tbuckley/cabot-search huggingface dataset:
Heparin decreases mesangial matrix accumulation after selective antibody-induced mesangial cell injury.
Authors: W W Tang, C B Wilson
Journal: Journal of the American Society of Nephrology (1992)

Anti-rat thymocyte antibody-induced injury of glomerular mesangial cells is characterized initially by lysis (1 h) and is followed by proliferation (beginning at 3 to 4 days), with resolution that can include a focal increase in mesangial matrix (by 28 days). Chronic administration (every 12 h) of heparin (anticoagulant or nonanticoagulant) resulted in a decrease in antibody-induced mesangial cell proliferation, which, in turn, was associated with a decrease in the size and number of areas of focal mesangial matrix increase. The effect could not be attributed to the effect of heparin on complement, to alterations in the small numbers of la-positive cells that characterize the lesion, or to binding of antibody to glomeruli. The beneficial effects of heparin in reducing mesangial cell proliferation, with a subsequent reduction in matrix increase, suggest that mesangial cell responses are a major element in the development of at least some forms of glomerulosclerosis. The possible mechanisms by which these effects of heparin may be achieved are discussed.
사례보고 : 하수오 복용 후 발생한 재발성 독성 간염 1예
Authors: 배상훈 ( Sang Hoon Bae ), 김동현 ( Dong Hyun Kim ), 배영석 ( Young Seok Bae ), 이광재 ( Kwang Jae Lee ), 김동완 ( Dong Wan Kim ), 윤정빈 ( Jeoung Bin Yoon ), 홍준호 ( Joon Ho Hong ), 김상현 ( Sang Hyun Kim )
Journal: Clinical and Molecular Hepatology (2010)

Toxic hepatitis has been reported as a major cause of acute hepatitis, but its potential induction by herbal remedies and/or health foods is usually neglected. We experienced a case of toxic hepatitis associated with Polygoni multiflori, a Chinese herb commonly known as Ho-Shou-Wu. A 54-year-old woman consumed Ho-Shou-Wu for 1 month, after which she experienced fatigue and overall weakness. A diagnosis of toxic hepatitis was made based on her clinical history, the findings for viral markers and other laboratory data, and ultrasonography. Her condition improved considerably after she stopped taking Ho-Shou-Wu. However, she resumed taking Ho-Shou-Wu immediately after discharge from hospital, which aggravated her symptoms and liver function. She was immediately readmitted and stopped taking Ho-Shou-Wu. Her relapse into hepatitis immediate after resuming consumption of the herb is strongly indicative of the validity of Koch`s postulate in this case.
Neoadjuvant chemotherapy followed by extrapleural pneumonectomy for malignant pleural mesothelioma (MPM): A multicenter phase II trial of the SAKK
Authors: R. A. Stahel, W. Weder, P. Ballabeni, D. Betticher, R. Schmid, R. Stupp, H.-B. Ris, A. Roth, W. Mingrone, S. Bodis
Journal: Journal of Clinical Oncology (2004)

