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Carcinoma Progression (carcinoma + progression)
Selected AbstractsMonocyte chemoattractant protein-1 (MCP-1)/CCL2 secreted by hepatic myofibroblasts promotes migration and invasion of human hepatoma cellsINTERNATIONAL JOURNAL OF CANCER, Issue 5 2010Maylis Dagouassat Abstract The aim of our study was to investigate whether myofibroblasts and the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 may play a role in hepatocellular carcinoma progression. We observed that hepatic myofibroblast LI90 cells express MCP-1/CCL2 mRNA and secrete this chemokine. Moreover, myofibroblast LI90 cell-conditioned medium (LI90-CM) induces human hepatoma Huh7 cell migration and invasion. These effects are strongly reduced when a MCP-1/CCL2-depleted LI90-CM was used. We showed that MCP-1/CCL2 induces Huh7 cell migration and invasion through its G-protein,coupled receptor CCR2 and, to a lesser extent, through CCR1 only at high MCP-1/CCL2 concentrations. MCP-1/CCL2's chemotactic activities rely on tyrosine phosphorylation of focal adhesion components and depend on matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, we observed that Huh7 cell migration and invasion induced by the chemokine are strongly inhibited by heparin, by ,-D-xyloside treatment of cells and by anti-syndecan-1 and -4 antibodies. Finally, we developed a 3-dimensional coculture model of myofibroblast LI90 and Huh7 cells and demonstrated that MCP-1/CCL2 and its membrane partners, CCR1 and CCR2, may be involved in the formation of mixed hepatoma-myofibroblast spheroids. In conclusion, our data show that human liver myofibroblasts act on hepatoma cells in a paracrine manner to increase their invasiveness and suggest that myofibroblast-derived MCP-1/CCL2 could be involved in the pathogenesis of hepatocellular carcinoma. [source] E-cadherin expression in early gastric carcinoma and correlation with lymph node metastasisJOURNAL OF SURGICAL ONCOLOGY, Issue 5 2007Dong Yi Kim MD Abstract Objective Abnormal expression of E-cadherin plays an important role in the differentiation and progression of gastric carcinoma. However, the relationship between molecular changes in E-cadherin and metastasis in early gastric carcinoma (EGC) is poorly understood. Materials and Methods Sixty cases of EGC with or without lymph node metastasis (30 node-positive cases and 30 node-negative cases) were investigated to evaluate hypermethylation status using bisulfate-MSP and immunohistochemistry using antibody against E-cadherin. Results Twenty-seven (45.0%) of 60 primary EGCs exhibited methylation in the CpG island of E-cadherin. Abnormal expression of E-cadherin was significantly correlated with patient age, tumor size, Lauren classification, differentiation, and lymph node metastasis. Using multiple logistic regression analysis, two factors were independent, statistically significant parameters associated with lymph node metastasis: abnormal expression of E-cadherin (risk ratio, 2.62; 95% confidence interval, 0.917,7.457; P,<,0.05) and lymphatic invasion (risk ratio, 8.11; 95% confidence interval, 1.612,40.766; P,<,0.05). Conclusion Our results suggest that methylation of E-cadherin is a frequent, early event in gastric carcinoma progression, and is correlated significantly with downregulated E-cadherin expression. Inactivation of E-cadherin might be involved in metastasis in EGC and play an important role in microscopic differentiation. J. Surg. Oncol. 2007;96:429,435. © 2007 Wiley-Liss, Inc. [source] Low COX2 in tumor and upregulation in stroma mark laryngeal squamous cell carcinoma progressionTHE LARYNGOSCOPE, Issue 9 2009Konstantinos Kourelis MD Abstract Objectives/Hypothesis: Invasive squamous cell carcinomas (SCC) of the larynx, like most solid tumors, are surrounded by a reactive stroma, in which cancer associated fibroblasts (CAFs) are the predominant cell type. This mesenchymal reaction may affect cancer progression multiply. The proinflammatory enzyme cyclooxygenase-2 (COX-2) has been correlated with head and neck cancer. This study aims to explore the impact of epithelial and stromal COX-2 expression on SCC behavior. Study Design: Retrospective case review study performed in a tertiary health center institution. Methods: Double immunohistochemistry of COX-2 and the CAF marker ,-smooth muscle actin (,-SMA) was utilized in 97 laryngeal cancer patients. Follow-up data were collected in 52 cases. Results: Low COX-2 immunostaining in cancer cells was associated with advanced grade (P = .044) and shorter recurrence-free period (P = .035). CAF expression was positively correlated with the grade of the infiltrating tumor (P = .030). Conclusions: In laryngeal SCCs, COX-2 may exert its deleterious effect by alterations in the tumor microenvironment. CAF-derived, COX-2-mediated paracrine influences on malignant cells possibly facilitate cancer progression. Overlooking the stromal remodeling could account for unsuccessful treatments of epithelial neoplasms. Laryngoscope, 2009 [source] Human embryonic stem cell genes OCT4, NANOG, STELLAR, and GDF3 are expressed in both seminoma and breast carcinomaCANCER, Issue 10 2005Uche I. Ezeh M.D. Abstract BACKGROUND The seminoma class of testicular germ cell tumor (TGCT) are characterized by a morphological resemblance to primordial germ cells (PGCs) or gonocytes, and chromosome duplications at 12p. Recently, it was determined that human embryonic