tbuckley/cabot-search huggingface dataset:
Schistosoma Mansoni Infection
Authors: D. Mustafa
Journal: BMJ (1950)

SCHISTOSOMA MANSONI INFECTION BIRJOAL (4) Such patients can be better controlled by a twice-daily dose of soluble insulin, or a combination of soluble insulin and zinc protamine insulin.It is a pleasure to acknowledge the help and criticism of Dr. R. R. Bomford and Professor Clifford Wilson in preparing these notes, and the permission to use the case histories of their patients.
Eribulin mesylate (halichondrin B Analog E7389) in platinum-resistant epithelial ovarian cancer (PR-EOC): A CTEP-sponsored phase II study
Authors: M. L. Hensley, S. Kravetz, C. Sima, W. Tew, L. Pereira, P. Sabbatini, C. Whalen, C. A. Aghajanian, C. Zarwan, S. Berlin
Journal: Journal of Clinical Oncology (2009)

5561 Background: Eribulin mesylate is a tubulin inhibitor whose mechanism of action differs from that of other anti-tubulin agents, suppressing microtubule growth without affecting depolymerization, and sequestering tubulin into non-functional aggregates. In NIH:OVCAR-3 human EOC xenograft models, eribulin increased survival and reduced size and number of metastases, with activity superior to paclitaxel. We sought to determine the frequency of objective response to treatment with eribulin in patients (pts) with PR-EOC. Methods: Pts with PR-EOC, fallopian tube or peritoneal cancer (progression-free interval from last platinum-based therapy &lt; 6 months), measurable disease, &lt; 2 prior cytotoxic regimens, ECOG performance status 0–1, and adequate organ function were eligible. Treatment: eribulin 1.4 mg/m2 over 15 minutes IV days 1 and 8, every 21 days. Response assessed by CT for RECIST every other cycle. Results: 36 pts (median age 61, range 38–80; median platinum-free interval 3 months, range 0.1–5.9; all having received platinum-taxane first-line treatment) enrolled. 35 are evaluable for response (1 pt off-study for unrelated myocardial infarction in cycle 1). Two pts achieved partial responses (PR-5.7%), with response durations of 84 days and 128 days. Time to PR was 2.8 months in both. &gt;50% decrease in CA125 for more than two measurements was observed in 3/31 CA125-evaluable pts. 16/35 (46%) had stable disease as best response. Median progression-free survival was 2 months (range 1–7 months). Per patient, at least possibly-related grade 3–4 toxicities were: neutropenia 44%, leucopenia 31%, anemia 3%, lymphopenia 3%, febrile neutropenia 3%, muscle weakness 3%, hypophosphatemia 3%, hypokalemia 6%, infection 6%, thrombosis 6%. Conclusions: Eribulin has minimal activity in PR-EOC with objective response observed in only 5.7% of pts. Time to objective response was nearly 3 months. Median PFS was 2 months. Activity of eribulin in platinum-sensitive patients is being studied in a separate phase II cohort. [Table: see text]
Erythrocyte concentrations of the lithium ion: clinical correlates and mechanisms of action
Authors: A Frazer, J Mendels, D Brunswick, J London, M Pring, T A Ramsey, J Rybakowski
Journal: American Journal of Psychiatry (1978)

When lithium carbonate is administered to individuals, there is considerable intersubject variation in the extent of accumulation of Li+ by erythrocytes. The primary reason for this is differences in the activity of a Li+-Na+ counterflow system, which, under clinical conditions, removes Li+ from the cell. It appears that some bipolar patients accumulate more Li+ in their red cells than either unipolar depressives or normal controls. The precise clinical characteristics of the bipolar patients who accumulate relatively large amounts of erythrocyte Li+ need to be clarified in future research. Finally, the measurement of red cell concentrations of Li+, in addition to the usual plasma measurement, can be used as an indicator of patient compliance.
Targeting Androgen Receptor Activation Function-1 with EPI to Overcome Resistance Mechanisms in Castration-Resistant Prostate Cancer
Authors: Yu Chi Yang, Carmen Adriana Banuelos, Nasrin R. Mawji, Jun Wang, Minoru Kato, Simon Haile, Iain J. McEwan, Stephen Plymate, Marianne D. Sadar
Journal: Clinical Cancer Research (2016)

