Clinical outcomes of sentinel node navigation surgery in patients with preoperatively estimated stage IA endometrial cancer and evaluation of validity for continuing sentinel node navigation surgery based on dispersion of recurrence probability.

BACKGROUND: To evaluate the feasibility of the use and continuation of sentinel lymph node navigation surgery (SNNS) as an alternative to pelvic lymph node dissection (PLND) for patients with preoperatively estimated stage IA endometrial cancer. METHODS: This retrospective study selected the electronic medical records of all patients who had received CT scans and MRI imaging before surgery from April 1, 2009 to March 31, 2021. Sentinel lymph nodes (SLNs) were detected by administrating 99mTc-phytate and/or indocyanine green into the cervix, and the clinical outcomes of the patients who underwent SNNS or PLND were evaluated. Furthermore, in case of nodal recurrence, a new procedure to determine whether the facility should continue with SNNS or not was developed that compares the maximum likelihood hypothesis and an alternative one based on recurrence rates. RESULTS: Among 137 patients, SLN biopsies with ultrastaging were performed on 91 patients. The SLN detection rate was 95.6%. Over a 59-month median observation period, no statistically significant differences were shown in overall survival, disease-specific survival and disease-free survival between the SNNS and PLND groups when introducing the propensity score method (p-values: 0.06, 0.153, and 0.625, respectively). Our procedure demonstrated that, in our department without recurrence up to the 65th attempt, it was possible to continue SNNS if a recurrence occurs at the 66th attempt. CONCLUSION: This study suggests the validity of SNNS as an alternative to PLND. Even in the absence of evidence from randomized controlled trials, we can confirm the validity of continuing SNNS using our procedure.

Tumor-Infiltrating CD8-Positive T-Cells Associated with MMR and p53 Protein Expression Can Stratify Endometrial Carcinoma for Prognosis.

BACKGROUND: Inspired by the molecular classification of endometrial carcinoma (EC) proposed by The Cancer Genome Atlas Research Network (TCGA), we investigated tumor-infiltrating CD8-positive T-cell as well as DNA mismatch repair (MMR) protein and p53 protein expression, and we developed a new classification system for ECs to predict patients' prognosis using immunohistochemical methods. METHODS: The study included 128 patients with ECs who underwent surgery. Paraffin-embedded tissue sections of the tumor were stained using antibodies against MMR protein, p53, and CD8. Cases were stratified into four classes by a sequential algorithm. An immunohistochemical classification system for ECs (ICEC) was created, including HCD8, MMR-D, LCD8, and p53 LCD8. RESULTS: In ICEC, 16 cases (12.5%), 27 cases (21.09%), 67 cases (52.34%), and 18 cases (14.06%) belonged to HCD8, MMR-D, LCD8, and p53 LCD8, respectively. ICEC did not show any correlation with clinical stage, lymphovascular space invasion, or lymph node metastasis. However, the p53 LCD8 class contained a significantly higher proportion of G3 ECs and serous carcinoma (p < 0.0001). ICEC showed prognostic significance in overall survival (OS) (p < 0.0001) and disease-free survival (DFS) (p < 0.0001). The class of p53 LCD8 showed the worst prognosis among the classes. CONCLUSIONS: ICEC classification is useful in predicting the prognosis of ECs.

Questionnaire survey regarding current status of minimally invasive surgery for endometrial cancer in Japan: A cross-sectional survey for JSGOE members.

