression. (more...)

It is estimated that 1 in 6 men will be diagnosed with prostate cancer in their lifetime. One of the consequences of removing the prostate for prostate cancer is a non-permanent injury of the cavernosal nerve during open radical prostatectomy (RP) or robot-assisted radical prostatectomy (RARP), which may result in post-operative sexual dysfunction. These sexual side effects can severely affect the quality of life for men and their loved ones. Researchers at the University of California, Irvine have developed a new use for an existing compound that can be used to prevent, mitigate, or treat erectile dysfunction associated with prostate removal surgery. (more...)

The ability to study the microstructural and physiological properties of biological tissue in vivo has benefited greatly from the exquisite sensitivity of water diffusion magnetic resonance imaging (MRI). However, the ability to effectively and non-invasively probe biological tissue microstructures requires that one resolve both scale and orientation information. While current approaches (such as diffusion spectrum imaging (DSI) and high angular resolution diffusion imaging (HARDI)) are designed to capture either parameter separately, these methods do not allow simultaneous estimation of both scale and orientation. (more...)

New use for Sorafenib as a p21 inhibitor for cancer treatment (more...)

Cytokines, such as interferon-alpha and interfleukin-2, have been used to treat cancer patients with limited success. The most advanced use of cytokines to treat cancer is in the setting of human melanoma patients (e.g. recombinant interferon-alpha or interleukin-2 given to melanoma patients). Unfortunately, these cytokines also have profound side effects that limit their use. (more...)

Tachycardia is a type of abnormally fast heart beating arrhythmia-a heart rate greater than 100 beats per minute at rest, whose symptoms include palpitations, dizziness, angina, heart failure, or ultimately a heart attack. One of the commonly used non-surgical methods to treat this disease is Radiofrequency Ablation (RFA). Physicians guide a catheter with an electrode at the tip to the area of the heart muscle where there is an accessory extra pathway where heart cells give off the electrical signals that stimulate the abnormal heart rhythm. A radiofrequency energy is transmitted to the pathway and destroys carefully selected cells in a very small area. By doing so, the area stops conducting the extra impulses that cause the tachycardia. Researchers at the University of California, Irvine have developed a novel therapy modality, which combines optical coherence tomography and ultrasound with a electrophysiology catheter for real-time monitoring of the RFA treated area of the heart. The invention will provide images with high resolution and high penetration depth. (more...)

Statins are a class of small molecule drugs used for lowering blood cholesterol levels and preventing cardiovascular disease. Atorvastatin, sold by Pfizer under the trade name Lipitor, is the best-selling drug in history, with sales exceeding $11 billion in 2010. This figure is expected to drop dramatically with U.S. patent expiry and the availability of a generic version in November 2011. All statins, including atorvastatin, inhibit HMG-CoA reductase (HMGCR), an enzyme found in liver tissue that plays a key role in cholesterol production. Experimental evidence suggests that this key biochemical pathway also plays an important role in the oncogenic process, and statin administration in vivo has been shown to inhibit tumor growth. However, a number of rare but serious side effects have been attributed to statins, including muscle and liver damage. Researchers are working to identify the next generation of cholesterol-lowering small molecule drugs with greater efficacy and reduced side effects, and to understand and modulate the HMGCR pathway for cancer therapy. (more...)

Cancers of the head and neck and the breast are common in the United States with more than 55,000 and 200,000 new cases being diagnosed every year, respectively. Although different treatment modalities currently exist, none of the current treatments specifically target resident cancer stem cells (CSCs), which facilitate tumor initiation, tumor maintenance, and cancer relapse [1][2]. These CSCs are similar to embryonic stem cells in that their self-renewal and pluripotency rely on developmental signaling pathways, one of which is the Wnt/frizzled signaling pathway. Since CSCs are resistant to radiation and chemotherapy, cancer therapeutics that exclusively target components of the Wnt/Frizzled signaling pathway may prevent tumor reinitiation and metastasis by eliminating CSCs[3]. (more...)

Metastasis is a leading cause of death in cancer patients.  In this process, cells shed by a primary tumor, known as circulating tumor cells, enter the circulatory and lymph systems and spread to different organs where they can initiate the growth of new tumors.  An accurate quantification of these cells would provide invaluable information regarding the staging and prognosis of a patient's cancer, as well as helping to determine the most appropriate treatment options.  However, such cells are extremely rare and very diffcult to detect using current techniques, hampering the potential of this approach.  Furthermore, current techniques can suffer from either high false positive or false negatie rates, depending on the assay used. (more...)

Researchers at the University of California, Irvine have developed a novel, label-free imaging and evalution method that enables users to track cell metabolism in vivo.The technique is a novel phasor approach to Fluorescence Lifetime Imaging Microscopy (FLIM), a multi-photon microscopy technique that excites cells and then detects their fluorescence activity over time. In this approach, the data from these images is transformed mathematically into a phasor representation. The subsequent analysis identifies, locates, and calculates the concentration of important metabolic cell components, such as: collagen, FAD, free and bound NADH, retinol, and retinoic acid.Overall, this novel method provides a straightforward and quantitative interpretation of the physiological processes occurring in tissues. It enables users to visualize cellular metabolism and retinoid gradients, distinguish between the unique metabolic states of cells, and map their level of differentiation. (more...)

The biggest limitation in the field of ultrasound triggered in vivo delivery is the need for an ultrasound antenna particle that is sensitive enough to the ultrasound to initiate a release event. Microbubbles have been the historical antenna of choice, but they are too large to leave the vasculature and have a circulation half-life that is too short, which has been holding back this field from clinical realization. (more...)

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Researchers at the University of California, Irvine have developed a novel method for capturing cellular resolution images of biological tissue at depths of up to several millimeters. Conventional fluorescence detection methods utilize microscope objectives for emission light collection, a less effective approach that is only capable of imaging up to one millimeter deep.To improve upon this standard, the UC researchers minimized light losses by optimizing the system’s excitation and detection optics. (more...)

The spine is the most common site of tumor metastases to bone. Many different cancer types metastasize to the spine with lung, prostate, breast, kidney, and gastrointestinal cancers accounting for the majority of spinal column tumors. Current therapies for these cancers in bone include hormone treatment, external beam radiation, radioisotopes, prophylactic surgery for osteolytic lesions, and small molecule administration. These approaches, however, are all limited by toxicity, specificity, the potential for adverse side effects, and cost. The development of new therapeutic agents could lengthen and improve the quality of life for cancer patients. (more...)

Vaccines traditionally have and still consist of whole-inactivated or live-attenuated pathogens or toxins. The usage of these modified pathogens is however unattractive for several reasons. Live-attenuated pathogens can cause disease by reverting to a more virulent phenotype, especially in the non-developed immune system of newborns or immunodeficient patients, and whole-inactivated pathogens contain reactogenic components that can cause undesirable vaccine side effects. Therefore, there is growing interest and ongoing research to develop a new generation of vaccines containing recombinant protein subunits, synthetic peptides, and plasmid DNA. While these new modalities promise to be less toxic, many are poorly immunogenic when administered without an immune-stimulating adjuvant. As adjuvants are a crucial component of the new generation of vaccines, there is a great need for safer and more potent adjuvants. (more...)

