tbuckley/cabot-search huggingface dataset:
Serum IGFBP4 levels in combination with miliary disease: A candidate predictor of ovarian cancer progression-free survival.
Authors: Samantha Cohen
Journal: Journal of Clinical Oncology (2012)

5079 Background: Insulin-like growth factor binding protein, IGFBP4, was shown to be highly expressed across all stages of epithelial ovarian cancer (EOC) and serum levels are elevated in EOC. Moreover, IGFBP4 levels are ~3x greater in women with malignant pelvic masses. We investigated whether ascites volume and the presence of miliary disease in combination with serum levels of IGFBP4 are independent predictors of survival. Methods: A prospective and retrospective analysis was performed. Patients were enrolled at the time of cytoreductive surgery. Ascites volume was either absent, &lt;500 cc (low), or &gt;= 500 cc (high), and the presence of miliary disease was recorded. The IGFBP4 cutoff was 1064.5 ug/ml based upon previous results. The Kaplan-Meier product limit method was used to estimate PFS probabilities. The Cox proportional hazards model was used to estimate hazard ratios (HR) and corresponding 95% CI. Results: 57 cases were included in the analysis of ascites volume and miliary disease. Cytoreductive outcomes were complete gross resection (44.8%), optimal (&lt;=1cm residual disease; 44.8%), and suboptimal ( &gt;1cm residual disease; 10.3%). Histologic subtypes: papillary serous (n=35; 61.4%), mucinous (n=15; 26.3%), endometrioid (n=4; 7.0%), and clear cell (n=3; 5.3%). Stage distribution was 21.1% I/II, and 78.9% III/IV. PFS was unaffected by ascites volume (p=0.341) or miliary disease. Among this cohort, 29 had IGFBP4 levels available for a separate analysis. Patients with high IGFBP4 and miliary disease were 5.5 times as likely to recur compared with patients with miliary disease and low IGFBP4 (HR=5.55 [0.77, 39.82]), and the statistical significance was borderline (p&lt;0.088). No statistically significant differences were detected between rates of recurrence among patients with high and low IGFBP4 values in combination with ascites volume. Conclusions: These exploratory studies suggest that patients with high IGFBP4 serum levels and miliary disease were &gt; 5 times as likely to recur compared to women with miliary disease and low IGFBP4 levels. Future studies examining these variables using a larger population and examining the biologic basis of this relationship are planned.
Decision to Publish Study on Maternal Fluoride Exposure During Pregnancy
Authors: Dimitri A. Christakis
Journal: JAMA Pediatrics (2019)

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Association Between Electronic Cigarette Use and Marijuana Use Among Adolescents and Young Adults
Authors: Nicholas Chadi, Rachel Schroeder, Jens Winther Jensen, Sharon Levy
Journal: JAMA Pediatrics (2019)

<h3>Importance</h3> Use of electronic cigarettes (often called<i>e-cigarettes</i>) has increased considerably among young people in the past 5 years. Use of e-cigarettes has been associated with higher rates of marijuana use, which is associated with several adverse health outcomes in youth. <h3>Objective</h3> To characterize and quantify the association between e-cigarette and marijuana use among youth using a meta-analysis. <h3>Data Sources</h3> PubMed, Embase, and Web of Science &amp; ProQuest Dissertations and Theses were searched from inception to October 2018. A gray-literature search was also conducted on conference abstracts, government reports, and other sources. <h3>Study Selection</h3> Included studies compared rates of marijuana use among youth aged 10 to 24 years who had used e-cigarettes vs those who had not used e-cigarettes. Two reviewers independently assessed studies for inclusion; disagreements were discussed with a third reviewer and resolved by consensus. <h3>Data Extraction and Synthesis</h3> Data were extracted by 2 independent reviewers following Meta-analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines and pooled using a random-effects analysis. The Newcastle-Ottawa Scale was used to assess data quality and validity of individual studies. <h3>Main Outcomes and Measures</h3> Adjusted odds ratios (AORs) of self-reported past or current marijuana use by youth with vs without past or current e-cigarette use. <h3>Results</h3> Twenty-one of 835 initially identified studies (2.5%) met selection criteria. The meta-analysis included 3 longitudinal and 18 cross-sectional studies that included 128 227 participants. Odds of marijuana use were higher in youth who had an e-cigarette use history vs those who did not (AOR, 3.47 [95% CI, 2.63-4.59];<i>I2</i>, 94%). Odds of marijuana use were significantly increased in youth who used e-cigarettes in both longitudinal studies (3 studies; AOR, 2.43 [95% CI, 1.51-3.90];<i>I2</i>, 74%) and cross-sectional studies (18 studies; AOR, 3.70 [95% CI, 2.76-4.96];<i>I2</i>, 94%). Odds of using marijuana in youth with e-cigarette use were higher in adolescents aged 12 to 17 years (AOR, 4.29 [95% CI, 3.14-5.87];<i>I2</i>, 94%) than young adults aged 18 to 24 years (AOR, 2.30 [95% CI, 1.40-3.79];<i>I2</i>, 91%). <h3>Conclusions and Relevance</h3> This meta-analysis found a significant increase in the odds of past or current and subsequent marijuana use in adolescents and young adults who used e-cigarettes. These findings highlight the importance of addressing the rapid increases in e-cigarette use among youths as a means to help limit marijuana use in this population.
CRISPR Interference-Based Platform for Multimodal Genetic Screens in Human iPSC-Derived Neurons
Authors: Ruilin Tian, Mariam A. Gachechiladze, Connor H. Ludwig, Matthew T. Laurie, Jason Y. Hong, Diane Nathaniel, Anika V. Prabhu, Michael S. Fernandopulle, Rajan Patel, Mehrnoosh Abshari, Michael E. Ward, Martin Kampmann
Journal: Neuron (2019)

