tbuckley/cabot-search huggingface dataset:
Value of CYFRA 21–1,carcinoembryonic antigen, and squamous cell carcinoma antigen as tumor markers in non-small cell lung cancer patients
Authors: J. L. Patel, J. A. Erickson, D. G. Grenache, W. L. Roberts
Journal: Journal of Clinical Oncology (2008)

19042 Background: Non-small cell lung cancer (NSCLC) represents a major health burden in terms of incidence and mortality. Sensitive serum tumor markers are needed to identify early recurrence in post-surgical patients and monitor response to therapy. CYFRA 21–1 measures cytokeratin 19 fragments and has been reported as a sensitive tumor marker for NSCLC. We hypothesize that CYFRA 21–1 may complement other NSCLC markers including carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCCa). Methods: The CYFRA 21–1 assay is an automated immunochemiluminometric assay performed on serum. The assay utilizes KS19.1 and BM19.21 monoclonal antibodies in a standard sandwich format. Validation studies revealed favorable performance characteristics including limit of blank of 0.01 ng/mL, linearity from 0.1 to 100 ng/mL, and overall imprecision of < 4%. The upper 95th percentile reference limit was 1.5 ng/mL for healthy adult subjects. CEA and SCCa assays were performed using established immunoassay protocols, with upper reference limits of 3.0 and 2.2 ng/mL, respectively. Serum samples from 78 NSCLC patients were tested. Tumor histology within this group included adenocarcinoma (n=16) and squamous cell carcinoma (n=44) as well as a variety of other NSCLC types (n=18). Results: Our data show increasing sensitivity of CYFRA 21–1 with stage and in combination with CEA and SCCa (see table). Conclusion: Sensitive serum tumor markers for recurrent disease in NSCLC patients have the potential for significant clinical utility, as they may help optimize patient management. Biochemical evidence of recurrence would likely precede clinical signs and symptoms. Our data show that CYFRA 21–1 is complimentary to CEA and SCCa in a stage-dependent manner. While none of the markers performed well when used alone, a panel consisting of these three markers has high sensitivity and should be considered in the evaluation of NSCLC patients. Tumor marker positivity in NSCLC patients by stage Stage Number CYFRA 21–1 (%) CEA (%) SCCa (%) CYFRA 21–1 or CEA (%) CYFRA 21–1 or SCCa (%) CEA or SCCa (%) Any one of these three (%) I 46 30.4 43.5 21.7 58.7 39.1 54.3 67.4 II 12 50.0 75.0 0.0 75.0 50.0 75.0 75.0 III 12 66.7 58.3 41.7 91.7 83.3 75.0 100.0 IV 8 75.0 75.0 50.0 100.0 87.5 100.0 100.0 No significant financial relationships to disclose.
L. reuteri can inhibit the cytotoxic effects of S.aureus on keratinocytes in vitro.
Authors: Tessa Prince, Catherine O'Neill, A.J. McBain
Journal: British Journal of Dermatology (2011)

Probiotics such as lactic acid producing bacteria are defined as ?Live microorganisms which when administered in adequate amounts confer a health benefit on the host?. The beneficial effects of probiotics in the gut are well described and roles including immunomodulation and colonisation resistance are documented. Recent reports have suggested that topical use of probiotic bacteria may be an effective strategy to promote skin health or inhibit disease. Little is known, however, about potential mechanisms and cellular interactions between either commensal skin bacteria (such as Staphylococcus epidermidis) or enteric probiotics (e.g. Lactobacilli spp.) with the skin. We have investigated the effect of a probiotic Lactobacillus reuteri strain on S. aureus-induced cytotoxicity in keratinocyte cell cultures. Normal human epidermal keratinocytes (NHEK) were grown to confluence and infected with S. aureus (108) in the presence or absence of L.reuteri ATCC 55730 (108). Keratinocyte viability was measured using trypan blue exclusion assays. Cells exposed to the lactobacillus at the same time as infection with S.aureus were significantly less susceptible to inactivation by the staphylococcus (53.12 % survival vs. 8.82% in unprotected cells; P< 0.001). Well diffusion assays indicated that whilst the lactobacillus inhibited the staphylococci, this was wholly attributable to lactic acid production; an effect not detectable in cell culture. Therefore, L.reuteri ATCC 55730 inhibits the cytotoxic effect of S.aureus on keratinocytes though mechanisms other than direct inhibition of S.aureus growth.
Implementing the Concept of Continuous Clinical Response Into Clinical Practice for Ulcerative Colitis
Authors: Laurent Peyrin-Biroulet, Gert Van Assche, Alessandro Armuzzi, Laura Garcia-Alvarez, Nuria Lara, Christopher M. Black, Ahmed Khalifa, Freddy Cornillie, Sumesh Kachroo
Journal: Clinical Gastroenterology and Hepatology (2016)
Long-term survival from the initial trial of bevacizumab and irinotecan.
Authors: A. Desjardins, J. J. Vredenburgh, D. A. Reardon, J. E. Herndon, J. Marcello, K. Peters, S. Gururangan, S. Sathornsumetee, J. N. Rich, H. S. Friedman
Journal: Journal of Clinical Oncology (2010)

