tbuckley/cabot-search huggingface dataset:
Inflammatory bowel diseases, chronic liver diseases and the lung
Authors: Roberto Rodriguez-Roisin, Sonja D. Bartolome, Gérard Huchon, Michael J. Krowka
Journal: European Respiratory Journal (2016)

This review is devoted to the distinct associations of inflammatory bowel diseases (IBD) and chronic liver disorders with chronic airway diseases, namely chronic obstructive pulmonary disease and bronchial asthma, and other chronic respiratory disorders in the adult population. While there is strong evidence for the association of chronic airway diseases with IBD, the data are much weaker for the interplay between lung and liver multimorbidities. The association of IBD, encompassing Crohn's disease and ulcerative colitis, with pulmonary disorders is underlined by their heterogeneous respiratory manifestations and impact on chronic airway diseases. The potential relationship between the two most prevalent liver-induced pulmonary vascular entities, i.e. portopulmonary hypertension and hepatopulmonary syndrome, and also between liver disease and other chronic respiratory diseases is also approached. Abnormal lung function tests in liver diseases are described and the role of increased serum bilirubin levels on chronic respiratory problems are considered.
Reporting outcomes in Hodgkin's disease and lymphoma.
Authors: D O Dixon, P McLaughlin, F B Hagemeister, E J Freireich, L M Fuller, F F Cabanillas, E A Gehan
Journal: Journal of Clinical Oncology (1987)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1987.5.10.1670 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3655864 Reporting outcomes in Hodgkin's disease and lymphoma. D O DixonxD O DixonSearch for articles by this author , P McLaughlinxP McLaughlinSearch for articles by this author , F B HagemeisterxF B HagemeisterSearch for articles by this author , E J FreireichxE J FreireichSearch for articles by this author , L M FullerxL M FullerSearch for articles by this author , F F CabanillasxF F CabanillasSearch for articles by this author , E A GehanxE A GehanSearch for articles by this author Show More Department of Biomathematics, University of Texas M.D. Anderson Hospital and Tumor Institute, Houston 77030. https://doi.org/10.1200/JCO.1987.5.10.1670 First Page PDF © 1987 by American Society of Clinical Oncology
ErbB3, Cyclin D1 and Ki67 nuclear staining predicts biochemical recurrence in prostate cancer treated by radical prostatectomy
Authors: I. H. Koumakpayi, P. O. Gannon, C. Le Page, M. Alam-Fahmy, J. Madore, A. Mes-Masson, F. Saad
Journal: Journal of Clinical Oncology (2006)

10096 Background: The nuclear accumulation of growth factor receptor was reported to be associated to increased cell proliferation. Cyclin D1 and Ki67 are nuclear markers of cell proliferation. Deregulation of Cyclin D1 and Ki67 expression play a role in tumorigenesis and metastasis. Recently, we observed that nuclear localization of ErbB3 was associated with prostate cancer progression. The objective of this study was to determine if the association of cell proliferation markers and nuclear localization of ErbB3 could predict biochemical recurrence (BCR) in patients with prostate cancer following radical prostatectomy. Methods: Using immunohistochemistry we analyzed a tissue microarray containing 386 cores from 64 formalin-fixed paraffin embedded specimens from prostate cancer patients who had undergone radical prostatectomy. No patient had received hormone therapy prior to surgery and prior to BCR. Antibodies against Cyclin D1, ErbB3 and Ki67 proteins were used. Results: Nuclear staining was 60%, 67% and 86% for Cyclin D1, ErbB3 and Ki67 respectively. In our cohort, 29 of 64 PCa patients (45%) had a BCR after a median 3 years of follow-up. Thirty seven (37) percent of patients had positive nuclear staining for all three markers. BCR free survival probability at 3 years was not significant for each marker individually, except for ErbB3 in positive surgical margin patients. When all three markers were combined for nuclear staining Kaplan-Meier analysis BCR free was 0.4 and 0.1 for positive and negative nuclear staining respectively (p=0.0068). Univariate COX regression analysis shows a 2.98 fold (95% CI: 1.29 - 6.86, p=0.01) higher rate of BCR in patients positive for these three markers. In addition, in a multivariate model, including pre-operative PSA (p=0.19), pathologic stage (p=0.29), Gleason grade (p=0.40) and specimens that had positive nuclear staining for the 3 markers were associated with a 3.97 fold higher rate of BCR (95% CI: 1.54 - 10.25, p=0.0068). Conclusion: These results suggest that the association of cell proliferation markers and nuclear localization of ErbB3 could be useful in predicting recurrence following radical prostatectomy and guide therapeutic decisions. Large scale trials are needed to confirm these results. No significant financial relationships to disclose.
Quantification of sunitinib in sweat secretion.
Authors: N. Lankheet, H. Mallo, J. B. Haanen, A. Huitema, J. Schellens, J. Beijnen, C. U. Blank
Journal: Journal of Clinical Oncology (2010)

