tbuckley/cabot-search huggingface dataset:
Maternal Hematologic Status and Outcome of Pregnancy in Blacks and Whites
Journal: New England Journal of Medicine (1988)

It seems very odd that the large studies by both Lieberman et al. and Kleinman and Kessel (Sept. 17 issue) should all but ignore the basic biologic influence of maternal nutrition on the course and outcome of pregnancy.  Central to current obstetrical practice are the classical results of the Collaborative Perinatal Project of the National Institute of Neurological Diseases and Stroke.  This study based on 55908 pregnancies demonstrated that for both blacks and whites an increase in birthweight and a decrease in the incidence of low birthweight occurred as maternal height increased above 147.3 cm.  Also for both races the mean birthweight increased and the proportion of infants with low birthweight decreased with increasing weight before pregnancy.  When maternal height and prepregnancy weight were considered together the rate of low birthweight was reduced 5-fold among whites and 3-fold among blacks.  Kleinman and Kessel neglect to include these variables in their analysis and Lieberman and her associates include them inaccurately through the ponderal index.  This ratio which is traditionally used to quantify the proportionality of intrauterine growth in newborns identifies only extreme cases of low pregravid weight-for-height.  For example a woman 152 cm tall would have to weigh less than 41.4 kg (20% underweight) to have a ponderal index of less than 18 the investigators identified risk level.  The American College of Obstetricians and Gynecologists has identified low prepregnant and weight-for-height as 10% or less.  Women with short stature moderate or massive obesity or low weight-for-height (less than 10% to less than 20%) are not detected by this index.  In addition weight gain during pregnancy as a variable influencing birthweight and length of gestation is missing in both studies.  All these variables have been shown to influence intrauterine growth dramatically.  (full text)
Combination chemotherapy with paclitaxel and platinum in the treatment for advanced or recurrent ovarian clear cell adenocarcinoma: Multicenter trial
Authors: K. Ota, J.-I. Akahira, H. Utsunomiya, T. Takano, H. Niikura, K. Ito, N. Yaegashi
Journal: Journal of Clinical Oncology (2004)

5101 Background: Patients with clear cell adenocarcinoma of the ovary (CC) have a poor response to chemotherapy and have a significantly worse prognosis than other histological types of ovarian cancer. However, the therapeutic effect of a combination of paclitaxel (PTX) and platinum (PLT) in CC patients with measurable disease has yet to be elucidated. In this study, we evaluated the treatment results of a combination of PTX and PLT in CC patients with measurable disease by retrospective review. Methods: Twenty–eight patients with measurable residual CC (12 primary cases and 16 recurrent cases), who were treated with combination chemotherapy with PTX and PLT, were identified through the medical records from 10 institutions. Patients with serous adenocarcinoma were selected as a control for comparison. Histological evaluation was performed under the central pathological review. Clinical response to chemotherapy was compared between CC and serous adenocarcinoma patients using RECIST criteria. Results: In primary cases, 7 of 12 CC patients (58.3%) and 17 of 22 serous adenocarcinoma patients (77.3%) responded to chemotherapy, and the difference was not significant. In recurrence CC cases, 3 of 16 CC patients (18.8%) responded to the chemotherapy. The difference of response rate between primary and recurrent cases in CC patients was statistically significant (P<0.05). Conclusion: The response rate of this combination chemotherapy for primary residual CC patients was relatively high and was comparable with those of serous adenocarcinoma. Our results indicate that the combination of PTX and PLT has a sufficient potential as first–line chemotherapy to this ‘assumed’ chemo–resistant tumor. No significant financial relationships to disclose.
α-Conotoxin Vc1.1 inhibits human dorsal root ganglion neuroexcitability and mouse colonic nociception via GABA<sub>B</sub>receptors
Authors: Joel Castro, Andrea M Harrington, Sonia Garcia-Caraballo, Jessica Maddern, Luke Grundy, Jingming Zhang, Guy Page, Paul E Miller, David J Craik, David J Adams, Stuart M Brierley
Journal: Gut (2016)

