tbuckley/cabot-search huggingface dataset:
Increasing Treatment Adherence Among Outpatients With Depression and Cocaine Dependence: Results of a Pilot Study
Authors: Dennis C. Daley, Ihsan M. Salloum, Allan Zuckoff, Levent Kirisci, Michael E. Thase
Journal: American Journal of Psychiatry (1998)

Objective:This pilot study examined the effect of a modified motivational therapy intervention on outpatient treatment adherence and completion for patients with comorbid depressive disorder and cocaine dependence.Method:Depressed cocaine patients, stabilized with antidepressant medications on an inpatient psychiatric unit, were consecutively assigned on discharge to motivational therapy (N=11) or treatment-as-usual (N=12) during the first month of outpatient care. Patients were compared on treatment adherence and completion and on 1-year rehospitalization rates. Results:Motivational therapy patients attended significantly more treatment sessions during month 1, completed 30 and 90 days of outpatient care at higher rates, and experienced fewer psychiatric rehospitalizations and days in the hospital during the first year from entry into outpatient treatment.Conclusions:An outpatient program combining individual and group motivational therapy sessions holds promise for improving treatment adherence and completion among depressed patients with cocaine dependence. Am J Psychiatry 1998; 155: 1611-1613
Elucidating Distinct Roles for <i>NF1</i> in Melanomagenesis
Authors: Ophélia Maertens, Bryan Johnson, Pablo Hollstein, Dennie T. Frederick, Zachary A. Cooper, Ludwine Messiaen, Roderick T. Bronson, Martin McMahon, Scott Granter, Keith Flaherty, Jennifer A. Wargo, Richard Marais, Karen Cichowski
Journal: Cancer Discovery (2012)

Abstract BRAF mutations play a well-established role in melanomagenesis; however, without additional genetic alterations, tumor development is restricted by oncogene-induced senescence (OIS). Here, we show that mutations in the NF1 tumor suppressor gene cooperate with BRAF mutations in melanomagenesis by preventing OIS. In a genetically engineered mouse model, Nf1 mutations suppress Braf-induced senescence, promote melanocyte hyperproliferation, and enhance melanoma development. Nf1 mutations function by deregulating both phosphoinositide 3-kinase and extracellular signal–regulated kinase pathways. As such, Nf1/Braf–mutant tumors are resistant to BRAF inhibitors but are sensitive to combined inhibition of mitogen-activated protein/extracellular signal–regulated kinase kinase and mTOR. Importantly, NF1 is mutated or suppressed in human melanomas that harbor concurrent BRAF mutations, NF1 ablation decreases the sensitivity of melanoma cell lines to BRAF inhibitors, and NF1 is lost in tumors from patients following treatment with these agents. Collectively, these studies provide mechanistic insight into how NF1 cooperates with BRAF mutations in melanoma and show that NF1/neurofibromin inactivation may have an impact on responses to targeted therapies. Significance: This study elucidates the mechanism by which NF1 mutations cooperate with different BRAF mutations in melanomagenesis and shows that NF1/neurofibromin loss may desensitize tumors to BRAF inhibitors. Cancer Discov; 3(3); 338–49. ©2012 AACR. See related commentary by Gibney and Smalley, p. 260 This article is highlighted in the In This Issue feature, p. 239
High-dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis
Authors: Keith D. Lindor, Kris V. Kowdley, Velimir A. C. Luketic, Edwyn M. Harrison, Timothy McCashland, Alex S. Befeler, Denise Harnois, Roberta Jorgensen, Jan Petz, Jill Keach, Jody Mooney, Carol Sargeant, Julie Braaten, Tamara Bernard, Debra King, Ellen Miceli, Jeff Schmoll, Tanya Hoskin, Prabin Thapa, Felicity Enders
Journal: Hepatology (2009)

