tbuckley/cabot-search huggingface dataset:
Shackleton’s heart
Authors: Ian Calder, Jan Till
Journal: Journal of the Royal Society of Medicine (2016)

One hundred years ago, from October 1915 to April 1916, Sir Ernest Shackleton and his men were forced to camp on ice floes in the Weddell Sea after the Endurance was crushed and sank. After escaping from the ice in three small open boats, the crew of the Endurance spent six months living under two of the boats on Elephant Island, while Sir Ernest with five companions sailed 800 miles in the third, and made the first crossing of the mountains and glaciers of South Georgia. The Endurance expedition was the third of four expeditions towards Antarctica undertaken by Sir Ernest between 1901 and 1922 and was the only one during which he did not suffer a physical breakdown. We believe that his breakdowns were the result of a congenital cardiac defect. The evidence rests mainly on diary entries made by Dr Eric Marshall, the medical officer on Shackleton’s second expedition to the Antarctic (1907–1909) in the Nimrod. On 20 January 1908, Dr Marshall wrote in his diary ‘Heard S was very unwell after pulling on a rope. Will not hold myself responsible until he allows me to examine him. Something wrong?’. As medical officer, Dr Marshall was able to insist on an examination and on two occasions found a ‘pulmonary systolic murmur’. Shackleton, Marshall, Wild and Adams sledged south, discovered the Beardmore Glacier and the Polar plateau, but realising they would perish from starvation if they carried on, turned back when about 100 miles from the Pole. Back on the Beardmore, some 380 miles from base, Dr Marshall wrote ‘Shacks collapsed after dinner tonight’, and the next day ‘Sh very unwell, walked by the sledge all day – Midday-Pulse on march thin & thready, irregular about 120’. However, Shackleton recovered within a few days, and was one of the strongest of the party by the end of the journey, performing a forced march of thirty miles with Frank Wild to prevent the Nimrod leaving without them. As well as the two episodes recorded by Dr Marshall, Sir Ernest suffered a breakdown in 1903, during his first Antarctic expedition in the Discovery. He was unable to pull the sledge, due to breathlessness and weakness, towards the end of a sledge journey southwards with Robert Scott and Edward Wilson. Shackleton’s collapse was attributed to scurvy and ‘a sort of asthma’, and he was invalided home against his will. Dr James McIlroy, medical officer on Shackleton’s third and fourth expeditions, told of two other incidents, one in 1919, during an expedition to Spitzbergen ‘ – when he [Shackleton] changed colour very badly – he had a very bad bout that time but he wouldn’t undress and let me listen to his heart’, and a similar episode in 1922 on Shackleton’s last expedition. Figure 1. Frank Hurley (L) and Sir Ernest Shackleton on an ice-floe in the Weddell Sea. Image provided by the Scott Polar Research Institute, University of Cambridge.
Yes‐associated protein 1 and transcriptional coactivator with PDZ‐binding motif activate the mammalian target of rapamycin complex 1 pathway by regulating amino acid transporters in hepatocellular carcinoma
Authors: Yun‐Yong Park, Bo Hwa Sohn, Randy L. Johnson, Myoung‐Hee Kang, Sang Bae Kim, Jae‐Jun Shim, Lingegowda S. Mangala, Ji Hoon Kim, Jeong Eun Yoo, Cristian Rodriguez‐Aguayo, Sunila Pradeep, Jun Eul Hwang, Hee‐Jin Jang, Hyun‐Sung Lee, Rajesha Rupaimoole, Gabriel Lopez‐Berestein, Woojin Jeong, Inn Sun Park, Young Nyun Park, Anil K. Sood, Gordon B. Mills, Ju‐Seog Lee
Journal: Hepatology (2015)

