tbuckley/cabot-search huggingface dataset:
A combined strategy of serial analysis of gene expression (SAGE) and quantitative PCR (qPCR) to identify four genes that predict outcome in non-small cell lung cancer patients.
Authors: J. De Castro, C. Belda-Iniesta, J. Sanchez, R. Machado-Pinilla, V. Rodríguez-Fanjúl, J. Feliu, I. Ibañez de Cáceres, M. Nistal, R. Perona, P. Cejas
Journal: Journal of Clinical Oncology (2010)

e17502 Background: Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small cell lung cancer. However, objective response rates are in the range of 30% to 50%. Thus, prediction of treatment response and outcome before CRT is a major challenge for clinicians. Methods: In a first stage we perfomed a SAGE analysis on snap-frozen surgical specimens from three good responder and three bad responder patients. Response sensibility to cisplatin was evaluated using cytotoxicity assays in primary cultures of tumor cells from the surgical specimens. In a second stage we analyzed the expression of 22 genes and 2 controls using TaqMan low density arrays in snap-frozen surgical specimens from 51 operable stages non-small cell lung cancer patients. Disease-free survival was used as the endpoint of the study. All patients received cisplatin-based adjuvant chemotherapy. Multivariate Cox methods were applied to build an optimized predictor of outcome. Results: The combination of mTOR, TWIST1, AKCR1C2, and HSPB1 gene expression was able to predict clinical outcome in pretreated tissues. In addition, DFS analysis revealed that the gene signature- based score was the only statistically significant prognostic factor remaining in the multivariate analysis. Conclusions: A basal 4-gene signature, obtained from surgical specimens of non-small cell lung cancer, efficiently predicted clinical outcome in the patients. These preliminary results are very encouraging and, if they are validated in larger series, could have clinical implications. No significant financial relationships to disclose.
Cardiac Mechano-Gated Ion Channels and Arrhythmias
Authors: Rémi Peyronnet, Jeanne M. Nerbonne, Peter Kohl
Journal: Circulation Research (2016)

Mechanical forces will have been omnipresent since the origin of life, and living organisms have evolved mechanisms to sense, interpret, and respond to mechanical stimuli. The cardiovascular system in general, and the heart in particular, is exposed to constantly changing mechanical signals, including stretch, compression, bending, and shear. The heart adjusts its performance to the mechanical environment, modifying electrical, mechanical, metabolic, and structural properties over a range of time scales. Many of the underlying regulatory processes are encoded intracardially and are, thus, maintained even in heart transplant recipients. Although mechanosensitivity of heart rhythm has been described in the medical literature for over a century, its molecular mechanisms are incompletely understood. Thanks to modern biophysical and molecular technologies, the roles of mechanical forces in cardiac biology are being explored in more detail, and detailed mechanisms of mechanotransduction have started to emerge. Mechano-gated ion channels are cardiac mechanoreceptors. They give rise to mechano-electric feedback, thought to contribute to normal function, disease development, and, potentially, therapeutic interventions. In this review, we focus on acute mechanical effects on cardiac electrophysiology, explore molecular candidates underlying observed responses, and discuss their pharmaceutical regulation. From this, we identify open research questions and highlight emerging technologies that may help in addressing them.
Alcohol abuse, depression, and suicidal behavior in schizophrenia
Authors: S J Bartels, R E Drake, G J McHugo
Journal: American Journal of Psychiatry (1992)

Alcohol use was correlated with depression and suicidal behavior in two independent studies of schizophrenic outpatients. Depression alone accounted for over 80% of the explained variance in suicidal behavior in both studies; alcohol use alone and the correlation between depression and alcohol use accounted for only small amounts of variance.
A phase I trial of the proteosome inhibitor PS-341 in combination with carboplatin in platinum and taxane resistant ovarian cancer patinets
Authors: C. N. Landen, R. Coleman, M. R. Milam, T. Johnston, R. Iyer, D. M. Gershenson, P. Ramirez
Journal: Journal of Clinical Oncology (2007)

