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Tumor Sections (tumor + section)
Selected AbstractsHyaluronidase reduces human breast cancer xenografts in SCID miceINTERNATIONAL JOURNAL OF CANCER, Issue 2 2002Svetlana Shuster Abstract A hyaluronan-rich environment often correlate with tumor progression. and may be one mechanism for the invasive behavior of malignancies. Eradication of hyaluronan by hyaluronidase administration could reduce tumor aggressiveness and would provide, therefore, a new anti-cancer strategy. Hyaluronan interaction with its CD44 receptor and the resulting signal transduction events may be among the mechanisms for hyaluronan-associated cancer progression. We have shown previously that hyaluronidase treatment of breast cancer cells in vitro not only eradicates hyaluronan but also modifies expression of CD44 variant exons of tumor cells. We now determine if such effects occur in vivo and if it is accompanied by tumor regression. SCID mice bearing xenografts of human breast carcinomas were given intravenous hyaluronidase. Tumor volumes decreased 50% in 4 days. Tumor sections showed decreased hyaluronan. Intensity of staining for CD44s was not affected, whereas staining for specific CD44 variant exon isoforms was greatly reduced in residual tumors. Necrosis was not evident. Hyaluronidase, used previously as an adjunct in cancer treatment, presumably to enhance penetration of chemotherapeutic drugs, may itself have intrinsic anti-cancer activity. Removing peritumor hyaluronan appears to cause an irreversible change in tumor metabolism. Continuous hyaluronan binding to CD44 variant exon isoforms may also be required to stabilize inherently unstable isoforms that participate perhaps in tumor progression. Further investigation is required to confirm a cause and effect relationship between loss of hyaluronan, changes in CD44 variant exon expression and tumor reduction. If confirmed, hyaluronidase may provide a new class of anti-cancer therapeutics and one without toxic side effects. © 2002 Wiley-Liss, Inc. [source] AMACR is not applicable as a diagnostic tool in hepatocellular carcinomaAPMIS, Issue 2 2010GRO LINNO WILLEMOE Willemoe GL, Vainer B. AMACR is not applicable as a diagnostic tool in hepatocellular carcinoma. APMIS 2010; 118: 85,90. ,-methylacyl coenzyme A racemase (AMACR or P504S) is a mitochondrial and peroxisomal protein present in a variety of human cells. Demonstration of increased expression is used diagnostically in prostatic adenocarcinoma. AMACR is also produced by normal hepatocytes and it has been postulated that the demonstration of AMACR expression or its pattern of distribution is useful in the diagnosis of hepatocellular carcinoma (HCC) (Jiang et al., Hum Pathol 2003;34, Guzman et al., Appl Immunohistochem Mol Morphol 2006;14, Li et al., J Exp Clin Cancer Res 2008;27). The aim of the present study was to evaluate whether immunohistochemical staining for AMACR can be used in a routine histopathologic setting. Immunohistochemical staining for AMACR was performed on paraffin-embedded tissue from livers resected for HCC during 1980,2006 at Rigshospitalet, Copenhagen, Denmark (n = 44). Tumor sections as well as surrounding non-neoplastic tissues were studied. In both tumor and non-tumor tissues, intracellular localization and staining pattern were assessed and the staining intensity of AMACR was graded. The fraction of stained tumor cells was not significantly different from that of stained non-tumor cells in the same patients (p = 0.97). A significantly lower staining intensity was observed in clear cell areas (p = 0.005), but the AMACR expression did not correlate with the HCC type and could not distinguish neoplastic from non-neoplastic liver cells. AMACR is not applicable as a tool in the histopathologic diagnosis of HCC. [source] Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinomaDISEASES OF THE ESOPHAGUS, Issue 2 2001M. Tomita The association of mast cells with tumor angiogenesis was investigated in patients with esophageal squamous cell carcinoma. Surgical specimens from 48 patients with esophageal squamous cell carcinoma were studied. Mast cells in tumor sections were stained with Alcian blue and safranin O. The number of mast cells was counted under light microscopy and the average count recorded. To highlight the microvessels, endothelial cells were stained with anti-human factor VIII antibody. Microvessel density was also counted. We found a significant correlation between mast cell count and microvessel density in patients with esophageal squamous cell carcinoma. Double