tbuckley/cabot-search huggingface dataset:
Coexpression of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT, and p21 in colorectal cancer patients can have IHC variability between metastases and primary tumours and for EGFR-targeted therapies, p21 and VEGF appear reliably as predictive factors of response
Authors: A. Bardier, J. Golmard, J. Dômont, C. Genestie, J. Vaillant, J. Taieb, G. Auclerc, D. Khayat, F. Capron, J. Spano
Journal: Journal of Clinical Oncology (2008)

22074 Background: Recent studies have suggested substantial differences between primary tumours and metastases for EGFR expression in colorectal cancer (CCR). Few data are available for other biological markers from major downstream signalling pathways that could subsequently emerge as new molecular predictive factors to anti-EGFR therapies Methods: We analyzed the expression of a panel of molecular markers in primary colorectal tumours and metastases with the aims to define their staining and correlation between the two sites and for some patient cases treated by Cetuximab (anti-EGFR monoclonal antibody) to find any correlation with the response. Immunohistochemical methodology was performed on formalin-fixed, paraffin-embedded sections from 48 patients with colon adenocarcinomas, and the molecular profiles were evaluated by tissue micro-array (TMA). Relationships concerning molecular markers expression between primary sites and metastases were evaluated by Spearman's rho correlation coefficient and the relationships between markers expression and response to Cetuximab were analysed by a fisher's test. Results: Among 60 CCR cancer samples (T=28, M=32), 44 cases were EGFR negative (75%), 37 were VEGF negative (62%), 23 PTEN deleted (39%), 42 (58%) cases were positive for pAKT, 15 (25%) cases were positive for pVEGF, and 24 (38%) cases were positive for pEGFR. The absence of expression of constitutive p21 was found in 28 cases (49%). A significant correlation between primary tumours and metastases was only found for pAKT (p=0.04) and pEGFR (p=0.0004) status. Among a subgroup of 18 patients treated by Cetuximab-based therapy (anti-EGFR monoclonal antibodies) p21 and VEGF appeared as significant predictive factors of response (p=0.036 and p=0.04 respectively). Conclusions: In CCR patients, discrepancies can be found for some biological markers status between primary tumours and metastases. New predictive markers of response to anti-EGFR therapies seems to be obviously promising (VEGF).These results may have implications for the identification of patients who are likely to respond to anti-EGFR treatment. No significant financial relationships to disclose.
Systemic Therapy for Small Cell Lung Cancer
Authors: Benjamin Levy, Ashish Saxena, Bryan J. Schneider
Journal: Journal of the National Comprehensive Cancer Network (2013)

Small cell lung cancer is an aggressive tumor characterized by genetic complexity, rapid doubling time, and early development of disseminated disease. Unfortunately, few chemotherapeutic advances have been made in the treatment of extensive-stage disease, and cisplatin/etoposide has remained the standard of care for more than 30 years. Other regimens with comparable efficacy include cisplatin/irinotecan and carboplatin/etoposide. Each of these combinations is associated with a different toxicity profile that must be considered when selecting an initial regimen. Several strategies, including maintenance chemotherapy, 3-drug combinations, alternating combination chemotherapy regimens, and high-dose chemotherapy, have consistently failed to demonstrate improvements in survival when compared with 4 to 6 cycles of platinum doublets. Several options are available for patients who experience progression during or relapse after induction therapy, although topotecan is the only FDA-approved agent for second-line treatment. Recently, scientific efforts have identified potentially actionable genetic alterations in small cell tumors that may lead to the development of effective, targeted therapies.
Chronic myeloid leukemia: Second‐line drugs of choice
Authors: Carlo Gambacorti‐Passerini, Andrea Aroldi, Nicoletta Cordani, Rocco Piazza
Journal: American Journal of Hematology (2015)