7052 Background: We previously reported our single center experience of preoperative chemotherapy with cisplatin and gemcitabine followed by extrapleural pneumonectomy (EPP) in patients with potentially resectable MPM (Kestenholz, ASCO 2000). The concept was now examined in a multicenter setting. Methods: Eligible patients had ≤T2N2M0 MPM of all histological types. The primary endpoint was the percentage of patients benefiting from proper resection and the tolerability of the approach with the purpose of inferring whether preoperative chemotherapy is sufficiently promising to justify further larger studies. The target sample size for the whole trial was later increased from 30 to 61 patients to address questions about quality of life. Chemotherapy included three cycles of cisplatin 80 mg/m2 day 1 and gemcitabine 1000 mg/m2 days 1, 8 and 15 and was to be followed by EPP within 6 weeks and optional radiotherapy to areas of incomplete resection or risk. Results: Accrual of 61 patients was completed in April 2003. Stage at study entry was ≤ T2N0–1 in 45, T3N0–1 in 8, T1–3N2 in 7 and T2Nx in 1 patient. 58 patients completed chemotherapy as planned. Major toxicities included leucopenia (15%), thrombocytopenia (7%) and nausea (6% of 178 cylces). 45 of 58 patients completing chemotherapy underwent EPP. Four patients were unresectable at surgery, 7 patients were inoperable because of tumor progression, myocardial infarction or decrease in PS, and 2 patients refused surgery. Complete resection was achieved in 37 patients. 21 patients had one or more postoperative complications and there was one postoperative death. 36 patients had postoperative radiotherapy. The one-year survival for all patients was 67%. Survival and on quality of life data will be presented. Conclusion: With 45 patients being operated, we conclude, according to the trial design, that preoperative chemotherapy and EPP is an important approach to be investigated in large trials of patients with MPM. No significant financial relationships to disclose.
Characteristics of 51 asthmatics autopsied in São Paulo, Brazil from 2005-2009
Authors: Diogenes Ferreira, Marisa Dolhnikoff, Thais Mauad
Journal: European Respiratory Journal (2011)

Introduction:  Deaths attributed to asthma in the city of Sao Paulo, Brazil have decreased since 2005. We have previously reported the clinical characteristics of asthmatics autopsied in the city of Sao Paulo from 1996-2004 (Mauad, 2008). Our aim was to describe the clinical characteristics of 51 fatal asthmatics autopsied in Sao Paulo from 2005 to 2009.   Methods:  Fifty-one patients who were autopsied at the Death Verification Service of Sao Paulo from 2005-2009 and had deaths confirmed macro and microscopically as due to status asthmaticus were studied. An interview with the next of kin assessed demographics, history and treatment of asthma and events surrounding the last attack; written informed consent was obtained from the next of kin.   Results:  There were 28 females and 23 males, with a median age of 50 years (range 20-73). Thirty-nine patients were whites and 26 patients had at least 8 years of education. Thirty-one individuals were non-smokers, 11 were current smokers and 9 were ex-smokers. The age at onset of asthma  24 hours for 55% of the patients. These characteristics are similar to those described for asthmatics deceased from 1996-2004.   Conclusion:  Fatal asthmatics deceased in the city of Sao Paulo from 2005-2009 have similar characteristics to those deceased from 1996-2004, despite of a decreasing number of asthma deaths.
Rabbit Antiserum Against a Non-T, Non-B Leukemia Cell Line That Carries the Ph&lt;sup&gt;1&lt;/sup&gt; Chromosome (NALM-1): Antibody Specific to a Non-T, Non-B Acute Lymphoblastic Leukemia Antigen&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H Koshiba, J Minowada, D Pressman
Journal: JNCI Journal of the National Cancer Institute (1978)

Rabbit immune sera against human cells of a non- T, non-B leukemia cell line bearing the Ph1 chromosome (NALM- 1) were characterized. After proper and exhaustive absorption, the sera were tested by indirect membrane immunofluorescence on a panel of 19 human hematopoietic cell lines with T-, B-, or non-T, non-B cell surface characteristics. The absorbed sera reacted specifically with NALM-1 cells but not with cells of another Ph1-positive cell line, K-562. Four of the 6 leukemia T-cell lines, 2 of the 4 leukemia-lymphoma B-cell lines, all of 4 acute lymphoblastic leukemia (ALL) lines with non-T, non-B cell characteristics, and uncultured cells of all patients with non-T, non-B cell ALL were reactive with the antisera. A cross-absorption study of the antisera suggested that a single antigenic complex is involved in this antigen specificity. The antigen involved appears to be a common non-T, non-B ALL one that has been described previously.
MDM2 309 single nucleotide polymorphisms (SNP) and clinical outcome in patients with advanced squamous cell carcinoma of head and neck (SCCHN).
Authors: M. Gasco, D. Vivenza, M. Monteverde, L. Lattanzio, I. Colantonio, G. Natoli, E. Miraglio, A. Comino, N. Syed, T. Crook, M. C. Merlano, C. Lo Nigro
Journal: Journal of Clinical Oncology (2011)