staining of the microvessels revealed highly angiogenic areas densely populated with mast cells. There appears to be a direct correlation between the number of mast cells and tumor angiogenesis in patients with esophageal squamous cell carcinoma. [source] Gene silencing of transcription factor Gli2 inhibits basal cell carcinomalike tumor growth in vivoINTERNATIONAL JOURNAL OF CANCER, Issue 1 2008Jingmin Ji Abstract Basal cell carcinoma (BCC) belongs worldwide to the most frequent malignancy among Caucasians. The understanding of the molecular mechanisms of BCC formation, which is a prerequisite for the development of efficient new therapies, is still incomplete. The formation of sporadic BCCs in the skin is associated with uncontrolled hedgehog signaling, and the transcription factor Gli2 has been identified as a key mediator or effector of this signaling. There is indication in the literature that preventing Gli2 function may inhibit BCC formation and growth in vivo; however, the mechanism is unclear and difficult to study in humans. Therefore, we used a mouse tumor allograft model to investigate the role of Gli2 in tumor formation. A constitutively Gli2 expressing mouse tumor cell line was stably transfected with Gli2-specific shRNA to induce Gli2 gene silencing or with control shRNA. Injecting the Gli2 gene silenced cells into nude mice for tumor formation we detected a strongly retarded tumor growth compared with control tumor cells. Investigating the mechanisms, we found that Gli2 gene silencing has led to the disruption of the tumor structure as demonstrated by staining tumor sections with hematoxylin. Two main reasons for the tumor destruction were identified. We found that apoptosis was markedly increased while vascularization was strongly decreased in these tumors. Thus, important functions of the transcription factor Gli2 in this tumor model are the prevention of apoptosis and the promotion of microvascularization. © 2007 Wiley-Liss, Inc. [source] High cerebral blood volume in human gliomas predicts deletion of chromosome 1p: Preliminary results of molecular studies in gliomas with elevated perfusionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 6 2007Meng Law MD Abstract Purpose To determine if increased perfusion using dynamic susceptibility contrast perfusion MRI (DSC MRI) in gliomas may be predictive of 1p19q deletions. Loss of heterozygosity of chromosomes 1p and 19q confers responsiveness to chemotherapy improving survival in gliomas. Materials and Methods We retrospectively reviewed 16 patients who had DSC MRI and molecular studies of their excised gliomas for 1p19q deletions. Allelic status was assessed by loss of heterozygosity using polymerase chain reaction (PCR). DNA was extracted from paraffin curls of brain tumor sections and nail clippings. Relative cerebral blood volume (rCBV) measurements were then statistically compared with the presence of 1p and 19q deletions. Results Patients with 1p19q deletions (N = 7) demonstrated rCBV values of 10.54 ± 2.93. Patients without 1p deletions (N = 9) had rCBV values of 4.84 ± 2.4 (P = 0.012). Logistic regression demonstrated that rCBV was able to predict the presence of a 1p deletion to significance levels of 0.038 and 0.044, adjusted and not adjusted for age and sex, respectively. The kappa coefficient for the agreement between predicted deletion status using rCBV and the truedeletion status was 0.746 (P = 0.0028). Deletions of 19q alone, or together with 1p deletions, were not associated with high rCBV. Conclusion Histopathologic, molecular, and imaging evidence supports increased neovascularity in gliomas with 1p deletions in this preliminary study. We propose a diagnostic algorithm to obtain molecular studies in gliomas demonstrating high rCBV. J. Magn. Reson. Imaging 2007;25:1113,1119. © 2007 Wiley-Liss, Inc. [source] Single nucleotide polymorphisms in the hypoxia-inducible factor-1 gene and colorectal cancer riskMOLECULAR CARCINOGENESIS, Issue 9 2010Gudrun Knechtel Abstract With an incidence of about 300,000 new cases colorectal cancer (CRC) is the second leading cause of cancer-related death in Europe and the United States. Environmental and genetic factors influence CRC risk. Hypoxia-inducible factor-1 (HIF-1), a heterodimeric protein composed of two subunits, HIF-1 alpha and HIF-1 beta, plays a critical role in oxygen homeostasis and is involved in angiogenesis and cell proliferation. The gene for the HIF-1 alpha subunit (HIF1A) carries two common missense mutations,P582S (rs11549465) and A588T (rs11549467),which both have been related to increased