2045 Background: The prognosis for recurrent glioblastoma multiforme (GBM) is poor, with median overall survivals of 5- 7 months, and < 10% survival at two years. GBMs are highly vascular tumors, with the highest concentration of vascular endothelial growth factor (VEGF) of any tumor. Bevacizumab is a humanized monoclonal antibody to VEGF. We performed a phase II trial of bevacizumab and irinotecan for patients with recurrent GBM from April, 2005 to November 2005. Methods: 35 patients with recurrent GBM were enrolled. All of the patients had received standard radiation therapy and temozolomide. Patients were treated with bevacizumab at 10 mg/kg every 14 days (N = 23) in cohort 1 or 15 mg/kg every 21 days (n = 12) in cohort 2. The irinotecan was dosed at 125 mg/m2 for patients not on enzyme-inducing anti- epileptic drugs (EIAED) and 340 mg/m2 for patients on EIAEDs given every 14 days for the first cohort. For cohort 2, the irinotecan was given on day 1, 8, 22 and 29. Each cycle was 6 weeks, with an MRI after each cycle. Patients were treated for up to 9 cycles. Two investigators independently reviewed each MRI, and used the modified MacDonald criteria using T1 + C and FLAIR sequences. Results: The regimen was the first to produce a response rate > 20%, 20/35 (57%) had a partial response. The clinical benefit was durable with a 6 month PFS of 46% compared to historical controls of < 20%. The median overall survival was 9.7 months. In this small phase II study, the 4-year overall survival was 11%. One patient remains progression-free. Of the other three patients alive at 4 years, all three responded to a bevacizumab containing regimen at the time of progression. Conclusions: Bevacizumab and irinotecan is an active regimen for recurrent GBM, with durable improvements in overall survival for a subset of patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Roche Genentech Genentech
Deferasirox Significantly Reduces Liver Iron Concentration In Non-Transfusion-Dependent Thalassemia Patients with Iron Overload: Results From the 1-Year Randomized, Double-Blind, Placebo-Controlled Phase II THALASSA Study
Authors: Ali T Taher, John B. Porter, Vip Viprakasit, Antonis Kattamis, Suporn Chuncharunee, Pranee Sutcharitchan, Noppodol Siritanaratkul, Renzo Galanello, Zeynep Karakas, Tomasz Lawniczek, Jacqueline Ros, Yiyun Zhang, Dany Habr, M. Domenica Cappellini
Journal: Blood (2011)
Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution
Authors: Natascha Luther, Fatemeh Shahneh, Melanie Brähler, Franziska Krebs, Sven Jäckel, Saravanan Subramaniam, Christian Stanger, Tanja Schönfelder, Bettina Kleis-Fischer, Christoph Reinhardt, Hans Christian Probst, Philip Wenzel, Katrin Schäfer, Christian Becker
Journal: Circulation Research (2016)

Rationale: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. Objective: This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. Methods and Results: CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (T EM ) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis–recruited T EM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4 + and CD8 + T EM cells. Reducing the number of T EM cells through a depletion recovery procedure, we show that intravenous T EM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. Conclusions: T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.
Paclitaxel plus platinum-based chemotherapy versus conventional platinum-based chemotherapy in women with relapsed ovarian cancer: the ICON4/AGO-OVAR-2.2 trial (vol 361, pg 2099, 2003)
Authors: JA Ledermann, N Colombo, A du Bois, Torri, I Floriani, W Qian, HP Adams, Mkb Parmar, S Collins, S Wheeler, D Poli, M Santillo, A Buda, G Elser, P Schantl
Journal: The Lancet (2003)
Prolonged Survival in Stage III Melanoma with Ipilimumab Adjuvant Therapy
Authors: Alexander M.M. Eggermont, Vanna Chiarion-Sileni, Jean-Jacques Grob, Reinhard Dummer, Jedd D. Wolchok, Henrik Schmidt, Omid Hamid, Caroline Robert, Paolo A. Ascierto, Jon M. Richards, Céleste Lebbé, Virginia Ferraresi, Michael Smylie, Jeffrey S. Weber, Michele Maio, Lars Bastholt, Laurent Mortier, Luc Thomas, Saad Tahir, Axel Hauschild, Jessica C. Hassel, F. Stephen Hodi, Corina Taitt, Veerle de Pril, Gaetan de Schaetzen, Stefan Suciu, Alessandro Testori
Journal: New England Journal of Medicine (2016)

