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Gelatin Methacryloyl Based Microneedle

UCLA researchers in the Department of Bioengineering have developed gelatin methacryloyl microneedles (GelMA MN) for minimally invasive, sustained transdermal drug delivery.

Brain-Specific Kinase Inhibition to Mitigate Systemic Toxicity

The goal of this invention is to overcome the challenges of previous approaches by selectively targeting treatments to the CNS without peripheral toxicity. Kinase inhibition is targeted to the central nervous system (CNS) by combining brain-permeable kinase inhibitors and a brain-impermeable blocking molecule.

Chimeric Kinase Inhibitors with Increased Activity

This invention describes newly generated kinase inhibitors that demonstrate enhanced and attenuated action over their parent kinase inhibitors. These molecules can be used alone but, when combined with novel blocking molecules, the action of these chimeric kinases can be targeted for action in the central nervous system (CNS).

TRM: Mouse Mammary Tumor Virus-PyMT Transgenic Mice

Transgenic mouse models that develop spontaneous mammary adenocarcinomas have proven valuable in revealing molecular mechanisms underlying tumorigenesis and metastasis . Models target specific pathways depending on the transgene being expressed under the control of the mouse mammary tumor virus long terminal repeat (MMTV-LTR) or whey acid protein (WAP) mammary gland promoters and thereby replicate genetic defects in subsets of human tumors.

NOVEL ANTIBODIES AGAINST EPHA2 FOR RESEARCH, DIAGNOSIS, AND TREATMENT OF CANCER

A novel monoclonal human antibody specific to the cell-surface exposed protein EphA2, which is over-expressed in many forms of cancer and is a validated therapeutic target.

TRM:Murine Pancreatic Cancer Cell Lines

Brief description not available

Strategy for in vivo Depalmitoylation of Proteins and Therapeutic Applications Thereof

The neuronal ceroid lipofuscinoses (NCLs), commonly grouped together as Batten disease, are the most common neurodegenerative lysosomal storage diseases of the pediatric population. No cure for NCL has yet been realized. Current treatment regimens offer only symptomatic relief and do not target the underlying cause of the disease. Although the underlying pathophysiology that drives disease progression is unknown, several small molecules have been identified with diverse mechanisms of action that provide promise for the treatment of this devastating disease. On this point, several researchers have reported the use of potential drugs for NCL patient lymphoblasts and fibroblasts, along with neurons derived from animal models of NCL disease. Unfortunately, most of these studies were inconclusive or clinical trials or follow-up results were not available. High concentrations employed and toxicity of the small molecules are clear disadvantages to the use of some of the corresponding derivatives as potential drugs. To circumvent these effects, development of nontoxic alkyl cysteines would be useful for the non-enzymatic and chemo-selective depalmitoylation of S-palmitoyl proteins, which hold good promise as an effective treatment for neuronal ceroid lipofuscinoses.

Probe Immune Checkpoint Self-Cancellation Using Reconstitution Method

Programmed cell death protein 1 (PD-1), is a protein found on the surface of cells that has a role in regulating the immune system's response to the cells of the human body by down-regulating the immune system and promoting self-tolerance by suppressing T cell inflammatory activity. This prevents autoimmune diseases, but it can also prevent the immune system from killing cancer cells.   PD-1 is an immune checkpoint and guards against autoimmunity through two mechanisms. First, it promotes apoptosis (programmed cell death) of antigen-specific T-cells in lymph nodes. Second, it reduces apoptosis in regulatory T cells (anti-inflammatory, suppressive T cells)The PD-1 pathway, consisting of the co-inhibitory receptor PD-1 on T cells and its ligand (PD-L1) on antigen-presenting cells (APCs), is a major mechanism of tumor immune evasion. PD-1 and PD-L1 blockade antibodies have produced remarkable clinical activities against a subset of cancers. Binding between T cell-intrinsic PD-1 and APC-intrinsic PD-L1 triggers inhibitory signaling to attenuate the T cell response.   It is challenging to determine whether PD-L1 and PD-1 bind in cis on the same cell membrane, and if so, what is the functional consequence. This is because of the co-existence of cis and trans interactions at the cell–cell interface. Methods to decouple cis and trans-interactions are urgently needed.

