tbuckley/cabot-search huggingface dataset:
The relationship between RASSF1A aberrant methylation and survival in small sized lung adenocarcinoma
Authors: K. Miyajima, T. Ohira, J. Usuda, H. Saji, M. Tsuboi, T. Hirano, H. Kato, M. Suzuki, S. Toyooka, A. F. Gazdar
Journal: Journal of Clinical Oncology (2006)

7199 Background: Aberrant methylation of CpG islands in promoter regions of tumor cells is one of the major mechanisms for silencing of tumor suppressor genes. The RAS association domain family 1A (RASSF1A) gene was isolated from the 3p21.3 region homozygously deleted in lung cancer cell lines, and it was shown to be inactivated by hypermethylation of the promoter region in lung cancers. In this study, we investigated the clinicopathological significances of RASSF1A methylation in the development and/or progression of small-sized (less than 2.0cm) lung adenocarcinoma. It is important to identify a marker for high-risk early stage patients who should benefit from new investigational adjuvant therapies. Methods: Surgically resected specimens from 77 cases of small-sized primary lung adenocarcinoma. We determined the frequency of aberrant promoter methylation of the RASSF1A genes in small-sized adenocarcinoma. Aberrant promoter methylation was examined using methylation-specific PCR (MSP). Results: Twenty-five of 77 (32.5%) tumors showed RASSF1A methylation. RASSF1A methylation was dominantly detected in smoker (P &lt; 0.03). There was no significant correlation of RASSF1A methylation with gender, age, T stage, N stage and pathological stage. RASSF1A methylation correlated with adverse survival by univariate analysis (P &lt; 0.005) as well as multivariate analysis (P = 0.0062; RR 4.251; 95% C.I., 1.507–11.993). Furthermore, RASSF1A promoter hypermethylation in resected stage I small-sized lung adenocarcinoma was associated with impaired patient survival (P &lt; 0.01). Conclusions: Aberrant promoter methylation of the RASSF1A was present in 25 of 77 (32.5%) of small-sized lung adenocarcinoma by MSP assay. These results indicated that epigenetic inactivation of RASSF1A plays an important role in the progression of small-sized lung adenocarcinoma, and that RASSF1A hypermethylation appears to be a useful molecular marker for the prognosis of patients with small-sized and stage I lung adenocarcinoma. RASSF1A is a potential tumor suppressor gene that undergoes epigenetic inactivation in lung adenocarcinoma through hypermethylation of its promoter region. RASSF1A methylation was significantly related to unfavorable prognosis in small-sized lung adenocarcinoma. No significant financial relationships to disclose.
Abstract 16499: Association of Soluble Endothelial Cell Selective Adhesion Molecule (sESAM) with Cardiovascular Outcomes in Patients with Stable Ischemic Heart Disease: A Report from the Heart and Soul Study
Authors: Ameya Kulkarni, Alexis Beatty, Peter Ganz, Mathilda Regan, Mary Whooley
Journal: Circulation (2012)

Introduction:  Recently discovered endothelial cell-selective adhesion molecule (ESAM) is selectively expressed on vascular endothelium and activated platelets and is postulated to play a role in atherogenesis. We investigated the association of serum ESAM (sESAM) levels with subsequent cardiovascular outcomes in a cohort of patients with stable ischemic heart disease.   Methods:  We measured sESAM levels in 985 patients with stable ischemic heart disease enrolled between September 2000 and December 2002 in a prospective cohort study. Cox proportional hazards models were used to define the relationship between baseline sESAM levels and cardiovascular outcomes (composite of myocardial infarctions, all-cause mortality and heart failure hospitalizations).   Results:  There were 451 occurrences of the composite endpoint over a median follow-up of 8.9 years. Events occurred more frequently in participants with sESAM levels in the highest quartile, 64% (158/246) vs. 34% (83/247) in the lowest quartile (p   Conclusion:  ESAM levels are robustly associated with myocardial infarction, heart failure, and death after adjusting for demographic and clinical risk factors. The link between ESAM, cardiovascular risk and renal disease deserves further exploration.
Incidence of deep venous thrombosis associated with central venous catheters (DVT-CVC) in cancer patients: A multicenter study
Authors: J. Feliu, R. Lecumberri, A. Jerez, A. Cantalapiedra, T. García, E. Gonzalez, J. García Frade, V. Vicente, E. Rocha
Journal: Journal of Clinical Oncology (2006)

