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Background Juvenile dermatomyositis (JDM), a rare autoimmune disease, accounts for more than 80% of idiopathic inflammatory myopathy childhood cases, making it the most common idiopathic inflammatory myopathy among children. The average age of onset is approximately 7 years and commonly leads a chronic course. Symptoms of JDM include cutaneous features (Gottron's rash, heliotrope rash, or nail fold capillary changes), musculoskeletal features, calcinosis and lipodystrophy (a symmetrical deficit of subcutaneous fatty tissue), and acanthosis (thickening of the skin). Despite improvement in treatment regimens and the lowering of mortality rates, some children still lose their lives to JDM. This study assessed the effects of caring for a child diagnosed with JDM on the family system. Methods Participants included 36 mothers and 3 fathers of a child diagnosed with JDM. Parents were administered self-report measures, which assessed the overall family functioning (PedsQL-Family Impact Module), and the parents' mood and level of distress (profile of mood states). Additionally, parents were administered a semi-structured interview that included background information, psychosocial information, and sources of support. Results and conclusion Families of children with JDM reported difficulties in family functioning, communication problems, and an increased number of conflicts. Parents appeared to be experiencing higher than average levels of worry, worse physical functioning, and family relationships when compared to normative populations. Parents would benefit from psychosocial support due to the many challenges associated with caring for a child with JDM.

Thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor (PD-ECGF) and has angiogenic activity. Since dThdPase seems to have an important role in angiogenesis of tumours, we measured the activity and expression of dThdPase in various tumours and the adjacent non-neoplastic tissues. We assayed dThdPase activity by spectrophotometric means, and the expression of dThdPase was examined by immunoblotting and by immunohistochemical staining using a monoclonal antibody against dThdPase. In the oesophagus, stomach, colorectum, pancreas, and lung, dThdPase activity in carcinomas was significantly higher (P0.05) than that in the adjacent non-neoplastic tissues. The expression level of dThdPase detected by immunoblotting correlated well with the activity of dThdPase. In the oesophagus, stomach, colorectum, gall bladder, pancreas and lung, the proportion of dThdPase-positive tumours was significantly higher (P0.05 or 0.01) than that of the dThdPase-positive adjacent normal tissues. In oesophageal, gastric colorectal and lung carcinomas, the proportion of dThdPase positivity in advanced carcinomas was significantly higher (P0.01) than that in early carcinomas. Tumour-infiltrative macrophages or lymphocytes in the lymph node, alveolar macrophages and Kupffer cells expressed high levels of dThdPase. The results indicate that dThdPase activity and expression level in many tumours are higher than those in the adjacent non-neoplastic tissues, and that dThdPase may have an important role in the proliferation of these solid tumours.

For both cervical cancer (UCC) and endometrial cancer (EMC) there are no effective prognostic markers. In this study, we evaluated HIG2 protein expression in 332 uterine cancers (186 UCCs and 146 EMCs) and examined the relationship between HIG2 protein expression and clinical factors, including prognosis. Totally, HIG2 expression was detected in 58% of UCC and 66% of EMC. However, there was no significant relationship between HIG2 expression and age, clinical stage and histology in either UCC or EMC. In addition, HIG2 protein expression was not related to prognosis of UCC or EMC. The positivity rate of HIG2 protein was 56% and 61% in early-stage UCC and EMC, respectively and 67% in non-squamous cell carcinoma of UCC. The positivity rate of HIG2 protein was high even in early-stage UCC and EMC

In this study, we compared second-line chemotherapy effects of nodal metastases with other metastases sites.The medical records of 44 women with recurrent ovarian cancer who received second-line chemotherapy were retrospectively reviewed.Median age at the time of second-line chemotherapy was 55 years (range: 31-74). Recurrent sites were as follows: 29 patients had a solitary site (abdominal cavity: 8; lymph node: 3; pelvic cavity: 10; liver: 4; lung: 4) and 15 patients had multiple sites In total, the response rate was 30% (CR: 8, PR: 5). The response rate in sensitive cases was higher than in refractory/resistant cases (50% vs 5% p = 0.002). However, age, chemotherapy regimen, histologic type and number of diseases were not related with chemotherapy effect. In all diseases, response rate tended to be higher in lymph node disease than in the others (44% vs 27%). In both sensitive and refractory/resistant cases, response rate tended to be higher in lymph node disease.The response rate for lymph node diseases tended to be relatively high. Further study analyzing survival will be required to conclude the chemotherapy effect.

