cefoxitin and Carcinoma--Squamous-Cell

In order to determine whether the expression of tumour-associated carbohydrate antigens (Tn/sTn) and a representative inflammation marker, nuclear factor-κB (NF-κB), is associated with the invasiveness of oral squamous cell carcinoma (OSCC), this study has attempted to investigate the correlation of the aforementioned markers with the well-established invasive pattern grading score (IPGS) and clinicopathological parameters.. Specimens from 143 OSCC patients with classified clinicopathological parameters and IPGS were stained immunohistochemically using anti-Tn, sTn and NF-κB antibodies. Our results showed that the expression of both Tn and NF-κB was correlated positively with staging (P = 0.036; P = 0.015), recurrence (P < 0.001; P < 0.001) and distant metastasis (P = 0.005; P = 0.009), as well as with IPGS, while the expression of sTn was correlated inversely. In addition, poor survival was associated with overexpression of Tn and NF-κB but not with expression of sTn.. Our results indicate that a reciprocal relationship between Tn and sTn expression may serve as a reliable indicator for OSCC prognostic evaluation. In addition, expression of Tn rather than sTn may play an important role in deeply invasive OSCC via regulation of NF-κB signalling.

Topics: Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Squamous Cell; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Mouth Neoplasms; Neoplasm Invasiveness; NF-kappa B; Prognosis; Signal Transduction

Tumor-associated antigens are appreciated as diagnostic markers, but they have also prompted tremendous efforts to develop tumor-specific immunotherapy. A previously cloned tumor-associated antigen, EBAG9, was initially defined by reactivity with the monoclonal antibody 22-1-1. Functionally, the EBAG9-encoded gene-product was believed to induce apoptosis in activated immune cells. However, using a cell-biological approach we identified EBAG9 as a Golgi-resident modulator of O-linked glycan expression, the latter product was then recognized by the 22-1-1 antibody. Secondly, EBAG9 expression was found physiologically in all murine tissues examined. This raised the question if EBAG9 is tumor-specific and mediates apoptosis itself or through O-linked glycans generated, among them the cognate 22-1-1 antigen Tn.. We have used immunohistochemistry to detect the expression of 22-1-1 and EBAG9 in various tissues. Correlation between expression of both antigens in cell lines was analysed by immunoblot and flow cytometry. Apoptosis was studied by using flow cytometry and Caspase-Glo 3/7 assay kit. Cellular distribution of EBAG9 was analysed by electron and confocal microscopy.. Here, we compared expression of the 22-1-1 and EBAG9-defined antigens in normal and neoplastic tissues in situ. In contrast to 22-1-1 staining, EBAG9 is a ubiquitously expressed antigen in all normal and cancerous tissues. Functional studies on the role of 22-1-1 reactive material did not support any evidence for apoptosis induction. Employing electron and confocal microscopy, a refined subcellular localization of EBAG9 at the Golgi was obtained.. We suggest that the estrogen-inducible EBAG9 gene-product and the 22-1-1 defined antigen are structurally and functionally separate antigens.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Brefeldin A; Carcinoma; Carcinoma, Squamous Cell; Caspase 3; Caspase 7; Caspases; Cell Line; Cell Line, Tumor; Cell Nucleus; Colorectal Neoplasms; Flow Cytometry; Golgi Apparatus; Humans; Immunoblotting; Immunohistochemistry; Immunotherapy; Lung Neoplasms; Male; Microscopy, Confocal; Microscopy, Electron; Mouth Neoplasms; Nocodazole; Polysaccharides; Prostatic Neoplasms; Protein Synthesis Inhibitors; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms; Subcellular Fractions; Tissue Distribution

To investigate the influence of sialic acid removal on MUC1 peptidic and carbohydrate epitope reactivity in head and neck squamous cell carcinoma (HNSCC), tumor samples belonging to 24 HNSCC patients were studied by standard immunohistochemistry (IHC) with and without desialylation with 0.1 U/ml neuraminidase. From each tumor sample, subcellular fractions were obtained and analyzed by SDS-PAGE and Western blotting (WB). Three monoclonal antibodies (MAbs) were used: C595 MAb directed to MUC1 protein core, an anti-Tn hapten MAb, and an anti-sTn hapten MAb; a comparative analysis between desialylated and sialylated samples was performed. By IHC without neuraminidase treatment, 19 of 24 samples reacted with anti-MUC1 peptidic epitope, while Tn hapten was not detected and sTn was found in 1 of 24 cases. Desialylation increased either the number of reacting cells or the intensity of the reaction with C595 and anti-Tn MAbs, and some negative samples became positive. On the other hand, sTn expression decreased with desialylation. By WB, several bands from >200 to 25 kDa were found; desialylation increased high-molecular-weight bands, diminishing the detection of low-molecular-weight ones. The use of desialylation is a suitable treatment that contributes to the exposure of MUC1-associated epitopes, which may be related to the spreading of HNSCC.

