tbuckley/cabot-search huggingface dataset:
Tolerability and toxicity profile of chemotherapy with oxaliplatin in combination with infusional fluorouracil (FOLFOX) and capecitabine (XELOX) in a community oncology setting.
Authors: Raimundas Galiauskas, Edel Hassett, Kate Murphy, Donna Spillane, Gul Ahmed, Brian Richard Bird, Conleth G. Murphy
Journal: Journal of Clinical Oncology (2012)

e14111 Background: Chemotherapy regimens combining oxaliplatin with infusional fluorouracil (folfox) and capecitabine (xelox) have been found to be superior to fluoropyrimidine chemotherapy alone in colon cancer and are also useful in other gastrointestinal tumor types, including gastro-oesophageal cancers. We retrospectively assessed the tolerability and deliverability of the folfox and xelox regimens in a community oncology setting. Methods: Patients (pts) receiving folfox or xelox chemotherapy for gastrointestinal malignancies over a five year period from 2006 to 2011 were identified through a pharmacy database. Patient and tumour characteristics were recorded. For each regimen, delays in planned chemotherapy administration (&gt;3 days) as well as dose reductions were recorded. Reasons for dose modification and/or treatment discontinuation were recorded. Regimens were compared for these outcomes using Fisher's exact test for categorical variables and unpaired t-test for continuous variables. Results: Of 138 pts with adequate information for assessment, 94 received folfox and 44 received xelox. Pts who received folfox were more likely to experience dose delays (64% vs. 36%, 2-sided p=0.003). The mean dose delays during folfox and xelox were not significantly different (12.2 vs. 10.8 days, t-test p=0.657). Pts who received folfox were less likely to require any dose reductions during therapy (31% vs. 50%, 2-sided P=0.038). Similar numbers of pts receiving folfox and xelox required dose reductions of oxaliplatin (27% vs. 32%, 2-sided p=0.548), while fewer pts receiving folfox required dose reductions of the fluoropyrimidine component (14% vs. 39%, 2-sided p=0.002). Conclusions: We found that more pts required dose delays during treatment with infusional fluorouracil-based versus capecitabine-based oxaliplatin regimens. However, the infusional regimen was associated with considerably less dose reductions, largely related to the fluoropyrimidine component. We favour infusional fluoropyrimidine-based chemotherapy unless other factors (e.g., distance to the oncology unit) support oral fluoropyrimidine use.
Tomorrow's doctors want more teaching and training on physical activity for health
Authors: Scott Alexander Osborne, Jacob Matthew Adams, Samantha Fawkner, Paul Kelly, Andrew D Murray, Christopher W Oliver
Journal: British Journal of Sports Medicine (2016)

Physical activity (PA) promotes good health, and the challenge of physical inactivity is a major global issue.1 PA levels in the UK remain low, with many not achieving the Chief Medical Officer's recommendation of at least 150 min per week of moderate-intensity PA.2

With limited funds and increasing rates of non-communicable disease, the NHS is prioritising more cost-effective preventive approaches.3 PA is preventive and cost-effective. Doctors have an important role in PA promotion as they provide a point of contact for individuals who are healthy, at risk or have diagnosed chronic illnesses. Doctors are also trusted sources of health information.4 ,5 Therefore, training of medical professionals is key to strategies for increasing PA levels.5 ,6 Tomorrow's doctors should be adequately trained to discuss, advise and engage in the topic of PA.

PA promotion and prescription should be a fundamental element for all medical school curricula. Despite this, in 2015, many medical schools including the University of Edinburgh (UoE) Medical School had no PA content on the …
The Biodistribution and Immune Suppressive Effects of Breast Cancer–Derived Exosomes
Authors: Shu Wen Wen, Jaclyn Sceneay, Luize Goncalves Lima, Christina S.F. Wong, Melanie Becker, Sophie Krumeich, Richard J. Lobb, Vanessa Castillo, Ke Ni Wong, Sarah Ellis, Belinda S. Parker, Andreas Möller
Journal: Cancer Research (2016)