e15094 Background: Skin toxicities, such as Hand Foot Syndrome (HFS), are side effects of sunitinib with an adverse impact on quality of life and treatment efficacy. In our outpatient clinic we observed that patients (treated at least for a full year's period) suffered from more severe HFS in the summer than in the winter. Moreover, this did not correlate to other adverse events like thrombocytopenia, liver and kidney function disorders. Therefore, it is unlikely that HFS is only correlated with toxic sunitinib plasma levels. Thus, we hypothesize that aggravation of skin toxicities is caused by the secretion of sunitinib in sweat. Methods: To determine the relationship between cumulative sunitinib secretion in sweat and the severity of HFS and the seasonal influence on the sunitinib sweat secretion, sweat samples from patients receiving sunitinib at various dose levels were analyzed for their content of sunitinib and its metabolite N-desethyl-sunitinib. Cumulative sweat samples were collected by application of sweat patches for seven consecutive days during the sunitinib on-treatment and the off-treatment period. Sunitinib and metabolite levels in sweat were quantified by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Results: We established that sunitinib and its metabolite can be detected in sweat samples of patients during the sunitinib on-treatment and off-treatment period. Cumulative sunitinib secretion was found to be regularly higher in the on-treatment sweat samples compared to the off-treatment samples. The opposite was found for cumulative metabolite secretion. We found ranges of 14.4- 119 and 1.42-31.6 ng/patch for cumulative secretion of sunitinib and its metabolite, respectively. The observed sunitinib levels in sweat did not correlate with applied oral doses of sunitinib. Moreover, apparent inter-patient differences were observed in sunitinib sweat secretion. Conclusions: To our knowledge this is the first exploratory study establishing that sunitinib secretion in sweat is quantifiable. The inter-patient variability in sunitinib sweat secretion justifies further substantiation of our hypothesis on the relationship between occurrence of HFS and local exposure to sunitinib in sweat in an extended cohort of patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
Human nasal epithelial cells derived from multiple subjects exhibit differential responses to H3N2 influenza virus infection in vitro
Authors: Yan Yan, Kai Sen Tan, Chunwei Li, Thai Tran, Siew Shuen Chao, Richard J. Sugrue, Li Shi, Vincent T. Chow, De-Yun Wang
Journal: Journal of Allergy and Clinical Immunology (2016)
Phase II randomized trial of gallium nitrate plus fluorouracil versus methotrexate, vinblastine, doxorubicin, and cisplatin in patients with advanced transitional-cell carcinoma.
Authors: J A McCaffrey, S Hilton, M Mazumdar, S Sadan, M Heineman, J Hirsch, W K Kelly, H I Scher, D F Bajorin
Journal: Journal of Clinical Oncology (1997)

