作者: Tripathi, Piyush ; Bhatia, Vipul ; Singhai, Atin ; Palanisamy, Nallasivam ; Biswas, Tanay ; Husain, Nuzhat ; Ateeq, Bushra ; Goel, Apul ; Chauhan, Abhishek ; Vats, Pankaj ; Mehrotra, Sanjeev ; Tewari, Anjali ; Ahmad, Manzoor ; Srivastava, Alok

AbstractIn India, prostate cancer (PCa) has the third highest incidence rate among males and is often diagnosed at the advanced stage. PCa is known to be molecularly heterogeneous, and an in-depth characterization of its subtypes by geographical ethnicities may aid in the understanding of its etiology and disparities. Hence, we perform molecular characterization of PCa patients from India. Integrative genomics studies categorized PCa into molecular subtypes based on genetic aberrations (e.g., somatic mutations, INDEL, etc.). Although genetic factors are known to impact PCa pathobiology, genomic profiling of Indian PCa patients and its clinical utility remain largely unexplored. Thus, in a prospective study, we performed whole exome sequencing (WES) of treatment-naive primary PCa (N=90) and benign prostatic hyperplasia specimens (N=14) along with matched blood. Our findings reveal distinct genetic alterations unique to the Indian cohort, wherein an elevated somatic tumor mutational burden and an increased percentage of clinically actionable alterations were noted. About 80% of the somatic variants (called using Mutect2) were found to be missense mutations with a high recurrence of C>T transitions, a signature of age-related human malignancies. Several novel pathogenic alterations affecting critical domains of the cancer-associated genes (e.g., APC, BRCA2, PI3KCA, etc.) were found, which have not been reported in the dbSNP or COSMIC databases. Systematic comparison of our findings with primary PCa data available at The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) revealed distinct genomic alterations in Indian PCa patients: specifically, 35% of the patients showed presumed actionable lesions in the RTK-Ras pathway genes, while 10% had mutations in the PI3K pathway genes, and 21% of all the specimens harbored putative inactivating mutations of genes involved in the homologous recombination repair pathway. We also found major differences in the mutational frequency of some driver genes, such as ATRX, PIK3C2G, TAL1, etc., compared to the TCGA-PRAD cohort. Furthermore, GISTIC2 analysis revealed significant arm-level amplification at 8q (MYC, GLI4), 7q (GNB2, PDIA4), and 16p (TELO2, TSC2) regions and deletion at 8p (NKX3.1, MSR1), 9p (CDKN2A, CDKN2B), and 13q (RB1, BRCA2) regions. We also identified recurrent focal amplifications at 9q, 14q, and 11q, and deletions at 16q, 10q, and 5q loci. Further, integrating WES data with transcriptome data would be helpful in categorizing PCa patients based on gene fusion status and prioritizing functionally impactful and actionable variants. Collectively, our findings reveal molecular heterogeneity among PCa patients from India, leading to the identification of clinically relevant candidates that need to be further validated and would help in strategizing therapies and clinical management of this disease.Citation Format:Tanay Biswas, Pankaj Vats, Vipul Bhatia, Atin Singhai, Alok Srivastava, Abhishek Chauhan, Manzoor Ahmad, Piyush Tripathi, Sanjeev Mehrotra, Anjali Tewari, Nuzhat Husain, Apul Goel, Nallasivam Palanisamy, Bushra Ateeq. The landscape of somatic mutations and copy-number alterations in the Indian Cohort of Prostate Cancer Patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5351.

2025-04-21·Cancer Research

Abstract 6805: DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis

作者: Khan, Umar Khalid ; Bajpai, Anjali ; Carskadon, Shannon ; Tewari, Anjali ; Ateeq, Bushra ; Chaudhary, Nazia ; Palanisamy, Nallasivam ; Nigam, Shivansh ; Chandra, Abhijit ; Shendre, Akshay ; Goel, Ayush ; Dalal, Sorab N. ; Kapoor, Abhimanyu ; Praveen, Ayush