Small membranous secretions from tumor cells, termed exosomes, contribute significantly to intercellular communication and subsequent reprogramming of the tumor microenvironment. Here, we use optical imaging to determine that exogenously administered fluorescently labeled exosomes derived from highly metastatic murine breast cancer cells distributed predominantly to the lung of syngeneic mice, a frequent site of breast cancer metastasis. At the sites of accumulation, exosomes were taken up by CD45+ bone marrow-derived cells. Subsequent long-term conditioning of naïve mice with exosomes from highly metastatic breast cancer cells revealed the accumulation of myeloid-derived suppressor cells in the lung and liver. This favorable immune suppressive microenvironment was capable of promoting metastatic colonization in the lung and liver, an effect not observed from exosomes derived from nonmetastatic cells and liposome control vesicles. Furthermore, we determined that breast cancer exosomes directly suppressed T-cell proliferation and inhibited NK cell cytotoxicity, and hence likely suppressed the anticancer immune response in premetastatic organs. Together, our findings provide novel insight into the tissue-specific outcomes of breast cancer-derived exosome accumulation and their contribution to immune suppression and promotion of metastases. Cancer Res; 76(23); 6816-27. ©2016 AACR.
Increased 18F-2-Fluorodeoxysorbitol (18F-FDS) Activity in a Pituitary Spindle Cell Carcinoma
Authors: Xin Cheng, Wenjia Zhu, Ruixue Cui
Journal: Clinical Nuclear Medicine (2016)

A 33-year-old woman presented with progressive visual loss. An MRI examination revealed a pituitary lesion which was suspicious of abscess. FDG and F-2-fluorodeoxysorbitol (F-FDS) PET were performed to differentiate malignancy from inflammation. FDS is a new tracer with potential in differentiating inflammatory tissues based on results from animal studies. However, intense tracer uptake was found in the pituitary in both PET studies. The lesion was proved to be spindle cell carcinoma following biopsy.
Abstract B02: Oncogene MCT-1 deregulates oxidative metabolism and promotes tumor metastasis via YY1 signaling network
Authors: Hong-Yu Tseng, Yen-An Chen, Yi-Rong Chen, Hsin-Ling Hsu
Journal: Cancer Research (2016)

Abstract The underlying mechanism of oncogene activation that induces reactive oxygen species (ROS) generation and promotes tumor progression and metastasis is still ambiguous. We now demonstrate that the oncogenic MCT-1 activation protects cells from oxidative damage via increase of YY1 and subsequently enhances EGFR expression and activation. Overexpressing MCT-1 induces cell invasion, intracellular ROS generation and MnSOD expression in mitochondria via YY1 pathway, thus targeting YY1 suppresses cancer cell invasion and blocks EGFR-MnSOD signaling function enhanced by MCT-1. Recapitulating in vitro outcomes, MCT-1 increment promotes tumor angiogenesis, necrosis and metastasis with oxidative metabolism deregulation and malignant microenvironment development in xenograft mice. Clinical data also confirms that MCT-1 enrichment connects to poor survival and prognosis coincident with YY1, EGFR and MnSOD upregulation in patients with lung cancer. Collectively, MCT-1 is a key inducer of YY1-EGFR-MnSOD axis involving the redox mechanism in the process of carcinogenesis. Citation Format: Hong-Yu Tseng, Yen-An Chen, Yi-Rong Chen, Hsin-Ling Hsu. Oncogene MCT-1 deregulates oxidative metabolism and promotes tumor metastasis via YY1 signaling network. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B02.
Addition of Cladribine to the Standard AML Treatment Improves Long-Term Outcome in High Tumor Burden and Older Than 40 Years Acute Myeloid Leukemia Patients. Five-Year Follow-Up of the Polish Adult Leukemia Group (PALG 1999 DAC vs. DA Study).
Authors: Jerzy Holowiecki, Sebastian Grosicki, Tadeusz Robak, Slawomira Krzemien, Sebastian Giebel, Andrzej Hellmann, Aleksander Skotnicki, Wieslaw W. Jedrzejczak, Lech Konopka, Kazimierz Kuliczkowski, Barbara Zdziarska, Anna Dmoszynska
Journal: Blood (2004)
GP referral to weight loss programme is quick and effective, finds study
Authors: Susan Mayor
Journal: BMJ (2016)