On the basis of data from a phase 2 trial that compared the checkpoint inhibitor ipilimumab at doses of 0.3 mg, 3 mg, and 10 mg per kilogram of body weight in patients with advanced melanoma, this phase 3 trial evaluated ipilimumab at a dose of 10 mg per kilogram in patients who had undergone complete resection of stage III melanoma.After patients had undergone complete resection of stage III cutaneous melanoma, we randomly assigned them to receive ipilimumab at a dose of 10 mg per kilogram (475 patients) or placebo (476) every 3 weeks for four doses, then every 3 months for up to 3 years or until disease recurrence or an unacceptable level of toxic effects occurred. Recurrence-free survival was the primary end point. Secondary end points included overall survival, distant metastasis-free survival, and safety.At a median follow-up of 5.3 years, the 5-year rate of recurrence-free survival was 40.8% in the ipilimumab group, as compared with 30.3% in the placebo group (hazard ratio for recurrence or death, 0.76; 95% confidence interval [CI], 0.64 to 0.89; P<0.001). The rate of overall survival at 5 years was 65.4% in the ipilimumab group, as compared with 54.4% in the placebo group (hazard ratio for death, 0.72; 95.1% CI, 0.58 to 0.88; P=0.001). The rate of distant metastasis-free survival at 5 years was 48.3% in the ipilimumab group, as compared with 38.9% in the placebo group (hazard ratio for death or distant metastasis, 0.76; 95.8% CI, 0.64 to 0.92; P=0.002). Adverse events of grade 3 or 4 occurred in 54.1% of the patients in the ipilimumab group and in 26.2% of those in the placebo group. Immune-related adverse events of grade 3 or 4 occurred in 41.6% of the patients in the ipilimumab group and in 2.7% of those in the placebo group. In the ipilimumab group, 5 patients (1.1%) died owing to immune-related adverse events.As adjuvant therapy for high-risk stage III melanoma, ipilimumab at a dose of 10 mg per kilogram resulted in significantly higher rates of recurrence-free survival, overall survival, and distant metastasis-free survival than placebo. There were more immune-related adverse events with ipilimumab than with placebo. (Funded by Bristol-Myers Squibb; ClinicalTrials.gov number, NCT00636168 , and EudraCT number, 2007-001974-10 .).
What do we need to know about the presidential candidates’ health?
Authors: Douglas Kamerow
Journal: BMJ (2016)

Standardized information may not really help



In the circus that is the 2016 US presidential election campaign, one of the newest sideshows has been the issue of the health of the candidates.

Hillary Clinton, now 68, began her campaign in 2015 by releasing a conventional report from her doctor describing recent examinations and her overall physical fitness to serve as president. This was updated in the past few weeks to include a discussion of Clinton’s widely publicized case of pneumonia and a recent sinus and ear infection.1 These became especially relevant because of Donald Trump’s continuing insistence that Clinton does not have the “stamina” to be president.

Trump, 70, at first refused to release his own medical records, instead publicizing a rather strange letter from his doctor stating …
A Pilot Trial of the Combination of Vemurafenib with Adoptive Cell Therapy in Patients with Metastatic Melanoma
Authors: Drew C. Deniger, Mei Li M. Kwong, Anna Pasetto, Mark E. Dudley, John R. Wunderlich, Michelle M. Langhan, Chyi-Chia Richard Lee, Steven A. Rosenberg
Journal: Clinical Cancer Research (2016)