Persistent androgen receptor (AR) transcriptional activity is clinically evident in castration-resistant prostate cancer (CRPC). Therefore, AR remains as a viable therapeutic target for CRPC. All current hormonal therapies target the C-terminus ligand-binding domain (LBD) of AR. By using EPI to target AR activation function-1 (AF-1), in the N-terminal domain that is essential for AR transactivation, we evaluate the ability of EPI to overcome several clinically relevant AR-related mechanisms of resistance.To study the effect of EPI on AR transcriptional activity against overexpressed coactivators, such as SRC1-3 and p300, luciferase reporter assays were performed using LNCaP cells. AR-negative COS-1 cells were employed for reporter assays to examine whether the length of polyglutamine tract affects inhibition by EPI. The effect of EPI on constitutively active AR splice variants was studied in LNCaP95 cells, which express AR-V7 variant. To evaluate the effect of EPI on the proliferation of LNCaP95 cells, we performed in vitro BrdUrd incorporation assay and in vivo studies using xenografts in mice.EPI effectively overcame several molecular alterations underlying aberrant AR activity, including overexpressed coactivators, AR gain-of-function mutations, and constitutively active AR-V7. EPI inhibited AR transcriptional activity regardless of the length of polyglutamine tract. Importantly, EPI significantly inhibited the in vitro and in vivo proliferation of LNCaP95 prostate cancer cells, which are androgen independent and enzalutamide resistant.These findings support EPI as a promising therapeutic agent to treat CRPC, particularly against tumors driven by constitutively active AR splice variants that are resistant to LBD-targeting drugs. Clin Cancer Res; 22(17); 4466-77. ©2016 AACRSee related commentary by Sharp et al., p. 4280.
Perioperative Rosuvastatin in Cardiac Surgery
Authors: Zhe Zheng, Raja Jayaram, Lixin Jiang, Jonathan Emberson, Yan Zhao, Qi Li, Juan Du, Silvia Guarguagli, Michael Hill, Zhengming Chen, Rory Collins, Barbara Casadei
Journal: New England Journal of Medicine (2016)

Complications after cardiac surgery are common and lead to substantial increases in morbidity and mortality. Meta-analyses of small randomized trials have suggested that perioperative statin therapy can prevent some of these complications.We randomly assigned 1922 patients in sinus rhythm who were scheduled for elective cardiac surgery to receive perioperative rosuvastatin (at a dose of 20 mg daily) or placebo. The primary outcomes were postoperative atrial fibrillation within 5 days after surgery, as assessed by Holter electrocardiographic monitoring, and myocardial injury within 120 hours after surgery, as assessed by serial measurements of the cardiac troponin I concentration. Secondary outcomes included major in-hospital adverse events, duration of stay in the hospital and intensive care unit, left ventricular and renal function, and blood biomarkers.The concentrations of low-density lipoprotein cholesterol and C-reactive protein after surgery were lower in patients assigned to rosuvastatin than in those assigned to placebo (P<0.001). However, the rate of postoperative atrial fibrillation did not differ significantly between the rosuvastatin group and the placebo group (21.1% and 20.5%, respectively; odds ratio 1.04; 95% confidence interval [CI], 0.84 to 1.30; P=0.72), nor did the area under the troponin I-release curve (102 ng×hour per milliliter and 100 ng×hour per milliliter, respectively; between-group difference, 1%; 95% CI, -9 to 13; P=0.80). Subgroup analyses did not indicate benefit in any category of patient. Rosuvastatin therapy did not result in beneficial effects on any of the secondary outcomes but was associated with a significant absolute (±SE) excess of 5.4±1.9 percentage points in the rate of postoperative acute kidney injury (P=0.005).In this trial, perioperative statin therapy did not prevent postoperative atrial fibrillation or perioperative myocardial damage in patients undergoing elective cardiac surgery. Acute kidney injury was more common with rosuvastatin. (Funded by the British Heart Foundation and others; STICS ClinicalTrials.gov number, NCT01573143.).
Effect of a Web-Based Guided Self-help Intervention for Prevention of Major Depression in Adults With Subthreshold Depression
Authors: Claudia Buntrock, David Daniel Ebert, Dirk Lehr, Filip Smit, Heleen Riper, Matthias Berking, Pim Cuijpers
Journal: JAMA (2016)