The efficacy of second‐line treatment for chronic myeloid leukemia (CML) plays an important role in allowing CML patients to enjoy a normal life expectancy. Four tyrosine kinase inhibitors (TKIs) are presently available: bosutinib, dasatinib, nilotinib, ponatinib. Each one has different safety and activity profiles, which are reviewed here. No controlled studies are available to guide treatment decision, which must be based on the characterization of leukemic cells, especially in cases of resistance to TKI, coupled with the safety profile of each TKI. Patient comorbidities also play an important role in the treatment decision, which can achieve a new durable response in over 50% of treated patients. Am. J. Hematol. 91:67–75, 2016. © 2015 Wiley Periodicals, Inc.
Enhancing neurogenesis and angiogenesis with target delivery of stromal cell derived factor-1α using a dual ionic pH-sensitive copolymer
Authors: Dong Hee Kim, Young Kyu Seo, Thavasyappan Thambi, Gyeong Joon Moon, Jung Pyo Son, Guangri Li, Jae Hyung Park, Jung Hee Lee, Hyeon Ho Kim, Doo Sung Lee, Oh Young Bang
Journal: Biomaterials (2015)
Abstract 11176: Exosomes From CXCR4 Overexpressing Mesenchymal Stem Cells (MSCCR4 ) Reduce Ischemic Heart Injury via Upregulation of Paracrine Factors
Authors: Kai Kang, Wenfeng Cai, Wei Huang, Jialiang Liang, Yuhua Wang, Meifeng Xu, Guo-Chang Fan, Ronald W Millard, Muhammad Ashraf, Yi-gang Wang
Journal: Circulation (2013)
Opioids in Psychiatric Disorders: Back to the Future?
Authors: Alan F. Schatzberg
Journal: American Journal of Psychiatry (2015)

The article by Yovell and colleagues in the May issue (1) points to the potential use of low doses of a buprenorphine, a mu-opioid partial agonist, to decrease suicidal ideation in psychiatric patients.The findings are in keeping with earlier work of Bodkin et al. ( 2), who found that buprenorphine could provide relief to patients with refractory depression, and the more recent work of Ehrich et al. (3), who found that buprenorphine in combination with a mu-opioid antagonistsamidorphan-may be effective in refractory major depression.The Yovell et al. data are intriguing on several counts.For one, they offer a possible approach to helping acutely suicidal patients, particularly those with borderline personality disorder, for whom we have little in the way of effective treatments.For another, they point to a possible role for opioids in the treatment of depressed or suicidal patients, particularly those whose illness has been refractory to standard therapy.The latter is in some ways encouraging but presents a number of important issues that we need to address for the sake of our patients, our profession, and the society at large.In these pages, the concern has been raised that the rapid benefits of intravenous ketamine might reflect its mu agonist properties and that ultimately could pose problems for our patients and the field (4).The present report that low oral doses of a mu partial agonist results in relief of suicidal ideation only reinforces our need to begin to address a number of issues that will arise from the use of potential drugs of abuse to treat psychiatric disorders.As Yovell et al. remark, opioids were commonly used for the treatment of depression before the introduction of effective antidepressant agents, and they were abandoned in favor of effective agents that did not connote risk for addiction.And for many of our patients, these second-generation agents have provided great relief of suffering.Unfortunately, many patients do not respond to them, and suicide remains a major public health problem on which we have made little progress.Some compounds with abuse potential offer considerable acute relief, much as an opioid would help postoperative pain.The problem is that patients generally require ongoing therapy, and with that comes the potential risk of dependence, withdrawal, and other ill effects.We have already witnessed this with the epidemic opioid use often stemming from legitimate medical uses (5).In the Yovell et al. study, withdrawal symptoms were not formally evaluated, although they were not elicited after 4 weeks, and the buprenorphine dosages used were very low, ranging from 0.2 to 0.8 mg/day.But what of patients who require higher dosages or for longer
VEGF pharmacodynamics during bevacizumab treatment
Authors: H. M. Verheul, S. Paesante, J. Jaspers, H. Hammers, B. Salumbides, R. Pili
Journal: Journal of Clinical Oncology (2008)