Topics: Aged; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Binding Sites, Antibody; Blotting, Western; Carcinoma, Squamous Cell; Electrophoresis, Polyacrylamide Gel; Epitopes; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Mucin-1; N-Acetylneuraminic Acid

The progression from uncontrolled cell proliferation to invasion and metastasis of epithelial tumors is partially understood. Alteration of epithelial mucin expression have been described in different malignant localizations but only few attempts have been made to identify mucin expression in malignant laryngeal tumors. In the present report, results are shown of studies on the expression of mucins and carbohydrate related antigens in laryngeal cancer and on the isolation of MUC1 mucin from this tumor tissue. Malignant laryngeal specimens were processed for immunohistochemical analysis and for extranuclear membrane fractions (ENM) which were obtained by ultracentrifugation. Subsequently, ENM samples were centrifuged in density-gradient; the analysis of fractions was performed by means of SDS-PAGE and Western-blotting. The panel of monoclonal antibodies (MAbs) included anti MUC1 mucin, anti Lewis x, anti sialyl Lewis x, anti Lewis y, anti MUC-5B, anti oral mucin (gp230), anti Tn hapten, anti p53 and anti cytokeratins. By immunohistochemistry, it was possible to detect MUC1 mucin, Lewis x and Lewis y showing strong reactions while sialyl-Lewis x and Tn antigen only reacted weakly in a few cells; cytokeratins were detected in all samples. In ENM derived fractions obtained by CsCl centrifugation, MUC1 was demonstrated by Western blotting.. (1) laryngeal cancer antigenic expression comprises mostly MUC1 mucin, Lewis x, Lewis y as well as Tn antigen and (2) the methodology here employed is useful to isolate MUC1 from tumor samples.

Topics: Aged; Antigens, Tumor-Associated, Carbohydrate; Blotting, Western; Carcinoma, Squamous Cell; Humans; Immunohistochemistry; Laryngeal Neoplasms; Lewis Blood Group Antigens; Lewis X Antigen; Male; Mucin-1; Mucins

An immuno- and lectin-histochemical study was performed to investigate the aberrant expression of blood group-related antigens and poly-N-acetyllactosamine structures in squamous cell carcinomas of the maxillary sinus, the larynx, the apipharynx, the hypopharynx, the oral cavity, the parotid gland and the tonsil from 52 patients using monoclonal antibodies against A, B and H antigens, and six lectins, UEA-I, PNA, VVA-B4, PWM, LEA and DSA. In addition, GSA-II staining following endo-beta-galactosidase digestion procedure was also applied. A, B and H antigens were expressed in most normal epithelial cells of head and neck organs, and depended on the patient blood type. However, in squamous cell carcinoma, A antigen was not detected in eight out of 25 individuals of blood groups A and AB, although B antigen was consistently expressed in carcinoma cells from all the B and AB individuals. On the other hand, H antigen was expressed in carcinoma cells not only from all blood group O individuals, but from 32 out of 35 individuals of blood groups A, B and AB. T and Tn antigens, which are recognized by PNA and VVA-B4, were strongly expressed in carcinoma cells from 40 and 42 out of 52 individuals respectively. Reactivity with GSA-II staining following endo-beta-galactosidase digestion, which recognizes linear poly-N-acetyllactosamine structures, was found in a few malignant cells from 21 individuals. Staining with anti-A, -B and -H monoclonal antibodies and UEA-I lectin was diminished after endo-beta-galactosidase digestion in some cases. Lectins specific for poly-N-acetyllactosamine, such as PWM, LEA and DSA, exhibited reactivity in some malignant cells from 30, 22 and 32 out of 52 individuals respectively. These results suggested that the expression of the blood group-related antigens is suppressed and immature carbohydrate chains, that is H, T and Tn antigens, are accumulated in squamous cell carcinomas of the head and neck. The results further suggested that poly-N-acetyllactosamine structures are simultaneously synthesized along with the deletion of A antigen and the accumulation of precursors.

