cefoxitin and Uterine-Cervical-Neoplasms

We report the results of a randomized, double-blind comparison of short-term versus long-term cefoxitin prophylaxis against infections after radical abdominal hysterectomy with pelvic and para-aortic lymphadenectomy. Of 113 evaluable patients, 54 (47.8%) received short-term (three doses) and 59 (52.2%) long-term (12 doses) prophylaxis with intravenous cefoxitin (2 g per dose). No significant differences in demographics, preoperative risk factors, or clinical course were detected between the two groups; nor did we detect significant differences in the incidence of surgical-site-related infections (7.4 versus 5.1%, respectively, P = .61), postoperative urinary tract infection, or other febrile morbidity. We conclude that short-term and long-term cefoxitin prophylaxis are equally effective for the prevention of post-operative surgical-site-related infections after radical hysterectomy.

Topics: Adult; Bacterial Infections; Cefoxitin; Female; Follow-Up Studies; Humans; Hysterectomy; Middle Aged; Postoperative Complications; Prospective Studies; Surgical Wound Infection; Uterine Cervical Neoplasms

Detection of lymph node metastases in cervical cancer patients is important for guiding treatment decisions, however accuracies of current detection methods are limited. We evaluated associations of abnormal glycosylation, represented by Tn and STn antigens on mucin (MUC) proteins, in primary tumor specimens with lymph node metastasis or recurrence of cervical cancer patients.. Surgical specimens were prospectively collected from 139 patients with locally-advanced cervical cancer undergoing lymphadenectomy enrolled in a nation-wide clinical trial (NCT00460356). Of these patients, 133 had primary cervix tumor, 67 had pelvic lymph node (PLN) and 28 had para-aortic lymph node (PALN) specimens. Fixed tissue serial sections were immunohistochemically stained for Tn, STn, MUC1 or MUC4. Neuraminidase was used to validate Tn versus STn antibody specificity. Stain scores were compared with clinical characteristics.. Primary tumor STn expression above the median was associated with negative PLN status (p-value: 0.0387; odds ratio 0.439, 95% CI: 0.206 to 0.935). PLN had higher STn compared to primary tumor, while primary tumor had higher MUC1 compared to PALN, and MUC4 compared to PALN or PLN (p = 0.017, p = 0.011, p = 0.016 and p < 0.001, respectively). Tn and STn expression correlated in primary tumor, PALN, and PLN, Tn and MUC1 expression correlated in primary tumors only (Spearman correlation coefficient [r] = 0.301, r = 0.686, r = 0.603 and r = 0.249, respectively).. STn antigen expression in primary cervical tumors is a candidate biomarker for guiding treatment decisions and for mechanistic involvement in PLN metastases.

Topics: Female; Humans; Lymph Node Excision; Lymph Nodes; Pelvis; Uterine Cervical Neoplasms

Tn antigen (GalNAc-α-O-Ser/Thr), a mucin-type O-linked glycan, is a well-established cell surface marker for tumors and its elevated levels have been correlated with cancer progression and prognosis. There are also reports that Tn is elevated in inflammatory tissues. However, the molecular mechanism for its elevated levels in cancer and inflammation is unclear. In the current studies, we have explored the possibility that cytokines may be one of the common regulatory molecules for elevated Tn levels in both cancer and inflammation. We showed that the Tn level is elevated by the conditioned media of HrasG12V-transformed-BEAS-2B cells. Similarly, the conditioned media obtained from LPS-stimulated monocytes also elevated Tn levels in primary human gingival fibroblasts, suggesting the involvement of cytokines and/or other soluble factors. Indeed, purified inflammatory cytokines such as TNF-α and IL-6 up-regulated Tn levels in gingival fibroblasts. Furthermore, TNF-α was shown to down-regulate the COSMC gene as evidenced by reduced levels of the COSMC mRNA and protein, as well as hypermethylation of the CpG islands of the COSMC gene promoter. Since Cosmc, a chaperone for T-synthase, is known to negatively regulate Tn levels, our results suggest elevated Tn levels in cancer and inflammation may be commonly regulated by the cytokine-Cosmc signaling axis.

