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Purpose Surgery is the standard treatment for early-stage non-small cell lung cancer (NSCLC), including ground-glass opacity (GGO)-type lung cancer. However, some patients are inoperable or refuse to undergo surgery. To explore whether proton beam therapy (PBT) can be an alternative to surgical resection in these patients, this study aimed to examine the retrospective treatment outcomes of patients with GGO-type lung cancer who underwent PBT. Patients and methods Patients with stage I NSCLC and GGOs who underwent PBT at the Medipolis Proton Therapy and Research Center (Kagoshima, Japan) between April 2011 and September 2015 were included. Patients were treated with a total dose of 66 GyE delivered in 10 fractions. Survival curves were calculated using the Kaplan-Meier method, and treatment-related adverse events (AEs) were assessed. Results A total of 48 patients (median age: 70.9 ± 9.2 years; men: 54.2%) were analyzed, among whom 53 tumors were observed. The 3-year overall survival rate after PBT was 91.7% (95% confidence interval [CI], 79.3-96.8%), the 3-year disease-free survival rate was 85.4% (95% CI: 71.8-92.8%), and the 3-year local control rate among 53 tumors was 92.5% (95% CI: 81.1-97.1%). During the 3-year follow-up period, 4 patients died, and 3 survived despite recurrence or metastasis. Common AEs were radiation pneumonitis (89.6%), rib fracture (27.1%), and cough (27.1%). None of the patients developed grade ≥3 treatment-related AEs. Conclusion The results of this study suggest that PBT may be a promising alternative for patients with GGO-type lung cancer when surgical resection is not feasible, with excellent survival outcomes and tolerable treatment-related AEs.

Background Receptor for advanced glycation end-products (RAGE), a receptor for amyloids, is constitutively expressed in lungs and generally observed to be downregulated in lung cancer tissues. However, increasing levels of RAGE or serum amyloids is associated with poor outcome in lung cancer patients. We report a rare case of primary systemic amyloid light-chain (AL) amyloidosis in biopsy-proven multiple organs with early-stage non-small cell lung cancer (NSCLC) that displayed strong staining for RAGE in the tumour tissue. Interestingly, compared with randomly selected lung cancer biopsy samples, including all representative histological subtypes of NSCLC and small-cell lung cancer, only the NSCLC in the present case showed strong expression for RAGE that can bind amyloids. Case presentation A 71-year-old woman was admitted to our hospital for comprehensive investigation of nephrotic syndrome. Computed tomography showed a small nodule in the right upper lung lobe with hilar mediastinal lymph node enlargement. Pathological examination of transbronchial biopsy samples of the nodule yielded a diagnosis of lung adenocarcinoma. Furthermore, the pathological detection of amyloid deposition in biopsy samples of a subcarinal lymph node, gastric and duodenal mucosa, cardiac muscle, and bone marrow led to a diagnosis of primary systemic AL amyloidosis with nephrotic syndrome and cardiomyopathy. In addition, RAGE was detected in lung tumour tissues surrounded by normal lung tissues with amyloid deposition. Conclusion The RAGE positivity of the lung cancer cells in this case suggests an interaction between amyloid-containing tissues and RAGE-expressing cancer cells. Lung adenocarcinoma with RAGE expression may be a complication of underlying amyloidosis.

To have deliveries occur during the daytime on weekdays, programmed induction of labor was attempted. Uncomplicated primiparous pregnant women were randomly divided into induced and non-induced labor groups at the beginning of pregnancy. In the induced group, labor was induced by prostaglandin E2 oral tablet and prostaglandin F2α drip infusion when the prerequisites, (1) 38 weeks or more of pregnancy, (2) 32 cm or more of uterine fundal height, and (3) approximately 9 cm of biparietal diameter of the fetal head on the ultrasonography, were satisfied. Laminaria tents and/or a soft rubber metreurynter were applied to the unripe uterine cervix before induction of labor. In the induced group (n = 588), the rate of daytime delivery (09: 00–17: 00 h) was 80.4% and that of night delivery (00: 00–09: 00 h) was 3.2%. The duration of labor was significantly shorter in the induced group than in the non-induced group. There was no significant difference between the 2 groups in the amount of intrapartum hemorrhage, cesarean section rate, infant birth weight, or one-minute and five-minute Apgar scores.