Researchers at the University of California San Francisco (UCSF) have identified a specific biomarker set for accurately detecting oral squamous cell carcinomas that are unlikely to metastasize and thus these patients could avoid major surgery. (more...)

Although combination therapies are routinely used to treat patients, the approach is challenged by the different therapeutic indices, cellular uptake mechanisms, and in-vivo clearance time of the combined drugs. In sum, the ability to maximize the efficacy of one drug is compromised by the use of many. A method to precisely control the delivery of defined ratios of multiple drugs may allow one to optimize combination therapeutic regimens. (more...)

  Background Over a dozen companies have pursued the development of TGF- β modulators for the treatment of cancer, pulmonary fibrosis, and renal disease. However, the near-ubiquitous presence of the three mammalian TGF- β isoforms across tissue types, as well as its complex and diverse effects on downstream signaling pathways, mean there is a high likelihood that chronic global suppression of TGF-β will result in undesirable off-target effects. An agent effecting tissue and disease-specific mitigation of TGF- β activity while sparing much of its contribution to normal cellular function would be of extremely high therapeutic value for a wide range of inflammatory, fibrotic and neoplastic diseases.   The integrin family of cell surface receptors are emerging as promising targets for tissue type-selective modulation of TGF- β. Because TGF- β activation in a given tissue type requires association with a specific integrin, it is believed that targeting such interactions will lead to effective therapeutics while avoiding many of the possible systemic effects of indiscriminate TGF- β suppression. In mice, conditional deletion of avb8 blocks airway inflammation and fibrosis in COPD and asthma models and can completely inhibit experimental autoimmune encephalitis. In human biospecimens, activation of TGF- β by avb8 has been directly implicated in both fibrotic and inflammatory processes of the airway in COPD.  Until now, no chemical, small molecule, or high affinity antibody agent was available that selectively blocks the interaction of TGF- β and integrin avb8.                                                                            Description UCSF investigators have developed the first mouse anti-human neutralizing monoclonal antibody that prevents the binding of two TGF- β isoforms to integrin avb8. This is the sole agent of any type that selectively targets these associations, without which TGF-b activation in vivo is severely compromised. UCSF investigators have characterized the target epitope of the antibody. In vivo, this antibody blocks airway inflammation in transgenic mice expressing only human and not mouse avb8. Short-term safety tests show no deleterious effects using high-concentrations of the antibody (7mg/kg). Animal model safety and additional efficacy tests are underway in humanized mice expressing human avb8.   This antibody offers several distinct advantages over current TGF- β modulators. First, the antibody only inhibits the activation of the TGF-b1 and b3 isoforms, sparing the neutralization of TGF-b2. The TGF-b1 isoform is widely considered to account for the majority of the disease-related biology of TGF-b.  Second, the specificity for cells expressing only the avb8 integrin isoform decreases off-target effects such as autoimmune responses, rapid-onset atherosclerosis, and carcinoma development. Third, the antibody selectively disrupts the binding of TGF- β to avb8 in a way that does not influence general cell adhesion properties mediated by this interaction, further minimizing non-TGF-b-related effects. (more...)

Heparin sulfate is found throughout all tissues and commonly bound to the cell surface.  Many signaling molecules such as  growth factors, chemokines and cytokines bind to heparin present at the  cell surface and in the  extracellular matrix of all tissues.  While this local heparin binding is an advantage when the cytokine is secreted in its normal environment to be locally retained, it may be a drawback when the cytokine is being delivered by a targeting device such as an antibody fusion protein. In a therapeutic antibody-cytokine fusion protein, the antibody provides the specificity to a tumor antigen and the fused cytokine provides an enhanced immune response to the tumor, thus concentrating the cytokine in the tumor microenvironment. However, the cytokine domain of the antibody fusion protein retains its ability to bind heparin, with the potential  to bind non-specifically to a broad variety of cells and the extracellular matrix, thereby reducing its specificity, increasing the effective dose, and creating the potential for unfavorable side effects.  To overcome this limitation, UCLA researchers have developed mutants of IL-12 that are able to stimulate the immune system while disrupting its heparin-binding domain.  (more...)

Next generation sequencing technologies continue to provide scientists and clinicians with enhanced accuracy and increased sequence readout within a single reaction. However, further advancement has been limited by the ability to minimize the cross-reactivity among combined primer pairs. The linear padlock probe approach, physically linking two primers together, provides improved target specificity. The reduction in probe cross reactivity allows larger combinations of probes for multiplex genotyping reactions. Software capable of streamlining the design of probe pool with desirable characteristics is in much need to further progress the sequencing quest. (more...)

BACKGROUND:   In the United States, over 1.5 million new cancer cases are expected to be diagnosed in 2010. It has been long established that early cancer detection is key to successful treatment. However, current methods remain non-specific and insensitive. And unfortunately, even if cancer is detected, there exists few effective cancer therapies that prevent cancer growth and progression. Treatments are needed that can home in on cancer cells and kill them before they proliferate and spread.   A key strategy for advancing the treatment of cancer is to address two large unmet needs – accurate cancer detection and effective targeted therapeutics.   TECHNOLOGY:   Investigators at UCSF have developed a COX-2 sensitive trigger molecule capable of detecting cancerous cells and releasing therapeutic agents to carcinomas and tumors. The trigger molecule has been functionalized and modified to release either activatable fluorescent moieties or anti-cancer agents upon enzymatic catalysis by COX-2, a cyclooxygenase enzyme previously shown to be expressed in a variety of tumors including head and neck, colon, lung, pancreatic and breast cancers.   When activatable fluorescent compounds, bound to the trigger molecule, undergo COX-2 directed cleavage from the trigger, they selectively label the cancerous cells within a tissue or organ. This technology has the added advantage of a high signal to noise ratio, which essential for cancer detection.   UCSF investigators have also taken advantage of the versatility of the novel trigger molecule to develop a novel targeted cancer treatment platform. They have created a method of binding anti-cancer drugs to COX-2 sensitive trigger molecules. This allows for the release of multiple drug molecules into a cancerous cell. (more...)

During their lifetime, some form of cancer affects more than 40 percent of the U.S. population. It is known that the catch-all term “cancer” includes a variety of diseases with varying etiology and prognoses. It is also known that the progression to metastasis radically changes treatment options. Despite the trend toward better understanding of the nuances of various types of cancer, the critical aspect of effective therapy remains early detection. An early indicator of cancer would allow physicians to proactively test and choose appropriate treatments, before disease progression has ruled out the most effective, early options. (more...)

