Publications by authors named "Michael B Nicholl"

Background/aim: Pancreatic cancer is the second most common gastrointestinal cancer in the world, yet the five-year survival outcome rate of less than 5% urges for improvement in medical interventions of pancreatic cancer. Currently, high dose radiation therapy (RT) is used as an adjuvant treatment; however, the high level of RT required to treat advanced neoplasms leads to high incidence rates of side effects. In recent years, the utilization of cytokines as radiosensitizing agents has been studied, in order to reduce the amount of radiation required.

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Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients.

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Ovarian cancer is the leading cause of cancer‑ associated mortality in the female reproductive system. Interleukin (IL)‑33 and its receptor IL 1 receptor like 1 (also termed ST2) are expressed by many cell types including epithelial cells. The role of IL‑33 in the pathogenesis of neoplasia remains controversial.

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Interleukin-33 (IL-33), a damage-associated molecular pattern molecule, is a cytokine within the IL-1 interleukin family that binds to the plasma membrane receptor suppression of tumorigenicity 2 on numerous cell types. IL-33 has been extensively studied in its role in autoimmune diseases, host responses to pathogens and allergens, and has been associated with tumorigenic effects in cancer research. The present study was performed to investigate the effects of IL-33 on colon cancer cells, based off the previous data that have demonstrated an anti-tumor effect of IL-33 on pancreatic cancer cells.

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The utilization of robotics in general surgery has increased significantly including usage in the Veterans Affairs (VA) system. We implemented a robotic inguinal hernia repair (RIHR) program in our VA hospital and report on initial experience with safety and outcomes. The first 100 consecutive RIHR at a VA hospital were reviewed and compared against the results of contemporaneous open inguinal hernia repair (OIHR).

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Melanoma is the leading cause of death among all skin cancers and its incidence continues to rise rapidly worldwide in the past decades. The available treatment options for melanoma remain limited despite extensive clinical research. Melanoma is an immunogenic tumor and great advances in immunology in recent decades allow for the development of immunotherapeutic agents against melanoma.

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IL-33 is a member of the IL-1 family of cytokines, and no study has been performed to address its direct anti-tumor effect. This study is designed to investigate whether IL-33 has any direct effect on pancreatic cancer. Clonogenic survival assay, immunohistochemistry, TUNEL staining, proliferation, caspase-3 activity kits and RT-PCR were used to evaluate the effects of IL-33 on cell survival, proliferation and apoptosis of a pancreatic cancer cell line, MIA PaCa-2.

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Purpose: Primary gastrointestinal stromal tumors (GISTs) are typically treated with open resection. There is growing interest in laparoscopic GIST resection; however, data is limited. We report our experience with GIST resections using both open and laparoscopic techniques.

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Background: Interleukin-32 (IL-32) is a recently recognized intracellular, proinflammatory cytokine which may play a role in cancer metastasis and patient survival. The role of IL-32 in cancer, especially its direct effect on cancer cells, is not well understood.

Material And Methods: Clonogenic assay, PCNA staining, Quick Cell Proliferation assay, TUNEL staining, and caspase-3 activity assay were used to investigate the in vitro role for IL-32α in human melanoma growth.

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Background: IL-9 is a pleiotropic cytokine produced mainly by Th9 cells. IL-9 may have an anti-proliferative role in murine melanoma, however, its effect on human melanoma is unknown.

Methods: We examined the effects of IL-9 on proliferation and apoptosis in four human melanoma cell lines, HTB-65, HTB-72, CRL-11147, and SK-Mel-5.

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Interleukin-35 (IL-35), an IL-12 cytokine family member, mediates the immune inhibitory function of regulatory T cells (Treg). We assayed the presence of IL-35 in paraffin-embedded human pancreas cancer (PCAN) and unexpectedly found IL-35 was expressed mainly by epithelial derived PCAN cells, but not by Treg. We further examined the expression and effect of exogenous IL-35 in human PCAN cell lines and found IL-35 promoted growth and inhibited apoptosis in PCAN cell lines.

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Background: Pancreatic cancer (PanCA) is predominantly diagnosed in elderly patients; nevertheless, a significant number of young patients are affected. We hypothesized more aggressive treatment of young PanCA patients would result in better overall survival (OS).

Methods: A retrospective review of our institutional cancer database identified subjects for inclusion.

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Purpose: Percutaneous endoscopic gastrostomy (PEG) provides durable nutritional access for head and neck (HNC) patients as they undergo treatment. Continuing treatment of HNC may necessitate repeat PEG placement. We report our outcomes with repeat PEG compared to first-time PEG in HNC patients.

