Search

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2 , which are 95% identical in nucleotide sequence. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. We analyzed here the sequence and the promoter activity of the 5′-flanking region of the SCCA1 gene. Deletion analysis of SCCA1 and SCCA2 promoter identified a 471-bp core promoter region upstream of the transcription start site. The transcriptional activity of SCCA1 promoter was up-regulated in squamous cell carcinoma cells, compared with keratinocyte and adenocarcinoma cells. The ratios of SCCA1 to SCCA2 promoter activity in squamous cell carcinoma, keratinocyte and adenocarcinoma cells were respectively 1.6, 5.3 and 2.8. Position −50 of SCCA1 and SCCA2 promoters played an important role in determining the promoter activities of SCCA1 and SCCA2 . These findings suggest that the transcriptional regulation of SCCA1 and SCCA2 might differ among squamous cell carcinoma, keratinocyte and adenocarcinoma cells, and that SCCA1 promoter might be a potential target of gene therapy for squamous cell carcinoma.

Urinary disturbance frequently develops following therapy for cervical cancer; however, no effective medical treatment has so far been reported. Sixty-five patients who developed urinary disturbance after radiation therapy, radical hysterectomy or radical hysterectomy with radiation therapy for cervical cancer underwent urodynamic assessment. Those who underwent radical hysterectomy with radiation therapy experienced the most severe urine loss, as determined by the pad test. All patients showed markedly reduced bladder compliance. A beta2-agonist (mabuterol) significantly improved compliance, bladder capacity and flow rate. It is suggested that medication with mabuterol is a potential novel approach to the treatment of urinary disturbance after therapy for cervical cancer.

Microsatellite instability (MI) has been detected in certain sporadic cancers as well as in hereditary non-polyposis colorectal cancer (HNPCC). In order to determine the precise clinicopathological characteristics of MI in endometrial cancer, we examined 90 sporadic endometrial cancers (83 endometrioid adenocarcinomas, 3 adenosquamous carcinomas, 3 papillary serous carcinomas, and 1 clear cell carcinoma) and eight lesions of endometrial hyperplasia for replication error (RER) using polymerase chain reaction amplification of CA repeated microsatellite sequences at 15 loci. RER was observed in 23 (28%) of the 83 endometrioid adenocarcinomas at at least one locus and in 19 (23%) at two or more loci (RER+ phenotype) in the seven most commonly observed loci, but not in carcinomas of other histological types or in endometrial hyperplasia. Lymphocyte infiltration around carcinoma cells, which is one of the histological features seen in tumors from HNPCC, was severer in RER+ phenotype tumors (79%, 11/14) than in the RER- tumors (25%, 11/44) (marked/moderate infiltration versus slight, P < 0.001, chi 2 test), when 58 tumors with muscular invasion were examined. The RER+ phenotype was associated with a higher parity and gravidity (P < 0.05, Wilcoxon test). However, RER+ phenotype was not associated with tumor stage, histological grade, muscular invasion, lymph node metastasis or patient survival. In conclusion, MI occurs in a subset of endometrial cancers, which often show marked infiltration of lymphocytes around the tumor.

Many new members of the S-100 genes are known to be associated with cell differentiation, malignant transformation, and cell cycle. Of the S-100 genes examined in the present study, calcyclin, calpactin I light chain and calvasculin were expressed in most human epithelial tumor cells, and their expression levels differed according to various growth conditions. Their transcribed levels differed depending on each cell line, but their expression patterns were similarly changed under growth-modulatory conditions. Their messenger RNA levels increased parallel to the S phase population of cells, and decreased at G1/G2 phases. In contrast, this expression diminished in tumor cells under growth-inhibitory conditions, such as treatment with topoisomerase II inhibitor VP-16 or phorbol 12-myristate 13-acetate.

Deletion of certain chromosomal regions can be demonstrated in malignant cells. Chromosome 16q is one of the regions where allelic loss is frequently detected in carcinoma of the breast and many other tumors, suggesting that gene(s) which retard tumor growth may exist here. To elucidate the clinico-pathological significance of chromosome 16q, loss of heterozygosity (LOH) was investigated using microsatellite polymorphism analysis in 58 patients with endometrial lesions (50 with endometrial carcinoma and 8 who had hyperplasia with or without atypia). When 11 regions of chromosome 16q were examined, LOH was found in 20 patients with carcinoma (40%) and none of the patients with hyperplasia. The tumors of 9 of the 20 patients (45%) showed total loss of 16q, while the others (55%) showed partial deletion. Tumors with LOH were histologically less differentiated than those without LOH (P = 0.038, x 2 test). Patients with tumors showing LOH of 16q had a worse prognosis than those without LOH according to Kaplan-Meier survival analysis (P=0.0158, log-rank test). In addition, LOH of 16q showed a significant relationship to prognosis by Cox regression analysis. Deletion mapping of 16q demonstrated that two regions (16q22.1 and 16q22.2-23.1) were frequently involved. Patients with 16q22.1 LOH had a poorer prognosis than those with intact 16q22.1 (P=0.0003, log-rank test). These findings suggest that gene(s) of which defect is possibly related to the aggressiveness of endometrial cancer are localized on a limited region of 16q that includes 16q22.1.