Topics: Antigens, Tumor-Associated, Carbohydrate; Breast Neoplasms; Bronchi; Cell Line; CpG Islands; Culture Media, Conditioned; Disease Progression; DNA Methylation; Female; Fibroblasts; Gene Expression Regulation, Neoplastic; Genes, ras; Gingiva; Humans; Inflammation; Interleukin-6; Male; Molecular Chaperones; Prognosis; Promoter Regions, Genetic; Prostatic Neoplasms; Signal Transduction; Tumor Necrosis Factor-alpha; Uterine Cervical Neoplasms

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression.

Topics: Antigens, Tumor-Associated, Carbohydrate; Cell Line, Tumor; Colorectal Neoplasms; Female; Galactosyltransferases; Humans; Jurkat Cells; Melanoma; Molecular Chaperones; Neoplasms; Transfection; Uterine Cervical Neoplasms

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

The expression of simple mucin-type carbohydrate antigens, Tn and sialyl-Tn antigens, was evaluated by immunohistochemical staining with monoclonal antibodies in normal squamous epithelium, dysplasia, carcinoma in situ, and invasive squamous cell carcinoma of the uterine cervix. The expression of the Tn antigen detected by HB-Tn1 and B1.1 was found in 17 (20%) and 19 (23%) of the 83 invasive carcinomas, respectively, but was not found in the 36 normal squamous epithelia, 22 severe dysplasias, or 24 carcinomas in situ. The sialyl-Tn antigen was detected by HB-STn1 and TKH-2 in 14 (64%) and 11 (50%) of the 22 severe dysplasias, 13 (54%) and 10 (42%) of the 24 carcinomas in situ and 48 (58%) and 42 (51%) of the 83 invasive carcinomas, respectively, but was completely absent in 36 normal squamous epithelia. Coexpression of the sialyl-Tn antigen was observed in 89% of the cases expressing the Tn antigen. No significant difference was observed between the immunoreactivities of the antigens in the metastatic lymph nodes and primary tumors. No correlation was found between the expression of each antigen and clinical state, histologic type, depth of invasion, parametrial spread, lymphatic and vessel permeation, lymph node metastasis, or 5-year survival rate. The expression of Tn and sialyl-Tn demonstrates a specific change in the neoplastic progression from carcinoma in situ to invasive carcinoma and from normal to dysplasia, respectively, in squamous cell neoplastic lesions of the cervix. Tn and sialyl-Tn antigens may be useful markers for biologic investigation of neoplastic transformation in cervical squamous cell carcinoma.

Topics: Antigens, Tumor-Associated, Carbohydrate; Biomarkers, Tumor; Carcinoma; Epithelium; Female; Humans; Neoplasm Metastasis; Uterine Cervical Neoplasms; Uterus

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

Topics: Cefoxitin; Cervix Uteri; Combined Modality Therapy; Double-Blind Method; Female; Humans; Hysterectomy; Lymph Node Excision; Lymph Nodes; Neoplasm Recurrence, Local; Neoplasm Staging; Premedication; Surgical Wound Infection; Suture Techniques; Uterine Cervical Neoplasms

The concentration of cefoxitin (CFX, Merxin) in dead space exudate was studied in 14 patients following total extirpation of diffuse uterine cervical cancer. A two-compartment model was used for the analysis. The results obtained were as follows: Calculated maximum concentrations of CFX in the pelvic dead space exudate were 26.55 micrograms/ml at 2.11 hours, 31.07 micrograms/mg at 2.01 hours and 51.51 micrograms/ml at 2.10 hours after 1 hour intravenous drip infusions of CFX 2, 3 and 4 g, respectively. These concentrations were higher than the MIC80 of 12.5 micrograms/ml against E. coli and B. fragilis and were maintained for a sufficient period of time. Based on the results of this study, CFX is considered to be an important and valuable drug in the field of obstetrics and gynecology.

Topics: Adult; Aged; Bacterial Infections; Cefoxitin; Female; Humans; Infusions, Parenteral; Middle Aged; Pelvis; Surgical Wound Infection; Uterine Cervical Neoplasms