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Various Malignancies (various + malignancy)
Selected AbstractsImmunohistochemical Stains in Mohs Surgery: A ReviewDERMATOLOGIC SURGERY, Issue 7 2009DONALD STRANAHAN MD BACKGROUND During Mohs surgery, there are instances in which residual tumor cells may be difficult to detect, thereby increasing the risk of incomplete excision and tumor recurrence. It is possible to employ immunohistochemical techniques as an adjunct to routine hematoxylin and eosin staining to aid in ensuring negative margins. OBJECTIVE To review the literature regarding the use of immunostains in Mohs surgery. RESULTS Various immunostains have proved useful in detecting tumor cells in various malignancies, including melanoma, basal cell carcinoma, squamous cell carcinoma, dermatofibrosarcoma protuberans, extramammary Paget's disease, primary cutaneous mucinous carcinoma, granular cell tumor, and trichilemmal carcinoma. CONCLUSIONS In this article, we review immunohistochemical stains that have been employed in Mohs micrographic surgery and evaluate their utility in enhancing detection of residual tumors with respect to tumor type, particularly in situations in which detection of residual tumor may be difficult. [source] Determinants of urinary 8-hydroxy-2,-deoxyguanosine in Chinese children with acute leukemiaENVIRONMENTAL TOXICOLOGY, Issue 5 2009You Yang Abstract The 8-hydroxy-2,-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage, but might also be a risk factor for many diseases including cancer. Elevated level of urinary 8-OHdG has been detected in patients with various malignancies. In the present study, the level of urinary 8-OHdG was examined in 116 Chinese children with acute leukemia (94 acute lymphoid leukemia, ALL, 22 acute myeloid leukemia, AML), and its correlation with urinary metal elements was investigated. Our result showed that the level of urinary 8-OHdG in children with acute leukemia before treatment was significantly elevated compared with that in normal controls (11.92 ± 15.42 vs. 4.03 ± 4.70 ng/mg creatinine, P < 0.05). In particular, urinary 8-OHdG was higher in children with acute leukemia aged under 3 years (20.86 ± 21.75 ng/mg creatinine) than in those aged 3,15 years (8.09 ± 9.65 ng/mg creatinine), whereas no differences were shown in terms of gender, parental smoking and education, household income, place of residence, and use of paracetamol. In addition, urinary 8-OHdG levels were similar among different subtypes of acute lymphoid leukemia (ALL) patients. Furthermore, linear regression analysis revealed a significant correlation between urinary 8-OHdG and urinary Cr, but not Fe or As, in group aged <3 years compared with group aged 3,15 years (P = 0.041), indicating that the metal elements may be involved in increasing urinary 8-OHdG level in younger children with acute leukemia. Our results suggest that children with acute leukemia undergo an increased risk of oxidative DNA damage, which may be correlated with high level of Cr exposure in Chinese children with acute leukemia. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Vitamin D and skin: new aspects for dermatologyEXPERIMENTAL DERMATOLOGY, Issue 2004Bodo Lehmann Abstract:, It has been shown that epidermal keratinocytes have the capacity for the UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D3, and also for the enzymatically controlled hydroxylation of the photolysis product. This metabolic loop results in the formation of the biologically active final product 1,,25-dihydroxyvitamin D3 (1,,25(OH)2D3, calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and immunocompetent cells. Because of their anti-proliferative and prodifferentiating effects, calcitriol and other vitamin D analogs are highly efficient in the treatment of psoriasis vulgaris. In addition, the known therapeutic effect of UVB light therapy in the treatment of psoriasis may, at least in part, be mediated via UVB-induced synthesis of calcitriol. Increasing evidence now indicates that cutaneous vitamin D synthesis is of great importance for the prevention of a broad variety of diseases, including various malignancies. It has been postulated that cancer mortality could be reduced via careful UV exposure or, more safely, via oral substitution with vitamin D. These new findings must be taken into account when establishing new sun protection guidelines for the prevention of skin cancer. In addition, better understanding of the metabolism of vitamin D in the skin has opened up new perspectives for the therapeutic application of vitamin D analogs, e.g. in inflammatory skin diseases. [source] The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancersGENES, CHROMOSOMES AND CANCER, Issue 11 2008Chunguang Guo MicroRNAs (miRNA/miR) are a class of small noncoding RNAs implicated in the pathogenesis of various malignancies. In the current study, using micro(RNA) arrays, we found a ubiquitous loss of miR-126 expression in colon cancer lines when compared to normal human colon epithelia. Reconstitution of miR-126 in colon cancer cells resulted in a significant growth reduction as evidenced in clonogenic assays. A search for miR-126 gene targets revealed p85,, a regulatory subunit involved in stabilizing and propagating the phosphatidylinositol 3-kinase (PI3K) signal, as one of the potential substrates. Restoration