Most obese patients found it appropriate and helpful when their GP briefly advised them that losing weight would benefit their health on an unrelated issue, but offering referral to a weight loss programme was more effective in achieving weight loss, a randomised trial has found.1

In the trial 1882 obese patients from 137 general practices in England were randomly allocated to one of two 30 second interventions at the end of their consultation: referral to a weight management group or advice that their health would benefit from losing weight. The patients were aged 18 and over and had a …
Loss of Individual PIP5KI Isoforms Demonstrate That Spatial PIP2 Synthesis Is Required for Platelet Second Messenger Formation &amp; Integrity of the Actin Cytoskeleton
Authors: Yanfeng Wang, Lurong Lian, Aae Suzuki, Rustem I. Litvinov, Timothy J. Stalker, Alec A. Schmaier, Lawrence F. Brass, John Weisel, Charles S. Abrams
Journal: Blood (2008)
A tissue checkpoint regulates type 2 immunity
Authors: Steven J Van Dyken, Jesse C Nussbaum, Jinwoo Lee, Ari B Molofsky, Hong-Erh Liang, Joshua L Pollack, Rachel E Gate, Genevieve E Haliburton, Chun J Ye, Alexander Marson, David J Erle, Richard M Locksley
Journal: Nature Immunology (2016)
Establishment and Characterization of a Novel Human Cell Line of Triple Hit Lymphoma, AMU-ML1, Carrying t(2;18)(p11.2;q21) and t(3;8;14)(q27;q24;q32) That Involve BCL2, BCL6 and MYC
Authors: Norikazu Tsunekawa, Ichiro Hanamura, Hidesuke Yamamoto, Hisao Nagoshi, Motohiro Wakabayashi, Natsumi Sakamoto, Tomohiro Horio, Mineaki Gotoh, Shohei Mizuno, Miyuki Takahashi, Kazuto Suganuma, Mayuko Goto, Akihito Hiramatsu, Masaya Watarai, Masato Shikami, Akira Imamura, Hidetsugu Mihara, Tomohiko Taki, Masafumi Taniwaki, Hiroshi Miwa, Masakazu Nitta
Journal: Blood (2011)
Results of Immunosuppressive Therapy in Children with Acquired Severe Aplastic Anaemia (SAA). Report Polish Paediatric Leukaemia and Lymphoma Study Group.
Authors: K. Pawelec, M. Matysiak, E. Niewiadomska, R. Rokicka-Milewska, T. Jackowska, J. Kowalczyk, J. Stefaniak, W. Balwierz, E. Zalecka-Czerpko, A. Chybicka, K. Szmyd, D. Sonta-Jakimczyk, H. Bubala, A. Krauze, M. Wysocki, A. Kurylak, J. Wachowiak, M. Kaczmarek-Karnold, M. Stolarska, I. Karolczyk, M. Krawczuk-Rybak, E. Leszczynska, T. Urasinski, J. Peregud-Pogorzelski, M. Wlazlowski, A. Balcerska
Journal: Blood (2005)
Efficacy and safety of echoguided catheterisation approach in oncological and hematological patients. Report on 843 consecutive patients
Authors: A. Lazzaro, D. Vallisa, C. F. Moroni, R. Bertè, P. Bernuzzi, E. Anselmi, A. Arcari, C. Bosi, P. Mordenti, E. Trabacchi, L. Cavanna
Journal: Journal of Clinical Oncology (2007)