A new analog of prostaglandin E1 (PGE1) was administered vaginally to women with (n=20) and without (n=29) laminaria tents and metreurynter for therapeutic abortion during the 2nd trimester. All patients aborted successfully. The abortion time was short, bleeding was minimal, and there was little difference between patients treated with 16 DM-PGE1 alone and those treated with 16 DM-PGE1, laminaria tents, and metreurynter. However, amounts of 16 DM-PGE1 required for abortion were significantly greater in patients treated with 16 DM-PGE1 alone. Occurrences of side effects increased with increased amounts of 16 DM-PGE1 administered. Therefore, vaginal administration of that in combination with the use of laminaria tents and metreurynter successfully induced abortion in women during the midtrimester with minimal side effects, and was considered to be the best method presently available for midtrimester therapeutic abortion.

The aims of this study were, using fixed and fresh cadavers, to clarify how closely the pelvic splanchnic nerve, levator ani nerve (LAN), and sacrospinous ligament (SSL) are located and to examine how to avoid nerve injury during the posterior tension-free vaginal mesh procedure (TVMP), in which mesh is applied through the SSL. Macroscopic dissection of fixed cadavers demonstrated that the LAN crossed the inside of the SSL at a point 0-18 mm medial to the ischial spine and entered the muscle at a point 12-26 mm inferior to the ischial spine and 40-55 mm anterolateral to the coccyx. Dissection after TVMP of fresh cadavers revealed that the point of penetration of mesh through the SSL was close to the LAN. To preserve the LAN, penetration of the SSL should be within 5 mm of the lower margin at a point 20-25 mm medial to the ischial spine.

To get support from morphological findings to develop a novel surgical procedure for posterior vaginal defect repair, we histologically examined the rectum-vagina interface tissues obtained from 20 elderly female cadavers. The rectovaginal septum (RVS) was defined here as an elastic fiber-rich plate (EFRP) along the posterior vaginal wall. It lined the posterior surface of the vein-rich zone of the vaginal wall and extended between the bilateral paracolpiums. The septum was more evident in the lower half of the interface than in the upper half. The RVS was often thin and interrupted. Since the RVS was not so clearly demonstrated in the upper vagina histologically, augmentation using some implant is considered to be necessary for the enterocele and high rectocele. Since the thickness and tightness of the RVS vary with the case in the lower vagina, surgical procedures for low rectocele repair should be individualized, including implant-augmentation.

To reinforce the support of the vagina, concurrent use of iliococcygeus fascia colpopexy with the McCall culdeplasty was scheduled for primary uterine prolapse. Forty-five women with primary uterine prolapse without stress urinary incontinence were treated by McCall culdeplasty alone or McCall culdeplasty plus iliococcygeus fascia colpopexy for suspension of the upper portion of the vagina. Recurrence of vaginal support defects were carefully followed for 15-50 months. Additional iliococcygeus fascia colpopexy did not change with the axis of the vagina obtained by McCall culdeplasty, although it prolonged total operation time by 32 min and increased blood loss by 94 ml. Two cases (8.3%) had postoperative vaginal defects in the group undergoing combined procedures and seven recurrent cases (33.3%) were observed in the group undergoing McCall culdeplasty alone. The durability of the combined procedures was superior to that of the modified McCall culdeplasty alone by Kaplan-Meier analysis. These results suggest that iliococcygeus fascia colpopexy is reasonably safe and strengthens not only the attachment of the upper part of the vagina but also that of the anterolateral vaginal wall.