<h3>Importance</h3> Evidence-based treatments for major depressive disorder (MDD) are not very successful in improving functional and health outcomes. Attention has increasingly been focused on the prevention of MDD. <h3>Objective</h3> To evaluate the effectiveness of a web-based guided self-help intervention for the prevention of MDD. <h3>Design, Setting, and Participants</h3> Two-group randomized clinical trial conducted between March 1, 2013, and March 4, 2015. Participants were recruited in Germany from the general population via a large statutory health insurance company (ie, insurance funded by joint employer-employee contributions). Participants included 406 self-selected adults with subthreshold depression (Centre for Epidemiologic Studies Depression Scale score ≥16, no current MDD according to<i>Diagnostic and Statistical Manual of Mental Disorders</i>[Fourth Edition, Text Revision] criteria). <h3>Interventions</h3> All participants had unrestricted access to usual care (visits to the primary care clinician) and were randomized to either a web-based guided self-help intervention (cognitive-behavioral and problem-solving therapy supported by an online trainer; n = 202) or a web-based psychoeducation program (n = 204). <h3>Main Outcomes and Measures</h3> The primary outcome was time to onset of MDD in the intervention group relative to the control group over a 12-month follow-up period as assessed by blinded diagnostic raters using the telephone-administered Structured Clinical Interview for<i>DSM-IV</i>Axis Disorders at 6- and 12-month follow-up, covering the period to the previous assessment. <h3>Results</h3> Among 406 randomized patients (mean age, 45 years; 73.9% women), 335 (82%) completed the telephone follow-up at 12 months. Fifty-five participants (27%) in the intervention group experienced MDD compared with 84 participants (41%) in the control group. Cox regression analyses controlling for baseline depressive symptom severity revealed a hazard ratio of 0.59 (95% CI, 0.42-0.82;<i>P</i> = .002) at 12-month follow-up. The number needed to treat to avoid 1 new case of MDD was 5.9 (95% CI, 3.9-14.6). <h3>Conclusions and Relevance</h3> Among patients with subthreshold depression, the use of a web-based guided self-help intervention compared with enhanced usual care reduced the incidence of MDD over 12 months. Further research is needed to understand whether the effects are generalizable to both first onset of depression and depression recurrence as well as efficacy without the use of an online trainer. <h3>Trial Registration</h3> German Clinical Trial Registry Identifier:DRKS00004709
Limited influences of chemotherapy on healthy and metastatic liver parenchyma from colorectal cancer
Authors: N. Van Damme, P. Demetter, W. De Bock, B. De Hemptinne, M. Praet, M. Peeters
Journal: Journal of Clinical Oncology (2004)

3640 Background: Liver metastasis often occurs in patients who undergo surgical removal of the primary colorectal tumor. The adhesion molecules, E-cadherin/catenin complex, are closely involved in the development and growth of metastatic tumors. Today, no data are available on the effect of chemotherapy on liver parenchyma. Methods: Thirty-nine patients (27 males and 12 females, with a mean age of 60.3 years) who underwent liver resection for hepatic metastasis from colorectal cancer were included in the study. Tissue samples taken from the tumor and surrounding liver parenchyma were immunohistochemically stained for E-cadherin, α -, β -, and γ -catenin, VEGF and p53. The patients were divided in two groups: those (n=15) who had no chemotherpay for at least 6 months before the liver resections and those (n=24) who were treated with chemotherapy before liver resections. A score from 0 to 3 was given for the number of positive cells and from 0 to 3 for the intensity of staining in these cells, in both healthy and metastatic liver parenchyma. The sum of both scores, with a maximum of 6, was made. Changes were statistically evaluated with the Mann-Whitney U test. Results: In the non-involved liver parenchyma no differences could be observed for E-cadherin/catenin complex, VEGF and p53 between patients receiving or not receiving chemotherapy. In the metastatic liver parenchyma, VEGF expression was more pronounced in patients receiving chemotherapy in comparison with patients receiving no chemotherapy (p=0.048). There were no differences for the E-cadherin/catenin complex. Conclusions: No histochemical changes are observed in non-involved liver parenchyma. A limited influence of chemotherapy was noticed on metastatic liver parenchyma. No significant financial relationships to disclose.
Nonspecific Inhibitory Activity of Soluble Human Colon Carcinoma Extracts: Tentative Mechanism of Action&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G J Pommier, M M Remacle-Bonnet, R J Rance, R C Depieds
Journal: JNCI Journal of the National Cancer Institute (1981)

Soluble human colon carcinoma extract(s) (SCE) were potent nonspecific inhibitors of lymphoproliferative responses to mitogens. Inhibition was concomitant with induction in about 35% of cells of morphologic alterations for most of them comparable with the ones observed in mitogen-induced blast cells. Nonetheless, these blastlike cells did not proliferate. SCE did not interfere with mitogen binding to cell receptors. Moreover, SCE was unable to induce or activate suppressor cells, and its primary target cell was the unresponsive lymphoid cell itself. The inhibitory effect of SCE was early and irreversible. The differential activity of SCE can be correlated with an early [3H]uridine uptake, which was inhibited 6 hours later, as seen for the other biochemical parameters of cell activation. Also, SCE altered membrane-bound ATPase activities. Na,K-ATPase was strongly inhibited, whereas Ca2+-dependent and Mg2+-dependent ATPases were stimulated. These observations were discussed as an SCE-lymphocyte plasma membrane interaction translated into differential signals to the intracellular metabolic pathways.
Case 2-1974
Authors: Richard C. Cabot, Benjamin Castleman, Robert E. Scully, Betty U. McNeely, Barry W. Levine, Benjamin Castleman
Journal: New England Journal of Medicine (1974)