14633 Background: Bevacizumab has shown efficacy in combination with chemotherapy. We previously found that Bevacizumab is taken up by platelets and neutralizes platelet VEGF. Platelets transport VEGF and release it upon activation stimulating (tumor-) angiogenesis. Neutralization of circulating VEGF may be important for the clinical efficacy of bevacizumab. Circulating VEGF can be analyzed in platelets, serum, which is derived from coagulated blood containing high VEGF levels released by platelets or plasma, which is derived from anticoagulated blood containing low VEGF levels. Whether platelets, serum or plasma should be used to accurately determine the effect of bevacizumab on circulating VEGF is unknown. Methods: Blood from 13 patients during treatment with bevacizumab in combination with chemotherapy was obtained. Platelets, serum and platelet poor plasma (PPP) before start of treatment (13 pts), at 2 or 3 (12 pts), at 4 or 6 (10 pts) and at 12 weeks (5 pts) after start of treatment were sampled. In these samples, total protein concentrations and free VEGF concentrations with the VEGF-ELISA kit of R&D, which detects free- but no bevacizumab neutralized-VEGF, were determined. Western blotting was used to determine total VEGF of platelets in a subgroup of patients. Results: Mean platelet, serum and PPP VEGF concentrations before start of treatment were 113±25pg/mg protein, 425±52pg/ml and 111±52pg/ml respectively. At 2, 4 and 12 weeks after start of treatment, platelet and serum concentrations of free-VEGF decreased significantly (p<0.001) compared to pretreatment concentrations to 5±1pg/mg and 98±19pg/ml, while free-VEGF concentrations in PPP did not change significantly compared to pretreatment concentrations (mean concentration of 103±18pg/ml, p=0.7). Total VEGF content of platelets was unaffected during treatment. Conclusions: Free platelet- and serum VEGF is significantly, but not completely, reduced by bevacizumab treatment confirming our previous data that platelets take up bevacizumab. Free PPP VEGF concentrations remained unaffected during treatment. These data indicate that 2/3-weekly dosing of bevacizumab is insufficient to completely neutralize free VEGF. More frequent bevacizumab administrations may completely neutralize VEGF and may potentiate the clinical activity of bevacizumab. No significant financial relationships to disclose.
Former US army physician sentenced to prison for medical device kickback scheme
Authors: Michael McCarthy
Journal: BMJ (2015)

A former US army physician has been sentenced to 30 months in federal prison for his involvement in a $7.3m (£4.8m; €6.5m) healthcare fraud scheme in which he recommended medical devices to US military hospitals where he practiced while he was employed by the companies that developed and marketed the devices. The sentence was handed down on 25 September by Judge David Briones of the US District Court …
In early HIV infection, immediate vs deferred antiretroviral therapy reduced serious illnesses at 3 years
Authors: Fiona Smaill
Journal: Annals of Internal Medicine (2015)

ACP Journal Club15 December 2015In early HIV infection, immediate vs deferred antiretroviral therapy reduced serious illnesses at 3 yearsFiona Smaill, MSc, FRACP, FRCPCFiona Smaill, MSc, FRACP, FRCPCMcMaster University, Hamilton, Ontario, Canada (F.S.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-163-12-004 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationINSIGHT START Study Group, Lundgren JD, Babiker AG, et al. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795-807. https://pubmed.ncbi.nlm.nih.gov/26192873Clinical Impact RatingsGIM/FP/GP: Infectious Disease: References1. AIDSinfo. Statement by the HHS panel on antiretroviral guidelines for adults and adolescents regarding results from the START and TEMPRANO trials. 28 July 2015. www.aidsinfo.nih.gov/news/1592/statement-from-adult-arv-guideline-panel—start-and-temprano-trials (accessed 24 Sep 2015). Google Scholar2. World Health Organization. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. September 2015. apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf (accessed 6 Oct 2015). Google Scholar3. World Health Organization. Programmatic update. Maximizing the treatment and prevention potential of antiretroviral drugs: Early country experiences towards implementing a treat-all policy. July 2015. apps.who.int/iris/bitstream/10665/183599/1/WHO_HIV_2015.35_eng.pdf (accessed 21 Sep 2015). Google Scholar4. Cohen MS, Chen YQ, McCauley M, et al; HPTN 052 Study Team. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493-505. [PMID: 21767103] Google Scholar5. Shah M, Risher K, Berry SA, Dowdy DW. The epidemiologic and economic impact of improving HIV testing, linkage, and retention in care in the United States. Clin Infect Dis. 2015;Sep 11. [Epub ahead of print]. [PMID: 26362321] Google Scholar Author, Article, and Disclosure InformationAuthors: Fiona Smaill, MSc, FRACP, FRCPCAffiliations: McMaster University, Hamilton, Ontario, Canada (F.S.)This article was published at Annals.org on 1 December 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoIn HIV-1, immediate vs deferred antiretroviral therapy and isoniazid vs no isoniazid reduced severe illness at 30 mo Fiona Smaill Metrics Cited byInfection and depletion of CD4+ group-1 innate lymphoid cells by HIV-1 via type-I interferon pathway 15 December 2015Volume 163, Issue 12Page: JC4KeywordsAIDSAntiretroviral therapyDrugsHIVHIV infectionsHospitalizationsInfectious diseasesMortalityPopulation statisticsTreatment guidelines ePublished: 15 December 2015 Issue Published: 15 December 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Anticoagulation vs. vena caval filters in cancer patients with venous thromboembolism: Improved survival with anticoagulation
Authors: M. F. Barginear, M. L. Lesser, M. Strakhan, P. Khetarpal, T. Bradley, D. R. Budman, I. Shapira
Journal: Journal of Clinical Oncology (2006)