At present, it remains unclear whether the third-line chemotherapy has clinical benefit. In this study, we retrospectively evaluated the effect of third-line chemotherapy.We reviewed the medical records of 40 women with recurrent epithelial ovarian cancer (EOC) who received third-line chemotherapy after platinum/taxan regimens as first line chemotherapy.In the first recurrence, 23 cases were platinum-sensitive and 17 cases were platinum-resistant. The cases for which the treatment-free interval from second-line chemotherapy (TFI) was a 3 months had a higher non-PD rate than those with TFI3 months (86% vs 33%, p = 0.002). In addition, the median overall survival (OS) was longer for TFIor = 3 months than for TFI3 months (1195 days vs 235 days, p = 0.004). Finally, TFI was an independent significant prognostic factor by univariate (HR 3.28, p = 0.006) and multivariate (HR 3.21, p = 0.018) proportional hazard tests.TFI from second-line chemotherapy may predict a survival benefit of third-line chemotherapy.

An expression vector, pIN-GT, encoding the soluble form of beta 1,4-galactosyltransferase (GT) has been constructed from human GT cDNAs and the pIN-III-ompA2 expression vector. Escherichia coli strain SB221 harboring the pIN-GT plasmid produces and secretes a fusion protein consisting of the ompA signal and GT. The expression of GT was detected by assaying enzymatic activity as well as by Western blotting using anti-GT antibodies. The recombinant GT was purified to homogeneity by N-acetylglucosamine-Sepharose affinity chromatography. The NH2-terminal peptide sequence of purified GT confirmed the cleavage site of the fusion protein by bacterial signal peptidase. This expression system was utilized to produce mutant forms of GT in order to identify specific amino acids involved in substrate binding sites. Photoaffinity labeling of GT with UDP-galactose analog, 4-azido-2-nitrophenyluridylylpyrophosphate (ANUP), followed by cyanogen bromide (CNBr) cleavage revealed that ANUP bound to a fragment of GT composed of amino acid residues from Asp276 to Met328. Within this peptide segment, Tyr284, Tyr287, Tyr309, Trp310 and Trp312 were separately substituted into Gly and Tyr287 into Phe by site-directed mutagenesis. Enzymatic activity assay showed drastic reduction of the activity in all of the mutants except that Tyr287----Phe remained as active as wild-type GT. Kinetic studies of the mutated GT showed that Tyr284, Tyr309 and Trp310 are critically involved in the N-acetyglucosamine binding and Tyr309 is involved in UDP-galactose binding as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Recently, the number of cases of endometrial cancer has increased in Japan. Most of the increase are accounted for by premenopausal cases, which are frequently positive for ER or PR. Hormonal treatment using progestins such as MPA has been widely applied to endometrial cancer patients under 40 years old under the conditions of grade 1 well-differentiated endometrioid adenocarcinoma without myometrial invasion. In our hospital, we applied high-dose (600 mg/day) MPA for over 8 weeks in 14 cases of endometrial cancer, of which adenocarcinoma disappeared in 12 cases (86%), followed by cyclic administrations of low-dose MPA, with 7 subsequent recurrences. We think that a protocol for improving ovarian function, such as active induction of ovulation, should be established to induce intrinsic progesterone sufficient for the prevention of the recurrence of endometrial cancers. In the 2 cases, in which adenocarcinoma remained even after long administrations of MPA, myometrial invasion was noted in the surgically resected specimens. For advanced or recurrent endometrial cancers, MPA has been reported to be effective in an average of 26% in several reports, and effective in 42% cases when applied with combination chemotherapy, such as CAP, by virtue of the "chemical modulator" effect, which can delay the acquired resistance against ADM or CDDP. Furthermore, MPA has resulted in a significant improvement of 5-year disease-free survival rate when used as adjuvant therapy after complete operations and whole pelvic irradiation, compared with administrations of 5-FU in a randomized controlled study in Japan. Thus, in the future, we consider that hormonal therapy will play a more important role in endometrial cancer treatment.

