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Proliferation Index (proliferation + index)
Kinds of Proliferation Index Selected AbstractsEffect of granulocyte-macrophage colony-stimulating factor on hepatic regeneration after 70% hepatectomy in normal and cirrhotic ratsHPB, Issue 2 2002A Ero Background Post-hepatectomy liver insufficiency is one of the most serious postoperative problems and its prevention is important after major hepatic resection, especially in the cirrhotic liver. Some growth factors and cytokines appear to play important roles in liver regeneration. In the present study we have investigated the effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) on hepatic regeneration after 70% partial hepatectomy (PH) in cirrhotic and non-cirrhotic rats. Methods A rat model of liver cirrhosis was prepared using thioacetamide (TAA) (a dose of 20 mg/100 g body w, intraperitoneally) on three days a week for 12 weeks. Adult male rats were divided into four groups:Group 1 (n = 10) no cirrhosis and no GM-CSF; Group 2 (n = 10) no cirrhosis and GM-CSF; Group 3 (n = 10) cirrhosis and no GM-CSF; and Group 4 (n = 10) cirrhosis and GM-CSF. All the rats underwent a 70% hepatectomy, and GM-CSF was administrated immediately after operation in Groups 2 and 4. On postoperative days 2 and 7, fresh samples from the remnant liver were obtained to evaluate its regenerative capacity. The liver regenerative process was estimated by DNA synthesis, using flow cytometry. Results Proliferation index (PI) of hepatocytes at 48 h was higher in Group 4 rats than Group 3 rats (p < 0.05). On post-operative day 7, PI was elevated in Group 3 rats compared with Group 4 rats, but this difference was not statistically significant. In non-cirrhotic rats given GM-CSF, PI was increased compared with Group 1 rats at day 2 (p < 0.05), but not at day 7. Conclusions The findings suggest that the proliferative capacity of liver cells is impaired and delayed after 70% PH in cirrhotic rat liver. GM-CSF administration might enhance the liver PI in both normal and TAA-induced cirrhotic rats. [source] In vitro evaluation of the clastogenicity of fumagillinENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 8 2008Jevrosima Stevanovic Abstract Fumagillin, an antibiotic compound produced by Aspergillus fumigatus, is effective against microsporidia and various Amoeba species, but is also toxic when administered systemically to mammals. Furthermore, a recent in vivo study by Stanimirovic Z et al. 2007: (Mutat Res 628:1,10) indicated genotoxic effects of fumagillin. The aim of the present study was to investigate and explain the clastogenic effects of fumagillin (in the form of fumagillin dicyclohexylamine salt) on human peripheral blood lymphocytes in vitro by sister-chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests. The mitotic index (MI), proliferation index (PI), and nuclear division index (NDI) were calculated to evaluate the cytotoxic potential of fumagillin. Five concentrations of fumagillin (0.34, 0.68, 1.02, 3.07, and 9.20 ,g/ml) were applied to lymphocyte cultures. All the tested concentrations of fumagillin increased the frequency of SCE per cell significantly (P < 0.001 or P < 0.01) compared with the negative control. A significant (P < 0.001) increase in frequency of structural CA was observed at the three highest concentrations in comparison with the negative control. In addition, the three highest test concentrations increased MN formation and decreased MI, PI, and NDI significantly compared with the negative control. The present results indicate that fumagillin is clastogenic and cytotoxic to cultured human lymphocytes. Environ. Mol. Mutagen., 2008. © 2008 Wiley-Liss, Inc. [source] Effect of mangiferin on radiation-induced micronucleus formation in cultured human peripheral blood lymphocytesENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 1 2005Ganesh Chandra Jagetia Abstract Irradiation causes a variety of lesions in important biomolecules of the cell through generation of free radicals leading to genomic instability. DNA strand breaks, acentric fragments, or defective kinetochores are manifested as micronuclei after the first cell division. Chemicals that can trap free radicals may reduce the deleterious effects of ionizing radiation. Mangiferin (MGN), a glucosylxanthone derived from Mangifera indica (mango), was investigated for its ability to reduce the frequency of radiation-induced micronucleated binucleate cells (MNBNCs) in cultured human peripheral blood lymphocytes (HPBLs). HPBL cultures were pretreated with 0, 5, 10, 20, 50, and 100 ,g/ml of MGN for 30 min before exposure to 3 Gy of 60Co ,-radiation. The maximum decline in radiation-induced micronuclei was observed at a concentration of 50 ,g/ml MGN; thereafter, a nonsignificant elevation in MNBNC frequency was observed at 100 ,g/ml MGN. Since the lowest MNBNC frequency was observed for 50 ,g/ml MGN, dose-response studies were undertaken using this concentration. Irradiation of HPBLs with 0, 1, 2, 3, or 4 Gy of ,-radiation caused a dose-dependent elevation in the MNBNC frequency, while treatment of HPBLs with 50 ,g/ml MGN 30 min before radiation resulted in significant declines in these frequencies. MGN alone did not alter the proliferation index. Irradiation caused a dose-dependent decline in the proliferation index, while treatment of HPBLs with 50 ,/ml MGN significantly elevated the proliferation index in irradiated cells. MGN treatment reduced hydrogen peroxide-induced lipid peroxidation in HPBLs in a concentration-dependent fashion. In cell-free studies, MGN inhibited the induction of ·OH (hydroxyl), O2·, (superoxide), DPPH (1,1-diphenyl-2-picrylhydrazyl), and ABTS·+ (2,2-azino-bis-3-ethyl benzothiazoline-6-sulphonic acid) radicals in a dose-dependent manner. The results of this study indicate that MGN possesses radioprotective properties by suppressing the effects of free radicals. Environ. Mol. Mutagen. 