AIM: Minimally invasive surgery (MIS) has been introduced as an alternative to more radical surgical procedures. The Japan Society of Gynecologic and Obstetric Endoscopy and Minimally Invasive Therapy conducted a cross-sectional questionnaire survey to ascertain the status of MIS for endometrial cancer. METHODS: The survey was conducted between May 10 and June 30, 2022. The questionnaire included information on personal attributes, academic affiliations, qualifications, hysterectomies, and intraoperative procedures performed. RESULTS: The total number of questionnaire respondents was 436 (9.2% of the membership). The hysterectomy methods and percentage performed were as follows: simple total hysterectomy (equivalent to benign surgery), 3%; simple total hysterectomy with care to avoid shaving the cervix, 31%; extended total hysterectomy, 48%; and modified radical hysterectomy, 15%. An analysis of hysterectomies performed using MIS for endometrial cancer by qualified gynecologists of endoscopy or board-certified gynecologic oncologists showed a tendency not to choose simple total hysterectomy compared to the gynecologists who did not hold certification (p = 0.019, p = 0.045, and p = 0.010, respectively). Additionally, 67% of respondents did not use uterine manipulators, and 59% of the respondents did not perform lymph node dissection following the guidelines for treating endometrial cancer in Japan. CONCLUSION: This study provided the current status of MIS for endometrial cancer in Japan. The hysterectomy method, use of uterine manipulators, and criteria for omitting lymph node dissection were generally in agreement with the guidelines. Currently, an extra-fascial simple hysterectomy, including at least not shaving the cervix, was a major method for early invasive endometrial cancer using MIS.

A case of tricuspid valvular nonbacterial thrombotic endocarditis associated with advanced ovarian cancer.

Nonbacterial thrombotic endocarditis (NBTE) is characterized by the deposition of thrombi on the heart valves without bacteremia and predominantly affects patients with hypercoagulable state. Since the lesion of NBTE often exists in the left-sided valves, involvement of the tricuspid valve (TV) is rare. We herein report a 34-year-old woman with advanced ovarian cancer and pulmonary embolization showing NBTE on the TV. Plasma D-dimer level was markedly elevated and echocardiography showed highly mobile masses on the TV with moderate to severe regurgitation. After the initiation of heparin therapy, reduction of plasma D-dimer levels along with shrinkage of the TV vegetations was observed. However, she was forced to discontinue the heparin because its supply was interrupted in association with coronavirus disease 2019. Coupled with systemic metastasis of ovarian cancer, elevated plasma D-dimer level and exacerbation of NBTE were observed. Thereafter, she resumed subcutaneous injection of heparin, resulting in re-improvement. Learning objective: Involvement of tricuspid valve (TV) by nonbacterial thrombotic endocarditis (NBTE) is rare, especially when they are associated with advanced cancer. Our case underlines the importance of listing the NBTE as a differential diagnosis in cancer patients showing valve vegetations even in the TV.

Surgical skill and oncological outcome of laparoscopic radical hysterectomy: JGOG1081s-A1, an ancillary analysis of the Japanese Gynecologic Oncology Group Study JGOG1081.

OBJECTIVES: We investigated whether surgical skill and procedure were related to oncological outcomes in cervical cancer patients who underwent Laparoscopic Radical Hysterectomy (LRH). METHODS: We previously assessed data of LRH from 251 patients with FIGO stage (2009) IA2, IB1and IIA1 cervical cancer collected for JGOG 1081s study. 1) The JGOG 1081s cohort study was re-examined to refine the surgical details and extend the follow-up period as chart review. 2) Unedited videos for recurrent cases and matched non-recurrent control cases were newly compared by experts for various surgical skills and surgical procedures using the modified Objective Structured Assessment of Technical Skills (OSATS) tool, without awareness of the recurrence status as video review. RESULTS: After a median follow-up of 46 months, tumors had recurred in 31 of the 251 patients. The five-year Recurrence-Free Survival rate was 86.9% (81.8-90.6) and five-year Overall Survival rate was 93.7% (87.5-96.8). Multivariate analysis from chart reviews found that an experience with LRH of less than 20 cases per institution was an independent prognostic factor for recurrence (Hazard Ratio (HR) 2.49, 95%CI 1.12-5.53, p = 0.025). For the surgical video review, we compared 23 videos of recurrent cases with 23 background-matched non-recurrent controls. Lower modified OSATS scores from the video review were consistently trended to have a higher risk of recurrence. CONCLUSIONS: Our new study has found that LRH surgical experience and skill trended to have better oncological outcomes.

A Case of Endometrial Carcinosarcoma Containing Sertoliform Endometrioid Carcinoma Component.