α-Conotoxin Vc1.1 is a small disulfide-bonded peptide from the venom of the marine cone snail Conus victoriae. Vc1.1 has antinociceptive actions in animal models of neuropathic pain, but its applicability to inhibiting human dorsal root ganglion (DRG) neuroexcitability and reducing chronic visceral pain (CVP) is unknown.We determined the inhibitory actions of Vc1.1 on human DRG neurons and on mouse colonic sensory afferents in healthy and chronic visceral hypersensitivity (CVH) states. In mice, visceral nociception was assessed by neuronal activation within the spinal cord in response to noxious colorectal distension (CRD). Quantitative-reverse-transcription-PCR, single-cell-reverse-transcription-PCR and immunohistochemistry determined γ-aminobutyric acid receptor B (GABABR) and voltage-gated calcium channel (CaV2.2, CaV2.3) expression in human and mouse DRG neurons.Vc1.1 reduced the excitability of human DRG neurons, whereas a synthetic Vc1.1 analogue that is inactive at GABABR did not. Human DRG neurons expressed GABABR and its downstream effector channels CaV2.2 and CaV2.3. Mouse colonic DRG neurons exhibited high GABABR, CaV2.2 and CaV2.3 expression, with upregulation of the CaV2.2 exon-37a variant during CVH. Vc1.1 inhibited mouse colonic afferents ex vivo and nociceptive signalling of noxious CRD into the spinal cord in vivo, with greatest efficacy observed during CVH. A selective GABABR antagonist prevented Vc1.1-induced inhibition, whereas blocking both CaV2.2 and CaV2.3 caused inhibition comparable with Vc1.1 alone.Vc1.1-mediated activation of GABABR is a novel mechanism for reducing the excitability of human DRG neurons. Vc1.1-induced activation of GABABR on the peripheral endings of colonic afferents reduces nociceptive signalling. The enhanced antinociceptive actions of Vc1.1 during CVH suggest it is a novel candidate for the treatment for CVP.
Abstract 17425: Utilization of Radiofrequency Catheter Ablation for Treatment of Atrial Fibrillation in United States
Authors: Abhishek Deshmukh, Sadip Pant, Kaustubh Dabadhkar, Apurva Badheka, Tushar Tuliani, Vikas Singh, Madhu Reddy, Maithili Shenoy, Hakan Paydak
Journal: Circulation (2012)

INTRODUCTION: Utilization of radiofrequency catheter ablation (RFA) for treatment of atrial fibrillation (AF) is increasing.It is increasingly being performed outside of the specialized centers . T...
Targeting Cdk4/6 in combination therapy of chemoresistant multiple myeloma
Authors: S. Chen-Kiang, M. Di Liberto, T. Louie, J. Liang, D. S. Jayabalan, S. Ely, M. A. Moore, R. Niesvizky, X. Huang
Journal: Journal of Clinical Oncology (2008)

8503 Background: Deregulation of Cdk4 or Cdk6 is a hallmark in cancer. However, conventional cancer therapy centers on empirical cytotoxic killing. Targeting the cell cycle with broad-spectrum inhibitors has proven ineffective so far due to cross- reactivity with cell survival and the transcriptional machinery. In myeloma, over-expression of Cdk4-cyclin D1 or Cdk6-cyclin D2 predisposes primary bone marrow (BM) myeloma cells to proliferation in vivo. Conversely, silencing Cdk4/6 by its physiologic inhibitor, p18INK4c, is required for cell cycle termination during the generation of normal plasma cells. Targeting Cdk4/6, therefore, represents a rational strategy to control disease progression and drug resistance in myeloma. Methods: An orally bioactive, small molecule PD 0332991 selectively and reversibly inhibits Cdk4/6 (IC50 ∼ 60 nM) in primary myeloma cells ex vivo. This leads to exclusive G1 cell cycle arrest unaccompanied by apoptosis by BrdU labeling and apoptotic assays. Results: By inducing synchronous S phase entry upon release of G1 block or prolonging G1 arrest, inhibition of Cdk4/6 by PD 0332991 profoundly sensitizes primary myeloma cells to killing by proteasome inhibitors bortezomib and NPI-0052, or dexamethasone. Sequential treatments with PD 0332991 and bortezomib rapidly reduces tumor burden in animal models. Importantly, it overcomes chemoresistance in myeloma cells isolated from refractory relapse patients, despite stromal protection. Synergistic killing of myeloma cells lies in induction of cell cycle-specific mitochondria depolarization. Base On this basis and a favorable outcome of Phase I clinical trial, a Phase I/II PD 0332991-bortezomib clinical trial for myeloma is in progress. Conclusion: Targeting Cdk4/6 by PD 0332991 in combination with a selective cytotoxic agent represents a new class of promising cell cycle-based therapy in myeloma, and possibly other cancers. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ortho Biotech Amgen, Merck, Millennium, Novartis Johnson & Johnson MMRF, NIH/NIAMS, Ortho Biotech, VA Merit Review
Transient inhibition of ROR-γt therapeutically limits intestinal inflammation by reducing TH17 cells and preserving group 3 innate lymphoid cells
Authors: David R Withers, Matthew R Hepworth, Xinxin Wang, Emma C Mackley, Emily E Halford, Emma E Dutton, Clare L Marriott, Verena Brucklacher-Waldert, Marc Veldhoen, Judith Kelsen, Robert N Baldassano, Gregory F Sonnenberg
Journal: Nature Medicine (2016)
Triggering of CD40 Antigen Inhibits Fludarabine-Induced Apoptosis in B Chronic Lymphocytic Leukemia Cells
Authors: Maria Fiammetta Romano, Annalisa Lamberti, Pierfrancesco Tassone, Fiorella Alfinito, Silvia Costantini, Federico Chiurazzi, Thierry Defrance, Patrizio Bonelli, Franca Tuccillo, Maria Caterina Turco, Salvatore Venuta
Journal: Blood (1998)
P0627 : Monoclonal gammopathy in patients with acute hepatitis E and other causes of acute viral hepatitis
Authors: K.L. Woolson, A. Forbes, R.G. Madden, P. Oppong, J.G. Hunter, R. Martin, R.P. Bendall, J. Palmer, B. Haywood, H.R. Dalton
Journal: Journal of Hepatology (2015)
Circulating tumor cells (CTC), [18F]fluorodeoxyglucose positron emission tomography, and computed tomography (PET/CT) for treatment monitoring in patients with metastatic breast cancer (MBC)
Authors: D. Tamkus, S. R. Chandana, K. Berger, T. Aung
Journal: Journal of Clinical Oncology (2009)