97 Background: Although there are many patterns of treatment in localized prostate caner, proton beam therapy has no definite role in them. We aimed to assess the outcomes of proton beam therapy (PBT) alone for patients with intermediate- and high-risk prostate cancer, and to clarify the role of PBT in the treatments. Methods: Between Jan. 2011 and Sep. 2014, 204 patients with intermediate- and high-risk prostate cancer who declined to receive hormonal treatments until biochemical or clinical recurrence were enrolled in the study. All patients were irradiated a 70-78 GyE in 28-39 fractions, and pre-treatment risk groups were classified in accordance with the D’Amico criteria. The 5-year (biochemical or clinical) recurrence-free survival (RFS), late gastrointestinal (GI) and genitourinary (GU) toxicity (NCI-CTCAE ver.4.0) were evaluated. We conducted a survey on sexual quality of life (QOL) every six months to evaluate any long-term damage to the sexual function using the Expanded Prostate Cancer Index Composite (EPIC). Results: The mean age and the follow-up period were 66 (range: 39-86) and 52 months (range: 24-76 months), respectively. The 5-year RFS rates in intermediate- (n = 112) and high- (n = 92) risk groups were 96.9% and 83.4%, respectively. There was a significant difference between the two groups (p = 0.002). The incidence of grade 2+ GI and GU toxicity were 4% and 3%, respectively. We found a significant difference in the GI toxicity between the two radiation protocols of 78GyE/39fractions (n = 6, 11%) and 70GyE/28fractions (n = 0, 0%) (p < 0.01). A 5.8% decrease in average after adjusting for aging was found in sexual summary score in six years after treatment, which was equivalent to aging of three years. Conclusions: Proton beam therapy alone demonstrated favorable results in patients with intermediate- and high-risk prostate cancer. Although more patients and longer follow-up are necessary to confirm the outcomes, these results suggested a hypothesis that proton beam therapy might not require androgen deprivation therapy in the treatment of localized prostate cancer, which could lead to a possibility of preserving of sexual function. Clinical trial information: MPTRC-N2 and N3.

We performed genome-wide linkage analysis in 58 patients and nine unaffected members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTER program. As a result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and non-parametric LOD (NPL) = 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using dense markers, this 3p22-p25 region showed a P-value0.05 at 10 markers and there is suggestive evidence for linkage at two markers within approximately 19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explore whether the candidate gene in this 3p22-p25 region contributed to carcinogenesis of familial ovarian cancer in a similar fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH) analysis. It was observed that the frequency of LOH at four markers in this region was50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.

To compare the effectiveness and safety of once- versus twice-weekly high-dose-rate (HDR) brachytherapy for cervical cancer.From 1980 to 1997, 124 consecutive previously untreated patients with cervical cancer were treated with external-beam irradiation (50 Gy) and HDR brachytherapy. Clinical stages were I, 4 (3%) patients; II, 51 (41%); III, 64 (52%); and IV, 5 (4%). From 1980 to 1992, 74 patients (group A) were treated with HDR brachytherapy once weekly (about three fractions of 7 Gy each to point A [2 cm superior and 2 cm lateral to the inferior end of the intrauterine radioactive source]), while from 1992 to 1997, 50 patients (group B) were treated twice weekly (about six fractions of 4.5 Gy each to point A).Overall survival rate at 5 years was 65.2% in group A and 65.3% in group B (P=.96). Local recurrence-free survival rate at 5 years was 69% (51 of 74 patients) in group A and 90% (45 of 50 patients) in group B (P.001). The rate of grade 2 (moderate) and grade 3 (severe) complications was significantly lower in group B (6% vs. 32% in group A, P.001). At multivariate analysis, the variables significantly associated with increased local-regional recurrence rates were having stage III-IV lesions (P=.04) and with fewer than six sessions of HDR brachytherapy (P=.02).The twice-weekly HDR regimen may improve the local control rate with fewer complications.

