Expression In Epithelial Tumors Research Articles

Challenges of Androgen Receptor Expression in Epithelial Tumors of the Breast and Ovary

Challenges of Androgen Receptor Expression in Epithelial Tumors of the Breast and Ovary

Analysis of proliferative activity and levels of diagnostic cytokeratins expression in epithelial tumors of the ovaries with different malignancy potential

Analysis of proliferative activity and levels of diagnostic cytokeratins expression in epithelial tumors of the ovaries with different malignancy potential

Epidermal growth factor receptor gene expression evaluation in colorectal cancer patients.

Background: Colorectal cancer is one of the most common causes of death in the world and third and fourth most common cancer among men and women in Iran respectively. Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that shows over expression in epithelial tumors and regulates important processes in tumorigenesis. Incidence and characteristics of colorectal cancer are based on the geographic region and race. Aim: In this research work, the over expression of EGFR in formalin fixed paraffin-embedded (FFPE) colorectal cancer tumor tissue of patients was studied. Materials and Methods: Fifteen FFPE colorectal cancer tumor tissues (10 women and 5 men; 25-65 years old and stage IV) and 15 non-patients (nine women and six men; 25-65 years old) that were collected during 2006-2012. EGFR gene expression level was analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (PCR). All PCR reactions were performed in triplicate for both target gene and internal control (18s ribosomal ribonucleic acid) with the 2-ΔΔCT method. Gene expression differences in patients and controls were evaluated with t-test. Results: The results were showed EGFR gene over expression in 12 (80%) of 15 patients. There was a statistically significant difference in the prevalence of EGFR expression between patients and control (P < 0.05). Conclusion: Our results demonstrated EGFR gene over expression in colorectal cancer tumor tissue compared with controls.

Epithelial cell adhesion molecule-targeted drug delivery for cancer therapy

Introduction: The epithelial cell adhesion molecule (EpCAM) is abundantly expressed in epithelial tumors, on cancer stem cells and circulating tumor cells. Together with its role in oncogenic signaling, this has sparked interest in its potential for tumor targeting with antibodies and drug conjugates for safe and effective cancer therapy. Recent advances in protein engineering, linker design and drug formulations have provided a multitude of EpCAM-targeting anticancer agents, several of them with good perspectives for clinical development.Areas covered: This article reviews the biological, therapeutic and technical aspects of EpCAM-targeted drug delivery for cancer therapy. The authors discuss seminal findings, which distinguish EpCAM as a target with oncogenic function and abundant expression in epithelial tumors. Moreover, recent trends in engineering improved anti-EpCAM antibodies, binding proteins that are not derived from immunoglobulins and drug conjugates derived from them are highlighted and their therapeutic potential based on reported preclinical and clinical data, originality of design and perspectives are critically assessed.Expert opinion: EpCAM has shown promise for safe and efficient targeting of solid tumors using antibodies, alternative binding molecules and novel drug conjugates. Among the myriad of EpCAM-targeting drug delivery systems investigated so far, several could demonstrate therapeutic benefit, other formulations engineered to become tailor-made missiles are on the brink.

Poster 11: Exploring the Relationship Between Integrin αvβ6 and αβ1 in Oral Squamous Cell Carcinoma

Poster 11: Exploring the Relationship Between Integrin αvβ6 and αβ1 in Oral Squamous Cell Carcinoma

Expression Levels of the microRNA Processing Enzymes Drosha and Dicer in Epithelial Skin Cancer

