Is PCNA unloading the central function of the Elg1/ATAD5 replication factor C-like complex?

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Expressional patterns of chaperones in ten human tumor cell lines

BACKGROUND: Chaperones (CH) play an important role in tumor biology but no systematic work on expressional patterns has been reported so far. The aim of the study was therefore to present an analytical method for the concomitant determination of several CH in human tumor cell lines, to generate expressional patterns in the individual cell lines and to search for tumor and non-tumor cell line specific CH expression. Human tumor cell lines of neuroblastoma, colorectal and adenocarcinoma of the ovary, osteosarcoma, rhabdomyosarcoma, malignant melanoma, lung, cervical and breast cancer, promyelocytic leukaemia were homogenised, proteins were separated on two-dimensional gel electrophoresis with in-gel digestion of proteins and MALDI-TOF/TOF analysis was carried out for the identification of CH. RESULTS: A series of CH was identified including the main CH groups as HSP90/HATPas_C, HSP70, Cpn60_TCP1, DnaJ, Thioredoxin, TPR, Pro_isomerase, HSP20, ERP29_C, KE2, Prefoldin, DUF704, BAG, GrpE and DcpS. CONCLUSIONS: The ten individual tumor cell lines showed different expression patterns, which are important for the design of CH studies in tumor cell lines. The results can serve as a reference map and form the basis of a concomitant determination of CH by a protein chemical rather than an immunochemical method, independent of antibody availability or specificity

The Prognostic Implications of Cystic Change in Clear Cell Renal Cell Carcinoma

Background : Cystic renal cell carcinoma has been reported to have a good prognosis. However, previous studies included cases of multilocular cystic renal cell carcinoma, which has an excellent prognosis, and renal cell carcinoma with cystic necrosis, which has an adverse prognosis. Therefore, we analyzed the prognostic influence of cystic change in clear cell renal cell carcinoma after excluding those morphological features. Methods : We identified 225 patients with clear cell renal cell carcinoma who underwent nephrectomy between 2001 and 2003. The clinicopathologic features were compared with clinical outcomes. Results : Cystic change in clear cell renal cell carcinoma (n = 66) was significantly associated with younger patient age (< 55), smaller tumor size (<= 4 cm), lower pT stage (pT1, T2), M0 stage at initial diagnosis, lower tumor, node, and metastasis stage (I, II), and lower nuclear grade (1, 2). Patients with cystic change in clear cell renal cell carcinoma had significantly longer cancer-specific (p = 0.015) and progression-free survival (p = 0.004) than those without cystic change, by univariate analysis. Multivariate analysis revealed that cystic change significantly decreased the risk of cancer progression (risk ratio, 0.27; 95% confidence interval, 0.11 to 0.69). Conclusions : In patients with clear cell renal cell carcinoma, cystic change is a good independent predictor for survival.This work was supported by grant No. 04-2009-007 from the SNUH Research Fund.Jemal A, 2009, CA-CANCER J CLIN, V59, P225, DOI 10.3322/caac.20006Lopez-Beltran A, 2009, INT J UROL, V16, P432, DOI 10.1111/j.1442-2042.2009.02302.xGobbo S, 2008, AM J SURG PATHOL, V32, P1239Gong K, 2008, J CANCER RES CLIN, V134, P433, DOI 10.1007/s00432-007-0302-1Webster WS, 2007, UROLOGY, V70, P900, DOI 10.1016/j.urology.2007.05.029Lopez-Beltran A, 2006, EUR UROL, V49, P798, DOI 10.1016/j.eururo.2005.11.035Suzigan S, 2006, AM J CLIN PATHOL, V125, P217, DOI 10.1039/AH6FC77PYR2V6YAYFrank I, 2005, J UROLOGY, V173, P1889, DOI 10.1097/01.ju.0000158043.94525.d6Patard JJ, 2005, J CLIN ONCOL, V23, P2763, DOI 10.1200/JCO.2005.07.055Kim H, 2004, HUM PATHOL, V35, P1556, DOI 10.1016/j.humpath.2004.06.011Ficarra V, 2004, EUR UROL, V46, P559, DOI 10.1016/j.eururo.2004.07.002Han KR, 2004, UROL ONCOL-SEMIN ORI, V22, P410, DOI 10.1016/S1078-1439(03)00173-XImura J, 2004, APMIS, V112, P183Cheville JC, 2003, AM J SURG PATHOL, V27, P612Frank I, 2002, J UROLOGY, V168, P2395, DOI 10.1097/01.ju.0000035885.91935.d5Nassir A, 2002, UROLOGY, V60, P421GREENE FL, 2002, AJCC CANC STAGING MACorica FA, 1999, J UROLOGY, V161, P408Bielsa O, 1998, BRIT J UROL, V82, P16USUBUTUN A, 1998, INT UROL NEPHROL, V30, P391LYNCH CF, 1995, CANCER, V75, P316HARTMAN DS, 1986, UROLOGY, V28, P145