We conducted a dose-finding study for combination therapy of paclitaxel (Taxol; TXL) and carboplatin (Paraplatin; CBDCA). TXL is a novel plant-derived anticancer agent that is a diterpene derivative possessing the taxane ring. The subjects were patients with ovarian carcinoma, who were evaluated by a modified Fibonacci method. The dosage of TXL was 150 to 180 mg/m2. CBDCA was administered by dose escalation from AUC = 4 to 7. The administration schedule was as follows. Pre-medication was administered before TXL was given. TXL was then administered by intravenous infusion over 3 hours, followed by CBDCA. The dose of CBDCA was determined using the Calvert formula: [AUCX (GFR + 25)]. GFR was calculated with the Jelliffe equation. The non-hematological toxicities observed in 15 eligible cases were mainly grade 1, with no grade 3 or above, and no increase in severity was observed with stepping up. The hematological toxicities were grade 3 leukopenia in 5 of 15 cases, neutropenia in 5 cases and thrombocytopenia in 0 cases. No grade 4 toxicity was observed. The lowest counts of leukocytes and neutrophils were reached after 10.8 and 11.7 days, respectively. The toxicities were reversible in most cases with subsequent recovery. The above findings indicate that the recommended dosages for TJ therapy for Japanese ovarian cancer patients should be TXL 180 mg/m2 and CBDCA at a target of AUC = 6.

The histoculture drug sensitivity assay (HDRA) has been demonstrated to have high predictability for resistance, sensitivity, and survival for gastrointestinal cancer (Clin Cancer Res 1: 305-311, 1995; Clin Cancer Res 1: 1537-1543, 1995). In this report, we evaluated the clinical usefulness of the HDRA in ovarian cancer. HDRA was performed on tumors from patients with ovarian cancer. Eighty-five cases (97%) were evaluable. Tumor fragments were cultured on collagen-sponge gels. The cultures were incubated with cisplatin (CDDP) for seven days. Cell viability were assessed with the MTT end point. The optimal cut off concentration of CDDP was determined to be 25 micrograms/ml by correlation with the historical clinical response rate to CDDP. HDRA results were correlated to clinical response of 15 patients who received CDDP-based therapy that included doxorubicin and cyclophosphamide (CAP therapy). The true positive rate was 88%, the true negative rate was 86%, the sensitivity was 88%, the specificity was 86%, and the accurate prediction rate was 87% when HDRA results were compared to the response of the treated patients. The data suggest that the HDRA is capable of predicting the response to antitumor chemotherapy in patients with ovarian cancer and that measuring response to CDDP can be useful for optimization of CAP chemotherapy for patients with this disease.

Ovarian carcinomas are known to be diverse in their histological types and response to therapeutic agents. Specific immunotherapy by the use of mucins or carbohydrate vaccines has been attempted, in which expression of these epitopes by each histotype should clearly be assessed. Seventeen human ovarian carcinoma cell lines were evaluated for their expression of mucin core polypeptide mRNAs (MUC1, MUC2, MUC3, MUC5AC, MUC5B, and MUC6) by the reverse transcription-polymerase chain reaction. They were also examined for their expression of mucin-associated carbohydrate epitopes by flow cytometry. Eleven monoclonal antibodies, including those specific for Lewis antigen-related epitopes and Tn-related epitopes, were used. Expression of the MUC1 gene and sialyl Lewis X was characteristic to all five cell lines derived from clear cell adenocarcinomas. Multiple mucin genes and a diverse range of carbohydrate epitopes were observed with all six cell lines derived from mucinous adenocarcinomas. Mucin-associated carbohydrate epitopes were not detected on three of four serous adenocarcinoma cell lines, although MUC1 and MUC2 mRNAs were detected in all of them. Therefore, ovarian carcinoma cells from tumors of different histological types showed characteristic expression patterns of mucin genes and carbohydrate epitopes.