of miR-126 in cancer cells induced a ,3-fold reduction in p85, protein levels, with no concomitant change in p85,, a gene that is functionally related to p85, but not a supposed target of miR-126. Additionally, using reporter constructs, we show that the p85,-3, untranslated region is directly targeted by miR-126. Furthermore, this miR-126 mediated reduction of p85, was accompanied by a substantial reduction in phosphorylated AKT levels in the cancer cells, suggesting an impairment in PI3K signaling. Finally, in a panel of matched normal colon and primary colon tumors, each of the tumors demonstrated miR-126 down-regulation together with an increase in the p85, protein level. Taken together, we propose that miR-126 regulates PI3K signaling partly by targeting p85,, and that the loss of miR-126 may provide a selective growth advantage during colon carcinogenesis. © 2008 Wiley-Liss, Inc. [source] DLEU2 encodes an antisense RNA for the putative bicistronic RFP2/LEU5 gene in humans and mouseGENES, CHROMOSOMES AND CANCER, Issue 4 2004Martin M. Corcoran Our group previously identified two novel genes, RFP2/LEU5 and DLEU2, within a 13q14.3 genomic region of loss seen in various malignancies. However, no specific inactivating mutations were found in these or other genes in the vicinity of the deletion, suggesting that a nonclassical tumor-suppressor mechanism may be involved. Here, we present data showing that the DLEU2 gene encodes a putative noncoding antisense RNA, with one exon directly overlapping the first exon of the RFP2/LEU5 gene in the opposite orientation. In addition, the RFP2/LEU5 transcript can be alternatively spliced to produce either several monocistronic transcripts or a putative bicistronic transcript encoding two separate open-reading frames, adding to the complexity of the locus. The finding that these gene structures are conserved in the mouse, including the putative bicistronic RFP2/LEU5 transcript as well as the antisense relationship with DLEU2, further underlines the significance of this unusual organization and suggests a biological function for DLEU2 in the regulation of RFP2/LEU5. © 2004 Wiley-Liss, Inc. [source] Thalidomide as an anti-cancer agentJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 2 2002S. Kumar Abstract Thalidomide is a glutamic acid derivative initially introduced as a sedative hypnotic nearly forty years ago. It was withdrawn following numerous reports linking it to a characteristic pattern of congenital abnormalities in babies born to mothers who used the drug for morning sickness. It has gradually been re-introduced into clinical practice over the past two decades, albeit under strict regulation, since it was found to be useful in the management of erythema nodosum leprosum and HIV wasting syndrome. Recognition of its anti-angiogenic effect led to its evaluation in the treatment of various malignancies, where angiogenesis has been shown to play an important role. Numerous clinical trials done over the past four years have confirmed the significant anti-myeloma activity of this drug. It has also shown promise in preliminary trials in the treatment of a variety of different malignant diseases. The mechanisms of its antineoplastic effects continue to be the focus of ongoing research. It has become clear that even though its anti angiogenic effects play a significant role in the anti-tumor activity, there are other properties of this drug which are responsible as well. It also possesses anti-TNF alpha activity, which has led to its evaluation in several inflammatory states. In this concise review, we briefly describe the historical background and pharmacological aspects of this drug. We have concisely reviewed the current knowledge regarding mechanisms of its anti-neoplastic activity and the results of various clinical trials in oncology. [source] Association between Waste Management and Cancer in Companion AnimalsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2009L. Marconato Background: Increased cancer rates have been documented in people residing in areas around Naples characterized by illegal dumping and incineration of waste. Hypothesis: Risk of cancer in dogs and cats is associated with waste management. Animals: Four hundred and fifty-three dogs and cats with cancer and 1,554 cancer-free animals. Methods: Hospital-based case-control study in Naples (low danger) and nearby cities having a history of illegal waste dumping (high danger). Odds ratio (OR) between high- and low-danger areas was calculated for all tumors and various malignancies in dogs and cats. Results: An increased risk for cancer development was identified in dogs but not in cats residing in high-danger areas (OR: 1.55; 95% confidence interval: 1.18,2.03; P < .01). A 2.39-fold increased risk of lymphoma (P < .01) accounted for the greater tumor frequency in dogs residing in high-danger areas. The risk of mast cell tumor and mammary cancer did not differ in dogs residing in high- or low-danger areas. Conclusions and Clinical Importance: Waste emission from illegal dumping sites increases cancer risk in dogs residing in high-danger areas. An increased prevalence of lymphoma has been previously recognized in humans living close to illegal waste dumps. Thus, epidemiological studies of spontaneous tumors in dogs might suggest a role for environmental factors