45:000,000, 2005. © 2005 Wiley-Liss, Inc. [source] Altered patterns of the interferon-inducible gene IFI16 expression in head and neck squamous cell carcinoma: immunohistochemical study including correlation with retinoblastoma protein, human papillomavirus infection and proliferation indexHISTOPATHOLOGY, Issue 6 2004B Azzimonti Aims:, To investigate whether the expression of interferon (IFN)-inducible gene IFI16 is inversely related to proliferative activity in vivo, we compared immunohistochemical reactivity of IFI16 in a series of head and neck squamous cell carcinomas (HNSCCs) with their proliferation index and the cell cycle regulator pRb. As human papillomavirus (HPV) infection is manifested by changes in the function or expression level of host genes such as IFN-inducible genes, we also investigated the presence of HPV DNA to determine whether head and neck cancers associated with HPV DNA can be distinguished from tumours that are presumably transformed by other mechanisms. Methods:, Thirty-six HNSCCs were evaluated for IFI16, pRb and Ki67 expression by immunohistochemistry. The presence of HPV was also detected by polymerase chain reaction. Nine tumours were located in the oropharynx (tonsillar area) and 27 in the larynx. Results:, HPV DNA was found in 14 of 25 (56%) laryngeal SCCs and in five of nine (56%) tonsillar SCC specimens examined; 17 out of the 19 HPV-DNA-positive cases showed high-grade IFI16 expression. Overall, proliferative activity was significantly related to tumour differentiation and histological grading. IFI16 protein expression was significantly inversely correlated with Ki67 (P = 0.039). Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. Conclusions:, To our knowledge, this is the first expression analysis of the IFN-inducible IFI16 gene in HNSCC. Low-proliferating tumours positive for IFI16 staining showed a marked expression of pRb and a better prognosis than those whose tumours had low IFI16, pRb levels and a high proliferation index. [source] Apoptotic activity in gestational trophoblastic disease correlates with clinical outcome: assessment by the caspase-related M30 CytoDeath antibodyHISTOPATHOLOGY, Issue 3 2001P M Chiu The objective of this study was to assess apoptotic activity in gestational trophoblastic disease (GTD) and its prognostic value in hydatidiform mole (HM). Expression of the specific caspase cleavage site within cytokeratin 18 was assessed immunohistochemically using the monoclonal antibody M30 CytoDeath in 12 spontaneous abortions, 22 partial and 57 complete HM, eight choriocarcinoma (CCA) and 28 normal placentas. The M30 immunoreactivity occurred predominantly in the syncytiotrophoblasts. A significantly higher M30 index in HM and CCA was found when compared with normal placentas and spontaneous abortions (P < 0.001). The M30 index of those HM which spontaneously regressed was significantly higher than those HM which developed persistent disease requiring chemotherapy (P < 0.001). The M30 index correlated with another apoptotic index previously detected by TdT-mediated dUTP nick-end labelling (TUNEL) (P = 0.007) and the proliferation index assessed by the Ki67 antigen (P = 0.034). We conclude that apoptosis is important in the pathogenesis of GTD. Assessment of apoptotic activity in HM by the M30 index may be considered as an alternative prognostic indicator for predicting the clinical behaviour. [source] The degradation of cell cycle regulators by SKP2/CKS1 ubiquitin ligase is genetically controlled in rodent liver cancer and contributes to determine the susceptibility to the diseaseINTERNATIONAL JOURNAL OF CANCER, Issue 5 2010Diego F. Calvisi Abstract Previous work showed a genetic control of cell cycle deregulation during hepatocarcinogenesis. We now evaluated in preneoplastic lesions, dysplastic nodules and hepatocellular carcinoma (HCC), chemically induced in genetically susceptible F344 and resistant Brown Norway (BN) rats, the role of cell cycle regulating proteins in the determination of a phenotype susceptible to HCC development. p21WAF1, p27KIP1, p57KIP2 and p130 mRNA levels increased in fast growing lesions of F344 rats. Lower/no increases occurred in slowly growing lesions of BN rats. A similar behavior of RassF1A mRNA was previously found in the 2 rat strains. However, p21WAF1, p27KIP1, p57KIP, p130 and RassF1A proteins exhibited no change/low increase in the lesions of F344 rats and consistent rise in dysplastic nodules and HCC of BN rats. Increase in Cks1-Skp2 ligase and ubiquitination of cell cycle regulators occurred in F344 but not in BN rat lesions, indicating that posttranslational modifications of cell cycle regulators are under genetic control and contribute to determine a phenotype susceptible to HCC. Moreover, proliferation index of 60 human HCCs was inversely correlated with protein levels but not with mRNA levels of P21WAF1, P27KIP1, P57KIP2 and P130, indicating a control of human HCC proliferation by posttranslational modifications of cell cycle regulators. [source] Establishment, characterization and drug sensitivity testing in primary cultures of human thymoma and thymic carcinomaINTERNATIONAL JOURNAL OF CANCER, Issue 12 2008Volker Ehemann Abstract Thymomas and thymic carcinomas are peculiar epithelial tumors of the anterior mediastinum. They may show aggressive clinical behavior and are a paradigm for the interaction between the tumor and the immune system. So far, adequate functional studies enabling a better understanding of this malignancy have not been performed, since human thymoma/thymic carcinoma cell lines have not been available. Here, the authors describe the establishment, characterization and functional analyses of epithelial cell lines from a Type B1-thymoma and a poorly differentiated thymic carcinoma. By Fluorescence-activated cell sorting (FACS) analyses, both cell lines were aneuploid. The aneuploid cell fraction of the thymic carcinoma cell line was characterized by a high proliferation index of 55.9%, in contrast to a lower proliferation rate of the aneuploid cell fraction of the thymoma (19.7%). Array-based comparative genomic hybridization (aCGH) and conventional cytogenetic analysis of the thymoma revealed only minor imbalances whereas the thymic carcinoma was characterized by a complex karyotype in the hyperdiploid range that was readily defined with multicolor FISH (mFISH). Application of a selective COX-2 inhibitor reduced cell viability in both cell lines in a dose-dependent manner. In conclusion, these first cell lines of a thymoma and a CD5-positive thymic carcinoma are useful tools for further in vitro studies of cellular, molecular and genetic aspects of the disease and for functional tests to evaluate new therapeutic targets. © 2008 Wiley-Liss, Inc. [source] Flaxseed attenuates the tumor growth stimulating effect of soy protein in ovariectomized athymic mice with MCF-7 human breast cancer xenograftsINTERNATIONAL JOURNAL OF CANCER, Issue 4 2006Niina M. Saarinen Abstract In several epidemiological studies, a phytoestrogen-rich diet containing lignans and isoflavones is associated with reduced breast cancer risk, but experimental findings are controversial. In postmenopausal mammary cancer