Clarence Clark

CCR6 expression in colon cancer is associated with advanced disease and supports epithelial-to-mesenchymal transition

Background:Adjuvant chemotherapy offered to treat colon cancer is based on the TNM staging system, which often fails due to molecular heterogeneity and undefined molecular mechanisms independent of TNM. Therefore, identification of markers to better predict therapeutic option and outcome is needed. In this study we have characterised the clinical association of CCR6 with colon cancer and defined CCR6-mediated molecular pathway.Methods:Immunohistochemistry, RT-qPCR, western blot and FACS were used to determine expression of CCR6 and/or EMT markers in colon tissues/cells. BrdU assay and trans-well system were used to determine cell proliferation, migration and invasion in response to CCL20.Results:CCR6 was higher in cancer cases compared to normal adjacent tissue and expression was associated with nodal status and distant metastasis. Similarly, CCR6 expression was higher in cells derived from node-positive cases and highest expression was in cells derived from metastatic cases. Significant changes in EMT markers, that is, E-cadherin, vimentin, β-catenin, N-cadherin, α-SMA, SNAILl and ZEB1 were observed in response to CCL20 along with decreased proliferation, increased migratory and invasive potential.Conclusions:Results suggest CCR6 as a potential therapeutic target as well as biomarker in addition to nodal status for predicting therapeutic option.

Diagnostic Modalities for Inflammatory Bowel Disease: Serologic Markers and Endoscopy

The evaluation, diagnosis, and monitoring of inflammatory bowel disease (IBD) has improved significantly over the past few decades. However, differentiation and management of the subtypes of IBD (Crohns disease, ulcerative colitis, and indeterminate colitis) can still be challenging. The evolution of serologic markers has improved our understanding of the pathogenesis and natural history of IBD. In addition, advancements in endoscopy and endoscopic scoring systems have improved the accuracy of diagnosis and the efficacy of surveillance of IBD patients. This article reviews the recent literature on serologic markers, endoscopy, and endoscopy scoring systems.

Rare case of a strangulated intercostal flank hernia following open nephrectomy: A case report and review of literature

Highlights • Urgent abdominal examination with palpation of the region is necessary in the diagnosis of strangulated hernias but may be misleading so further studies are necessary.• Serological testing of a patient with a strangulated hernia may show lactic acidosis and leukocytosis.• Operative management is necessary for strangulated hernias especially in patients with altered mental status and a clinical picture showing decline.• Intercostal incisional herniation following a previous surgical procedure is a rare entity which should be diagnosed and treated rapidly.• This case highlights the clinical picture associated with an emergent strangulated hernia and highlights the critical steps in its management.

Fluorescence Imaging in Anorectal Advancement Flaps

Rectal advancement procedures are commonly used for fistula-in-ano. these procedures can have a <30% early complication rate. flap separation is a complication likely attributed to poor perfusion or technical error. flap separation is associated with recurrence of disease and repeat anorectal procedures, which may increase the risk for fecal incontinence and prolonged postoperative pain. Currently, gross observation is the standard for determining the distal margin of anorectal flaps. fluorescence angiography has emerged as an intraoperative tool used to assess perfusion of the intestinal microcirculation to decrease the risk of postoperative ischemic events. fluorescence angiography can reduce observer variability when applied to anorectal procedures. in this video (see Supplemental Digital Content 1, http://links.lww.com/DCR/a235), we demonstrate a novel application of imaging technology to assess anorectal flap perfusion in the repair of a complex recurrent fistula-inano with the aim of preventing flap ischemia and failure. the procedure in this video begins with identification of the external and internal openings. the epinephrine with bupivacaine is injected distal to the internal opening along the length of the flap and does not appear to have an overall effect on anal perfusion. We used electrocautery to raise the mucosal and submucosal flaps. nearing the proximal anal canal, the dissection transitions from a mucosal/submucosal flap to a musculomucosal flap with a wide base to ensure adequate perfusion. We then used fluorescence angiography with indocyanine green to determine a more accurate distal point of transection for the apex of the flap maximizing the use of viable tissue. We divided the flap at the line of demarcation, thus creating a new apex. We advanced the tension-free flap and secured the edges. the perfusion of the flap is reimaged. fluorescence angiography is a safe, intraoperative tool to assess anorectal perfusion in advancement flaps.