Metabolic activation is a common feature of many cancer cells and is frequently associated with the clinical outcomes of various cancers, including hepatocellular carcinoma. Thus, aberrantly activated metabolic pathways in cancer cells are attractive targets for cancer therapy. Yes‐associated protein 1 (YAP1) and transcriptional coactivator with PDZ‐binding motif (TAZ) are oncogenic downstream effectors of the Hippo tumor suppressor pathway, which is frequently inactivated in many cancers. Our study revealed that YAP1 / TAZ regulates amino acid metabolism by up‐regulating expression of the amino acid transporters solute carrier family 38 member 1 ( SLC38A1 ) and solute carrier family 7 member 5 ( SLC7A5 ). Subsequently, increased uptake of amino acids by the transporters ( SLC38A1 and SLC7A5 ) activates mammalian target of rapamycin complex 1 (mTORC1), a master regulator of cell growth, and stimulates cell proliferation. We also show that high expression of SLC38A1 and SLC7A5 is significantly associated with shorter survival in hepatocellular carcinoma patients. Furthermore, inhibition of the transporters and mTORC1 significantly blocks YAP1/TAZ‐mediated tumorigenesis in the liver. These findings elucidate regulatory networks connecting the Hippo pathway to mTORC1 through amino acid metabolism and the mechanism's potential clinical implications for treating hepatocellular carcinoma. Conclusion: YAP1 and TAZ regulate cancer metabolism and mTORC1 through regulation of amino acid transportation, and two amino acid transporters, SLC38A1 and SLC7A5, might be important therapeutic targets. (H epatology 2016;63:159–172)
P-036 Phase II study of gemcitabine and curcumin as first line treatment for locally advanced or metastatic pancreatic cancer: preliminary data
Authors: C. Soldà, R. Bardini, C. Sperti, G. Da Dalt, M. Gion, P. Fiduccia, F. Ursini, C. Aliberti, D. Pastorelli
Journal: Annals of Oncology (2015)
Macrophage Infiltration and Alternative Activation during Wound Healing Promote MEK1-Induced Skin Carcinogenesis
Authors: Christine Weber, Stephanie B. Telerman, Andreas S. Reimer, Ines Sequeira, Kifayathullah Liakath-Ali, Esther N. Arwert, Fiona M. Watt
Journal: Cancer Research (2016)

Abstract Macrophages are essential for the progression and maintenance of many cancers, but their role during the earliest stages of tumor formation is unclear. To test this, we used a previously described transgenic mouse model of wound-induced skin tumorigenesis, in which expression of constitutively active MEK1 in differentiating epidermal cells results in chronic inflammation (InvEE mice). Upon wounding, the number of epidermal and dermal monocytes and macrophages increased in wild-type and InvEE skin, but the increase was greater, more rapid, and more sustained in InvEE skin. Macrophage ablation reduced tumor incidence. Furthermore, bioluminescent imaging in live mice to monitor macrophage flux at wound sites revealed that macrophage accumulation was predictive of tumor formation; wounds with the greatest number of macrophages at day 5 went on to develop tumors. Gene expression profiling of flow-sorted monocytes, macrophages, and T cells from InvEE and wild-type skin showed that as wound healing progressed, InvEE macrophages altered their phenotype. Throughout wound healing and after wound closure, InvEE macrophages demonstrated sustained upregulation of several markers implicated in alternative macrophage activation including arginase-1 (ARG1) and mannose receptor (CD206). Notably, inhibition of ARG1 activity significantly reduced tumor formation and epidermal proliferation in vivo, whereas addition of L-arginase to cultured keratinocytes stimulated proliferation. We conclude that macrophages play a key role in early, inflammation-mediated skin tumorigenesis, with mechanistic evidence suggesting that ARG1 secretion drives tumor development by stimulating epidermal cell proliferation. These findings highlight the importance of cancer immunotherapies aiming to polarize tumor-associated macrophages toward an antitumor phenotype. Cancer Res; 76(4); 805–17. ©2016 AACR.
Cancer statistics for Asian Americans, Native Hawaiians, and Pacific Islanders, 2016: Converging incidence in males and females
Authors: Lindsey A. Torre, Ann M. Goding Sauer, Moon S. Chen, Marjorie Kagawa‐Singer, Ahmedin Jemal, Rebecca L. Siegel
Journal: CA A Cancer Journal for Clinicians (2016)