xenograft model, flaxseed (FS), a rich source of plant lignans, reduced breast cancer growth, while soy protein (SP), a rich source of isoflavones, enhanced it. The intake of phytoestrogens is increasing particularly among postmenopausal women, emphasizing the importance of elucidating their interactive effects on breast cancer. Our study determined the effect of FS and SP diets, alone and in combination, on the established human breast cancer MCF-7 tumor growth in ovariectomized athymic nude mice. Tumor bearing mice were divided into 4 groups and fed for 25 weeks either the basal diet (BD), or BD supplemented with 10% FS, 20% SP or 10% FS and 20% SP. After estrogen deprivation, FS regressed the tumor size similar to that of control. SP initially regressed the tumors but starting at week 13, the tumors regressed significantly less than in control and 43% of the tumors were regrowing until the end of the experiment and were significantly larger in size than in control. The combination of SP with FS reduced the tumor growth similar to that of control, as suggested also by the reduced tumor cell proliferation index. In conclusion, dietary FS did not stimulate the growth of estrogen responsive MCF-7 cancers in ovariectomized mice, while long-term consumption of SP did. Furthermore, FS reduced the tumor growth stimulating effect of SP to the same level as control, suggesting tumor growth attenuating effect of FS. © 2006 Wiley-Liss, Inc. [source] Apoptosis in prostate cancer: Bax correlation with stageINTERNATIONAL JOURNAL OF UROLOGY, Issue 4 2005ZAHRA AMIRGHOFRAN Abstract Background:, Dysregulation of apoptosis may contribute to the process of prostate tumorigenesis by reducing the rate of cell death. Bcl-2 and bax are important molecules involved in the regulation of apoptosis. The aim of the present study is to examine apoptosis and related regulatory molecular markers in a group of Iranian patients with prostate cancer. Methods:, Paraffin-embedded tissues from 50 patients of prostate carcinoma were examined for the expression of bcl-2 antiapoptotic and bax proapoptotic markers and also proliferation marker, Ki-67, by immunohistochemistry. Detection of apoptotic cells was performed using TUNEL method. Correlation between apoptotic index, proliferation index and bcl-2 and bax expression with stage, pathological grade and Gleason score was determined. Results:, Apoptosis was detected in 12% of prostate cancers. No correlation was observed between apoptosis and differentiation status of carcinoma. Bcl-2 expression was detected in 21 of samples. A significant correlation between bcl-2 expression and Ki-67 staining index (r = 0.349, P = 0.012) was observed. High bax protein expression was shown in our study. We found a significant correlation between bax expression and stage of carcinoma (r = 0.388, P = 0.031), but not with the apoptosis index, suggesting the presence of a non-functional bax protein or the role of other proapoptotic molecules. Conclusion:, The patients in the present study showed a different pattern of apoptosis positivity compared to other reports. Bax expression may be a useful marker for prognosis of prostate cancer. [source] Angiogenic and lymphangiogenic microvessel density in recurrent pleomorphic adenomaJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2009Andresa B. Soares Background:, Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to determine if there is a difference between RPA and the pleomorphic adenoma (PA) without recurrence related to tumor blood and lymphatic vascularization. Moreover, we compared the microvessel density (MVD) between cell-rich areas (predominance of epithelial cells) and cell-poor areas (predominance of myxoid and chondroid areas) of the stroma of PA and RPA. In addition, immunohistochemical staining for the Ki-67 antigen was conducted simultaneously to evaluate cell proliferation in PA and RPA. Methods:, A total of 19 cases of PA and 24 cases of RPA, blood, and lymphatic vessels were analyzed by immunohistochemical technique using the antibodies CD34, CD105, D2-40, and Ki-67. Results:, Comparing no recurrent with recurrent tumor, no significant difference was found in terms of lymphatic vessel density, MVD, and proliferation index. When MVD and proliferation index were compared with different areas in cellular composition (cell-rich and cell-poor areas), there was a significant difference in PA, as well as in RPA. Conclusion:, This study shows that although RPA presents more aggressive clinical behavior than PA, there is no difference between tumor blood and lymphatic vascularization, suggesting that there is no correlation between vascularity and risk of recurrence. Furthermore, vascularized stroma in PA, as well as RPA, depends on the proportion of the cellular composition. [source] Low Ki-67 proliferation index is an indicator of poor prognosis in gastric cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 3 2010Hee Eun Lee MD Abstract Background and Objectives We designed this study to assess the biologic significance of Ki-67 proliferation index (PI) in gastric cancer. Methods Gastric cancer tissue from 245 patients were immunostained for Ki-67. Ki-67 PI was defined as the percentage of tumor cells positive for Ki-67. In addition, we have previously evaluated the expressions of nine epithelial mesenchymal transition (EMT)-related proteins. The relationship between Ki-67 PI and clinicopathologic parameters, patient survival, and EMT data were sought. Results Low Ki-67 PI was correlated with poorly differentiated histology (P,=,0.034), an advanced T stage (P,<,0.001), and lymph node metastasis (P,=,0.011). Also, the low PI group was found to have a significantly worse prognosis than the high PI group (P,=,0.003, log-rank test). Multivariate analysis revealed that Ki-67 PI remained as an independent prognostic factor (hazard ratio (95% CI),=,0.670 (0.450,0.999)). Furthermore, greater expressional changes of EMT-related proteins were found to be significantly associated with low Ki-67 PI (P,=,0.025). Conclusions These findings suggest that Ki-67 PI is an effective tool for predicting survival in gastric cancer. In addition, we found that an invasive property presented as EMT-related protein expressional changes was inversely correlated with a proliferative activity in gastric cancer. J. Surg. Oncol. 