AbstractColorectal cancer (CRC) is the second most frequent lethal malignancy globally. It has been associated with limited treatment effectiveness in most cases, leading to modest clinical outcomes with first-line therapies. Despite the recent advancements in the treatment modalities, most patients fail to respond by switching to alternative bypass mechanisms and acquiring drug resistance. This emphasizes an urgent need to discover the underlying mechanistic circuitry in CRC pathogenesis and explore alternative robust drug targets to overcome the lack of treatment response thereby improving the patient's survival. In addition, molecular heterogeneity associated with tumor profiles also influences treatment outcomes, prompting a fundamental need for molecular characterization of colorectal tumors to design targeted therapies. Here, we used a bottom-up approach to delineate the clinical significance of Dyskerin pseudouridine synthase 1 (DKC1) in CRC patients. We observed elevated DKC1 levels in tumor specimens compared to adjacent normal tissue, associated with aggressive disease and poor recurrence-free survival. Moreover, patients acquiring resistance against standard treatment regimen (FOLFOX/FOFIRI) showed increased expression of DKC1. Importantly, loss-of-function studies suggest high DKC1 imparts oncogenicity by promoting cell cycle progression, suppressing cell death, and conferring stem cell-like phenotype. Notably, gene signature profile from DKC1-high patient tumors exhibit similarity to Consensus Molecular Subtype 2 (CMS2) of CRC. We deciphered a positive feedback loop operating between canonical WNT signaling and DKC1, responsible for orchestrating DKC1 expression and its associated tumorigenicity. Comprehensive lipidomic and transcriptomic analyses reveal perturbed sphingolipid metabolism and an abundance of very-long-chain fatty acid ceramides, particularly Cer(d18:2/23:0) and Cer(d18:1/24:0) in DKC1-positive CRC. Mechanistically, Co-IP and ChIP-PCR results confirmed that DKC1 and SOX2 together drive the expression of SGPP2, modulating sphingolipid biosynthesis and targeting SGPP2 in DKC1-positive CRC alleviates oncogenic properties. Taken together, we demonstrate that elevated DKC1 expression imparts chemoresistance, and pharmacological inhibition of DKC1 and WNT signaling effectively attenuates the growth of therapy-resistant patient-derived organoids as well as CRC cells in a synergistic manner. Conclusively, we propose the DKC1/WNT axis as a promising therapeutic target for chemotherapy non-responding CRC patients. The study also highlights the utility of complex sphingolipids as a plasma-based biomarker providing a new paradigm for the non-invasive diagnosis of advanced-stage CRC patients.Citation Format:Umar Khalid Khan, Ayush Goel, Shivansh Nigam, Nazia Chaudhary, Anjali Bajpai, Ayush Praveen, Akshay Shendre, Shannon Carskadon, Abhimanyu Kapoor, Anjali Tewari, Abhijit Chandra, Sorab N. Dalal, Nallasivam Palanisamy, Bushra Ateeq. DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6805.

2025-04-01·Urologic Oncology: Seminars and Original Investigations

The use of nephron-sparing intervention does not appear to be compromised after a period of active surveillance for patients with cT1 renal masses

Article

作者: Wang, Michael ; Goorman, Samuel ; Rogers, Craig G ; Ginsburg, Kevin ; Vercnocke, Jack ; Van Til, Monica ; McElroy, Andrew ; Maatman, Thomas ; Kozminski, Michael ; Lane, Brian R ; Moser, Ana Maria ; Mirza, Mahin ; Wilke, Aaron ; Semerjian, Alice

INTRODUCTION AND OBJECTIVEIt remains unknown whether the use of nephron sparing intervention (NSI) is impacted with delayed intervention after a period of active surveillance (AS) compared with immediate intervention for patients with clinically localized renal masses ≤7cm (cT1RMs). We hypothesized that the proportion of patients undergoing NSI is similar among patients undergoing immediate and delayed intervention for cT1RMs.METHODSWe retrospective reviewed the prospectively maintained Michigan Urological Surgery Improvement Collaborative (MUSIC) registry for patients undergoing intervention for cT1RMs from 05/2017 to 09/2023. The primary outcome was type of treatment received: radical nephrectomy (RN) or NSI (partial nephrectomy, ablation, or stereotactic body radiation therapy). The main independent variable was timing of treatment: immediate (treatment within 90 days) vs. delayed intervention (>90 days). We fit a mixed-effects multivariable logistic regression model to assess for the adjusted association of immediate vs delayed intervention with the receipt of NSI and estimate an adjusted probability of NSI.RESULTSWe identified 2,156 patients, of whom 93% underwent immediate intervention and 7% underwent a period of AS prior to delayed intervention. Median time from initial visit to intervention was 1.4 (IQR 0.9-2.0) and 13 (IQR 7.7-21) months in the immediate vs delayed intervention groups, respectively. In the multivariable model, we did not appreciate a significant association between delayed intervention with receipt of NSI (OR 0.99, 95% CI 0.57-1.70, P >0.9). The adjusted proportion of NSI was 75% and 78% for patients in the immediate and delayed intervention cohorts, respectively.CONCLUSIONPatients undergoing delayed intervention after AS had similar use of NSI compared with those undergoing immediate intervention. Active surveillance for patients with cT1RMs does not appear to compromise the ability to perform nephron sparing interventions.

