tbuckley/cabot-search huggingface dataset:
A Systematic Analysis Reveals Heterogeneous Changes in the Endocytic Activities of Cancer Cells
Authors: Sarah R. Elkin, Nawal Bendris, Carlos R. Reis, Yunyun Zhou, Yang Xie, Kenneth E. Huffman, John D. Minna, Sandra L. Schmid
Journal: Cancer Research (2015)

Abstract Metastasis is a multistep process requiring cancer cell signaling, invasion, migration, survival, and proliferation. These processes require dynamic modulation of cell surface proteins by endocytosis. Given this functional connection, it has been suggested that endocytosis is dysregulated in cancer. To test this, we developed In-Cell ELISA assays to measure three different endocytic pathways: clathrin-mediated endocytosis, caveolae-mediated endocytosis, and clathrin-independent endocytosis and compared these activities using two different syngeneic models for normal and oncogene-transformed human lung epithelial cells. We found that all endocytic activities were reduced in the transformed versus normal counterparts. However, when we screened 29 independently isolated non–small cell lung cancer (NSCLC) cell lines to determine whether these changes were systematic, we observed significant heterogeneity. Nonetheless, using hierarchical clustering based on their combined endocytic properties, we identified two phenotypically distinct clusters of NSCLCs. One co-clustered with mutations in KRAS, a mesenchymal phenotype, increased invasion through collagen and decreased growth in soft agar, whereas the second was enriched in cells with an epithelial phenotype. Interestingly, the two clusters also differed significantly in clathrin-independent internalization and surface expression of CD44 and CD59. Taken together, our results suggest that endocytotic alterations in cancer cells that affect cell surface expression of critical molecules have a significant influence on cancer-relevant phenotypes, with potential implications for interventions to control cancer by modulating endocytic dynamics. Cancer Res; 75(21); 4640–50. ©2015 AACR.
MicroRNA-21 is a potential link between non-alcoholic fatty liver disease and hepatocellular carcinoma via modulation of the HBP1-p53-Srebp1c pathway
Authors: Heng Wu, Raymond Ng, Xin Chen, Clifford J Steer, Guisheng Song
Journal: Gut (2015)

<h3>Background</h3> Non-alcoholic fatty liver disease (NAFLD) is a major risk factor for hepatocellular carcinoma (HCC). However, the mechanistic pathways that link both disorders are essentially unknown. <h3>Objective</h3> Our study was designed to investigate the role of microRNA-21 in the pathogenesis of NAFLD and its potential involvement in HCC. <h3>Methods</h3> Wildtype mice maintained on a high fat diet (HFD) received tail vein injections of microRNA-21-anti-sense oligonucleotide (ASO) or miR-21 mismatched ASO for 4 or 8 weeks. Livers were collected after that time period for lipid content and gene expression analysis. Human hepatoma HepG2 cells incubated with oleate were used to study the role of miR-21 in lipogenesis and analysed with Nile-Red staining. microRNA-21 function in carcinogenesis was determined by soft-agar colony formation, cell cycle analysis and xenograft tumour assay using HepG2 cells. <h3>Results</h3> The expression of microRNA-21 was increased in the livers of HFD-treated mice and human HepG2 cells incubated with fatty acid. MicroRNA-21 knockdown in those mice and HepG2 cells impaired lipid accumulation and growth of xenograft tumour. Further studies revealed that <i>Hbp1</i> was a novel target of microRNA-21 and a transcriptional activator of <i>p53</i>. It is well established that p53 is a tumour suppressor and an inhibitor of lipogenesis by inhibiting <i>Srebp1c</i>. As expected, microRNA-21 knockdown led to increased <i>HBP1</i> and <i>p53</i> and subsequently reduced lipogenesis and delayed G1/S transition, and the additional treatment of <i>HBP1</i>-siRNA antagonised the effect of microRNA-21-ASO, suggesting that <i>HBP1</i> mediated the inhibitory effects of microRNA-21-ASO on both hepatic lipid accumulation and hepatocarcinogenesis. Mechanistically, microRNA-21 knockdown induced <i>p53</i> transcription, which subsequently reduced expression of genes controlling lipogenesis and cell cycle transition. In contrast, the opposite result was observed with overexpression of microRNA-21, which prevented <i>p53</i> transcription. <h3>Conclusions</h3> Our findings reveal a novel mechanism by which microRNA-21, in part, promotes hepatic lipid accumulation and cancer progression by interacting with the <i>Hbp1</i>-<i>p53</i>-<i>Srebp1c</i> pathway and suggest the potential therapeutic value of microRNA-21-ASO for both disorders.
microRNA profiling in duodenal ulcer disease caused by Helicobacter pylori infection in a Western population
Authors: S. Lario, M.J. Ramírez-Lázaro, A.M. Aransay, J.J. Lozano, A. Montserrat, Á. Casalots, F. Junquera, J. Álvarez, F. Segura, R. Campo, X. Calvet
Journal: Clinical Microbiology and Infection (2012)
Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin's disease, including Radiation Therapy Oncology Group 87-01.
Authors: H M Vriesendorp, J M Herpst, M A Germack, J L Klein, P K Leichner, D M Loudenslager, S E Order
Journal: Journal of Clinical Oncology (1991)

