tbuckley/cabot-search huggingface dataset:
The effects of frozen gloves and socks on paclitaxel-induced peripheral neuropathy among patients with breast cancer: A self-controlled clinical trial.
Authors: Akiko Hanai, Hiroshi Ishiguro, Takashi Sozu, Moe Tsuda, Takayuki Nakagawa, Satoshi Imai, Yoko Hamabe, Masakazu Toi, Hidenori Arai, Tadao Tsuboyama
Journal: Journal of Clinical Oncology (2016)

10022 Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect with no proven effective treatment or prevention. In this prospective study, we aimed to evaluate the effectiveness of frozen gloves and socks (FGS) in preventing CIPN. Methods: The study included breast cancer patients who were treated weekly with paclitaxel (80 mg/m2 for 1 h) for at least 12 cycles. Each patient wore FGS on the dominant hand (H) and foot (F) for 90 min during infusion. The non-dominant side acted as the untreated control. The primary endpoint was an incidence of CIPN (any grade) assessed by the Semmes–Weinstein monofilament test (MF; tactile changes from baseline) at 12 weeks. We also assessed FGS tolerability, thermal threshold using a thermal stimulator (TS), subjective symptoms using the Patient Neurotoxicity Questionnaire (PNQ), and manipulative dexterity using the grooved pegboard (GP) test. The McNemar’s test (MF, TS, and PNQ) and paired t-test (GP) were used for statistical analysis. Results: Of 44 patients registered, four did not undergo any intervention (two did not meet inclusion criteria and two withdrew). An additional four did not complete 12 cycles of paclitaxel due to pneumonia (n = 1), severe fatigue (n = 1), hepatopathy (n = 1), and macular edema (n = 1), leaving 36 patients for the analysis. No patient dropped out because of cold intolerance. The incidence of CIPN assessed by MF (primary endpoint), TS (hot), and moderate to severe tingling, pain, or numbness, which interfered with daily living (PNQ), were significantly lower in the intervention side than in the control side (Table). The GP test showed that the deterioration of manipulative dexterity was also significantly prevented (mean delay, −2.5 vs 8.6 sec; p <0.01). Conclusions: FGS is useful in mitigating the objective and subjective symptoms of CIPN and its resultant dysfunction. Clinical trial information: UMIN000013398.n (%) Intervention (n = 36) Control (n = 36) p Objective CIPN (MF) H 10 (28%) 29 (81%) <0.01 F 9 (25%) 23 (64%) <0.01 (TS Hot) H 3 (8%) 12 (33%) 0.01 F 12 (33%) 20 (56%) 0.04 (TS Cold) H 1 (3%) 5 (14%) 0.13 F 4 (11%) 7 (19%) 0.45 Subjective CIPN (PNQ) H 3 (8%) 21 (58%) <0.01 F 7 (19%) 24 (67%) <0.01
Personalized Genomic Analyses for Cancer Mutation Discovery and Interpretation.
Authors: Valsamo Anagnostou, Siân Jones, Karli Lytle, Sonya Parpart-Li, Monica Nesselbush, Vilmos Adleff, David Riley, Manish Shukla, Bryan Chesnick, Maura Kadan, Eniko Papp, Kevin Galens, Derek M Murphy, Theresa Zhang, Lisa M. Kann, Mark Sausen, Samuel V. Angiuoli, Luis A. Diaz, Victor E Velculescu
Journal: Journal of Clinical Oncology (2015)

1529 Background: The anticipated widespread adoption of large scale genomic analyses in precision oncology mandates the development of a gene actionability framework. Previous efforts of clinical interpretation of genomic alterations mainly rely on expert opinion and manual curation of the primary literature. Furthermore, analytic challenges such as distinguishing somatic -driver- mutations from germline alterations have limited the interpretation of genomic information. Methods: We comprehensively evaluated 815 tumor-normal paired samples from 15 tumor types and identified genomic alterations using next generation sequencing of whole exomes or 111 targeted genes. Tumor and normal data were compared to identify somatic and germline alterations. We extracted information from consensus guidelines (fda.gov), the centralized registry of clinical trials (ClinicalTrials.gov) and published clinical trials to generate a database with actionable genes according to graded levels of evidence. Results: These analyses revealed an average of 140 and 4.3 somatic mutations per exome and targeted sequencing respectively. We identified at least one somatic alteration in genes with potentially actionable consequences in 77% of patients analyzed. Most of the actionable changes were associated with current clinical trials (67%) rather than established therapies (33%). More than 90% of genes with actionable alterations were mutated in < 5% of individual tumors. Analyses of matched normal DNA identified germline alterations in cancer predisposing genes in 3% of patients with apparently sporadic cancers. In contrast, a tumor-only sequencing approach followed by bioinformatic removal of common germline variants led to a 31% and 65% false discovery rate in alterations identified in targeted and exome analyses, respectively. Conclusions: Our comprehensive actionability framework was used to classify genomic alterations based on existing levels of evidence and could be used as a platform for clinical interpretation of somatic alterations. Our findings suggest that matched tumor-normal sequencing analyses are essential for precise identification of somatic alterations and have important implications in clinical decision making.
