Browsing by Subject "Therapeutic targets"

Now showing 1 - 4 of 4
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    Clinical and Genomic Features of Androgen Indifferent Prostate Cancer
    (MDPI, 2025-01-15) Masur, Jack; Ratan, Aakrosh; Wierbilowicz, Krzysztof; Ayanambakkam, Adanma; Churchman, Michelle L.; Graham, Laura S.; Grass, George Daniel; Gupta, Sumati; Kern, Sean Q.; King, Jennifer; Myint, Zin; Rounbehler, Robert J.; Salhia, Bodour; Singer, Eric A.; Zakharia, Yousef; Paschal, Bryce M.; Viscuse, Paul V.; Medicine, School of Medicine
    Androgen-indifferent prostate cancer (AIPC) is increasingly common and particularly lethal. Data describing these tumors are sparse, and AIPC remains a poorly understood malignancy. Utilizing the Oncology Research Information Exchange Network (ORIEN) database, we enriched for tumors with features of AIPC using previously described characteristics. Our AIPC cohort included three subgroups: aggressive variant prostate cancer (AVPC), neuroendocrine PC (NEPC), and double-negative PC (DNPC). Of 1496 total PC patients available for analysis, we identified 323 (22%) as MCRPC. Of those, 39 (12%) met AIPC criteria (17 AVPC, 13 NEPC, 9 DNPC) and 284 (88%) were non-AIPC. Forty-three percent of AIPC patients had de novo metastatic disease vs. 15% for non-AIPC (p = 0.003). Homologous recombination deficiency (HRD) and tumor mutational burden (TMB) did not differ between cohorts, but microsatellite instability scores (MSI) were significantly higher in AIPC (p = 0.019). Using Gene Set Enrichment Analysis (GSEA), we found that genes defining response to androgens and genes involved in oxidative phosphorylation were the most downregulated, whereas genes involved in epithelial-mesenchymal transition (EMT) and immune signaling were significantly upregulated in AIPC vs. non-AIPC. Our study demonstrates the potential for predefined criteria that aim to enrich for AIPC and suggests opportunities for therapeutic investigation.
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    Hypertension in Chronic Kidney Disease (CKD): Diagnosis, Classification, and Therapeutic Targets
    (Oxford University Press, 2021) Georgianos, Panagiotis I.; Agarwal, Rajiv; Medicine, School of Medicine
    Blood pressure (BP) in the office is often recorded without standardization of the technique of measurement. When office BP measurement is performed with a research-grade methodology, it can inform better therapeutic decisions. The reference-standard method of ambulatory BP monitoring (ABPM) together with the assessment of BP in the office enables the identification of white-coat and masked hypertension, facilitating the stratification of cardiorenal risk. Compared with general population, the prevalence of resistant hypertension is 2- to 3-fold higher among patients with chronic kidney disease (CKD). The use of ABPM is mandatory in order to exclude the white-coat effect, a common cause of pseudoresistance, and confirm the diagnosis of true-resistant hypertension. After the premature termination of Systolic Blood Pressure Intervention Trial due to an impressive cardioprotective benefit of intensive BP-lowering, the 2017 American Heart Association/American College of Cardiology guideline reappraised the definition of hypertension and recommended a tighter BP target of <130/80 mm Hg for the majority of adults with a high cardiovascular risk profile, inclusive of patients with CKD. However, the benefit/risk ratio of intensive BP-lowering in particular subsets of patients with CKD (i.e., those with diabetes or more advanced CKD) continues to be debated. We explore the controversial issue of BP targets in CKD, providing a critical evaluation of the available clinical-trial evidence and guideline recommendations. We argue that the systolic BP target in CKD, if BP is measured correctly, should be <120 mm Hg.
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    Long non-coding RNAs as critical regulators and novel targets in cervical cancer: current status and future perspectives
    (Springer Nature, 2023) Ranga, Shalu; Yadav, Ritu; Chhabra, Ravindresh; Chauhan, Meenakshi B.; Tanwar, Mukesh; Yadav, Chetna; Kadian, Lokesh; Ahuja, Parul; Medicine, School of Medicine
    Cervical cancer is among the leading causes of cancer-associated mortality in women. In spite of vaccine availability, improved screening procedures, and chemoradiation therapy, cervical cancer remains the most commonly diagnosed cancer in 23 countries and the leading cause of cancer deaths in 36 countries. There is, therefore, a need to come up with novel diagnostic and therapeutic targets. Long non-coding RNAs (lncRNAs) play a remarkable role in genome regulation and contribute significantly to several developmental and disease pathways. The deregulation of lncRNAs is often observed in cancer patients, where they are shown to affect multiple cellular processes, including cell cycle, apoptosis, angiogenesis, and invasion. Many lncRNAs are found to be involved in the pathogenesis as well as progression of cervical cancer and have shown potency to track metastatic events. This review provides an overview of lncRNA mediated regulation of cervical carcinogenesis and highlights their potential as diagnostic and prognostic biomarkers as well as therapeutic targets for cervical cancer. In addition, it also discusses the challenges associated with the clinical implication of lncRNAs in cervical cancer.
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    Potential roles of microRNAs and ROS in colorectal cancer: diagnostic biomarkers and therapeutic targets
    (Impact Journals, 2017-03-07) Lin, Jingmei; Chuang, Chia-Chen; Zuo, Li; Pathology and Laboratory Medicine, School of Medicine
    As one of the most commonly diagnosed cancers worldwide, colorectal adenocarcinoma often occurs sporadically in individuals aged 50 or above and there is an increase among younger patients under 50. Routine screenings are recommended for this age group to improve early detection. The multifactorial etiology of colorectal cancer consists of both genetic and epigenetic factors. Recently, studies have shown that the development and progression of colorectal cancer can be attributed to aberrant expression of microRNA. Reactive oxygen species (ROS) that play a key role in cancer cell survival, can also lead to carcinogenesis and cancer exacerbations. Given the rapid accumulating knowledge in the field, an updated review regarding microRNA and ROS in colorectal cancer is necessary. An extensive literature search has been conducted in PubMed/Medline databases to review the roles of microRNAs and ROS in colorectal cancer. Unique microRNA expression in tumor tissue, peripheral blood, and fecal samples from patients with colorectal cancer is outlined. Therapeutic approaches focusing on microRNA and ROS in colorectal cancer treatment is also delineated. This review aims to summarize the newest knowledge on the pathogenesis of colorectal cancer in the hopes of discovering novel diagnostic biomarkers and therapeutic techniques.