Topics: ABO Blood-Group System; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Squamous Cell; Female; Glycosylation; Head and Neck Neoplasms; Humans; Male; Middle Aged; Polysaccharides

Alterations in the normal glycosylation process are often associated with oncogenic transformation. Using an anti-Tn monoclonal antibody, MLS128, we have investigated the immunohistochemical localization of Tn antigen in normal and malignant tissues of the digestive tract. In normal tissues, MLS128 was immunoreactive with the squamous epithelium of the esophagus and was weakly reactive with the columnar epithelia of the stomach, duodenum, colon, bile duct and pancreatic duct. In malignant tissues, positive immunostaining was detected with high frequency (75%-100%) in carcinomas of the esophagus, stomach colon, biliary tract and pancreas, whereas 2 of 11 (18%) hepatocellular carcinomas were positive. Tn antigen was detected in the upper two-thirds of the normal squamous epithelium, and was often detected in squamous cell carcinomas with cancer pearls (keratinization). These results suggest that the expression of Tn antigen is related to the differentiation of squamous epithelium, or to keratinization. In normal columnar epithelial cells. Tn antigen was localized mainly to the Golgi area. This intracellular localization was preserved in well-differentiated papillary adenocarcinomas of the colon, but was lost in most cases of tubular adenocarcinomas.

Topics: Adenocarcinoma; Antibodies, Monoclonal; Antibody Specificity; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Squamous Cell; Digestive System; Digestive System Neoplasms; Epithelium; Humans; Immunohistochemistry

The significance of altered expression of MN blood group antigens was examined by studies on the expressions of Thomsen-Friedenreich antigen (T antigen) and Tn antigen in primary and metastatic lesions of 29 human uterine cervical cancers. These antigens were measured by the avidin-biotin-peroxidase (ABC) method with peanut agglutinin (PNA) lectin for T antigen and Vicia villosa agglutinin (VVA) lectin for Tn antigen. Proportion of cancer cells expressing Tn antigen was higher in the metastatic lesions than in the primary tumors in 10 of the 29 cases, less in the metastasis than in the primary tumor in one case, and similar in the primary and metastatic lesions in the other 18 cases. Reaction for Tn antigen was positive in 24 (82.8%) of the 29 metastases, and in 17 (58.5%) of the 29 primary lesions. Thus, the rate of Tn antigen expression was significantly higher in the metastases than in the primary lesions (P < 0.05). On the other hand, there was no significant difference between the immunoreactivities of T antigen in metastases and primary tumors. These findings support our previous suggestion that expression of Tn antigen is closely related to the metastasis to regional lymph nodes and may reflect an important role of this carbohydrate in the process of metastasis of cervical cancer.

Topics: Adenocarcinoma; Antigens, Neoplasm; Antigens, Tumor-Associated, Carbohydrate; Carcinoma, Squamous Cell; Female; Humans; Lymphatic Metastasis; Uterine Cervical Neoplasms

The expressions of Thomsen-Friedenreich antigen (T-Ag) and Tn antigen (Tn-Ag), precursors of MN blood group antigens, were examined in the tissues of squamous cell carcinoma of the uterine cervix from 111 patients to determine their clinicopathologic significance with regard to the biologic behaviors of cancer cells and the clinical course of the patients.. T-Ag and Tn-Ag were measured by the avidin-biotin-peroxidase (ABC) method with peanut (Arachis hypogaea) lectin (PNA) and Vicia villosa agglutinin (VVA), respectively.. Unlike expression of T-Ag, that of Tn-Ag was correlated closely with vascular permeation of cancer cells, their parametrial spread and metastasis to the pelvic lymph nodes, and also with a low 5-year survival rate. No correlation was found between expression of Tn-Ag and other parameters, such as the clinical stage or histologic type. Furthermore, Tn-Ag expression was independent of the degree of cancer involvement in the fibromuscular stroma of the cervix, which seems to be a marker of the aggressiveness of cancer cell proliferation.. These results indicate that Tn-Ag expression is a useful indicator of the potential for metastatic potential of cancer cells. Thus, a combination of estimations of the degree of cancer involvement in the cervical stroma and Tn-Ag expression seems the most useful for predicting the prognosis of patients with cervical cancer.

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma, Squamous Cell; Female; Humans; Neoplasm Metastasis; Prognosis; Survival Analysis; Uterine Cervical Neoplasms

We present a case of pulmonary infection with Mycobacterium fortuitum demonstrating the development of multidrug resistance during therapy with multiple drugs. Emergence of drug resistance in a previously sensitive M fortuitum has been described with single drug therapy, but never before with multiple drug treatment. Development of resistance in the setting of multiple drug therapy illustrates the importance of repeated susceptibility testing during therapy.

Topics: Carcinoma, Squamous Cell; Cefoxitin; Drug Resistance, Microbial; Drug Therapy, Combination; Erythromycin; Humans; Lung Neoplasms; Male; Middle Aged; Mycobacterium Infections, Nontuberculous; Tuberculosis, Pulmonary