Abstract Previous controlled trials are inconclusive regarding the efficacy of ursodeoxycholic acid (UDCA) for treating primary sclerosing cholangitis (PSC). One hundred fifty adult patients with PSC were enrolled in a long-term, randomized, double-blind controlled trial of high-dose UDCA (28-30 mg/kg/day) versus placebo. Liver biopsy and cholangiography were performed before randomization and after 5 years. The primary outcome measures were development of cirrhosis, varices, cholangiocarcinoma, liver transplantation, or death. The study was terminated after 6 years due to futility. At enrollment, the UDCA (n = 76) and placebo (n = 74) groups were similar with respect to sex, age, duration of disease, serum aspartate aminotransferase and alkaline phosphatase levels, liver histology, and Mayo risk score. During therapy, aspartate aminotransferase and alkaline phosphatase levels decreased more in the UDCA group than the placebo group ( P &lt; 0.01), but improvements in liver tests were not associated with decreased endpoints. By the end of the study, 30 patients in the UDCA group (39%) versus 19 patients in the placebo group (26%) had reached one of the pre-established clinical endpoints. After adjustment for baseline stratification characteristics, the risk of a primary endpoint was 2.3 times greater for patients on UDCA than for those on placebo ( P &lt; 0.01) and 2.1 times greater for death, transplantation, or minimal listing criteria ( P = 0.038). Serious adverse events were more common in the UDCA group than the placebo group (63% versus 37% [ P &lt; 0.01]). Conclusion: Long-term, high-dose UDCA therapy is associated with improvement in serum liver tests in PSC but does not improve survival and was associated with higher rates of serious adverse events. (Hepatology 2009.)
HEXIM1 controls satellite cell expansion after injury to regulate skeletal muscle regeneration
Authors: Peng Hong, Kang Chen, Bihui Huang, Min Liu, Miao Cui, Inna Rozenberg, Brahim Chaqour, Xiaoyue Pan, Elisabeth R. Barton, Xian-Cheng Jiang, M.A.Q. Siddiqui
Journal: Journal of Clinical Investigation (2012)

The native capacity of adult skeletal muscles to regenerate is vital to the recovery from physical injuries and dystrophic diseases. Currently, the development of therapeutic interventions has been hindered by the complex regulatory network underlying the process of muscle regeneration. Using a mouse model of skeletal muscle regeneration after injury, we identified hexamethylene bisacetamide inducible 1 (HEXIM1, also referred to as CLP-1), the inhibitory component of the positive transcription elongation factor b (P-TEFb) complex, as a pivotal regulator of skeletal muscle regeneration. Hexim1-haplodeficient muscles exhibited greater mass and preserved function compared with those of WT muscles after injury, as a result of enhanced expansion of satellite cells. Transplanted Hexim1-haplodeficient satellite cells expanded and improved muscle regeneration more effectively than WT satellite cells. Conversely, HEXIM1 overexpression restrained satellite cell proliferation and impeded muscle regeneration. Mechanistically, dissociation of HEXIM1 from P-TEFb and subsequent activation of P-TEFb are required for satellite cell proliferation and the prevention of early myogenic differentiation. These findings suggest a crucial role for the HEXIM1/P-TEFb pathway in the regulation of satellite cell–mediated muscle regeneration and identify HEXIM1 as a potential therapeutic target for degenerative muscular diseases.
Highlights and summary of the 28th annual meeting of the Society for Immunotherapy of Cancer
Authors: Paolo A Ascierto, David H Munn, Anna K Palucka, Paul M Sondel
Journal: Journal for ImmunoTherapy of Cancer (2014)

The 28th annual meeting of the Society for Immunotherapy of Cancer (SITC) was held November 8–10, 2013 in National Harbor MD, and was organized by Paolo Ascierto (Instituto Nazionale Tumori – Fondazione 9G. Pascale’), David Munn (Georgia Regent’s University), A. Karolina Palucka (Baylor Institute for Immunology Research) and Paul Sondel (University of Wisconsin). This meeting included over 1100 registered participants from 32 separate countries, making it the largest SITC meeting held to date. It highlighted significant worldwide progress in the development and application of cancer immunology to the practice of clinical oncology, including advances in diagnosis, prognosis and therapy, utilizing a variety of immunological pathways and mechanisms for a variety of oncologic conditions. Presentations and posters demonstrated that many concepts that had been pursued preclinically in the past are now being translated into clinical practice, with clear benefits for patients. One month after this 28th annual meeting, the Journal Science selected the field of Cancer Immunotherapy as the overall #1 scientific “breakthrough” for 2013.
Identification of antileucoprotease in remodelled human adult nasal surface epithelium
Authors: V Marchand, JM Tournier, M Chevillard, M Polette, A Beorchia, JM Klossek, E Puchelle
Journal: European Respiratory Journal (1995)

