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Intensive Screening (intensive + screening)
Selected AbstractsBreast magnetic resonance image screening and ductal lavage in women at high genetic risk for breast carcinomaCANCER, Issue 3 2004Anne-Renee Hartman M.D. Abstract BACKGROUND Intensive screening is an alternative to prophylactic mastectomy in women at high risk for developing breast carcinoma. The current article reports preliminary results from a screening protocol using high-quality magnetic resonance imaging (MRI), ductal lavage (DL), clinical breast examination, and mammography to identify early malignancy and high-risk lesions in women at increased genetic risk of breast carcinoma. METHODS Women with inherited BRCA1 or BRCA2 mutations or women with a > 10% risk of developing breast carcinoma at 10 years, as estimated by the Claus model, were eligible. Patients were accrued from September 2001 to May 2003. Enrolled patients underwent biannual clinical breast examinations and annual mammography, breast MRI, and DL. RESULTS Forty-one women underwent an initial screen. Fifteen of 41 enrolled women (36.6%) either had undergone previous bilateral oophorectomy and/or were on tamoxifen at the time of the initial screen. One patient who was a BRCA1 carrier had high-grade ductal carcinoma in situ (DCIS) that was screen detected by MRI but that was missed on mammography. High-risk lesions that were screen detected by MRI in three women included radial scars and atypical lobular hyperplasia. DL detected seven women with cellular atypia, including one woman who had a normal MRI and mammogram. CONCLUSIONS Breast MRI identified high-grade DCIS and high-risk lesions that were missed by mammography. DL detected cytologic atypia in a high-risk cohort. A larger screening trial is needed to determine which subgroups of high-risk women will benefit and whether the identification of malignant and high-risk lesions at an early stage will impact breast carcinoma incidence and mortality. Cancer 2004. © 2004 American Cancer Society. [source] An optimized method for intensive screening of molecules that stimulate , -defensin 2 or 3 (hBD2 or hBD3) expression in cultured normal human keratinocytesINTERNATIONAL JOURNAL OF COSMETIC SCIENCE, Issue 3 2005I. Pernet Synopsis Normal human skin controls the intrusion of microorganisms by the production of peptide antibiotics such as defensins. The aim of our study was to develop a culture model of normal human keratinocytes for optimal , -defensin mRNA detection which allows the screening of molecules able to stimulate hBD2 and hBD3 without inducing pro-inflammatory cytokines. A keratinocyte culture model in 96-well plates, in high calcium medium (1.7 mm) allowed to analyze hBD2 and hBD3 mRNA expression in basal condition and after cell stimulation by products from diverse vegetal extracts. The release of IL-8 and the chemokine MIP-3, was also evaluated in cell supernatants by ELISA. Among the 184 extracts tested, 75 showed a stimulatory effect on , -defensin expression: 40 on hBD2, 26 on hBD3 and nine on both defensins. Fifteen of these substances which also induced the release of pro-inflammatory cytokines were eliminated. Among the other substances, four were selected and were analyzed in a dose-dependent study (n = 4) by real-time quantitative RT-PCR and completed by a measure of MIP-3,, IL-8 and IL-1, levels. These data underline the important necessity of screening result controls by a quantitative method reproduced at least three times. This new method of intensive screening allowed us to exhibit vegetal extracts that were able to stimulate epidermal , -defensin expression without inducing an up-secretion of pro-inflammatory cytokines. Résumé La peau humaine normale exerce une fonction barrière contre l'intrusion de microorganismes par la production de peptides antibiotiques comme les défensines. Le but de cette étude a consistéà mettre au point un modèle de culture de kératinocytes humains normaux permettant une détection optimale des ARNm des défensines en général, et adapté au screening de molécules aptes à stimuler les défensines épidermiques hBD2 et hBD3 en particulier, sans induire de cytokines pro-inflammatoires. Un modèle de culture de kératinocytes en plaques 96 puits, en milieu riche en calcium (1,7 mm) permet une analyse de l'expression des ARNm de hBD2 et hBD3 en condition basale et après stimulation par divers extraits végétaux. La sécrétion d'IL-8 et de la chimiokine MIP-3, a étéévaluée dans les surnageants de culture par ELISA. Parmi les 184 extraits testés, 75 montrent un effet stimulant sur l'expression des , -défensines : 40 ont un effet sur hBD2, 26 sur hBD3 et 9 sur les 2 types de défensines. Quinze de