8627 Background: The reported incidence of DVT-CVC is extremely variable (0.3–28.3% for symptomatic thrombosis and 27–66% for asymptomatic thrombosis). Data in regarding new catheter materials and insertion techniques are very limited. Likewise, the use of antithrombotic prophylaxis in cancer patients with a CVC remains debatable. Methods: A prospective epidemiologic study was performed, which included adult patients with active cancer and no history of venous thromboembolism, in whom a long term CVC was inserted. Patients were followed-up for 90 days and a bilateral upper extremity Doppler-ultrasound was performed on days 45±5 and 90±5. Likewise, basal blood samples were taken and have been analyzed for hypercoagulability markers and prothrombotic factors. Results: Inclusion period lasted from July 2004 until May 2005. 141 patients have completed the follow up, with a mean age of 52.1±14.3 years (range 21–87). The cumulative incidence of DVT-CVC was 14.2% (20/141): 6.4% were symptomatic (9/141) and 8.9% were asymptomatic (11/123). All thrombotic events, excluding 4 cases, occurred before day 45. Neither age, gender, type of tumor (solid or haematological cancer), tumor stage, type of CVC (Port or tunnelled), number of lumens, side of insertion, platelet count or use of antithrombotic prophylaxis were significantly associated with the incidence of DVT-CVC, although only 1/8 patients with DVT-CVC receiving antithrombotic prophylaxis (12.5%) used high risk prophylaxis. Patients with prior central catheters tended to have a greater incidence of DVT-CVC (P=0.10). None of the basal plasma markers analyzed (fibrinogen, D dimer, F VIII, proteine C resistance, prothrombin fragments 1+2, thrombin-antithrombin complex) have been significantly associated with increased risk of DVT-CVC. Conclusions: DVT-CVC is a frequent complication in cancer patients, as with solid tumors so with haematologic malignancies. The incidence of DVT-CVC seems to be specially high the first few weeks following catheter placement. None of the basal plasma markers analyzed in this study have been associated with the incidence of DVT-CVC. New studies must be performed to allow identification of at risk patients who might benefit from antithrombotic prophylaxis. No significant financial relationships to disclose.
Antibody to Herpes Simplex Virus Type 2-Induced Nonstructural Proteins in Women With Cervical Cancer and in Control Groups&lt;xref ref-type="fn" rid="fn2"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: T Anzai, G R Dreesman, R J Courtney, E Adam, W E Rawls, M Benyesh-Melnick
Journal: JNCI Journal of the National Cancer Institute (1975)

Sera obtained from 15 patients with cervical cancer, 10 patients with breast cancer, and 15 control women, individually matched with the cervical cancer patients, were examined for antibodies to early proteins synthesized in herpes simplex virus type 2 (HSV-2)-infected cells. The method used was an indirect radioimmune precipitation test followed by polyacrylamide gel electrophoretic analysis of immune precipitates. The relative reactivity to a major early nonstructural protein (VP134) was used to compare these selected sera. The results obtained suggest that cervical cancer patients possess sera with a higher reactivity to VP134 than breast cancer patients or matched healthy women,and that serum reactivity is independent of the level of neutralizing antibodies to HSV-2.
Pirarubicin (THP) therapy for elderly aggressive non-Hodgkin’s lymphoma— T-COP vs reduced CHOP, and reduced T-COP in the patients with poor physical status
Authors: M. Mori, M. Oota, H. Taguchi, T. Ohno, M. Tanimoto, A. Miyata, T. Naoe, Y. Murai, M. Masuda
Journal: Journal of Clinical Oncology (2006)