Radiolabeled antiferritin immunoglobulin (Ig) preparations were tested in patients with advanced, end-stage Hodgkin's disease. Four patients received indium-111 (111In)-labeled monoclonal antiferritin (QCI). Targeting was not observed in tumor-bearing areas. Instead, scans showed rapid accumulation of QCI in normal liver. Forty-five patients were injected with 111In-labeled polyclonal antiferritin (rabbit, pig, or baboon). Forty (89%) patients showed tumor uptake, with dosimetric estimates ranging from 300 to 3,000 cGy in 1 week for the subsequently administered yttrium-90 (90Y)-labeled antiferritin. Yttrium-labeled antibody caused hematologic toxicity. Treatment-induced toxicity was not observed in any other organ system. Intravenous autologous bone marrow cells, 18 days after the yttrium infusion, accelerated hematopoietic recovery in eight patients receiving 30 mCi or 40 mCi. Hematopoietic recovery after a 20 mCi 90Y-labeled antiferritin infusion was not influenced by an autologous bone marrow transplant. Two patients receiving 20 mCi and one patient receiving 50 mCi remained aplastic after transplantation for unknown reasons. In 29 assessable patients, a 62% response rate was observed; nine of the 18 responses were complete. Responses ranging from 2 to 26 months were more commonly noted in patients with small tumors and long disease histories. Dosimetric calculations did not predict for responses. Recurrences frequently occurred in new areas instead of areas exhibiting bulky disease at the start of the treatment. Complete responses after 90Y antiferritin were significantly (P less than .02) more frequent than in a previous study with iodine-131 (131I) antiferritin. Further improvements are needed to make this new treatment modality curative.
Linking clinical phenotypes of chronic lung allograft dysfunction to changes in lung structure
Authors: Stijn E. Verleden, Dragoş M. Vasilescu, John E. McDonough, David Ruttens, Robin Vos, Elly Vandermeulen, Hannelore Bellon, Rachel Geenens, Erik K. Verbeken, Johny Verschakelen, Dirk E. Van Raemdonck, Wim A. Wuyts, Youri Sokolow, Christiane Knoop, Joel D. Cooper, James C. Hogg, Geert M. Verleden, Bart M. Vanaudenaerde
Journal: European Respiratory Journal (2015)

Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term success after lung transplantation. This report compares gross and microscopic features of lungs removed from patients receiving a redo-transplant as treatment for CLAD. Lungs donated by patients with either the bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS) phenotype of CLAD and appropriate control lungs (eight per group) were air-inflated, frozen solid and kept frozen while a multi-detector computed tomography (MDCT) was obtained. The lung was then cut into 2-cm thick transverse slices and sampled for micro-CT and histopathology. The MDCT showed reduced lung volume with increased lung weight and density in RAS versus BOS and control (p&lt;0.05). Although pre-terminal bronchioles were obstructed in both phenotypes, RAS lungs showed a reduction of pre-terminal bronchioles (p&lt;0.01). Micro-CT and matched histopathology showed that RAS was associated with reduced numbers of terminal bronchioles/lung compared to BOS and controls (p&lt;0.01), with expansion of the interstitial compartment and obliteration of the alveolar airspaces by fibrous connective tissue. RAS is associated with greater destruction of both pre-terminal and terminal bronchioles. Additionally, the interstitial compartments are expanded and alveolar airspaces are obliterated by accumulation of fibrous connective tissue.
Fixed erythrodysaesthesia plaque due to intravenous injection of docetaxel
Authors: C-Y. Chu, C-H. Yang, C-Y. Yang, G-H. Hsiao, H-C. Chiu
Journal: British Journal of Dermatology (2000)

Docetaxel (Taxotere), a semisynthetic taxoid, acts as an antimicrotubule agent and is considered to have great potential in the treatment of non-small cell lung cancer, advanced breast cancer, ovarian cancer and some other tumours. Well-recognized side-effects include dose-limiting neutropenia, fluid retention, myalgia, neuropathy, hypersensitivity reaction, alopecia, mucositis, nail changes and cutaneous reactions such as acral erythema. We describe a unique docetaxel-induced cutaneous reaction presenting as fixed erythematous plaque(s) unrelated to extravasation or previous skin injury; histopathological studies were performed in three of the four cases.
Neutrophil ROS production in obese and non-obese men with different severity of obstructive sleep apnoea
Authors: Guoda Pilkauskaite, Skaidrius Miliauskas, Simona Lavinskiene, Raimundas Sakalauskas
Journal: European Respiratory Journal (2012)

Obstructive sleep apnoea (OSA) is characterized by pauses of breathing during sleep followed by hypoxia/re-oxygenation circles that increase production of reactive oxygen species (ROS). Literature data are controversial regarding obesity impact on generation of ROS in OSA. The aim was to evaluate neutrophil ROS production in obese and non-obese men with different severity of OSA. Methods: 40 newly diagnosed men with OSA having no actively treated comorbidities were included. OSA was confirmed by whole-night polysomnography (PSG), when apnoea/hypopnea index (AHI) was >5/h. Body mass index (BMI) was calculated. Blood samples were taken in the morning after PSG. Neutrophils were isolated by high density centrifugation. DHR-123 was used for detection of generated ROS. ROS production was measured by mean fluorescence intensity (MFL) using flow cytometer. All subjects were divided into 4 groups: AHI
Ultrastructure of thrombocytes in bronchial asthma and modeling of experimental allergic process
Authors: Tatyana Barkhina, Valentina Golovanova, Mikhail Guschin, Veronika Ksenofontova
Journal: European Respiratory Journal (2013)

The aim: establish the role of thrombocytes in the pathogenesis of allergic diseases and in experimental models.  Materials and methods: scrapings of the mucosa of the nasal cavity (SMNC), bronhobioptates (BB) and peripheral blood cells of 33 patients with allergic rhinitis and bronchial asthma (BA) in order to study the thrombocytes by transmission (TEM) and scanning electron microscopy (SEM). Experimental simulation was carried out on guinia pigs using intravenous injection of heterologic mitochondrial antibodies to get an allergic reaction.  Results. We detected marked changes of thrombocytes by SEM: aggregation, changing of the configuration and of pseudopodia. With TEM we revealed in SMNC and BB a lot of damaged thrombocytes inside the vessels, in pericapillar and in perivascular spaces. Submicroscopic picture varied depending on the severity of the disease. We found the destruction and enlightmen of cell organells. In the experimental simulation we investigated thrombocytes in the microvessels of airways. Noteworthy that thrombocytes were detected outside of microvessels. Aggregation was observed especially in the area of aero-blood-vesse barrier. Contacts of thrombocytes with white blood cells and an interchange of dark and light thrombocytes were found. Ultra-changes of thrombocytes by TEM in the experiment were identical to the ones we observed in clinic material.Conclusion. All our findings suggest that thrombocytes play a significant role in the pathogenesis of BA and in the dynamics of experimental allergic process. The detected changes are a sign hypoxic conditions, which can be interpreted as one of the pathogenetic system features of BA.
The role of Foxc2 gene in lung development
Authors: Mayoko Tsuji, Masae Morishima, Kazuhiko Shimizu, Tsutomu Kume, Jun Tamaoki, Taichi Ezaki
Journal: European Respiratory Journal (2014)