Antileucoprotease (ALP) is generally considered as a specific marker for glandular serous cells, and plays a major role in the defence of the respiratory tract against proteolytic damage. Nevertheless, several studies have identified ALP in bronchial and bronchiolar surface epithelial cells, and also an increased number of ALP-containing cells in bronchiolar tissue during the development of pulmonary diseases. In order to define more clearly whether the surface epithelium might be involved in the defence of the respiratory mucosa, we have investigated the expression of ALP by cells of the nasal surface epithelium. Indirect immunocytochemistry and in situ hybridization for ALP were performed on human nasal polyp sections. The height of the surface epithelium, its morphology, and the degree of local inflammation were assessed in parallel. Surface epithelium morphology was highly heterogeneous. ALP-containing cells were identified, but only in remodelled areas of the surface epithelium (foldings, basal cell and/or mucous cell hyperplasia), with no association to the degree of inflammation. These results demonstrate that the surface epithelial cells of the human adult nasal mucosa can express ALP in remodelled surface epithelium, and may be actively involved in the biochemical defence of the airways.
Attack rates of acute nephritis after Type 49 streptococcal infection of the skin and of the respiratory tract
Authors: Bascom F. Anthony, Edward L. Kaplan, Lewis W. Wannamaker, Franklin W. Briese, S. Stephen Chapman
Journal: Journal of Clinical Investigation (1969)

Prospective studies in a population of American Indian children during an outbreak of acute nephritis associated with the Type 49 Group A streptococcus permitted a comparison of attack rates of renal complications after infection at different sites and at different ages. Acute nephritis or unexplained hematuria developed in 10 of 42 children (23.8%) with Type 49 streptococcal skin infection, in 2 of 44 (4.5%) with Type 49 throat infection, and in 3 of 16 (18.8%) with simultaneous Type 49 infection at both sites. The higher attack rate of nephritis and hematuria in children with pyoderma indicates that skin lesions played a direct and quantitatively greater role than respiratory infection in the pathogenesis of acute nephritis during this outbreak. Skin infections with the Type 49 strain were followed by evidence of renal complications more often in children younger than 6.5 yr (9 of 21 or 43%) than in older children (1 of 21 or 5%). Attack rates of renal complications after Type 49 skin infection were approximately equal in males and females.
Prediction of chronic lung allograft dysfunction: a systems medicine challenge
Authors: Christophe Pison, Antoine Magnan, Karine Botturi, Michel Sève, Sophie Brouard, Benjamin J. Marsland, Florian Ernst, Tobias Paprotka, Kevin Deplanche, Andreas Fritz, Valérie Siroux, Jean-Pierre Boissel, Paul A. Corris, Charles Auffray, Laurent P. Nicod
Journal: European Respiratory Journal (2014)

The International Society for Heart and Lung Transplantation registry recorded that 3631 adult heart-lung transplants and 39 835 adult lung transplants have been performed in centres throughout the world up to 2012, establishing lung transplantation (LT) as the standard of care for selected patients with end-stage respiratory disease [1]. The long-term success of LT is limited by chronic lung allograft dysfunction (CLAD), of which the two most common phenotypes are an abnormal remodelling of the small airways resulting in progressive airflow obstruction called bronchiolitis obliterans syndrome (BOS) and, less frequently, a restrictive ventilatory process referred to as restrictive allograft syndrome (RAS) [2, 3]. Almost 50% of LT recipients will develop CLAD within 5 years post-LT, rising to 75% after 10 years [1]. Despite a range of therapeutic approaches, median survival figures from the time of diagnosis remain very poor at ∼2 years, resulting in 27% overall 10-year survival, the poorest long-term survival after solid-organ transplantations for the period of 2000–2008 in the USA [4].

In clinical practice, CLAD is a diagnosis of exclusion once the possible confounding diseases related either to allograft, such as persistent acute rejection, azithromycin-reversible allograft dysfunction, infection, anastomotic stricture, disease recurrence, and/or to extra-allograft complications, such as pleural disease, diaphragm dysfunction or native lung hyperinflation, have been ruled out. CLAD diagnosis relies on persistent and irreversible decline ≥20% in post-bronchodilator mean of two best forced expiratory volume in 1 s (FEV1) and/or forced vital capacity (FVC) measurements for >3 weeks, accordingly to a new proposed classification for CLAD. [3]. Pulmonary functional tests are used to define CLAD since pathology samplings display important limitations [3]. Treating CLAD remains a challenge because underlying molecular events and triggers are not well understood and unfortunately are …
Skin Cancers after Organ Transplantation
Authors: Sylvie Euvrard, Jean Kanitakis, Alain Claudy
Journal: New England Journal of Medicine (2003)