Background. Alterations of the p53 gene are involved in the development of diverse human malignancies, but their incidence and clinicopathologic features are still not well characterized for endometrial carcinoma. Methods. To investigate the clinicopathologic significance of p53, mutations and loss of heterozygosity (LOH) in endometrial carcinoma in 92 patients with this disease were examined. Results. Mutations of p53 were detected in 20 (22%) of the 92 patients with carcinoma, and LOH was detected in 23 (32%) of the 72 patients in whom heterozygosity of the gene was available. There was a significant correlation between the occurrence of mutation and LOH. Mutations and LOH were more frequent in patients with Grade 3 tumors than in those with Grades 1 and 2 tumors (P = 0.0498, P = 0.0051, respectively). Patients with LOH had a poorer postoperative survival than those without LOH (P = 0.0022, log-rank test), and patients with both LOH and mutation showed the worst prognosis (P < 0.0001, log rank test). Loss of heterozygosity of the p53 gene showed a significant relation to prognosis that was independent of tumor stage, histologic grade, and muscular invasion. Conclusions. Mutation and LOH of the p53 gene are prognostic indicators in patients with endometrial carcinoma, suggesting that alterations of p53 may play an important role in the development of this cancer.

Background. The overexpression of c-erbB-2 protein is a prognostic marker in patients with breast cancer. Alteration of the c-erbB-2 oncogene in development of adenocarcinoma of the uterine cervix, an unfavorable gynecologic neoplasm, is unknown. Methods. To clarify the role of the c-erbB-2 oncogene in adenocarcinoma of the uterine cervix, formalin-fixed, paraffin-embedded tissue sections from 44 cases of cervical adenocarcinoma were immunohistochemically examined for expression of c-erbB-2 protein and for c-erbB-2 gene amplification in DNA by slot blot-hybridization analysis. Results. The expression of c-erbB-2 protein was detected in 34 cases (77%). Strong expression on cell membranes was detected in 11 cases (25%). Most cases with strong membrane expression of c-erbB-2 protein also showed amplification of the c-erbB-2 gene by slot blot-hybridization. Expression of the protein on cell membranes was more often seen at clinical Stage II or III (9 of 23 [39%]) than at Stage 0 or I (2 of 21 [9%]) (P < 0.05, Fisher's exact test). Expression of the c-erbB-2 protein was also associated with poorer prognosis of patients with cervical adenocarcinoma by comparison of survival curves (P < 0.005) and by the Cox regression model analysis. Conclusions. Overexpression of c-erbB-2 protein is associated with amplification of c-erbB-2 gene and frequently occurred in cervical adenocarcinomas of the patients with poor prognoses.

Using the polymerase chain reaction and single-strand conformation polymorphism analysis, p53 gene mutations were examined in 24 cases of ovarian tumor including 14 ovarian carcinomas and 2 borderline cases of common epithelial type, 7 germ cell tumors, and one stromal tumor. Abnormal bands indicating mutations were detected in 12 (50%) of the cases examined, being present most frequently in common "epithelial" ovarian carcinoma (71%, 10/14). One case each of squamous cell carcinoma originating in a dermoid cyst and anaplastic dysgerminoma were positive for mutation. Direct sequencing confirmed 12 mutations and revealed G-->A and G-->C nucleotide changes in 5 and 3 cases (42% and 25%), respectively. The mutation was localized at the CpG site of the gene in 3 cases. Immunohistochemical examination of p53 protein in 21 cases and DNA flow-cytometrical analysis in 17 cases were also performed. Nuclear accumulation of the p53 protein and DNA aneuploidy pattern were detected in 11 (52%) and 9 (53%) cases, respectively. These were significantly correlated with p53 gene mutation (P < 0.01 and P < 0.05, respectively; Fisher's exact test). Neither mutation of the p53 gene, nuclear accumulation of p53 protein nor DNA aneuploidy was detected in borderline cases of common "epithelial" type, typical dysgerminoma and immature teratoma. These results suggest that p53 gene mutation, nuclear accumulation of the protein and the DNA aneuploidy pattern are events occurring almost simultaneously in the progression of ovarian tumors, and that p53 abnormalities seem to be correlated with a high grade of malignancy.