Foxc2  gene is one of the forkhead transcriptional factors which are expressed in several embryonic tissues, and plays a significant role in vascularization. During investigation of the cardiovascular anomalies in  Foxc2  knockout fetuses, we have found some abnormalities in the lung, although the relationship between  Foxc2  gene and the developmental lung morphogenesis is unknown. In this study, we sought to characterize the fetal lung tissue in  Foxc2  mutant mice. Mutant fetuses at embryonic days 15.5-18.5 of gestation were obtained from the mating between ICR- Foxc2  heterozygotes. (Control: Wild type littermates, WT). To characterize tissue morphology, cryo-sections (5µm) of the lung were made and stained either with hematoxylin-eosin or immunohistochemically for CD31, Type IV collagen, and CXCR4. As markers for the cell differentiation efficacy, pro-SPC, T1αwere used.  Foxc2  null fetuses showed relatively thicker alveolar septums and narrower lumens, but there was almost no difference in the staining of septum with CD31 and Type IV collagen between mutants and WT fetuses. Since there was no significant difference in the number and distribution of Pro-SPC+ and T1α+ cells, the differentiation efficacy was relatively preserved in mutants. However, T1α+ cells in  Foxc2  mutant was morphologically different from those in WT. Proximal T1α+ cells in the lung of  Foxc2  mutant fetuses did not become flat as those of WT. Our data indicate that Foxc2 gene is also involved in the lung maturation, especially the development of T1α+ cells in the alveolar epithelium. As a next step, the  Foxc2  gene expression in the lungs of the mutants is now under investigation.
Family-Centered Care and High-Consequence Pathogens
Authors: Preeti Mehrotra, Andi L. Shane, Aaron M. Milstone
Journal: JAMA Pediatrics (2015)

This Viewpoint proposes cultivating a new role in family centeredness in the setting of high-consequence pathogens by optimizing virtual technology, having health care professionals assume an active role in family centeredness, and thinking creatively.
Immunostimulation of Cytomegalovirus-Transformed Cells and Its Inhibition by Blocking Sera 2
Authors: Donna M. Murasko, Robert N. Lausch
Journal: JNCI Journal of the National Cancer Institute (1976)

Spleen cells cytotoxic at high effector cell: target cell ratios specifically enhanced target cell survival at low ratios. Both cytotoxicity and immunostimulation could be specifically blocked by sera from tumor-bearing or virus-sensitized hosts. The results suggested that serum factors participate in the regulation of the cell-mediated immune response.
Airflow obstruction, functional disability and psychological dysfunction in bronchiectasis
Authors: Graham Miller, Helmy Haja Mydin, Anthony De Soyza
Journal: European Respiratory Journal (2011)