Skin cancers are the most common tumors in patients who have received organ transplants. This review discusses the epidemiology, pathogenesis, and management of squamous-cell and basal-cell carcinomas, cancers of the anogenital region, Kaposi's sarcoma, melanoma, neuroendocrine skin carcinoma, and cutaneous manifestations of lymphoma in transplant recipients.
Multidrug Resistance in Breast Cancer: a Meta-analysis of MDR1/gp170 Expression and Its Possible Functional Significance
Authors: B. J. Trock, F. Leonessa, R. Clarke
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: P-glycoprotein (gp170; encoded by the MDR1 gene [also known as PGY1]) is a membrane protein capable of exporting a variety of anticancer drugs from cells. MDR1/ gp170 expression has been studied in breast cancer, but the prevalence of this expression and its role in breast tumor drug resistance are unclear. Purpose: We conducted a critical review and meta-analysis of studies examining MDR1/ gp170 expression in breast cancer to estimate the likely prevalence and clinical relevance of this expression. We also explored reasons for differences in the findings from individual studies. Methods: Published papers on MDR1/gp170 expression in breast cancer were identified by searching several literature databases and reviewing the bibliographies of identified papers. Variability across the studies in the proportion of tumors expressing MDR1/gp170 was assessed by use of chi-squared tests of homogeneity, weighted means, and weighted linear regression. Pooled relative risks (RRs) for the association between the induction of MDR1/gp170 expression and prior chemotherapy and associations between MDR1/gp170 expression and several clinical outcomes were estimated by use of Mantel-Haenszel methods. Heterogeneity among the pooled RRs was explored by use of chisquared tests. Reported P values are two-sided. Results: Thirty-one studies were identified and evaluated. The proportion of breast tumors expressing MDR1/gp170 in all of the studies was 41.2%, but there was substantial heterogeneity in the values across individual studies (P<.0001). Regression analyses demonstrated that a considerable portion of the observed heterogeneity was a consequence of the change, over time, from RNA hybridization-based assays to immunohistochemistry-based assays of MDR1/gp170 expression. Measuring MDR1/gp170 expression before versus after chemotherapy and use of cytotoxic drugs that are not substrates for gp170 also contributed to the heterogeneity. Treatment with chemotherapeutic drugs or hormonal agents was associated with an increase in the proportion of tumors expressing MDR1/gp170 (RR = 1.77; 95% confidence interval [CI] = 1.46-2.15). Patients with tumors expressing MDR1/gp170 were three times more likely to fail to respond to chemotherapy than patients whose tumors were MDR1/ gp170 negative (RR = 3.21; 95% CI = 2.28-4.51); this RR increased to 4.19 (95% CI = 2.71-6.47) when considering only patients whose tumor expression of MDR1/gp170 was measured after chemotherapy. MDR1/gp170 expression was not associated with lymph node metastases, estrogen receptor status, tumor size, tumor grade, or tumor histology. Conclusions and Implications: MDR1/gp170 expression in breast tumors is associated with treatment and with a poor response to chemotherapy. The data are consistent with a contributory role for MDR1/gp170 in the multidrug resistance in some breast tumors.
Serum Proteomics and Biomarkers in Hepatocellular Carcinoma and Chronic Liver Disease
Authors: Noah T. Zinkin, Franck Grall, Killimangalam Bhaskar, Hasan H. Otu, Dimitrios Spentzos, Brett Kalmowitz, Meghan Wells, Manuel Guerrero, John M. Asara, Towia A. Libermann, Nezam H. Afdhal
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Proteomic profiling using surface enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF MS) enables the identification of biomarkers for cancer. We evaluated the sensitivity and specificity of SELDI-TOF MS for detection of established hepatocellular cancer (HCC) and compared it against α-fetoprotein (AFP), Lens culinaris agglutinin–reactive AFP (AFP-L3), and prothrombin induced by vitamin K absence-II (PIVKA-II). Experimental Design: Forty-one patients with HCC and 51 patients with hepatitis C cirrhosis were enrolled. Serum was analyzed by SELDI-TOF MS using three Ciphergen protein array types. Results: An 11-peak algorithm for HCC detection was identified. Using the AFP cutoff of 20 ng/mL, the sensitivity was 73% and the specificity was 71%. Using the AFP-L3 cutoff of 10% yielded a sensitivity of 63% and a specificity of 94%. Using the PIVKA-II cutoff of 125 milliabsorbance units (mAU), the sensitivity was 84% and the specificity was 69%. Overall, the sensitivity and specificity of SELDI-TOF MS for HCC were 79% and 86%, respectively. In multivariate analysis, the 11-peak SELDI profile was predictive of HCC independent of AFP, PIVKA, and AFP-L3. Among eight patients with the largest tumor size of &amp;lt;2 cm, SELDI-TOF MS correctly identified seven whereas AFP, AFP-L3, and PIVKA-II identified only three, one, and one, respectively. One of the 11 peaks in the SELDI-TOF MS 11-peak predictor from SELDI-TOF MS was identified as cystatin C. Conclusions: SELDI-TOF MS accurately distinguished patients with HCC from those with hepatitis C virus cirrhosis, was more accurate than traditional biomarkers in identifying small tumors, and should be further evaluated.
Therapeutic Challenges of AIDS-Related Non-Hodgkin's Lymphoma in the United States and East Africa
Authors: Mwanda W. Otieno, Cecily Banura, Edward Katongole-Mbidde, John L. Johnson, Mahmoud Ghannoum, Afshin Dowlati, Rolf Renne, Eric Arts, Christopher Whalen, Michael M. Lederman, Scot C. Remick
Journal: JNCI Journal of the National Cancer Institute (2002)

