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Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester Apr 2024

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …


Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz Apr 2024

Discovery Of A Small-Molecule Inhibitor That Traps Polθ On Dna And Synergizes With Parp Inhibitors, William Fried, Mrityunjay Tyagi, Leonid Minakhin, Gurushankar Chandramouly, Taylor Tredinnick, Mercy Ramanjulu, William Auerbacher, Marissa L Calbert, Timur Rusanov, Trung Hoang, Nikita Borisonnik, Robert Betsch, John Krais, Yifan Wang, Umeshkumar Vekariya, John Gordon, George Morton, Tatiana Kent, Tomasz Skorski, Neil Johnson, Wayne Childers, Xiaojiang Chen, Richard Pomerantz

Department of Biochemistry and Molecular Biology Faculty Papers

The DNA damage response (DDR) protein DNA Polymerase θ (Polθ) is synthetic lethal with homologous recombination (HR) factors and is therefore a promising drug target in BRCA1/2 mutant cancers. We discover an allosteric Polθ inhibitor (Polθi) class with 4-6 nM IC50 that selectively kills HR-deficient cells and acts synergistically with PARP inhibitors (PARPi) in multiple genetic backgrounds. X-ray crystallography and biochemistry reveal that Polθi selectively inhibits Polθ polymerase (Polθ-pol) in the closed conformation on B-form DNA/DNA via an induced fit mechanism. In contrast, Polθi fails to inhibit Polθ-pol catalytic activity on A-form DNA/RNA in which the enzyme binds in …


Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe Mar 2024

Remodeling Anaplastic Thyroid Cancer's Aggressive Profile And Metabolic Signature By Natural Alkaloid Berberine, Tara Elizabeth Jarboe

NYMC Student Theses and Dissertations

Anaplastic thyroid cancer is a rare, fatal cancer with a five-year survival of 4%. Universally diagnosed at stage IV, anaplastic thyroid cancer is characterized by its lack of differentiation, rapid proliferative rate, highly inflammatory tumor microenvironment, and metabolic dysregulation. Refractory to all established therapies, anaplastic thyroid cancer requires a novel therapeutic approach that targets all of these drivers of anaplastic thyroid cancer carcinogenesis. We propose natural alkaloid berberine as a therapeutic with multitarget efficacy to alter mitochondrial metabolism and reprogram anaplastic thyroid cancer’s aggressive phenotype. Our in vitro model uses monocyte cell line U937, anaplastic thyroid cancer cell lines T238 …


The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Eric Venner, Karynne Patterson, Divya Kalra, Marsha M Wheeler, Yi-Ju Chen, Sara E Kalla, Bo Yuan, Jason H Karnes, Kimberly Walker, Joshua D Smith, Sean Mcgee, Aparna Radhakrishnan, Andrew Haddad, Philip E Empey, Qiaoyan Wang, Lee Lichtenstein, Diana Toledo, Gail Jarvik, Anjene Musick, Richard A Gibbs Feb 2024

The Frequency Of Pathogenic Variation In The All Of Us Cohort Reveals Ancestry-Driven Disparities, Eric Venner, Karynne Patterson, Divya Kalra, Marsha M Wheeler, Yi-Ju Chen, Sara E Kalla, Bo Yuan, Jason H Karnes, Kimberly Walker, Joshua D Smith, Sean Mcgee, Aparna Radhakrishnan, Andrew Haddad, Philip E Empey, Qiaoyan Wang, Lee Lichtenstein, Diana Toledo, Gail Jarvik, Anjene Musick, Richard A Gibbs

Journal Articles

Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups …


Correlation Between Salivary Levels And Tissue Expression Status Of Her2 In Breast Cancer Patients - A Cross-Sectional Study, Arthi Sri A.S, Massillamani F, Vinothkumar Thilla Sekar Feb 2024

Correlation Between Salivary Levels And Tissue Expression Status Of Her2 In Breast Cancer Patients - A Cross-Sectional Study, Arthi Sri A.S, Massillamani F, Vinothkumar Thilla Sekar

Annual Research Symposium

The study aims to investigate if soluble salivary human epidermal growth factor receptor-2 (HER2) would play a role in the diagnosis of breast cancer patients and also to find out the influence of demographic and hormonal factors on the salivary HER2 levels in breast cancer.


Alopecia As An Early Clinical Marker For Azathioprine Induced Myelosuppression: A Case Report, Nilanjana Dutta , Final Year Mbbs, Dr. M Suresh Babu , Professor, Dr. Subramanian Ramaswamy , Professor, Dr. Mahabaleshwar Mamadapur , Assistant Professor Jan 2024

Alopecia As An Early Clinical Marker For Azathioprine Induced Myelosuppression: A Case Report, Nilanjana Dutta , Final Year Mbbs, Dr. M Suresh Babu , Professor, Dr. Subramanian Ramaswamy , Professor, Dr. Mahabaleshwar Mamadapur , Assistant Professor

Digital Journal of Clinical Medicine

Azathioprine is a pro-drug and is metabolized by the TPMT enzyme in the body. In South Asians, Azathioprine is known to cause alopecia and bone marrow suppression in patients with TPMT enzyme deficiency. In India, the prevalence of TPMT mutation varies from 1.2- 10%. A new mutation was detected in 2014, NUDT15 whose incidence varies from 8.5-16%. Patients with mutation in both TPMT and NUDT15 develop myelosuppression faster. In our case, alopecia manifested as the first clinical feature of Azathioprine myelosuppression. Physicians need to recognize early clinical clues (alopecia) to avoid the impending development of myelosuppression and to look for …