Obesity is a major health problem and is associated with metabolic consequences such as diabetes, cardiovascular disease, stroke, osteoarthritis, and cancer. Two types of fat exist, white (WAT) and brown adipose tissue (BAT). WAT stores energy in the form of triacylglycerol (TAG) to hydrolyze and release fatty acids into the circulation during times of energy shortage. BAT, on the other hand, hydrolyzes TAG to use fatty acids to activate the enzyme, uncoupling protein 1 (UCP-1), and generate heat (thermogenesis). Therefore, strategies aimed at converting WAT to BAT could be an ideal for treating and preventing obesity and related diseases. We have recently identified a major adipocyte-lipase, desnutrin, which is involved in the regulation of lipolysis (fat breakdown). Furthermore, we have shown that as a major regulator of adipocyte lipolysis, densutrin is critical in the conversion of WAT to BAT. We found that mice overexpressing desnutrin are resistant to obesity and have WAT that resembles BAT. We also found that mice lacking desnutrin in adipose tissue are obese and exhibit a conversion of BAT to WAT. Desnutrin appears to promotes FA oxidation in adipose tissue and thereby reduces obesity. The modulation of adipocyte lipolysis via pharmacological activation of desnutrin may be a useful therapeutic target for treating obesity. (more...)

Volumetric modulated arc therapy (VMAT) is a new technique for radiation therapy treatment that provides superior conformal radiation treatment after just one or two arcs of gantry rotation. Compared to currently used intensity modulated radiation therapy (IMRT) techniques, VMAT reduces treatment time and the number of required monitor units. If well-designed, VMAT delivers a more conformal dose to targets and reduces dosage to organs at risk (OARs). However, the currently used optimization algorithms (such as heuristic simulated annealing) for VMAT planning are based on locating a good approximation to the global minimum across a large search space. Unfortunately, this computationally intensive approach typically requires anywhere from thirty to hundreds of minutes of processing time in order to optimize a single treatment plan, thus limiting its wide-spread use in clinical settings. (more...)

Integrin plays a key role in the angiogenesis and metastasis of human tumors. αvβ3 integrin binding ligands have value in cancer diagnostic imaging and targeted therapy. The RGD motif binds to several integins, including αvβ3, αIIbβ3, αvβ5, and α5β1. It is known that amino acids lateral to RGD affect RGD binding specificity to different integrins. Researchers at the University of California Davis have discovered a novel RGD-containing peptide useful in cancer imaging and as a targeted-therapy ligand. (more...)

UCSF researchers have created new small molecule activators of executioner procaspases 3, 6 and 7 and initiator caspase 9. These compounds have been shown to activate the relevant caspase targets in vitro and to induce apoptosis in a p53 deficient cell line. In addition, a coupled screening assay has been developed which can identify compounds that activate the executioner procaspases in the presence of caspase 9. (more...)

Determining oxygen levels in tumors is critical for advancing cancer diagnosis and therapy. A detailed knowledge of real-time changes in oxygen gradients within a tumor can assist in the profiling of tumor growth and improve the effectiveness of current treatment strategies, which function optimally at different oxygen concentrations. Small molecule luminescence has been suggested as a low cost, non-invasive alternative to traditional methods for sensing oxygen levels that are invasive, expensive, and/or lack sufficient spatio-temporal resolution to monitor real-time changes. In addition to sensing oxygen in tumors, luminescent small molecules, such as porphyrins, have been used for photodynamic therapy (PDT) to treat certain cancers by sensitizing oxygen for the production of cytotoxic reactive oxygen species (ROS). However, the utility of porphyrins has been hampered by low biocompatibility, lack of targetable delivery, and limited photophysical properties. The current invention describes a method for incorporating emissive porphyrins into proteins that offers a novel platform to enhance both oxygen sensing capabilities and targeted delivery to tumors. The bioluminescent proteins described not only have promising photophysical properties for biological use, but also are readily modifiable, biocompatible, and biostable. (more...)

Researchers at the University of California, Irvine have developed a dual modality MR/nuclear imaging system for diagnosing breast cancer. (more...)

Researchers at the University of California, Irvine have developed a breast anatomy imaging system that combines a position tracking system with a handheld optical imaging device. This combined technology allows the researcher and/or clinician to image cancerous versus normal breast tissue at intervals throughout the course of the therapy. A non-invasive near-infrared technology based upon diffuse optical spectroscopy (DOS) has been developed to quantitatively monitor tumor response to the pres-surgical chemotherapy. A tracking device associated with a handheld device can measure a region of interest in the breast tissue at each visit with approximately 1 mm system accuracy. Thus, diffuse optical spectroscopy is used to monitor tumor response in patients with locally advanced cancer throughout the course of the therapy. (more...)

The immune response plays a critical role in protecting humans and animals from infection and the development of tumors. Compositions that increase the immune response (adjuvants) are therefore valuable for improving vaccine efficacy and the control of tumor growth and metastasis. Novel combinations of molecules that are immunostimulatory have been discovered. Certain of these adjuvants have been used to treat a variety of tumor types in mouse models and the results demonstrate dramatic reductions in tumor size and increased survival rates. Additionally, a combination of the molecules has been tested as an adjuvant for an anti-infective vaccine and has produced improved protective effects. This technology is simple, inexpensive, and has broad potential utility for improving existing vaccines against a variety of microbial infections and for improving immunotherapeutic approaches for treating cancer. (more...)

UCLA Researchers have developed a novel mouse model for prostate cancerwhich will be useful for preclinical trials and biochemical assays. Themouse model is unique in that it incorporates a naturally occuring oncogeneimplicated in a significant fraction of human prostate cancer and accuratelyreflects the gradual progression of human prostate cancer from prostaticintraepithelial neoplasia (PIN) to localized adenocarcinoma, to locallyinvasive disease and metastatis, with essentially 100% penetrance. The timecourse of disease progression allows therapeutic testing against all stagesof disease, including prevention strategies. The model offers significantadvantages over current transgenic prostate cancer models such as TRAMP,which require expression of the SV40 T antigen and generate mice with alarge percentage of neuroendocrine, rather than adenocarcinomas of theprostate. (more...)

Renal cell carcinoma (RCC) accounts for 2% of adult cancers. One-third of patients who are diagnosed with RCC have evidence of metastatic disease at the time of diagnosis and up to half of those treated for localized disease eventually relapsed. The high mortality rate in RCC plus the poor prognosis for the metastatic form of the disease post a need for molecular markers that can both diagnose RCC early and predict outcome reliably in response to therapeutic interventions. (more...)

Cervical cancer is the second most common cancer responsible for cancer-related deaths in women around the world. The incidence is increasing, with 450,000 new cases diagnosed annually worldwide. Currently, cervical cancer is commonly diagnosed by screening pap smears for abnormal cells. A cervical biopsy can then aid in the determination of the nature of these abnormal cells, indicating whether or not they should be removed. However, these current methods do not provide information concerning the potential aggressiveness of cancers resulting from these abnormalities. Before progressing to tumors, the earliest stage of cervical cancer is characterized by an abnormality known as cervical intraneoplasia (CIN). It would be beneficial to be able to reliably diagnose and understand the potential invasiveness of the cervical cancer at this stage so that proper treatment could begin as early as possible. (more...)