8553 Background: Cancer patients (pts) have an increased incidence of venous thromboembolism (VTE). Inferior vena caval (IVC) filters are used extensively in the US; over 40,000 are inserted annually. The impact on survival of cancer pts receiving IVC filters has not been studied. Methods: A retrospective study examined 154 consecutive cancer pts with VTE in order to compare the effects of IVC filter placement with anticoagulation (AC) therapy on overall survival (OS), as measured from the time of VTE. Pts were classified into three treatment groups: AC (n=58), IVC filter (73), or combination IVC filter+AC (23). OS was analyzed using survival analysis methods (e.g., Kaplan-Meier Product-Limit Method, logrank test). Multivariate Cox regression was used to account for the possible confounders: ECOG performance status (PS) and type of thrombus. Results: Treatment groups did not differ with respect to age, gender, or albumin levels. Groups did differ for PS (P&lt;0.033 chi-square test, better PS was associated with AC only) and for type of thrombus (P&lt;0.007 chi-square, DVT was associated with AC, PE with IVC, and DVT/PE with AC+IVC). Median OS was significantly greater in pts treated with AC (11 mos) compared to IVC filters (3 mos) or IVC+AC (3.5 mos) (p&lt;0.0046). IVC pts were 1.73 times more at risk of death than AC only (hazard ratio; 95%CI 1.18–2.52). Multivariate analysis revealed that PS and type of thrombus were not confounders and had no effect on OS. Conclusion: AC should be considered primary therapy for cancer pts with VTE. IVC filters should be considered a therapeutic option only when AC is strictly contraindicated. Prospective randomized trials are needed to address this issue. No significant financial relationships to disclose.
Randomized Trial of Autologous Filgrastim-Primed Bone Marrow Transplantation Versus Filgrastim-Mobilized Peripheral Blood Stem Cell Transplantation in Lymphoma Patients
Authors: Daniela Damiani, Renato Fanin, Federico Silvestri, Stefania Grimaz, Laura Infanti, Antonella Geromin, Michela Cerno, Mariagrazia Michieli, Cristina Rinaldi, Chiara Savignano, Gabriella Trani, Mauro Fiacchini, Michele Baccarani
Journal: Blood (1997)
Use of Computed Tomography in Emergency Departments in the United States
Authors: Frank S. Drescher, Brenda E. Sirovich
Journal: JAMA Internal Medicine (2015)

Mathew Mercuri, PhD; Thomas N. B. Pascual, MD; John J. Mahmarian, MD; Leslee J. Shaw, PhD; Madan M. Rehani, PhD; Diana Paez, MD; Andrew J. Einstein, MD, PhD; for the INCAPS Investigators Group
Transmission of HIV from mother to infant depends on many factors
Authors: M. Berer
Journal: BMJ (1996)

Tuberculosis Research Unit for the streptomycin trial,4 which subsequently (from 1948) served as a model for randomisation in many later randomised controlled trials?Or is it because the results of the patulin trial were negative and those of the streptomycin trial made medical history?I have previously quoted Bradford Hill's re- collection that his statistical, and my medical, experiences in this field converged when we pre- pared for the streptomycin project.56The patulin trial certainly influenced my thinking.Yet, so far as I am aware, the literature on the modem clinical trial contains no recognition of this trial, despite its many deserving features.Should not this omission be rectified?
Pulmonary involvement in patients with Marfan syndrome
Authors: Isa Cerveri, Angelo Corsico, Bianca Tripon, Federica Albicini, Amelia Grosso, Erica Gini, Andrea Mazzetta, Eti Maria Giulia Di Vincenzo, Roberto Dore, Eloisa Arbustini, Maurizio Luisetti
Journal: European Respiratory Journal (2012)