2010;102:201,206. © 2010 Wiley-Liss, Inc. [source] Osteopontin expression correlates with prognostic variables and survival in clear cell renal cell carcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2006Koviljka Matusan MD Abstract Background and Objectives Osteopontin (OPN) is a phosphorylated glycoprotein with diverse functions including tumorigenesis and tumor cell metastasis. Recently, it has been detected in a growing number of human tumors, and assessed as a potential prognostic marker. The aim of this study was to analyze the expression of OPN in normal renal tissue and clear cell renal cell carcinomas (CRCCs), and to assess its prognostic significance. Methods The expression of OPN protein was immunohistochemically analyzed in 171 CRCCs and compared to usual clinicopathological parameters such as tumor size, nuclear grade, pathological stage, Ki-67 proliferation index, and cancer-specific survival. Results In normal renal parenchyma, the expression of OPN was seen in distal tubular epithelial cells, calcifications, and some stromal cells. The upregulation of OPN was observed in 61 CRCCs (35.7%) in the form of cytoplasmic granular staining of various intensities. Statistical analysis showed correlation of the OPN expression with tumor size (P,<,0.001), Fuhrman nuclear grade (P,<,0.001), pathological stage (P,=,0.011), and Ki-67 proliferation index (P,<,0.001). Moreover, patients with OPN-positive tumors had significantly worse prognosis in comparison to patients with tumors lacking OPN protein (P,=,0.004). Conclusion Our results suggest that overexpression of OPN is involved in the progression of CRCC. J. Surg. Oncol. 2006;94:325,331. © 2006 Wiley-Liss, Inc. [source] The effect of the ionic products of Bioglass® dissolution on human osteoblasts growth cycle in vitroJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 2007Jun-Ying Sun Abstract In this study, in order to observe the effect of Bioglass® and its ionic products on human esteoblasts growth cycle in vitro, the ionic products of Bioglass have been introduced to a cell culture medium by dissolving Bioglass particles in Dulbecco's modified Eagle's medium (DMEM) at 37 °C for 24 h; this was used as the experimental medium, while DMEM without Bioglass modification was used as the control medium. Human osteoblasts isolated from trabecular bone were treated by the two media and the timing of the osteoblast growth cycle was examined. Cell growth curves were derived after 7 days. Also, human osteoblasts were treated for 1,6 days by the two media, and the G1, S, G2 phase percentages of osteoblasts were recorded by flow cytometry every day, resulting in the cell proliferation activity index: SPF (S-phase fraction) and PI (proliferation index). The difference in cell growth was shown after the second day of culture (p < 0.01), and cell growth in the experimental groups was greater than in control groups. The SPF and PI of the experimental groups were also higher than the control groups in 2 days of culture (p < 0.05 and p < 0.01), which indicates that the growth cycle of the human osteoblasts in experimental medium is about 2 days. In conclusion, Bioglass can promote osteoblast proliferation, reducing the human osteoblast growth cycle to pass through G1 and S phase and then enter G2 phase quickly. Copyright © 2007 John Wiley & Sons, Ltd. [source] Liver transplantation for gastroenteropancreatic neuroendocrine cancers: Defining selection criteria to improve survivalLIVER TRANSPLANTATION, Issue 3 2006Frederike G.I. van Vilsteren Liver transplantation for gastroenteropancreatic neuroendocrine cancer (GEP) is controversial. The aim of this study was to assess patient outcomes after liver transplantation for hepatic metastases from GEP. Medical records of patients who underwent liver transplantation for GEP were reviewed. Immunohistochemistry for assessing the Ki67 proliferation index was performed on explanted liver tissue. Nineteen patients who underwent liver transplantation had a mean follow-up of 22 months with a range of 0 to 84 months. There was 1 intraoperative death, and 3 patients had disease recurrence after liver transplantation leading to death in 1 patient. Overall estimated 1-year survival for 17 patients included in the treatment protocol (mean follow-up, 15 months) was 87% with an estimated 1-year recurrence-free rate (conditional on survival) of 77%. Three of 11 patients with pancreatic islet cell GEP developed disease recurrence, whereas all 8 patients with carcinoid GEP remain free of disease. Analysis of the Ki67 proliferation index in 18 patients did not differentiate those with recurrence from those without disease recurrence. In conclusion, liver transplantation for patients with hepatic metastases from GEP is a viable therapeutic option in highly selected patients. Liver Transpl 12:448,456, 2006. © 2006 AASLD. [source] Concise semiquantitative histological scoring system for immunoglobulin A nephropathyNEPHROLOGY, Issue 6 2009LEI JIANG SUMMARY: Aim: Immunoglobulin A nephropathy (IgAN) is a common and progressive glomerulonephritis. Histological lesions of IgAN are variable and considered as a risk factor for renal outcome. Establishing a relatively concise histological semiquantitative scoring system would be valuable in clinical practice. Methods: Renal biopsy sections of 293 patients with primary IgAN from two centres in China were reviewed. A histological scoring system was established based on multivariate survival analysis of semiquantitative histological indices, using end-stage renal disease (ESRD) as the end-point event. Results: Four indices , extracapillary glomerular activity index (exGAI), mesangial proliferation index (MsI), glomerular chronicity index (GCI) and tubulointerstitial chronicity index (TCI) , independently correlated with ESRD (relative risk (RR) = 1.16, 2.27, 1.29 and 1.80, respectively). The four indices and the sum of their scores (Total I) constituted the scoring system. Patients with exGAI of 4 or more, GCI of 4 or more, MsI of 2 or more and TCI of 2 or more were considered as having a higher risk for progression (P < 0.05). A score of 4 or more on the exGAI index could identify the patients who should be treated with immunosuppressive drugs, which showed a lower incidence of ESRD than that without (24.3% vs 52.4%, P = 0.031). Conclusion: It suggested that the present concise scoring system could serve as prognostic and therapeutic indications. [source] Determination of genomic damage in neuroblastic tumors by arbitrarily primed PCR: MYCN amplification as a marker for genomic instability in neuroblastomasNEUROPATHOLOGY, Issue 3 2006Jorge Muñoz The aim of this study is to establish an estimation of the global genomic alteration in neuroblastic tumors (ganglioneuromas, ganglioneuroblastomas and neuroblastomas) and