Virtually all B cell malignancies express a tumor-specific immunoglobulin, whose unique variable region sequences contain antigenic determinants known as the idiotype (Id). The Id protein can be produced from individual patients tumor cells by hybridoma or recombinant DNA techniques, thus yielding a patient-specific protein that can be formulated into a vaccine. To render the Id protein more recognizable by the immune system, the Id protein is usually chemically-linked to an immunogenic foreign carrier protein. The protein most often used for this purpose is keyhole limpet hemocyanin (KLH), the oxygen-carrying protein from a Pacific mollusk. The traditional method for linking tumor Id proteins to KLH involves glutaraldehyde. However, not all subjects immunized with glutaraldehyde Id-KLH vaccines demonstrate immune responses to the Id proteins. (more...)

Cancer is one of the leading causes of death worldwide, killing millions of people every year. Of the different types of cancers, breast cancer is the leading cause of death among women, affecting over one million women worldwide every year. Currently, dasatinib is approved to treat chronic myeloid leukemia (CML) and is in development to treat solid tumors, including breast cancer. However, there is a need to be able to identify patients most likely to respond to drugs like dasatinib. New diagnostics methods will be especially useful for women whose breast cancers fall under a specific triple negative subtype (estrogen receptor negative, progesterone receptor negative, and HER2 negative), and therefore lack effective treatments. Due to the lack of effective treatments, there is a need to identify the patients that might benefit from dasatinib. (more...)

Transferrin (Tf) is a critical iron transport protein found in the blood. Tf loaded with iron binds to the cell surface Tf receptor (TfR) and is taken into the cell. Once inside the cell, Tf releases its iron load and both Tf and TfR are then recycled back to the cell surface and Tf is released into the extracellular space. Due to the observation that TfR is overexpressed in a broad range of cancers, Tf is currently being investigated in clinical trials as a potential drug carrier to allow specific targeting to cancer cells. It has been shown previously that the duration of Tf cellular trafficking is correlated with effectiveness of drug delivery. Therefore, increasing the cellular association of Tf should result in more efficient drug delivery. (more...)

Conventional antibiotics are often used in the treatment of skin infections and inflammation. Topical and oral antibiotics are common in the treatment of acne, which is aimed at killing the Propionibacterium acnes, the bacteria linked to the pathogenesis of acne vulgaris. Erythromycin and tetracycline are frequently prescribed for reducing P. acnes, though the efficacy of antibiotics has been declining as the prevalence of this microbe has become widespread. Excessive utilization of antibiotics due to improper use and inaccurate diagnosis is contributing to microbes gaining resistance to conventional therapeutics. Due to random genetic mutations that occur from natural selection and evolution, microbes develop resistance genes that make it impervious to antibiotics, exposing many current compounds to obsolescence. The new generation of antimicrobial compounds must therefore eradicate microbes independent of its survival machinery, such as cell wall or RNA synthesis. Novel strategies for killing pathogenic cells can also yield alternative uses for treating other skin diseases. (more...)

Over 190,000 new cases of breast cancer are diagnosed each year. Of all breast cancer patients, two thirds have a positive estrogen receptor (ER) profile. The ER is an intracellular transcription factor that interacts with estrogen to initiate the transcription of growth factor genes. Growth factors are important constituents in the growth and development of breast cells. Blockade of the estrogen pathway by interfering with the binding of estrogen to its respective receptor is the basis of many breast cancer treatments. One example is the use of tamoxifen, an anti-estrogen that works by competitively binding to the ER.Antiestrogen therapy has had a significant impact on disease-free survival in breast cancer patients with a positive ER profile. However, tamoxifen has some undesirable side effects such as formation of liver and endometrial tumors. Moreover, as breast cancer progresses, it usually becomes resistant to estrogen and hence, the strategy of binding the ER with a competitive inhibitor becomes ineffective. (more...)

Lung cancer causes more deaths than the next three most common cancers (colon, breast, and prostate) combined, accounting for more than 174,000 new cancer diagnoses and greater than 160,000 deaths each year. In lung cancer management, surgical resection is generally beneficial only for early-stage disease, and even if diagnosed when the tumor is still localized in the lung, about 50% of the cases will succumb to relapse and subsequent death. Therefore, it is critical to understand details of the biologic features of lung tumor cell proliferation and to develop targeted therapies aimed at specific proteins involved in these biologic behaviors. As well known, smoking is the most important cause of lung cancers accounting for 90% for the men and 70% of the cases in women. Life-time smokers have 20 to 30 fold higher risk of developing lung cancer compared to life-time non-smokers. However, only 11% of heavy smokers ultimately develop lung cancer, suggesting implication of genetic factors predisposing to lung cancer risk. Identification of the genes that undergo frequent somatic mutation in the lung, the so-called lung cancer genes, should facilitate the development of effective treatment as well as better detection and prevention strategies. (more...)

UCSF investigators have identified a novel endogenous agent that activates the Aryl Hydrocarbon Receptor. (more...)

Matrix metalloproteinases (MMPs) are a class of zinc-dependent hydrolytic enzymes that function in the degradation and restructuring of extracellular proteins. Overexpression of MMPs has been associated with a variety of diseases, including cancer, arthritis, and cardiovascular disease. Commercialization of MMP inhibitors (MMPi) has not been successful, as the inhibition of MMPs systemically has resulted in adverse events such as musculoskeletal syndrome. The researchers have approached this problem by developing prodrug MMPi or "proinhibitors" that are triggered in a localized fashion, minimizing the systemic effects of the drugs. A protected zinc-binding group was used to develop the proinhibitor. The researchers demonstrated that it is possible to protect the MMPi, activate it through an enzymatic reaction, and inhibit MMPs in a controlled manner. The ability to create MMP proinhibitors may provide a new approach to MMPi therapy of disease. (more...)

Background: Cigarette smoking is the single most preventable cause of premature death in the United States. Each year, one in every five deaths, (about 443,000 in total) is smoking related. The health risks associated with smoking translate into annual healthcare costs of more than $96 billion, with costs associated with second hand smoking averaging $10 billion. Interestingly, 70% of the 43.4 million U.S. adult smokers report that they want to quit completely and more than 40% try to quit each year. However, smoking cessation is extremely difficult; in fact, only about 4% - 7% of people are able to remain smoke free for six months on any given attempt. These success rates dramatically increase to between 14% - 27% if smokers use medicines or behavioral therapies, but such methods may be expensive for both the insurer and patient, inconvenient, or difficult to access. Therefore, it is imperative that a successful, convenient, and cost-effective smoking cessation aid be developed. Invention: Prominent University of California clinicians, Ricardo F. Muñoz, Ph.D. and Eliseo J. Pérez-Stable, M.D. have developed an extremely successful, web-based, smoking cessation program. The program takes eight weeks to complete and combines a smoking cessation guide with individually tailored advice, optional email reminders, and an optional mood management program. Since 2002, over 17,500 smokers from over 155 countries have participated in a series of randomized controlled smoking cessation trials using this program. The study boasts an impressive success rate, with 20% of the participants remaining smoke-free after one year. Significantly, this success rate is comparable to those seen for nicotine replacement therapies, or smoking cessation groups, yet the web program has the important advantages of reducing the cost per patient and increasing the ease of patient access. Furthermore, this fully developed stand alone program is available in both English and Spanish, making it accessible to virtually every American smoker. http://www.stopsmoking.ucsf.edu or http://www.dejardefumar.ucsf.edu (more...)