5509 Background: Disruptive TP53 alterations have been associated with decreased survival in patients with SCCHN. A T>G polymorphism in the promoter region of mouse double minute 2 homologue (MDM2) has been associated with higher MDM2mRNA and protein levels. Overexpression of MDM2 is thought to interfere with p53-mediated apoptosis and growth inhibition. We hypothesized that the MDM2genotypes containing the G allele (GT+ GGgenotype) may be associated with worse survival in SCCHN patients (pts). Methods: We directly sequenced the MDM2 polymorphism on both strands. We then evaluated the correlations between MDM2 polymorphism status and overall survival (OS) in 58 pts with stage III and IV SCCHN. Median follow-up was 6.5 years. All pts received cisplatin-based chemo-radiotherapy in our Department from 1997 to 2007. The Kaplan-Meier method and log-rank test were used to compare survival according to MDM2polymorphism status. Cox proportional hazards model was used to calculate hazard ratio (HR) adjusted for possible confounding variables, with 95% confidence interval (95% CI). Results: Median age was 56 years; 50 pts (86%) were male and 52 pts (90%) were stage IV. The genotype frequencies for the MDM2 polymorphism were: T/T 32 (55%), T/G 17 (30%), G/G 9 (15%). Median overall survival (OS) and 5-years survival rates were significantly shorter in patients with genotypes containing the G allele (GT + GG genotype) compared to those with TT genotype (63 months vs. 124 months; log- rank p = 0.006 and 10/26 vs. 27/32; Fisher's exact p = 0.02, respectively). Notably, after adjusting for age, stage and performance status, genotypes containing the G allele appeared to be associated with worse survival (HR for death 2.90; 95% CI 1.37–6.12; p = 0.005). Conclusions: Our findings support the hypothesis that MDM2SNP309 polymorphism is an independent survival determinant among advanced stage SCCHN patients treated with cisplatin-based chemo-radiotherapy.
Hybridization of powdery mildew strains gives rise to pathogens on novel agricultural crop species
Authors: Fabrizio Menardo, Coraline R Praz, Stefan Wyder, Roi Ben-David, Salim Bourras, Hiromi Matsumae, Kaitlin E McNally, Francis Parlange, Andrea Riba, Stefan Roffler, Luisa K Schaefer, Kentaro K Shimizu, Luca Valenti, Helen Zbinden, Thomas Wicker, Beat Keller
Journal: Nature Genetics (2016)
Effect of Smoking During Pregnancy on the Risk of Cancer in Children&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C. Ineke Neutel, Ph.D., Carol Buck, M.D.
Journal: JNCI Journal of the National Cancer Institute (1971)

From the Ontario Perinatal Mortality Study and the British Perinatal Mortality Survey, 89,302 babies surviving at least 7 days served as a base population (or a prospective study of the relationship between smoking in pregnancy and cancer in the offspring. The smoking habits of the mother during pregnancy were recorded before or just after the birth of the child. In the two base populations combined, there were 65 cancer deaths and 32 cancer survivors in the period from birth to a minimum of 7 and a maximum of 10 years of age. For cancer of all sites, the children of smokers had a relative risk of 1.3 with 95% confidence limits of 0.8–2.2. Evidence of a dose-response relationship was lacking. Although these results make it most unlikely that in utero exposure to tobacco smoke has a broadly carcinogenic effect on the fetus, a response confined to one tissue or expressed over a narrow age range cannot be ruled out.
Dual blockade of epidermal growth factor receptor (EGFR) and cyclooxygenase 2 (COX 2) may be dependent upon the EGFR mutational status in non-small cell lung cancer (NSCLC) cell lines
Authors: S. M. Gadgeel, S. Ali, P. Philip, A. Wozniak, F. Sarkar
Journal: Journal of Clinical Oncology (2006)