We examined the subcellular localization of BRCA1 proteins using immunohistochemical staining with C‐terminal (GLK‐2 antibody) and N‐terminal (Ab‐2 antibody) monoclonal antibodies in 44 familial ovarian cancers. Among these, 24 cases were associated with 13 independent germ‐line mutations of BRCA1, and loss of heterozygosity (LOH) at one or more BRCA1 microsatellite markers was found in all 21 informative tumors tested. With GLK‐2 antibody, cytoplasmic staining was observed in 15 of 16 tumors (93.8%) with mutation in exon 11, and BRCA1 staining was absent in 8 of 8 tumors (100%) with mutation in exons other than exon 11. When immunohistochemical staining was performed with Ab‐2 antibody, both nuclear and cytoplasmic staining were observed in 14 of 16 tumors (87.5%) with mutation in exon 11. Interestingly, nuclear staining was observed in 3 of 3 tumors (100%) with mutation downstream of exon 11, even though no staining was detected in 5 of 5 tumors (100%) with mutation upstream of exon 11. On the other hand, in familial ovarian cancers without BRCA1 mutations, nuclear staining or both nuclear and cytoplasmic staining was observed in 18 of 20 specimens (90%) and 20 of 20 specimens (100%) with GLK‐2 antibody and with Ab‐2 antibody, respectively. These results suggest that an immunohistochemical assay in combination with employing the C‐terminal and the N‐terminal antibodies appears to have potential as a reliable and useful technique for the screening of BRCA1 mutations, at least to predict the status of mutation, upstream or downstream of exon 11.

Purpose: The aim of this study was to determine whether taxol can circumvent cisplatin resistance, using a KF28 cell line derived from human ovarian carcinoma and a cisplatin-resistant line, KFr13, derived from the parental cell line, KF28, and taxol-resistant cell lines, KF28TX and KFr13TX, derived from the respective parental counterpart. Methods: KF28 is a single-cell clone of the human ovarian carcinoma cell line KF. The cisplatin-resistant KFr13 subline was established by repeated exposure of the parent KF28 cell line to escalating doses of cisplatin. Similarly, KF28TX and KFr13TX were established by repeated exposure of the KF28 and KFr13 cell lines to escalating doses of taxol. A cytotoxicity assay was performed using a crystal violet staining method. Platinum and taxol accumulation were assayed by atomic absorption and reverse-phase high-performance liquid chromatography. The quantitative assay of MDR1 mRNA used polymerase chain reaction. Results: KFr13 cells were about 4.8-fold more resistant to cisplatin and about 1.8-fold more sensitive to taxol than were KF28 cells. When taxol resistance was induced in KF28 and KFr13 cells, sensitivity to cisplatin rose about 1.3- and 1.6-fold respectively. Elevation of sensitivity was correlated with platinum uptake by both KF28TX and KFr13TX cells. Expression of multidrug resistance (MDR1) mRNA, which was not observed in KF28 and KFr13 cells, was observed after induction of taxol resistance. Conclusions: These results may suggest rational therapeutic strategies for patients with cisplatin-resistant or refractory ovarian carcinoma.

Telomeres are unique DNA tandem repeats that form the ends of eukaryotic chromosomes to protect the chromosomes from degradation and illegitimate recombination. In yeast, loss of telomere may be compensated for through the acquisition of new telomere by RAD52-mediated or RAD52-independent recombinational repair. In this report, the effects of cis-dichlorodiammine-platinum (II) (cisplatin) on telomere length and the role of nucleotide excision repair in telomere maintenance were examined in the yeast Saccharomyces cerevisiae. We showed that the SSL2 (RAD25) DNA repair yeast mutant exhibited a gradual shortening of the telomere in the presence of cisplatin. Further telomere shortening was prevented upon the withdrawal of cisplatin. Complementation of the mutant with the wild-type SSL2 (RAD25) gene abolished the cisplatin-induced telomere degradation. These results suggest that telomeres are susceptible to cisplatin-induced intrastrand crosslinks and that Ssl2 (Rad25) or the nucleotide excision repair pathway may play a critical role in the repair and the maintenance of telomere integrity.