A case of pyonephrosis with high levels of serum CA19-9 antigen is reported. A 71-year-old woman was admitted with right flank pain. Computed tomography and ultrasonography showed severe hydronephrosis and hydroureter due to a right ureter stone. Laboratory data revealed a high level of serum CA19-9. However, no tumor was found in the pancreas, gallbladder, liver, gastrointenstinal tract or genitourinary tract. Drip infusion pyelography showed a non-functioning pattern of right kidney. Therefore, right nephroureterectomy was performed for right pyonephrosis. Histological examination revealed chronic inflammation. Malignant cells were not seen in the resected specimen. The serum CA19-9 levels before and after operation were 102.9 U/ml and 24 U/ml, respectively, being normal after the operation. Immunohistochemical examination revealed the presence of CA19-9 antigen in the urethelium, indicating its expression in the specimen. To our knowledge this might be the first case of pyonephrosis associated with high levels of serum CA19-9 antigen.

SKG-3a and SKG-3b are two distinct human uterine cervical epidermoid carcinoma cell lines derived from a single donor. We studied these two closely related cell lines from the standpoint of drug susceptibility. The growth inhibitory effects of cisplatin (CDDP), doxorubicin (ADM), etoposide (VP-16), and paclitaxel (taxol) on SKG-3a and SKG-3b cells assessed by crystalviolet dye uptake assay were almost the same. SKG-3b cells treated with CDDP, ADM, VP-16, and taxol showed the apoptotic cell death, whereas apoptosis in SKG-3a cells was not induced by these anticancer drugs. Caspase-3 activity was increased only in the SKG-3b cell lysate after treatment with CDDP, ADM, and VP-16 but was not found in the SKG-3a cell lysate. These results indicate that despite growth inhibitory effects of anticancer drugs being almost the same, there may be differences in the common signaling pathways involved in the apoptotic process between SKG-3a and SKG-3b obtained from the same tumor.

To investigate the effect of acute hyperbaric oxygen therapy (HBOT) on post-operative sinusoidal endothelial cell (SEC) damage caused by activated neutrophils.12 non-cirrhotic patients (Group H), who underwent elective hepatectomy for liver cancer, were given 2 courses of HBOT: 2.0 atm with inhalation of 100% oxygen, for 60 min, at 3 hours and 24 hours after hepatectomy; they were then compared with the 12 patients (Group C) who had been treated to maintain normal hemodynamic values.In group H, peak levels of polymorphonuclear leukocyte elastase (PMNE) and thrombomodulin (TM) were clearly diminished and delayed compared to Group C. All subjects in Group C showed more than a 10% increase in CD18 12 hours after surgery; however, in Group H, the elevation of CD18 expression was clearly suppressed compared to Group C. No patient in Group H had post-operative hyperbilirubinemia or hepatic failure; however, 3 had post-operative hyperbilirubinemia and 1 had intraperitoneal infection in Group C.Our results provide direct evidence that HBOT, especially at 3 hours after hepatectomy, has favorable effects on the activation of neutrophiles decreasing SEC injury.

Clinically relevant animal models of human cancer are important for studies of cancer biology, invasion and metastasis, and for investigating new forms of prognostic diagnosis and therapy. An ovarian tumor line (RMG-1: human clear cell carcinoma of the ovary) previously grown subcutaneously was implanted orthotopically as intact tissue into the ovarian capsule of 22 nude mice. The tumors showed progressive growth at the orthotopic site in all animals. Tumor-associated serum galactosyltransferase (GAT) tended to be positive in all nude -mice. The tumors invaded or metastasized to the contralateral ovary, retroperitoneum, mesentery and peritoneum, and omentum, and metastasized to the subcutaneous tissue, lymph nodes and distant organs including the liver, kidney, pancreas, and diaphragm. In striking contrast, subcutaneous transplantation of this tumor resulted in growth in only 2 of 5 animals with local lymph node and kidney involvement but no retroperitoneal or peritoneal involvement. These findings suggest that orthotopic implantation provides a suitable micro-environment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the clinical features of ovarian cancer and is thought to be a useful model for studies of therapy for this cancer.