This pilot feasibility clinical trial evaluated the coadministration of vemurafenib, a small-molecule antagonist of BRAFV600 mutations, and tumor-infiltrating lymphocytes (TIL) for the treatment of metastatic melanoma.A metastatic tumor was resected for growth of TILs, and patients were treated with vemurafenib for 2 weeks, followed by resection of a second lesion. Patients then received a nonmyeloablative preconditioning regimen, infusion of autologous TILs, and high-dose interleukin-2 administration. Vemurafenib was restarted at the time of TIL infusion and was continued for 2 years or until disease progression. Clinical responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. Metastases resected prior to and after 2 weeks of vemurafenib were compared using TCRB deep sequencing, immunohistochemistry, proliferation, and recognition of autologous tumor.The treatment was well tolerated and had a safety profile similar to that of TIL or vemurafenib alone. Seven of 11 patients (64%) experienced an objective clinical response, and 2 patients (18%) had a complete response for 3 years (one response is ongoing at 46 months). Proliferation and viability of infusion bag TILs and peripheral blood T cells were inhibited in vitro by research-grade vemurafenib (PLX4032) when approaching the maximum serum concentration of vemurafenib. TCRB repertoire (clonotypes numbers, clonality, and frequency) did not significantly change between pre- and post-vemurafenib lesions. Recognition of autologous tumor by T cells was similar between TILs grown from pre- and post-vemurafenib metastases.Coadministration of vemurafenib and TILs was safe and feasible and generated objective clinical responses in this small pilot clinical trial. Clin Cancer Res; 23(2); 351-62. ©2016 AACRSee related commentary by Cogdill et al., p. 327.
Allergic asthma is distinguished by sensitivity of allergen-specific CD4 <sup>+</sup> T cells and airway structural cells to type 2 inflammation
Authors: Josalyn L. Cho, Morris F. Ling, David C. Adams, Lucas Faustino, Sabina A. Islam, Roshi Afshar, Jason W. Griffith, Robert S. Harris, Aylwin Ng, Giorgia Radicioni, Amina A. Ford, Andre K. Han, Ramnik Xavier, William W. Kwok, Richard Boucher, James J. Moon, Daniel L. Hamilos, Mehmet Kesimer, Melissa J. Suter, Benjamin D. Medoff, Andrew D. Luster
Journal: Science Translational Medicine (2016)

Despite systemic sensitization, not all allergic individuals develop asthma symptoms upon airborne allergen exposure. Determination of the factors that lead to the asthma phenotype in allergic individuals could guide treatment and identify novel therapeutic targets. We used segmental allergen challenge of allergic asthmatics (AA) and allergic nonasthmatic controls (AC) to determine whether there are differences in the airway immune response or airway structural cells that could drive the development of asthma. Both groups developed prominent allergic airway inflammation in response to allergen. However, asthmatic subjects had markedly higher levels of innate type 2 receptors on allergen-specific CD4+ T cells recruited into the airway. There were also increased levels of type 2 cytokines, increased total mucin, and increased mucin MUC5AC in response to allergen in the airways of AA subjects. Furthermore, type 2 cytokine levels correlated with the mucin response in AA but not AC subjects, suggesting differences in the airway epithelial response to inflammation. Finally, AA subjects had increased airway smooth muscle mass at baseline measured in vivo using novel orientation-resolved optical coherence tomography. Our data demonstrate that the development of allergic asthma is dependent on the responsiveness of allergen-specific CD4+ T cells to innate type 2 mediators as well as increased sensitivity of airway epithelial cells and smooth muscle to type 2 inflammation.
Multicenter phase I clinical trial of daily and weekly RAD001 in combination with vinorelbine and trastuzumab in patients with HER2-overexpressing metastatic breast cancer with prior resistance to trastuzumab
Authors: G. H. Jerusalem, V. Dieras, F. Cardoso, J. Bergh, A. Fasolo, A. Rorive, C. Manlius, I. Pylvaenaeinen, T. Sahmoud, L. Gianni
Journal: Journal of Clinical Oncology (2008)