trans-activation capacity of HIF1A. In our case,control study we investigated the association between these polymorphisms and CRC risk. We investigated 381 patients with histologically confirmed CRC and 2156 control subjects. HIF1A genotypes were determined by exonuclease (TaqMan) assays. For determination of microvessel density (MVD) tumor sections were stained using a mouse monoclonal antibody recognizing the pan-endothelial marker CD31. In a multivariate logistic regression analysis including age and sex neither the HIF1A 582S allele (Odds ratio: 1.204; 95% confidence interval 0.911,1.592; P,=,0.193) nor the 588T allele was significantly associated with CRC (Odds ratio: 0.851; 95% confidence interval 0.444,1.631; P,=,0.626). However, in an exploratory analysis, the HIF1A 588T allele was associated with tumor localization (P,=,0.016) and tumor size (P,=,0.003). MVD was similar in tumors of patients carrying HIF1A 588T allele and patients without this rare allele. We conclude that functional polymorphisms in the HIF1A gene do not modify CRC risk but maybe associated with clinic-pathological features of the disease. © 2010 Wiley-Liss, Inc. [source] A novel communication role for CYP17A1 in the progression of castration-resistant prostate cancerTHE PROSTATE, Issue 9 2009Jennifer A. Locke Abstract BACKGROUND CYP17A1 is currently a target for total androgen blockade in advanced prostate cancer (CaP) patients. After castration, or removal of testicular androgens, CYP17A1 can act as a rate-limiting enzyme in androgen synthesis from cholesterol or other adrenal precursors within the tumor microenvironment ultimately contributing to disease progression. Herein we provide evidence that CYP17A1 could also be a mediator of cell-to-cell communication within the CaP tumor microenvironment. METHODS CYP17A1 expression was evaluated by immunohistochemical analysis of human tumor sections and Western blot analysis of CaP patients' serum and exosome isolates. CYP17A1 activity assays were conducted in human serum (and positive control human liver and kidney microsomes) using progesterone as a precursor and an LC-MS endpoint. RESULTS These studies revealed that the expression pattern of CYP17A1 is typical of a secretory protein as it is localized to the luminal pole of the cells in exocrine secretory mode. CYP17A1 is expressed in human serum and in fact is elevated in the serum of CaP patients as compared to healthy controls. Serum CYP17A1 activity could not be confirmed, however, verification of CYP17A1 expression in exosomes suggests a role in cell-to-cell communication within the tumor microenvironment. CONCLUSIONS CYP17A1 is a crucial enzyme for de novo androgen synthesis within the tumor microenvironment after removal of testicular androgens by castration. We provide evidence for a novel role for CYP17A1 in serum and further reiterate the importance of targeting this enzyme in CaP progression. Prostate 69: 928,937, 2009. © 2009 Wiley-Liss, Inc. [source] Overexpression of TrkB promotes the progression of colon cancerAPMIS, Issue 3 2010YINGJIAO YU Yu Y, Zhang S, Wang X, Yang Z, Ou G. Overexpression of TrkB promotes the progression of colon cancer. APMIS 2010; 118: 188,95. Studies have confirmed that TrkB plays important roles in facilitating metastasis in various types of malignant tumors. In the present study, 30 cases of colon cancer and matched non-tumors were examined for the expression of TrkB by Western blot. The expression of TrkB was also examined in 90 colon tumor sections by immunohistochemical methods, and D2-40 staining was used to evaluate the correlation between TrkB expression and lymphatic vessel density. To investigate the effects of TrkB on the progression of colon cancer, siRNA specific for TrkB was transfected into LoVo cells, and proliferation, apoptosis and invasion of trasfected cells were examined using MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], flow cytometry and Transwell assays, respectively. Our results showed that TrkB was up-regulated in colon tumors compared with the non-tumorous counterparts, and the overexpression of TrkB was closely correlated with lymphatic vessel density (LVD) and metastasis. Inhibition of TrkB by siRNA increased the apoptotic rates of transfected cells, while the numbers of proliferative and invasive cells were decreased. In summary, our data suggest that overexpression of TrkB in colon cancer possibly plays roles in inhibiting apoptosis, promoting proliferation and invasion, facilitating tumor progression by lymphangiogenesis-associated metastasis. [source] | ||||||||||