Non-Hodgkin's lymphoma (NHL) remains the second most common malignant complication in patients with human immunodeficiency virus (HIV) infection. As we enter the third decade of the acquired immunodeficiency syndrome (AIDS) epidemic, it is apparent that the evolution of antiretroviral therapy and the emergence of combination antiviral strategies have greatly affected the natural history of HIV infection and its neoplastic complications. For example, there may be a trend for declining incidence of AIDS-related lymphoma in the United States for the first time. However, in regions of the world where the burden of HIV infection is greatest, such as in East Africa, AIDS-related lymphoma is an increasing cause of morbidity and mortality. Treatment of lymphoma has evolved coincident with improvements in antiretroviral therapy. Infusional chemotherapy regimens may offer advantages over other regimens and schedules, but comparative trials have not been done. Clinical trial data are available on which to develop therapeutic strategies to treat this disease in East Africa where pragmatic approaches are needed. Both the differences in manifestations of HIV infection and the inherent difficulties in administering cytotoxic chemotherapy in this part of the world must be taken into consideration in planning therapeutic strategies. Improved understanding of the pathogenesis of HIV infection and lymphoma will likely yield improved therapeutic interventions as well.
Rapid and complete recovery of responsiveness to adenosine and norepinephrine by regenerating arterioles of the tibialis anterior muscle of the hamster after in situ autografting.
Authors: L M Messina, B M Carlson
Journal: Circulation Research (1991)

Intravital microscopy studies of small bundles of fibers of the extensor digitorum longus muscle grafted onto the hamster cheek pouch revealed a persistent reduction in the responsiveness of regenerated arterioles to vasoactive agents. We tested the hypothesis that the recovery of responsiveness to vasoactive agents by regenerating arterioles within whole, in situ autografted tibialis anterior muscles occurs earlier and more completely than that reported for regenerating arterioles within bundles of fibers of the extensor digitorum longus muscle grafted ectopically to the hamster cheek pouch. The tibialis anterior muscles of Syrian golden hamsters were excised and soaked in bupivacaine (0.75%) for 10 minutes to ensure uniform degeneration of muscle fibers. The tendons were resutured, and the graft became revascularized spontaneously. Fluorescent intravital microscopy was used to measure the responsiveness of 10-40-microns arterioles to topically applied adenosine and norepinephrine at 7, 14, and 30 days after grafting. Nine to 25 arterioles were studied at each time period. Both intravital and light microscopy were used at each time period to characterize the structural development of the microcirculation. We found that the responsiveness of regenerated arterioles returned to control values for topically applied norepinephrine by 14 days and for adenosine by 30 days. Light microscopy showed regenerated blood vessels in the center of the grafts early in the second week after grafting. The structure of the microcirculation at 7 days was characterized by a plexiform microvascular pattern, long spiderlike capillaries, and arterioles and venules that had irregular walls and an irregular branching pattern. Rhodamine-labeled albumin extravasated spontaneously. The 14-day grafts had a more linear capillary pattern, and the arterioles and venules often contained loops that had circular flow patterns. By 30 days, a parallel capillary structure had developed, no vascular loops were present, and the arteriolar-venular pattern was nearly normal.(ABSTRACT TRUNCATED AT 250 WORDS)
Biomarker identification in serum samples from patients with recurrent cervical cancer treated with ADXS11-001 immunotherapy
Authors: Poonam Molli, Inga Malinina, Anu Wallecha
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts Cervical Cancer is the third most common cancer worldwide and is almost always caused by human papilloma virus (HPV) infection. The HPV genes E6 and E7 are known to be oncogenes that promote cellular changes in infected cells leading to malignant transformation. We have previously