Molecular Mechanism Linking BRCA1 Dysfunction to High Grade Serous Epithelial Ovarian Cancers with Peritoneal Permeability and Ascites

Ovarian cancer constitutes the second most common gynecological cancer with a five-year survival rate of 40%. Among the various histotypes associated with hereditary ovarian cancer, high-grade serous epithelial ovarian carcinoma (HGSEOC) is the most predominant and women with inherited mutations in BRCA1 have a lifetime risk of 40-60%. HGSEOC is a challenge for clinical oncologists, due to late presentation of patient, diagnosis and high rate of relapse. Ovarian tumors have a wide range of clinical presentations including development of ascites as a result of deregulated endothelial function thereby causing increased vascular permeability of peritoneal vessels. The molecular mechanisms remain elusive. Studies have shown that fallopian tube cancers develop in women with BRCA1 gene mutations more often than previously suspected. Recent studies suggest that many primary peritoneal cancers and some high-grade serous epithelial ovarian carcinomas actually start in the fallopian tubes. In this article we have addressed the molecular pathway of a recently identified potential biomarker Ubc9 whose deregulated expression due to BRCA1 dysfunction can result in HGSEOC with peritoneal permeability and formation of ascites. We also discuss the role of downstream targets Caveolin-1 and Vascular Endothelial Growth Factor (VEGF) in the pathogenesis of ascites in ovarian carcinomas. Finally we hypothesize a signaling axis between Ubc9 over expression, loss of Caveolin-1 and induction of VEGF in BRCA1 mutant HGSEOC cells. We suggest that Ubc9-mediated stimulation of VEGF as a novel mechanism underlying ovarian cancer aggressiveness and ascites formation. Agents that target Ubc9 and VEGF signaling may represent a novel therapeutic strategy to impede peritoneal growth and spread of HGSEOC.

Abstract 312: Anti-proliferative effects of cinnamon extract in colon cancer

Colon cancer is the third most lethal cancer worldwide, and is estimated to cause 49,190 cancer-related deaths in the U.S. in 2016 alone. Current treatments for colon cancer are limited in their capacity to target tumor cells employing adaptive mechanisms necessary for survival and proliferation, often resulting in poor prognosis. Therefore, it is critical to develop novel target-specific therapeutic approaches with minimal cytotoxicity to normal cells, in order to mitigate potential side effects. Proanthocyanidins represent a subclass of flavonoids, which have been widely investigated for their chemopreventive and therapeutic potential. Cinnamtannin B-1 (CTB-1) is a proanthocyanidin shown to have anti-cancer effects in several cancers, but its anti-cancer potential in colon cancer has not been tested. Hence, the focus of this study was to determine the anticancer effects of CTB-1 in colon cancer. Our results show that CTB-1 treatment significantly decreases the cell viability and proliferation of DLD-1 and COLO 201 human colon cancer cells in a time and dose-dependent manner. In addition, CTB-1 treatment modulated the cell cycle progression of colon cancer cells via G2/M arrest, coupled with a reduction of cells in the S phase. The expression and/or phosphorylation of key molecules involved in apoptosis and cell cycle progression were also modulated in response to CTB-1 treatment. Collectively, these findings, for the first time, shed light on the anti-proliferative effects of CTB-1 in colon cancer, and further demonstrate its potential as a novel therapeutic/preventive agent. Citation Format: Patrick P. Carriere, Hina Mir, Neeraj Kapur, Clarence E. Clark, Shailesh Singh. Anti-proliferative effects of cinnamon extract in colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 312. doi:10.1158/1538-7445.AM2017-312

Abstract B21: Functional Role of ETS/ETV1-Fusion Proteins in Prostate Cancer and Other Cancers