17571 Background: We have previously reported that T-COP using pirarubicin (THP) is useful in treatment of NHL in elderly patients. In the present study on elderly aggressive NHL, the usefulness and safety were compared between THP and ADM using the optimum dose of THP (ML1). In patients with poor physical status, reduced dose T-COP was conducted (ML2). Methods: ML1 protocol: PS 0–3 and Alb ≥ 3.0 g/dl Patients in their 70s were assigned randomly to either T-COP (A group) or CHOP (B group) receiving THP (A) or ADM (B) 40 mg/m 2 ,CPA 650 mg/m 2 , VCR 1 mg/m 2 dayl, P 40 mg/m 2 dayl -5. Patients in their 80s were assigned randomly to either T-COP (C) or CHOP (D) receiving THP (C) or ADM (D) 30, CPA 400, VCR 1, P 30. ML2 protocol: PS 4 or Alb &lt; 3.0 g/dl. Patients in their 70s (E group) received THP 26, CPA 430, VCR 1, P 40. Patients in their 80s (F group) received THP 20, CPA 260, VCR 1, P 30. Each group underwent 3 courses every 3 weeks. CR (CR+CRu) patients underwent 6 courses or more. Results: Analyzed as competent cases were 173 out of 207 patients who were registered between Aug 99 and Dec 03. The CR rates were A: 83% (39/47), B: 74% (37/50), C: 67% (14/21), D: 74% (14/19), E: 58% (7/12), F: 33% 2/6, and 78% in T-COP (A + C) and 74% in CHOP (B + D). The 5-year survival rates were A: 50%, B: 35% (p &lt; 0.05) and C: 26% D: 55% (p &lt; 0.05.), demonstrating that T-COP in their 70s and CHOP in their 80s were significantly higher. The 5-year survival rate in ML1 was 41%. In multivariate analysis, factors influencing the survival (p &lt; 0.01) in ML1 were age, the primary effect and treatment method. There were no significant differences in PS, CS, LDH and lesions outside nodes. Conclusions: Patients aged 70 years or older had the CR rate at 75.9% and a 5-year survival rate at 41%, demonstrating satisfactory outcomes. The results suggested that in 70s, THP 40 mg/m 2 was more effective than ADM 40 mg/m 2 . In their 80s, ADM30 mg/m 2 was more effective than THP30 mg/m 2 . ML2 was feasible in elderly patients with poor physical status. No significant financial relationships to disclose.
Neoplasms of Urinary Bladders of Hamsters Treated With 2-Acetylaminofluorene and Indole&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Oyasu, H Sumie, H E Burg
Journal: JNCI Journal of the National Cancer Institute (1970)

Tested in hamsters was the effect of neonatal treatment with 2-acetylaminofluorene (AAF) followed by prolonged feeding in combination with indole on the development of bladder tumors. Neonatal males and females were given intraperitoneal injections of AAF, 5 mg/100 g body weight, 3 times weekly until weaning. They were then fed a synthetic diet containing 0.06% AAF and 1.6% indole. The 26 hamsters surviving 10-12 months developed transitional cell carcinomas of the bladder, all but 2 of which were invasive. No hamsters had malignant tumors in the liver. Seven hamsters developed peliosis of the spleen.
Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition
Authors: Aaron N Hata, Matthew J Niederst, Hannah L Archibald, Maria Gomez-Caraballo, Faria M Siddiqui, Hillary E Mulvey, Yosef E Maruvka, Fei Ji, Hyo-eun C Bhang, Viveksagar Krishnamurthy Radhakrishna, Giulia Siravegna, Haichuan Hu, Sana Raoof, Elizabeth Lockerman, Anuj Kalsy, Dana Lee, Celina L Keating, David A Ruddy, Leah J Damon, Adam S Crystal, Carlotta Costa, Zofia Piotrowska, Alberto Bardelli, Anthony J Iafrate, Ruslan I Sadreyev, Frank Stegmeier, Gad Getz, Lecia V Sequist, Anthony C Faber, Jeffrey A Engelman
Journal: Nature Medicine (2016)
Evaluation of the effects of chemically different linkers on hepatic accumulations, cell tropism and gene silencing ability of cholesterol-conjugated antisense oligonucleotides
Authors: Shunsuke Wada, Hidenori Yasuhara, Fumito Wada, Motoki Sawamura, Reiko Waki, Tsuyoshi Yamamoto, Mariko Harada-Shiba, Satoshi Obika
Journal: Journal of Controlled Release (2016)
Splenectomy and the risk of developing leukemia.
Authors: J Demeter, D Lehoczky
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.11.2287 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8229146 Splenectomy and the risk of developing leukemia. J DemeterxJ DemeterSearch for articles by this author , D LehoczkyxD LehoczkySearch for articles by this author https://doi.org/10.1200/JCO.1993.11.11.2287 PDF "Splenectomy and the risk of developing leukemia.." Journal of Clinical Oncology, 11(11), p. 2287© 1993 by American Society of Clinical Oncology
Abstract P129: G Protein--Coupled Receptor Kinase-2 (GRK2) Is a Novel Regulator of Collagen Synthesis in Adult Human Cardiac Fibroblasts
Authors: Karen M D'Souza, Ricky Malhotra, Jennifer L Philip, Michelle L Staron, Tiju Theccanat, Shahab A Akhter
Journal: Circulation Research (2011)