Introduction:  The impact of airflow obstruction, functional disability and psychological dysfunction has previously been described in COPD but not in bronchiectasis. We hypothesised that anxiety and depression may be commoner in bronchiectasis patients with poor functional capacity or evidence of airflow obstruction (AO).   Methods:  Adults attending a bronchiectasis clinic from Dec 2010-Jan 2011 were screened. Spirometry was performed & GOLD criteria for COPD were used to categorise AO. Functional ability was assessed using the MRC dyspnoea (MRCD) scale. The Hospital Anxiety and Depression Scale (HADS) was used to screen for anxiety and depression. A score of ≥8 in either sub-scale (HADS-A, HADS-D) was deemed clinically significant.   Results:  N=52 (34F, 18M). Mean age: 61 (SD 13.4). 30 patients (57.7%) had evidence of AO. 6 patients (20%) had mild AO, 11 patients (37%) had moderate AO, 11 patients (37%) had severe AO and 2 patients (6%) had very severe AO. 27 patients (48%) had a MRCD score of ≥3. 30 patients (42.3%) had a HADS-A score of ≥8. 19 patients (37%) had a HADS-D score of ≥8. 15 patients (28.8%) had both HADS-A and D scores of ≥8. Chi-square analysis showed significant association of clinically significant HADS-A (p 1  (% predicted) and HADS-A (p=0.43) or D (p=0.98) scores.   Discussion:  Many patients had severe or very severe airflow obstruction. 50% of patients had a MRCD score of ≥3, indicating significant functional impairment. These patients have higher burdens of psychological morbidity. Studies addressing functional impairment and psychological dysfunction are required.
Evaluation of sequential organ failure assessment (SOFA) based models for predicting mortality in ICU patients
Authors: Maria Khan
Journal: European Respiratory Journal (2013)

Introduction:In critically ill patients,SOFA might be a useful tool for prediction of mortality.  Objective:To evaluate optimal recurrence of SOFA acquisition in severity of organ dysfunctions and the associated mortality rates in critically ill patients.  Method:A prospective observational study was conducted from Jan 1 to June 30,2011.Including randomly selected patients(age >18)admitted to the SICU and MICU of tertiary care hospital,for whom SOFA score was calculated after every 24 hours till 72 hours.Initial,highest and mean SOFA scores obtained during their ICU stay and their correlations with mortality.  Result:Initial,highest and mean SOFA scores correlated well with mortality.Highest score of 11 and mean score of more than 7 indicates mortality> 80%(p 90%) a decreasing score during the first 72 hours is associated with mortality rate of less than 15%,while an unchanged and increasing score is associated with a mortality rate of 37% when the score was 2 or 7 and 60% when the score was 8 to 11.  Conclusion:SOFA score during the first three days of ICU admission is a good indicator of prognosis.This study conducted for the first time in Pakistan and have comparitively same results as done in Belgium.
Frequency of Dissociative Disorders Among Psychiatric Inpatients in a Turkish University Clinic
Authors: Hamdi Tutkun, Vedat Sar, L. Ilhan Yargiç, Tuba Özpulat, Medaim Yanik, Emre Kiziltan
Journal: American Journal of Psychiatry (1998)

The aim of this study was to determine the rate of dissociative disorders among psychiatric inpatients in a university clinic in Turkey.The Dissociative Experiences Scale was used to screen 166 consecutive inpatients admitted to the psychiatry clinic of a university hospital. The patients who had scores higher than 30 were matched for age and gender with 19 of the patients who scored below 10 on the scale. The patients in both groups were then interviewed with the Dissociative Disorders Interview Schedule by interviewers who were blind to their diagnoses and scores on the Dissociative Experiences Scale. Patients who were diagnosed as having a dissociative disorder according to the Dissociative Disorders Interview Schedule were then interviewed by a clinician.Twenty-four (14.5%) of the 166 patients had a score higher than 30 on the Dissociative Experiences Scale; 17 patients (10.2%) were diagnosed as having a dissociative disorder according to the Dissociative Disorders Interview Schedule. Nine patients (5.4%) had clinically confirmed dissociative identity disorder.A considerable proportion of the psychiatric inpatients in a Turkish university psychiatry clinic had dissociative disorder. Clinicians who work in general psychiatric inpatient units should be alert for chronic complex dissociative disorders.
BRIM-2: An open-label, multicenter phase II study of vemurafenib in previously treated patients with <i>BRAF</i> V600E mutation-positive metastatic melanoma.
Authors: A. Ribas, K. B. Kim, L. M. Schuchter, R. Gonzalez, A. C. Pavlick, J. S. Weber, G. A. McArthur, T. E. Hutson, K. T. Flaherty, S. J. Moschos, D. P. Lawrence, P. Hersey, R. F. Kefford, B. Chmielowski, I. Puzanov, J. Li, K. B. Nolop, R. J. Lee, A. K. Joe, J. A. Sosman
Journal: Journal of Clinical Oncology (2011)

