Factors Predictive of Publication Among Medical Students Participating in School-Sponsored Research Programs.

INTRODUCTION: Publishing research is an important component of medical students' career development and becoming a more competitive residency applicant. Many medical schools offer structured programs to enable students to participate in research during their preclinical and clinical years, but the majority of student-mentor partnerships do not culminate in publication across a variety of institutions and medical specialties. The primary objective of this study is to determine if any factors associated with mentee-mentor partnerships are predictive of publication from two school-sponsored research programs at a single US medical school. METHODS: The PubMed-indexed publications of all student-mentor pairings from a summer internship (after year 1 of medical school) or research elective (during year 4 of medical school) at a single institution from 2008 to 2018 were retrospectively reviewed. Student/mentor demographic information was associated with the probability of publication. RESULTS: A total of 124 students participated in the summer internship with 32 (26%) achieving publication. The publication was significantly more likely for students that were from highly ranked undergraduate institutions (p = 0.04; likelihood ratio (LR) = 5.788), were future Alpha Omega Alpha (AOA) members (p = 0.03; LR = 4.597), or worked with a mentor focused on clinical rather than basic science research (p = 0.02; LR = 5.662). Forty-four students participated in the fourth-year elective with 11 (25%) achieving publication. The publication was more likely if the student worked with a mentor without a Doctor of Medicine (MD)/Doctor of Osteopathic Medicine (DO) degree (p = 0.001; LR = 7.051), with a PhD degree (p = 0.002; LR = 7.820), or a mentor with prior publication(s) with prior mentee(s) (p = 0.03; LR = 5.368). CONCLUSION: Only one-quarter of mentor-mentee research pairings resulted in publication, with student-related factors more predictive for publication from the internship and mentor-related factors more predictive of publication from the elective. Approaches to promote successful completion of medical student research projects should be considered to yield the greatest value from students' work and strengthen the development of future physician-scientists.

Methods of Academic Course Planning for Cancer Biology PhD Students to Enhance Knowledge of Clinical Oncology.

Little is known about how clinical oncology concepts are taught to PhD students or the most effective methods of doing so. In this study, electronic surveys were sent to faculty and students at PhD training programs, assessing their institution's methods of clinical oncology education and their perspective on optimal approaches to clinical oncology education. Only 40.0% of students reported any clinical oncology component to their institution's training, and only 26.5% had a clinician on their graduate advisory committee. Forty-three percent of students believed that they had a good understanding for translating basic science research into clinical practice, and 77.2% of all participants believed dual degree MD/PhD students were superior to PhD students in this regard. Lectures on clinical oncology research topics were the most valuable type of experience for all participants and were also the most common type of experience utilized. Working with a clinician to develop a clinical trial with correlative endpoints was also highly valued, but was only utilized by approximately 10% of programs. Faculty rated the value of nearly all types of clinical oncology exposure significantly lower than did students. Inclusion of the approaches identified in this study is likely to enhance PhD training in oncology-related disciplines. Cancer Res; 77(18); 4741-4. ©2017 AACR.

Inferior vena cava filter placement in late-stage cancer.

Inferior vena cava (IVC) filters are increasingly used in patients with advanced-stage cancer for prophylaxis of pulmonary embolus. We evaluated the survival benefit of placing IVC filters in patients with late-stage malignancy and assessed their effectiveness in preventing pulmonary embolism. Between 1998 and 2003, 5,970 patients were treated with a primary diagnosis of malignancy at a tertiary care facility. Retrospective analysis identified 55 consecutive patients with stage III or IV malignant disease and venous thromboembolism (VTE) who received IVC filters. Retrospective review of electronic hospital charts identified subsequent pulmonary emboli, procedure-related complications, and survival. In a case control study, 16 patients with VTE but without IVC filter were matched for age, sex, type of malignancy, and stage of disease. IVC filter placement effectively prevented computed tomography (CT) scan or ventilation/perfusion ratio (V/Q) scan-proven pulmonary embolus in 52/55 (94.5%) patients. Complications developed in 4/55 or 7.3% of patients; 13/55 (23.6%) patients with late-stage cancer survived less than 30 days following placement of the filter. Another 23.6% of this group survived longer than 1 year. Ambulatory status differed significantly (p = 0.01) between these 2 subgroups. In the case control study, IVC filter placement conferred no survival benefit compared to the control group. One recurrent pulmonary embolism was observed in both the filter group and the control group. No deaths due to thromboembolic complications were observed in either group. In late-stage cancer, patient survival is limited primarily by the malignant process. While IVC filter placement is effective in preventing pulmonary emboli, there may be limited survival benefit in this particular patient population. However, there exists a subset of this population whose functional status predicts longer survival times after filter placement.