Cardiac fibroblasts (CF) make up 70% of the total cell number in the heart and play a critical role in regulating normal myocardial function and in adverse remodeling following myocardial infarction. Recent studies have shown that increased intracellular cAMP can inhibit CF transformation and collagen synthesis in adult rat CF; however, mechanisms by which cAMP production is regulated in CF have not been elucidated. The objective of this study was to investigate the potential role of GRK2 in modulating CF transformation to myofibroblasts and collagen synthesis in adult human CF isolated from normal and failing left ventricles. CF isolated from failing ventricles showed a significant increase in expression of collagen I, III and VI compared with controls. α-SMA was increased 2-fold over controls, consistent with CF transformation to myofibroblasts. Baseline collagen synthesis was elevated 2-fold in failing CF and was not inhibited by isoproterenol (ISO)-stimulation in contrast to normal controls. β-adrenergic receptor (β-AR) signaling was markedly uncoupled in failing CF as assessed by basal and ISO-stimulated cAMP production. The primary mechanism appears to be a 2.5-fold increase in GRK2 activity as GRK2 phosphorylates and uncouples agonist-occupied β-ARs. Overexpression of GRK2 in normal CF recapitulated a heart failure phenotype with minimal inhibition of collagen synthesis following ISO stimulation. In contrast, siRNA-mediated knockdown of GRK2 expression in normal CF enhanced cAMP production and led to greater β-agonist-mediated inhibition of basal and TGFβ-stimulated collagen synthesis versus control. Inhibition of GRK2 activity by adenoviral-mediated βARKct expression or GRK2 knockdown in failing CF led to a significant decline in collagen and α-SMA expression. GRK2 inhibition restored β-AR signaling and ISO-stimulated inhibition of collagen synthesis and also significantly decreased collagen synthesis in response to TGFβ stimulation. In conclusion, GRK2 appears to play a significant role in regulating CF transformation and collagen synthesis in adult human CF and increased activity of this kinase may be an important mechanism of maladaptive ventricular remodeling as mediated by cardiac fibroblasts.
원저 : 혈청 Alpha - Fetoprotein ( AFP ) 치가 의미있게 상승하면서 복부 초음파상 종괴가 없는 만성 간질환 환자에서 Lens Culinaris Agglutinin - A 에 반응하는 AFP 분획 측정의 간세포암 진단에 대한 유용성
Authors: 이준성, 윤정환, 이효석, 김정룡 ( June Sung Lee), Jung Hwan Yoon, Hyo Suk Lee, Chung Yong Kim
Journal: Clinical and Molecular Hepatology (1998)

