A5030923245- Renal cell carcinoma treatment
- Renal and related cancers
- Renal Diseases and Glomerulopathies
- Cancer Immunotherapy and Biomarkers
- Computational Drug Discovery Methods
- Cancer-related Molecular Pathways
- BRCA gene mutations in cancer
- Nutrition, Genetics, and Disease
- CAR-T cell therapy research
- Cancer, Hypoxia, and Metabolism
- Metabolism, Diabetes, and Cancer
- Cancer, Lipids, and Metabolism
- Estrogen and related hormone effects
- Science, Research, and Medicine
- Monoclonal and Polyclonal Antibodies Research
- Medication Adherence and Compliance
- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Radiation Therapy and Dosimetry
- HIV/AIDS drug development and treatment
- Telomeres, Telomerase, and Senescence
- Menopause: Health Impacts and Treatments
AstraZeneca (United States)
2019-2024
Center for Cancer Research
2016-2020
National Cancer Institute
2013-2020
AstraZeneca (Japan)
2020
AstraZeneca (Netherlands)
2019
George Washington University
2016-2018
Division of Cancer Epidemiology and Genetics
2016
NRG Oncology
2015
Allegheny General Hospital
2015
National Institutes of Health
2013-2015
Li-Fraumeni syndrome (LFS) is a cancer predisposition disorder caused by germline mutations in TP53 that can lead to increased mitochondrial metabolism patients. However, the implications of altered function for tumorigenesis LFS are unclear. Here, we have reported genetic or pharmacologic disruption respiration improves cancer-free survival mouse model expresses mutant p53. Mechanistically, inhibition autophagy and decreased aberrant proliferation signaling In pilot study, patients treated...
Background MEDI9197 is an intratumorally administered toll-like receptor 7 and 8 agonist. In mice, modulated antitumor immune responses, inhibited tumor growth increased survival. This first-time-in-human, phase 1 study evaluated with or without the programmed cell death ligand-1 (PD-L1) inhibitor durvalumab and/or palliative radiation therapy (RT) for advanced solid tumors. Patients methods Eligible patients had at least one cutaneous, subcutaneous, deep-seated lesion suitable intratumoral...
Tamoxifen provides a 50% reduction in the incidence of breast cancer (BC) among high-risk women, yet many do not adhere to five-year course therapy. Using prospective double-blind National Surgical Adjuvant Breast and Bowel Project P-1 study, we evaluated whether participant-reported outcomes were associated with drug adherence baseline behavioral risk factors modified those associations. participants randomly assigned placebo vs tamoxifen (20mg/day). Mixed effects logistic regression was...
The safety, efficacy, pharmacokinetics, and pharmacodynamics of the anti-programmed cell death-1 antibody MEDI0680 were evaluated in a phase I, multicenter, dose-escalation study advanced solid malignancies. was administered intravenously once every 2 weeks (Q2W) or 3 at 0.1, 0.5, 2.5, 10 20 mg/kg. Two cohorts received mg/kg week for 4 weeks, then Q2W. All treated 12 months until progression. primary endpoint safety. Secondary endpoints efficacy pharmacokinetics. Exploratory included...
A few dietary studies have found elevated testicular cancer risks for higher red meat, fat, and milk intakes lower of fruits, vegetables, fiber. Because hormonal modulation by intake plant estrogens could affect risk cancer, we chose to explore the possible relationship between phytoestrogens cancer. We conducted a hospital-based case-control study 159 cases diagnosed 1990 1996 136 adult friend-matched controls at University Texas M. D. Anderson Cancer Center. Amounts phytoestrogenic...
Abstract Purpose: MEDI0680 is a humanized anti–programmed cell death-1 (PD-1) antibody, and durvalumab an anti-PD-L1 antibody. Combining treatment using these antibodies may improve efficacy versus blockade of PD-1 alone. This phase II study evaluated antitumor activity safety plus nivolumab monotherapy in immunotherapy-naïve patients with advanced clear-cell renal carcinoma who received at least one prior line antiangiogenic therapy. Patients Methods: either (20 mg/kg) (750 mg) or (240 mg),...
Genetic testing for inheritable cancer syndromes is becoming a critical part of preventive health services. The Patient Protection and Affordable Care Act (PPACA) Essential Health Benefits package addresses breast susceptibility-gene women who are unaffected by cancer. absence provisions 1) men, 2) patients, 3) other syndromes, 4) risk-reducing interventions limitations PPACA. We discuss PPACA pertaining to genetic effects on high-risk populations, in particular minorities. the beginning an...
