tbuckley/cabot-search huggingface dataset:
Abstract 60: PTEN expression, cholesterol metabolism, and lethal prostate cancer
Authors: Konrad H. Stopsack, Travis A. Gerke, Lorelei A. Mucci, Jennifer R. Rider
Journal: Cancer Research (2016)

Abstract BACKGROUND: We previously showed that mRNA expression of squalene monooxygenase (SQLE), part of the cholesterol synthesis pathway, is associated with lethal prostate cancer. In-vitro studies suggest that loss of PTEN expression and resulting PI3K pathway activation drive cholesterol ester accumulation in aggressive prostate cancers through sterol regulatory element-binding protein (SREBP) and acyl coenzyme A-cholesterol acyltransferase (ACAT1) activity. In two prospective cohorts, we studied whether lower PTEN expression is associated with cholesterol metabolism and how this relates to lethal prostate cancer. METHODS: We analyzed men with prostate cancer from the prospective prostatectomy Health Professionals Follow-up Study and Physicians’ Health Study. 105 men had lethal cancer and 284 men non-lethal disease without metastases at 8 years of follow-up. Whole-transcriptome mRNA expression profiling data was available from diagnostic prostate tumor specimens. Linear regression models were used to assess continuous and categorical associations, and Pearson correlation coefficients were calculated. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs) of lethal prostate cancer. RESULTS: Both lower PTEN and higher SQLE expression were associated with higher Gleason grade (p trend &amp;lt; 0.001 each). Correlations of PTEN with SREBF1 (r = -0.08, p = 0.1), SREBF2 (r = -0.09, p = 0.07), and ACAT1 (r = 0.04, p = 0.4) were weak. SREBF2 was correlated with SQLE (r = 0.33, p &amp;lt; 0.001) but not with ACAT1 (r = -0.01, p = 0.8). Low PTEN was associated with lethal cancer (OR, 1.50 per 1 standard deviation [SD] decrease; 95% CI, 1.20 to 1.87; p = 0.001). High SQLE was associated with lethal cancer (OR 2.13 per 1 SD increase, 95% CI, 1.63 to 2.79; p &amp;lt; 0.001). SREBF1, SREBF2, and ACAT1 were not associated with lethal cancer (all p &amp;gt; 0.05). Adjusting for PTEN mildly attenuated the association of SQLE with lethal cancer (OR, 2.07; 95% CI, 1.57 to 2.73), as did additional adjustment for age, Gleason grade, and stage (SQLE: OR, 1.75; 95% CI, 1.29 to 2.40). In the lowest quartile of PTEN expression, SQLE was less strongly associated with lethal cancer (OR 1.74; 95% CI, 1.20 to 2.52) compared to the upper three quartiles (OR 2.47; 95% CI, 1.69 to 3.60; p interaction = 0.2). CONCLUSION: Low PTEN mRNA expression and high SQLE are features of aggressive prostate cancers. However, at the time of prostatectomy, SREBF1/2 expression and resulting ACAT1 expression do not appear to be major characteristics of prostate cancers with lethal outcomes. Citation Format: Konrad H. Stopsack, Travis A. Gerke, Lorelei A. Mucci, Jennifer R. Rider. PTEN expression, cholesterol metabolism, and lethal prostate cancer. [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 60.
Caring for High-Need, High-Cost Patients — An Urgent Priority
Authors: David Blumenthal, Bruce Chernof, Terry Fulmer, John Lumpkin, Jeffrey Selberg
Journal: New England Journal of Medicine (2016)

Interview with Dr. David Blumenthal on approaches to caring for the 5% of patients who account for 50% of annual health care spending. (10:42)Download Five foundations aim to improve care for high-need, high-cost patients by building U.S. capabilities in three vital areas: clarifying the needs of such patients, elucidating the best ways of caring for them, and assisting with the spread of proven approaches.
Cancer imaging: principles and practice
Authors: S. E. M. Clarke, K. E. Britton
Journal: Clinical Nuclear Medicine (1998)