7170 Background: Recent data has shown that the benefit of EGFR TKIs (tyrosine kinase inhibitors) in NSCLC is in patients with tumors that have EGFR mutations and /or gene amplification. Even among these patients, the median survival with EGFR TKIs is only 22 months. Pre-clinical data has shown that dual blockade of EGFR and COX 2 pathways may be beneficial. A recent clinical trial conducted at our center suggested that this combination primarily impacted NSCLC tumors that have the EGFR biomarkers. We therefore hypothesized that the EGFR biomarker status determines the outcome of dual blockade of these pathways in NSCLC. Methods: Three different cell lines with varying biomarker status and sensitivities to EGFR TKIs were used- H3255 (L858R; gene amplified), H1650 (del E746-A750; gene amplified), H1781 (wild type). Cells were treated with erlotinib, EGFR TKI- 10nM-100nM or celecoxib, COX 2 inhibitor- 5 μM and with the combination of two drugs. Cell survival was determined by a standard MTT assay and apoptosis was measured by ELISA method. Western blot analysis was conducted to assess COX 2, EGFR and pAkt levels. Results: Celecoxib by itself had no effects on any of the cell lines. Erlotinib showed a concentration dependent growth inhibition of both H3255 (IC50–41.72nM; surviving fraction at 50nM was 52%) and H1650 (IC50 &gt; 100nM; Surviving fraction at 50nM was 70%) but had no effect on H1781. Celecoxib added to erlotinib significantly enhanced the growth inhibition of H3255 (p = 0.001) and H1650 (p = 0.014) as well as apoptosis (H3255- p = 0.016; H1650- p = 0.011) at all concentrations of erlotinib but had no effect in H1781 cells. In western Blot analysis the combination significantly reduced levels of COX-2, EGFR and pAkt compared to baseline and either agent alone in H3255 cells. Conclusions: The addition of celecoxib to erlotinib has a differential effect in NSCLC cell lines based on their EGFR biomarker status. This beneficial effect of celecoxib addition may be through improved inhibition of each pathway. [Table: see text]
The Prevalence of Latent Tuberculosis Infection in the United States
Authors: James D. Mancuso, Jeffrey M. Diffenderfer, Bijan J. Ghassemieh, David J. Horne, Tzu-Cheg Kao
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Individuals with latent tuberculosis infection (LTBI) represent a reservoir of infection, many of whom will progress to tuberculosis (TB) disease. A central pillar of TB control in the United States is reducing this reservoir through targeted testing and treatment.Objectives: To estimate the prevalence of LTBI in the United States using the tuberculin skin test (TST) and an IFN-γ release assay.Methods: We used nationally representative data from the 2011–2012 National Health and Nutrition Examination Survey (n = 6,083 aged ≥6 yr). LTBI was measured by both the TST and QuantiFERON-TB Gold In-Tube test (QFT-GIT). Weighted population, prevalence, and multiple logistic regression were used.Measurements and Main Results: The estimated prevalence of LTBI in 2011–2012 was 4.4% as measured by the TST and 4.8% by QFT-GIT, corresponding to 12,398,000 and 13,628,000 individuals, respectively. Prevalence declined slightly since 2000 among the U.S. born but remained constant among the foreign born. Earlier birth cohorts consistently had higher prevalence than more recent ones. Higher risk groups included the foreign born, close contact with a case of TB disease, and certain racial/ethnic groups.Conclusions: After years of decline, the prevalence of LTBI remained relatively constant between 2000 and 2011. A large reservoir of 12.4 million still exists, with foreign-born persons representing an increasingly larger proportion of this reservoir (73%). Estimates and risk factors for LTBI were generally similar between the TST and QFT-GIT. The updated estimates of LTBI and associated risk groups can help improve targeted testing and treatment in the United States.
Functional polymorphic variants of methionine metabolism influence neurotoxicity and survival in primary central nervous system lymphoma (PCNSL) treated with high-dose methotrexate
Authors: M. Linnebank, S. Moskau, A. Juergens, M. Simon, A. Semmler, K. Orlopp, H. Urbach, H. Pels, U. Bode, I. G. Schmidt-Wolf, U. Schlegel
Journal: Journal of Clinical Oncology (2008)