Intralesional triamcinolone for flares of hidradenitis suppurativa (HS): A case series
Authors: Peter Theut Riis, Jurr Boer, Errol P. Prens, Ditte M.L. Saunte, Inge E. Deckers, Lennart Emtestam, Karin Sartorius, Gregor B.E. Jemec
Journal: Journal of the American Academy of Dermatology (2016)
No increase of leukemia relapse in newly diagnosed patients with acute myeloid leukemia who received granulocyte colony-stimulating factor for life-threatening infection during remission induction and consolidation therapy. Japan Adult Leukemia Study Group [letter]
Authors: R Ohno, A Hiraoka, M Tanimoto, N Asou, K Kuriyama, T Kobayashi, M Yoshida, H Teshima, H Saito, K Fujimoto
Journal: Blood (1993)
Higher Aspirin Dose is Associated with Reduced Mortality and More Serious Bleeding in Patients with Recent Cerebrovascular or Coronary Ischemic Events: Insights from the BRAVO Trial
Authors: HD Aronow, RM Califf, RA Harrington, M Vallee, C Graffagnino, A Shuaib, D Fitzgerald, JD Easton, Frans Van de Werf, HC Diener, J Ferguson, PJ Koudstaal, P Amarenco, P Theroux, S Davis, EJ Topol
Journal: Circulation (2003)
Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation
Authors: Ji Hye Jun, Jong Ho Choi, Si Hyun Bae, Seh Hoon Oh, Gi Jin Kim
Journal: Clinical and Molecular Hepatology (2016)

Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL).The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP.The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP.CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.
Array-based comparative genomic hybridization (CGH) identifies chromosomal imbalances between Interleukin-2 complete and non-responders
Authors: E. Jaeger, F. Waldman, R. Roydasgupta, T. Klatte, D. F. McDermott, S. Signoretti, M. B. Atkins, J. LaRochelle, A. S. Belldegrun, A. J. Pantuck
Journal: Journal of Clinical Oncology (2008)

5043 Background: IL-2 is the only FDA approved treatment for metastatic renal cell cancer capable of producing durable complete responses (CR). However, it is associated with toxicity and a low CR rate. We used array-based CGH to detect a chromosomal profile that distinguishes between IL-2 responders and non-responders. Methods: 10-μm paraffin-embedded tumour sections were cut from 16 RCC patients (5 CRs and 11 Non-Responders (NRs)), tumor areas with >90% clear cell RCC were microdissected, and DNA extracted using phenol/chloroform. Labeled tumor and reference DNAs were applied to Human array 2.0 CGH arrays in triplicate. Fluorescence images were collected using a CCD camera, and analyzed with Spot 2.0 software. For each clone, an average single log2 ratio of test over reference intensity was calculated from replicate spots. The frequency of gains and losses for a given clone was calculated as the proportion of samples in which a clone was gained or lost in that group. Clones with significantly different copy number between different groups were compared using Fisher’s Exact Test. Results: CRs showed fewer whole chromosome changes, more genomic gains, and fewer genomic losses than NRs, who were distinguished by loss of chromosomes 4, 9, and 17p. Of CRs, there was 0% loss of 9p clones, compared to 65% of NRs and 90% of lymph node positive NRs (p<0.001). On 9p, frequently involved regions of loss in NR subjects included 9p13, 9p21, and 9p24 on which CAIX, p16 and S6, and B7H1 genes are located, respectively. In a separate analysis of 282 RCC patients using standard cytogenetics, loss of 4p and 9p were associated with worse survival, and 3 IL-2 responders analyzed had no loss on either 4p or 9p. Conclusions: Patterns of chromosomal imbalance are significantly different in IL-2 Complete and Non-Responders. Loss of chromosome 4, 9, and 17p may identify alterations that can serve as predictors of IL-2 non-response. Further investigation of genes located on these regions may lead to better understanding of the molecular biology of RCC and IL-2 response. If prospectively validated, CGH analysis of genetic alterations may aid clinicians in targeted selection of appropriate treatment options. Funding: NIH K23CA095151–01; NCI P50CA101942 No significant financial relationships to disclose.