Cancer is the leading cause of death among Asian Americans, Native Hawaiians, and Pacific Islanders (AANHPIs). In this report, the American Cancer Society presents AANHPI cancer incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Among AANHPIs in 2016, there will be an estimated 57,740 new cancer cases and 16,910 cancer deaths. While AANHPIs have 30% to 40% lower incidence and mortality rates than non‐Hispanic whites for all cancers combined, risk of stomach and liver cancers is double. The male‐to‐female incidence rate ratio among AANHPIs declined from 1.43 (95% confidence interval, 1.36‐1.49) in 1992 to 1.04 (95% confidence interval, 1.01‐1.07) in 2012 because of declining prostate and lung cancer rates in males and increasing breast cancer rates in females. The diversity within the AANHPI population is reflected in the disparate cancer risk by subgroup. For example, the overall incidence rate in Samoan men (526.5 per 100,000) is more than twice that in Asian Indian/Pakistani men (216.8). Variations in cancer rates in AANHPIs are related to differences in behavioral risk factors, use of screening and preventive services, and exposure to cancer‐causing infections. Cancer‐control strategies include improved use of vaccination and screening; interventions to increase physical activity and reduce excess body weight, tobacco use, and alcohol consumption; and subgroup‐level research on burden and risk factors. CA Cancer J Clin 2016;66:182‐202. © 2016 American Cancer Society .
Phase II randomized study of gefitinib alone or plus UFUR treatment in Taiwanese patients with adenocarcinoma of the lung who failed at least two regimens
Authors: Y. Chen, R. Perng, J. Shih, J. Whang-Peng
Journal: Journal of Clinical Oncology (2008)

19031 Background: UFUR (tegafur/uracil) is suitable for metronomic chemotherapy with its underlying anti-angiogenesis mechanism. Present study is to assess the feasibility and the efficacy of adding daily low dose of oral UFUR into gefitinib treatment in lung cancer patients with adenocarcinoma who failed previous two regimens of chemotherapy. Methods: Taiwanese patients who had adenocarcinoma and failed at least 2 regimens, including taxanes and platinum, were enrolled and randomized into two arms: Oral gefitinib 250 mg daily alone (G) or plus oral UFUR (tegafur 100mg, uracil 224mg) twice daily (GU). From November 2005 to November 2007, 49 patients were enrolled. Results: Forty-four patients were evaluable for treatment response and toxicity at the end of 2007, including 21 patients in G and 23 patients in GU. Objective response rates were 33% in G and 26% in GU (p=0.703). Disease control rate (partial response plus stable disease) was 62% in G and 78% in GU. No grade 3 or higher toxicity occurred in present study. There was no statistical significant difference regarding toxicity profiles between two treatment arms, except grade 1 or 2 anemia that occurred more frequently in GU (43%) than G (19%). Median time to disease progression was higher in GU than G (10.5 months vs 5.4 months, p=0.5637). Six- month progression-free survival was 44.4% in G and 54.4% in GU. Median survival was longer than one year in both arms. Plasma cytokine (IL- 6, IL-8, VEGF, PDGF, and TGFα) analysis, including pre-treatment, 2 weeks and 4 weeks after treatment, and after disease progression will be performed soon and the results will be presented at the annual meeting. Conclusions: Gefitinib are effective in Taiwanese patients with adenocarcinoma of lung and failed previous platinum and taxane treatment. Addition of daily UFUR treatment produced a statistically insignificant better disease control rate and progression free survival, while toxicities were not increased. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca Oncology, Lilly Oncology, Roche
Abstract 16327: Aging and Senescence of Endogenous Cardiac Stem Cells (eCSCs) Determines Their Growth and Differentiation Potential
Authors: Georgina M Ellison, Joanna Polydorou, Rebecca Mercaldi, Anna Burdina, Carla Vicinanza, Thomas Theologou, Aung Oo, Manoj Kuduvalli, David J Wright, Mark Field, Bernardo Nadal-Ginard, Daniele Torella
Journal: Circulation (2012)

The adult myocardium harbours resident (endogenous) multi-potent cardiac stem cells (eCSCs). Manipulation of eCSCs ex-vivo and in situ has opened new therapeutic avenues for anatomical and function...
Patient-reported outcomes for determining prognostic groups in veterans with advanced cancer.
Authors: V. T. Chang, C. B. Scott, H. Yan, M. L. Gonzalez, J. Einhorn, B. Zhou, J. Cogswell, B. Crump, M. McPherson, B. Kasimis
Journal: Journal of Clinical Oncology (2010)