Carcinosarcomas (CSs) of the endometrium have admixture of malignant epithelial and mesenchymal components. The carcinomatous component exhibit endometrioid, serous, or clear cell differentiation, or are undifferentiated. CSs are considered homologous or heterologous according to the type of sarcomatous component. Sertoliform endometrioid carcinomas (SECs) of the endometrium which comprise a rare subtype of endometrial cancer, typically occur in the ovary. SECs as a carcinomatous component of CS of the endometrium have not been reported. Here, we report an endometrial carcinosarcoma that contains an SEC component. An 88-year-old female presented to a clinic with atypical genital bleeding. She was referred to our hospital and underwent total hysterectomy, bilateral adnexectomy and partial omentectomy due to endometrial carcinoma. Gross examination revealed a polypoid mass in the uterine cavity with massive myometrial invasion. Histologically, the tumor was a high-grade endometrioid carcinoma. In addition to an ordinary conventional endometrioid carcinoma, approximately 30% of the area exhibited sex cord-like pattern and contained small hollow tubules, anastomosing cords and trabeculae, and tightly packed nests. Immunohistochemically, the SEC component showed diffuse p53 staining. Sex cord-like area, especially the solid area, showed positive staining for EMA, vimentin, α-inhibin, CD99, calretinin, p53, CD56, synaptophysin, and chromogranin A, which is a staining pattern similar to that previously reported SEC of the endometrium. Diminished membranous and positive cytoplasmic staining for ß-catenin was observed. This is the first case report of an endometrial carcinosarcoma containing an SEC component. SECs of the endometrium might exhibit sex cord-like differentiation in contrast to SECs of the ovary, which do not exhibit sex cord differentiation.

Survey of the clinical practice pattern of using sentinel lymph node biopsy in patients with gynecological cancers in Japan: the Japan Society of Gynecologic Oncology study.

BACKGROUND: Sentinel lymph node (SN) biopsy is essential for evaluating survival and minimal treatment-related morbidity associated with cervical, endometrial, and vulvar cancer in Japan. As such, our aim in this study was to evaluate the current practice pattern of using SN biopsy for cervical, endometrial, and vulvar cancer in Japan. METHODS: We deployed a 47-question survey on the use of SN biopsy for gynecological cancers to 216 gynecological oncology training facilities. The survey included information on the use of SN biopsy for uterine (cervical and endometrial) and vulvar cancers; details on the type, timing, and concentration of tracers used; surgical approach used for SN biopsy; method of biopsy and pathological examination; and facilities' experience with clinical research on SN biopsy. RESULTS: The response rate was 84% (181/216), with 40 facilities (22%) having experience in SN biopsy for gynecological cancers, 34 (85%) for uterine cancers, and 15 (37%) for vulvar cancers. Radioisotope, indocyanine green (ICG), and blue dyes were available for the detection of uterine cancers in 21 (52%), 25 (62%), and 19 (48%) facilities and for vulvar cancers in 9 (22%), 3 (7%), and 11 (27%) facilities, respectively. Thirty-four facilities (85%) used intraoperative frozen section procedure for diagnosis when possible, with 24 (71%) of these facilities using 2-mm specimen cuts. Diagnosis included pathological examination (85%), immunostaining (57%), and one-step nucleic acid amplification (5%). CONCLUSION: Increasing research evidence, providing insurance coverage for radioisotope tracers, and increasing the availability of training are expected to increase the use of SN biopsy in Japan.

[The current situation and agendas in the prevention and control of non-communicable diseases in Vietnam].