Background. Primary embryonal rhabdomyosarcoma of the uterine corpus is an extremely rare tumor. A case of rhabdomyosarcoma originating in the uterine myoma is presented with a review of the literature. Case. A 76-year-old female presented with a half-year history of abdominal swelling and fever of unknown origin. A 15 × 15 × 17 cm myoma-like tumor was noted on the anterior wall of the uterine myometrium. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. The histology and immunohistochemistry aided in the final diagnosis of a pure embryonal rhabdomyosarcoma of the uterine corpus. This patient received three courses of CYVADIC chemotherapy consisting of cyclophosphamide, vincristine, doxorubicin, and dacarbazine after the surgery and is now alive with no evidence of disease 10 months from her surgery. Conclusion. This case is extremely rare with respect to the uterine corpus origin, especially the myoma nodule and the age of the patient.

Objective: To evaluate the degree of psychological dysfunction and levels of stress hormones in postmenopausal women with climacteric syndromes and effect of Korean red ginseng (RG) on them. Methods: ACTH, cortisol and DHEA-S in peripheral blood from 12 postmenopausal women with climacteric syndromes or 8 postmenopausal women without any climacteric syndrome were measured before and 30 days after treatment with daily oral administration of 6 g RG. Blood samples were collected in the early morning on the bed-rest. In postmenopausal women with climacteric syndromes such as fatigue, insomnia and depression, psychological tests using the Cornell Medical Index (CMI) and the State-Trait Anxiety Inventory (STAI) were performed before and 30 days after treatment with RG. Results: CMI score as well as anxiety (A)-state in STAI score in postmenopausal women with climacteric syndromes was significantly higher than that without climacteric syndrome, while DHEA-S levels in postmenopausal women with climacteric syndromes were about a half of those without climacteric syndrome. Consequently, cortisol/DHEA-S (C/D) ratio was significantly higher in postmenopausal women with climacteric syndromes than in those without climacteric syndrome. When postmenopausal women with climacteric syndromes were treated with daily oral administration of 6 g RG for 30 days, CMI and STAI A-state scores decreased within normal range. Although the decreased DHEA-S levels were not restored to the levels in postmenopausal women without climacteric syndrome, the C/D ratio decreased significantly after treatment with RG. Conclusions: Improvement of CMI and STAI scores in postmenopausal women suffering climacteric syndromes, particularly fatigue, insomnia and depression, by RG seemed to be brought about in part by effects of RG on stress-related hormones as shown by a decrease in C/D ratio.

This retrospective study of ovarian cancer aimed to elucidate whether expression of apoptosis-related proteins, bcl-2, p53 or MDM-2, is associated with resistance to chemotherapy, especially cisplatin (CDDP) based chemotherapy. Expression of bcl-2, p53 and MDM-2 was assessed by immunohistochemical staining of tumour tissues collected at initial surgery prior to treatment with CDDP-based chemotherapy. Among 66 patients with advanced ovarian cancer with measurable tumour following surgery and evaluable for response to chemotherapy, 42, 45 and 56% were positive for bcl-2, p53 and MDM-2, respectively. Significantly fewer tumours of patients who had a complete response to chemotherapy (CR) showed positivity for bcl-2 (2/20) than for p53 (6/20) and MDM-2 (8/20, P < 0.001). There was an inverse correlation between bcl-2 staining and initial response to chemotherapy, especially in serous and endometrial adenocarcinomas. In patients with stage III-IV, serous or endometrioid adenocarcinomas, significantly poorer survival was seen for those with bcl-2 positive tumours than those with negative bcl-2 staining (P = 0.0064). p53 and MDM-2 were not correlated with initial response to chemotherapy. Multivariate analysis revealed that bcl-2, residual tumour size and histology were significant independent prognostic factors. These results suggest that bcl-2 can be a possible predictor of response to chemotherapy and prognosis in patients with advanced ovarian carcinoma.