Unlike the majority of imaging modalities used in the management of patients with suspected or proven malignancy, which rely on alterations in structure to visualize the tumour site, nuclear medicine imaging techniques utilize the ability to visualize alterations in metabolism. These alterations in metabolism may occur in the tissues surrounding the tumour site or may occur in the tumour itself. Radiopharmaceuticals used in tumour imaging may also be divided into those that are specifically taken up by tumours and those whose uptake is non-specific. These non-specific agents also localize in other pathological processes such as inflammation. In this chapter, the principles underlying the localization of radiopharmaceuticals used for tumour imaging will be discussed (Table 2.1) and the role of nuclear medicine in the management of cancer patients will be explored.
Case 6-1973
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Edwin O. Wheeler, Robert E. Scully
Journal: New England Journal of Medicine (1973)

Presentation of CaseA 78-year-old woman was admitted to the hospital because of dyspnea.She had diphtheria at the age of 18 months and scarlet fever during childhood. She was always unable to keep up with other children in physical activity. When she was 12 years of age a physician found that her pulse rate was 40. She was first seen at this hospital at the age of 24 years, at which time she was receiving thyroid hormone because of a diagnosis of hypothyroidism, based on bradycardia. Physical examination revealed a moderately loud systolic murmur over the precordium. An electrocardiogram . . .
When Intensive Insulin Therapy (MDI) Fails in Patients With Type 2 Diabetes: Switching to GLP-1 Receptor Agonist Versus Insulin Pump
Authors: Ohad Cohen, Sebastiano Filetti, Javier Castañeda, Marianna Maranghi, Mariela Glandt
Journal: Diabetes Care (2016)

Treatment with insulin, alone or with oral or injectable hypoglycemic agents, is becoming increasingly common in patients with type 2 diabetes. However, approximately 40% of patients fail to reach their glycemic targets with the initially prescribed regimen and require intensification of insulin therapy, which increases the risks of weight gain and hypoglycemia. Many of these patients eventually reach a state in which further increases in the insulin dosage fail to improve glycemic control while increasing the risks of weight gain and hypoglycemia. The recently completed OpT2mise clinical trial showed that continuous subcutaneous insulin infusion (CSII) is more effective in reducing glycated hemoglobin (HbA1c) than intensification of multiple daily injection (MDI) insulin therapy in patients with type 2 diabetes who do not respond to intensive insulin therapy. CSII therapy may also be useful in patients who do not reach glycemic targets despite multidrug therapy with basal-bolus insulin and other agents, including glucagon-like peptide (GLP)-1 receptor agonists; current guidelines offer no recommendations for the treatment of such patients. Importantly, insulin and GLP-1 receptor agonists have complementary effects on glycemia and, hence, can be used either sequentially or in combination in the initial management of diabetes. Patients who have not previously failed GLP-1 receptor agonist therapy may show reduction in weight and insulin dose, in addition to moderate improvement in HbA1c, when GLP-1 receptor agonist therapy is added to MDI regimens. In subjects with long-standing type 2 diabetes who do not respond to intensive insulin therapies, switching from MDI to CSII and/or the addition of GLP-1 receptor agonists to MDI have the potential to improve glycemic control without increasing the risk of adverse events.
TCT-250 Long-term Clinical Outcomes of Transient and Persistent No-Reflow Following Percutaneous Coronary Intervention (PCI): Insights from a Multi-center Australian Registry
Authors: Stavroula Papapostolou, Nick Andrianopoulos, Angela Brennan, Andrew Ajani, David Clark, Christopher Reid, Gishel New, Martin Sebastian, Laura Selkrig, Anthony Dart, Stephen Duffy, William Chan
Journal: Journal of the American College of Cardiology (2016)
Abstract 1683: Dual role of semaphorin5A in maintaining epithelial and mesenchymal phenotype in metastatic pancreatic cancer
Authors: Sugandha Saxena, Abhilasha Purohit, Michelle Varney, Surinder K. Batra, Rakesh K. Singh
Journal: Cancer Research (2016)