Trophinin, tastin, and bystin comprise a complex mediating a unique homophilic cell adhesion between trophoblast and endometrial epithelial cells at their respective apical cell surfaces. In this study, we prepared mouse monoclonal antibodies specific to each of these molecules. The expression of these molecules in the human placenta was examined immunohistochemically using the antibodies. In placenta from the 6th week of pregnancy, trophinin and bystin were found in the cytoplasm of the syncytiotrophoblast in the chorionic villi, and in endometrial decidual cells at the utero placental interface. Tastin was exclusively present on the apical side of the syncytiotrophoblast. Tissue sections were also examined by in situ hybridization using RNA probes specific to each of these molecules. This analysis showed that trophoblast and endometrial epithelial cells at the utero placental interface express trophinin, tastin, and bystin. In wk 10 placenta, trophinin and bystin were found in the intravillous cytotrophoblast, while tastin was not found in the villi. After wk 10, levels of all three proteins decreased and then disappeared from placental villi.

Dienogest is an orally active synthetic steroid that is used for contraception and is currently being studied for the possible treatment of endometriosis. Earlier we demonstrated that dienogest had therapeutic effects on experimental endometriosis in rats and that its mechanisms of action were different from those of drugs currently on the market for the treatment of endometriosis. We also reported preclinically that dienogest showed a potential anticancer action against hormone-dependent cancers that was different from that of progestins. Accordingly, we obtained preclinical background data for the above-described clinical applications and extension of the clinical use of the drug in the near future by investigating the endocrinological profile of dienogest in rabbits and rats. Dienogest was characterized by having a moderate binding affinity for progesterone receptors and by progestational activities: it stimulated endometrial proliferation (or = 0.01 mg/kg) that was only partially inhibited by RU-486, and induced carbonic anhydrase activity in endometrium (or = 0.01 mg/kg). Also, it was slightly uterotrophic (or = 1 mg/kg) with very low binding affinity for oestrogen receptors but without biological androgenic and anabolic activities (100 mg/kg), with neither glucocorticoid activity nor mineralocorticoid activity (100 mg/kg), and with very slight binding affinity for human sex hormone-binding globulin. These findings suggest that dienogest is not a pure progestin and appears to induce fewer side effects than drugs currently on the market for the treatment of endometriosis.

In the treatment of endometrial cancer, surgical treatment, radiotherapy, chemotherapy, and hormonal therapy are available. Since endometrial cancers are adenocarcinoma with a relatively low response to irradiation in most a cases, surgical operation is the first choice in these cases. The operative procedure is chosen according to the cancer staging currently used in Japan (FIGO, 1982), because it is a preoperative staging. In principle, total hysterectomy is done for cases of stage 0, modified radical hysterectomy for stage I, radical hysterectomy for stage II, and radical hysterectomy combined with resection of the metastatic lesions for stage III and IV. In addition, adnexa has to be resected bilaterally. In cases of stage II or higher stages, resection of para-aortic lymph nodes is done in addition to pelvic lymphadenectomy according to the depth of myometrial invasion and histologic type. On the other hand, the new international corpus cancer staging employed by FIGO in 1988 is a surgical staging which determines the stage on the basis of the intraoperative and postoperative histopathological findings. This staging takes into account more prognostic factors, reflecting the prognosis more precisely. In the near future, the Japan Society of Obstetrics and Gynecology will introduce a new staging. Since this staging is, however, determined postoperatively, it cannot be a criterion for choosing operative procedures. In addition, it is well known that preoperative diagnosis is not always consistent with intraabdominal findings. Therefore, it is important to determine most appropriate operative procedure by checking preoperatively the prognostic factors such as histopathology, degree of differentiation, cervical involvement, myometrial invasion and presence or absence of extrauterine progression precisely as far as possible. At the same time, by taking into consideration the intraoperative findings, an extended operation not limited to the above mentioned procedures should be undertaken in cases with higher risk factors.