UC San Diego inventors have devised a new structure, isolated from a natural product that can inhibit progression through the cell cycle. The new structure's use as an anti-cancer agent is in the early stage of preclinical studies. The novel structure inhibits mitosis in a fashion that differs from known natural products, with the current hypothesis being that an aspect of its structure inhibits the exit from anaphase. This effect was observed in both colon cancer cells (HCT111), breast cancer cells (HeLa), and neuroblastoma cells (Neuro2a). Cytotoxicity data has been collected in HCT111 cell lines and complete cytotoxicity data is being collected via analyses by the NCI-60 cell screen. Cell cycle screening, uptake, and localization data are complete in HCT111 cells and shall be expanded to other cell lines. (more...)

BACKGROUND:  Patients with certain types of tumors, in particular brain tumors, will frequently rely on radiologic imaging, such as magnetic resonance imaging (MRI), for diagnosis and treatment monitoring. Unfortunately, MRI and similar modalities are often subject to interpretation and can be highly subjective in nature, making it difficult to differentiate between actual tumor recurrence and treatment effect. Subsequent or alternate methodology involving biopsy or other surgical procedures, can be highly invasive, dangerous, and lead to an extensive recovery time in patients undergoing such procedures. A less invasive method to reliably identify tumor recurrence would be valuable to clinicians and their patients during evaluations following treatment and/or surgical resection of a tumor.   TECHNOLOGY:   UCSF inventors have discovered a novel cancer biomarker that is expressed on the surfaces of myeloid cells, so that tumors can be evaluated for recurrence by screening small amounts of peripheral blood in patients. So far, these findings have been done in glioblastoma and prostate cancer patients, but further studies are underway for other types of solid tumors. (more...)

DNA vaccination is a technique whereby somatic cells are transfected in vivo with naked plasmid DNA directing synthesis of a target antigen. However, many of the antigens synthesized from these DNA vaccines result in an antibody-mediated immune response, but fail to elicit a substantial cellular immune response. Inducing an antibody directed immune response may lead to additional treatment complications as: antibodies directed to these antigens may inhibit cellular immune responses to antigens, antibodies may enhance the growth/survival of tumor cells expressing an antigen, and antibodies may also cause pathology when cross reactive with self antigens. Therefore, there is a significant demand for a DNA vaccination technology that results in a strong and specific cellular immune response for the treatment or prevention of cancer or infection. (more...)

Chronic myeloid leukemia (CML) is a hematological stem cell disorder characterized by excessive proliferation of cells of the myeloid lineage.  The distinguishing characteristic of CML is the Philadelphia chromosome, which arises from a reciprocal translocation between chromosomes 9 and 22.  The molecular consequence of this translocation is the replacement of the first exon of c-Abl with sequences from the Bcr gene resulting in a Bcr-Abl fusion gene whose protein product shows enhanced tyrosine kinase activity.  The Bcr-Abl oncoprotein in CML is a 210-kD protein and is found in 95% of patients with CML and in approximately 5-10% of adults with acute lymphocytic leukemia (ALL) for whom there is no evidence of antecedent CML.  It is believed that this single chromosomal rearrangement is sufficient to initiate the development of these diseases and may be the only molecular abnormality in early stage disease.  The Bcr-Abl kinase activates a number of signal transduction pathways involved in cell proliferation and apoptosis. (more...)

Researchers at UC San Diego have discovered a novel method of detecting and inhibiting angiogenesis. In vivo experiments have shown that angiogenesis induced by a wide range of pro-angiogenic factors can be completely or significantly inhibited with antibody, peptide or organic molecule inhibitors of the newly identified target. Because angiogenesis plays a key role in the growth and spread of tumors, neovascular eye diseases, and inflammatory diseases, such as rheumatoid arthritis, this method has great potential as a highly specific therapeutic approach to the management of these diseases. (more...)

UCSD researchers have discovered new synthetic oligodeoxynucleotides (15-mers) useful in treating cancer and certain autoimmune diseases. These compounds induce apoptosis in chronic lymphocytic leukemia cells but actually stimulate normal human B cells. Their mechanism of action does not depend on CpG dinucleotides, and they do not require the addition of cationic lipids or any other adjuvant to exert their effects. (more...)

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UCSD researchers have discovered that a certain gene encoding a glycosyltransferase is able to regulate levels of glucose transporters on pancreatic beta cells. Over-expression of this gene in mice promoted glucose transporter activity on the plasma membrane, increasing glucose uptake and insulin secretion. When the expression of this gene was impaired, the mice developed type II diabetes. (more...)

Cancer is in part a result of the ability of pathologically altered cells to evade apoptosis. Therefore, there is a need to identify compounds that can key regulate the key interactions between proteins involved in apoptotic regulation in order to treat cancer. ZAP-70 is considered the best prognostic factor for disease progression and is correlated with poor clinical outcome in CLL patients, in part through its ability to serve an anti-apoptotic function in these cells. A compound with the ability to down regulate ZAP-70 and induce apoptosis specifically in CLL cells would provide an invaluable therapy for patients with aggressive disease. (more...)

Today there are a variety of treatment options for cancer, but many are non-specific, which results in normal cells being destroyed along with the malignant ones. Anemia, fatigue, immunodeficiency, and vomiting are just a few side effects of chemotherapy. Current monoclonal antibody lymphoma treatments most B cells in the patient, thus crippling the immune system. Rare infections and skin cancers can result. Moreover, a specific marker for Chronic Lymphocytic Leukemia (CLL) does not exist on the market today. Patients "wait and see" if the symptoms progress in the early stages of the disease before a diagnosis is made. Instead of being treated immediately, the disease could lurk for years. Detection of residual disease after therapy is problematic as well. (more...)

Therapeutic options for patients with chronic lymphocytic leukemia (CLL) are limited, and in most cases ineffective, or with a limited period of effectiveness. Relapse of the disease often occurs and patients acquire resistance, not only to the drug used, but to other drugs as well. Moreover, a specific marker for CLL does not exist on the market today. Patients ‘wait and see’ if the symptoms progress in the early stages of the disease before a diagnosis is made. Instead of being treated immediately, the disease could lurk for years. (more...)

Lymphangiogenesis, or the development of new lymphatic vessels, plays roles in tissue repair and in pathological processes such as tumor growth and metastasis. The growth of lymphatic vessels is thought to play a crucial role in the formation of both local and distant tumor metastases, including those to the bone marrow. The mechanisms regulating lymphangiogenesis, however, have not been well understood. A target molecule that is differentially regulated during pathological lymphangiogenesis has been identified. This molecule is not expressed on resting lymphatic vessels but exhibits induced expression on proliferating lymphatic vessels in tumors and in lymph nodes proximal and distal to primary tumors. An antagonist of this molecule has been shown to inhibit lymphangiogenesis and lymph node metastasis in animals. Antagonists of the target molecule, such as small molecules or antibodies, therefore, have the potential to inhibit lymphangiogenesis and subsequent lymph node metastases in humans. Very few methods currently exist to inhibit lymphangiognesis; the identification of an alternative target molecule provides the potential for novel therapeutics to be developed that prevent or reduce tumor metastasis in humans. (more...)