Bivalves are important fishery resources. For example, surf clam (Pseudocardium sybillae), lives in sandy beaches along the open sea in northern Japan. It has been reported that an increase in young bivalves of surf clams in tranquil areas around newly constructed ports. A large number of young bivalves are often cast onto the shore by high waves in winter. The process of mortality and behavior of young bivalves due to waves must be clarified. In this study, in order to grasp the behavior of bivalves after released out of sand, the behavior of bivalves over sand ripples under oscillatory flow was experimentally investigated.

In 5-day incubation of an estrogen receptor-negative human ovarian cancer cell line (KF) with N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine-HCl (DPPE), the concentration of DPPE required for 50% inhibition of KF cell proliferation (IC50) was 1.7 microM. The IC50 of DPPE for inhibition of protein kinase C (PKC) activity was 3.0 microM, a similar value to those of other antiestrogens such as tamoxifen and clomiphene. DPPE also inhibited phosphorylation of mitogen-activated protein kinase in KF cells. When treatment with DPPE was started 7 days after inoculation of KF cells into nude mice, 50 mg/kg DPPE alone resulted in a significant growth retardation in the early stage of tumor growth. Although 25 mg/kg DPPE showed a similar effect to 2 mg/kg cisplatin (CDDP), the combination had the most marked tumor growth-inhibitory effect. Nude mice treated with combinations of CDDP and DPPE survived significantly longer than not only untreated, but also CDDP-alone-treated mice, while 50 mg/kg but not 25 mg/kg DPPE alone had an effect comparable to that of 2 mg/kg CDDP alone. If treatment with DPPE was begun from the day after tumor inoculation, the inhibitory effect of DPPE was further enhanced, especially when combined with CDDP. If treatment with DPPE was started in nude mice with a lower tumor burden, 25 mg/kg as well as 50 mg/kg DPPE had a similar effect to 2 mg/kg CDDP, in terms of survival. When DPPE was combined with CDDP, the effect was significantly enhanced, compared to that of either alone. These treatments could be done without any adverse side effect. Thus, we conclude that DPPE has an antiestrogen action and its tumor growth-inhibiting activity is enhanced on administration in combination with CDDP.

This study was designed to elucidate the mechanisms of cisplatin (CDDP) resistance using two human ovarian cancer cell lines, KF and TYK, and two CDDP-resistant lines, KFr and TYK/R, derived from the former lines. KFr and TYK/R showed about 3-fold higher resistance to the cytotoxic effects of CDDP than their parental lines. They also showed a significant increase in sensitivity to not only etoposide, but also (+)-(4S)-4, 11-diethyl-4-hydroxy-9-[(4-piperidino -piperidino)carbonyloxy]-1H -pyrano[3',4':6,7]inodolizino[1,2-b]quinoline-3,14(4H, 12H)-dione hydrochloride trihydrate (CPT-11). Cellular CDDP accumulation levels in KFr and TYK/R were decreased from those of the parental cells. By contrast, the cellular glutathione (GSH) content in KFr cells was 1.7-fold higher than that in KF, whereas TYK/R cells had a 40% lower content than TYK cells. Cellular mRNA levels of drug-resistance-related genes, such as DNA topoisomerase (topo) I and topo II, glutathione S-transferase-pi (GST-pi), gamma-glutamylcysteine synthetase (gamma-GCS), and metallothionein (hMT) genes, were compared between drug-sensitive KF or TYK and KFr or TYK/R. KFr cells had 8.5- and 24.7-fold higher mRNA levels of gamma-GCS and topo II genes than KF cells while KFr had only a slight increase in GST-pi mRNA level as compared with KF. By contrast, TYK/R cells had 2.9- and 1.7-fold higher hMT and topo I mRNA levels than TYK cells. Acquisition of CDDP resistance in human ovarian cancer cells thus appeared to be related mainly to expression of gamma-GCS, topo II and hMT genes, and partly to that of topo I and GST-pi genes, in addition to a decrease in CDDP accumulation.