correlate them with different clinical parameters (age, sex, diagnosis, Shimada index, proliferation index, tumor location, and 1p and v-myc avian myelocitomatosis viral-related (MYCN) status) in order to find new molecular and/or prognostic markers for neuroblastoma. To assess the genomic damage in neuroblastic tumors, we used an arbitrarily primed PCR approach, a technique based on the reproducibility of band profiles obtained by a PCR with a low annealing temperature in its first cycles. Genomic damage was assessed by comparing band profiles of tumors and normal paired samples. Gains and losses in the intensity of the bands were computerized and referred to the total number of bands analyzed. We found a higher genomic damage fraction (GDF) in the female's group (U-Mann,Whitney, P = 0.025), but we could not find any association between GDF and tumor location, proliferation index, diagnosis or age of the patient. There was no relationship between 1p status and GDF, but tumors with MYCN amplification had a slightly higher GDF. MYCN amplification might in some way contribute to genomic instability of neuroblastomas. [source] TrkA expression is associated with an elevated level of apoptosis in classic medulloblastomasNEUROPATHOLOGY, Issue 3 2006Takashi Ohta Medulloblastomas represent the most common central nervous system malignancies in children. Despite intensive modality treatment with craniospinal irradiation and multiple drug chemotherapy, their prognosis remains dismal. In the present study, we examined the potential roles of cellular differentiation, proliferation and apoptosis in 21 pediatric patients with newly diagnosed classic medulloblastomas treated by conventional radiation therapy and adjuvant chemotherapy. The expression of glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC, and the proliferation index of MIB-1 were evaluated by immunohistochemistry and the apoptotic index was determined using terminal deoxytransferase-mediated deoxyuridine-5,-triphosphate nick-end labeling assay. The prognostic value of these biological markers was also assessed. Immunoreactive glial fibrillary acidic protein, S-100, synaptophysin, TrkA and TrkC were observed in seven (33%), four (19%), 12 (57%), 14 (67%) and 11 (52%) of the 21 cases, respectively. TrkA expression was positively correlated with the MIB-1 staining index (P = 0.0228) and the apoptotic index (P = 0.0058). None of the immunohistochemical markers was found to be of value in predicting the prognosis. Although the present small sample size does not provide sufficient power to discount biological variables as prognostic markers, it was the well-established clinical prognostic factors, i.e. tumor stage and extent of surgery, that stood out as the most important predictors of survival. The close association between apoptosis and TrkA expression is consistent with in vitro data demonstrating the capacity of the NGF/TrkA signaling pathway to increase medulloblastoma apoptotic cell death, suggesting that this pathway may yield alternative therapeutic targets for novel therapies. [source] Skull base chordomas: correlation of tumour doubling time with age, mitosis and Ki67 proliferation indexNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 6 2000J. L. Holton The aim of the study was to assess the relationship between the rate of clinical tumour growth and various histological features, including Ki67 labelling index, in skull base chordoma. Cases of skull base chordoma from 19 patients (six female, 13 male; age range 8,63 years) were reviewed and the diagnosis confirmed based on histological and immunohistochemical features. In each biopsy cellularity, pleomorphism, mitotic activity, apoptotic bodies, necrosis and inflammatory cell infiltrate were graded and Ki67 labelling index (LI) calculated as a measure of proliferation. Tumour doubling time was assessed by quantitative analysis of tumour volumes in post-operative magnetic resonance images and correlated with age, sex, histological parameters and Ki67 LI. It was shown that increasing patient age, the presence of mitotic figures or a Ki67 LI in excess of 6% were associated with faster growing tumours. [source] Quantification of metabolites in breast cancer patients with different clinical prognosis using HR MAS MR spectroscopyNMR IN BIOMEDICINE, Issue 4 2010Beathe Sitter Abstract Absolute quantitative measures of breast cancer tissue metabolites can increase our understanding of biological processes. Electronic REference To access In vivo Concentrations (ERETIC) was applied to high resolution magic angle spinning MR spectroscopy (HR MAS MRS) to quantify metabolites in intact breast cancer samples. The ERETIC signal was calibrated using solutions of creatine and TSP. The largest relative errors of the ERETIC method were 8.4%, compared to 4.4% for the HR MAS MRS method using TSP as a standard. The same MR experimental procedure was applied to intact tissue samples from breast cancer patients with clinically defined good (n,=,13) and poor (n,=,16) prognosis. All samples were examined by histopathology for relative content of different tissue types and proliferation index (MIB-1) after MR analysis. The resulting spectra were analyzed by quantification of tissue metabolites (,-glucose, lactate, glycine, myo-inositol, taurine, glycerophosphocholine, phosphocholine, choline and creatine), by peak area ratios and by principal component analysis. We found a trend toward lower concentrations of glycine in patients with good prognosis (1.1,µmol/g) compared to patients with poor prognosis (1.9,µmol/g, p,=,0.067). Tissue metabolite concentrations (except for ,-glucose) were also found to correlate to the fraction of tumor, connective, fat or glandular tissue by Pearson correlation analysis. Tissue concentrations of ,-glucose correlated to proliferation index (MIB-1) with a negative correlation factor (,0.45, p,=,0.015), consistent with increased energy demand in proliferating tumor cells. By analyzing several metabolites simultaneously, either in ratios or by metabolic profiles analyzed by PCA, we found that tissue metabolites correlate to patients' prognoses and health status five years after surgery. This study shows that the diagnostic and prognostic potential in MR metabolite analysis of breast cancer tissue is greater when combining multiple metabolites (MR Metabolomics). Copyright © 2010 John Wiley & Sons, Ltd. [source] Pediatric diffuse large B-cell lymphoma demonstrates a high proliferation index, frequent c-Myc protein expression, and a high incidence of germinal