1057 Background: RAD001 (everolimus) is an oral inhibitor of the mTOR serine-threonine kinase, a downstream component of the PI3K/AKT signaling pathway playing a critical role in regulation of protein synthesis and ultimately cell growth, proliferation, and angiogenesis. RAD001 shows activity in breast cancer patients (pts) as both monotherapy and in combination with letrozole. Preclinical models demonstrate that RAD001 enhances the efficacy of trastuzumab. Loss of PTEN and AKT/mTOR activation have been reported to mediate resistance to trastuzumab. Methods: Vinorelbine was administered at a dose of 25 mg/m2, IV over 10–15 min on days 1 and 8 q3w. Trastuzumab 4 mg/kg loading dose administered IV over 90 min on day 1 (if pt was not already receiving trastuzumab), followed by weekly trastuzumab 2 mg/kg IV over 30 min. In the daily RAD001 arm, 2 cohorts were planned (5 and 10mg) and in the weekly RAD001 arm, 4 cohorts were planned (20, 30, 50 and 70mg). Treatment continues until progression or unacceptable toxicity. Results: As of Jan 8, 2008, 19 heavily pretreated pts were enrolled: nine to the 5mg daily, six to 20mg weekly and four to the 30mg weekly cohorts. All pts received prior taxane. Median number of prior chemotherapy regimens was 3 (range: 1–5). In the 5mg daily arm, the main safety concern was grade 2 and 3 stomatitis which led to dose reduction in three patients and dose interruption in three more. Neutropenia was also reported. Preliminary efficacy: eight pts have been evaluated; 2 pts had PR (22+, 26+ weeks) and four pts SD (12, 13+, 28, 42+ weeks). Among the 10 pts recruited to the weekly arm, grade 4 neutropenia was reported in 4 and 3 pts in the 20 and 30mg cohorts, respectively. No other serious adverse reactions were observed to date. Preliminary efficacy: Nine pts were evaluated; 1 pt had PR (23+ weeks) and seven pts SD (11+, 14+, 19, 26+, 26+, 37+, 43+ weeks). Recruitment continues. Conclusions: Initial findings show that RAD001 is generally well tolerated in combination with vinorelbine and trastuzumab and shows promising activity in heavily pretreated pts with HER2-overexpressing metastatic breast cancer. We aim to present updated results at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Pharmaceuticals Novartis, Roche, Genentech Novartis Novartis, Roche, Genentech Novartis
Secukinumab shows significant efficacy in palmoplantar psoriasis: Results from GESTURE, a randomized controlled trial
Authors: Alice Gottlieb, John Sullivan, Martijn van Doorn, Alexey Kubanov, Ruquan You, Anne Parneix, Sophie Hugot, Marina Milutinovic
Journal: Journal of the American Academy of Dermatology (2016)

Plaque psoriasis affecting palms and soles is disabling and often resistant to treatment.Evaluate the efficacy and safety of secukinumab, an anti-interleukin 17A antibody, in subjects with palmoplantar psoriasis.In this double-blinded, randomized controlled trial, 205 subjects were randomized 1:1:1 to secukinumab 300 mg, 150 mg, or placebo. The primary endpoint was Palmoplantar Investigator's Global Assessment (ppIGA) 0 (clear) or 1 (almost clear/minimal) response at week 16.At week 16, the percentage of subjects who achieved clear or almost clear palms and soles (or ppIGA 0/1) with secukinumab 300 mg (33.3%) and 150 mg (22.1%) was superior to the percentage achieved with placebo (1.5%, P < .001). Palmoplantar Psoriasis Area and Severity Index (ppPASI) was significantly reduced with secukinumab 300 mg (-54.5%) and 150 mg (-35.3%) compared with placebo (-4.0%, P < .001). Dermatology Life Quality Index (DLQI) 0/1 responses from subjects in the secukinumab groups were also significantly higher compared with placebo at week 16 (P < .01) and pain and function of palms and soles was markedly improved with secukinumab as measured by the palmoplantar Quality-of-Life Instrument. Secukinumab 300 mg consistently showed the best outcomes. The safety profile was favorable and similar to previous studies.Lack of active comparator.In GESTURE, the largest randomized controlled trial in palmoplantar psoriasis, secukinumab demonstrated the greatest efficacy to date for treating difficult-to-treat psoriasis.
T Cell Suicide Gene Therapy Prompts Thymic Renewal in Adults After Haploidentical Hematopoietic Stem Cell Transplantation in the Absence of Post-Transplant Immunesuppression
Authors: Luca Vago, Giacomo Oliveira, Attilio Bondanza, Maddalena Noviello, Corrado Soldati, Domenico Ghio, Immacolata Brigida, Raffaella Greco, Maria Teresa Lupo Stanghellini, Jacopo Peccatori, Sergio Fracchia, Matteo Del Fiacco, Catia Traversari, Alessandro Aiuti, Antonio Lambiase, Alessandro Del Maschio, Claudio Bordignon, Fabio Ciceri, Chiara Bonini
Journal: Blood (2011)