Erythropoietin (EPO) is a naturally occurring hormone that stimulates the production of red blood cells. Recombinant EPO, marketed as Epogen® or Procrit®, have been used as a treatment for anemia and neutropenia, especially in those patients suffering from the effects of cancer chemotherapy, chronic renal failure, or treatment for HIV. Recombinant EPO is administered intravenously, with patients traveling to a clinic or hospital periodically to receive it. (more...)

Causes of blood cell diseases range from genetic, as in myeloproliferative disorders (MPDs) and cancer, to infectious, as in malaria. In all cases, treatments are directed at modulating the survival or differentiation of the affected cell population. Unfortunately, drug and vaccine development are continuously hampered by the absence of good, in vivo models that can mimic the complexity of the human immune system. (more...)

While the link between inflammation and tumor promotion has been known for some time, it has recently been shown that IKK complex and NF-kB play a role in tumor promotion. In this invention, the scientists describe a mechanism in which IKK alpha activation specifically promotes prostate cancer metastasis, and how this can then be prevented. The inventors teach a way to inhibit a signaling pathway, through which activation of IKK alpha results in a repression of maspin, a critical suppressor of prostate and breast cancer metastasis. By blocking the pathway with a small molecule inhibitor at IKK alpha, the emergence of metastasis can be blocked. In mice, it was shown that levels of activated nuclear IKK alpha correlate with prostate cancer progression and links inflammatory signaling to metastasis. (more...)

Mice Lacking Ikkß In Intestinal Epithelial Cells - Models For Acute Organ Failure, Radiation Sensitivity, Colitis-Associated Cancer (more...)

The compound prosaposin and its methods of use, already tested successfully in Phase I clinical trials, is available for licensing. Prosaposin is the precursor of the saposins and has both neurotrophic and myelinotrophic activity in vitro and in vivo. It is an injury-repair protein that acts on both neurons and glia.Prosaposin also has myotrophic properties and can attenuate loss of muscle mass after nerve injury. Prosaposin and peptide derivatives of it will promote neurite outgrowth in vitro. A peptide consensus sequence was determined by comparing the active neurite outgrowth-inducing saposin C peptide sequence with that of various hematopoietic and neuropoietic cytokines. These cytokine-derived peptides will promote the same processes as their corresponding cytokines. In addition, prosaposin and saposin C promote increased nerve cell myelination ex vivo. Demyelination is a defect common to a number of central nervous system disorders, the most common being multiple sclerosis. (more...)

Salinosporamide A (Sal A) is a potent proteasome inhibitor produced by the marine bacterium Salinispora tropica. This natural product is biosynthesized from three metabolic building blocks, namely acetate, a chlorinated tetrose from S-adenosylmethionine, and the non-proteinogenic amino acid cyclohexenylalanine. Sal A exhibits potent cancer cell cytotoxicity apparently through inhibition of the 20S proteasome, a multisubunit protease responsible for proteolysis of proteins targeted for degradation in the cell. Tumor cells may be more sensitive to proteasome inhibitors than normal cells and proteasome inhibition increases the sensitivity of cancer cells to anticancer agents. (more...)

Chronic lymphocytic leukemia (CLL) is a disease that leads to the fatal accumulation of B cells. It is the most common adult leukemia. The cause of CLL is unknown and there are no animal models of this disease. There are two forms of CLL, indolent and aggressive. Patients with aggressive CLL should immediately undergo chemotherapy but patients with the indolent form should not be treated. Currently there are no biomarkers that enable the facile distinction of the two forms of CLL and, consequently, patients do not always receive the appropriate treatment. (more...)

The invention is a method and probe design for obtaining quantitative optical properties and chromophore concentrations of tissue components in-vivo at superficial depths and "short" source-detector separations. (more...)

Overexpression of the neu oncogene is a factor in a significant percentage of all human breast cancers and is correlated with reduced survival and higher recurrence. This plasmid was developed to study the protective effects of the neu gene when used as a naked DNA vaccine. The expression vector encode either a 1) full length neu gene, 2) a truncated gene lacking the cytoplasmic kinase doman or 3) a truncated gene lacking both the cytoplasmic and transmembrane domains. The Tg1-1 cell line was established from a neu-expressing mammary tumor which arose spontaneously in a FVB/N neu-transgenic mouse. (reference) (more...)

New materials and methods that enable the simple inclusion of 18F into cancer-targeting peptides that can be used as radiolabels for PET imaging (more...)

This invention features methods to reduce androgen-independent prostate cancer. Currently, the most common way to treat primary non-metastatic prostate cancer entails treatment with anti-androgen drugs. In addition, surgical removal or radioablation are also practiced. While these procedures are effective, a major problem is the re-emergence of androgen independent cancer a few years later. Thus, what are needed are methods to reduce (including delay and/or complete inhibition of) the re-emergence of hormone resistant cancer. The inventors have demonstrated in mouse models that B cells remain in the tumor environment, even after castration. These B cells have been shown to assist in the re-emergence of the tumor. In vitro, the same phenomenon has been observed in 90 percent of the samples obtained from humans with malignant prostate cancer. By removing the B cell population, re-emergence of disease is significantly delayed. To older men (the most likely patient population to get prostate cancer), the delay of several years to re-emergence could be considered significant. (more...)

Radiolabeled PEGylated peptide radiotracer for detection of integrin alpha-v beta-6 in vitro and in vivo (more...)

Background: Due to genetic variations between individuals, patients with the same disease do not respond uniformly to the same drug. This results in unacceptably high levels of side-effects, ineffective treatment, and inefficient clinical trial design. To combat these issues, the emerging field of personalized medicine exploits the molecular genetic differences between patient populations to determine whether an individual patient will respond to a particular drug. This approach has been particularly successful in cancer treatment because of the large number of tumor markers and mutated genes involved. For example, the success of lucrative drugs such as Genentechs Herceptin and Novartis Gleevec is based upon the availability of companion diagnostic assays to determine if a cancer patient will benefit from the drug. An added advantage of the personalized medicine approach is that companies can reduce the time and cost of clinical trials by pre-screening patients for susceptibility to a drug. Technology: UCSF scientists have discovered a biomarker for susceptibility to aurora kinase inhibitor cancer therapy. Uniquely, the biomarker is not an aurora kinase. Cancer cells expressing the biomarker are killed by brief pulses of aurora kinase inhibitor treatment, while cells not expressing the biomarker do not respond. This technology has been successfully tested both in cancer cell lines and in a mouse model of lymphoma. (more...)

UCSF researchers have identified biomarkers for the diagnosis and prognosis of malignant tumors (including primary and metastatic tumors and cancers) resistant to anti-tumor therapeutics or that will develop resistance to anti-tumor therapeutics. These biomarkers are also useful in the diagonosis and prognosis of multidrug resistant (MDR) tumors. This technology also provides methods of sensitizing treatment of MDR turmors to anti-cancer therapeutics. (more...)