Highlights•A CRISPR interference platform for genetic screens in human iPSC-derived neurons•Survival screens uncover genes essential for neurons, but not iPSCs or cancer cells•Single-cell RNA-seq screens reveal distinct neuronal roles for ubiquitous genes•Arrayed high-content screens uncover genes controlling neuronal morphologySummaryCRISPR/Cas9-based functional genomics have transformed our ability to elucidate mammalian cell biology. However, most previous CRISPR-based screens were conducted in cancer cell lines rather than healthy, differentiated cells. Here, we describe a CRISPR interference (CRISPRi)-based platform for genetic screens in human neurons derived from induced pluripotent stem cells (iPSCs). We demonstrate robust and durable knockdown of endogenous genes in such neurons and present results from three complementary genetic screens. First, a survival-based screen revealed neuron-specific essential genes and genes that improved neuronal survival upon knockdown. Second, a screen with a single-cell transcriptomic readout uncovered several examples of genes whose knockdown had strikingly cell-type-specific consequences. Third, a longitudinal imaging screen detected distinct consequences of gene knockdown on neuronal morphology. Our results highlight the power of unbiased genetic screens in iPSC-derived differentiated cell types and provide a platform for systematic interrogation of normal and disease states of neurons.Video Abstract/cms/asset/c2672569-5397-4e97-a52a-74b50c33ac04/mmc10.mp4Loading ...Download video (mp4, 134 MB)Graphical abstract
Utilization of subspecialty care by Hispanic pediatric oncology patients, California 1983-2010.
Authors: Elysia Alvarez, Lisa J. Chamberlain, Neyssa Marina, Olga Saynina, Paul Wise
Journal: Journal of Clinical Oncology (2013)

e17504 Background: Previous analysis has shown that Hispanic pediatric oncology patients in California have decreased utilization of pediatric cancer specialty centers (PCSC). The purpose of this study was to examine the clinical and non-clinical factors associated with decreased inpatient utilization of PCSCs by Hispanic pediatric oncology patients. Methods: Using the California Office of Statewide Health Planning and Development private database we performed a retrospective population based analysis of Hispanic patient discharges 0-18 years of age to explore the influence of age, gender, payer, income, distance to admission site, tumor type and diagnosis of fever and neutropenia on the utilization of PCSCs by Hispanic patients. Results: Analysis of 82,832 Hispanic pediatric oncology discharges showed concentration of hospitalization in PCSCs increasing from 64% in 1983 to 94% in 2010. In addition, an increased percentage of acute lymphoblastic leukemia discharges was seen for Hispanics (28.3%) compared to all discharges (22.4%). The adjusted regression analysis revealed decreased utilization of PCSCs for patients ages 15-18 (OR 0.466; CI 0.441-0.493) and for those residing 6 - 10 miles from a PCSC (OR 0.927; CI 0.883 - 0.974). Increased utilization of PCSCs was seen for Hispanic patients living in zip codes where household income was &gt;4 times the Federal Poverty Level. Payer status was not significantly associated with discharge from a PCSC. None of these findings changed when Los Angeles County was removed from the analysis. A separate analysis was done on Hispanic pediatric oncology patients with a discharge diagnosis of fever and neutropenia. For this subset decreased utilization was seen for those with private insurance (OR 0.84; CI 0.81-0.887), age &lt;1 (OR 0.719; CI 0.64-0.808), ages 15-18 (OR 0.596; CI 0.558-0.636) and those residing &gt;40 miles from a PCSC (OR 0.913; CI 0.854-0.975). Conclusions: Utilization of inpatient pediatric oncology care by Hispanic patients in California has become regionalized in PCSCs since 1983 and is influenced by age, and geography, with payer status not being a significant contributor. Clinical outcomes as they relate to access to PCSCs for Hispanic patients should be examined.
Two Ebola treatments halve deaths in trial in DRC outbreak
Authors: Owen Dyer
Journal: BMJ (2019)

