cefoxitin and Cell-Transformation--Neoplastic

RCAS1 is a receptor-binding cancer antigen which is expressed on human uterine cervical adenocarcinoma cell line (SiSo). Finding a correlation between the expression of this gene and the overall survival of patients with 14 different types of cancer points to the clinical significance of this gene. Moreover, the expression RCAS1 correlates with other clinicopathological parameters including the histological type of cancer, its differentiation, tumor size, clinical stage, the depth of invasion, lymphovascular space involvement, lymph node metastasis, and positive peritoneal cytological results. RCAS1 can induce apoptosis in peripheral lymphocytes in vitro as well as in an increased number of apoptotic tumor-infiltrating lymphocytes. RCAS1 is also believed to contribute to the escape of tumor cells from immune surveillance. RCAS1 is secreted via ectodomain shedding, and its expression is related to changes in the characteristics of the extracellular matrix and to a reduced number of vimentin-positive tumor stromal cells, findings that suggest that RCAS1 may induce connective tissue remodeling. The concentration of RCAS1 in serum or pleural effusions has been found to be significantly higher in patients with several different types of cancer as compared to normal controls. Together, the available data shows that RCAS1 may have value as a biomarker for monitoring therapeutic efficacy. Further exploration of the biological function of RCAS1 should help in the development of new therapeutic strategies against human malignancies.

Topics: Animals; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Apoptosis; Biomarkers, Tumor; Cell Transformation, Neoplastic; Endometrium; Female; Gastric Mucosa; Gene Expression Regulation, Neoplastic; Genital Neoplasms, Female; Humans; Immune System; Lymphocytes; Models, Biological

Malignant transformation is often associated with abnormal protein glycosylation expressed, amongst others, by the accumulation of simple mucin-type carbohydrates namely Tn and Sialyl-Tn (STn) antigens. These are usually limited in normal tissues and their increased expression has been associated with cancer progression and poor prognosis. This study aims to evaluate the role of Tn and STn antigens in the neoplastic transformation of the canine gastric mucosa and to correlate their putative immunoexpression alterations with some pathological features. Tn and STn antigens expression were immunohistochemically evaluated in canine normal gastric mucosa (n = 3), gastric polyps (n = 9) and gastric carcinomas (n = 25), neoplastic emboli (n = 12) and metastases (n = 8). In normal gastric mucosa, Tn antigen was detected in the gastric epithelial cells, while STn antigen was absent. Similarly, all gastric polyps expressed Tn antigen, but none displayed STn antigen immunostaining. In carcinomas, Tn antigen was expressed in 96% of the cases and STn antigen in 68% of the neoplasms. STn antigen was significantly higher in carcinomas compared with normal mucosa (P < .05). No correlation was found between each antigen and the different subtypes of tumours according to WHO classification, tumour differentiation, lymph vascular invasion or metastasis. All neoplastic emboli expressed both antigens, and the expression score was similar or higher than that displayed by the neoplastic cells of the primary tumour. The high prevalence of STn antigen in gastric carcinomas compared with normal mucosa highlights the cancer-associated nature of this antigen. Our results link STn antigen expression to neoplastic transformation and suggest that it may be a useful marker of gastric cancer progression in dogs.

Topics: Animals; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma; Cell Transformation, Neoplastic; Dog Diseases; Dogs; Female; Male; Polyps; Stomach Neoplasms

Chronic inflammation and composition of the colon microbiota have been associated with colorectal cancer in humans. The human commensal enterotoxigenic Bacteroides fragilis (ETBF) is linked to both inflammatory bowel disease and colorectal cancer and, in our murine model, causes interleukin 17A (IL-17A)-dependent colon tumors. In these studies, we hypothesized that persistent colonization by ETBF is required for tumorigenesis.. We established a method for clearing ETBF in mice, using the antibiotic cefoxitin. Multiple intestinal neoplasia mice were colonized with ETBF for the experiment duration or were cleared of infection after 5 or 14 days. Gross tumors and/or microadenomas were then evaluated. In parallel, IL-17A expression was evaluated in wild-type littermates.. Cefoxitin treatment resulted in complete and durable clearance of ETBF colonization. We observed a stepwise increase in median colon tumor numbers as the duration of ETBF colonization increased before cefoxitin treatment. ETBF eradication also significantly decreased mucosal IL-17A expression.. The timing of ETBF clearance profoundly influences colon adenoma formation, defining a period during which the colon is susceptible to IL-17A-dependent tumorigenesis in this murine model. This model system can be used to study the microbiota-dependent and molecular mechanisms contributing to IL-17A-dependent colon tumor initiation.