The number of murine models for human cancer has grown rapidly in recent years and there now exist mouse models for almost all tumor types. Evaluating the effect of specific molecular alterations or therapeutic interventions in these animal models requires the ability to temporally and spatially assess the tumor burden. In many cases, however, this entails sacrificing the animal thereby limiting ability to perform follow up analysis, and necessitating the use of many more experimental animals. To address these problems, UCSF investigators have generated a general tumor reporter transgenic mouse strain designed to selectively expresses firefly luciferase in malignant tissue. (more...)

UCSF investigators have designed a software package called DoseTailor that allows clinicians to use pharmacokinetically guided models to dose the chemotherapy agent docetaxel. DoseTailor can be easily expanded to include a wide variety of other antineoplasics including carboplatin, vinorelbine, ifosfamide, and 5-fluorouracil. Multiple models are available for use by the clinician, each with varying degrees of precision or error. Features of the software include automatic selection of the best precision model given the data available for an individual patient and a graphing function to allow visual assessment of the patients status within the dosing parameters. Both desktop Java-based and PALM-OS C-based applications are available for immediate use. (more...)

Membrane type serine protease 1 (MT-SP1), or matriptase, is a serine protease that is over-expressed on the surface of epithelial cells involved in a variety of cancers, including breast, colon and prostate. UCSF inventors have developed a novel antibody inhibitor of MT-SP1 (A11) which gains potency and specificity through interactions with the protease surface loops and binds in the active site in a catalytically non-competent manner.  The A11 antibody has applications as a therapeutic, diagnostic, and research tool. (more...)

BACKGROUND: Vaccine targets for prostate cancer have generally been identified either by tissue specific expression in prostate cancer or by assessing immune responses in cancer patients. However, UCSF investigators have taken a novel approach to identify the targets of an immune response in patients who are either responding or not responding to an immune-based treatment (anti-CTLA4 antibody) in a clinical trial at UCSF. CTLA4 blockade with antibody treatment can augment endogenous anti-tumor immunity in animal models and is being developed as an immunotherapy for cancer patients. Defining the antigen-specific responses induced by this treatment can lead to immunological identification of therapeutic targets that may be relevant in prostate cancer patients. These studies provide a unique opportunity to determine the antigen-specific responses that are relevant for immune-mediated clinical responses in prostate cancer, can provide opportunities to predict which patients may respond to therapy, and can provide novel approaches to prostate cancer treatment and vaccination. DESCRIPTION: UCSF investigators found that immune-mediated clinical responses to CTLA4 blockade is seen in the absence of a specific vaccination, suggesting that endogenous antigen-specific immune responses can be potentiated through this treatment. By focusing on immune responses unique to those patients that responded to immunotherapy, the UCSF investigators were able to identify candidate antigens that correlated with clinical outcome in prostate cancer patients. In addition, a patient’s immune response to the prostate cancer-associated antigens can be used as a diagnostic assay to determine the likelihood that an individual having prostate cancer will exhibit a clinically beneficial response to an immunomodulatory treatment. Furthermore, targeting these antigens with antibodies and/or vaccination may lead to novel therapies for prostate cancer. One antigen in particular has shown promise because it is expressed at a higher intensity in prostate cancer patients and in prostate cancer cell lines compared to other previously described antigens. Kaplan-Meier survival curves for tumor challenge were plotted for C57BL/6 and FVB mice (5 control and 5 test mice per mouse model) that were immunized with a mouse homolog of the particular antigen. The mice were challenged with Tramp cells or Myc-Cap prostate cancer cells respectively. Immunization with the novel antigen induced anti-tumor responses in both models of prostate cancer. (more...)

UCSF investigators have developed a novel targeted pro-drug technology that can selectively deliver a chemotherapeutic payload to cells in areas of high concentrations of endogenous free ferrous iron. The pro-drug can be conjugated to a variety of existing and novel pharmacologically active compounds to increase their therapeutic window and lower systemic toxicity by increasing the selectivity of their delivery. Applications include therapies for cancer and malaria and as imaging agents.  (more...)

BACKGROUND: Breast cancer is one of the most commonly diagnosed cancers among women in the US. There are 2.4 million women living with breast cancer in the US and upwards of ~180,000 new cases each year. Breast cancer tumors are currently evaluated on the basis of several histopathological features including tumor size, grade, and lymph node status, all of which contribute to assessing the overall stage of cancer development. In addition, hormone receptor (ER, PR) and HER2 expression in tumors, together with the histopathological features, are used to classify the progression of the disease (e.g. tendency to stay localized or metastasize) and thus currently provide the rational basis for aggressiveness of treatment. Despite these common biomarker analyses and the information they provide regarding molecular features and stage of breast tumors, they still do not enable accurate predictions as to which early stage breast cancers will progress or recur if removed surgically; thus, many women with breast cancer end up being over-treated or under-treated for the disease. For example, some women receive chemotherapy or anti-hormone therapy, which both can reduce the risk of metastasis by one third but also can have dangerous side-effects. Moreover, 70-80% of patients receiving these treatments could have survived without them, as those patients presumably have a less aggressive form of breast cancer. In addition, 40% of women diagnosed with breast cancer die from the disease regardless of the treatment regimen, and there are no reliable biomarkers to predict the fate of this subset of breast cancers as of yet. Thus, the current cellular, molecular, and histopathological classifications of breast cancer have limited prognostic ability. There is a need for a more accurate means of predicting the progression of breast cancer in a wider range of cases in order to improve the selection of patients for adjuvant treatments such as systemic chemotherapy. DESCRIPTION: University College Dublin and UCSF investigators have discovered that the immune environment around tumor cells can influence the outcomes of cancer patients. Specifically, they have found that the relative expression of three leukocyte proteins can predict the clinical outcome of breast cancer patients. This “immune signature” has been validated by evaluating the progression-free survival of two independent cohorts of invasive breast cancer patients that had 5 year follow-up data available, now totaling about 1000 samples. Based on relative protein expression as a measure of leukocyte infiltration, assessed in a multivariate manner, the investigators found that the biomarkers could be used to predict clinical outcomes, such as recurrence or metastatic progression, of early stage breast cancer. Importantly, these predictions can be made independently of tumor grade, stage, lymph node status, and ER, PR and HER2 gene expression, indicating that the immune signature is applicable to a wide range of breast cancer types. The investigators have also provided compelling evidence from 5000 samples that two of the markers could be assayed at the RNA level to predict outcomes (see Denardo et al 2011). While most other breast cancer tests currently available focus on genes expressed within the cancer cells themselves, this signature focuses on the immune environment and its influence on the cancer cells. Therefore, the signature has the potential to stratify and classify different groups of patients than current tests on the market. Specifically, the investigators believe that the main utility of the immune signature biomarkers will be to identify patients with tumors designated as "high-risk" under current classifications, but whose immune environment may nonetheless suppress aggressive growth and distant metastases. These patients would normally be prescribed adjuvant therapy, but may do well even in the absence of toxic adjuvant therapy. Conversely, patients with tumors designated as "low-risk" by current classifications may possess an immune environment that is permissive or promotes progression of the tumor. These patients normally would not be prescribed adjuvant therapy due to their "low-risk" status, however, their immune signature suggests that over the long-term, they could benefit from adjuvant therapy.  The investigators have also evaluated the utility of the signature in ovarian cancer and pancreatic ductal adenocarcinoma (PDAC) cohorts. (more...)