TLR-9 and IL-15-Driven Clonal Expansion of B-CLL Cells
Authors: Patricia K. A. Mongini, Rashmi Gupta, Charles C. Chu, Joanna Stein, Tatjana Stankovic, Jacqueline C. Barrientos, Jonathan E. Kolitz, Steven L. Allen, Kanti R. Rai, Nicholas Chiorazzi
Journal: Blood (2014)
OC-110 Covered metal stent placement using santorini’s duct (Minor Papilla) for pain management in chronic calcific pancreatitis – feasibility and safety: Abstract OC-110 Table 1
Authors: A Sangwaiya, MA Butt, C Wadsworth, D Bansi, P Vlavianos, D Westaby
Journal: Gut (2015)

<h3>Introduction</h3> Pain control in chronic calcific pancreatitis is often unsatisfactory. Both endoscopic and surgical drainage procedures have been described for management of intractable or recurrent severe pain. Pancreatojejunostomy has been shown to be more effective than endoscopic management (using plastic stents) of main pancreatic duct stricture (PDS).<sup>1,2</sup>Fully Covered-Self expanding metal stent (FC-SEMS) placement across PDS has been assessed as a new endoscopic approach with the aim of achieving enhanced PD drainage.<sup>3,4</sup>As a part of a larger series, we have identified 8 cases in which access for PD drainage has been achieved via Santorini’s Duct. <h3>Method</h3> 8 patients (M:F 3:5 mean age 58 years) had FC-SEMS placed using Santorini’s Duct. 5 patients had pancreatic divisum confirmed on imaging and ERCP. 5 patients had prior placement of plastic stents and 3 had no prior endoprostheses. Planned outpatient follow up was at 3, 6 and 12 months. Mean duration of stent insertion was 3 months and response (i.e. pain control) was assessed at 3 months by using a 1–10 visual analogue scale to compare pre- and post-intervention symptoms. A score of 2 or less was classified as complete response, whereas a score of 3 or above was classified as partial response or if there was an improvement by 4 or more points in the scale. <h3>Results</h3> FC-SEMS insertion using Santorini’s Duct was feasible in all patients. The SEMS was removed at a median of 3 months (range 1.2 to 4 months). Mean follow up duration was 8.7 months. 5 patients (62.5%) reported complete response to pain while 2 (25%) had a partial response. One (12.5%) patient reported no response post endotherapy and was considered for surgical drainage. In one patient (partial response), the stricture had not resolved on FC SEMS withdrawal. A short stricture at the upstream stent margin was seen in one patient and responded to balloon dilatation. There were no instances of stent migration. <h3>Conclusion</h3> We describe the first series reporting the use of Santorini’s Duct to deliver FC-SEMS in PDS due to chronic pancreatitis. This approach is feasible, safe with early evidence of efficacy. The duration of duct patency and as a consequence success of pain management requires longer term follow up. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> N Engl J Med. 2007;356(7):676–84 J Gastrointest Surg. 2012;16(7):1362–9 Endoscopy 2012;44(08):784–800 <i>Heptogastroenterology</i>2011;58(112):2128–31
Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits
Authors: Renata Batista-Brito, Martin Vinck, Katie A. Ferguson, Jeremy T. Chang, David Laubender, Gyorgy Lur, James M. Mossner, Victoria G. Hernandez, Charu Ramakrishnan, Karl Deisseroth, Michael J. Higley, Jessica A. Cardin
Journal: Neuron (2017)
Estramustine, zoledronic acid and weekly docetaxel in metastatic androgen independent prostate cancer (MAIP)
Authors: B. Dabaja, F. L. Nasr, G. Y. Chahine, W. T. Moukaddem, F. S. Farhat, E. A. Tueini, J. G. Kattan, J. E. Dagher, F. C. Younes, M. G. Ghosn
Journal: Journal of Clinical Oncology (2004)