e12007 Background: Use of [18F]-fluorodeoxyglucose PET /CT and/or CTC is being investigated to follow up response to treatment in patients with MBC. It is not clear if these tests can be a surrogate for one another. Methods: We retrospectively analyzed a database of female patients with MBC undergoing chemotherapy or hormonal therapy. Most of these patients received at least 2 lines of therapy. Standard CT scan tumor measurements were used to assess response to therapy. CTC were defined either low (0–5) or high (&gt;5). Maximum standard uptake values (max SUV) on PET scan were defined either low (&lt;3) or high (&gt;3). Correlation between the max SUV and CTC counts was statistically analyzed. Sensitivity, specificity, positive and negative predictive values were calculated from 2 x 2 table. Results: A total of 9 female patients with MBC were identified (mean age of 52 years). The receptor status of these patients includes 67 % positive for ER and 33 % positive for HER-2/neu. Median follow up was 9.8 months. There were 59 time points (&gt; or = 4 weeks apart) when either PET/CT or CTC were performed. The results of PET/CT scans were compared with CTC at 38 events. The sensitivity of CTC to detect metastatic disease shown on PET/CT was 32% and specificity of 100%. The positive and negative predictive values were 100% and 32% respectively. There was a positive correlation between the max SUV and CTC count (p = 0.001). However in three patients, despite of progression of disease per PET/CT, CTC were undetectable at three different time points. Interestingly, two out of these three patients were triple negative. Disease progression was confirmed by biopsy in two of these patients. Conclusions: Our data suggest positive correlation between PET/CT scan and CTC. However, CTC had poor sensitivity and negative predictive value to detect progressive metastatic disease. Normal CTC values have to be interpreted cautiously in patients with MBC. We are now planning to investigate the utility of these tests, prospectively, in a large cohort of MBC patients. No significant financial relationships to disclose.
Oncogenic driver genes and the inflammatory microenvironment dictate liver tumor phenotype
Authors: Matthias S. Matter, Jens U. Marquardt, Jesper B. Andersen, Cristina Quintavalle, Nikolay Korokhov, Jim K. Stauffer, Kosuke Kaji, Thomas Decaens, Luca Quagliata, Fathi Elloumi, Tanya Hoang, Alfredo Molinolo, Elizabeth A. Conner, Achim Weber, Mathias Heikenwalder, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Hepatology (2016)