PURPOSE A phase II randomized trial of gallium nitrate/fluorouracil (5-FU) versus dose-intense methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) was performed in poor-risk patients with advanced urothelial tract tumors. The efficacy and toxicity of these regimens were compared. Assessment of dose-intense M-VAC as salvage treatment in patients who failed to respond to the gallium nitrate/5-FU regimen was also performed. PATIENTS AND METHODS Thirty-four patients who had not received prior systemic chemotherapy were randomized to either arm of the study. All patients had one or more clinical features predicting a low likelihood of durable complete response to standard chemotherapy, ie, weight loss, visceral metastases, and low performance status. Gallium nitrate and 5-FU were each administered by continuous 5-day infusions every 28 days. M-VAC was recycled every 21 days, with prophylactic recombinant human granulocyte colony-stimulating factor (rh-G-CSF). RESULTS Two of 17 patients (12%; 95% confidence interval [CI], 1.4% to 36.4%) had a major response to gallium nitrate/5-FU. Sixteen of 17 patients treated with M-VAC (94%; 95% CI, 71.3% to 99.8%) demonstrated a major response. Five of 12 patients who failed to respond to the gallium nitrate/5-FU combination responded to M-VAC as second-line therapy (42%; 95% CI, 15.2% to 72.3%). Median survival for the gallium nitrate and 5-FU arm was 19 versus 17 months for the M-VAC arm, with a median follow-up duration of 35 months (range, 2 to 51) for all patients. Dose-intense M-VAC was associated with a greater incidence of neutropenia and thrombocytopenia. CONCLUSION Dose-intense M-VAC is superior to gallium nitrate/5-FU in poor-risk patients (P &lt; .0001). Despite the overall high response rate, the median survival for patients with M-VAC remained unsatisfactory. Similar survival distributions were observed for patients who received investigational therapy followed by cisplatin-based therapy and patients treated with initial cisplatin-based therapy.
Phenylarsine Oxide Blocks Interleukin-1β–Induced Activation of the Nuclear Transcription Factor NF-κB, Inhibits Proliferation, and Induces Apoptosis of Acute Myelogenous Leukemia Cells
Authors: Zeev Estrov, Sunil K. Manna, David Harris, Quin Van, Elihu H. Estey, Hagop M. Kantarjian, Moshe Talpaz, Bharat B. Aggarwal
Journal: Blood (1999)
Phase III double-blind study of depot octreotide versus placebo in the prevention of acute diarrhea during pelvic radiation therapy: Results of North Central Cancer Treatment Group protocol N00CA
Authors: J. A. Martenson, J. A. Sloan, R. L. Deming, D. B. Wender, K. J. Stien, T. H. Tai, G. M. Proulx, A. W. Zhu, R. C. Miller, P. J. Atherton
Journal: Journal of Clinical Oncology (2006)

8506 Background: A randomized study (Int J Rad Oncol Biol Phys 54:195–202, 2002) demonstrated a beneficial effect for octreotide in the treatment of diarrhea in patients receiving pelvic radiation therapy. This North Central Cancer Treatment Group study was undertaken to determine the effectiveness of depot octreotide in the prevention of diarrhea during pelvic radiation therapy. Methods: Patients receiving pelvic radiation therapy, with a planned minimum dose of 45 Gy at 1.70–2.1 Gy per day, were eligible for this study. The study was designed for a Wilcoxon test, with 112 evaluable patients, to have 85% power to detect a further one grade decrease in diarrhea over and above that experienced by patients treated with placebo. Between June 13, 2002 and October 28, 2005, 120 evaluable patients were randomly allocated, in double blind fashion, to receive octreotide (62 patients) or placebo (58 patients), prior to the fourth radiation therapy fraction. Octreotide dosing: Octreotide, 100 micrograms subcutaneously on day 1 followed by depot octreotide, 20 milligrams intramuscularly on days 2 and 29. Results: Grade 0, 1, 2 and 3 diarrhea was observed in 17%, 32%, 26% and 26% of patients treated with octreotide and 18%, 34%, 22%, and 26% of patients treated with placebo (P=0.86). Grade 0, 1, 2 and 3 tenesmus was observed in 55%, 30%, 11% and 4% of patients treated with octreotide and 76%, 16%, 4%, and 4% of patients treated with placebo (P=0.04). No other statistically significant differences in toxicity were observed. Conclusions: Octreotide, as administered in this study, did not decrease diarrhea during pelvic radiation therapy. [Table: see text]
A Small-Molecule Antagonist of the β-Catenin/TCF4 Interaction Blocks the Self-Renewal of Cancer Stem Cells and Suppresses Tumorigenesis
Authors: Liang Fang, Qionghua Zhu, Martin Neuenschwander, Edgar Specker, Annika Wulf-Goldenberg, William I. Weis, Jens P. von Kries, Walter Birchmeier
Journal: Cancer Research (2015)

