A5068141849- Synthesis and biological activity
- Synthesis of Tetrazole Derivatives
- PI3K/AKT/mTOR signaling in cancer
- Cancer Genomics and Diagnostics
- Melanoma and MAPK Pathways
- Advanced Breast Cancer Therapies
- Trace Elements in Health
- Genetic factors in colorectal cancer
- BRCA gene mutations in cancer
- Cancer-related Molecular Pathways
- DNA Repair Mechanisms
- Plant Micronutrient Interactions and Effects
- Synthesis and Characterization of Heterocyclic Compounds
- Nutrition, Genetics, and Disease
- Synthesis of Organic Compounds
- Estrogen and related hormone effects
- Cancer-related cognitive impairment studies
- Ovarian cancer diagnosis and treatment
- Computational Drug Discovery Methods
- Occupational and environmental lung diseases
- Chronic Lymphocytic Leukemia Research
- Child Nutrition and Water Access
- Iron Metabolism and Disorders
- Multiple and Secondary Primary Cancers
- Colorectal Cancer Treatments and Studies
Memorial Sloan Kettering Cancer Center
2013-2024
Kettering University
2013-2024
Cornell University
2013-2023
Pediatrics and Genetics
2023
The effects of selective phosphoinositide 3-kinase (PI3K) and AKT inhibitors were compared in human tumor cell lines which the pathway is dysregulated. Both caused inhibition AKT, relief feedback receptor tyrosine kinases, growth arrest. However, only PI3K rapid induction death. In seeking a mechanism for this phenomenon, we found that inhibition, but not causes wild-type RAS RAF-MEK-ERK signaling. Inhibition RAS-ERK signaling transient, rebounding few hours after drug addition, required...
1. Male hooded Lister rats given a diet containing 40 mg zinc/kg were described as Zn-adequate. Other subsequently diets less than 1 Zn/kg. After period of approximately 5 d these animals ceased to grow and Zn-deficient. 2. Zn-deficient offered ad lib. 200 g egg albumen/kg ate only 55% the weight eaten by Zn-adequate similar supplemented with Zn. The intake deficient increased when metabolizable energy content was decreased also environmental temperature lowered. 3. showed high day-to-day...
Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority patients experience long-term disease control. Using large, clinically annotated cohort with metastatic hormone receptor-positive (HR+) cancer, we identify TP53 loss (27.6%) and MDM2 amplification (6.4%) be associated lack Human cancer models reveal that p53 does not alter activity or G1 blockade but instead promotes drug-insensitive p130 phosphorylation by CDK2. The persistence...
1. Both albumin and transferrin have been suggested as carriers of zinc in plasma. Their relative importance Zn transport was therefore investigated a preliminary to study the rates passage through 2. The apparent log stability constant for binding human apotransferrin at pH 7.4 estimated be approximately 5.9 which is substantially lower than previous reports 7.0 corresponding value (Giroux & Henkin, 1972). 3. When abilities compete with low-molecular-weight chelators were compared same...
Abstract Background: Germline genetic alterations are established mediators of breast carcinogenesis, often giving rise to specific forms genomic instability. BRCA1/2 pathogenic variants (PVs) emblematic this phenomenon through their induction homologous recombination deficiency. While patterns instability may sensitize cancers therapies such as PARP inhibitors (PARPi) or platinum chemotherapy, implications for lineage-directed endocrine therapy (ET) CDK4/6 (CDK4/6i) unknown. Herein, we...
The co-occurrence of germline and somatic oncogenic alterations is frequently observed in breast cancer, but their combined biologic clinical significance has not been evaluated. To assess the role germline-somatic interactions on outcomes routine practice, we developed an integrated clinicogenomic pipeline to analyze genomes over 4,500 patients with cancer. We find that (g)
We sought to determine the prevalence of germline pathogenic variants (gPVs) in unselected patients with endometrial cancer (EC), define biallelic gPVs within tumors, and describe their associations clinicopathologic features.
1. 65 Zn uptake by blood cells in vitro has been compared with plasma concentration and alkaline phosphatase ( EC 3.1.3.1) activity as indicators of an animal's status. 2. Dietary deficiency, low food intake, reduced dietary protein content endotoxin administration all the rat. In each case there was a parallel reduction increase whole blood. 3. A similar relationship between three measurements existed sheep lowered concentrations whether these were caused deficiency or post-surgical stress....