MEDI2228 is an antibody drug conjugate (ADC) comprised of a fully human B-cell maturation antigen (BCMA) conjugated to pyrrolobenzodiazepine (PBD) dimer. This phase 1 trial evaluated in patients with relapsed/refractory (R/R) multiple myeloma (MM), who received prior treatment approved agents from 3 classes antimyeloma drugs (proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies). Primary endpoint was safety tolerability; secondary endpoints included efficacy,...
Abstract Background Li-Fraumeni syndrome (LFS) is a highly penetrant autosomal dominant cancer predisposition disorder caused by germline TP53 pathogenic variants. Patients with LFS have increased oxidative phosphorylation capacity in skeletal muscle and stress blood. Metformin inhibits phosphorylation, reducing available energy for cell proliferation decreasing production of reactive oxygen species that cause DNA damage. Thus, metformin may provide pharmacologic risk reduction patients LFS,...
1556 Background: LFS is a highly-penetrant, autosomal dominant, cancer predisposition disorder characterized by early onset cancer; germline mutations in TP53are present 70% of LFS. We previously observed metformin inhibition on mitochondrial function patients. Metformin may reduce TCA cycle and glycolytic intermediates during cellular transformation, indicating complex I the mitochondria. To further explore this, we performed untargeted metabolomics profiling stored serum study...
1501 Background: Tamoxifen (T) is underutilized as a chemopreventive agent for breast cancer (BC), despite 50% reduced risk of developing in high women with use T vs. placebo (P). Vasomotor symptoms (VS - hot flashes, night sweats, cold sweats) were the most frequently cited reasons stopping tamoxifen P-1 study and occurred arm. BMI may modify experience vasomotor women, higher associated worse symptoms. Methods: 13,388 at BC randomly assigned to (20 mg/day) P from June 1992 September 1997....
Abstract Purpose: This phase I chemoprevention pilot study in LFS patients will: 1) assess tolerability of 2000 mg/day oral metformin with LFS, 2) the effect on circulating serum insulin biomarkers, and 3) use non-invasive technology to hepatic skeletal muscle mitochondria these patients. Background: is a highly-penetrant, autosomal dominant, cancer predisposition disorder characterized by early onset spectrum cancers. Approximately 70% “classic” families have germline TP53 mutations....
Abstract Numerous observational studies have reported decreased cancer incidence and cancer-related mortality in patients with diabetes receiving standard doses of metformin. A recent meta-analysis these suggested a 31% reduction overall incidence, summary relative risk (0.69; 95% confidence interval, 0.52-0.90), subjects taking metformin as compared other antidiabetic drugs. Separate meta-analyses that adjusted for BMI or time-related bias an attenuation this signal, but still showed...
1512 Background: Despite a 50% reduction in the risk of breast cancer (BC) for tamoxifen (T) vs. placebo (P), many women at BC do not adhere to 5 year course. Using prospectively-collected data from double-blind NSABP P-1, we evaluated whether patient-reported outcomes were associated with drug adherence, and baseline behavioral factors modified those associations. Methods: 13,338 high randomly assigned T P (20 mg/day); analyzed 11,064 enrolled more than 3 years before trial unblinding 5/98....
Abstract Background: Metformin is FDA approved for the treatment of type II diabetes. Frequently reported side effects metformin use in diabetics are abdominal cramping, nausea, and diarrhea. Lactic acidosis, a life-threatening accumulation lactic acid blood, also potential adverse effect metformin. The primary goal this phase I study was to assess safety tolerability non-diabetic patients with germline mutations TP53 clinical diagnosis LFS. LFS highly-penetrant, autosomal dominant, cancer...
Abstract Introduction: Li-Fraumeni Syndrome (LFS) is a hereditary cancer predisposition syndrome causing range of cancers across the lifespan. About 70% families meeting classical LFS criteria have detectable germline mutations in TP53 gene, vs 40% those classified as Li-Fraumeni-like (LFL). The psychological, social, and behavioral issues faced by individuals with LFS/LFL their relatives comprise an important, but under-studied, topic. Methods: Ours prospective, cohort study LFS/LFL....
Supplementary Figure from A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy Patients Advanced or Metastatic Clear-cell Renal Cell Carcinoma