This study was designed to the elucidate sensitising effects of the intracellular histamine antagonist, N,N-diethyl-2-[4-(phenylmethyl)phenoxy] ethanamine· HCl (DPPE) on the antitumour activity of cis-diamminedichloroplatinum (II) (CDDP) using human ovarian cancer cell lines with different sensitivities to CDDP (KF, sensitive) KFra (acquired CDDP resistant derived from KF), and KK and MH, intrinsically CDDP resistant. The KF cells were most sensitive to CDDP among cell lines used in this study and followed by MH, KK and KFra showing approximately 3.5, 4.0 and 9.1-fold IC50 values to KF, respectively. The acquired CDDP resistant KFra cells were approximately 6.1-fold more sensitive to DPPE than the parent KF cells, while MH and KK cells were more than 10-fold more resistant to DPPE than the KF cells. With regard to the inhibition of human ovarian cancer cell proliferation, phenyltoloxamine and L-histidinol were 5–2500-fold less cytotoxic than DPPE. Analysis of flow cytometry (FCM) revealed that with concentrations based on the IC50 to KF and KFra cells, DPPE resulted in G2-M accumulation in the KF (but not KFra) cells in a time-dependent manner during the course of 48 h incubation time. In addition, from a median effect analysis, DPPE seemed to have additive and somewhat synergistic effects on the antitumour activity of CDDP in KK and MH cells with intrinsic CDDP resistance, while minor antagonism in KFra cells with acquired CDDP resistance was observed. Although DPPE alone did not significantly inhibit the tumour growth of nude mice bearing KF cells, combinations of DPPE with CDDP resulted in improved survival compared with treatment with only CDDP. Adverse side-effects, as confirmed by monitoring haematocrit and the body weight were not observed during the experimental period. These results suggest that DPPE may be of clinical use for the treatment of intrinsically refractory ovarian carcinoma when combined with CDDP.

Parathyroid-hormone-related protein (PTHrP) is found in high concentrations in human milk. One of the possible physiological roles of PTHrP may be the regulation of calcium transport through the mammary gland. The relationship between milk PTHrP and Ca concentrations was evaluated in lactating women in the present study. Milk PTHrP has been quantified by immunoradiometric assay (IRMA) and radioimmunoassay (RIA). The IRMA detects PTHrP 1-72, and the RIA carboxyterminal region of PTHrP (C-PTHrP). Milk PTHrP 1-72 and C-PTHrP concentrations did not significantly change by breast-feeding. Milk PTHrP 1-72 changed significantly by the time of day, in contrast to C-PTHrP. Thus, PTHrP 1-72 rather than C-PTHrP may reflect an acute change in mammary PTHrP secretion. In lactating women in whom milk PTHrP and calcium concentrations were serially measured at 5-day intervals up to 26-30 days after delivery, milk PTHrP 1-72 progressively increased with duration of lactation. In contrast to PTHrP 1-72, milk C-PTHrP decreased during this period. And milk PTHrP 1-72 levels inversely correlated with C-PTHrP levels. Milk C-PTHrP but not PTHrP 1-72 levels correlated significantly with milk Ca concentrations. Although it is not certain whether the correlation between milk C-PTHrP and Ca levels is causally related, it may be that fragments of PTHrP detected as C-PTHrP are involved in the regulation of Ca transport through the mammary gland in women.