ABSTRACTBackground: Dysregulation of microRNA (miRNA) metabolism has been observed in a variety of human cancers. In this pilot study, we investigated expression profiles of the two most important enzymes of the miRNA machinery, Drosha and Dicer, in relation to epithelial skin cancer and its premalignant stage.Methods: Patients with premalignant actinic keratoses (AK, n = 6), basal cell carcinomas (BCC, n = 15), and squamous cell carcinomas (SCC, n = 7) were included in the study. Punch biopsies were harvested from the center of the tumors (lesional) as well as from sites of healthy skin (intraindividual controls). Skin samples (n = 14) were also obtained from healthy subjects for additional controls. Dicer and Drosha mRNA levels were detected by quantitative real-time reverse transcriptase polymerase chain reaction.Results: Drosha expression levels were significantly upregulated in both the BCC and SCC groups compared to those in the healthy controls (p < .01), while Dicer expression levels in the BCC group were significantly lower (p < .05). Dicer expression in the SCC group was significantly higher compared to intraindividual controls (p < .05), while Dicer expression levels in both the SCC and AK groups were not significantly different from healthy control samples (p > .05). In the premalignant AK group, we could not observe any significant difference in Drosha or Dicer expression levels compared to either healthy or intraindividual controls (p > .05).Conclusions: We observed dysregulation of Drosha and Dicer expression in epithelial tumors when compared to healthy control samples. Therefore, we favor the hypothesis that miRNAs are involved in the carcinogenesis of epithelial skin cancer.

Apin participates in establishment of the incompletely‐differentiated junctional epithelium around teeth

A novel gene, Apin (Odam), belonging to a gene cluster encoding for proteins involved in the regulation of mineralization, was cloned in our laboratory. Initial studies suggested that Apin might mediate adhesion of the portion of the gingiva that attaches to the tooth surface (junctional epithelium; JE). It is also expressed in many epithelial cancers, including odontogenic tumors.PurposeTo validate the implication of Apin in JE formation by comparing its distribution in normal and regenerating gingiva. Materials and methods: Gingivectomies were done on the maxillae of adult rats. The contralateral maxilla was left intact as a control. Animals were sacrificed on days 0‐7 after surgery and maxillae were processed for paraffin embedding and immunolabeling for Apin.ResultsIn control samples, Apin was localized among cells of the JE and along its interface with the tooth. No labeling was seen in the residual gingiva at day 0. Over time, Apin labeling reappeared in the regenerating JE emerging from the gingiva. By day 7, the labeling pattern was similar to controls.ConclusionThe interfacial localization of Apin suggests that it plays a role in adhesion. Its presence among cells of the JE, an incompletely differentiated epithelium, and its expression in epithelial tumors indicates that Apin may also be implicated in other cellular activities such as differentiation. Support by CIHR and Department of Foreign Affairs.

Epigenetic regulation of the human mucin gene MUC4 in epithelial cancer cell lines involves both DNA methylation and histone modifications mediated by DNA methyltransferases and histone deacetylases

The human gene MUC4 encodes a transmembrane mucin, ligand of ErbB2, that is associated with pancreatic tumor progression. In the normal pancreas, MUC4 is not expressed, whereas activation of its expression is observed in the early steps of pancreatic carcinogenesis. The molecular mechanisms responsible for MUC4 gene activation are however still unknown. The MUC4 5'-flanking region being GC-rich and including two CpG islands, we hypothesized that epigenetic regulation may be involved and undertook to decipher the molecular phenomenons implied. By treating cancer cell lines with 5-aza-2'-deoxycytidine (5-aza) and trichostatin A (TSA), we were able to restore MUC4 expression in a cell-specific manner. We showed by bisulfite-treated genomic DNA sequencing and chromatin immunoprecipitation that methylation of five CpG sites and establishment of a repressive histone code at the 5'-untranslated region were associated with MUC4 silencing and impaired its activation by Sp1. Direct involvement of DNMT3A, DNMT3B, HDAC1, and HDAC3 was demonstrated by RNA interference and chromatin immunoprecipitation. Moreover, inhibition of histone deacetylation by TSA was associated with strong MUC4 repression in high-expressing cells. In conclusion, this work shows for the first time the importance of epigenetics in regulating MUC4 expression and may represent a new strategy to inhibit its expression in epithelial tumors.

