Medicine and Health Sciences Commons^™

A Rare Metastatic Primary Rectal Melanoma In A Geriatric Male, Onyinye Ugonabo, Mujtaba Mohamed, Ebubechukwu Ezeh, Joseph Simmons, Jonathan Cuda, Shima Ghavimi

Internal Medicine

Primary rectal melanoma (PRM) is an uncommon malignancy whose etiology remains unknown. Most patients present with rectal bleeding. Distant metastasis is commonly seen in the lung and liver. The incidence rates for locoregional lymph node metastases on initial presentation are almost 60%. Histology and immunochemistry are useful and are the gold standard for diagnosis. The prognosis is very poor due to the late presentation of patients. Optimum surgical treatment remains controversial. Abdominoperineal resection was considered traditionally but over time, has been found to have no survival benefit. Current literature and studies, therefore, recommend wide local excision. The beneficial effects of …

Genetic And Epigenetic Determinants Of Diffuse Large B-Cell Lymphoma, Tanner Bakhshi, Philippe T. Georgel

Biomedical Sciences

Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma and is notorious for its heterogeneity, aggressive nature, and the frequent development of resistance and/or relapse after treatment with standard chemotherapy. To address these problems, a strong emphasis has been placed on researching the molecular origins and mechanisms of DLBCL to develop effective treatments. One of the major insights produced by such research is that DLBCL almost always stems from genetic damage that occurs during the germinal center (GC) reaction, which is required for the production of high-affinity antibodies. Indeed, there is significant overlap between the mechanisms that …

Management And Treatment Of Hepatocellular Carcinoma With Immunotherapy: A Review Of Current And Future Options, Shima Ghavimi, Tehila Apfel, Hamed Azimi, Alana Persaud

Internal Medicine

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to …

Exploring The Excluded Stomach: A Case Series Of Novel Endoscopic Techniques To Diagnose Gastric Cancer In The Excluded Stomach After Roux-En-Y Gastric Bypass Surgery, Saeed Ali, Abdelkader Chaar, Wesam Frandah, Rola Altoos, Zeeshan Sattar, Muhammad Hasan

Internal Medicine

Gastric cancer is the fifth most common malignancy worldwide and the fourth leading cause of cancer-related deaths. The diagnosis is usually made by direct visualization with supporting histopathology. However, patients with gastric bypass surgery pose a challenge in diagnosis due to the difficulty in the evaluation of the excluded stomach. We present two cases of gastric cancer in the excluded stomach after Roux-en-Y gastric bypass (RYGB) surgery was diagnosed using two different endoscopic approaches.

Small Cell Carcinoma Of Prostate: A Case Report Of A Patient With Concomitant Transitional Cell Cancer Of The Bladder, Waiel Abusnina, Eric Y. Auyoung, Mohammed Megri, Toni H. Pacioles

Internal Medicine

Small cell carcinomas (SCCs) are aggressive neoplasms commonly associated with a pulmonary origin. However, albeit rare, extrapulmonary SCC can occur in a variety of sites with an incidence in North America approximated to be 0.1% to 0.4%. Among these sites, approximately 10% of extrapulmonary SCC cases occur in the prostate and are associated with a poor mortality with a median survival of 10 months. Because of the rarity of the prostatic SCC, there is no formal treatment protocol. In this case report, we present a patient who was diagnosed with SCC in the prostate as primary origin. Adjuvant concurrent chemoradiotherapy …

Prospect Of The Use Of Checkpoint Inhibitors In Hepatocellular Cancer Treatments, Ali Raufi

Internal Medicine

Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%–3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC. The introduction of immune checkpoint inhibitors (cytotoxic T-lymphocyte antigen 4, programmed death 1, and programmed death-ligand 1) has …

Primary Retroperitoneal Melanoma Presented In A Rare Extracutaneous Site For Malignant Melanoma, Mohamed Alsharedi, Nadim Bou Zgheib, Yousef Khelfa, Ali Raufi, Nabiha Elmsherghi, Yehuda Lebowicz

Hematology and Oncology

Malignant melanoma, as the name implies, is a malignant tumor of melanocytes, found in the skin, eyes, meningeal lining and the mucosal epithelium of the aero-digestive and genitourinary tracts. Malignant melanoma is typically skin malignancy, which rarely presents at extracutaneous site. Here we present a rare case of primary retroperitoneal melanoma and review the findings in comparison with other cases described in literature.