8579 Background: Methotrexate (MTX) is the most efficient chemotherapeutic drug in primary central nervous system lymphoma (PCNSL); it directly interferes with methionine metabolism. Patients and Methods: Eight functional polymorphic variants influencing methionine metabolism were investigated in 65 PCNSL patients and were analyzed for their impact on the occurrence of confluent CNS white matter changes (WMC) (Pearson’s Chi-square test and multinominal regression analysis) and for their influence on survival (univariate Log Rank and multivariate COX regression analyses). Results: Twenty/65 (31%) patients developed WMC, which was significantly predicted by the genotype of methylenetetrahydrofolate reductase c.1298A>C (p.E429A; patients with WMC, AA/AC/CC: 0.80/0.10/0.10; patients without WMC: 0.40/0.47/0.13; nominal logistic regression: χ2=11.54; p=0.003). In addition, the transcobalamin 2 variant c.776C>G (p.P259R) influenced the occurrence of WMC (patients with WMC: 0.20/0.45/0.35; patients without WMC: 0.33/0.47/0.20; χ2=11.15; p=0.003) and survival (c.776CC: 105±7 months; c.776CG/GG: 69±9 months; Log Rank 4.79; p=0.029; Wald 4.15; p=0.042). Conclusions: The mutant c.776G-allele of the cobalamin transporter transcobalamin 2 leads to a reduced availability of methylcobalamin as cofactor for the synthesis of methionine and S-adenosylmethionine (SAM) from homocysteine. Since SAM is mandatory for DNA methylation and for CNS myelination, depletion of SAM may lead to WMC during MTX treatment. Further, the synthesis of methionine/SAM from homocysteine leads to a conversion of 5-methyltetrahydrofolate to 5,10-methylenetetrahydrofolate. We speculate that the effects of the transcobalamin 2 c.776C allele on tetrahydrofolate conversion and on SAM synthesis may be involved in the observed effect of this allele on occurrence of WMC and on survival. If confirmed in an independent patient sample, these observations may have an impact on MTX-based cancer treatment: Modification of methionine metabolism, e.g. by vitamine or amino acid supplementation, could have beneficial effects on both, treatment efficacy and neurotoxicity. No significant financial relationships to disclose.
Routine Bone Marrow Biopsy Adds Little Diagnostic Information in Patients with Newly Diagnosed Hodgkin Lymphoma Undergoing PET/CT Staging
Authors: Tarec Christoffer El-Galaly, Francesco d'Amore, Peter de Nully Brown, Ilse Christiansen, Lena Specht, Annika Loft, Anne Bukh, Hans E. Johnsen, Charlotte Madsen, Martin Hutchings
Journal: Blood (2011)
Pemetrexed (Pem), oxaliplatin (Ox), and bevacizumab (Beva) as first-line therapy in patients (pts) with stage IV lung adenocarcinoma.
Authors: P. Boudou-Rouquette, O. Mir, J. Chapron, S. Ropert, J. Durand, R. Coriat, T. Bui, D. Dusser, F. Goldwasser
Journal: Journal of Clinical Oncology (2011)