Researchers at the University of California have developed a fiber-based spectroscopic technique that can be used to quantify optical properties in superficial layers of tissue. (more...)

Her2/neu is over-expressed in various types of tumor cells, including 20-30% of breast cancers, adenocarcinomas of the ovary, salivary gland, stomach and kidney, colon cancer, and non-small cell lung cancer. Passive immunotherapeutics like Herceptin control and prevent further tumor cell growth. Unlike active immunotherapeutics, Herceptin does not mediate the immunological cellular destruction. Active immunotherapeutics such as vaccines elicit T helper-1 (Th1) and Cytotoxic T lymphocytes (CTL) biased immune responses and are generally observed for proteins expressed in the intracellular compartment, and less prominently with extracellular or secreted proteins. Rapid degradation of a protein containing polyepitopes can contribute to establishing a bias in the immune response, facilitate antigen presentation and, perhaps assist in establishing specificity of the immune response. This type of immunological response should result in immunological cellular destruction. (more...)

Nicotinic acetylcholine receptors (nAChRs) belong to the superfamily of ligand-gated ion channels and are distributed widely in the human and nonhuman brain. Several nAChRs have been identified and characterized pharmacologically and have distinct patterns of distribution in the brain. The nicotine alpha 4 beta 2 receptor subtypes are thought to play a role in various diseases, including various brain disorders (e.g., Alzheimer's disease), behavioral disorders (e.g., schizophrenia or substance abuse), various neoplasms (e.g., lung cancer), and other diseases, and may also be involved in the addiction to nicotine in chronic tobacco users (tobacco use may increase the number of the alpha 4 beta 2 receptor sites). The development of noninvasive imaging methods using PET and SPECT of the alpha 4 beta 2 receptor system has gained significant interest. Therefore, and not surprisingly, the development of noninvasive imaging methods using PET and SPECT of the alpha 4 beta 2 receptor system has gained significant interest. However, current radiotracers suffer from several drawbacks, including rapid clearance, toxicity, and undesirable kinetic parameters. Consequently, there is still a need to provide improved compositions and methods for radioligands for receptors of the alpha 4 beta 2 receptor type. (more...)

Sodium/potassium ATPases (Na+/K+-ATPases), a family of multi-subunit ion pumps, are the most important active transporters in animal cells. They are required for maintaining the electrochemical gradient responsible for resting membrane potentials in neuronal cells and for the function of other transport proteins in a variety of cell types. The important regulatory activities of Na+/K+-ATPases make them an attractive therapeutic target for the treatment of neurodegenerative, cardiac, and other diseases. To date, there are unmet medical needs for the treatment of these diseases, and it is desirable to discover and develop novel therapeutic agents aimed at treating ion pump related disorders. (more...)

BRCA1 is a breast cancer susceptibility gene. According to estimates of lifetime risk, 36 to 85 percent of women with an altered BRCA1 or BRCA2 gene will develop breast cancer. (more...)

Angiogenesis drugs act to inhibit survival of newly formed blood vessels required for tumor growth and progression. These drugs have recently shown good activity in the clinic for breast, lung, colon and kidney cancer. However, these drugs can be toxic and even cause death. Only about half of patients benefit from this treatment approach. It would therefore be of value to be able to predict in advance if a patient has a better or worse probability of responding in order to avoid this treatment if the chances for success are low. (more...)

Histone deacetylase inhibitors are currently being evaluated in clinical trials as anti-cancer drugs. They are likely to affect cancer cells because they alter the distribution of heterochromatin with resultant multiple downstream effects that cancer cells cope with only poorly. There is great interest in identifying additional chemical compounds that affect heterochromatin. (more...)

Method of Using Lunasin as a Transcriptional Activator to Prevent Cancer (more...)

Lymphoma diagnosis through the identification of specific cell antigen  (more...)

Cloning of an enediyne biosynthetic gene cluster used to understand genes from streptomyces globisporus which may be considered anticancer agents (more...)

One-pot Synthesis for Alpha Glycolipids and their Analogs Using Glycosyl Iodide Donors (more...)

Construction of Multivalent Antibody scFv Through Cu(I) Catalyzed 1,3-Dipolar Cycloaddition (more...)

Technology for engineering antibodies to bind irreversibly to their receptor has been developed by UC Davis researchers. This technology, enabling the formation of permanent antibody-antigen complexes has a number of potential applications in chemistry and biology, including: targeted medical imaging targeted medical therapies (e.g., cancer therapeutics) synthetic tag to replace avidin-biotin no competition from endogenous ligands no dissociation after capture humanized format Furthermore, UC Davis researchers have constructed a bispecific fusion protein that has tumor targeting properties and irreversibly captures a metal chelate. This combines irreversible metal chelate binding with tumor targeting activity for the first time in a highly homogenous genetic construction that can be expressed at high yields. In addition, this allows the substitution of other targeting sequences allowing for a wide range of cellular targets. The irreversible nature of the chelate binding has not been previously achieved in a single expressed protein fused to a tumor targeting functional segment. (more...)

Anti-CD22 Monoclonal Antibodies used for the Treatment of Lymphoma and Leukemia (more...)

Drug-peptide conjugates permeate cells and are biologically activated and trapped intracellularly. Their inhibition of intracellular urokinase plasminogen activator (uPA) kills disseminated cancer cells, notably breast and high grade malignant glioma, and is associated with high selectivity and low toxicity. (more...)

Chromosome abnormalities are often associated with genetic disorders, degenerative diseases, and cancer. In fact, the deletion or multiplication of copies of whole chromosomes, chromosomal segments, or specific regions of chromosomes are common occurrences in cancer, and can be the cause of some cancers. One such amplified region found in studies of breast and colon cancer cells is on chromosome 20, specifically 20q13.2. Increased copy number of 20q13.2 is found in greater than 25% of cancers of the ovary, colon, head-and-neck, brain, and pancreas. However, it is unknown what gene target(s) is/are responsible for this increase in cancer. (more...)

University of California researchers have developed an antibody fusion protein that functions as a novel cytotoxic drug, though both, the antibody and the non-antibody partner by themselves are not cytotoxic. This fusion protein serves to decrease or eliminate cell proliferation by stopping cell division and causing cell death (apoptosis). In addition, it could be used as a universal delivery system to selectively deliver proteins, nucleic acids, and other chemicals into various kinds of cancer cells. Initial studies have demonstrated promising results using the antibody fusion protein specially against cancer cells of hematopoietic origin such as lymphomas, leukemias, and myelomas. (more...)