Objectives　In Vietnam, the number of patients with non-communicable diseases (NCDs) has been increasing in recent years in association with the country's remarkable economic growth and corresponding changes in its population's lifestyle. The purposes of this research were to identify the challenges in the prevention and control of NCDs in Vietnam and to discuss countermeasures for NCDs in Vietnam and Japan.Methods　As a 2015 Regional Public Health Overall Promotion Project, an investigation team consisting of 11 public health physicians visited Hanoi, the capital of Vietnam, and its vicinities from January 11, 2016 to January 15, 2016. In Hanoi and its vicinities, we visited local healthcare institutions, such as the World Health Organization(WHO) Representative Office in Vietnam and Ministry of Health of Vietnam, and discussed the prevention and control of NCDs in Vietnam and Japan.Results　According to a survey in 2014, 73% of people of all age groups in Vietnam died from NCDs and the number of people suffering from NCDs has been sharply increasing in recent years. Major behavioral risk factors are dietary risks, tobacco smoke, alcohol use, and physical inactivity. There are four main problems with prevention and control of NCDs: 1) low awareness among the people of NCDs, 2) regional disparity of medical services, 3) shortage of healthcare staff members with professional knowledge, and 4) poor NCD surveillance.　In Vietnam, an NCD program with screening methods and medical guidelines for respective diseases was developed in 2002. However, it only covered tertiary prevention and did not fully describe the primary and secondary prevention measures. Currently, with the technical assistance of the WHO, the implementation of countermeasures emphasizing prevention and control to reduce NCD risk factors has only just begun.Conclusion　It was considered that educating each person in Vietnam on NCD prevention measures would be necessary and that a national policy, like Healthy Japan 21 of Japan, and a nationwide screening project, such as specific medical checkups, could serve as a useful reference. We found that public health activities in Japan to penetrate a region mainly involving public health nurses had played important roles for Japanese people's health. Furthermore, Japan shares with Vietnam the challenges including the shortage of human resources, and therefore, the securement of healthcare staff members who confront health challenges and the enhancement of their abilities is required.

Management of pelvic lymph nodes by sentinel node navigation surgery in the treatment of invasive cervical cancer.

OBJECTIVE: Diagnosis of lymph node metastasis is a critical issue in the treatment of cervical cancer. Many studies describing sentinel node navigation surgery (SNNS) for examination of node status have been reported in the past decade. In this study, the feasibility of node status diagnosis by SNNS, including intraoperative frozen section diagnosis, in patients with early and advanced cervical cancer was evaluated. PATIENTS AND METHODS: Fifty-eight cervical cancer patients with early and advanced stage disease were enrolled. All patients were treated with backup pelvic lymphadenectomy after SNNS. To detect sentinel lymph nodes (SLNs), radioactive material and/or blue dye were used as tracers. Lymph nodes confirmed as SLNs were immediately sent to pathologists and diagnosed by frozen section intraoperatively. RESULTS: A total of 118 and 16 SLNs were pathologically investigated in early and advanced stage cervical cancer, respectively. The detection rate of SLNs in the early and advanced stages was 94.7% and 66.7%, respectively, whereas the detection rate using 1 or 2 tracers was 62.5% and 90%, respectively. The false-negative rate and negative predictive value was 0% and 100% for all stages. Pathological diagnosis by frozen section was completed within 30 minutes in all cases. CONCLUSIONS: Our data demonstrate that SNNS in cervical cancer is a promising procedure for patients with early stage (up to Ib1) disease, especially patients with small tumor diameter (<2.0 cm). However, SNNS raises several points for discussion before it can be established as a practical clinical procedure or as part of a subsequent radical hysterectomy.

TP53 codon 72 polymorphism and cervical cancer: a pooled analysis of individual data from 49 studies.