项与 Vattikuti Urology Institute 相关的新闻（医药）

2024-08-12

·Business Wire

Sara Q. Perkins, M.D., Joins Central Ohio Urology Group, an Affiliate of U.S. Urology Partners

COLUMBUS, Ohio--( BUSINESS WIRE )-- Central Ohio Urology Group is pleased to announce that Sara Q. Perkins, M.D. , has joined its award-winning care team . Dr. Perkins is returning home to serve the Columbus community after completing her residency at the Vattikuti Urology Institute at Henry Ford Hospital, which is internationally recognized for innovation in robotic surgery. Central Ohio Urology Group is an affiliate of U.S. Urology Partners , one of the nation’s largest independent providers urological services, which is backed by NMS Capital . With a clinical network of 15 offices in the region, Central Ohio Urology Group provides comprehensive urological services , including general urology , men’s health , women’s health , interventional radiology , cancer care , advanced cancer treatment and radiation oncology . Central Ohio Urology Surgery Center is one of the first ambulatory surgery centers in the country to offer urologic robotic surgery . Jason Guagenti, Chief Operating Officer of Central Ohio Urology Group , stated, “We are very excited to have Dr. Sara Perkins join our physician team . Dr. Perkins will bring high-quality patient care and great bedside manner to our patients. As an award winning physician with extensive skills and research experience, she will be an excellent addition to our care team in furthering our purpose of providing an individualized, compassionate experience for every person we are honored to serve.” After growing up in the Columbus area, Dr. Perkins received her undergraduate degree at Miami University and doctoral medical degree at the University of Toledo College of Medicine, where she was named to the AOA Medical Honor Society. Dr. Perkins completed her urology residency at the prestigious Vattikuti Urology Institute at Henry Ford Hospital, where she spent time learning from leaders and innovators in robotic surgery. During her time there she received the Ramesh Kumar Humanitarian Award (Resident of the Year) and the Peabody Award, given to support an exceptional educational experience where she traveled to Honduras providing urologic surgeries to those in need. A prolific researcher and writer, Dr. Perkins’ studies are published in numerous internationally recognized peer-reviewed journals. While she is a skilled robotic surgeon with expertise in treating prostate, kidney and bladder cancers, Dr. Perkins also is experienced in serving patients with BPH/enlarged prostate , incontinence , kidney stones , and general urology issues . Dr. Perkins is located at the Central Ohio Urology Group office at 350 W. Wilson Bridge Road, Worthington, OH 43085 . Sara Q. Perkins, M.D. , stated, “I am proud to join the care team at Central Ohio Urology Group, which focuses on providing collaborative, comprehensive urologic care while leveraging advanced technologies. I look forward to helping patients by using the large breadth of my knowledge and urologic training, and collaborating with the clinical team to provide the best care for our patients.” “My philosophy of patient care begins with treating every patient with dignity and respect, and providing the level of care that I would want my family to receive,” said Dr. Perkins . “Through open communication and transparency with my patients, I make sure they fully understand all aspects of their conditions and treatment options. By carefully considering my patients’ individual needs, I am able to provide truly personalized care.“ To learn more about Dr. Perkins or to schedule an appointment with the Central Ohio Urology Group care team , please visit www.centralohiourology.com or call (614) 396-2684. About U.S. Urology Partners U.S. Urology Partners is one of the nation’s largest independent providers of urology and related specialty services, including general urology, surgical and robotic procedures, advanced cancer treatment and other ancillary services. The U.S. Urology Partners clinical network consists of more than 50 locations throughout the East Coast and Midwest, including affiliate practices Associated Medical Professionals of NY , Central Ohio Urology Group , Florida Urology Center, Greater Boston Urology and Urology of Indiana . U.S. Urology Partners was formed to support urology practices with an experienced team of healthcare executives and resources, and is backed by NMS Capital . The U.S. Urology Partners corporate office is in Nolensville, Tennessee, just outside of Nashville. For additional information about U.S. Urology Partners, visit www.us-uro.com .