center subtype: Report of the French,American,British (FAB) international study group,PEDIATRIC BLOOD & CANCER, Issue 3 2008Rodney R. Miles MD Abstract Background Diffuse large B-cell lymphoma (DLBCL) makes up 10,20% of pediatric non-Hodgkin lymphoma, and these patients have a significantly better prognosis than adults with DLBCL. The difference in prognosis may be related to clinical, phenotypic, and/or biological differences between adult and pediatric DLBCL. In adult DLBCL, the germinal center (GC) phenotype is associated with a better prognosis than the activated B-cell (ABC) phenotype. However, a high proliferative index and expression of Bcl2 and c-Myc protein have all been associated with worse outcomes. While multiple studies have addressed the phenotype and expression patterns of adult DLBCL, relatively little is known about these biological variables in pediatric DLBCL. The goal of this study was to investigate the proliferative index, the relative frequencies of the GC and non-GC subtypes, and the expression of Bcl2 and c-Myc protein in a cohort of children with DLBCL treated in a uniform manner. Procedure We performed immunohistochemistry (IHC) for MIB1, CD10, Bcl6, MUM1, Bcl2, and c-Myc on DLBCL tissue from children treated uniformly in the FAB LMB96 trial (SFOP LMB96/CCG5961/UKCCSG/NHL 9600). Results Compared to published adult DLBCL studies, pediatric DLBCL demonstrated moderate to high proliferation rates (83%), increased c-Myc protein expression (84%), decreased Bcl2 protein expression (28%), and an increased frequency of the GC phenotype (75%). Conclusions These findings suggest that there are significant biologic differences between pediatric and adult forms of DLBCL, which may contribute to the superior prognosis seen in the pediatric population relative to adult disease. Pediatr Blood Cancer 2008;51:369,374. © 2008 Wiley-Liss, Inc. [source] Role and prognostic significance of the Ki-67 index in non-Hodgkin's lymphoma,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2009Adi Broyde Expression of Ki-67, a nuclear antigen protein present in all cycling cells, is used to determine the growth fraction of tumors. The aim of this study was to evaluate the role and prognostic significance of the Ki-67 proliferation index (PI) in non-Hodgkin's lymphoma. Ki-67 was assayed immunohistochemically in tissue samples of 319 patients with newly-diagnosed non-Hodgkin's lymphoma. In 268 patients, the Ki-67 PI was correlated with clinical course and outcome. The mean Ki-67 PI ranged from 26.6% in indolent lymphomas to 97.6% in very aggressive lymphomas (P < 0.001). The index was <45% in 82.8% of indolent lymphomas and >45% in 85% of aggressive lymphomas (AUC = 0.877, P < 0.001). In patients with diffuse large B-cell lymphoma (n = 141), a Ki-67 PI of 70% was found to significantly discriminate patients with good or bad prognosis (AUC = 0.65, P = 0.004). Three-year survival was 75% ± 5.6% in patients with a low Ki-67 index compared with 55.9% ± 6% in patients with a high index (P = 0.015). In patients with a low IPI (,2), 3-year survival was 94% ± 4% in those with a Ki-67 index ,70% and 64% ± 8.1% in those with a higher index (P = 0.002); in patients with bulky disease (>10 cm), the corresponding 3-year survival by Ki-67 index was 100% and 25% ± 12% (P = 0.012). Our results suggest that the mean Ki-67 PI differs by type of lymphoma. A cut-off value of 45% can help differentiate indolent from aggressive disease. In diffuse large B-cell lymphoma, a cut-off value of 70% can distinguish patients with a good and bad prognosis when combined with other prognostic factors of low IPI score and bulky disease. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Differential expression of the calcium sensing receptor and combined loss of chromosomes 1q and 11q in parathyroid carcinomaTHE JOURNAL OF PATHOLOGY, Issue 1 2004Carola J Haven Abstract Malignant transformation of parathyroid tumours is rare. Nevertheless, this small subset of malignant tumours often creates diagnostic and therapeutic problems. In this work, the morphological characteristics of 26 primary parathyroid carcinomas and seven metastases have been studied. Furthermore, immunohistochemical expression profiles for the calcium sensing receptor (CASR), cyclin D1 (CCND1), and Ki-67 were determined for parathyroid carcinomas and compared with adenomas and hyperplasias using a tissue microarray. Loss of heterozygosity (LOH) of the chromosome 1q region containing the HRPT2 gene and chromosome 11q (MEN1) was determined in the carcinomas. In contrast to the adenomas and hyperplasias, 31% of carcinomas demonstrated down-regulation of CASR. A significant correlation was found between CASR expression and the Ki-67 proliferation index. Chromosome 1q and chromosome 11q LOH were found in 12 of 22 (55%) and 11 of 22 (50%) carcinomas tested, respectively. Combined 1q and 11q LOH was seen in 8 of 22 (36%) carcinomas, in contrast to the low percentage of LOH reported in both regions in adenomas. In conclusion, this study demonstrates that combined 1q and 11q LOH in parathyroid tumours is suggestive of malignant behaviour. Strong down-regulation of the CASR protein is seen in a proportion of parathyroid carcinomas with a high proliferation index. Copyright © 2004 John Wiley & Sons, Ltd. [source] hTERT expression in sporadic renal cell carcinomasTHE JOURNAL OF PATHOLOGY, Issue 2 2001Valérie Paradis Abstract Human telomerase is a specialized reverse transcriptase that catalyses telomeric repeat addition at the ends of chromosomes. Activation of this enzyme is one of the key steps in cell immortalization and carcinogenesis, and one of its components, hTERT, is considered as the rate-limiting factor. While telomerase activity was found to be prognostically relevant in various cancers, results obtained from renal cell carcinomas (RCC) failed to show any correlation with the usual prognostic factors. The aim of the study was to reassess the role of telomerase and its hTERT component in the biological behaviour of RCC using new quantitative techniques, such as the quantitative evaluation of hTERT mRNA level by a real-time RT-PCR procedure and the mesuring of telomerase activity by an ELISA TRAP assay. Since experimental evidence supports a relationship between cell proliferation or c-myc expression and telomerase, the proliferation index and c-myc mRNA levels were also studied. Forty-one RCC (29 conventional renal cell carcinomas (CRCC), 10 papillary RCC and two urothelial carcinomas) were studied. In 73% of cases, normalized hTERT mRNA expression was