To establish an experimental system useful for long-term evaluation of human endometrial tissue by its heterotransplantation to SCID mice.Human endometrium was transplanted subcutaneously into SCID mice, nude mice, or nude mice given anti-asialo GM1 antibody, a natural killer activity suppressor. The transplant was observed by ultrasonography for up to 10 weeks and then morphologically. To assess the drug susceptibility of the transplant, danazol (10-100 mg/kg/day orally), buserelin (0.01 mg/kg/day subcutaneously), or estradiol (0.5 mg/kg/day intraperitoneally) was administered to the host mice for up to 10 weeks after the transplantation. Multiple-comparison procedures were used for statistical evaluation.The heterotransplant was accepted 100% in SCID mice and natural killer activity-suppressed nude mice, but was significantly inferior (40%) in nude mice at 10 weeks after the transplantation. The transplant size was volumetrically measurable noninvasively by ultrasonography. Using this SCID mouse model, we could evaluate drug effects on the transplanted endometrium.This system in SCID mice may be useful for evaluating drug actions on human endometrium and endometriotic tissues.

MSN-1 is a monoclonal antibody, which was raised by immunizing mice with a human endometrial cancer cell line, SNG-II. The MSN-1 specifically recognizes a blood group carbohydrate antigen, Leb. We investigated the subcellular and suborganellar localization of the MSN-1-reactive carbohydrate antigens in the endometrial adenocarcinomas and the normal endometria using immunofluorescence microscopy, confocal laser scanning microscopy, and immunoelectron microscopy. In normal endometrium, the apical plasma membranes of endometrial glandular cells were weekly positive. In contrast, in endometrial adenocarcinoma specimens, the apical plasma membranes, the lateral plasma membranes, intracytoplasmic vesicular structures, and the Golgi apparatus were strongly positive. We also found that there are differences in the manner of the distribution of the MSN-1 antigen within the Golgi apparatus between the normal and tumor samples; namely, in the endometrial adenocarcinoma cells the antigens are found abundantly throughout the Golgi apparatus or tend to be located not only at the trans side but also close to the cis side, while the localization of this antigen in normal counterpart is restricted to the trans-Golgi cisternae. These findings imply that aberrant glycosylation occurs in endometrial adenocarcinomas, presumably as a result of abnormal expression of some glycosyltransferases involving the expression of the Leb carbohydrate antigen in the Golgi apparatus.

We conducted preclinical and clinical studies on GAT: Galactosyltransferase Associated with Tumor, a newly developed tumor marker of ovarian carcinoma. This paper presents the results of evaluation of a GAT assay kit, the normal range of its values, and analysis of its value relative to age, menstrual cycle, and stage of pregnancy. Calibration curve, reproducibility, analytical recovery test, and dilution test all yielded favorable results, and the assay system was proved to be reliable in both precision and reproducibility. However, special attention must be paid to highly hemolytic samples because of a positive error in GAT value for samples with a high concentration of hemoglobin. The cut-off value was set at 16U/ml based on the mean+2SD of healthy females. A uniform cut-off value could be employed since neither age nor stage of menstrual cycle had any observable influence on the level. The positive rate for healthy subjects was 3.1%, when the cut-off value of 16 U/ml was used. On the other hand, elevation of the GAT value was observed during the progression of pregnancy.