e18038 Background: Pem and Beva are particularly active against lung adenocarcinoma. Ox has less haematological toxicity than cisplatin and carboplatin, and its efficacy in NSCLC has been established by phase 2 studies. The Pem-Ox-Beva triplet is a well tolerated and active second-line regimen in pts with stage IV NSCLC (Heist R. S. et al, ASCO 2007), but its role as first-line therapy remains to define. Methods: From August 2008 to October 2010, consecutive chemo-naïve pts with stage IV lung adenocarcinoma received Pem 500 mg/m2, Ox 100 mg/m2 and Beva 7.5 mg/kg every 3 weeks for 6 cycles, in the outpatient setting. For pts with response or stable disease, Pem and Beva were continued until disease progression or unacceptable toxicity. The primary evaluation criterion was safety. Secondary evaluation criteria were RR, PFS and OS. Results: All pts (n = 33, 51.5% males, 57.6% smokers, median age: 54 years, range 38-76) were eligible for toxicity and efficacy analysis. Thirteen pts (39.4%) had a PS of 2, 6 pts (18.2%) had CNS metastases and 5 pts (15.2%) had liver metastases. A total of 175 cycles (median/pt: 6, range 2-6) were given, plus 75 cycles of maintenance therapy. The more frequent toxicities were hypertension (grade 2-3: 12 pts, 36.4%), hoarseness (grade 2: 11 pts, 33.3%) and peripheral neuropathy (grade 2-3: 6 pts, 18.2%). Grade 3-4 haematological toxicities were grade 4 neutropenia (1 pt, 3.0%) and grade 3 thrombocytopenia (2 pts, 6.1%). Neither febrile neutropenia nor thrombo-embolic event occurred. Two unscheduled hospitalizations were required: 1 pt had grade 3 haemoptysis, and another pt. had wound healing impairment after central venous access insertion. The objective RR was 54.6% (95%CI: 37.6-71.5). At a median follow-up of 11.1 months (range: 1.5-26.6), the median PFS and OS were 6.4 (95%CI: 5.4-9.0) and 14.6 (95%CI: 9.6-19.5) months respectively. Conclusions: The combination of Pem, Ox and Beva was well tolerated and had promising activity as first-line therapy in unselected pts with lung adenocarcinoma. These results justify further prospective studies in this pts population.
Adjuvant chemoradiotherapy for gastric adenocarcinoma: Kaiser institutional experience with INT 0116
Authors: T. L. Kerwin, M. J. Miller, M. A. Tome
Journal: Journal of Clinical Oncology (2006)

14114 Background: The standard of care for resectable gastric or gastroesophageal adenocarcinoma is total or partial gastrectomy followed by adjuvant chemoradiotherapy as defined by the Intergroup 0116 study. We have reviewed our institutional experience with this regimen in hopes of defining patient subsets which are most likely to benefit, as well as those who are least likely to benefit, such that alternative therapies may be recommended. Methods: A retrospective review was conducted for 38 consecutive patients treated for gastric or gastroesophageal adenocarcinoma with total or partial gastrectomy followed by chemoradiotherapy. Chemotherapy was with 5-FU 425 mg/m 2 /day and Leukovorin 20 mg/m 2 . Radiotherapy was with 45 Gy in 25 fx delivered through AP-PA fields or a 3-field technique, at the discretion of the treating physician. Results: The median patient age is 55 years old. The median follow-up is 29 months. There were 14 D0 resections, 21 D1 resections, and 3 D2 resections. The number of patients with N0, N1, N2, and N3 disease are respectively 4, 20, 11, 3. One patient did not complete treatment due to disease progression. There were positive margins in 8 patients. Four patients developed fatal treatment-related complications. Median overall survival for patients with positive margins is 19 months and for negative margins is 34 months. Median overall survival for N0/N1 patients is 36 months and for N2/N3 patients is 22 months. Eighteen patients recurred at a median of 14 months - 5 locally, 9 regionally in the abdomen, and 4 distantly. Death occurred in 16/18 recurrences. Conclusions: The overall survival of patients in this study is consistent with previously-reported data. The adequacy of surgical resection is relevant as it affects nodal staging. Positive margin status and advanced nodal involvement are predictors for poor outcomes, indicating that alternative therapies may be more appropriate for these patients given the potential toxicity of the current recommended treatments. No significant financial relationships to disclose.
Treatment of Ras mutation-bearing solid tumors using whole recombinant <i>S. cerevisiae</i> yeast expressing mutated Ras: Preliminary safety and immunogenicity results from a phase 1 trial
Authors: A. Cohn, M. A. Morse, B. O’Neil, D. Bellgrau, R. C. Duke, A. J. Franzusoff, S. Munson, J. Ferraro, T. C. Rodell
Journal: Journal of Clinical Oncology (2005)

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