19581 Background: A central venous catheter (CVC) represents the most frequently adopted intravenous line for patients undergoing infusional chemotherapy, bone marrow transplantation (BMT) and parenteral nutrition. The aim of this study was to explore the feasibility and safety of CVC insertion under ultrasound (US) control. US offers the advantage of real-time, multiplanar imaging as well as Doppler analysis. Methods: The echoguided approach allowed us to insert CVC in right supraclavicular site nearby the clavicular head of sternocleidomastoid muscle. Using a 7.5-MHz probe we were able to perform a real time control of the hip of the needle while it was inserted in the last side of internal jugular vein. At the end of the procedure chest Rx was executed to evaluate CVC position and to detect pneumotorax. Mainly Sekalon Seldy, Becketon Dickinson was employed. For PBSC collection, 14-gauge Arrow double lumen revealed to be highly efficacious (46 PBSC collections, no one failure). Results: From November 1999 to December 2006 the echoguided CVC insertion method was applied 1003 times in 843 patients. The procedure was applied 288 times in haematological malignancies, in 698 solid tumors, in 3 neurological autoimmune diseases. Among solid tumors colon carcinoma was the first indication, while gastric carcinoma the second. Among haematological patients: non-Hodgkin lymphoma was the first indication, then acute leukemia. Ten patients underwent allogenic BMT and 92 autologous BMT. Nine in 1003 procedures failed (1%). Failures were caused by: arterial puncture in 3, CVC dislocation in 1, vein collapse in 3 and no efficacious “eco window” in 2. No pneumotorax was registered. The safety of this procedure was confirmed by 35 catheterisations obtained with platelets under 20000/μl, by 7 procedure with prothrombin activity under 50%. In 44 patients catheter was inserted with neutrophil count below 100/μl and in 66 below 500/μl without any increase in infections. Mean time of catheter permanence was 151 days with 1,7 infectious events every 1000 days of permanence. Symptomatic deep veins thrombotic complications were 9 (1%). Conclusions: This procedure is safe, cheap with high accuracy and success rate, and above all US-guidance avoids pneumothorax. No significant financial relationships to disclose.
Preliminary efficacy of bevacizumab with first-line FOLFOX, XELOX, FOLFIRI and monotherapy for mCRC: First BEATrial
Authors: A. Kretzschmar, E. Van Cutsem, M. Michael, F. Rivera, S. Berry, M. DiBartolomeo, M. Mazier, B. Lutiger, D. Cunningham
Journal: Journal of Clinical Oncology (2007)

4072 Background: In a phase III pivotal trial in patients (pts) with metastatic colorectal cancer (mCRC), BEV (BEV, Avastin®) increased overall survival (OS) by 30% when added to first-line IFL chemotherapy (CT). Recently, a second trial reported a significant improvement in progression free survival (PFS) when BEV was added to FOLFOX/XELOX in a similar patient population. Although, First BEAT was opened to evaluate the safety profile of BEV in a broader pt population using a variety of CT regimens, efficacy endpoints were investigated. Methods: First BEAT enrolled 1,927 mCRC patients in 41 countries between June 2004 and February 2006. Eligible pts were treated with first-line CT (physician’s choice) in combination with BEV (5mg/kg q2w [5-FU-based CT] or 7.5mg/kg q3w [capecitabine [cap, Xeloda®]-based CT]) until disease progression. Secondary endpoints included OS, time to progression (TTP) and PFS. Disease progression was assessed by investigators. Results: By Nov 15 th , 2006, 1,914/1,927 pts had data available for analysis (male 58%; median age 59 years, 33% =65 years; ECOG PS 0/1 65%/34%). Median follow-up was 15 months; 60-day mortality was 2.5%. Patients receiving 5-FU/cap CT appeared to have poorer prognosis with respect to age =65 years (41%), ECOG PS 0/1 (58%/42%) and 60-day mortality rate (6.6%), compared with those receiving doublet CT regimens. The most common first-line CT regimens used with BEV were FOLFOX (28%), FOLFIRI (26%), XELOX (18%) and 5-FU or cap CT (16%). Median PFS was 10.4 (95% CI: 10.1–10.9 months, based on 882 events), 10.5 (9.7 - 11.6) in FOLFOX, 10.3 (9.7 - 10.7) in XELOX, 11.1 (10.2–12.0) in FOLFIRI and 9.1 (8.1–10.3) in pts receiving 5-FU or cap CT, respectively. TTP was 10.8 (95% CI: 10.4–11.3 months, based on 805 events). Updated analyses will be presented. Conclusions: In this ongoing, large community-based study, the preliminary efficacy of first line BEV in mCRC pts receiving a variety of CT regimens appears consistent with that observed in large phase III randomised trials. [Table: see text]
Assessment of the total cost of FNAC as a diagnostic tool in patients with thyroid nodules
Authors: I. Borget, P. Vielh, M. Allyn, M. Schlumberger, G. De Pouvourville
Journal: Journal of Clinical Oncology (2007)