Abstract Wnt/β-catenin signaling is a highly conserved pathway essential for embryogenesis and tissue homeostasis. However, deregulation of this pathway can initiate and promote human malignancies, especially of the colon and head and neck. Therefore, Wnt/β-catenin signaling represents an attractive target for cancer therapy. We performed high-throughput screening using AlphaScreen and ELISA techniques to identify small molecules that disrupt the critical interaction between β-catenin and the transcription factor TCF4 required for signal transduction. We found that compound LF3, a 4-thioureido-benzenesulfonamide derivative, robustly inhibited this interaction. Biochemical assays revealed clues that the core structure of LF3 was essential for inhibition. LF3 inhibited Wnt/β-catenin signals in cells with exogenous reporters and in colon cancer cells with endogenously high Wnt activity. LF3 also suppressed features of cancer cells related to Wnt signaling, including high cell motility, cell-cycle progression, and the overexpression of Wnt target genes. However, LF3 did not cause cell death or interfere with cadherin-mediated cell–cell adhesion. Remarkably, the self-renewal capacity of cancer stem cells was blocked by LF3 in concentration-dependent manners, as examined by sphere formation of colon and head and neck cancer stem cells under nonadherent conditions. Finally, LF3 reduced tumor growth and induced differentiation in a mouse xenograft model of colon cancer. Collectively, our results strongly suggest that LF3 is a specific inhibitor of canonical Wnt signaling with anticancer activity that warrants further development for preclinical and clinical studies as a novel cancer therapy. Cancer Res; 76(4); 891–901. ©2015 AACR.
Possible therapeutic reversal of immune suppression in patients with metastatic melanoma by timed delivery of temozolomide chemotherapy: A pilot study
Authors: F. Quevedo, M. L. Ashdown, V. J. Suman, A. Robinson, L. A. Kottschade, J. S. Kaur, E. T. Creagan, R. R. McWilliams, S. N. Markovic
Journal: Journal of Clinical Oncology (2009)

e20013 Background: Recent evidence suggests that patients with advanced cancer exhibit an underlying anti-tumor immune response that is continuously attenuated by regulatory T cells (Treg). Depletion of Treg using conventional chemotherapy may be feasible and clinically beneficial. C-reactive protein (CRP) is reported to rise/fall with initiation/termination of the immune response, and may be a surrogate for the periodicity of Treg proliferation that could be utilized for timing of anti-proliferative therapy. Timed delivery of chemotherapy therapy based on CRP cycling may deplete Treg and yield clinical benefit. Methods: We conducted a pilot clinical for 12 patients with metastatic melanoma who underwent serial CRP measurements (every 2–3 days) for 2 weeks. The CRP oscillation cycle was identified and chemotherapy with temozolomide (200mg/m 2 for 5 days, every 28 days) was initiated at the estimated peak of plasma CRP. Patients were evaluated for clinical and immune response endpoints every 8 weeks until progression. Results: All 12 patients (median age 61; 4 female; 7 with M1c disease) exhibited oscillating CRP levels with an average periodicity of 7.8 days. Only 11 patients were treated (1 patient had rapid tumor progression). The two patients who remain progression-free for &gt;2 years (1 PR, 1 CR), were treated in the pre-peak section of the CRP cycle, distinctly separate from the other patients treated post CRP-peak (all progressed &lt;5 months). Presented are peripheral blood immunological laboratory correlates (cellular and cytokine) to CRP oscillation. Conclusions: These data suggest that patient clinical outcome may be dependent on the timing of therapy relative to an individual patient's immune response cycle and outline the dynamic equilibrium of systemic immune homeostasis in patients with advanced melanoma. Further investigations of these observations are under way. [Table: see text]
OC-095 Performance of a novel optical sensor for intraoperative assessment of intestinal viability – ‘proof of principle’ study
Authors: Z Abdollahi, MA Thaha, A Ramsanahie, S Ahmed, P Kyriacou, JP Phillips
Journal: Gut (2015)