Theaflavin-3, 3'-Digallate Induces Apoptosis And G2 Cell Cycle Arrest Through The Akt/Mdm2/P53 Pathway In Cisplatin-Resistant Ovarian Cancer A2780/Cp70 Cells, Youying Tu, Eunhye Kim, Ying Gao, Gary O. Rankin, Bo Li, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Ovarian cancer is the most lethal gynecological cancer among women worldwide. Adverse side effects and acquired resistance to conventional platinum based chemotherapy are major impediments in ovarian cancer treatment, and drive the development of more selective anticancer drugs that target cancer-specific defects. In this study, theaflavin-3, 3'-digallate (TF3), the major theaflavin monomer in black tea, exhibited a potent growth inhibitory effect on the cisplatinresistant ovarian cancer A2780/CP70 cells (IC50, 23.81 μM), and was less cytotoxic to a normal ovarian IOSE‑364 cells (IC50, 59.58 μM) than to the cancer cells. Flow cytometry analysis indicated that TF3 induced preferential apoptosis and G2 …

Esophageal Diagnosis Of A Malignant Aspergilloma, Muneer Al Zoby, Nancy Munn,, Yousef Shweihat

Internal Medicine

A 59-year-old male patient developed a new 4 cm × 6 cm cavitary left upper lung lesion over a 2 months period. The patient had a prior history of a surgically resected Stage IA non-small cell lung cancer in the right upper lobe 3 years prior. He was treated for possible infection with radiographic improvement on subsequent imaging. Further imaging after 3 months revealed an oval soft tissue density within the cavity with air crescent sign. Bronchoscopy with transbronchial biopsies showed an acute and chronic granulomatous inflammation. Aspergillus fumigatus was noted on culture and voriconazole was initiated. Subsequent imaging showed …

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Biochemistry and Microbiology

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC.

Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided in …

Gallic Acid, A Phenolic Compound, Exerts Anti-Angiogenic Effects Via The Pten/Akt/Hif-1Α/Vegf Signaling Pathway In Ovarian Cancer Cells, Zhiping He, Allen Y. Chen, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and …

Theaflavin-3, 3'-Digallate Decreases Human Ovarian Carcinoma Ovcar-3 Cell-Induced Angiogenesis Via Akt And Notch-1 Pathways, Not Via Mapk Pathways, Ying Gao, Gary O. Rankin, Youying Tu, Yi Charlie Chen

Biochemistry and Microbiology

Theaflavin-3, 3'-digallate (TF3) is a black tea polyphenol produced from polymerization and oxidization of the green tea ployphenols epicatechin gallate and (-)-epigallocatechin-3-gallate (EGCG) during fermentation of fresh tea leaves. TF3 has been reported to have anticancer properties. However, the effect of TF3 on tumor angiogenesis and the underlying mechanisms are not clear. In the present study, TF3 was verified to inhibit tumor angiogenesis. Compared with EGCG, TF3 was more potent. TF3 inhibited human ovarian carcinoma OVCAR-3 cell-induced angiogenesis in human umbilical vein endothelial cell model and in chick chorioallantoic membrane model. TF3 reduced tumor angiogenesis by downregulating HIF-1α and VEGF. …

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmacology, Physiology and Toxicology

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatinresistant cancer …

Smartphone Mobile Application To Enhance Diagnosis Of Skin Cancer: A Guide For The Rural Practitioner, Shane E. Cook, Louis C. Palmer Md, Franklin D. Shuler Md, Phd

MIIR Faculty Research

Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier …

The Tri-State Experience: Outcome Analysis Of Patients With Triple Negative Breast Cancer Treated At Marshall University, Laurie Matt Md, Mph, Mohammad Mozayen Md, Todd W. Gress Md, Maria Tria Tirona Md

Internal Medicine

Breast cancer is the most frequently diagnosed malignancy in women in the United States. It is the second most common malignancy to cause death, with approximately 39,000 women dying of breast cancer in the United States in 2013. Triple negative breast cancer is defined as the absence of estrogen, progesterone and human epidermal growth factor receptor 2 receptors. It has been associated with a higher incidence in African American women, a younger age and a more advanced stage at diagnosis, and an inferior overall survival. To recognize the differences of our West Virginia community population when compared to the national …