6628 Background: The prevalence of thyroid nodules in the general population ranges from 4 to 7% and fine-needle aspiration cytology (FNAC) is a widely used diagnostic procedure. As the final diagnosis is based on post-surgical pathology of the lesion, a number of patients with nodules classified as benign or indeterminate by cytology may have a postponed final diagnosis, impacting the procedure cost. This study aims to determine the total cost of FNAC, by taking into account of diagnostic mistakes (false-positive and false-negative), failures of FNAC (indeterminate results) and the follow-up of non operated patients. Methods: A Markov model was built to describe the management of patients through time, from the first FNA-t. We derived estimates for diagnostic accuracy values and follow-up from a retrospective study, including all patients who had their first FNAC from 2003 to 2005 at Institut Gustave Roussy. Costs were computed from the viewpoint of the hospital. A microcosting study was performed to determine the unit cost of FNAC. Sensitivity analyses were performed. Results: Out of the 624 patients who had FNAC, 15 were cytologically classified as malignant, 57 as suspicious and 171 as indeterminate. Surgical excision was carried on in 155 cases. The unit cost of FNAC was 121 €. Markov modelling showed that the mean total cost of a true diagnosis including unnecessary surgeries, repeat FNAC and follow-up was 1,145 Euros. The number of false negative and false positive cases had little impact on total cost, whereas it was significantly affected by the percentage (27%) of unsatisfactory specimens. The absence of such specimens would reduce the total cost to 738 Euros (35%). Conclusions: The cost of FNAC exceeds its unit production cost. It depends on the performance of the cytologist and on the rate of indeterminate results that might be reduced by routine ultrasound-guidance. No significant financial relationships to disclose.
GW26-e1553 Long-Term Treatment With Ivabradine in Transgenic Atrial Fibrillation Mice Counteracts HCN Channel Overexpression and Reduces Atrial Fibrillation Incidence
Authors: Juan Wang, Yang Li, Jun Zhu, Chao Zhu, Bi Huang, Xinghui Shao, Han Zhang, Huaibin Wan, Yanmin Yang
Journal: Journal of the American College of Cardiology (2015)
P0564 : Increased IL-17, TNF α secretion by TFH and their subtype (TFH17) (CD4+CXCR5+CCR6+) cells help in HBV seroconversion
Authors: A.K. Vyas, S. Sharma, P. David, A. Bhardwaj, N. Trehanpati, S.K. Sarin
Journal: Journal of Hepatology (2015)
The HIV protease inhibitor ritonavir and the proteasome inhibitor bortezomib induce synergistic cytotoxicity on soft tissue sarcoma cells in vitro
Authors: C. Driessen, M. Kraus, H. Müller, J. Gogel, L. Kanz, K. Simon-Klingenstein, E. Koscielniak, J. T. Hartmann
Journal: Journal of Clinical Oncology (2006)