BACKGROUND: Cervical cancer is caused primarily by human papillomaviruses (HPV). The polymorphism rs1042522 at codon 72 of the TP53 tumour-suppressor gene has been investigated as a genetic cofactor. More than 80 studies were done between 1998 and 2006, after it was initially reported that women who are homozygous for the arginine allele had a risk for cervical cancer seven times higher than women who were heterozygous for the allele. However, results have been inconsistent. Here we analyse pooled data from 49 studies to determine whether there is an association between TP53 codon 72 polymorphism and cervical cancer. METHODS: Individual data on 7946 cases and 7888 controls from 49 different studies worldwide were reanalysed. Odds ratios (OR) were estimated using logistic regression, stratifying by study and ethnic origin. Subgroup analyses were done for infection with HPV, ethnic origin, Hardy-Weinberg equilibrium, study quality, and the material used to determine TP53 genotype. FINDINGS: The pooled estimates (OR) for invasive cervical cancer were 1.22 (95% CI 1.08-1.39) for arginine homozygotes compared with heterozygotes, and 1.13 (0.94-1.35) for arginine homozygotes versus proline homozygotes. Subgroup analyses showed significant excess risks only in studies where controls were not in Hardy-Weinberg equilibrium (1.71 [1.21-2.42] for arginine homozygotes compared with heterozygotes), in non-epidemiological studies (1.35 [1.15-1.58] for arginine homozygotes compared with heterozygotes), and in studies where TP53 genotype was determined from tumour tissue (1.39 [1.13-1.73] for arginine homozygotes compared with heterozygotes). Null results were noted in studies with sound epidemiological design and conduct (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes), and studies in which TP53 genotype was determined from white blood cells (1.06 [0.87-1.29] for arginine homozygotes compared with heterozygotes). INTERPRETATION: Subgroup analyses indicated that excess risks were most likely not due to clinical or biological factors, but to errors in study methods. No association was found between cervical cancer and TP53 codon 72 polymorphism when the analysis was restricted to methodologically sound studies. FUNDING: German Research Foundation (DFG).

Limitations on work and attendance rates after employees with cancer returned to work at a single manufacturing company in Japan.

OBJECTIVES: The purpose of this study was to evaluate the work limitations and attendance rates after employees diagnosed with cancer returned to work from sick leave, and to identify the related factors for the limitations and attendance rates at a single manufacturing company in Japan. METHODS: This study retrospectively analyzed 129 men and 4 women, employed in a single manufacturing industry, who returned to work after sick leave due to newly diagnosis of cancer. Limitations on work after the return to work were enforced in the workplace based on an industrial physician's evaluation. All the employees who needed measures for work were examined by the industrial physicians every 1-6 months until the termination of such work limitations. RESULTS: Limitations on work after the return to work were enforced for 79 (59%) employees (36 employees with alteration of work, 31 with prohibition of shift work and 55 with prohibition of overtime work). A higher degree of work limitations was significantly correlated with work-related factors before sick leave (i.e. shift work, production line) as well as disease/treatment-related factors (i.e. chemotherapy, recurrence/metastasis), while the attendance rates after the return to work were not correlated with adverse work-related factors before sick leave. CONCLUSION: The enforcement of work limitations for employees with cancer was relatively common and was based on both disease/treatment- and work-related factors, and this phenomenon may play an important role in the return to work as well as the successful continuation of work after cancer survivors return to work.

Suppression of invasive characteristics by antisense introduction of overexpressed HOX genes in ovarian cancer cells.

HOX genes encode transcription factors that function to establish basic body pattern during embryogenesis and maintain the function of specific organs in the adult. Recent studies have demonstrated that HOX genes are also involved in oncogenesis in a range of malignancies. To elucidate whether HOX genes contribute to ovarian carcinogenesis, we created an expression profile of HOX genes using ovarian derived materials from surgical samples and epithelial ovarian cancer cells derived from five different cell lines. Real-time quantitative RT-PCR assay indicated overexpression of 14 HOX genes in clusters A and B but only 2 genes in clusters C and D. Of the 16 HOX genes, overexpression of paralogs of HOX3, HOX4 and HOX7 is seen in cluster A and B, and of HOX13 in all paralogs. In addition, HOXB7, HOXA13 and HOXB13 showed high levels of overexpression in cancer cells and tissues whereas no or little expression was observed in normal controls. To examine whether overexpressed HOX genes regulate invasion of ovarian cancer cells directly, we introduced an antisense DNA fragment of overexpressed HOXB7 and HOXB13, and HOXC5 that did not show overexpression into SKOV3 cells by electroporation. Antisense introduction followed by chemoinvasion assay using matrigel chamber demonstrated that SKOV3 cells introduced an antisense of each HOXB7 and HOXB13 showed 85% and 50% reduction of invasion ability compared to the parental SKOV3 cells, respectively. In contrast, antisense of HOXC5 introduced cells showed no significant difference of the invasion ability. These results suggest an important role of overexpressed HOX genes, especially for invasive characteristics of ovarian cancer cells.