Identification of a New Molecular Target and Methods for Treating Pancreatic Cancer

Pancreatic cancer is an aggressive disease with limited treatment options and a high mortality rate. Pancreatic cancer is the 3rd leading cause of cancer death in the United States; despite some recent advances in systemic therapy, survival remains dismal in large part due to its profound drug resistance and its propensity for early metastasis. Typically, diagnosis of pancreatic cancer occurs only with advanced stages of the disease since there are currently no early markers for detection. Individuals with pancreatic cancer have a poor prognosis due to the late diagnosis, the extent of metastasis, and ineffective treatments. Survival rates are dismal, with a one-year survival rate of 25% and a 5-year survival rate of 6%. Currently, approximately 20% of pancreatic cancer patients are able to undergo the Whipple procedure; this surgical procedure involves removal of the affected portion of the pancreas, leading to an increased survival rate. However, the remaining 80% of pancreatic cancer patients cannot undergo this treatment because their tumors or the extent of metastasis are too severe. In addition, pancreatic cancer is not typically responsive to radiation and chemotherapy. An alternative approach for the treatment of pancreatic cancer is a complete pancreatectomy followed by continual supplementation with digestive enzymes and insulin. Thus, more effective drugs are needed to increase the survival rate of pancreatic cancer patients. Targeting RORγ may lead to the design of a new class of therapeutics that can be used to treat this devastating disease.

Clinical Prognostication Test In Uveal Melanoma

Uveal melanoma commonly known as ocular or choroidal melanoma, is a rare cancer of the eye. It is an intraocular malignancy that arises from melanocytes of the choroid, ciliary body, and iris of the eye. Ocular melanoma is diagnosed in approximately 2,000-2,500 adults annually in the United States. In both the U.S. and Europe, this equates to about 5 - 7.5 cases per million people per year and, for people over 50 years old, the incidence rate increases to around 21 per million per year. While the primary tumor is highly treatable, about half of the patients will develop metastasis —typically to the liver. Metastatic disease is universally fatal. While traditional staging methods such as tumor size and location, still play a role in assessing metastatic risk, they are rarely used to individualize patient management plans. Newer methods include chromosomal gene expression analysis, yet these methods have their technical limitations. Clearly, what is needed is a better, cheaper and reproducible prognostic test.

Small Molecules Against IRE1 To Prevent Pd-L1 Upregulation

The strategy to treat cancer by modulating the immune response has been the subject of research for the last twenty years, including the use of vaccines or activating cytokine therapies. Recently, in the last few years, a breakthrough was achieved by the discovery of immune checkpoints, particularly the cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programed cell death receptor-1 (PD-1), or programed cell death ligand-1 (PD-L1).   The blockade of the pathway for PD-L1 and PD-1 has been used therapeutically for the treatment of a variety of cancers and has achieved long-term remissions in some patients and there are a number of active clinical trials ongoing that target PD-1 and PD-L1. However, a number of cancers are resistant to checkpoint inhibitor-based immunotherapy. The majority of the drugs used for the blockade of the PD-1 and PD-L1 pathways are humanized antibodies. The fact that there have been immune related toxicities associated with PD pathway blockade using the current technologies suggests that an alternative approach may be necessary.

HSC-Engineered Off-The-Shelf iNKT Cell Therapy For Cancer

UCLA researchers in the Department of Microbiology, Immunology, and Molecular Genetics, and the Department of Pathology & Laboratory Medicine have developed novel methods to produce invariant natural killer T (iNKT) cells from hematopoietic stem cells (HSCs) at high efficiency and yield for the development of off-the-shelf universal HSC-engineered iNKT cell therapy for cancer.