stem cells (hESCs) express genes in common with PGCs, and that three of these genes, GDF3, STELLAR, and NANOG, are located on 12p. The current study was designed to identify whether expression of these 12p genes were elevated in seminoma relative to normal testis, and to determine whether elevated expression was unique to seminoma. METHODS Real-time polymerase chain reaction (PCR) and immunohistochemistry were used to assess gene expression in seminoma samples relative to normal testis and endpoint PCR was used to identify the presence or absence of these genes in breast carcinoma. RESULTS GDF3 expression was increased in eight of nine seminomas compared with normal testis, whereas NANOG, OCT4, or both were expressed at the highest levels in seminoma compared with all other markers analyzed. In addition, the NANOG protein was expressed in the majority of seminoma cells. The adult meiotic germ cell markers BOULE and TEKT1 were undetectable in seminoma, whereas the embryonic and adult germ cell markers DAZL and VASA were significantly reduced. Analysis of these markers in breast carcinoma and the MCF7 breast carcinoma cell line revealed that a core hESC-transcriptional profile could be identified consisting of OCT4, NANOG, STELLAR, and GDF3 and that NANOG protein could be detected in breast carcinoma. CONCLUSIONS These observations suggest that seminoma and breast carcinoma express a common stem cell profile and that the expression of DAZL and VASA in seminoma mark the germ cell origin of seminoma that is absent in breast carcinoma. Our findings suggest that stem cell genes may either play a direct role in different types of carcinoma progression or serve as valuable markers of tumorigenesis. Cancer 2005. © 2005 American Cancer Society. [source] Evaluation of HER-2/neu expression in prostatic adenocarcinomaCANCER, Issue 8 2002A request for a standardized, organ specific methodology Abstract BACKGROUND Some evidence suggests a role for HER-2/neu overexpression in prostate carcinoma progression. Reported rates of HER-2/neu overexpression in patients with prostate carcinoma vary greatly. METHODS The authors studied radical prostatectomy specimens from 38 patients who had biochemical failure after undergoing radical prostatectomy for prostate carcinoma. Immunohistochemistry for HER-2/neu overexpression using the HercepTest kit (Dako Corporation, Carpenteria, CA) was employed. Two different antigen-retrieval techniques were used: 1) the standard U.S. Food and Drug Administration (FDA)-approved HercepTest assay and 2) a modified HercepTest, which employed an alkaline citrate buffer, pH 9.0, for antigen retrieval and a 1-hour primary antibody incubation time. The level of HER-2/neu expression was evaluated on a scale from 0 (no staining) to 3+ according to the published guidelines. Fluorescent in situ hybridization for gene amplification was performed on all specimens. RESULTS With the standard technique, only one specimen had 2+ staining, and no specimens had 3+ staining. With the modified technique, 10 specimens (26%) had 2+ staining, and 9 specimens (24%) had 3+ staining. There was a significant association between the level of HER-2/neu expression shown with the modified technique and tumor stage (P = 0.03) as well as Gleason grade (P = 0.01). None of the specimens had HER-2/neu gene amplification. CONCLUSIONS The authors report a simple modification of the HercepTest that resulted in an increased rate of HER-2/neu expression, which was correlated with poor-risk pathologic findings. The findings suggest that adenocarcinoma of the prostate should be evaluated for HER-2/neu expression with a prostate specific immunohistochemical procedure that differs from the FDA-approved standard procedure. Cancer 2002;95:1650,5. © 2002 American Cancer Society. DOI 10.1002/cncr.10839 [source] In vivo manipulation of V,9V,2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patientsCLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2010S. Meraviglia Summary The potent anti-tumour activities of ,, T cells have prompted the development of protocols in which ,,-agonists are administered to cancer patients. Encouraging results from small Phase I trials have fuelled efforts to characterize more clearly the application of this approach to unmet clinical needs such as metastatic carcinoma. To examine this approach in breast cancer, a Phase I trial was conducted in which zoledronate, a V,9V,2 T cell agonist, plus low-dose interleukin (IL)-2 were administered to 10 therapeutically terminal, advanced metastatic breast cancer patients. Treatment was well tolerated and promoted the effector maturation of V,9V,2 T cells in all patients. However, a statistically significant correlation of clinical outcome with peripheral V,9V,2 T cell numbers emerged, as seven patients who failed to sustain V,9V,2 T cells showed progressive clinical deterioration, while three patients who sustained robust peripheral V,9V,2 cell populations showed declining CA15-3 levels and displayed one instance of partial remission and two of stable disease, respectively. In the context of an earlier trial in prostate cancer, these data emphasize the strong linkage of V,9V,2 T cell status to reduced carcinoma progression, and suggest that zoledronate plus low-dose IL-2 offers a novel, safe and feasible approach to enhance this in a subset of treatment-refractory patients with advanced breast cancer. [source] | ||||||||||