Leptin receptor expression and cell signaling in breast cancer.

Obesity is considered a risk factor for many cancers, including breast cancer. Our laboratory has previously shown that leptin is mitogenic in many cancer cell lines, including breast. Information regarding the effects of high leptin levels on leptin receptor expression and signaling is lacking. The purpose of this study was to characterize leptin receptor expression in response to leptin in breast cancer cells. In addition, SOCS-3 expression (a leptin inducible inhibitor of leptin signaling), plus MAPK and PI3K signaling, were examined to determine their role in leptin-induced cell proliferation. Breast cancer cell lines, ZR75-1 and HTB-26, were treated with 0, 4, 40 or 80 ng/ml of leptin. Multiplex RT-PCR was performed to determine relative mRNA expression levels of the human short (huOB-Ra) or long (huOB-Rb) leptin receptor isoforms, or SOCS-3. MAPK and PI3K signaling was analyzed by phosphorylation of ERK and Akt, respectively, via Western blotting. Cell proliferation and inhibitor studies were analyzed by MTT assay. HTB-26 and ZR75-1 both expressed huOB-Ra, huOB-Rb and SOCS-3 mRNA; however, mRNA expression levels generally remained unchanged over time with leptin treatment. MAPK and PI3K pathways were activated in the presence of leptin over time. MAPK and PI3K inhibitors significantly blocked leptin-induced proliferation. Higher levels of circulating leptin contribute to breast cancer proliferation by activation of the MAPK and PI3K signaling pathways involved in cell growth and survival. The mitogenic effects of leptin are not a consequence of altered leptin receptor or SOCS-3 mRNA expression.

Expression of STAT3 and SOCS3 in pancreatic acinar cells.

BACKGROUND: The signal transducer and activator of transcription (STAT) and suppressor of cytokine signaling 3 (SOCS3) pathways are involved in organ inflammation. In the pancreas, however, the STAT3 and SOCS3 response to inflammatory stimuli is unknown. Therefore, we hypothesized that mRNA expression for these signaling proteins would be induced in response to pro-inflammatory mediators TNFalpha and LPS. Because activation of STAT3 and SOCS3 is also linked to cytokine stimulation, we tested TNFalpha and LPS, either alone or in combination with IL-1beta or IL-6 in an in vitro model using rat pancreatic acinar cells. METHODS: Rat pancreatic acinar cells (AR42J) were treated with combinations of LPS (10 microg/ml) or TNFalpha (10, 100, or 200 ng/ml) in the presence or absence of IL-1beta or IL-6 for 15, 30, 45, 60, 180, or 360 min. At each time point, total RNA was purified and analyzed via RT-PCR for STAT3 and SOCS3 mRNA expression. RESULTS: LPS and TNFalpha activated STAT3 and SOCS3 in pancreatic acinar cells. STAT3 mRNA expression was significantly (P < 0.01) increased above controls without further stimulation by IL-6 or IL1-beta. Significant increases in SOCS3 expression were observed with LPS + IL-6 at 30, 45, 60, 180, min (P < 0.05). SOCS3 mRNA expression with LPS + IL-1beta treatment was maximal by 1 h (P < 0.05). Enhanced STAT3 expression was evident by 3 h with TNFalpha alone (P < 0.01). The addition of cytokines kept STAT3 mRNA levels high. At 200 ng/ml TNFalpha, SOCS3 mRNA levels were increased, but significantly reduced in the presence of IL-1beta or IL-6 (P < 0.05). CONCLUSIONS: We have shown that LPS and TNFalpha are potent mediators of STAT3 and SOCS3 expression in the pancreas and that the cytokines IL-6 and IL-1beta are indirectly involved in the signaling pathway. Alteration of the STAT pathway should be explored as a therapeutic target for treatment of pancreatic inflammation.