Galactosyltransferase Associated with Tumor (GAT) was clinically studied in cases of ovarian cancer. When two cut-off levels of GAT were compared, the cut-off level of 16 U/ml (which corresponds to mean + 2SD among healthy females) was found to be more suitable than the cut-off level of 14 U/ml (the level maximizing the diagnostic efficiency between malignant and benign ovarian tumors). When the GAT positive rate was examined for gynecologic tumors, the rate was 5.7% for benign ovarian cyst, 6.6% for endometriosis, 20.5% for cervical cancer, 19.5% for endometrial cancer, and 52.9% for ovarian cancer. The GAT positive rate for different histologic types of ovarian carcinoma was relatively high for each type, e.g., 55.0% for clear cell adenocarcinoma and 66.7% for endometrioid adenocarcinoma. The GAT positive rate increased gradually with the stage of ovarian cancer. In patients with benign diseases, in particular endometriosis, the GAT positive rate was lower than the positive rate with any other simultaneously determined marker (CA602, CA125, CA54/61, CA72-4, STN, and SLX). The GAT level most weakly correlated with the level of any of the other markers assessed. An assay combining GAT with CA602 or CA54/61 resulted in a higher positive rate and a higher diagnostic efficiency, when compared with the assay for GAT alone. The lower positive rate of GAT in endometriosis, when compared with the positive rate of other markers, suggests the usefulness of GAT in distinguishing malignant ovarian tumors from benign ovarian tumors. The use of GAT in a combination assay is expected to overcome the disadvantages of CA602 or CA125.

Using a new one-step, double-determinant enzyme immunoassay, we performed quantitative measurements of a mucin-type glycoprotein antigen (CA54/61) that we recently detected in sera of ovarian carcinoma patients. When the cutoff value was set at 12 units/ml, at which a high diagnostic efficiency was demonstrated [or at 20 units/ml (mean + 3 SD of healthy females)], the positive rates of ovarian serous, mucinous, clear cell, and endometrioid carcinomas were 76% (or 63%), 63% (or 55%), 57% (or 52%), and 50% (or 38%), respectively. Even in mucinous cystadenocarcinoma, more than one-half of the cases were positive, indicating the potential utility of the assay in the diagnosis of mucinous tumors. In sera from patients with benign ovarian tumors, only 9% (or 4%) of the cases were positive, indicating the quite high specificity of this test for ovarian carcinomas. To make a comparison between CA54/61 and CA125, we set the cutoff level of CA125 at 110 units/ml, at which value a high diagnostic efficiency was demonstrated [or at 35 units/ml (mean + 3 SD of healthy females)]. When both CA54/61 and CA125 were assessed in sera from 36 patients with mucinous cystadenocarcinoma, the positive rates of CA54/61 and CA125 were 64% (or 56%) and 36% (or 56%), respectively, suggesting that CA54/61 is of clinical value as a new tumor marker for ovarian cancers, including mucinous tumors.

The poly-N-acetyllactosamines on neutrophils and monocytes have been shown to serve as ligands for various selectins present on endothelial cells and platelets. We have previously shown that only a limited number of glycoproteins contain poly-N-acetyllactosamine and found that lysosomal membrane glycoproteins (lamps) are the major glycoproteins carrying poly-N-acetyllactosamine. In order to understand the reason why only certain glycoproteins can be modified by poly-N-acetyllactosamine, we have utilized 21 degrees C incubation conditions, which were previously shown to cause the accumulation of glycoproteins at the trans-Golgi. HL-60 cells were labeled with [3H]galactose at 21 or 37 degrees C for 6 or 24 h, and lamp-1 and lamp-2 were immunoprecipitated. Upon examination by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, each lamp from HL-60 cells incubated at 21 degrees C exhibited a much broader, slower migrating band than that isolated from the cells incubated at 37 degrees C. The number of N-glycans containing poly-N-acetyllactosamine, estimated by their binding to tomato lectin column, increased approximately 30-50% after incubation at 21 degrees C than incubation at 37 degrees C. The analysis of oligosaccharides released by endo-beta-galactosidase digestion demonstrates that the amount of side chains containing three or more N-acetyllactosamine repeats increased about 100% after incubation at 21 degrees C, and methylation analysis confirmed these results. The same analysis and the results obtained by ion-exchange chromatography also provided evidence that the N-glycans of lamps are sialylated at 21 degrees C as much as at 37 degrees C. Pulse-chase experiments using [35S]methionine labeling indicated that the time necessary for processing of lamps is much longer at 21 degrees C than at 37 degrees C. These results therefore indicate that incubation at 21 degrees C causes the lamps to reside longer within the Golgi complex, and such longer residence allows lamps to acquire more polylactosaminoglycan. These results also suggest that the time necessary for moving through the Golgi complex is a critical factor for poly-N-acetyllactosamine formation.