4706 Background: Docetaxel and estramustine phosphate have been shown to have synergistic and significant activity in patients with MAIP. Zoledronic acid is a third generation biphosphonate, which reduces skeletal events by inhibiting bone destruction in MAIP patients. Methods: We conducted a phase II trial with the combination of estramustine, zoledronic acid and weekly docetaxel. Eligibility consisted of metastatic prostate adenocarcinoma with objective progression or rising prostate specific antigen (PSA) levels despite androgen deprivation therapy. Prior chemotherapy was not allowed; radiation was permitted. A PS of £ 2, adequate bone marrow, hepatic, renal and cardiac functions were required. Estramustine was administered orally at a dose of 140mg three times daily on days 1 to 21 on a 28-day cycle. 25mg/m2 of docetaxel was administered intravenously on days 1,8 and 15 of each cycle. Zoledronic acid was given at a dose of 4mg in 15 minutes infusion on D1 of each cycle. Results: Between March 2002 and October 2003, 24 patients (pts) were enrolled. Median age was 71 years [range 53–83y]. 20 pts had only bone metastases and 4 pts had measurable disease. One hundred and four cycles of therapy have been delivered with a median of four cycles per patient, [range 1–7]. Predominant toxicities consisted of: grades II-III anemia (20.8%), grades III thrombocytopenia (4.1%), fatigue (20.8%), grades II-III alopecia (12.5%), and severe hypocalcaemia (8.3%). 2 pts presented Deep Venous Thrombosis with deadly pulmonary embolism. One patient died from Stevens Johnson syndrome and grade IV hepatic toxicity at D15 of cycle 2. 22 pts were evaluable for response. 12 pts (54.5%) had biological response (> 50% PSA decline) which lasted from 5 to 63 weeks. 2 among the 4 measurable disease pts had objective response. 12 pts experienced clinical benefit with pain reduction. Conclusion: This combination is well tolerable, effective and worthy to be proposed as a standard therapy for MAIP. No significant financial relationships to disclose.
Paclitaxel and carboplatin sequenced with radiotherapy in women with advanced uterine serous carcinoma: Is this the optimal therapy?
Authors: P. A. Gehrig, E. N. Skinner, J. F. Boggess, K. A. Moller, D. M. Boruta, A. P. Dunlap, W. C. Fowler, L. Van Le
Journal: Journal of Clinical Oncology (2004)

5084 Background: Uterine serous carcinoma (USC) often presents in advanced stages. The optimal post-operative therapy for women with USC has not been elucidated, as this histologic variant comprises a small proportion of the cases enrolled in clinical trials. Methods: A retrospective analysis of women diagnosed with USC from 1992–2002 was conducted. Data collected included demographics, stage at diagnosis, post-operative therapy, progression free survival (PFS), location of recurrence and overall survival (OS). Comparisons were performed using non-parametric ANOVA. Results: Between 1992–2002, there were 137 women diagnosed with USC, of whom 85 presented with either stage III or IV disease. Of these 85 women, 11 refused post-operative therapy, 12 underwent 6 cycles of paclitaxel (175 mg/m2) and carboplatin (AUC 6), 14 underwent whole abdominal radiotherapy (WAR), 9 had sequential therapy and the remaining 39 were treated with a variety of regimens. Sequential therapy consisted of paclitaxel and carboplatin at the above doses for 3 cycles, followed by volume-directed pelvic +/- para-aortic radiotherapy and an additional 3 cycles of chemotherapy. There was no significant difference between the groups with regards to age or stage of disease. Data regarding PFS and OS is presented in the table below. Median follow-up for the 46 women included in the analysis is 17.5 months. Only 1 woman treated with sequential therapy experienced a recurrence (21 months) with a median follow-up in this group of 38 months. Conclusions: Sequential chemotherapy and radiotherapy extends progression free and overall survival in women with advanced stage USC. Further investigation using combined modality therapy in women with advanced endometrial carcinoma is being conducted by the GOG, however efforts should focus on enrolling women with USC in protocols using multimodality therapy. No significant financial relationships to disclose.