After lung cancer prostate cancer is the most common age related cancer among men in the United State. African American men have the highest incidence of, and mortality rate from, this disease in the United States (American Cancer Society). According to the American Cancer Society, 29% of all cancer cases and 9% of all cancer deaths are a result of prostate cancer. By the age of 75, one out of nine men will develop prostate cancer. Individuals who are at higher risk include African-American men, men over 60 years of age and those with a family history of the disease. African-Americans also have twice the risk of developing prostate cancer as Caucasians. E26 transforming sequence (ETS) factors play an important role in cancers. ETV1, an ETS factor, is notable for its association in prostate cancers, where truncated ETV1 (dETV1) or its full length counterpart is overexpressed in approximately 10% of the patients. Formation of cancers may be brought on by deregulation of Wnt/β-catenin pathway. Mutations that stabilize β-catenin may contribute to loss of cell growth control in tumorigenesis. ETV19s interaction with components of the Wnt/β-catenin pathway may alter β-catenin interaction with downstream tumor suppressor genes, which are critical in regulating apoptosis and cell growth properties. Our results show that ETV1 regulates Wnt/β-catenin activity. We provide evidence that ETV1 activates kinases that regulate Wnt/β-catenin activity by post translational modification. Also, we demonstrate that therapeutic agents that reverse ETV1-regulated Wnt/β-catenin activity can be used to target ETV1-positive prostate cancer cells. These therapeutic agents will have a profound impact on prevention and treatment of prostate cancer and this may help to reduce health disparity seen in the minority patients. Citation Format: Sharif Morsalin, Chunshu Yang, Jinbo Fang, Yasuo Fujimura, Shubhalaxmi Kayarthodi, Huali Xu, Ujwala Gunnal, Clarence Clark, Julian Menter, Veena Rao, Shyam Reddy. Functional Role of ETS/ETV1-Fusion Proteins in Prostate Cancer and Other Cancers. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B21.

Hospital-based, Multidisciplinary, youth mentoring and medical exposure program positively influences and reinforces health care career choice: “The Reach One Each One Program early Experience”

BACKGROUND According to the National Center for Educational Statistics, underrepresented minorities (URMs) are more likely to leave science, technology, engineering and mathematics (STEM) fields at higher rates than their peers during undergraduate studies. Many institutions of higher learning have implemented pipeline programs aimed at preparing and inspiring high school and college aged students in select careers in health sciences with varying levels of success. Research has shown that a health care workforce that mirrors the community they serve is more effective in reducing health disparities and increasing positive health outcomes. We hypothesize that a hospital-based, multidisciplinary youth mentoring and medical exposure program will enhance the decision of URM high school students to choose healthcare careers. MATERIALS AND METHOD A retrospective analysis of the Reach One Each One Program (ROEO) was performed. ROEO is a hospital based, 11-week multidisciplinary youth mentoring and medical exposure program for inner-city high school students. The analysis was based on a phone survey of the twenty-six (26) seniors who completed the program and subsequently graduated from high school between May 2013 and May 2015 to assess the following: 1) College enrollment/attendance, 2) Health profession majors, and 3) Pre-med status. The study was approved by the Morehouse School of Medicine Institutional Review Board. RESULTS Of the twenty-six students, 23 were female and 3 were male; 25 (96%) of the students were African American and one student was a Caucasian female. Twenty-four (92.3%) of the students were enrolled in college and 2 (7.7%) were scheduled to begin in the spring semester of 2016. Twenty-one of the 24 attending college at the time of the survey (87.5%) were enrolled in a health science degree program and 16 (66.7%) confirmed that they were enrolled in pre-medical (Pre-med) curriculum. CONCLUSION Hospital-based, multidisciplinary medical mentoring programs can have a positive impact on the lives and health care career decisions of aspiring URM high school students. Further study will be necessary to validate the most influential components needed for the success of such programs.

Improving Workforce Diversity in Minority and Majority Institutions

To improve healthcare workforce diversity in minority and majority institutions, one must not only examine the supply (medical students, nursing students, etc.) but also the forces that may impede progress to healthcare workforce diversity. Here, we will tackle these key elements and then discuss current and future strategies that may provide meaningful solutions to this important dilemma.

Abstract 1701: CCR6 associates with colon cancer metastasis

Despite established benefits of screening, colon cancer remains a leading cause of cancer death in the U.S. Majority of colon cancer deaths result from metastasis. Effective treatments are not available for advanced disease because molecular mechanisms of initiation and progression of this disease are yet to be defined. Chemokine-chemokine receptor interaction plays an important role in cancer progression. In this study, using colon cancer tissue microarray, we have shown that expression of CCR6 was significantly higher in advanced colon cancer (p Citation Format: Neeraj Kapur, Hina Mir, Clarence E. Clark, Uma Krishnamurti, Derrick J. Beech, James W. Lillard, Shailesh Singh. CCR6 associates with colon cancer metastasis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1701.