A human gestational uterine choriocarcinoma cell line (NJG) was established in vitro. The NJG cell line had been subcultured more than 73 times over 7 years. The cells consisted mainly of Langhans-like cells, while multinucleated cells were occasionally seen. The cells grew in a monolayered sheet, showing a tendency to pile up, with the population doubling in 80 hrs. Electron-microscopically, desmosomes were characteristically observed, which suggested that the cultured cells were of epithelial origin. Chromosomal analysis revealed aneuploidy with a hypertriploid mode and 4 marker chromosomes. Immunocyto- and-histochemical staining for tumor markers of the cultured cells and the transplanted tumors to nude mice showed close similarity. SP1 was occasionally demonstrated and PP5 was faintly stained only in the heterotransplanted tumors, although PP10 and PP12 were not demonstrable. HCG was localized not only in syncytial cells, but also in Langhans cells, and syncytial cells without hCG were also observed in the tumors. A single cell clone was also established from the original NJG cells by a limiting dilution method. The heterotransplanted tumor consisted of Langhans and syncytial cells, indicating that both cells originated from the same cell.

A 59-year-old woman was admitted to our hospital complaining of weight loss. Fourteen years earlier, she had undergone gastrectomy for gastric carcinoma of the Borrmann III type on the lesser curvature of the body. Biopsy specimens of the lesion revealed poorly differentiated adenocarcinoma. On the fifth hospital day of the admission under study, she complained of vaginal bleeding, and a diagnosis of endometrial carcinoma was made by a gynecologist. Transverse colectomy and total hysterectomy were done. The lesion was localized only in the transverse colon, was histologically poorly differentiated adenocarcinoma similar to the specimen of gastric carcinoma resected 14 years earlier and involved mainly the serosa. Therefore, secondary linitis plastica of the transverse colon was diagnosed.

Early malignant lymphoma is rare and cases with scattering over the whole stomach are extremely rare. Malignant lymphoma is frequently accompanied by R.L.H. or multiple malignant lymphoma. In our case, some lesions were difficult to distinguish from reactive lesions because cellular atypia was of a low grade. As preoperative radiograpic and endoscopic examination had suggested the lesions to be widespread, the surgical stump was carefully inspected to avoid leaving malignant cells. We discuss the surgical treatment of malignant lymphoma of the stomach.

A cell line designated SNG-II was established from the operation specimen of human endometrial adenocarcinoma, and by means of an immunization procedure using intact SNG-II cells, a monoclonal antibody (Mab) named MSN-1 which reacts immunohistochemically with endometrial cancers was obtained. The cell line grew well without interruption for over 5 years, and, SNG-II cells produced tumors of cell differentiated adenocarcinoma in nude mice. The modal chromosomal number was diploid without a marker chromosome. The production of human chorionic gonadotropin and its beta-subunit, CA-125, tissue polypeptide antigen, and placental proteins such as PP6 and PP7 in SNG-II was confirmed. MSN-1 was of IgM subclass. As the antigenic reactivity was unchanged by trypsin treatment, but lost by periodic treatment, it was suggested that the antigen corresponding to MSN-1 was a carbohydrate sequence. Immunohistochemically MSN-1 reacted with about 70% cases of endometrial adenocarcinoma, but seldom with normal endometrium. Furthermore, the staining pattern of MSN-1 was different in benign cells from that in malignant cells: only the luminal surface of the normal endometrium was positive, whereas the cytoplasma was also stained in many of adenocarcinoma cells.