in canine and human carcinogenesis and can predict health hazards for humans. [source] Dietary-feeding of grape seed extract prevents azoxymethane-induced colonic aberrant crypt foci formation in fischer 344 ratsMOLECULAR CARCINOGENESIS, Issue 7 2010Balaiya Velmurugan Abstract Chemoprevention by dietary agents/supplements has emerged as a novel approach to control various malignancies, including colorectal cancer (CRC). This study assessed dietary grape seed extract (GSE) effectiveness in preventing azoxymethane (AOM)-induced aberrant crypt foci (ACF) formation and associated mechanisms in Fischer 344 rats. Six-week-old rats were injected with AOM, and fed control diet or the one supplemented with 0.25% or 0.5% (w/w) GSE in pre- and post-AOM or only post-AOM experimental protocols. At 16,wk of age, rats were sacrificed and colons were evaluated for ACF formation followed by cell proliferation, apoptosis, and molecular analyses by immunohistochemistry. GSE-feeding caused strong chemopreventive efficacy against AOM-induced ACF formation in terms of up to 60% (P,<,0.001) reduction in number of ACF and 66% (P,<,0.001) reduction in crypt multiplicity. Mechanistic studies showed that GSE-feeding inhibited AOM-induced cell proliferation but enhanced apoptosis in colon including ACF, together with a strong decrease in cyclin D1, COX-2, iNOS, and survivin levels. Additional studies showed that GSE-feeding also decreased AOM-caused increase in ,-catenin and NF-,B levels in colon tissues. Compared to control animals, GSE alone treatment did not show any considerable change in these biological and molecular events in colon, and was nontoxic. Together, these findings show the chemopreventive efficacy of GSE against the early steps of colon carcinogenesis in rats via likely targeting of ,-catenin and NF-,B signaling, and suggest its potential usefulness for the prevention of human CRC. © 2010 Wiley-Liss, Inc. [source] Prognostic significance of Fas (CD95/APO-1) positivity in patients with primary nodal diffuse large B-cell lymphomaAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2006Bulent Eser Abstract Fas (CD95/APO-1) is a protein that is mainly related to apoptosis of lymphoid cells. The increment of Fas expression is associated with long-term survival in various malignancies. However, there are limited studies regarding the effect of Fas expression on the course and prognosis of non-Hodgkin's lymphoma. The aim of this study was to investigate the significance of immunohistochemical Fas expression on the prognosis of nodal diffuse large B-cell lymphoma. A total of 63 patients with primary nodal diffuse large B-cell lymphoma diagnosed in the Erciyes University Department of Hematology between 1990 and 2003 were included in the study. The median age of the patients was 55 years old (range 19,102 years old). The median follow-up period was 19 months (2,132 months). Histopathological sections were stained immunohistochemically and evaluated by light microscopy for Fas, bcl-2, and p53. Clinical and laboratory parameters including Fas, bcl-2, and p53 positivity, age, sex, performance status, clinical stage, presence of B symptoms, bone marrow involvement, extranodal involvement, and lactic dehydrogenase levels were evaluated to compare overall survival. Complete remission was obtained in 28 patients (44.4%) after first-line chemotherapy. Fas positivity, male gender, good performance status, clinical stage I-II, absence of B symptoms, normal lactic dehydrogenase value, and absence of bone marrow involvement were favorable prognostic factors for complete remission in statistical analysis. Multivariate analysis revealed that positive Fas expression and ECOG performance status were independent prognostic factors for overall survival. Also, Fas-positive patiens had significantly prolonged progression-free survival. Immunohistochemical Fas positivity was a favorable prognostic factor for complete remission and overall and progression-free survival in primary nodal diffuse large B-cell lymphoma. Am. J. Hematol. 81:307,314, 2006. © 2006 Wiley-Liss, Inc. [source] Expression of CD44s and CD44v6 in transitional cell carcinomas of the urinary bladder: comparison with tumour grade, proliferative activity and p53 immunoreactivity of tumour cells,APMIS, Issue 11 2007JITKA KUNCOVÁ Alterations of CD44 glycoproteins have been shown to play an important role in progression of various malignancies, including urothelial cancer. We investigated expression patterns of CD44s and CD44v6 in transitional cell carcinoma (TCC) of the urinary bladder in relation to tumour grade, proliferative activity, and immunoreactivity for p53. The selected markers were detected immunohistochemically in 122 samples of TCC. We found a close relationship between CD44s and CD44v6 expression and tumour grade. The extension of positive staining for CD44s and CD44v6 towards the luminal surface was a predominant feature of differentiated carcinomas (grades 1 and 2), suggesting deranged maturation of cancer cells related to their neoplastic transformation. Heterogeneous expression of CD44s and CD44v6 predominated in poorly differentiated tumours (G3,4). However, areas of squamous differentiation within the high-grade tumours displayed strong immunoreactivity for both CD44s and CD44v6. The proliferative activity and p53 overexpression increased with