A clinical trial conducted in the midst of an Ebola epidemic in the Democratic Republic of Congo (DRC) has identified two new drugs that can dramatically cut mortality from the disease, and both are being immediately offered to all patients in an effort to control the country’s worst ever outbreak.

The Pamoja Tulinde Maisha (“together save lives” in Swahili) trial began last November, in four towns stricken by the outbreak. It compared four potential treatments proposed by four different companies: ZMapp, remdesivir, mAb114, and REGN-EB3.

Preliminary data has convinced the trial’s monitoring board to stop the study and …
A critical role of E-cadherin expression during the progression of metastatic prostate cancer cells with the microenvironment as a driving force
Authors: Clayton C. Yates, Chris Shepherd, Alan Wells
Journal: Cancer Research (2006)

2769  Background: Metastasis is a multi-step processes wherein tumor cells must be able to move from the primary tumor, disseminate throughout the body, and survive to grow in the ectopic locale. At the molecular level, during the initial invasion, cells undergo epithelial mesenchymal like transition where there is typically noted an increase of EGFR expression at the same time there is a loss of E-cadherin, thus driving motility and the ability to separate from the primary tumor mass. Recently, however we have shown that abrogation of EGFR signaling results in reexpression of E-cadherin in DU-145 prostate cancer cells, thus highlighting the plasticity of these cells. Therefore we hypothesize that there is phenotypic variability throughout prostate cancer progression; the decreased E-cadherin expression is transient and E-cadherin becomes reexpressed at the ectopic site. Methods: We utilized DU-145 and PC-3 human prostate cancer cells that expression very low levels of E-cadherin in culture and primary rat hepatocytes. Results: Immunofluorescence staining for E-cadherin in 2D co-cultures of GFP expressing hepatocytes and RFP DU-145 prostate cancer cells reveal E-cadherin expression at the peripheral regions of contact by day 2 of coculture with eventual gain of homotypic E-cadherin expression as the DU-145 cells cluster around hepatocytes. A cell adhesion assay (CAFCA) demonstrated that this resulted in functional binding, which was abrogated by the calcium chelator EDTA or siRNA to E-cadherin. This suggested that reexpression of E-cadherin secondary to juxtaposition of prostate cancer cells to hepatocytes (heterotypic binding) is essential for prostate cancer cells to adhere to the parenchymal heptatocytes. As a physiological correlation to our in vitro findings we were able to find significant reexpression of E-cadherin within tumor mass of two human patients with prostate metastases to the liver. Conclusions: The loss of E-cadherin is an epigenetic event that is modulated by the tumor microenvironment, and E-cadherin is necessary for disseminated prostate cancer cells adhere to parenchymal cells at ectopic site. We also conclude that the term epithelial mesenchymal transition only summarizes the transient down regulation E-cadherin for invasion, and that reexpression of E-cadherin is part of the “normal” process of metastatic tumor development. Therefore, we propose Meschenymal Epithelial reverting Transition (MErT) as the term that describes this re-attainment of cell-cell communication later in tumor progression.
PTH-049 What is the concordance for the diagnosis of laterally spreading-type lesions (lsts) amongst western and japanese expert endoscopists?
Authors: B Manoharan, A Jiménez, S Sansone, M Yamada, M San Juan, N Gonzalez, E Albéniz, MA Bianco, R Bisschops, K Homma, H Ikematsu, M Yoshinori, T Uraoka, K Ragunath, A Parra-Blanco
Journal: Gut (2017)