“Polyp-Print”: A Methodology To Identify Which Colon Polyps Are Likely To Proceed To Colorectal Cancers

Colorectal cancer (CRC) is the second leading cause of cancer deaths in men and women combined in the United States, according to the American Cancer Society. Every day, patients undergo routine screening colonoscopies around the world for assessment of their risk of CRC. CRCs always arise from precursor lesions, called polyps. Since most patients with polyps are asymptomatic, tracking these lesions through fecal occult blood, rectosigmoidoscopy and colonoscopy enables the suspicion, detection and removal of the lesion. Since 2000, colonoscopy has become the most important examination to track polyps and CRC. Nowadays, in the USA, one out of four colonoscopies aim to track polyps. Besides detecting polyps, their removal through endoscopic polypectomy has proved to be effective to reduce the incidence of this tumor. Anatomopathological analysis enables the histological classification of adenomas, and also allows checking for dysplasia or neoplasm, as well as vascular and/or lymphatic invasion. This assessment determines if polypectomy and/or mucosectomy were effective to heal the patient who presented with polyp or CRC, or if therapeutics will be necessary. Typically, screening colonoscopies begin at age 50, and are done every 10 years. If polyps are encountered, based on their size and number and location, the risk is determined to be high vs low (completely arbitrarily, with no molecular basis at all). Bottomline, right now, there is no way to tell which polyp will become a cancer and which will not. Hence, some patients may be receiving over Rx and some may be under Rx. Clearly, what is needed is an invention that can predict the timing and consequences of multiple host events during CRC initiation and progression.

Method for the detection of specific cells in bodily fluids with a small fluorescent probe

Using standard cellular biology techniques, researchers at UCI have developed a method for detecting the cellular components of blood easily, cheaply, and quickly with accurate quantification using fluorescence techniques.

Novel Protease for Oncology and Inflammatory Diseases

The technology is a novel protease that reduces the ability of cells to respond to the inflammatory cytokine Tumor Necrosis Factor (TNF). High TNF levels have been linked to rheumatoid arthritis, Crohn’s disease and many types of cancers.

4D-seq: Single Cell RNA-sequencing with in situ Spatiotemporal Information

To develop a novel imaging-based single cell RNA-sequencing (scRNA-Seq) platform that allows capturing of spatiotemporal information and cellular behavior of the sequenced cells within tissue.

Very-Small-Nuclear Circulating Tumor Cell (vsnCTC) as a Diagnostic Biomarker of Visceral Metastasis in Advanced Prostate Cancer

UCLA researchers in the Department of Molecular and Medical Pharmacology have identified a novel biomarker that can be used to diagnose prostate cancer patients for the presence of visceral metastasis with 54% sensitivity and 100% specificity.

An Algorithm For Automatic Histologic Grading Of Prostate Cancer

UCLA researchers in the Departments of Radiological Sciences and Pathology and Laboratory Medicine have developed a novel computer-aided diagnostic tool for histologic grading of prostate cancer.

Plod3-Targeted Anti-Cancer Treatment

UCLA researchers in the department of Dentistry have developed a novel anti-cancer treatment that directly targets enzyme expression necessary to sustain cancer growth.

Novel Methods To Enhance Immunity

Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Previous studies on tumor inflammation revealed that immune cell adhesion receptors play unique but critical roles during tumor progression. CD11b/CD18 has been shown to mediate macrophage adhesion, migration, chemotaxis and accumulation during inflammation. Accordingly, a need exists for novel methods of treating cancer that utilize the role that integrin CD11b plays during inflammation.

Carborane-Based Histone Deacetylase (HDAC) Inhibitors

UCLA researchers from the Department of Chemistry & Biochemistry have developed a new class of Histone Deacetylase (HDAC) inhibitors that can be tuned for isoform specificity and other properties.

Metabolite-Responsive Hybrid Biomaterials

Researchers have developed a “smart” biomaterial for drug delivery systems capable of responding to signature cancer metabolite concentrations in tumor environments. This response triggers the release of encapsulated drugs at a specific tumor target.

Protein Nanoparticles For Cancer Immunotherapy

Though new therapeutics for the treatment of cancer are constantly being developed, they often show low efficiency for long-term remission, adverse side effects, and low immune response. Scientists at UCI have found a way to combat these issues with a combination therapy delivered by nanoparticle of both a vaccine, to prime the immune system, and a checkpoint inhibitor to shut down anti-cancer immune responses. This has been shown to prolong survival and promote immune response and immunological memory related to long-term survival.

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