Background/Aims' Lens culinaris agglutinin-A reactive alpha-fetoprotein (AFP L3) has been reported to be highly specific for the diagnosis of hepatocellular carcinoma (HCC). The present study was to evaluate the clinical usefulness of AFP-L3 for the diagnosis of HCC in the patients either with chronic liver disease or with HCC in complete remission who showed significant increment of serum AFP level and no mass lesion in the liver on ultrasonography. Methods' A total numer of 34 patients (24 with chronic liver disease, 10 with HCC in complete remission) were enrolled, who showed significant increment of serum AFP level and no mass lesion in the liver on ultrasonography. Serum AFP L3 levels were analysed by AFP differentiation kit L. Abdominal spiral CT or ultrasonogram was performed at 1-3 month intervals and all of the patients were followed up for more than 6 months. Results- Among 24 patients with chronic liver disease, two were positive (higher than 15%) for AFP L3; however, HCC was not detected in these patients, while HCCs were detected in two of 22 patients negative for AFP L3 during followe-up. Eight of the 10 patients with HCC in complete remission were positive for AFP L3; recurrent HCCs were detected in 7 of those 8 patients as well as in the rest 2 patients negative for AFP L3 during follow-up. The overall sensitivity and specificity of AFP L3 measurement for the detection of HCC within 6 months  of follow-up were 63.6% and 87.0%, respectively. The positive and negative predictive value for HCC in patients with chronic liver disease were O% and 90.9% and for recurrent HCC in HCC patients in remission were 87.5% and ON, respectively. Conclusion - The measurement of AFP L3 is suggested to be useful for the diagnostic strategy in patients either with chronic liver disease or hepatocellular carcinoma in complete remission, who showed progressive increment of serum AFP level and no mass lesion in liver on ultrasonogram. (Korean J Hepatol 1998;4:120 - 130)
Phase II study of capecitabine and cisplatin as first-line therapy in patients with recurrent or metastatic esophageal carcinoma
Authors: J. Lee, Y.-H. Im, J. H. Kang, E. Nam, S.-H. Lee, J.-O. Park, Y.-S. Park, W. K. Kang, K. Park
Journal: Journal of Clinical Oncology (2005)

4221 Background: 5-Fluorouracil and cisplatin remains as the standard treatment for metastatic esophageal carcinoma, producing response rates of 20 - 35% in phase II trials. Preclinical studies suggest synergistic anti-tumor activity of capecitabine (X) and cisplatin (P). XP has demonstrated activity in advanced gastrointestinal cancer (Kim et al, Ann Oncol 2002;13:1893). Methods: This non-randomised open label phase II study evaluated the efficacy and safety of capecitabine 1250 mg/m2 on days 1 to 14 twice daily and cisplatin 60 mg/m2 on day 1 every 21 days as first-line chemotherapy in metastatic or recurrent esophageal cell carcinoma patients. Patients with; histologically proven, bidimensionally measurable, metastatic esophageal squamous cell or adenocarcinoma, age 18 - 75 years, with a performance status 0 - 2, no prior chemotherapy, life expectancy > 3 months, signed written informed consent were eligible. Results: From May 2003 to Nov 2004, 20 patients were prospectively enrolled. The median age was 60 years (47 - 71) and male:female ratio was 19:1. In total, 76 cycles were administered with a median of 4 cycles per patient (range, 1 - 9 cycles), and 17/20 patients were evaluable for response (3 inevaluable pts included; 1 patient with broncho-esophageal fistula after 1st cycle; 1 patient’s refusal for further chemotherapy; too early for assessment in 1 patient). The objective RR was 47.1% (95% CI, 23.4 - 70.8) with no CR and 8 PRs. Six patients (35.3%) had SD and only 3 patients (17.6%) had PD. Median OS of all patients was 11.1 months (95% CI, 9.3 - 13.0 months). Median TTP was 5.8 months (95% CI, 4.0 - 7.6 months). In total of 76 cycles administered, grade 3/4 hematological toxicities were observed as follows: neutropenia (13.2% of all cycles), anemia (1.3%). Grade 3/4 non-hematological toxicities included anorexia (13.2%), constipation (5.3%), and diarrhea (4.0%). Grade II/III hand-foot syndrome occurred in 15% and 10% of patients, respectively. Conclusions: XP chemotherapy showed a very promising preliminary anti-tumor activity and was well tolerated with convenient administration as a first-line treatment for patients with metastatic esophageal carcinoma. Supported by Roche Korea. No significant financial relationships to disclose.
Analysis of correlation between oncogene mutation and response to chemotherapy in all RAS wild type metastatic colorectal cancer, using next-generation sequencing technology.
Authors: Akio Higuchi, Rika Kasajima, Manabu Shiozawa, Masahiro Asari, Masaaki Murakawa, Yusuke Katayama, Koichiro Yamaoku, Toru Aoyama, Amane Kanazawa, Soichiro Morinaga, Yasushi Rino, Makoto Akaike, Munetaka Masuda, Yohei Miyagi
Journal: Journal of Clinical Oncology (2015)