5558 Background. PS-341 (Millenium Pharmaceuticals, Inc.), a proteosome inhibitor, affects p53, NFκB, cell adhesion molecules, and sensitivity to cytotoxic agents to promote apoptosis and inhibit metastasis in cancer cells. PS-341 alone rarely causes myelosupression or renal toxicity, and therefore is an attractive agent to use in combination with cytotoxic chemotherapy. This phase I study evaluates the safety, dose-limiting toxicities (DLTs), and optimal dose of PS-341 when combined with carboplatin in ovarian cancer patients with recurrent, platinum- and taxane-resistant disease. Methods: After IRB approval, patients with recurrent ovarian cancer, platinum and taxane resistant (progression on platinum and/or taxane therapy or recurrence within 6 months of completing platinum and/or taxane therapy), measurable disease, and performance status 0–2 were eligible and enrolled after giving informed consent. As guided by toxicity and pharmacokinetic data from single-agent phase I trials, PS-341 was administered on days 1, 4, 8, and 11 by IV push every 28 days with carboplatin (AUC 5) on day 1. Four dose levels were evaluated: 0.8, 1.0, 1.3, and 1.5 mg/m 2 . Dose was escalated if 0 of 3 or 1 of 6 patients had a DLT. The MTD was defined as 2 or more patients out of 6 with a DLT. Results: 21 women (median age 63, range 43–83), were treated with carboplatin and PS-341 at 0.8mg/ m 2 (n=6), 1.0 mg/m 2 (n=3), 1.3 mg/m 2 (n=6), or 1.5 mg/m 2 . (n=6). At each level, respectively, there were 1, 0, 1, and 3 DLT’s attributable to PS- 341; all were grade 3, consisting of fatigue (n=3), nausea/vomiting/dehydration (n=1), and anorexia/dehydration/syncope (n=1). There were no Grade 4 toxicities. Common grade 2 toxicities included fatigue (n=12), nausea (n=10), anorexia, anemia, and dyspnea (n=7 each). 18 patients evaluable for response had stable disease (SD) or progression of disease (PD): at 0.8 mg/m 2 , SD=2, PD=3; at 1.0 mg/m 2 , PD=3; at 1.3 mg/m 2 , SD=3, PD=3; at 1.5 mg/m 2 , SD=3, PD=1. Median duration of stable disease was 4 months (range 3–10). Conclusions: The recommended dose of PS-341 in combination is 1.3 mg/m 2 . Treatment was well-tolerated with reversible side effects and no grade 4 toxicities, and at the optimal dose, there was a 50% rate of stable disease. No significant financial relationships to disclose.
Gray platelets – artifact or real?
Authors: Ylenia Pancione, Maurizio Fumi, Silvia Sale, Vincenzo Rocco, Barbara J. Bain
Journal: American Journal of Hematology (2016)

A blood count for assessment of platelet numbers was performed on a 6-year-old boy suffering from phenylketonuria. He was being treated with levetiracetam, an anti-epileptic drug that has been associated with thrombocytopenia. The platelet count was 167 × 109/l but the automated instrument output (Siemens ADVIA 2120) showed reduced refraction indicating hypogranular platelets. This was confirmed by observation of the peripheral blood film, the platelets appearing completely agranular and somewhat larger than normal (left). There were no platelet aggregates. Examination of a second blood specimen confirmed the observations. There was no history of abnormal bleeding and a diagnosis of the gray platelet syndrome therefore appeared unlikely. For this reason a blood film was made from a finger-prick sample; this showed platelets of normal size and granularity, forming small aggregates. A citrated blood sample showed another artifact, the presence of pseudothrombocytopenia due to significant platelet aggregation; however the platelets had retained their normal granularity and size (right). The 'pseudo-gray platelet syndrome' is an in vitro artefact, attributable to an antibody that, after chelation of extracellular calcium by EDTA, induces release of the contents of alpha and delta granules leaving the platelet 'gray' 1, 2. Falsely 'gray' platelets can also be the result of in vitro activation of platelets but in this circumstance there are platelet aggregates and sometimes also fibrin strands. Observation of a blood film is important in the evaluation of thrombocytopenia and of abnormal platelet characteristics shown by automated blood cell analyzers. The hematologist must be alert to the possibility that either abnormality is artifactual, due either to activation of platelets or to the presence of an antibody that is of no significance in vivo but causes either degranulation or aggregation when its activity is unmasked by the presence of a calcium chelator.
Cytokine profiling of specific T cells in patients after BCG-therapy allows distinction between patients with primary infection and prior contact
Authors: Julia Elsäßer, Martin Janssen, Urban Sester, Frank Becker, Henrik Suttmann, Carsten Ohlmann, Kai Schmitt, Michael Stöckle, Martina Sester
Journal: European Respiratory Journal (2013)