Presentation of CaseA 61-year-old man was admitted to the hospital because of a pleural effusion.He was well until six months previously, when a respiratory-tract infection developed, followed by a nonproductive cough and right pleuritic pain. The pleuritic pain lessened, but the cough persisted. Dyspnea occurred, and he lost 4 kg in weight. A physician found signs of a right pleural effusion, and the patient was admitted to the hospital.There was a past history of sinusitis, treated with repeated antral irrigations. The patient had smoked one package of cigarettes daily for 50 years. Pneumonia developed 20 years before . . .
Failure Patterns to Crizotinib and Survival Benefit in Advanced Alk-Positive Lung Adenocarcinoma
Authors: H. Chen, J. Yang, H. Yan, B. Gan, Y. Yang, X. Zheng, X. Zhang, Y. Wu
Journal: Annals of Oncology (2014)

ABSTRACT   Aim: Lung adenocarcinoma harboring gene fusion of EML4 and anaplastic lymphoma kinase (ALK) was proved responsive to crizotinib, but acquired failure inevitably developed after a median of 7.7 months. The failure patterns and their correlation with survival benefit remain unclear.  Methods: Patients with fluorescent in situ hybridization assay (FISH)-proven ALK fusion and with failure to crizotinib treatment were enrolled into the study. Demographic and clinicopathalogic factors were reviewed. Failure patterns were defined as dramatic, gradual, and local progression according to the published criteria. Survival benefit in different patterns was analyzed.  Results: Totally 61 patients with lung adenocarcinoma, including 60 trial patients and one routine patient were enrolled. Fifty-four percent of the cohort was female, and 77% of patients were non-smokers. Brain metastasis occurred in 21% of the group. Six patients had concurrent EGFR gene mutations and ALK fusion. Twelve patients received first-line crizotinib, and ninety-five percent (41/43) of patients were switched to crizotinib after failure to prior chemotherapy. Sixty-eight percent (36/53) of patients were radiologically assessed as failure to crizotinib treatment. Seventy-five percent (27/36) of patients manifested dramatic progression on failure to crizotinib. One patient was with gradual progression, and 8 patients (22%) had local progression. The subgroup of dramatic progression had an inferior progression-free survival (PFS1) than other patients (3.5 vs 10.5 months, P   Conclusions: Dramatic progression was prevalent in ALK-positive lung adenocarcinoma when failure to crizotinib occurred, and predicted poor overall survival.  Disclosure: All authors have declared no conflicts of interest.
The EGFR-specific antibody cetuximab combined with chemotherapy triggers immunogenic cell death
Authors: Chiara Pozzi, Alessandro Cuomo, Ilaria Spadoni, Elena Magni, Alessio Silvola, Alexia Conte, Sara Sigismund, Paola Simona Ravenda, Tiziana Bonaldi, Maria Giulia Zampino, Carlotta Cancelliere, Pier Paolo Di Fiore, Alberto Bardelli, Giuseppe Penna, Maria Rescigno
Journal: Nature Medicine (2016)
Electrochemotherapy guided by intraoperative fluorescence imaging for the treatment of inoperable peritoneal micro-metastases
Authors: V. Josserand, M. Kéramidas, J. Lavaud, C. Righini, J. Vollaire, E. Bellard, M.P. Rols, J. Teissié, J.L. Coll, M. Golzio
Journal: Journal of Controlled Release (2016)
Controlled comparison of buspirone and clomipramine in obsessive- compulsive disorder
Authors: M T Pato, T A Pigott, J L Hill, G N Grover, S Bernstein, D L Murphy
Journal: American Journal of Psychiatry (1991)

Eighteen outpatients with obsessive-compulsive disorder were treated with either buspirone, a partial serotonin agonist, or clomipramine, a serotonin uptake inhibitor, in a double-blind, random-assignment study. Both drugs led to statistically significant and similar improvements in scores on the Yale-Brown Obsessive-Compulsive Rating Scale and other obsessive-compulsive and depression scales. This preliminary result warrants further exploration with a larger sample and other serotonergic agents.
Induction of Cd44 Variant 9-Expressing Cancer Stem Cells Attenuates the Efficacy of Chemoradioselection and Worsens the Prognosis of Patients with Advanced Head and Neck Cancer
Authors: M. Masuda, T. Aso, M. Matsuo, F. Rikimaru, K. Taguchi, N. Kunitake, Y. Higaki
Journal: Annals of Oncology (2014)
Community dynamics and the lower airway microbiota in stable chronic obstructive pulmonary disease, smokers and healthy non-smokers
Authors: G G Einarsson, D M Comer, L McIlreavey, J Parkhill, M Ennis, M M Tunney, J S Elborn
Journal: Thorax (2016)