Myricetin Inhibits Proliferation Of Cisplatin-Resistant Cancer Cells Through A P53-Dependent Apoptotic Pathway, Haizhi Huang, Allen Y. Chen, Xingqian Ye, Bingyun Li, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmaceutical Science and Research

Cisplatin is a commonly used drug for cancer treatment by crosslinking DNA, leading to apoptosis of cancer cells, resistance to cisplatin treatment often occurs, leading to relapse. Therefore, there is a need for the development of more effective treatment strategies that can overcome chemoresistance. Myricetin is a flavonoid from fruits and vegetables, showing anticancer activity in various cancer cells. In this study, we found myricetin exhibited greater cytotoxicity than cisplatin in two cisplatin-resistant ovarian cancer cell lines, OVCAR-3 and A2780/CP70, and it was less cytotoxic to the normal ovarian cell line IOSE-364. Myricetin selectively induced apoptosis in both cisplatin-resistant cancer …

Gallic Acid, A Phenolic Compound, Exerts Anti-Angiogenic Effects Via The Pten/Akt/Hif-1Α/Vegf Signaling Pathway In Ovarian Cancer Cells, Zhiping He, Allen Y. Chen, Yon Rojanasakul, Gary O. Rankin, Yi Charlie Chen

Pharmaceutical Science and Research

Gallic acid (GA), a polyphenol, is widely found in numerous fruits and vegetables, particularly in hickory nuts. In the present study, we found that gallic acid, a natural phenolic compound isolated from fruits and vegetables, had a more potent growth inhibitory effect on two ovarian cancer cell lines, OVCAR-3 and A2780/CP70, than the effect on a normal ovarian cell line, IOSE-364. These results demonstrated that GA selectively inhibits the growth of cancer cells. Gene expression was examined by ELISA and western blot analysis, and gene pathways were examined by luciferase assay. It was found that GA inhibited VEGF secretion and …

The Flavonoid Nobiletin Inhibits Tumor Growth And Angiogenesis Of Ovarian Cancers Via The Akt Pathway, Jianchu Chen, Allen Y. Chen, Haizhi Huang, Xingqian Ye, William D. Rollyson, Haley E. Perry, Kathleen C. Brown, Yon Rojanasakul, Gary O. Rankin, Piyali Dasgupta, Yi Charlie Chen

Pharmaceutical Science and Research

Despite its importance, the death rate of ovarian cancer has remained unchanged over the past five decades, demanding an improvement in prevention and treatment of this malignancy. With no known carcinogens, targeted prevention is currently unavailable, and efforts in early detection of this malignancy by screening biomarkers have failed. The inhibition of angiogenesis, also known as angioprevention, is a promising strategy to limit the growth of solid tumors, including ovarian cancers. Nobiletin, a polymethoxy flavonoid compound isolated from the tiansheng plant, has been shown to inhibit the growth of multiple types of human cancers. However, there are no reports involving …

An Update On Braf Inhibitors And Other New Molecular Targets For The Treatment Of Malignant Melanoma Of The Skin, M. O. Faruk Khan, Carroll L. Ramos

Pharmaceutical Science and Research

Malignant melanoma of the skin originates from mutations in melanocytes and can be lethal if unrecognized or untreated in its earlier stages. Deaths from melanoma are increasing in the United States and around the world every year. The available treatments produce low rates of response with modest survival impact. Among potential molecular targets under investigation, which are mostly in the tyrosine kinase pathway, the BRAF (V-raf murine sarcoma viral oncogene homolog B1) gene is the best studied and most frequently reported mutation in melanoma. The molecular targets for melanoma treatment, promising drugs for future melanoma treatment as well as the …

Screening Mammograms In Alzheimer’S Disease Patients, George M. Yousef, Piyush Sovani, Sirisha Devabhaktuni, Lynne J. Goebel

Internal Medicine

Very little guidance exists to help clinicians and families decide whether mammograms are useful in elderly women with Alzheimer’s Disease (AD). We present a case of a patient with moderate AD who had a positive mammogram and discuss the dilemma faced by the family and clinician in deciding what was best to do for the patient. In this case, the family opted for breast conserving surgery (BCS) followed by palliative care which brought up the question of whether screening was appropriate with this treatment goal in mind. We reviewed the literature on AD and breast cancer screening and summarize these …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Biochemistry and Microbiology

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

0789: George J. Hill Collection, 1889-2011, Marshall University Special Collections

Guides to Manuscript Collections

This collection includes research materials used by Dr. Hill, pertaining to his research interests in medical, military, and New Jersey history, in addition to cancer and leprosy, Dr. Hill's medical specialties. It also includes copies of articles, reports, and abstracts written about Dr. Hill. Additionally, the collection has an assortment of historical pamphlets about leprosy.