Specific T cell immunity in active tuberculosis (TB) is associated with a decrease in multifunctionality. However, it is unknown whether cytokine profiles differ in patients with primary infection and those with prior contact. We therefore used BCG instillation therapy in patients with urothelial carcinoma as a model to characterise the induction of systemic immunity towards PPD and to study whether cytokine profiles differ depending on pre-existing immunity.  IFNγ and IL2 producing PPD-specific CD4 T cells were analysed longitudinally before each instillation in 18 patients using flow-cytometry. 54 age-matched subjects without TB served as controls.  Baseline levels of IFNγ producing PPD-specific T cells were comparable to controls. T cells showed a 5fold increase to 0.23% by week 2/3, and further increased 8fold by week 4/5 (to 0.42%, p  Decreased functionality is a typical feature of specific immunity in both patients with active TB and BCG therapy. Among patients with active infection, the percentage of IL2 single positive cells may allow distinction between patients with primary infection and cases with boosted immunity after prior contact.
Histochemical Studies of Mouse Embryo Cell Lines. I. Properties of Cells Cultivated in Medium Containing Fetal Calf or Horse Serum&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: P. Farnes, F. M. Price, B. E. Barker, V. J. Evans
Journal: JNCI Journal of the National Cancer Institute (1968)

Morphologic and histochemical studies were performed on a non-neoplastic cell line 4823 (NCTC), derived from minced C3H mouse embryo grown in a medium of NCTC 135 with 10% fetal calf serum and also on a subline, 5645 (NCTC), grown in a medium of NCTC 135 with 10% v/v horse serum. The latter underwent neoplastic transformation. Five cell types with distinctive morphologic and histochemical properties were identified in the parent line. The subline consisted primarily of a new cell type, which displayed many properties characteristic of the lymphocytic series and, compared to the parent line, several metabolic alterations. “C”-like particles in the cells and positive viral complement-fixation studies suggest that the transformation is an example of viral oncogenesis. Intermuscular implantation of these cells gave tumors with characteristics of lymphomas. The transformed cells thus appeared to be derived from a cell type that retained potential for lymphocytic differentiation after more than 3 years in vitro. One adaptation found in the transformed cells, increased alkaline phosphatase activity, can occur in association with viral lymphoma development in vivo. The present studies indicate that mouse lymphocytes undergoing blastogenesis in response to phytomitogens are also characterized by an increased activity of this enzyme.
Effects of Glucose Starvation on Normal and Rous Sarcoma Virus-Transformed Chick Cells&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S Venuta, H Rubin
Journal: JNCI Journal of the National Cancer Institute (1975)

We studied the effect of glucose starvation on glucose uptake and thymidine uptake and incorporation in cultures of normal chicken embryo cells and those transformed by Rous sarcoma virus. Resting normal fibroblasts increased the rate of glucose transport up to tenfold when they were starved for glucose, whereas fast-growing normal cells doubled the rate of uptake after starvation. Transformed cells did not show any change in the rate of glucose uptake during starvation. Thymidine uptake and incorporation by normal and transformed cells were not affected by glucose starvation. These results showed that a decrease in the glucose concentration of the medium induced a specific increase in the rate of glucose transport by normal chick fibroblasts, but did not change the transport of glucose by transformed cells. Therefore, it is suggested that glucose or one of its metabolic products regulated the hexose uptake of normal chick fibroblasts. Virus-transformed cells were insensitive to this regulation.
Use of percutaneous kyphoplasty to treat painful vertebral compression fractures (VCF) in solid tumors
Authors: T. N. Elrafei, M. Hazza, N. Tindel
Journal: Journal of Clinical Oncology (2009)