significantly higher in the tumour sample than in the normal tissue. Telomerase activity was detected in 63% of RCC, while corresponding normal tissue was always negative. Analysis of correlations showed firstly that both telomerase activity and hTERT mRNA level were lower in the group of CRCC versus non-CRCC (TRAP: 0.3±0.1 versus 0.6±0.2, p<0.05; hTERT/PO mRNA: 5±3 versus 37±8, p<0.001, respectively); secondly, that in the group of CRCC, hTERT mRNA expression level was correlated with the stage of the tumour (p=0.01); and thirdly, that no correlation was observed between c-myc mRNA level and hTERT mRNA level. In conclusion, these results support the involvement of telomerase in RCC and the potential interest of hTERT mRNA quantification. Copyright © 2001 John Wiley & Sons, Ltd. [source] Aggressiveness and Quantification of Epithelial Proliferation of Middle Ear Cholesteatoma by MIB1THE LARYNGOSCOPE, Issue 2 2003Y. Mallet MD Abstract Objective To assess an easy method that predicts cholesteatoma aggressiveness. Study Design An experimental prospective study. Methods Monoclonal antibody MIB1 was used to determine epithelium proliferation in 91 cholesteatomatous ears. Clinical and surgical parameters were compared with proliferation activity to determine pathological and clinical correlation. Results Statistical correlations were established between hyperproliferation of the cholesteatoma and severe bone erosion (leading to major cholesteatoma complications) and between hyperproliferation and middle ear inflammation (associated with more surgical difficulties and a higher risk of recurrence). A high proliferation index was also found in children's cholesteatoma, which is known to have more aggressive behavior. Conclusion Immunohistochemical use of the MIB1 antibody is a simple technique that can help to determine the aggressiveness of a cholesteatoma. [source] Immunohistochemical expression of SPARC is correlated with recurrence, survival and malignant potential in meningiomasAPMIS, Issue 9 2009SUHEYLA UYAR BOZKURT Meningioma is a common neoplasm that constitutes almost 30% of all primary central nervous system tumors and is associated with inconsistent clinical outcomes. The extracellular matrix proteins play a crucial role in meningioma cell biology and are important in tumor cell invasion and in progression to malignancy. SPARC (secreted protein, acidic and rich in cysteine) (osteonectin) is a matricellular glycoprotein that regulates cell function by interacting with different extracellular matrix proteins. The aim of this study was to evaluate the expression of SPARC with proliferation index, p53 reactivity in WHO grade 1 (benign), grade 2 (atypical) and grade 3 (anaplastic) meningiomas and correlate with clinical features of the patients, including location of the tumor, recurrence of the tumor and survival of patients. We studied 111 meningiomas, 69 being benign, 34 being atypical and eight being anaplastic meningiomas of various histological types. Using immunohistochemical analysis, we evaluated the expression of SPARC, Ki-67 (MIB-1) and p53 in meningiomas. Immunohistochemical scores of SPARC were determined as the sum of frequency (0,3) and intensity (0,3) of immunolabeling of the tumor cells. A high immunohistochemical score (4,6) for SPARC was more frequent in atypical and in anaplastic meningiomas than in benign meningiomas (p < 0.01). MIB-1 proliferation index showed significant association between tumor grades in meningiomas (p < 0.01). At the end of a follow-up period of 47.53 ± 25.04 months, 30 tumors recurred. A high SPARC expression was significantly associated with tumor recurrence (p = 0.02). The immunoreactivity of p53 protein and MIB-1 score were significantly higher in recurrent meningiomas than in non-recurrent meningiomas. The cumulative survival of patients with high SPARC expression was significantly lower than patients with low SPARC expression. The high SPARC expression scores were predominantly identified in meningothelial, fibrous and chordoid meningiomas; low SPARC expression scores were mostly spotted in secretory and psammomatous meningiomas. Evaluating SPARC expression might help assessing recurrence risk and survival estimation in meningiomas. [source] Angiogenesis and the persistence of inflammation in a rat model of proliferative synovitisARTHRITIS & RHEUMATISM, Issue 7 2010Sadaf Ashraf Objective To determine whether blood vessel growth at the onset of resolving synovitis leads to its subsequent persistence and whether inhibiting this angiogenesis at the onset of persistent inflammation leads to its subsequent resolution. Methods Inflammation and angiogenesis were induced by injection of 0.03% carrageenan and/or 6 pmoles of fibroblast growth factor 2 (FGF-2) into rat knees. A brief treatment with the angiogenesis inhibitor PPI-2458 (5 mg/kg orally on alternate days) was administered 1 day before and up to 3 days after synovitis induction. Controls comprised naive and vehicle-treated rats. Synovial angiogenesis was measured using the endothelial cell proliferation index, and inflammation was determined by measuring joint swelling and macrophage percentage area. Data are presented as the geometric mean (95% confidence interval). Results Intraarticular injection of 0.03% carrageenan into rat knees produced acute synovitis, which was not associated with synovial angiogenesis and which resolved within 29 days. Injection of FGF-2 (6 pmoles) induced synovial angiogenesis without significant synovitis. Stimulation of angiogenesis with FGF-2 at the time of carrageenan injection was followed by synovitis that persisted for 29 days. Persistence of carrageenan/FGF-2,induced synovitis was prevented by systemic administration of 3 doses of the angiogenesis inhibitor PPI-2458 during the acute phase. Conclusion Our findings indicate that conversion of acute inflammation to chronic inflammation may be due to the stimulation of angiogenesis, and brief antiangiogenic treatment during the acute phase of synovitis may prevent its subsequent progression. Clinical studies will be needed to determine whether brief antiangiogenic treatment may reduce the burden of inflammatory joint diseases such as rheumatoid arthritis by facilitating the resolution of early synovitis. [source] Cytogenetic damage in human lymphocytes following GMSK phase modulated microwave exposureBIOELECTROMAGNETICS, Issue 1 2002Guglielmo d'Ambrosio Abstract The present study investigated, using in vitro experiments on human lymphocytes, whether exposure to a microwave frequency used for mobile communication, either