553 Background: Targeted therapies of monoclonal antibodies have changed the treatment of metastatic colorectal cancer (mCRC). A target therapy with chemotherapy regimen for mCRC was decided by KRAS mutation status (KRAS exon2 [codon12, codon13]). Currently, there are many reports suggesting that in addition to analysis of KRAS mutation status, the evaluation of EGFR gene copy number, levels of EGFR ligands, BRAF, NRAS, PIK3CA mutations could be helpful to have a more accurate selection of patients who may have a benefit from anti-EGFR targeted drugs. Methods: Mutation status of 50 oncogenes were analysed in 35 mCRC patients with all RAS wild type, using next-generation sequencing technology. The response for chemotherapy was classified response group (R group) and non-response group (N group) by RECIST. The relation between mutation status of 50 oncogenes and the response for chemotherapy was assessed. Results: There were 25 oncogene mutations in the 50 genes. Driver mutation associated with oncogenic mutation deeply were 5 oncogenes, which were PIK3CA, AKT1, BRAF, PDGFRA and TP53. Only BRAF mutation was significantly associated with poor chemo response in the 5 oncogenes. A case which had two driver mutations was only in the N group. One of the two driver mutations was tumor suppressor gene, TP53. Conclusions: BRAF mutation and the number of driver mutations are key predictors of chemosensitivity in the mCRC cases with all RAS wild type.
Interactions between glomerular mesangial cells, cytokines, and extracellular matrix.
Authors: R B Sterzel, E Schulze-Lohoff, M Weber, S L Goodman
Journal: Journal of the American Society of Nephrology (1992)

This brief overview summarizes recent information on the interactions of glomerular mesangial cells (MC) with soluble cytokines and nonsoluble extracellular matrix (ECM). The presently available knowledge stems largely from glomerular cell culture studies and from experimental work with laboratory animals. ECM production by MC appears to be regulated primarily by the paracrine or autocrine effects of cytokines, such as interleukin 1, platelet-derived growth factor, and transforming growth factor beta. However, ECM itself also affects the behavior of cultured MC, e.g., with regard to cell replication and the production of ECM components and other proteins. At present, little is known about the recognition of ECM and cytokines by MC that allows these interactions to take place. First results indicate that MC, like other cell types, possess surface proteins belonging to the beta 1 integrin family, which serve as specific receptors for ECM molecules. Receptors for the cytokines platelet-derived growth factor, insulin-like growth factor 1, epidermal growth factor, and transforming growth factor beta have also been demonstrated on MC. The expression of various receptors on MC appears to be affected by the ECM substratum. Thus, it is becoming apparent that mesangial ECM is not only important as a mechanical scaffold of the glomerular capillary tuft but that it also contains and conveys information relevant for the regulation of the MC phenotype, e.g., by modulating the MC response to cytokines. The available evidence suggests that alterations of ECM composition in glomerular disease can directly or indirectly affect MC behavior, e.g., by promoting cell replication and further accumulation of ECM, eventually resulting in progressive mesangial and glomerular sclerosis.