Topics: Animals; Bacteroides fragilis; Carcinogenesis; Cefoxitin; Cell Transformation, Neoplastic; Colon; Colonic Neoplasms; Enterotoxins; Humans; Mice

Testicular germ cell tumours (TGCT) exhibit remarkable ability to differentiate into virtually all somatic tissue types. In this study, we investigated changes in mucin-type O-glycosylation, which have been associated with somatic cell differentiation and cancer. Expression profile of simple mucin-type O-glycans (Tn, sialyl-Tn, T), histo-blood group H and A variants and six polypeptide GalNAc-transferases (T1-4, T6, T11) that control the site and density of O-glycosylation were analysed by immunohistochemistry during human testis development and in TGCT. Normal testis showed a restricted pattern; gonocytes expressed abundant sialyl-Tn and sialyl-T, and adult spermatogonia were devoid of any glycans, whereas spermatocytes and spermatids expressed exclusively glycans Tn and T and the GalNAc-T3 isoform. A subset of mature ejaculated spermatozoa expressed an additional glycan sialyl-T. The pattern found in testicular neoplasms recapitulated the developmental order: Pre-invasive carcinoma in situ (CIS) cells and seminoma expressed fetal type sialylated glycans in keeping with their gonocyte-like phenotype. Neither simple mucin-type O-glycans nor GalNAc-transferase isoforms were found in undifferentiated nonseminoma, i.e. embryonal carcinoma, whereas teratomas expressed them all to some extent but in a disorganized manner. We concluded that simple mucin-type O-glycans and their transferases are developmentally regulated in the human testis, with profound changes associated with neoplasia. The restricted O-glycosylation pattern in haploid germ cells suggests a role in their maturation or egg recognition/fertilization warranting further studies in male infertility, whereas the findings in TGCT provide new diagnostic tools and support our hypothesis that testicular cancer is a developmental disease of germ cell differentiation.

Topics: Antigens, Tumor-Associated, Carbohydrate; Antigens, Viral, Tumor; Cell Differentiation; Cell Transformation, Neoplastic; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; N-Acetylgalactosaminyltransferases; Phenotype; Polypeptide N-acetylgalactosaminyltransferase; Spermatogenesis; Spermatozoa; Testicular Neoplasms; Testis

VVA-B4 lectin was used to investigate the differences in Tn antigen expression in tissues of different types of human breast cancer (benign lesions, carcinoma in situ, invasive carcinoma) and in normal tissues neighboring lobular carcinoma. Locations in which Tn antigen was expressed were identified using the avidin-biotin-peroxidase labeling system. Tissues collected during cosmetic procedures and classified as normal were completely negative, except for one case. Benign proliferative changes including fibroadenoma, apocrine and cylindrical metaplasia showed a very weak positive reaction, although strongly positive cells were also observed. The reaction in non-invasive cases of atypical hyperplasia was diversified depending on site. Intralobular hyperplasia was characterized by a particularly high percentage of labeled cells. A majority (up to 80%) of ductal and lobular carcinoma in situ showed very strong or moderate staining. In invasive cancers, there were conspicuous differences between stage of cancer development and tendency towards a decrease in intensely labeled cell count in the most advanced stages. In normal tissues in the direct neighborhood of carcinoma in situ, the cytoplasm of 40% of cells was strongly labeled. However, the findings for normal tissues in the close vicinity of invasive cancer were the most surprising, since there was either no or only very weak positive reaction. It can be concluded that glycosylation modifications during carcinogenesis, as demonstrated by the presence of Tn epitope, develop very early, before any destructive changes in proliferation/apoptosis or cell differentiation become discernible.