Abstract Pancreatic cancer (PC) is a highly aggressive disease and in general has metastasized to distant organs by the time of its clinical diagnosis. Poor five-year survival rate of 7% with an average survival time of 5-8 months highlight the gravity of the situation and necessitate a better understanding of the molecules and mechanisms that lead to metastatic dissemination in PC. One of the key processes that lead to metastasis is the gain of cellular migration ability. Previous reports from our laboratory have identified semaphorin5A (SEMA5A), an axon guidance cue molecule regulating cellular migration, as a putative cell adhesion molecule which is involved in organ-specific homing during PC metastasis. Also, differential expression of SEMA5A was observed in cells derived from metastatic sites in comparison to those arising from primary tumors. On the basis of the these findings, we hypothesize that SEMA5A regulates epithelial to mesenchymal changes necessary to drive cellular migration and further leads to establishment of these cells at secondary sites. We utilized various cellular models such as the L3.3 and L3.6pl cell lines with different metastatic potential, cell lines derived from metastatic sites (Capan-1 and CD18/HPAF) with stable knock down of SEMA5A, and cell lines derived from primary tumors (Panc1) with overexpression of SEMA5A. We evaluated epithelial and mesenchymal markers, in vitro cellular migration and the metastatic potential of these cells. We observed down regulation of E-cadherin expression and re-localization of beta-catenin from the membrane to the nucleus in SEMA5A knockdown cells. Similarly, overexpression of SEMA5A in Panc1 cells resulted in higher E-cadherin expression. We also observed higher SEMA5A and E-cadherin expression in the highly metastatic L3.6pl cells in comparison with L3.3 cells. Furthermore, knock-down SEMA5A in Capan-1 cells resulted in enhanced in vitro cellular migration and higher metastasis when control or SEMA5A knockdown cells were orthotopically implanted in nude mice. Our observations suggest that SEMA5A plays a bi-functional role in mediating epithelial to mesenchymal transition at primary site while regulating mesenchymal to epithelial transition and establishment at secondary sites. Citation Format: Sugandha Saxena, Abhilasha Purohit, Michelle Varney, Surinder K. Batra, Rakesh K. Singh. Dual role of semaphorin5A in maintaining epithelial and mesenchymal phenotype in metastatic pancreatic cancer. [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 1683.
The use of computed body tomography in malignant melanoma
Authors: I. Kostrubiak
Journal: JAMA (1988)

Malignant melanoma has no predictable clinical behavior. The Breslow depth and Clark's level of invasion are important prognostic factors, but their prognostic values are overshadowed by the presence of regional lymph node metastasis (stage III disease). The authors reviewed the CT scans and charts of 67 patients who had a confirmed diagnosis of malignant melanoma. Excluding patients with stage I disease, all others had histological evidence of metastatic disease shown in one or more sites by biopsy or necropsy specimens. In addition, in some patients metastatic disease was documented by clinical course and follow-up study in sites such as the brain, lung, and liver, where biopsies were not performed. They tried to ascertain any change in the extent of disease or any alteration in therapy that was based on the findings on the CT scan.
Abstract 957: Regulation of PCGEM1 in castration resistant prostate cancer
Authors: Tsui-Ting Ho, Yin-Yuan Mo
Journal: Cancer Research (2016)

Abstract PCGEM1 has been shown to be prostate cancer specific long non-coding RNA (lncRNA). Our previous study indicates that PCGEM1 plays a role in castration resistance through regulation of androgen receptor (AR) splice variants. Although it is known that PCGEM1 is often upregulated in prostate cancer, little is known how PCGEM1 is regulated. In the present study, we show that p54/nrb is a positive regulator for PCGEM1. PCGEM1 is higher in castration resistant CWR22Rv1 than in androgen sensitive LNCaP cells. Moreover, androgen deprivation induces PCGEM1 in LNCaP cells. Histone ChIP assays suggest that the active binding site is within 500 bp upstream of putative transcriptional start site. By using biotin-labelled PCR product and pulldown assays combined with mass spectrometry analysis, we show that p54/nrb interacts with the promoter of PCGEM1. While ectopic expression increases, suppression of p54/nrb by RNAi or knockout (KO) suppresses PCGEM1, supporting a role for p54/nrb in PCGEM1 regulation. Moreover, rescue experiments indicate that re-expression of p54/nrb in KO cells restores the ability to induce PCGEM1. Finally, 3, 3’-Diindolylmethane (DIM), a known chemoprevention agent derived from plants such as broccoli, is capable of suppressing PCGEM1 expression by preventing the interaction of p54/nrb with the PCGEM1 promoter. In particular, DIM reduces tumor growth by suppression of PCGEM1 and promoting apoptosis in the castrated xenograft mouse model. Together, these results demonstrate a novel mechanism of how PCGEM1 and AR splicing are regulated. As a result, PCGEM1 may ultimately contribute to castration resistance. Citation Format: Tsui-Ting Ho, Yin-Yuan Mo. Regulation of PCGEM1 in castration resistant prostate cancer. [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 957.
Abstract LB-060: A novel target for genetic silencing of AXL mediates taxane resistance, invasion, and migration in uterine cancer
Authors: Marguerite Palisoul, Mai Nguyen, Hua Pan, Anne Lohrey, Samuel Wickline, Matthew Powell, David Mutch, Katherine Fuh
Journal: Cancer Research (2016)