e20568 Background: Vertebral compression fractures are a major source of morbidity in metastatic carcinoma. Kyphoplasty involves inflation of a balloon for painful kyphotic deformity restoring the vertebral body to its original height and creating a cavity for percutaneous injection of polymethylmethacrylate (PMMA). Contraindications include epidural spinal cord compression. Although it is FDA approved for cancer-associated VCF most of the data is in the myeloma population. Methods: We retrospectively assessed by electronic medical records the safety and efficacy of kyphoplasties performed by the orthopedic spine service in a single institution between 12/03 and 2/08. We identified those patients who had kyphoplasty as the only spine procedure and excluded those patients with incomplete documentation of pain scores. Comparison was made between patients selected for pathologic compression fractures and benign compression fractures secondary to trauma or osteoporosis. Results: Review of 447 consecutive orthopedic spine cases identified 40 kyphoplasty patients, 30 of which met the inclusion criteria - 21 with benign compression fractures secondary to osteoporosis/trauma and 9 with malignant disease (3 breast CA, 2 lung, 1 cervix, 1 RCC, 2 myeloma). 49 kyphoplasties and 23 concurrent spine biopsies were performed in this group. Median age was in the cancer group was 55 (37–81) vs. 68(41–93) in benign group. One patient had prior radiation in the cancer group. The average preoperative visual analog pain score was 7 (range 3–9) and postoperative pain score was 2.0 (0–9) in the cancer group. The average preoperative visual analog pain score 6.8 (0–9) and post-operative score was 0.8 (0–4) in the benign group. Most procedures did not require general anesthesia. There were no reported PMMA extravasations, and no hematologic or neurologic complications in either group. Conclusions: Kyphoplasty provided marked pain relief in patients with VCF secondary to solid tumors and myeloma. The results are comparable to non-cancer population in safety and efficacy, and are feasible in selected cancer patients with pain due to pathologic compression fractures. [Table: see text]
Colonization in advanced chronic obstructive pulmonary disease
Authors: Jessica Rademacher, Hendrik Suhling, Günter Auenhammer, Jens Gottlieb, Tobias Welte
Journal: European Respiratory Journal (2012)