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Breast Neoplasms; Carcinoma in Situ; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Cell Transformation, Neoplastic; Female; Fibroadenoma; Humans; Hyperplasia; Immunohistochemistry; Lectins; Precancerous Conditions

Mucins and simple mucin-type carbohydrates are cancer-associated antigens in several human tumors. Expression of Tn, sialosyl-Tn, Thomsen-Friedenreich (T), sialosyl-T and of a recently identified mucin-like glycoprotein (gp230) has not yet been thoroughly investigated in human cervix carcinogenesis. In the present study sections from normal cervix (n=10), CIN III lesions (n=10), and invasive carcinomas (n=47) were evaluated immunohistochemically using monoclonal antibodies. In normal cervix there was: cytoplasmatic expression of Tn in 1 case (10%); membranous expression of STn in 8 cases (80%); no expression of T and cytoplasmatic expression of ST in 1 case (10%); gp 230 was expressed in all cases with a membranous pattern. In CIN III lesions there was cytoplasmatic and membranous expression of Tn in 3 cases (30%) and of STn in 9 cases (90%); T and ST were not expressed; gp 230 was expressed in 5 cases (50%) both in the cytoplasm and at the cell membrane. In invasive carcinomas we observed Tn expression in 30 cases (63.8%) and STn in 31 cases (66%); T antigen was not expressed; expression of both ST and gp 230 in 24 cases (51.1%); all antigens showed membranous and cytoplasmatic staining. Our results show that Tn and ST are good markers of invasive carcinomas of the human cervix. We have also shown that loss of expression of the mucin-like glycoprotein gp 230 is associated with malignant transformation at a preinvasive stage.

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma; Carcinoma in Situ; Cell Transformation, Neoplastic; Cervix Uteri; Female; Glycoproteins; Humans; Mucins; Neoplasm Invasiveness; Reference Values; Sensitivity and Specificity; Uterine Cervical Dysplasia; Uterine Cervical Neoplasms

Topics: Adenoma; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoma; Cell Transformation, Neoplastic; Female; Formaldehyde; Glycosylation; Humans; Immunohistochemistry; Male; Mucins; Paraffin Embedding; Prognosis; Radiotherapy; Retrospective Studies; Salivary Gland Neoplasms; Salivary Glands; Tissue Fixation

Epithelial mucins are present at the apical membranes of gastrointestinal epithelial cells or in their secretions. In this study, we examined the occurrence of peptide epitopes of the mucins MUC1 and MUC3 and of three mucin-associated glycotopes (TF, Tn, and s-Tn) in a series of colorectal tissue samples (normal colon, adenomas with different grades of dysplasia, carcinoma in situ, and invasive carcinomas). A new monoclonal antibody to a conformation-dependent peptide epitope of MUC1 was employed, which does not react with the fully glycosylated mucin as found in normal gastrointestinal mucosa. We found that adenomas acquired the ability to expose Tn, s-Tn, TF and MUC1 epitopes, and this correlated with increasing malignant potential. The secretory mucin, MUC3, revealed a different pattern: it was detectable in all sections, with maximum expression in adenomas and decrease in carcinomas. Most importantly, normal mucosa and benign lesions showed supra-nuclear and/or apical distribution of these antigens, but malignant lesions and lesions with a very high risk of malignancy revealed diffuse cytoplasmic and basolateral membrane localization. The immunohistological response to a combination of MUC1-related antibodies may assist in assessing the malignant potential and status of lesions of the colon.

Topics: Adenoma; Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma; Cell Membrane; Cell Transformation, Neoplastic; Colonic Neoplasms; Cytoplasm; Humans; Immunohistochemistry; Intestinal Mucosa; Intracellular Membranes; Mucin-1; Mucin-3; Mucins; Precancerous Conditions