the dedifferentiation of the tumour. The results of this study are discussed in relation to the significance of CD44 expression in TCC and to the explanation for controversial results reported in previous studies on the relationship between CD44 expression and the biological behaviour of urothelial cells. [source] Vasculitic neuropathy , electrodiagnostic findings and association with malignanciesACTA NEUROLOGICA SCANDINAVICA, Issue 6 2007S. A., ivkovi Background,,, Vasculitic neuropathies occur in the context of systemic disorders or in isolation. Histopathologic evaluation remains the gold standard for diagnosis, but certain electrodiagnostic findings may heighten suspicion of vasculitic neuropathy and improve the yield of nerve and muscle biopsy. Aim of the study,,, Description of electrodiagnostic patterns associated with vasculitic neuropathies, and a report of a possible association with malignancies. Methods,,, Retrospective review of medical records of patients with histopathologically proven vasculitic and non-vasculitic axonal neuropathies evaluated at the University of Pittsburgh Medical Center from November 1995 to November 2003. Results,,, The most distinctive electrodiagnostic patterns associated with vasculitic neuropathy were mononeuritis multiplex (27.5% vs 4% in controls; P = 0.003) and axonal sensorimotor polyneuropathy with side-to-side amplitude asymmetry (50% vs 32%, P > 0.05). Additionally, six patients (15% vs 2%; P = 0.034) developed various malignancies within 2 years of onset of vasculitic neuropathy. Conclusions,,, While generalized polyneuropathy was the most common presentation of nerve vasculitis, our study affirms side-to-side amplitude asymmetry and mononeuritis multiplex as the most distinctive electrodiagnostic features. The frequent occurrence of malignancies suggests a possible association with the vasculitic neuropathy and warrants additional investigation. [source] Neoplastic stem cells: A novel therapeutic target in clinical oncologyCANCER, Issue 10 2006Axel Schulenburg MD Abstract Cancer is among the leading causes of morbidity and mortality in the Western world. Despite recent advances, most therapeutic approaches fail to eradicate the entire neoplastic clone. The remaining cells often develop metastasis and/or recurrences and therefore may represent attractive targets of therapy. A new exciting concept in this regard suggests that each neoplasm represents a heterogeneous population of cells that pertain to long-term tumor growth both in vivo in the natural host and in experimental animals. This concept postulates the existence of small fractions of ,tumor stem cells' that exhibit a capacity for self-renewal and unlimited growth and therefore are distinct from their progeny. Based on these hypotheses, the targeting of neoplastic stem cells is considered indispensable for eradication of the entire clone and for the development of curative treatment approaches. However, tumor stem cells often may be quiescent cells and may express a different profile of targets compared with ,more mature' tumor cells. Therefore, current efforts have attempted to characterize target expression profiles in cancer stem cells in various malignancies. In the this review, the authors have provided a brief summary of the current knowledge of neoplastic stem cells and the application of respective concepts in translational oncology with the ultimate objective of improving anticancer therapy. Cancer 2006. © 2006 American Cancer Society. [source] The basic and clinical implications of ABC transporters, Y-box-binding protein-1 (YB-1) and angiogenesis-related factors in human malignanciesCANCER SCIENCE, Issue 1 2003Michihiko Kuwano In our laboratories, we have been studying molecular targets which might be advantageous for novel cancer therapeutics. In this review, we focus on how ATP-binding cassette (ABC) transporter superfamily genes, Y-box-binding protein-1 (YB-1), and tumor angiogenesis-associated factors could contribute to the development of novel strategies for molecular cancer therapeutics. ABC transporters such as P-glycoprotein/MDR1 and several MRP family proteins function to protect cells from xenobiotics, drugs and poisons, suggesting that ABC transporters are a double-edged sword. In this regard, P-glycoprotein/MDR1 is a representative ABC transporter which plays a critical role in the efflux of a wide range of drugs. We have reported that gene amplification, gene rearrangements, transcription factor YB-1 and CpG methylation on the promoter are involved in MDR1 gene overexpression in cultured cancer cells. Among them, two mechanisms appear to be relevant to the up-regulation of MDR1 gene in human malignancies. We first reported that MDR1 gene promoter is activated in response to environmental stimuli, and is modulated by methylation/demethylation of CpG sites on the MDR1 promoter. We also demonstrated that YB-1 modulates not only transcription of various genes associated with cell growth, drug resistance and DNA synthesis, but also translation, mRNA stabilization and DNA repair/self-defense processes. Angiogene-sis is also involved in tumor growth, invasion and metastasis of various malignancies, and so angiogenesis-related molecules also offer novel molecular targets for anticancer therapeutics. (Cancer Sci 2003; 94: 9,14) [source] | ||||||||||||||||||||||