Background: Isolation of potentially pathogenic organism from the sputum is associated with at least one hospitalization for COPD exazerbation (Martinez-Garcia et al. Chest 2011; 140: 1130-1137). But there is still a lack of examinations in larger populations of patients with COPD and pathogenic colonization.  Aims: This examination was performed to evaluate the colonization in patients with advanced COPD.  Methods: In this single- center evaluation, 379 patients with advanced COPD (GOLD III and IV) in our pre- transplant outpatient clinic were screened between October 2008 and June 2011 by lung function, exacerbation rate within the last 12 month and sputum analysis.  Results: The median exacerbation rate within the last 12 months was 2 (IQR 1-3). 51,7% of the patients had expectoration and 40,9% had none (7,4% remains unknown). We analyzed the sputum of 196 patients and had a positive sputum culture in 31,6% of the patients, which is 16,4% of the whole examination group. Patients with a positive sputum culture were significant more often hospitalized due to exacerbation (p=0.02). 94 patients (24,8%) underwent lung transplantation in the observation period. 19% of the explanted lungs had a proof of pathogenic organism. In 71 patients (75,5%) analysis of the sputum before transplantation was concordant with the results of the explanted lung. 11 patients (11,7%) had a proof in the explanted lung and no positive sputum or expectoriation before.  Conclusion: Even in patients with end stage COPD chronic bacterial colonisation does play a role only in a minority of the patients (16%). The proof of pathogenic organism correlates with significant more hospitalization due to exacerbations.
Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation
Authors: Lirui Wang, Derrick E. Fouts, Peter Stärkel, Phillipp Hartmann, Peng Chen, Cristina Llorente, Jessica DePew, Kelvin Moncera, Samuel B. Ho, David A. Brenner, Lora V. Hooper, Bernd Schnabl
Journal: Cell Host & Microbe (2016)
A methodology concern of the meta‐analysis of antiviral therapy for chronic hepatitis B virus infection in adults
Authors: Zhi‐Feng Zhang, Zhi‐Jun Duan
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. To the Editor: Chronic hepatitis B virus (HBV) infection (CHB) is a global health problem.1 It is estimated that one‐third of the population worldwide has past or present infection with HBV.2 Complications of decompensated liver cirrhosis and hepatocellular carcinoma due to CHB cause 0.5‐1 million deaths per year.2 To date, therapies for suppressing HBV replication and lowering viral load in the host are still the mainstay for CHB. Pegylated interferon and nucleoside analogues are recommended by various clinical guidelines and used widely to suppress HBV replication. Systemic reviews about antiviral drugs for CHB are of great importance to both health care providers and CHB patients. So we read with great interest the systemic review and meta‐analysis of antiviral therapy for CHB in adults, published in a recent issue of hepatology.3 We appreciate the excellent work performed by Lok et al.3 This is the latest meta‐analysis on this issue and is likely to be included in guidelines for management of CHB. Coincidently, we are doing a similar meta‐analysis about CHB, and we have retrieved all of the randomized controlled trials (RCTs) included in the meta‐analysis conducted by Lok et al. When we read the meta‐analysis of RCTs evaluating death rates between the antiviral group and the no treatment group, we found that the hepatocellular carcinoma rate was used as the death rate in one study.4 Moreover, this study describes the study method by saying, "we reviewed the medical records of the patients who were diagnosed with HBV related liver disease at Yeungnam University hospital from Jan 1983 to Dec 2005" and "using [the] SPSS program, 111 patients of the oral antiviral agent‐treated group and the untreated group were randomly selected, respectively, matching an age variable, a gender variable, liver cirrhosis with Child‐Pugh class A and positive HBe antigen," which indicates that this is a retrospective study but not a prospective RCT.4 This study should not be included in the meta‐analysis of RCTs evaluating death rates between the antiviral group and the no treatment group. So we performed a meta‐analysis excluding this retrospective study, according to the Cochrane Handbook for Systemic Reviews of Interventions,5 and found that there was no significant difference of death rate between the antiviral group and the no treatment group (risk ratio = 0.78, 95% confidence interval 0.44‐1.40, P = 0.41) (Fig. 1). Although our reanalysis did not change the conclusions of the meta‐analysis conducted by Lok et al., our reanalysis would supplement their excellent meta‐analysis and help readers to evaluate it more comprehensively.Figure 1: Meta‐analysis of death rate of antiviral group versus no treatment group, the fixed model used.
Decitabine in older patients with acute myelogenous leukemia (AML)
Authors: J. Issa, H. I. Saba, G. Garcia-Manero, J. Shan, H. M. Kantarjian
Journal: Journal of Clinical Oncology (2007)

7021 Background: Advanced myelodysplasia and AML are age-related diseases with known poor prognosis in patients over age 60. AML is defined by World Health Organization (WHO) criteria as patients with =20% blasts in the bone marrow. SEER database analysis has indicated that 64% of AML patients over age 65 go untreated, other than with supportive care. Their median survival is 1.7 months. The main reason for this reluctance to treat is perceived toxicity of chemotherapy in this age group. Decitabine is a hypomethylating agent that provides a low-intensity alternative for patients with myeloid malignancies. Methods: We reviewed patients with =20% blasts in the bone marrow treated on a randomized study of decitabine vs. supportive care in myelodysplastic syndromes, and similar patients enrolled on two consecutive studies of decitabine alone or in combination with valproic acid, conducted at MD Anderson Cancer Center. Response to decitabine was analyzed by International Working Group criteria. Results: Overall, there were 33 patients with the WHO criteria of AML that were treated with decitabine alone (23 patients) or in combination with valproic acid (10 patients) as first-line therapy. There were 20 men (61%) and their median age was 72, range 39 to 85. Median bone marrow blasts at study entry was 26%, and 14 (42%) had &gt;30% blasts. There were three different schedules of decitabine IV, which gave a total of 100–150 mg/m 2 /course over 3–10 days. Of the 33 patients treated, there were 8 CRs (24%) and 9 marrow CR/PR/Hematologic improvement (27%) for a total response rate of 17 (52%). Overall mortality at 4 weeks and 8 weeks was 3% and 15%, respectively. At a median follow-up of 20 months, median survival of the entire group was 12.6 months (95% CI: 6.5–23.0), and 2-year survival was 25% (95% CI: 13–48), which compares favorably to reported AML survival in this age group in the United States. Conclusions: We conclude that decitabine is an effective and less toxic treatment in this AML age group and may prolong survival compared with supportive care. No significant financial relationships to disclose.