Point-mutational activation of the c-Ki-ras proto-oncogene has been shown to be rare in human hepatocellular carcinoma, the most common primary liver cancer and one usually associated with chronic viral infection. To reveal the association of c-Ki-ras activation with cholangiocarcinogenesis under different etiological backgrounds, the incidence of point mutation at codons 12 and 13 of the c-Ki-ras proto-oncogene was examined in three groups of human liver cancers with differentiation to biliary epithelial cells: Group 1, cholangiocellular carcinoma in Japanese with normal livers; Group 2, cholangiocellular carcinoma in Thais who had lived in an area where the liver fluke Opisthorchis viverrini is endemic; and Group 3, combined hepatocellular-cholangiocellular carcinoma, a rare type showing features of both hepatocellular and biliary epithelial differentiation, in Japanese with chronic viral hepatitis with or without cirrhosis. The polymerase chain reaction and direct sequencing of its product were used to detect the mutation. Point mutation at codon 12 of the c-Ki-ras gene was detected in five (56%) of nine cases in Group 1. In contrast, the mutation was not detected in any of the cases in Groups 2 and 3. Therefore, point-mutational activation of c-Ki-ras did not seem to be involved in the development of primary liver cancers associated with apparent chronic irritation of liver cells or biliary epithelial cells caused by exogenous liver-fluke or viral infection. On the other hand, point-mutational activation of the c-Ki-ras proto-oncogene may be involved in cholangiocarcinogenesis in liver without preexisting liver-fluke or viral infection. © 1992 Wiley-Liss, Inc.

A case of severe bladder dysfunction due to a high-dose irradiation of 180 Gy after radical hysterectomy for cervical cancer is presented. The patient had suffered from urinary disturbances for 11 years after operation and radiation therapy. The results of urodynamic studies were low capacity, low compliance and low urethral pressure. The β2-agonist mabuterol was administered for 3 years. Bladder capacity, compliance and urethral closure pressure improved significantly after the treatment. The voided volume increased significantly to twice the pretreatment state. Frequency, incontinence and urine loss by the 60-minute padweighing test decreased significantly to one-third to one-fifth of the pretreatment state. The patient is doing well without any side effects 3 years after initiation of the treatment.

The route of transmission of TT virus (TTV) was studied by examining the existence of TTV DNA in different body fluids from the new born infants and their mothers. A total of 52 pregnant women with normal serum alanine aminotransferase levels were enrolled in this study. TTV DNA was examined using a polymerase chain reaction method using Takahashi's primers which can detect all genotypes of TTV and Okamoto's primers which detect only some of the genotypes of TTV. TTV DNA was detected in the sera from 40/52 (77%), in the breast milk from 35/52 (67%), and in the amniotic fluid from 6/6 (100%) pregnant mothers using Takahashi's primers TTV DNA was also detected in the sera from 8 of 11 (73%) and in the cord blood from 25/52 (48%) new born infants using Takahashi's primers. However, TTV DNA was detected in only 5/52 maternal blood (10%) and 4/52 breast milk (8%) using Okamoto's primers. All samples positive for TTV DNA by Takahashi's primers, were also positive for TTV-like mini virus (TLMV) DNA. Our data suggest that intrauterine transmission or transmission via breast milk may contribute to maintaining the global TTV and TLMV reservoir.

Protein expression levels of E-cadherin and beta-catenin were examined in 39 primary and 10 metastatic ovarian carcinoma to elucidate the role of these molecules in the extension of ovarian carcinoma by immunohistochemistry. Twenty-two of 39 (56%) ovarian carcinomas were preserved type and 17 of 39 (44%) were reduced type of E-cadherin. In contrast, 36 of 39 (92%) ovarian carcinomas were preserved type and 3 of 39 (8%) were reduced type of beta-catenin. E-cadherin expression in well-differentiated carcinoma was higher than that in moderately/poorly-differentiated carcinoma (p