Leptin induces cell migration and the expression of growth factors in human prostate cancer cells.

BACKGROUND: The adipocyte hormone leptin has been shown to increase migration and angiogenesis in epithelial cells. Therefore, we hypothesized that leptin would induce prostate cancer cell migration and growth factor expression in vitro. METHODS: Prostate cancer cell lines DU145 and PC-3 (androgen-resistant) were treated with leptin over time. Supernatants were assayed for growth factor expression via enzyme-linked immunosorbent assay (ELISA). Becton Dickinson-Falcon Transwell systems were used to assay leptin-induced migration. RESULTS: Leptin significantly induced expression of vascular endothelial growth factor (VEGF), transforming growth factor-beta1 (TGF-beta1), and basic fibroblast growth factor (bFGF) in DU145 and PC-3 cells. Prostate cancer cell migration was enhanced by leptin and inhibited 50% to 70% with the addition of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) inhibitors. CONCLUSIONS: The mitogenic effects of leptin on cancer cells, in combination with the increased migration and expression of growth factors, overall likely contributes to the progression of prostate cancer. Therefore, obesity associated with high leptin levels should be considered a risk factor in prostate cancer patients.

Prostate cancer cell proliferation is influenced by leptin.

BACKGROUND: Obesity is considered a risk for many cancers. Serum leptin levels are often elevated in obese people. Leptin acts as a mitogenic agent in many tissues; therefore, it may act to promote cancer cell growth. We previously demonstrated that leptin acts as a growth factor for prostate cancer cells in vitro. The purpose of this study was to characterize leptin receptor isoform mRNA expression in leptin-treated DU145 and PC-3 prostate cancer cell lines. Expression levels of SOCS-3, a known leptin-inducible suppressor of leptin signaling, and known mitogenic signaling pathways of PI3K and ERK were also analyzed METHODS: DU145 and PC-3 cells were treated with 0, 4, 40, or 80 ng/ml leptin for 0, 0.5, 1, 2, 4, 24, or 48 h. Multiplex RT-PCR was performed to determine mRNA levels of the short (huOB-Ra) or the long (huOB-Rb) OB-R isoforms or SOCS-3. p-Akt and p-ERK were determined by Western blot. Cell viability and apoptosis were determined by MTT and nucleosomal fragmentation assay RESULTS: DU145 and PC-3 expressed huOB-Ra, huOB-Rb, and SOCS-3 mRNA. huOB-Ra mRNA levels increased in PC-3 at 48 h (P < 0.01); however, no significant changes were observed in DU145. huOB-Rb mRNA levels decreased at 48 h in DU145; however, a twofold increase at 48 h (P < 0.01) was observed with PC-3 and was dose-dependent (P < 0.05). Leptin increased SOCS-3 mRNA in DU145 at 24 and 48 h (P < 0.05) and in PC-3 at 1 h (2-fold) and 48 h (fivefold; P < 0.01). Leptin up-regulated p-Akt in a time- and dose-dependent manner in the DU145 prostate cancer cells via a suppression of apoptosis. Leptin up-regulated p-ERK in a time-dependent manner in PC-3 cells CONCLUSIONS: In prostate cancer cells, the mitogenic effects of leptin are not a consequence of altered receptor isoform mRNA expression. No defect in SOCS-3 signaling was observed, and proliferation appears to be working through the PI3K and MAPK leptin receptor-activated pathways, depending on cell type. Leptin stimulation may be selective for either pathway to suppress apoptosis, thereby enhancing prostate cancer growth.