<h3>Rationale</h3> The role bacteria play in the progression of COPD has increasingly been highlighted in recent years. However, the microbial community complexity in the lower airways of patients with COPD is poorly characterised. <h3>Objectives</h3> To compare the lower airway microbiota in patients with COPD, smokers and non-smokers. <h3>Methods</h3> Bronchial wash samples from adults with COPD (n=18), smokers with no airways disease (n=8) and healthy individuals (n=11) were analysed by extended-culture and culture-independent Illumina MiSeq sequencing. We determined aerobic and anaerobic microbiota load and evaluated differences in bacteria associated with the three cohorts. Culture-independent analysis was used to determine differences in microbiota between comparison groups including taxonomic richness, diversity, relative abundance, ‘core’ microbiota and co-occurrence. <h3>Measurement and main results</h3> Extended-culture showed no difference in total load of aerobic and anaerobic bacteria between the three cohorts<i>.</i> Culture-independent analysis revealed that the prevalence of members of <i>Pseudomonas</i> spp. was greater in the lower airways of patients with COPD; however, the majority of the sequence reads for this taxa were attributed to three patients. Furthermore, members of Bacteroidetes, such as <i>Prevotella</i> spp., were observed to be greater in the ‘healthy’ comparison groups. Community diversity (α and β) was significantly less in COPD compared with healthy groups. Co-occurrence of bacterial taxa and the observation of a putative ‘core’ community within the lower airways were also observed. <h3>Conclusions</h3> Microbial community composition in the lower airways of patients with COPD is significantly different to that found in smokers and non-smokers, indicating that a component of the disease is associated with changes in microbiological status.
Novel Targets for Therapeutic Agents in Small Cell Lung Cancer
Authors: Patrick C. Ma, Ravi Salgia
Journal: Journal of the National Comprehensive Cancer Network (2004)

Small cell lung cancer (SCLC) is known to have an aggressive phenotype and often presents with distant metastasis. Despite frequent initial response to chemotherapy, it inevitably relapses within 2 years in the majority of patients. Because of the poor overall prognosis of the disease and its unique tumor biology, the opportunity for improving clinical outcome of patients with development of novel therapeutics is great. This review provides current insights into the novel molecular targets in SCLC. Cellular signal transduction pathways and their relationship to cellular functions also are discussed. Discussion of the role receptor tyrosine kinases (RTKs) have in SCLC therapeutic inhibition is emphasized. In particular, the recent development of small molecule inhibitors of RTKs such as c-Kit, c-Met, and VEGF-R and the potential for clinical trials are highlighted.
Epithelial ovarian cancer: the molecular genetics of epithelial ovarian cancer
Authors: J. Krzystyniak, L. Ceppi, D.S. Dizon, M.J. Birrer
Journal: Annals of Oncology (2016)

BackgroundEpithelial ovarian cancer (EOC) remains one of the leading causes of cancer-related deaths among women worldwide, despite gains in diagnostics and treatments made over the last three decades. Existing markers of ovarian cancer possess very limited clinical relevance highlighting the emerging need for identification of novel prognostic biomarkers as well as better predictive factors that might allow the stratification of patients who could benefit from a more targeted approach.Patients and methodsA summary of molecular genetics of EOC.ResultsLarge-scale high-throughput genomic technologies appear to be powerful tools for investigations into the genetic abnormalities in ovarian tumors, including studies on dysregulated genes and aberrantly activated signaling pathways. Such technologies can complement well-established clinical histopathology analysis and tumor grading and will hope to result in better, more tailored treatments in the future. Genomic signatures obtained by gene expression profiling of EOC may be able to predict survival outcomes and other important clinical outcomes, such as the success of surgical treatment. Finally, genomic analyses may allow for the identification of novel predictive biomarkers for purposes of treatment planning. These data combined suggest a pathway to progress in the treatment of advanced ovarian cancer and the promise of fulfilling the objective of providing personalized medicine to women with ovarian cancer.ConclusionsThe understanding of basic molecular events in the tumorigenesis and chemoresistance of EOC together with discovery of potential biomarkers may be greatly enhanced through large-scale genomic studies. In order to maximize the impact of these technologies, however, extensive validation studies are required.