The majority of hepatocellular carcinoma develops in the background of chronic liver inflammation caused by viral hepatitis and alcoholic or nonalcoholic steatohepatitis. However, the impact of different types of chronic inflammatory microenvironments on the phenotypes of tumors generated by distinct oncogenes is largely unresolved. To address this issue, we generated murine liver tumors by constitutively active AKT‐1 (AKT) and β‐catenin (CAT), followed by induction of chronic liver inflammation by 3,5‐diethoxycarbonyl‐1,4‐dihydrocollidine (DDC) and carbon tetrachloride. Also, the impact of DDC‐induced chronic liver inflammation was compared between two liver tumor models using a combination of AKT‐CAT or AKT‐NRAS G12V . Treatment with DDC and carbon tetrachloride significantly facilitated the adenoma‐to‐carcinoma conversion and accelerated the growth of AKT‐CAT tumors. Furthermore, DDC treatment altered the morphology of AKT‐CAT tumors and caused loss of lipid droplets. Transcriptome analysis of AKT‐CAT tumors revealed that cellular growth and proliferation were mainly affected by chronic inflammation and caused up‐regulation of Cxcl16, Galectin‐3, and Nedd9, among others. Integration with transcriptome profiles from human hepatocellular carcinomas further demonstrated that AKT‐CAT tumors generated in the context of chronic liver inflammation showed enrichment of poor prognosis gene sets or decrease of good prognosis gene sets. In contrast, DDC had a more subtle effect on AKT‐NRAS G12V tumors and primarily enhanced already existent tumor characteristics as supported by transcriptome analysis. However, it also reduced lipid droplets in AKT‐NRAS G12V tumors. Conclusion : Our study suggests that liver tumor phenotype is defined by a combination of driving oncogenes but also the nature of chronic liver inflammation. (H epatology 2016;63:1888‐1899)
The complex of phosphatidylinositol 4,5-bisphosphate and calcium ions is not responsible for Ca(2+)-induced loss of phospholipid asymmetry in the human erythrocyte: a study in Scott syndrome, a disorder of calcium- induced phospholipid scrambling
Authors: EM Bevers, T Wiedmer, P Comfurius, J Zhao, EF Smeets, RA Schlegel, AJ Schroit, HJ Weiss, P Williamson, RF Zwaal
Journal: Blood (1995)
Changes in White Matter Microstructure Suggest an Inflammatory Origin of Neuropsychiatric Systemic Lupus Erythematosus
Authors: César Magro‐Checa, Ece Ercan, Ron Wolterbeek, Bart Emmer, Nic J. van der Wee, Huub A. Middelkoop, Nyika D. Kruyt, Itamar Ronen, Mark A. van Buchem, Tom W. Huizinga, Gerda M. Steup‐Beekman
Journal: Arthritis & Rheumatology (2016)

To assess white matter (WM) and gray matter (GM) magnetization transfer ratio histogram peak heights (MTR-HPHs) in different subsets of patients with neuropsychiatric systemic lupus erythematosus (NPSLE) who have unremarkable findings on 3T magnetic resonance imaging of the brain and to evaluate whether these values could be used to highlight different clinically suspected underlying pathogenic processes or identify the clinical NPSLE status or whether they could be associated with a specific NPSLE syndrome.Sixty-four SLE patients with neuropsychiatric symptoms were included. The initial NPSLE diagnosis and suspected underlying pathogenic process were established by multidisciplinary evaluation. The final diagnosis was made after also considering the disease course 6-18 months later. Thirty-three patients with central nervous system (CNS) NPSLE and 31 SLE patients with neuropsychiatric symptoms unrelated to SLE (non-SLE-related NP) were included. Twenty SLE patients without neuropsychiatric symptoms and 36 healthy control subjects were included for comparison. Differences in the WM and GM mean MTR-HPHs and between the different NPSLE subgroups (CNS NPSLE diagnosis, NPSLE phenotype [inflammatory or ischemic], and clinical changes after treatment) and the relationship to NPSLE syndromes were evaluated.Patients with inflammatory NPSLE had significantly lower WM MTR-HPHs than did the healthy controls, the SLE patients, and the non-SLE-related NP patients. Cognitive disorder, mood disorder, and psychosis were related to lower WM MTR-HPH values and cerebrovascular symptoms to higher values. Furthermore, the mean MTR-HPHs in the WM increased when the clinical status of the NPSLE patients improved.Measurement of MTR-HPH of the WM has the potential to identify inflammatory NPSLE with CNS involvement. This finding underscores the usefulness of this technique for the detection of cerebral changes in NPSLE patients and for the assessment of clinical changes after treatment.
Neoadjuvant treatment with paclitaxel and epirubicin in invasive breast cancer: A phase II study
Authors: D. Sarid, I. Ron, M. Inbar, N. Barak
Journal: Journal of Clinical Oncology (2005)