Introduction  The LST classification and Paris classification systems are internationally used to describe polyp morphology. Differences between Japanese and Western endoscopists in the use of classification systems, have been observed but never studied formally. We aimed to evaluate the inter-observer agreement of LST classification amongst Western and Japanese expert endoscopists.  Method  A total of 40 endoscopic video clips depicting LSTs (10% malignant) were assessed by 6 expert endoscopists; 3 from Japan and 3 from the Europe. Assessments included LST classification (LST-G homogeneous, LST-G mixed, LST-NG flat, LST-NG pseudodepressed), Paris classification, invasiveness, treatment suggestion and mean size of lesion. We calculated the interobserver agreement with weighted kappa and Chi square.  Results  Japanese endoscopists diagnosed more lesions as LST-G than Western (62.7 vs. 45.4%), Western diagnosed more LST-NG than Japanese (54.6 vs. 37.3%; p=0.007). Lesions were deemed invasive by 18.8% and 11.7% Western and Japanese endoscopists respectively (p=0.088). Interobserver agreement of the LST classification was good with a weighted Kappa of 0.61 (CI 95% 0.43–0.78) for Japanese endoscopists, and moderate at 0.45 (CI 95% 0.27–0.64) for Western endoscopists. Difference in concordance between the two cohorts was not significant (p=0.22). When only two categories were considered (LST-G vs NG), agreement was very good for Japanese (weighted Kappa of 0.81; 95% CI 0.65–0.97) and good for Western endoscopists (0.65; 95% CI 0.46–0.85). Difference in concordance was not statistically significant (p=0.22). Piecemeal Endoscopic Resection was suggested in 34.7% cases by Western endoscopists, but none by Japanese endoscopists, whereas Endoscopic Submucosal Dissection was recommended in 50.4% and 16.1% cases by Japanese and Western endoscopists respectively (p  Conclusion  Although there was significant differences in the subtypes of LST diagnosed, overall there was no significant difference between Japanese and Western endoscopists. The discordance in recommendations for treatment, ESD Vs EMR could be due to the differences in endoscopic skills and practice.  References  Disclosure of Interest  None Declared
Chemotherapy in the elderly (≥65) cancer patient: The relationship between premorbid level of function and treatment tolerance in a metropolitan Australian hospital.
Authors: Hayden Christie, Katherine Mary Lovat, Jasotha Sanmugarajah
Journal: Journal of Clinical Oncology (2013)

e20706 Background: The proportion of elderly patients treated by oncologists is gradually increasing due to demographic changes. This section of the population is generally underrepresented in clinical trials. This results in minimal guidance to dosage and tolerance. Improving assessment strategies in this group can help reduce the negative impact on quality of life from toxicity and hospital admission, which is also of benefit to the health system. Assessment of independence in the community and co-morbidities could provide a simple strategy to aid this process. Methods: Patients ≥65 years referred to the Medical Oncology clinic at the Gold Coast Hospital, Qld, Australia, undertook a questionnaire before their first out-patient appointment. This was used in conjunction with patient charts to determine patient assessment of level of function, knowledge of diagnosis and treatment aims, and also treating Oncologist assessment of function and predicted tolerance. Results: 75 patients were recruited. Patient characteristics are summarised below. 71% of patients were offered chemotherapy, 79% accepted, with 59% being for palliative treatment. 43% required dose reduction at some stage. Of those, 56% had 2 or more co-morbidities, 50% required assistance with IADLs and 22% with PADLs. 17% had an ECOG of ≥2 and 33% were aged ≥76. We are unable to comment on completion of treatment as many are still ongoing. Conclusions: Dose reduction is common in this population, with a correlation between this and self-reported performance status. It is proposed that the use of patient reported screening tools like this are a useful guide to determine need for dose reduction. Larger studies are needed to investigate this relationship further. [Table: see text]
Colistin for the treatment of urinary tract infections caused by extremely drug-resistant Pseudomonas aeruginosa: Dose is critical
Authors: Luisa Sorlí, Sonia Luque, Jian Li, Núria Campillo, Marc Danés, Milagro Montero, Concha Segura, Santiago Grau, Juan Pablo Horcajada
Journal: Journal of Infection (2019)
Central adiposity and prostate cancer survival in relation to tumor tissue expression of sex steroid hormone receptors
Authors: Anna Eisenstein, Stephen Finn, Jennifer Sinnott, Christopher Fiore, Jing Ma, Meir Stampfer, Edward Giovannucci, Massimo Loda, Lorelei Mucci
Journal: Cancer Research (2008)