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Context: Pancreatic dermoid cysts are rare, benign, germ cell tumors and part of the differential diagnosis for cystic neoplasms of the pancreas.

Case Report: A 35-year-old man presented with an incidentally discovered, 2 cm cystic pancreatic neoplasm of the pancreatic tail identified on CT scan. Endoscopic ultrasound (EUS) revealed a complex, honeycomb lesion.

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Sirtuin 1 (SIRT1) is an NAD+-dependent histone deacetylase which regulates many normal physiological and pathological processes. In addition to its place in cellular energy metabolism, increasing evidence shows a role for SIRT1 in tumorigenesis, wherein it can function as either a tumor promoter or suppressor. Its function in malignancy varies with concentration, cellular location, temporal and spatial distribution, and regulation by upstream and downstream factors.

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Cytoreductive surgery with heated intraperitoneal chemotherapy (CRS/HIPEC) remains a controversial treatment for malignant disease of the peritoneal cavity. We review the scientific principles underscoring the rationale for CRS/HIPEC, recent innovations and ongoing controversies. Lack of level 1 data limits the understanding of the true benefit of CRS/HIPEC.

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The efficacy of radiation therapy (RT) for melanoma is limited in part by its radioresistance. Here, we examined the radiosensitizing effect of hydrogen peroxide (H(2)O(2)) on a radioresistant melanoma cell line, HTB-65. We found that H(2)O(2) synergized with RT to inhibit melanoma cell proliferation and promote apoptosis.

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Background: Radiotherapy (XRT) is used to improve local control of melanoma and for palliation of metastatic disease. Clinical use of XRT for melanoma is often limited by extent of disease and the relative radioresistance of melanoma may limit the effectiveness of XRT. Our group and others have previously shown that resveratrol (RSV) enhances radiation sensitivity in radioresistant prostate cancer cell lines.

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Radiation therapy (XRT) for treatment of localized prostate cancer (PCA) has outcomes similar to surgery and medical therapy. Toxicities of XRT and the relative radioresistance of PCA limit the effectiveness of this treatment method. Safe and effective radiosensitizing agents are lacking to enhance the effectiveness for XRT for PCA.

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Perforin and granzyme B are expressed primarily by activated lymphocytes (cytotoxic T cells, natural killer cells, and natural killer T cells) and function together to induce apoptosis of target cells. Typically, these proteins are not expressed in tumor cells. In the present study, we established the constitutive expression of perforin and granzyme B by the PC-3 and DU145 prostate cancer (PCA) cell lines with reverse transcription polymerase chain reaction, immunohistochemistry, Western blot, or a combination of techniques.

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In the past decade, great interest has been shown in the role of sirtuin 1 (SIRT1) in tumorigenesis. The published data show SIRT1 can function as both a tumor promoter and tumor suppressor. In this review, we summarize the available data regarding the role of SIRT1 in tumorigenesis, with a focus on the potential mechanisms.

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Objective: To determine the long-term clinical significance of molecular upstaging in histopathology-negative, paraffin-embedded (PE) sentinel lymph nodes (SLNs) from melanoma patients.

Background: Histopathologic evaluation can miss clinically relevant melanoma micrometastases in SLNs. This longitudinal correlative study is the first 10-year prognostic evaluation of a multimarker quantitative real-time reverse transcriptase-polymerase chain reaction (qRT) assay for PE melanoma-draining SLNs.

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Hypermethylation of the promoter region of tumor-related genes (TRGs) has been shown to silence gene expression during melanoma progression, whereas microRNA-29(miR-29) has been found to downregulate DNA methyltransferases DNMT3A and DNMT3B which were shown as essential to the methylation of TRGs. We hypothesized that the expression level of miR-29 is associated to TRG methylation status and may have prognostic utility in melanoma. AJCC stage I-IV cutaneous melanoma paraffin-embedded archival tissue (PEAT) specimens (n=149) were assessed.

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Background: Primary small bowel adenocarcinoma (SBA) is a rare, chemoresistant tumor with an aggressive clinical nature. Surgery is the mainstay of therapy, but the extent of lymph node (LN) recovery necessary for optimal care of jejunoileal SBA is unknown.

Materials And Methods: The SEER database was queried to identify patients whose primary jejunoileal SBA was diagnosed between 1995 and 2005.

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Most colon cancer resections do not meet the 12-lymph node minimum recommended in 2001 National Cancer Institute (NCI) panel guidelines. Previous reports suggest surgical training influences lymph node recovery. We hypothesized that recent trends show improved results for lymphadenectomy regardless of specialty.

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