Abstract Objectives: We investigated the role of AXL expression in chemotherapy response in uterine papillary serous cancer, and sought to reverse chemoresistance through inactivation of AXL. Methods: In vitro cell viability (XTT) assays were performed to confirm response to chemotherapy in AN3CA (taxane sensitive) and ARK1 (taxane resistant) uterine cell lines. AXL knockdown by siRNA was performed with either a traditional transfection reagent (DharmaFECT) or with a novel serum-stable, cell-penetrating, endosomolytic amphipathic peptide delivery system (p5RHH). Following knockdown of AXL using siRNA and p5RHH, chemotherapy response was assessed by XTT assay and invasion and migration assays were performed. Cell viability assays were analyzed using multiple t-tests. P &amp;lt; 0.05 was considered statistically significant. Results: Expression of AXL was found to be associated with a worse prognosis in uterine cancer. Chemoresistance was validated with XTT assays for AN3CA and ARK1. Western blotting confirmed over-expression of AXL in the chemoresistant cell line, and lack of AXL expression in its chemosensitive counterparts. Reversal of paclitaxel resistance was achieved in ARK1 cells genetically by silencing AXL with shRNA. The novel delivery system, p5RHH, combined to siAXL, was shown to inactivate AXL in ARK1 cells at the RNA and protein level to a similar extent as traditional transfection technique (8.4-fold vs 8.7-fold decrease for RNA, respectively; 67% vs 83% knockdown at 48h and 84% vs 97% knockdown at 96 hours for protein, respectively). Reversal of paclitaxel resistance was achieved in ARK1 cells therapeutically and genetically using the p5RHH-siAXL complex. With AXL silencing using the p5RHH-siAXL complex, tumor cell invasion was inhibited by greater than 40%, and tumor cell migration was inhibited by greater than 60%. Conclusions: AXL expression is associated with chemoresistance in a uterine papillary serous cancer cells. Genetic inactivation of AXL in a taxane-resistant uterine cancer cells reverses chemoresistance. A novel siRNA nano-particle delivery system was successfully utilized to mimic genetic inactivation resulting in improved chemotherapy response and decreased invasion and migration. Citation Format: Marguerite Palisoul, Mai Nguyen, Hua Pan, Anne Lohrey, Samuel Wickline, Matthew Powell, David Mutch, Katherine Fuh. A novel target for genetic silencing of AXL mediates taxane resistance, invasion, and migration in uterine cancer. [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 LB-060.
Mutations in DCDC2 (doublecortin domain containing protein 2) in neonatal sclerosing cholangitis
Authors: Tassos Grammatikopoulos, Melissa Sambrotta, Sandra Strautnieks, Pierre Foskett, A.S. Knisely, Bart Wagner, Maesha Deheragoda, Chris Starling, Giorgina Mieli-Vergani, Joshua Smith, Laura Bull, Richard J. Thompson
Journal: Journal of Hepatology (2016)
Economic burden of hematologic malignancies in Calabar, Nigeria from the patient's perspective.
Authors: Marcus Inyama Asuquo, Enang Bassey Udah, Aniekan Etokidem
Journal: Journal of Clinical Oncology (2014)