LB-4  Introduction: Obesity is linked with poor prognosis for prostate cancer (PCa), but the mechanism is unknown. Adiposity is associated with lower circulating androgen levels and higher estrogen levels. Androgens and estrogens affect the prostate epithelium via their respective receptors. Thus, the link between obesity and PCa survival may be mediated via sex steroid hormone receptors.  Methods: We assessed the relation of central adiposity, expression of estrogen receptor-α (ERα) and androgen receptor (AR) with cancer survival among 534 men with incident PCa in the Health Professionals Follow-up Study. We retrieved archival tumor tissue blocks from men diagnosed and treated by prostatectomy between 1986 and 2002. AR and ERα expression was measured by automated semi-quantitative immunohistochemistry. In questionnaires administered prior to PCa diagnosis, study participants reported waist and hip circumference, which were used to calculate waist-to-hip ratio (WHR, reflecting central adiposity). We fit Cox proportional hazard models with PCa death (n=52) as the outcome to estimate hazard ratios and 95% confidence intervals (CI), adjusted for age at diagnosis, total energy intake and PSA at diagnosis.  Results: Of the 534 men, 56% had WHR at or above the recommended cut point of 0.95. We found no significant association between WHR and expression of AR or ERα in tumors. Overall, WHR had no statistically significant effect on PCa-specific survival. In addition, neither AR nor ERα tumor expression was associated with PCa- specific survival. However, among men with AR+ tumors (above the median expression), greater adiposity was associated with worse prognosis: men with WHR ≥0.95 were 5.6 times (95% CI 1.27-24.4, p-trend=0.01) more likely to die from PCa than men with WHR
Nanoelectropulse therapy for cancer: In vitro and in vivo analysis.
Authors: Edward B. Garon, P. Thomas Vernier, Jingjing Wang, Tao Tang, Mya Mya Thu, Xianyue Gu, Yinghua Sun, Laura Marcu, Martin Gundersen, H. Phillip Koeffler
Journal: Cancer Research (2006)

5465  Delivery of short duration electric pulses, known as nanoelectropulse therapy, is being developed as a potential local cancer therapy. In this modality, electric pulses with nanosecond scale duration and high field (MV/m) are applied to cells. Because the pulses are shorter than the charging time constant of the external plasma membrane (30-100 ns), voltage across the cell membrane is limited. Intracellular membranes are smaller, therefore having a shorter charging time constant. As a result, pulses disproportionately affect intracellular membranes. We extended study of these pulses to a range of malignant cells. By assessing viable cells by an MTT assay 96 hours after delivery of pulses, we have characterized elements of the pulse that lead to more effective killing of malignant cells. In the Jurkat T cell leukemia/lymphoma cell line, we show that at equivalent energy, 200 pulses of 20 ns duration lead to more effective cell killing than 570 pulses of 7 ns duration. We also show that increasing the voltage leads to increased cell killing. We demonstrate that many hematologic cell lines are extremely susceptible to nanoelectropulse therapy in vitro, including follicular lymphoma (SUDHL-6), diffuse large B cell lymphoma (SUDHL-16) and multiple myeloma (RPM8226) cell lines. The effects of pulsation on solid tumor cell lines varied more. Of the solid tumor cell lines tested, AsPC-1 pancreatic cancer cells were the most effectively killed. Based on these data, we extended our findings to in vivo work. We injected AsPC-1 cells into both flanks of eight athymic nude mice. We designed a catheter capable of delivering 6kV pulses, and pulsed one of the resultant tumors in each mouse, leaving the other tumor as a control. Effective killing occurred when 200 pulses of 20 ns duration were delivered at 20 Hz. Complete clinical responses were found in two of the tumors. One tumor recurred and the other was confirmed to be a pathologic complete response. In summary, we have demonstrated the ability of nanoelectropulse therapy to kill tumor cells both in vitro and in vivo. This technology may allow a unique approach to killing of cancer cells.