9040 Background: We previously reported 4 prognostic groups based upon Karnofsky performance status (KPS), Functional Assessment of Cancer Therapy (FACT) quality of life subscale for physical well-being (PWB), and Memorial Symptom Assessment Scale Short Form (MSAS-SF) subscale for physical symptom distress (PHYS). We performed prospective surveys to determine the validity of these 4 prognostic groups. Methods: A total of 880 VA pts: 417 retrospective cohort (RC) and 463 prospective cohort (PC), were analyzed. Both inpt and outpt were prospectively recruited in IRB approved studies from August 1999 to September, 2009. Survival was measured from the date of entry until death or December 1, 2009. Pts were evaluated with patient reported outcome (PRO) questionnaires including the FACT and MSAS-SF. ANOVA was used to test differences between groups in continuous variables; generalized Wilcoxon was used for differences between groups for survival. Results: The sample was elderly (average age 66.5 years) males (98%). The PC were 52% white and 45% black; 89% were current or former smokers. The majority of all pts had metastatic cancer (90%), with lung (28%) and prostate (26%) cancer being predominant. The median KPS was 80 in RC and 70 in PC. Evidence of greater physical distress in PC patients versus RC was reflected in PHYS (p<0.0001) and PWB (p = 0.0051). The median survival time (MST) for the 4 prognostic groups was 29 (KPS<50), 146 (KPS>40 and PWB<25), 292(KPS>40, PWB>24, PHYS>0.6), and 610 days (KPS>40, PWB >24, PHYS<0.6) in the RC. The MST for the PC was 33, 46.5, 124, and 209.5 days for the 4 prognostic groups (p<0.0001, all pairwise comparisons <0.02). Examination of the PRO collected in PC indicated that KPS and PHYS were best predictors of survival. Additional PRO did not improve prognostic groups. Conclusions: This study confirms the importance of physical dysfunction on prognosis and while the MST estimates are not consistent with original estimates, the groups remain distinct. These results have important considerations for end of life care and patient assessment. This work was supported by Project Death in America, VA HSRD PCC 98-068-02 and IIR 2-103. No significant financial relationships to disclose.
Short-term health-related quality of life with epirubicin and cyclophosphamide versus 5-fluorouracil, epirubicin and cyclophosphamide as adjuvant chemotherapy in Turkish patients with operable breast cancer
Authors: H. M. B. Demirkan, T. Yavuzsen, M. Dirioz, Y. Demiral, A. Alacacıoglu, Z. Baskan, H. Fidaner, M. Alakavuklar
Journal: Journal of Clinical Oncology (2005)

877 Background: Although adjuvant treatments improve disease free and overall survival in early breast cancer, one of the key issues is ensuring that patients have a worthwhile health-related quality of life (HRQOL). Our purpose is to compare short-term HRQOL in Turkish patients with operable breast cancer receiving the combination of epirubicin and cyclophosphamide (EC) or 5-fluorouracil, epirubicin and cyclophosphamide (FEC) as adjuvant chemotherapy. Methods: Between July 2001 and June 2003, eligible patients (n=60) with Stage I-II and Stage III breast cancer were assigned to EC (epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2) every three weeks for four cycles and FEC (5-fluorouracil 600 mg/m2, epirubicin 100 mg/m2 plus cyclophosphamide 600 mg/m2) every three weeks for six cycles respectively. HRQOL was assessed with WHOQOL-BREF, Beck Depression Inventory and State-Trait Anxiety Inventory at baseline and the start of cycles 2, 4 and 3 months after the last cycle. Treatment comparisons and scores changes between baselines were performed using statistical analysis software (SPSS 11.0 for Windows). All the scales were analyzed by using a two-sided t-test at the 5% significance level. Results: All the patients (n=60) completed baseline and subsequent measures. However, there were no statistically significant differences in global HRQOL between the two treatment groups. In both groups, selected aspects of HRQOL were impaired over time significantly, with decreased physical and social/family activities and impaired psychology; although significant improvements in emotional and physical functioning were seen after the end of both treatments except for continuous impaired social activity in FEC group. Conclusions: This information is important when advising women patients of the expected HRQOL consequences of treatment regimens and should help clinicians and their patients make informed treatment decisions. No significant financial relationships to disclose.
Evaluation and Treatment of Patients With Constipation
Authors: Todd Stern, Andrew M. Davis
Journal: JAMA (2016)