<h3>Introduction</h3> Objective assessment of intestinal viability during surgery will allow surgeons to make informed decisions on the safety of intestinal anastomosis and to predict anastomotic related complications.<sup>1</sup>We investigated the performance of a novel dual sensor incorporating two established methods – photoplethysmography (PPG) and laser Doppler flowmetry (LDF) in a ‘proof of principle’ study. <h3>Method</h3> Using the new probe, infrared and red PPG amplitude and LDF flux of the bowel surface were recorded by LDF and PPG simultaneously in 30 patients undergoing large bowel resection with or without anastomosis. Each patient had measurements at eight different time points: before and after colonic mobilisation, over the tumour, before and after ligation of major vascular pedicle, immediately before and after anastomosis (+/- 5 min) at distal and proximal limbs. Both laparoscopic and open resectional cases were included. The differences between the mean amplitude and flux between different measurements were analysed. <h3>Results</h3> Twenty four laparoscopic and six open bowel resection cases had a total of 121 measurements recorded using the new probe. The mean IR AC amplitude in pre-ligation was 433 (± 189) mV and the mean IR AC in post ligation was 301 (± 152) mV. A statistically significant difference (<i>P = 0</i>.047) was observed between pre-ligation and post-ligation for the mean infrared PPG amplitude (student’s t-test). A considerable difference in mean amplitude between pre and post ligation for the red PPG was also observed (the mean amplitude for the red PPG fell by –25.6%). The amplitude of the infrared PPG increased after anastomosis by 38.2% at the proximal site and by 37.8% at the distal site. The amplitude of the red PPG also increased after anastomosis (by 6.3%) at the proximal site although the equivalent increase was not seen at the distal site. The LDF measurements did not follow the same pattern of the changes seen in PPG amplitude. <h3>Conclusion</h3> The preliminary results show that simultaneous PPG/LDF measurements from a combined sensor is feasible and provide useful information on changes in pulse volume and blood flow. Although the differences in PPG amplitude achieved statistical significance, the LDF measurements produced confounding results, perhaps explained by motion artefacts. Further refinements in design of the probe are required to improve the probe-tissue optical interface and reduce motion artefact. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Urbanavičius L, Pattyn P, Van de Putte D, Venskutonis D. How to assess intestinal viability during surgery: a review of techniques. World J Gastrointest Surg. 2011;3(5):59–69
Pharmacogenetic analysis of CTLA4 gene polymorphisms and response to tremelimumab in patients with advanced melanoma
Authors: J. Richmond, F. Gao, L. Wood, C. A. Bulanhagui, M. Penny
Journal: Journal of Clinical Oncology (2008)

14003 Background: Tremelimumab is a fully-human, immune-enhancing, monoclonal antibody targeted against CTLA4 in clinical development for the treatment of solid tumors. In recognition of the fact that variation in the drug target or other proteins related to tumor immunity may influence a patient’s response to tremelimumab, pharmacogenomic analysis has been incorporated into the clinical development plan. Methods: Three polymorphisms in the CTLA4 gene, promoter (-318 C/T), exon 1 (+49 A/G) and intergenic (CT60) were genotyped in 268 patients from two tremelimumab trials. All patients had advanced melanoma that was refractory to prior treatment. Tremelimumab was administered at varying dosing regimes. Genotypes were correlated with clinical efficacy endpoints including progressive disease, objective tumor response, survival at one year, and safety endpoints related to diarrhea and severity of diarrhea via Fisher’s exact test for contingency tables as well as through logistic regression assessing the interaction effect of sex and genotype. This analysis was powered to detect a relative risk in the >2 range. Results: Allele frequencies were not significantly different from published data, and no significant deviations from Hardy Weinberg Equilibrium were observed (P < 0.05). The two studies were analyzed separately; data will be presented to show that no consistent trends were observed between any CTLA4 genotype and any clinical endpoint tested. Conclusions: No pharmacogenetic effect between the CTLA4 genotypes tested and response to tremelimumab was observed in these initial studies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer
Relationship of Selenium to Cancer. I. Inhibitory Effect of Selenium on Carcinogenesis
Authors: Raymond J. Shamberger
Journal: JNCI Journal of the National Cancer Institute (1970)

In 5 of 6 nondietary tumor-promotion experiments, sodium selenide significantly reduced the number of tumors in mice. In 2 of these 6 experiments, vitamin E also significantly reduced the number of animals with tumors. In all 6 experiments, both selenium and vitamin E decreased the total number of papillomas. Another antioxidant and 2 lysosomal stabilizers were ineffective. After 19 weeks of administration, sodium selenide did not significantly lower the number of mice with 3-methylchol-anthrene-induced papillomas nor after 30 weeks of administration did it reduce the number of cancers. Nonetheless, the total number of papillomas and cancers were greatly decreased. Torula yeast diets containing 1.0 parts per million (ppm) sodium selenite given to mice markedly decreased the number of skin tumors induced by 7,12-dimethylbenz[a]anthracene plus croton oil and benzo[a]pyrene. Torula diets containing 0.1 ppm sodium selenite and also a commercial diet (Rockland) did not decrease tumor incidence.
P0074 : Prevalence and risk factors of metabolic syndrome after liver transplantation: a single centre experience
Authors: V. Pepe, G. Germani, A. Ferrarese, A. Zanetto, I. Bortoluzzi, E. Nadal, F.P. Russo, M. Senzolo, U. Cillo, P. Burra
Journal: Journal of Hepatology (2015)