8509 Background: Most agents tested in large phase II trials in patients (pts) with metastatic melanoma have response rates of 10-20%. Approximately 50% of melanomas harbor a V600E activating mutation in the BRAF gene, which can now be targeted with specific inhibitors. In a Phase I study, treatment with vemurafenib (V), an orally available inhibitor of mutant BRAF, led to a high incidence of tumor regressions in BRAF-mutant melanoma (Flaherty et al. NEJM 2010). Here we report the results of BRIM-2, a pivotal Phase II trial of V in previously treated pts with BRAF-mutant melanoma. Methods: The primary endpoint was best overall response rate (BORR), with a target of 30% and a lower boundary of the exact 95% CI of at least 20% by independent review committee (IRC). BRAF mutation status was determined using a PCR-based investigational, companion diagnostic assay (cobas 4800 BRAF V600 Mutation Test, Roche Molecular Systems). Pts without active CNS metastasis who had received at least one prior line of therapy for metastatic melanoma received V (960 mg po twice daily) until progressive disease, unacceptable toxicity, or death. Results: 132 pts were enrolled (Oct 2009-Mar 2010), median age 51.5 yr, 54% ECOG PS 1, 61% M1c, 49% elevated LDH, and 49% >1 line of prior therapy. At the time of analysis (Sept 27, 2010, median follow-up 7 mo), BORR was 52.3% (95% CI: 43–61%; 2.3% CR, 50% PR) by IRC, with 29.5% SD and only 13.6% PD. Median duration of response was 6.8 mo (95% CI: 5.6-NR), and median PFS was 6.2 mo (95% CI: 5.6–6.8%). Median OS had not been reached. Most common adverse events (AEs; ≥25% pts, mostly Grade 1-2) were arthralgia, rash, photosensitivity, fatigue, alopecia, pruritis, and skin papilloma. The most common Grade 3 AE was cutaneous squamous cell carcinoma (24.2%), the majority centrally reviewed as keratoacanthoma-type. AEs were generally reversible with dose modification or interruption. 42% of pts required dose reductions, most commonly for rash, arthralgia and LFT abnormalities. Conclusions: BRIM2 met its primary endpoint based on BORR, confirming that V is an active agent in pts with BRAF mutation-positive melanoma who have completed prior first-line therapy.
Mistreatment of Patients' Families by Psychiatrists
Authors: WILLIAM S. APPLETON
Journal: American Journal of Psychiatry (1974)

Many schools of psychiatric thought implicate the patient's family in aggravating and even generating his illness. Thus psychiatrists often blame and mistreat the family, through either open hostility or vague innuendo; the family in turn becomes less willing to cooperate in the patient's treatment. As a solution, the author recommends that psychiatrists be taught to treat families with sympathy and understanding in order to win their confidence and cooperation and with respect rather than subtle contempt.
Abstract 20323: Bare Metal Stents versus Drug Eluting Stents in Saphenous Vein Grafts: A Systematic Review of Prospective and Retrospective Studies
Authors: Girum Mekonnen, Rahul Sharma, Steven Ettinger
Journal: Circulation (2010)

Background: Drug eluting stents (DES) have led to significant advancement but there are limits of evidence to their use in saphenous vein grafts (SVG). SVG disease after coronary bypass is a common...