unmodulated or in presence of phase only modulation, can cause modification of cell proliferation kinetics and/or genotoxic effects, by evaluating the cytokinesis block proliferation index and the micronucleus frequency. In the GSM 1800 mobile communication systems the field is both phase (Gaussian minimum shift keying, GMSK) and amplitude (time domain multiple access, TDMA) modulated. The present study investigated only the effects of phase modulation, and no amplitude modulation was applied. Human peripheral blood cultures were exposed to 1.748 GHz, either continuous wave (CW) or phase only modulated wave (GMSK), for 15 min. The maximum specific absorption rate (,5 W/kg) was higher than that occurring in the head of mobile phone users; however, no changes were found in cell proliferation kinetics after exposure to either CW or GMSK fields. As far as genotoxicity is concerned, the micronucleus frequency result was not affected by CW exposure; however, a statistically significant micronucleus effect was found following exposure to phase modulated field. These results would suggest a genotoxic power of the phase modulation per se. Bioelectromagnetics 23:7,13, 2002. © 2002 Wiley-Liss, Inc. [source] Impact of Morphology, MIB-1, p53 and MGMT on Outcome in Pilocytic AstrocytomasBRAIN PATHOLOGY, Issue 3 2010Craig Horbinski MD Abstract Pilocytic astrocytoma (PA) is the most common glioma in the pediatric population. PAs can exhibit variable behavior that does not always correlate with location, yet at present there is no way to predict which tumors will be more aggressive. To address this problem, an institutional cohort of 147 PAs (118 with outcome data) from both cerebellar and noncerebellar locations (spine, diencephalon, midbrain, brainstem and cortex) was utilized. Parameters included quantification of characteristic morphologic variables as well as genes previously shown to be of relevance in high-grade gliomas, including MIB-1, p53 and MGMT. In this cohort, the classic biphasic appearance was most common in cerebellar tumors, whereas noncerebellar tumors were predominantly microcystic. Associations with outcome suggest that the presence of degenerative atypia may be a favorable factor in PAs. Oligodendroglial morphology and the absence of leptomeningeal invasion are adverse histologic factors, but only in cerebellar tumors. Conversely, MIB-1 proliferation index and p53 and MGMT expression do not correlate with outcome. Morphologic biomarkers thus do exist for PAs, but the utility of each biomarker varies according to location. These results suggest that PAs differ fundamentally according to location; therefore, biological behavior may not simply depend on extent of resection. [source] Proliferation predicts failure-free survival in mantle cell lymphoma patients treated with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabineCANCER, Issue 5 2009Mar Garcia MD Abstract BACKGROUND: It has been demonstrated that the tumor proliferation index has prognostic significance in patients with mantle cell lymphoma (MCL). Patients in most of studies, however, have been treated with relatively traditional chemotherapy regimens. At the authors' institution, patients with MCL received an aggressive chemotherapy regimen: rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with rituximab plus high-dose methotrexate and cytarabine (R-hyper-CVAD). METHODS: The authors assessed the proliferation rate of MCL using immunohistochemistry and an antibody specific for Ki-67 in 71 untreated patients who subsequently received R-hyper-CVAD. The study group included 59 patients who had classic MCL and 12 patients who had the blastoid variant of MCL. RESULTS: For the entire study group and for the group of patients with classic MCL, a proliferation index of >20% Ki-67-positive cells was correlated significantly with shorter failure-free survival. There was no correlation between the proliferation index and overall survival. CONCLUSIONS: The current results indicated that the proliferation index in patients with MCL predicted prognosis in those who uniformly received the R-hyper-CVAD chemotherapy regimen. Cancer 2009. © 2009 American Cancer Society. [source] Chromosomal anomalies in oligodendroglial tumors are correlated with clinical featuresCANCER, Issue 5 2003M.D., Martin J. van den Bent Ph.D. Abstract BACKGROUND Patients who have oligodendrogliomas (OD) that demonstrate loss of both 1p and 19q appear to have a better prognosis after they receive chemotherapy and radiotherapy compared with patients who have OD without these characteristics. It is unclear whether this improvement in outcome is due only to a better response to treatment. The authors investigated the correlation between genetic and clinical characteristics of OD in 33 patients who received chemotherapy with procarbazine, lomustine, and vincristine for recurrent disease after receiving radiotherapy. METHODS The initial presentation, prior treatments, overall survival, and response to chemotherapy were assessed. The 1p and 19q status in OD lesions was determined with fluorescence in situ hybridization on paraffin embedded, archival material using locus specific probes. P53 mutations were assessed by polymerase chain reaction,single-strand conformation polymorphism analysis and immunohistochemistry for P53; the proliferation index was assessed with the MIB-1 antibody. RESULTS Patients who had OD lesions with a combined loss of 1p and 19q typically presented with low-grade tumors that manifested with seizures of long-standing duration. In contrast, patients who had OD lesions without a combined loss of 1p and 19q usually presented with focal deficits that required immediate treatment. Both the response rate to chemotherapy and the time to disease progression after chemotherapy were significantly better in patients who had a combined loss of 1p and 19. Tumors with classic OD morphology more often had a combined loss of 1p and 19q, although the genotype was better at identifying patients with chemoresponsive tumors. P53 mutations were observed in three tumors, none of which had a combined loss of 1p and 19q. CONCLUSIONS OD lesions with combined a loss of 1p and 19q have a more indolent nature compared with OD lesions that do not have these losses. Virtually all patients with these tumors present with low-grade tumors accompanied by seizures and remain stable for prolonged periods. Future trials must keep these tumor types apart. Cancer 2003;97:1276,84. © 2003 American Cancer Society. DOI 10.1002/cncr.11187 [source] | ||||||||||||||||||||||||||||