The squamous cell carcinoma antigen (SCCA) serves as a serological marker for squamous cell carcinomas. Molecular cloning of the SCCA genomic region has revealed the presence of two tandemly arrayed genes, SCCA1 and SCCA2. SCCA1 is a papain-like cysteine proteinase inhibitor, while SCCA2 is a chymotrypsin-like serine proteinase inhibitor. Little is known concerning how expression of the SCCA1 and SCCA2 genes is regulated in human cell lines. The purpose of this study was to determine whether the SCCA1 gene or SCCA2 gene is more strongly expressed in human cell lines. Squamous cell carcinoma cell lines secreted respectively 4 times and 50 times as much SCCA proteins into medium as normal human keratinocyte and non-squamous cell carcinoma cell lines, as measured by enzyme-linked immunosorbent assay. Quantitative RT-PCR ELISA digoxigenin-labeling assay demonstrated that SCCA1 mRNA expression in squamous cell carcinoma cell lines was respectively 2.8 times and 42 times that in keratinocyte and non-squamous cell carcinoma cell lines. The ratio of SCCA1 to SCCA2 mRNA expression differed distinctly among squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines (2.8, squamous; 24.1, keratinocyte; 11.0, non-squamous). These findings suggest that SCCA1 is mainly expressed in squamous cell carcinoma, keratinocyte and non-squamous cell carcinoma cell lines and that the ratio of SCCA1 to SCCA2 expression might be a novel marker for the detection of squamous cell carcinoma.

To determine whether p53 alterations, which are frequent in human breast cancers, are also common in rat mammary tumors, we examined 40 tumors from 24 rats treated with 7,12-dimethylbenz[a]anthracene (DMBA) and 34 tumors from 14 rats treated with N-nitroso-N-methylurea (NMU) (an N-nitroso compound). DMBA and NMU are known genotoxic mutagens. The entire coding regions of the p53 and Ha-ras genes were examined for mutations by polymerase chain reaction single-strand conformational polymorphism analysis and by direct sequencing. One of the 40 DMBA-induced mammary tumors had a p53 mutation, a single-base substitution (???AGC???GGC) at codon 307, resulting in an amino-acid change from Ser to Gly. No mutations were found in NMU-induced tumors. The incidence of Ha-ras gene mutation was 79% (27 of 34) at codon 12 in the NMU group and 23% (nine of 40) at codon 61 in the DMBA group. Thus, p53 mutation, in contrast to Ha-ras mutation, did not seem to be a prerequisite for carcinogenesis in chemically induced rat mammary tumors. © 1996 Wiley-Liss, Inc.

Recently case reports about latex allergy were increased. We have experienced severe latex allergy in a pregnant women after vaginal examination with a latex glove. A 33-year-old woman, 38 weeks pregenant, was hospitalized for management of fetal IUGR. She underwent a vaginal examination with a latex glove and soon developed severe anaphylactic reactions. Although two hours later her condition had remarkably improved, regular uterine contractions appeared, and fetal cardiotocogram showed late decelerations. So emergency cesarean section was performed under the situation without using any latex products. She delivered a male infant weighing 2,227 g (–2.21 SD) at 38 weeks gestation. His Apgar score was 5 points at 1 min and 8 points at 5 min. The latex-specific IgE of this patient was high and IgE for banana, avocado and kiwi were also positive. These foods showed cross-reactions with latex, but she had no history of allergic reactions against these foods. She had a history of atopic reactions and of atopic dermatitis while working as a nurse at the ICU. It is thought that this patient was in the high-risk group.

The presence of point mutation at codons 12, 13 and 61 of the c-Ki-ras oncogene was investigated in 7 cases of gastric adenoma and 35 cases of gastric adenocarcinoma using DNA samples from formalin-fixed and paraffin-embedded tissues. Oligonucleotides encompassing the three codons were amplified by using the polymerase chain reaction (PCR), and then examined for point mutation by the selective oligonucleotide hybridization technique. Point mutation was detected in three of the 7 adenomas (43%) and three of the 35 carcinomas (9%). All the gastric adenomas showed the histology of tubular adenoma, being very similar to that of colonic adenoma. The 35 cases of gastric adenocarcinoma were classified into 17 cases of differentiated type and 18 cases of undifferentiated type including signet-ring cell carcinoma. The point mutation of c-Ki-ras oncogene was detected only in the differentiated type (3/17, 18%), and there was no case with point mutation in the undifferentiated type. These results suggest that the genetic mechanism of carcinogenesis differs between the differentiated type and the undifferentiated type of gastric adenocarcinoma, and also that c-Ki-ras activation is possibly involved in a relatively early step of the "adenoma-carcinoma sequence," which leads to the development of a portion of differentiated adenocarcinomas in the stomach.