高管变更

2022-11-14

·PRNewswire

Global Robotic Surgery Conference Set for Miami

This Saturday, over 60 of the top robotic surgeons to attend the Vattikuti Foundation Robotic Surgery Symposium: Humans on the Cutting Edge of Robotic Surgery MIAMI, Nov. 14, 2022 /PRNewswire/ -- A gathering of more than sixty of the world's top robotic surgeons will meet in Miami for the "Humans at the Cutting Edge of Robotic Surgery" symposium on November 19th. Sponsored by the Vattikuti Foundation, the day-long program will feature sessions for surgeons in Orthopedics (Joint Repair/Replacement), Gastroenterology, Gynecology, Urology, Thoracic, and Head & Neck Surgery. Continue Reading Vattikuti Foundation Logo "While a surgical robot uses technology to exponentially improve patient outcomes, the surgeons are those who continuously innovate to create procedures with better patient outcomes. This is precisely why the symposium presents an opportunity to learn from eminent robotic surgeons, we call: 'humans at the cutting edge of technology,'' said Dr Mahendra Bhandari, Vattikuti Foundation CEO. "Attendees are encouraged to network and learn from their peers in an effort to continue in this path of progression." The Vattikuti Foundation received innovation submissions from 20 countries, with robotic surgeons from India, Greece, Italy, France, and the US who will present their work. Symposium sessions will examine topics ranging from "How Surgical Precision Improves Patient Outcomes'' to "What is New in Robotic Kidney Transplantation?" Twenty world-renown robotic surgeons will moderate the sessions such as: Mani Menon, MD and Peter Wiklund, MD, PhD of Mount Sinai Hospital, New York Alex Mottrie MD, Ph.D OLV Hospital, Aalst, Belgium, CEO of ORSI Academy, Melle, Belgium; Pier Cristoforo Giulianotti, MD, FACS, University of Illinois at Chicago Emre Gorgun, MD, FACS, FASCRS of Cleveland Clinic James O. Peabody, MD of Henry Ford Hospital, Detroit, MI Arnold P. Advincula, MD, FACOG, FACS of Columbia University Irving Medical Center Inderbir Singh Gill MD of USC Institute of Urology Alessandro Volpe, M.D. Maggiore della Carità Hospital, Novara, Italy. At an evening ceremony, the Vattikuti Foundation will award prizes for the robotic surgery innovation submissions for the "Best robotic surgery paper" and the 2022 KS International Robotic Surgery Innovation Awards. Previously focusing on robotic surgery in India, this is the first international iteration of the KS Robotic Surgery Innovation Awards, which has been run for seven years previously by the Vattikuti Foundation. The third prize award goes to a team of specialists, including Alberto Piana, Paolo Verri, and Alberto Breda of the Oncology Urology Unit and Kidney Transplant Surgical Team Urology Department from Fundació Puigvert in Barcelona, Spain for the video submission: 3D augmented reality guided robotic-assisted kidney transplant. The first prize is awarded to Jihad Kaouk, MD FACS FRCS, Professor of Surgery Zagarac Pollock Endowed Chair in Robotic Surgery, Director, Center for Robotic and Image Guided Surgery Vice Chair, Enterprise Surgical Operations, Cleveland Clinic for the submission: Single Port Robot-Assisted Kidney Transplantation Extraperitoneal Approach. In this innovation, Dr. Kaouk and his team modified the technique of robotic kidney transplant developed at the Vattikuti Urology Institute and Medanta Medicity. Kaouk used a da Vinci single-port robot for truly minimally invasive surgery. The Vattikuti Foundation has supported robotic surgery research, training, scholarships, and Fellowships. Over 100 young surgeons have been awarded one-year Fellowships with some of the world's top robotic surgeons. Many of these Vattikuti Fellows have gone on to lead programs in hospitals around the world. Following the symposium's conclusion, videos of the sessions will join nearly 900-videos about Robotic Surgery on the Vattikuti Foundation's website. This virtual library of procedures is an educational resource for robotic surgeons and the public seeking to learn more about minimally-invasive robotic surgery. About the Vattikuti Foundation The Vattikuti Foundation is a non-profit organization founded by Raj and Padma Vattikuti in 1997. The achievements of the Vattikuti Foundation stem from Indian-born Raj Vattikuti who immigrated to Detroit, Michigan to advance his education. Establishing his home in the United States, Vattikuti's innovative spirit and relentless work ethic forged prosperous international business ventures in the information technology industry. Equal parts entrepreneur and philanthropist, Raj along with his devoted wife Padma, made the commitment to share their wealth to elevate the health and well-being of others. Together they established the Vattikuti Foundation (VF) in southeast Michigan, where their business success had commenced. The surrounding communities in Detroit were the first to receive the benefits of their purposeful gifts. Yet the Vattikutis never forgot their roots in India and made intentional high-impact gifts in their country of origin. Today the Vattikuti Foundation spans the globe, enhancing the lives of countless individuals by facilitating medical and surgical advancements, education, humanitarian relief and social empowerment initiatives. Media Contact Kaitlyn Renzi Zen Media [email protected] SOURCE Vattikuti Foundation

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