To evaluate rates of germline pathogenic/likely pathogenic variants (PVs) and genetic counseling by ancestry in patients with epithelial ovarian cancer (EOC).
1. The rates of transport zinc through plasma have been investigated in normal and endotoxin-stressed pigs. 2.65Zn added to porcine vitro rapidly equilibrated with the Zn originally present. 3. 65 bound albumin injected intravascularly into pigs two kinetically distinguishable pools. first these pools was mainly associated but significantly larger than volume substantially so Zn-deficient second pool appeared represent a summation rapidly-exchangeable within extravascular tissues. 4. In...
Abstract Background: Inhibition of CDK4/6 kinases has led to improved clinical outcomes in hormone receptor positive (HR+) breast cancer. While these are highly effective therapies, only a minority patients experience long-term disease control. We sought determine the genomic configurations and underlying mechanisms associated with response. Methods: To identify patterns outcomes, we analyzed cohort 447 metastatic HR+ cancer treated at MSK first-line inhibitors (CDK4/6i) for which...
BAP1-Tumor Predisposition Syndrome (TPDS) is caused by germline variants in BAP1 and predisposes to solid tumors. After observation of a radiologically malignant-appearing splenic mass with benign pathology patient BAP1-TPDS, we sought retrospectively characterize lesions individuals BAP1-TPDS seen at comprehensive cancer center. A dedicated radiology review for abnormalities was performed. We identified 37 81% history cancer. Of 33 abdominal imaging, 10 (30%) had lesions, none were shown be...
Abstract Inhibition of CDK4/6 kinases has led to improved outcomes in breast cancer. Nevertheless, only a minority patients experience long-term disease control. Using clinically-annotated cohort with metastatic HR+ cancer, we identified TP53 loss (28.8%) and MDM2 amplification (6.7%) be associated lack Human cancer models revealed that p53 did not affect activity or G1-blockade, but instead promoted drug-insensitive p130 phosphorylation by CDK2. Persistence phospho-p130 prevented DREAM...
1. Deficiency of zinc inhibits growth and also increases the activity alkaline ribonuclease in certain tissues rat (Prasad & Oberleas, 1973). Zn could influence by direct effects on enzyme or its natural inhibitor, non-specifically as occurs when rate is affected various other factors. These possibilities were studied. 2. Alkaline was shown to be inhibited vitro, but concentrations required so high that probably not directly changes tissue concentration caused dietary deficiency. 3. At lower...
10510 Background: For most solid tumors, early age of onset, a marker for potential increased inherited risk, has been arbitrarily defined as diagnosis cancer at < 50. However, this disregards the variation in mean diagnoses across tumors resulting misclassification patients risk germline alterations. Methods: 25,305 prospectively ascertained patients, representing 32 tumor types, underwent sequencing analysis up to 90 predisposition genes using next-generation genetic with reporting...
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Abstract Background: Activation of PI3K alpha is among the most frequent oncogenic events in breast transformation, commonly occurring through mutations p110 subunit or amplification HER2 receptor tyrosine kinase. Therapeutic targeting activated signaling has been made feasible by development highly selective and potent ATP competitive inhibitors some which are late stage clinical development. Unfortunately, response to these compounds not seen for majority patients when occurs it often...
Abstract Hyperactivation of the PI3K/AKT/mTOR pathway in tumors causes feedback inhibition throughout signaling network, including receptor tyrosine kinase (RTK) expression and function. Exposure these to mTOR or AKT inhibitors relieves this reactivates RTK signaling. reactivation promotes PI3K activity attenuates antitumor effects drugs. We have now characterized details PI3K-induced using a selective class 1 inhibitor compared its with those elicited by allosteric AKT. In breast cancer...
<p>PDF file 93K, This contains detailed description of experimental procedures as well reagents utilized</p>
<div>Abstract<p>The effects of selective phosphoinositide 3-kinase (PI3K) and AKT inhibitors were compared in human tumor cell lines which the pathway is dysregulated. Both caused inhibition AKT, relief feedback receptor tyrosine kinases, growth arrest. However, only PI3K rapid induction death. In seeking a mechanism for this phenomenon, we found that inhibition, but not causes wild-type RAS RAF–MEK–ERK signaling. Inhibition RAS–ERK signaling transient, rebounding few hours after...