e19525 Background: Hematologic malignancies are not included in the Nigerian Health insurance scheme. All persons diagnosed of these diseases will receive treatment from out of pocket expenses. The cost of managing these disorders are very expensive. Patients are unable to commence, continue or complete treatment as a result of this burden. Family economies are depleted for those who successfully complete the recommended regimen. This study is aimed at answering two main questions. How great is the economic burden of treating patients with hematologic malignancies on the patient and family? How does this economic burden affect the treatment objectives and survival? Methods: Patients records were examined, questionnaires that looked at the sources of funding for treatment and follow up were administered. Cost of drugs and consumables were obtained from the hospital pharmacy and major pharmaceutical stores in the city. Information was collated and analysed using SPSS. Results: The cost of treatment of lymphoid malignancies ranged from USD192.94 to 846.35 for cytotoxic regimen and USD 12,400.59 to 124,699.41 for targeted regimen. Multiple myeloma USD 916.47 to 3,061.77 for cytotoxics and USD 39,870.59 for targeted drugs. Acute leukaemia patients USD 240.00 to 1,058.20 for Cytotoxics. Chronic leukaemias USD 194.12 to3,411.77 for cytotoxics and USD 12,400.59 to 12,352.94 for targeted regimen. Diagnostic work up and follow up expenditure ranged from USD 1,110.59 to 1,878.90. Patients will require USD 947.41 to 1,801.48 for supportive care. Out of this amount, 22-44% will be needed for blood transfusion requirement. The patient’s family was the main source of funding for treatment followed by sale of personal and family assets.Average minimum wage is USD105.88/ month. Conclusions: High cost of managing hematologic malignancies constitute a major contributing factor to poor compliance and survival. It impoverishes the patient, families and at times communities. Reliance on out of pocket expenditure instead of inclusion either whole or partly in the country’s National Health Insurance Scheme is a wrong policy that must be addressed by developing countries. Strategies aimed at reducing cost of treatment needs to be vigorously pursued.
Leading pancreatic cancer researcher is struck off for fabricating data
Authors: Clare Dyer
Journal: BMJ (2016)

A leading researcher into innovative treatments for pancreatic cancer has been struck off the UK medical register for “gross and clear fabrication of research data.”

Thorsten Hagemann, who worked at Bart’s Cancer Institute in London, was found guilty of 24 instances of misleading and dishonest conduct between 2012 and 2014.

He was found to have falsified data in grant applications to the Pancreatic Cancer Research Fund and Cancer Research UK, in a paper published in Nature ,1 in another paper which was submitted to Nature Medicine but rejected, and in a presentation to Cancer Research Technology.

Hagemann, who qualified in Germany in 1999, progressed rapidly in …
Abstract 649: Biobank collaboration enables cancer modeling with high quality biospecimens and data
Authors: Lindsay S. Shopland, Ivette Emery, Todd Hoffert, Rise Aalberg, Petra Helbig, Susan E. LaPierre, Vicky Sanders, Kevin D. Mills, Tara Hill, Aysha Sheikh, Michael Jones, Anne Breggia, Jens Rueter
Journal: Cancer Research (2016)

Abstract According to the National Cancer Institute, the lack of standardized, high-quality biospecimens is one of the most significant roadblocks to progress in cancer research. This shortage especially affects the generation of murine xenograft models of human cancers. Maine, with the third largest age-adjusted cancer incidence rate in the nation, has abundant cancer specimens potentially available for research. To meet the need for quality biospecimens, the biobanks at Eastern Maine Medical Center and Maine Medical Center have established a collaboration to jointly procure cancer specimens from Maine patients. Through this collaboration, the cooperating biobanks provide researchers with tissue, blood, bone marrow and other body fluid specimens from a broad spectrum of solid and hematologic cancers. The specimens from hematologic cancer patients have &amp;gt; 90% viability and demonstrate anticipated biomarker composition by flow cytometry. The comparatively high frequency of engraftment of solid tumors in immunodeficient mice is also indicative of the quality of the samples procured by both repositories. Currently, the biobanks are providing fresh ovarian tumors to develop new xenograft models for poorly engrafting tumors in collaboration with the Jackson Laboratory's Patient Derived Xenograft Program. Both biobanks are integrated with clinical and pathology practices and, therefore, the specimens are annotated with in-depth, de-identified patient datasets. With support from the Maine Cancer Foundation, the biobanks have created the Maine Cancer Biospecimen Portal (MBCP), a website that provides one-stop access to annotated cancer biospecimens and to consultation services for translational research study design. The collaboration of the EMMC and MMC biobanks provides a resource of high quality biospecimens for advancement of both in vivo and in vitro translational research such as mouse models of human cancers. Citation Format: Lindsay S. Shopland, Ivette Emery, Todd Hoffert, Rise Aalberg, Petra Helbig, Susan E. LaPierre, Vicky Sanders, Kevin D. Mills, Tara Hill, Aysha Sheikh, Michael Jones, Anne Breggia, Jens Rueter. Biobank collaboration enables cancer modeling with high quality biospecimens and data. [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 649.