Induction Therapy with Idarubicin and Etoposide Combined with Sequential or Concurrent Azacitidine In Patients with High-Risk Acute Myeloid Leukemia: Pilot-Phase of the AMLSG 12-09 Study
Authors: Frank G. Rücker, Stephan Stilgenbauer, Martin Bommer, Daniela Späth, Silja Mack, Konstanze Döhner, Hartmut Döhner, Richard F. Schlenk
Journal: Blood (2010)
Microarray gene expression study of the RESPECT trial for the identification of prognostic and predictive markers.
Authors: Mauro Delorenzi, Sarah Gerster, Josep Tabernero, Claus-Henning Köhne, Peter J. O'Dwyer, Alberto F. Sobrero, Eric van Cutsem, Rocio Garcia-Carbonero, Ramon Salazar, Fernando Rivera, Leslie M. Samuel, Vanessa Alice Potter, Yu-Lin Chang, Nathalie Andrienne Lokker, Sabine Tejpar
Journal: Journal of Clinical Oncology (2013)

e14561 Background: The RESPECT trial (n = 198) tested the addition of Sorafenib to standard mFOLFOX6 treatment in first line metastatic colorectal cancer (mCRC) patients but resulted in no statistical significant improvement in progression free survival, and no evidence for overall benefit. Sorafenib inhibits several Raf kinases (including B-Raf). Samples with high BRAF-mutant-like score were previously shown to identify a subset of colon tumors with a similar biology and outcome to BRAF mutant patients (Popovici et al. J. Clin. Oncol., 30(12):1288–95, 2012). Methods: A subset of 125 patients from the trial was available for gene expression analysis from their primary tumor FFPE samples, using the Colon DSA gene expression arrays from Almac. Mutation status for KRAS and BRAF was previously assessed. The potential prognostic and/or predictive effect of a high BRAF-mutant-like score was assessed. The analyses were performed using Cox proportional hazards regression models and Kaplan-Meier curves. The logrank test was used to compare the survival distributions (significance level: 5%). Results: Molecular profiling was performed on FFPE tissue samples from primary tumors of 125 mCRC patients, 95 samples (47 in the combined arm; 3 BRAF mutants) were successfully processed. Limitations in amount of material available in this retrospective analysis led to failure to reach the required RNA amount for amplification in 30 samples (dropout rate = 24%). The collected gene expression data was of good quality: all 95 array profiles could be used (10 were flagged for slightly inferior quality). The BRAF-mutant-like score was recognized as marker of poor OS in a Cox regression model (HR = 1.55 [95% CI: 1.12 - 2.13], 1 unit = 1 IQR, P = 0.007). The HR difference between the two arms (combined arm: HR = 1.36; reference arm: HR = 1.41) is not significant. Conclusions: The poor survival of metastatic colorectal cancer patients with a BRAF-mutated-like tumor is confirmed, but no predictive effect was found. FFPE tissues are well-suited for this kind of study and allow to accurately test the hypotheses of interest. Further analyses are planned to generate hypotheses about markers of sensitivity to mFOLFOX6 or Sorafenib.
Update On the Risk of Leukemia in Genetic Subgroups of Congenital Neutropenia (CN): Comparison of Patients with Known Gene Mutations (ELA2, HAX1, WASP, G6PC3, p14).
Authors: Cornelia Zeidler, Jean Donadieu, Audrey Anna Bolyard, Peter Vandenberghe, Gusal Pracht, Blandine Beaupain, Ludwig Hoy, Martin Zimmermann, Christine Bellanne-Chantelot, Daniel C Link, Christoph Klein, Manuela Germeshausen, David C. Dale, Karl Welte
Journal: Blood (2009)