Regulation of tumor invasion by HOXB13 gene overexpressed in human endometrial cancer.

During the last two decades, a group of homeobox-containing genes, the HOX gene family, has been studied both in the context of embryonic development and neoplasia. In particular, there is accumulating evidence of the involvement of HOX abnormalities in a variety of malignancies, including breast cancer. However, little is known about the association of HOX genes with endometrial cancer, which is the most common malignancy of the female genital tract and is thought to be dependent on estrogen, like breast cancer. In this study, we detected overexpression of the HOXB13 gene in endometrial cancer cells and tissues from patients by quantitative real-time RT-PCR. To investigate whether overexpression of HOXB13 is involved in invasion or metastasis of endometrial cancer, we transfected antisense HOXB13/pcDNA3.1+ plasmid vector into endometrial cancer AN3CA cells by electroporation and performed in vitro chemoinvasion assay. We revealed that the invasive ability of antisense-transfectants showed a 90% reduction compared with parental cells and control transfectants (p<0.01). In addition, administration of 17beta-estradiol induced time- and dose-dependent responses of the HOXB13 expression in endometrial cancer AN3CA cells. These results suggest that overexpression of HOXB13 in endometrial cancer may be associated with the invasive ability of cancer cells with regulation by estrogen.

Molecular cloning and expression analysis of the mouse Spot-2 gene in pituitary development.

Mouse Spot-1 is a DNA-binding protein with a domain (His-Thr) encoded by p(CA)n repeats. Spot-1 interacts with the nuclear localization signal (NLS) I of p53 through its His-Thr domain. In this study we describe the cloning and expression patterns of a novel gene encoding a protein containing a His-Thr domain, Spot-2. Spot-2 is exclusively expressed in the pituitary from stage E13.5 to E15.5. Mouse Lhx3 plays a critical role during early organogenesis in the pituitary. The Spot-2 gene appears to be a downstream gene of Lhx3. It is suggested that Spot-2 plays important roles in pituitary development.

Functional ablation of the mouse Ldb1 gene results in severe patterning defects during gastrulation.

The LIM domain-binding protein 1 (Ldb1) is found in multi-protein complexes containing various combinations of LIM-homeodomain, LIM-only, bHLH, GATA and Otx transcription factors. These proteins exert key functions during embryogenesis. Here we show that targeted deletion of the Ldb1 gene in mice results in a pleiotropic phenotype. There is no heart anlage and head structures are truncated anterior to the hindbrain. In about 40% of the mutants, posterior axis duplication is observed. There are also severe defects in mesoderm-derived extraembryonic structures, including the allantois, blood islands of the yolk sack, primordial germ cells and the amnion. Abnormal organizer gene expression during gastrulation may account for the observed axis defects in Ldb1 mutant embryos. The expression of several Wnt inhibitors is curtailed in the mutant, suggesting that Wnt pathways may be involved in axial patterning regulated by Ldb1.

Suppression of tumor necrosis factor alpha-induced matrix metalloproteinase 9 production in human salivary gland acinar cells by cepharanthine occurs via down-regulation of nuclear factor kappaB: a possible therapeutic agent for preventing the destruction of the acinar structure in the salivary glands of Sjögren's syndrome patients.

OBJECTIVE: Our previous results suggested that suppression of tumor necrosis factor alpha (TNFalpha)-induced matrix metalloproteinase 9 (MMP-9) could prevent the destruction of acinar tissue in the salivary glands of patients with Sjögren's syndrome (SS). The present study was undertaken to investigate the effect of cepharanthine on the suppression of TNFalpha-induced MMP-9 production in NS-SV-AC, an SV40-immortalized normal human acinar cell clone. METHODS: After pretreatment with or without cepharanthine, NS-SV-AC cells were treated with TNFalpha alone or with a combination of TNFalpha and cepharanthine. The expression of MMP-9 was then examined at the protein and messenger RNA levels. In addition, the effect of cepharanthine on the morphogenetic behavior of NS-SV-AC cells cultured on type IV collagen-coated dishes in the presence of TNFalpha was examined. RESULTS: Although TNFalpha induced the production of MMP-9 in NS-SV-AC cells, this production was greatly suppressed when cells were pretreated with cepharanthine, followed by treatment with both TNFalpha and cepharanthine. In addition, cepharanthine suppressed the TNFalpha-stimulated NF-kappaB activity by partly preventing the degradation of IkappaBalpha protein in NS-SV-AC cells. When NS-SV-AC cells were seeded on type IV collagen-coated dishes in the presence of both TNFalpha and plasmin, type IV collagen interaction with the cells was lost and the cells entered apoptosis. However, pretreatment with cepharanthine restored the aberrant in vitro morphogenesis of the NS-SV-AC cells. CONCLUSION: These results may indicate a molecular mechanism by which cepharanthine is able to protect against the destruction of the acinar structure in salivary glands from patients with SS.