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Biochemistry and Microbiology

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta

Biochemistry and Microbiology

Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.

Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …

Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman

Biochemistry and Microbiology

Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …

The P53-Induced Siva-1 Plays A Significant Role In Cisplatin-Mediated Apoptosis, John L. Barkinge, Radhika Gudi, Hawkins Sarah, Fei Chu, Alip Borthakur, Bellur S. Prabhakar

Clinical & Translational Sciences

Background: The pro-apoptotic protein Siva-1 functions in both extrinsic and intrinsic cell death signaling; however, the exact contribution of the endogenous Siva-1 to DNA damage-induced apoptosis is unclear. Using cisplatin, a chemotherapeutic drug, to induce DNA damage and cell death, we determined the role of Siva-1.

Methods: Cisplatin treated HCT116 colorectal carcinoma cells (p53+/+ and -/-) were used in the study. With the help of recombinant lentivirus that can express siSiva (siRNA that specifi cally targets Siva-1), we also generated Siva-1 knockdown HCT116 cells. Apoptosis was determined by tetramethyl rhodamine methyl ester (TMRM) staining and propidium iodide (PI) staining.

Results: …

Global Analysis Of Gene Expression Changes During Retinoic Acid-Induced Growth Arrest And Differentiation Of Melanoma: Comparison To Differentially Expressed Genes In Melanocytes Vs Melanoma, Mary H. Estler, Goran Boskovic, James Denvir, Sarah Miles, Donald A. Primerano, Richard M. Niles

Biochemistry and Microbiology

BACKGROUND: The incidence of malignant melanoma has significantly increased over the last decade. Some of these malignancies are susceptible to the growth inhibitory and pro-differentiating effects of all-trans-retinoic acid (RA). The molecular changes responsible for the biological activity of RA in melanoma are not well understood.

RESULTS: In an analysis of sequential global gene expression changes during a 4-48 h RA treatment of B16 mouse melanoma cells, we found that RA increased the expression of 757 genes and decreased the expression of 737 genes. We also compared the gene expression profile (no RA treatment) between non-malignant melan-a mouse melanocytes and …

Suppression Of Implanted Mda-Mb 231 Human Breast Cancer Growth In Nude Mice By Dietary Walnut, W. Elaine Hardman, Gabriela Ion

Biochemistry and Microbiology

Walnuts contain components that may slow cancer growth including omega 3 fatty acids, phytosterols, polyphenols, carotenoids, and melatonin. A pilot study was performed to determine whether consumption of walnuts could affect growth of MDA-MB 231 human breast cancers implanted into nude mice. Tumor cells were injected into nude mice that were consuming an AIN-76A diet slightly modified to contain 10% corn oil. After the tumors reached 3 to 5 mm diameter, the diet of one group of mice was changed to include ground walnuts, equivalent to 56 g (2 oz) per day in humans. The tumor growth rate from Day …

Retinoic Acid Decreases Atf-2 Phosphorylation And Sensitizes Melanoma Cells To Taxol-Mediated Growth Inhibition, Ying Huang, Jennifer Minigh, Sarah Miles, Richard N. Niles

Biochemistry and Microbiology

Cutaneous melanoma is often resistant to chemo- and radiotherapy. This resistance has recently been demonstrated to be due, at least in part, to high activating transcription factor 2 (ATF-2) activity in these tumors. In concordance with these reports, we found that B16 mouse melanoma cells had higher levels of ATF-2 than immortalized, but non-malignant mouse melanocytes. In addition, the melanoma cells had a much higher amount of phosphorylated (active) ATF-2 than the immortalized melanocytes. In the course of determining how retinoic acid (RA) stimulates activating protein-1 (AP-1) activity in B16 melanoma, we discovered that this retinoid decreased the phosphorylation of …