Prostaglandin E Receptor EP4 Antagonism Inhibits Breast Cancer Metastasis

Cyclooxygenase-2 (COX-2) expression in epithelial tumors is frequently associated with a poor prognosis. In a murine model of metastatic breast cancer, we showed that COX-2 inhibition is associated with decreased metastatic capacity. The COX-2 product, prostaglandin E(2) (PGE(2)), acts through a family of G protein-coupled receptors designated EP1-4 that mediate intracellular signaling by multiple pathways. We characterized EP receptor expression on three murine mammary tumor cell lines and show that all four EP isoforms were detected in each cell. Stimulation of cells with either PGE(2) or the selective EP4/EP2 agonist PGE(1)-OH resulted in increased intracellular cyclic AMP and this response was inhibited with either EP2 or EP4 antagonists. Nothing is known about the function of EP receptors in tumor metastasis. We tested the hypothesis that the prevention of EP receptor signaling would, like inhibition of PGE(2) synthesis, inhibit tumor metastasis. Our results show for the first time that antagonism of the EP4 receptor with either AH23848 or ONO-AE3-208 reduced metastasis as compared with vehicle-treated controls. The therapeutic effect was comparable to that observed with the dual COX-1/COX-2 inhibitor indomethacin. EP3 antagonism had no effect on tumor metastasis. Mammary tumor cells migrated in vitro in response to PGE(2) and this chemotactic response was blocked by EP receptor antagonists. Likewise, the proliferation of tumor cells was also directly inhibited by antagonists of either EP4 or EP1/EP2. These studies support the hypothesis that EP receptor antagonists may be an alternative approach to the use of COX inhibitors to prevent tumor metastasis.

Conserved antigen expression in epithelial tumors recognized by monoclonal antibody 4A9 generated against canine mammary carcinoma cells.

Hybridoma-derived murine monoclonal antibodies (MoAbs) were generated by fusing P3X63-Ag8.653 myeloma cells with splenic cells from BALB/c mouse which had been immunized with viable canine mammary adenocarcinoma cells, CMT-2. Fifteen MoAbs were shown to react with immunizing cells in indirect immunofluorescence (IFA) and enzyme-linked immunosorbent (ELISA) assays. The reactivity of one IgM MoAb, designated 4A9, was evaluated. The antigen recognized by 4A9 on CMT-2 cells appeared to be localized both in cell membrane and cytoplasm against fixed and unfixed preparations by IFA. The 4A9 MoAb was found to bind with four of five canine mammary carcinoma cell lines while no binding was detected with normal fibroblastic cell lines. In vivo tissue distribution of 4A9 antigen was evaluated by indirect immunoperoxidase (IP) assay against formalin-fixed, paraffin-embedded sections of normal and neoplastic tissues. 4A9 MoAb reacted strongly to moderately with 75% of mammary carcinomas, moderately to weakly with 57% of benign mammary tumors, and strongly with squamous cell and perianal gland carcinomas (100%), interstitial cell tumors (100%), transitional cell carcinomas (43%), lung adenocarcinomas (40%), colon carcinomas (33%), and pancreatic adenocarcinomas (20%). Moderate to weak staining was detected with granulosa cell tumors (25%) and apocrine gland adenocarcinomas (50%). Strong reactivity with perianal gland carcinomas contrasted to no reactivity with perianal gland adenomas. No immunostaining was detected with a large variety and number of normal adult and fetal tissues tested; negligible and very restricted staining was observed in a few adult and fetal tissues. Normal mammary gland was negative. Since the antigen is expressed on the cell surface and in the cytoplasm of most mammary carcinoma cells and a variety of other epithelial tumor cells, the 4A9 antibody may have potential application in diagnosis and management of canine mammary cancer and a variety of other epithelial tumors.

Involucrin expression in epithelial tumors of oral and pharyngeal mucosa and skin

Involucrin has been recognized recently as a marker of terminal differentiation of squamous epithelial cells and also as a useful marker for keratinization; its expression in epithelial tumors of oral and pharyngeal mucosa and skin was examined. Involucrin in normal oral mucosa and skin was restricted to the granular and upper spinous layers and was absent in the basal layer. Hyperkeratosis was characterized by strong positive staining for involucrum in spinous and granular cell layers. A similar pattern was noted in seborrheic keratosis and verruca vulgaris. Condyloma acuminatum specimens revealed slight staining, whereas Paget cells were negative. Calcifying epitheliomas of Malherbe were usually unreactive. Papillomas exhibited the regular distribution of involucrin, as found in normal squamous epithelium. Basal cell carcinomas were generally negative, whereas squamous cell carcinomas showed an irregular distribution of involucrin. Immunohistochemical staining for involucrin may be useful for identification of keratinizing cells in epithelial tumor foci, just as is the use of monoclonal antibody to keratin KL 1.