Cefpirome sulphate for gynaecological infections and prophylaxis of non-laparotomy surgery in patients with benign disease.

We organized a study group to conduct a clinical trial in patients with various gynaecological infections, and we also assessed the efficacy of a single dose of cefpirome sulphate as prophylaxis after vaginal hysterectomy. Cefpirome sulphate (CROM) was administered to 100 patients with gynaecological infections and the clinical and antibacterial efficacy was evaluated in 88 patients. The improvement rate was 77.0% (67/87) and the bacterial eradication rate 67.8% (40/59). Nineteen of the 210 patients enrolled in the comparison of CROM with cefmetazole sodium (CMET) prophylaxis developed postoperative infections. The incidence of infection showed no significant difference between the CROM group (n=11, 10.6%) and the CMET group (n=8, 7.5%) (P=0.56). Although these results suggest that CROM may be effective for the treatment of gynaecological infections and has a good safety profile, it was not superior to CMET as prophylaxis in women undergoing non-laparotomy procedures at our hospital.

Stable inhibition of NF-kappa B in salivary gland cells does not enhance sensitivity to TNF-alpha-induced apoptosis due to upregulation of TRAF-1 expression.

The transcription factor NF-kappa B inhibits the apoptotic response induced by TNF-alpha. However, in salivary gland cell clones (ACMT-6 and ACMT-7) in which NF-kappa B activation was suppressed by introduction of a super-repressor form of I kappa B-alpha cDNA, TNF-alpha did not cause apoptosis. Thus, to investigate the molecular mechanism involved in the unresponsiveness of these cell clones to TNF-alpha-induced apoptosis, we examined the effect of TNF-alpha on the expression of antiapoptotic proteins, including TNF receptor-associated factor (TRAF)-1, TRAF-2, cellular inhibitor of apoptosis protein (cIAP)-1, and cIAP-2. Here we show that expression of TRAF-1 was commonly detected by treatment with TNF-alpha in ACMT-6, ACMT-7, and an empty vector-transfected cell clone (ACpRc-1) and that downregulation of TRAF-1 protein by either treatment with an antisense oligonucleotide or introduction of an antisense plasmid resulted in the induction of apoptosis in these cell clones. Our results, therefore, suggest that one of the mechanisms by which cells acquire resistance to TNF-alpha-induced apoptosis is a TNF-alpha induction of TRAF-1.

Relationship between expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 and invasion ability of cervical cancer cells.

Constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumors. MMPs are a family of zinc endopeptidases consisting of at least 20 different members. In particular, MMP-2 and MMP-9 are reported to be closely associated with invasion and metastasis in several cancers. We investigated whether expression of MMP-2 and MMP-9 is associated with invasion ability of seven cervical cancer cells by administration of o-phenanthroline as MMP inhibitor. In two cell lines, Siha and Caski, MMP-2 mRNA and protein were expressed at high levels. After treatment with o-phenanthroline, the rate of invasion in these two cell lines was significantly decreased. In contrast, in the other two cell lines, HT-3 and Caski, high levels of MMP-9 mRNA and protein were expressed but there was no decrease in the rate of invasion in these cells after treatment with o-phenanthroline. The data suggest that expression level of MMP-2 mRNA may regulate with invasion ability of cervical cancer.