ces actifs qui induisent aussi la sécrétion de cytokines pro-inflammatoires ont étééliminés. Parmi les autres molécules, 4 ont été sélectionnées pour faire l'objet d'une étude de leurs effets-doses (n = 4) sur l'expression des , -défensines par une technique quantitative de RT-PCR en temps réel. Cette étude est complétée par le dosage des cytokines IL-1,, IL-8 et MIP-3,. Les résultats obtenus soulignent l'importante nécessitée de contrôler au moins trois fois par une méthode quantitative les résultats d'un screening. Cette nouvelle méthode de screening intensif nous a permis de mettre en évidence des extraits végétaux capables de stimuler les défensines épidermiques sans induire de cytokines pro-inflammatoires. [source] WHAT DO ECONOMISTS TELL US ABOUT VENTURE CAPITAL CONTRACTS?JOURNAL OF ECONOMIC SURVEYS, Issue 1 2007Tereza Tykvová Abstract Venture capital markets are characterized by multiple incentive problems and asymmetric information. Entrepreneurs and venture capitalists enter into contracts that influence their behaviour and mitigate the agency costs. In particular, they select an appropriate kind and structure of financing and specify the rights as well as the duties of both parties. The typical features of venture capital investments are an intensive screening and evaluation process, active involvement of venture capitalists in their portfolio companies, staging of capital infusions, use of special financing instruments such as convertible debt or convertible preferred stock, syndication among venture capitalists or limited investment horizon. [source] The knockdown of endogenous replication factor C4 decreases the growth and enhances the chemosensitivity of hepatocellular carcinoma cellsLIVER INTERNATIONAL, Issue 1 2009Masaaki Arai Abstract Aims: To identify differentially expressed genes and thereby detect potential molecular targets for future therapies directed against hepatocellular carcinoma (HCC). Methods: To isolate differentially expressed genes between HCC and adjacent non-cancerous liver tissues, cDNA microarray and quantitative reverse transcriptase polymerase chain reaction analyses were performed. Gene knockdown experiments in HepG2 cells were also performed using small interfering RNAs (siRNAs). Proteins were detected by immunostaining, and cell proliferation was analysed using the MTT/WST-8 assay. Apoptosis and cell cycle analyses were performed using flow cytometry. Results: After an intensive screening for differentially expressed genes in HCC tissues, we isolated 23 upregulated genes in these lesions. Among these, we focused on the replication factor C4 (RFC4) gene. The expression of endogenous RFC4 proteins in HepG2 cells was found to be significantly reduced by RFC4 -specific siRNA. This inhibition of RFC4 expression correlated with a decrease in cellular proliferation, increased levels of apoptosis and a sensitizing of the cells to the DNA-damaging chemotherapeutic agents, doxorubicin and camptothecin. Conclusion: The replication factor C4 gene may be a novel target for developing cancer therapeutics, which can enhance the antitumour activity of chemotherapeutic agents that induce DNA damage. [source] Monocyte Chemoattractant Protein-1 (CCL2) in Inflammatory Disease and Adaptive Immunity: Therapeutic Opportunities and ControversiesMICROCIRCULATION, Issue 3-4 2003CHRISTINE DALY ABSTRACT Monocyte chemoattractant protein (MCP)-1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small-molecule antagonists of the receptor of MCP-1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP-1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP-1/CCL2,/, and CCR2,/, mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP-1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP-1/CCL2/CCR2 axis in disease. [source] Bullous pemphigoid as a dermadrome associated with spindle cell carcinoma of the gallbladderTHE JOURNAL OF DERMATOLOGY, Issue 3 2010Ayano UMEKOJI Abstract Skin disorders that appear in association with internal malignancies are called dermadromes. Bullous pemphigoid (BP), which is a major autoimmune disease of the skin, is considered to be a dermadrome, although there have been conflicting reports. We report a case of BP that preceded the diagnosis of an internal malignancy. Although we could not detect any malignancies on chest, abdominal or pelvic computer tomography on the first hospital admission, intensive screening on the third admission revealed a gallbladder malignancy. Laparoscopic cholecystectomy was performed. Histopathology showed a spindle cell carcinoma of the gallbladder. To the best of our knowledge, this is the first report of a spindle cell carcinoma of the gallbladder in a patient with BP. [source] | ||||||||||