859 Background: A phase II study was conducted to assess the efficacy and availability of paclitaxel (Taxol) and epirubicin in neoadjuvant setting in women with locally advanced or high tumor-breast ratio cancer. None of the group of study patients was suitable for breast conserving surgery prior to chemotherapy. Methods: Patients were treated with 75 mg/m2 of Epirubicin and 175–200 mg/m2 of Paclitaxel (Taxol), both administered intravenously on day 1 every 21 days for 5 courses. Clinical and pathological response rates, rate of breast conserving surgery and adverse events were analyzed. Results: Fifty-eight (97%) of 60 registered patients (two of them with bilateral breast cancer) were assessable for toxicity and response. Twelve (12/60) patients (20%) achieved pathological complete response, seventeen (17/58) patients (29%) resulted in clinical complete response. Thirty four (34/58) patients (59%) achieved clinical response that enabled them to undergo breast conserving surgery. There were only grade 1 and 2 toxic effects. The major adverse reactions were neutropenia and neutropenic fever, nausea, vomiting and arthralgia-mialgia syndrome. Conclusions: The preoperative combination of Paclitaxel and Epirubicin is active and achieved a significant increase in lumpectomy rates. Mostly grade 1 or 2 toxicity with no need to stop or decrease the doses of chemotherapy was observed. No significant financial relationships to disclose.
Genetic Landscapes Of Childhood T-Cell Acute Lymphoblastic Leukemia
Authors: Masafumi Seki, Kenichi Yoshida, Yusuke Sato, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Motohiro Kato, Mitsuteru Hiwatari, Katsuyoshi Koh, Ryoji Hanada, Masashi Sanada, Satoru Miyano, Akira Oka, Yasuhide Hayashi, Seishi Ogawa, Junko Takita
Journal: Blood (2013)
<i>KRAS</i> mutation status and toxicity of cetuximab, paclitaxel, cisplatin, and concurrent radiation in Chinese patients with locally advanced esophageal squamous cell carcinoma: An open-label, multicenter, phase II study.
Authors: J. Yu, X. Meng, J. h. Wang, X. Sun, L. Wang, M. Ye, P. b. Feng, G. y. Zhu, Y. Lu, S. c. Zhu
Journal: Journal of Clinical Oncology (2011)

e14650 Background: The most common type of esophageal or gastroesophageal-junction cancer in Western countries is adenocarcinoma; however, in China more than 90% of esophageal malignancies are of squamous cell carcinoma (SCC). Thus data are lacking on the potential benefits from the use of cetuximab for Chinese patients with esophageal SCC. We conducted this Chinese multicenter trial to determine the toxicity of the addition of cetuximab with paclitaxel, cisplatin, and concurrent radiation for patients with esophageal SCC and to determine whether KRAS status predicts response. Methods: Patients with unresectable locally advanced cervical, upper or mid-esophageal SCC without distant metastasis were eligible for this open-label phase II trial. All patients received cetuximab (400 mg/m2 day 1 before chemoradiotherapy and 250 mg/m2 q1w × 7 weeks), paclitaxel (45 mg/m2 q1w × 7 weeks) and cisplatin (20 mg/m2 q1w × 7 weeks) with 59.4 Gy of radiation. KRAS mutation status was assessed in tumor specimen at a centralized facility. Results: Fifty-five patients were enrolled and evaluable for to toxicity. Non-hematological adverse events were generally grade 1 or 2, and were most often rash (94.5%), mucositis (58.2%), fatigue (45.5%), nausea (41.8%) and hepatic dyfunction (40%). Hematologic adverse events included grade 3 neutropenia (32.7%) and grade 3 anemia (1.82%). Ten patients did not complete the protocol therapy and were not assessable for response (6 for chemotherapy dose delays, 1 for paciltaxel hypersensitivity, 1 by the treating physicians for unstated reasons, 1 for concurrent unrelated infection, and 1 for tracheo-esophageal fistula). Forty-four of the 45 evaluable patients (97.7%) had a clinical response after chemoradiation. No mutations were detected at KRAS codons 12 or 13 in the 52 available specimens. Conclusions: Cetuximab can be safely administered with chemoradiation for Chinese patients with esophageal cancer and may improve the clinical response rate. KRAS mutations were too rare to be analyzed as a predictor of response.
Changes in Phytohemagglutinin Response Due to Presence of Tumors2
Authors: Ronald W. Gillette, Charles W. Boone
Journal: JNCI Journal of the National Cancer Institute (1973)

A variety of tumors caused depression of phytohemagglutinin (PHA) response of spleen cells. Lymph node cells were not affected similarly. Loss in the splenic PHA response was independent of the tumorigenicity, immunogenicity, or tissue of origin of the tumors.