Constipation occurs in approximately 12% to 19% of the population1 and increases with age, especially after 60 years. Constipation is a common problem in outpatient practices and a frequent reason for admission to the hospital2 and thus is associated with significant adverse effects on quality of life and health care expenditures. Chronic constipation is defined as presence for more than 3 to 6 months of 2 or more of the following symptoms: decreased stool frequency, straining, hard stools, sensation of incomplete emptying or anorectal blockage, requirement for manual maneuvers to pass stool, and rare loose stools in the absence of laxative use.3 Unlike chronic constipation, constipation-predominant irritable bowel syndrome (IBS-C) presents as recurrent abdominal pain or discomfort associated with hard or infrequent stools or relieved by defecation. There are 3 categories of chronic constipation: disorders of defecation (dyssynergy), STC, and NTC. Defecatory disorders can occur with either STC or NTC. Most patients can be treated without extensive testing. Systemic conditions and medications that aggravate constipation should be addressed.4 Diet, fluids, nonprescription medications, fiber supplements, osmotic agents, and stimulant cathartics can be effective but may challenge adherence. Refractory cases require specific testing and specialist referral. New drugs with novel mechanisms of action have shown promise.5,6 Biofeedback typically is recommended for defecatory disorders. Colorectal surgery is a last resort.
Abstract 3732: Pioglitazone and cardiovascular outcomes
Authors: Nagapradeep Nagajothi, Saravanan Balamuthusamy, Sasikanth Adigopula, Jose-Luis E Velazquez-Cecena, Kalpana Raghunathan, Ahmad Khraisat, Praven Naga, Namratha Mapakshi, Sarabjeet Singh, Sandeep Khosla, Daniel Benatar
Journal: Circulation (2007)
A Phase II Clinical Trial of Fludarabine and Cyclophosphamide Followed by Thalidomide for Angioimmunoblastic Lymphoma (AITL), an NCRI Clinical Trial. CRUK C17050/A5671
Authors: William M Townsend, Roderick J. Johnson, Nicholas Counsell, Humra Shah, Bryson Pottinger, Katy Evans, Caroline Wickham, Paul Smith, Rudin Claudius
Journal: Blood (2012)
Molecular basis for Glanzmann's thrombasthenia (GT) in a compound heterozygote with glycoprotein IIb gene: a proposal for the classification of GT based on the biosynthetic pathway of glycoprotein IIb-IIIa complex
Authors: A Kato, K Yamamoto, S Miyazaki, SM Jung, M Moroi, N Aoki
Journal: Blood (1992)
Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer: results from PREVAIL
Authors: J.N. Graff, G. Baciarello, A.J. Armstrong, C.S. Higano, P. Iversen, T.W. Flaig, D. Forer, T. Parli, D. Phung, B. Tombal, T.M. Beer, C.N. Sternberg
Journal: Annals of Oncology (2015)
Abstract 18531: Impact of MicroRNA-145 to Prevent Vein Graft Disease in Rabbit by Regulation of Smooth Muscle Cell Phenotype
Authors: Motoaki Ohnaka, Akira Marui, Kenichi Yamahara, Kenji Minakata, Kazuhiro Yamazaki, Motoyuki Kumagai, Hidetoshi Masumoto, Tadashi Ikeda, Ryuzo Sakata
Journal: Circulation (2012)

Backgrounds Intimal hyperplasia is the major cause of vein graft disease. Smooth muscle cell (SMCs) proliferation and migration into the intima are key mechanism in this process. Recent studies have reported that microRNA-145(miR-145) is a specific mediator in the regulation of proliferation, differentiation, and phenotype of SMCs. In this study, we sought to investigate the impact of miR-145 to intimal hyperplasia in rabbit model of vein graft disease using electropolation mediated gene transfer. Methods and Results Right jugular vein of male Japanese white rabbit was harvested (15mm) and endothelial cells of the graft were injured by balloon catheter. The graft was interposed in ipsilateral jugular artery in reversed fashion (Control group). Alternatively, harvested jugular vein was transduced with miR-145 encoding plasmids by electroporator after balloon injury, and then interposed in ipsilateral jugular artery in the same fashion (miR-145 group). Two weeks after surgery, venous graft was explanted. Four sections were obtained and each section was stained with both hematoxylin and eosin, and the elastica van Gieson method for elastic fiber staining. Neointima formation was quantified on cross sections of vein graft and reendothelialization and intima/media area ratio were evaluated. Optimal condition of the electroporator (Figure 1a) was confirmed by DsRed immunostaining (Figure 1b: positive red fluorescence on inner surface of the graft 1c: DsRed monoclonal antibody staining). Reendothelialization was significantly reduced in miR-145 transduced grafts at 2 weeks (Figure 1d, 1e). Arrowheads indicate the internal lamina. Intima/media area ratio was significantly lower in the miR-145 group compared to the control group (0.062±0.011 vs. 0.365±0.281, p=0.03) . Conclusion Transduction of miR-145, which specifically regulates smooth muscle cell phenotype, into the bypass graft may be a novel option to prevent intimal hyperplasia in vein graft disease.