Anti-proliferative effects of Bifidobacterium adolescentis SPM0212 extract on human colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as anti-tumor activity. The aim of the present work was to study the growth inhibition of tumor cells by butanol extract of <it>Bifidobacterium adolescentis </it>isolated from healthy young Koreans.</p> <p>Methods</p> <p>The anti-proliferative activity of <it>B. adolescentis </it>isolates was assessed by XTT assays on three human colon cancer cell lines (Caco-2, HT-29, and SW480). The effects of <it>B. adolescentis </it>SPM0212 butanol extract on tumor necrosis factor-α (TNF-α) and nitric oxide (NO) production were tested using the murine macrophage RAW 264.7 cell line.</p> <p>Results</p> <p>The butanol extract of <it>B. adolescentis </it>SPM0212 dose-dependently inhibited the growth of Caco-2, HT-29, and SW480 cells by 70%, 30%, and 40%, respectively, at 200 μg/mL. Additionally, the butanol extract of <it>B. adolescentis </it>SPM0212 induced macrophage activation and significantly increased the production of TNF-α and NO, which regulate immune modulation and are cytotoxic to tumor cells.</p> <p>Conclusion</p> <p>The butanol extract of <it>B. adolescentis </it>SPM0212 increased activity of the host immune system and may improve human health by helping to prevent colon cancer as a biological response modifier.</p

Serum Levels of Interleukin-8 and Tumor Necrosis Factor-alpha in Coal Workers' Pneumoconiosis: One-year Follow-up Study

Objectives: Various cytokines induced by inhalation of coal dust may mediate inflammation and lead to tissue damage or fibrosis, such as coal workers' pneumoconiosis (CWP).Methods: To investigate the relevance of serum cytokines in CWP, the levels of serum interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α) as CWP biomarkers in 110 retired coal miners (22 controls and 88 CWP subjects) were related to cross sectional findings and 1-year progressive changes of the pneumoconiosis. Progressive changes of CWP were evaluated by paired comparison of chest radiographs. Analysis by a receiver operating characteristic (ROC) curve assessed the biomarker potential of each cytokine.Results: The mean serum IL-8 level was significantly higher in CWP compared to controls and IL-8 levels correlated with the degree of CWP. The median serum TNF-α level was significantly higher in subjects with progressive CWP compared to subjects without CWP progression. The area under the ROC curve for IL-8 (0.70) and TNF-α (0.72) for CWP identification and progression, respectively, indicated the biomarker potential of the two cytokines. Serum cutoff values of IL-8 and TNF-α were 11.63 pg/ml (sensitivity 69%; specificity 64%) and 4.52 pg/ml (sensitivity 67%; specificity 79%), respectively.Conclusion: The results suggest that high levels of serum IL-8 are associated with the presence of CWP and those of serum TNF-α are associated with the progression of CWP

A multicenter, prospective, randomized, controlled trial evaluating the safety and efficacy of intracoronary cell infusion mobilized with granulocyte colony-stimulating factor and darbepoetin after acute myocardial infarction: study design and rationale of the 'MAGIC cell-5-combination cytokine trial'

<p>Abstract</p> <p>Background</p> <p>Bone marrow derived stem/progenitor cell transplantation after acute myocardial infarction is safe and effective for improving left ventricular systolic function. However, the improvement of left ventricular systolic function is limited. This study will evaluate novel stem/progenitor cell therapy with combination cytokine treatment of the long-acting erythropoietin analogue, darbepoetin, and granulocyte colony-stimulating factor (G-CSF) in patients with acute myocardial infarction.</p> <p>Methods</p> <p>The 'MAGIC Cell-5-Combination Cytokine Trial' is a multicenter, prospective, randomized, 3-arm, controlled trial with blind evaluation of the endpoints. A total of 116 patients will randomly receive one of the following three treatments: an intravenous darbepoetin infusion and intracoronary infusion of peripheral blood stem cells mobilized with G-CSF (n = 58), an intracoronary infusion of peripheral blood stem cells mobilized with G-CSF alone (n = 29), or conventional therapy (n = 29) at phase I. Patients with left ventricular ejection fraction < 45% at 6 months, in the patients who received stem cell therapy at phase I, will receive repeated cell therapy at phase II. The objectives of this study are to evaluate the safety and efficacy of combination cytokine therapy with erythropoietin and G-CSF (phase I) and repeated progenitor/stem cell treatment (phase II).</p> <p>Discussion</p> <p>This is the first study to evaluate the safety and efficacy of combination cytokine based progenitor/stem cell treatment.</p> <p>Trial registration</p> <p><url>http://www.ClinicalTrials.gov</url> identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00501917">NCT00501917</a>.</p

High dose therapy followed by autologous peripheral blood stem cell transplantation as a first line treatment for multiple myeloma: a Korean Multicenter Study.

We conducted a phase II multicenter trial to estimate the response and survival of patients with newly diagnosed multiple myeloma to high dose melphalan therapy followed by autologous peripheral blood stem cell transplantation. Eligible patients who had undergone induction with vincristine, adriamycin and dexamethasone (VAD) should have adequate cardiac, pulmonary and renal function (creatinine <2 mg/dL). Melphalan at 200 mg/m2 was used as a conditioning regimen. Eighty patients were enrolled from 13 centers. The median age of the patients was 53 yr (range; 20 to 68 yr). The initial stage was IA/IIA/IIB/IIIA/IIIB in 3/8/1/54/14 patients, respectively. Beta2-microglobulin, CRP and LDH were increased in 74, 42 and 34% of the patients examined. Cytogenetic data were available in 30 patients, and 6 patients showed numeric or structural abnormalities. Two therapy-related mortalities occurred from infection. Among the 78 evaluable patients, CR/PR/MR/NC/PD were achieved in 48/26/2/1/1 patients, respectively. After a median follow-up of 30 months, the median overall and event-free survivals were 66 months (95% CI: 20-112) and 24 months (95% CI: 18-29), respectively. This study verifies the efficacy and feasibility of high dose melphalan therapy with autologous stem cell transplantation in newly diagnosed multiple myeloma