9566 Background: HIV-protease inhibitors like Ritonavir produces regressions in HIV-associated Kaposi‘s sarcoma, reportedly due to proteasome inhibition. We have here assessed the effect of Ritonavir and the proteasome inhibitor Bortezomib on the viability and proteasome activity of the soft tissue sarcoma cell lines RD (rhabdomyosarcoma) and A-673 (ewing‘s sarcoma) in vitro. Methods: Cytotoxixity was assessed by MTS-test. To directly dissect proteasome activity in viable sarcoma cells, we used a recently developed cell-permeable affinity label that for the first time allows to assess the individual activity profile of the different catalytically active proteasomal subunits in living cells (Berkers et al., Nature Methods, May 2005). Results: Both types of cells were resistant towards Bortezomib and Ritonavir monotherapy at therapeutic concentrations (20 nM for Bortezomib, 20μM for Ritonavir). Ritonavir induced cytotoxicity in sarcoma cell lines with an IC50 of 40μM. The combination of clinically meaningful concentrations of Ritonavir (20μM) with Bortezomib (10–20 nM) induced robust synergistic cytotoxicity in both sarcoma cell lines. Using affinity labelling of proteasome activity, we directly demonstrate that a) Botezomib abrogates beta5, but also beta1-proteosomal activity in sarcoma cells and b) that Ritonavir at 20μM does not affect proteasom activity. Conclusions: We here present the first analysis of active proteasomal subunits in living human sarcoma cell lines. Ritonavir and Velcade induce synergistic cytotoxicity at clinically meaningful concentrations in vitro, which is not mediated through a direct effect of Ritonavir on proteasome activity. Based on our data, the synergistic combination of Ritonavir and Bortezomib might warrant further clinical testing in soft tissue sarcoma in vivo. No significant financial relationships to disclose.
Venothromboembolism (VTE) in Patients (pts) with Acute Lymphocytic Leukemia (ALL), Burkitt’s Leukemia/Lymphoma (BL) or Lymphoblastic Lymphoma (LL).
Authors: Khanh D. Vu, Julie C. Hubbard, E. Lin, Stefan H. Faderl, Jorge E. Cortes, Susan M. O’Brien, Hagop M. Kantarjian, Deborah A. Thomas
Journal: Blood (2007)
Viability and Engraftment of Hematopoietic Progenitor Cells (HPC) After Long Term Cryopreservation: Effect of Diagnosis and % Dimethylsulfoxide (DMSO) Concentration.
Authors: Muthu Kumaran Veeraputhiran, John Theus, Gina Pesek, Bart Barlogie, Michele H. Cottler-Fox
Journal: Blood (2009)
Clinical outcome of triple-negative early breast cancer in a non-African American women cohort: More fuel to the fire.
Authors: E. Gil Deza, F. Tognelli, M. Abal, H. Japaze, E. L. Morgenfeld, S. L. Ares, E. Rivarola, C. Diaz, N. Gercovich, F. G. Gercovich
Journal: Journal of Clinical Oncology (2010)

e11066 Background: Khan et al concluded, among others, that the evolution of triple-negative (TN) early breast cancer (EBC) in African American (AA) women is worse than non-TN tumors (JCO 26:2008, May 20 suppl; abstr 11039). The objective of the current study is to compare the clinical outcome of non AA EBC with TN tumors against double-negative Her2-positive tumors (DNHP) who did not receive adjuvant trastuzumab, in order to evaluate the biological aggressiveness of each tumor group. Material: We retrospectively reviewed the clinical data of all the tumors registered in our database, classified following the recommendations of the Directors of Surgical Pathology of the USA, and selected those cases of non AA, EBC, ER (-), PR (-), and Her2 (0-1+) (TN), or ER (-), PR (-) and Her2 (3+)(DNHP) who did not receive adjuvant trastuzumab. Methods: We compared population characteristics (see below) and result of therapies (see below) between TN and DNHP. Results: TN = 29 patients, DNHP = 26 pt. Both groups were comparable in terms of: a) clinical prognostic factors (age, menopause, stage), b) standard hystopathological prognostic factors (histological type or subtype, T, N, tumor grade, margins, vascular invasion, extensive intraductal component), c) local and systemic treatments and d) follow up. Clinical outcome: disease-free survival: TN 30.5 months (range 8-73) DNHP 33.3 months (range 16-74) (p = 0.4). Relapse rate: TN 9/29 DNHP 6/26 (p = 0.5). Death rate: TN 8/29 DNHP 1/26 (p = 0.01). Overall survival: TN 59 months (IC 95% 47-71 months) DNHP 92 months (IC 95% 82-102 months) (log rank test p = 0.016). Conclusions: a) TN in non- AA EBC is an aggressive tumor with a high relapse rate (9/29) and a high death rate (8/26). b) The comparison with a non-AA EBC DNHP reveals that TN cases have a statistically significant higher death rate and shorter OS. This could reflect both a visceral involvement at relapse of TN tumors and/or the efficacy of a target therapyin the DNHP group. c) New adjuvant chemotherapy schedules to treat TN EBC are urgently needed. No significant financial relationships to disclose.