Pulmonary involvement is not generally considered a main feature of Marfan syndrome, an autosomal connective tissue disorder caused by mutations in the extracellular matrix protein fibrillin1 particularly affecting vascular, skeletal and ocular systems. However, thanks to the substantial progress in treatments, life expectation of these patients has been dramatically improved in the last 20 years determining changes in different organ systems. The number of patients with a degree of underlying pulmonary pathology may be higher than expected. Clinical history, chest CT, spirometry, lung volumes,and diffusing capacity have been assessed in 64 patients of our national referral center (mean age 32±14 years; M 45%). None of the patients reported chronic respiratory symptoms and only 5 were smokers. Fourteen per cent reported a previous pneumothorax and 2 of them underwent surgery. Three reported bullae and 1 underwent bullectomy. Eleven per cent had radiological signs of emphysema and 32% apical blebs.Twenty-three per cent had cardiothoracic surgery. Forty-five per cent had moderate to severe rib cage abnormalities; 4 of them underwent repeated surgical corrections. Only 37% of our patients had normal lung function; 19% showed a restrictive pattern and 44% an obstructive pattern or an isolated diffusion impairment or an isolated hyperinflation. All patients with previous pneumothorax showed an obstructive pattern and diffusion impairment. In conclusion, in the absence of respiratory symptoms, pulmonary abnormalities should be actively detected and monitored and particular attention should be paid to prevent pneumothorax. Our results support the importance of lung volume determination and, when needed, chest CT in Marfan patients.
Nicotine Reduces Survival via Augmentation of Paracrine HGF–MET Signaling in the Pancreatic Cancer Microenvironment
Authors: Daniel Delitto, Dongyu Zhang, Song Han, Brian S. Black, Andrea E. Knowlton, Adrian C. Vlada, George A. Sarosi, Kevin E. Behrns, Ryan M. Thomas, Xiaomin Lu, Chen Liu, Thomas J. George, Steven J. Hughes, Shannon M. Wallet, Jose G. Trevino
Journal: Clinical Cancer Research (2015)

The relationship between smoking and pancreatic cancer biology, particularly in the context of the heterogeneous microenvironment, remains incompletely defined. We hypothesized that nicotine exposure would lead to the augmentation of paracrine growth factor signaling between tumor-associated stroma (TAS) and pancreatic cancer cells, ultimately resulting in accelerated tumor growth and metastasis.The effect of tobacco use on overall survival was analyzed using a prospectively maintained database of surgically resected patients with pancreatic cancer. Nicotine exposure was evaluated in vitro using primary patient-derived TAS and pancreatic cancer cells independently and in coculture. Nicotine administration was then assessed in vivo using a patient-derived pancreatic cancer xenograft model.Continued smoking was associated with reduced overall survival after surgical resection. In culture, nicotine-stimulated hepatocyte growth factor (HGF) secretion in primary patient-derived TAS and nicotine stimulation was required for persistent pancreatic cancer cell c-Met activation in a coculture model. c-Met activation in this manner led to the induction of inhibitor of differentiation-1 (Id1) in pancreatic cancer cells, previously established as a mediator of growth, invasion and chemoresistance. HGF-induced Id1 expression was abrogated by both epigenetic and pharmacologic c-Met inhibition. In patient-derived pancreatic cancer xenografts, nicotine treatment augmented tumor growth and metastasis; tumor lysates from nicotine-treated mice demonstrated elevated HGF expression by qRT-PCR and phospho-Met levels by ELISA. Similarly, elevated levels of phospho-Met in surgically resected pancreatic cancer specimens correlated with reduced overall survival.Taken together, these data demonstrate a novel, microenvironment-dependent paracrine signaling mechanism by which nicotine exposure promotes the growth and metastasis of pancreatic cancer.
Does systemic antipsoriatic therapy affect the cardiovascular risk?
Authors: A. Egeberg
Journal: British Journal of Dermatology (2015)

Journal Article Does systemic antipsoriatic therapy affect the cardiovascular risk? Get access A. Egeberg A. Egeberg Departments of Cardiology and Dermato‐Allergology Gentofte Hospital University of Copenhagen Kildegårdsvej 28 2900 Hellerup Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 6, 1 December 2015, Pages 1362–1363, https://doi.org/10.1111/bjd.14149 Published: 01 December 2015
Persistence of host-type hematopoiesis after allogeneic bone marrow transplantation for leukemia is significantly related to the recipient's age and/or the conditioning regimen, but it is not associated with an increased risk of relapse
Authors: JE van Leeuwen, MJ van Tol, AM Joosten, JT Wijnen, PJ Verweij, PM Khan, JM Vossen
Journal: Blood (1994)
The mAbXcite platform modifies the tumor microenvironment when applied to an immune-oncology anti-CTLA4 antibody
Authors: Isabelle Sansal-Castellano, Mark Carlson, Gabriel Reznik, James Siedlecki, John Kane, Zuzana Dostalova, Hua Miao, Ifat Rubin-Bejerano
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts The recent successes in the immunotherapy field demonstrate that a successful immune response to cancer can lead to meaningful anti-tumor responses. Antibodies blocking immune checkpoint molecules (e.g. CTLA4, and PD-1) lead to effective T cell responses especially in tumors that