Objective: In order to elucidate the roles of inositol trisphosphate (IP3) and oxytocin (OT) receptors in rabbit parturition, the concentration of IP3 induced by OT and the OT receptor levels were determined in rabbit myometria before and after parturition. Methods: The effects of OT on IP3 formation and OT receptor levels were determined in the myometria of non-pregnant rabbits, Days 26, 28 and 30 of pregnancy rabbits, postpartum rabbits within 12 hours and steroid-treated ovariectomized rabbits. Prostaglandins (PGs) levels were also measured in the myometrial and decidual tissues. Results: OT receptors were not detectable in the myometria of non-pregnant rabbits, and OT had no effect on the formation of inositol phosphates (IPs). On Day 28 of pregnancy, OT receptors became detectable, and then OT could induce the formation of IPs. Thereafter, the stimulatory effects of OT on IPs formation and the OT receptor levels dramatically increased toward the end of pregnancy and reduced rapidly after parturition. When the ovariectomized pregnant rabbits were treated with estrogen, OT receptors in the myometrium were induced, and OT acquired the ability to stimulate IP3 formation. However, OT had no effect on the production of cAMP, cGMP, prostaglandin (PG) E2 and F2α in the myometria, even if receptors existed, although PGE2 production in the decidual tissues was markedly stimulated. In addition, an OT receptor antagonist inhibited the stimulatory effects of OT on IP3 formation. Conclusions: These results suggest that the formation of IPs by OT, the OT receptor levels in the myometrium, and the production of PGE2 in the decidua might play crucial roles in parturition.

Experimental endometriosis in rats was induced by autotransplanting the uterine endometrium to the peritoneum. In all rats, endometrial implants developed into endometriotic tissues similar to those in humans about 2 weeks after transplantation. Natural killer (NK) activity of spleen cells in the endometriosis model rats was significantly (p < 0.05) lower than that in the sham-operated intact rats. The inhibited NK activity in the endometriosis rats recovered to the level in intact rats with danazol (but not buserelin). The supernatant after 24-hour culture of endometrial tissues from both intact and model rats seemed to have significant inhibitory effects on NK activity. The supernatant from endometrial grafts showed significantly (p < 0.05) higher inhibitory effects than that from the endometrial tissues. The inhibitory effects were significantly (p < 0.05) reduced by treatment with danazol or buserelin to the untreated level. In addition, supernatants of unaffected peritoneal tissues from the endometriosis rats had significantly (p < 0.01) higher inhibitory effects on NK activity than those from the intact rats. Even when uterine serosa or silicone was implanted to the peritoneum, the supernatants of the contralateral peritoneal tissues showed significantly (p < 0.05) higher inhibitory effects than those from the intact rats, while having significantly (p < 0.05) lower inhibitory effects than those from the endometriosis rats. These results suggest that this marked inhibitory effect on NK activity by the peritoneum may be associated with the development and progression of endometriosis.

In this study, we have determined the adjuvant effects of suramin to cis-diamminedichloroplatinum(II) (CDDP) on human ovarian cancer (KF) cell growth in vitro and in vivo . Suramin inhibited the ovarian cancer cell proliferation in vitro in a dose-dependent manner between 10 and 80μ M , showing the IC 50 of 29 μ M . From analysis of flow cytometry (FCM), suramin seemed to be a blocker of G 2 -M phase of the cell cycle. From the results of the isobologram, suramin appeared to have additive and somewhat synergistic effects on antitumor activity of CDDP. When 5 × 10 5 KF cells were inoculated sc into the right flank of nude mice, 8 of 10 mice formed solid tumor at 4 weeks. When 2 mg/kg CDDP was administered ip every week, the 80% tumor formation was prolonged to 10 weeks. Treatment with 5 and 10 mg/kg suramin decreased the formation rate of palpable tumor to 50 and 30%, respectively. When CDDP was followed by 5 or 10 mg/kg suramin, the tumor formation rate was 20 or 0%. On the other hand, if suramin was followed by CDDP, the tumor formation was not observed in any mouse during the experimental period. These results suggest that suramin may provide a new strategy for treatment of refractory ovarian carcinoma.

本邦では欧米に較べて乳癌の罹患率, 死亡率ともいまだ低率であり, 乳癌の女性生殖器への転移に関する報告も少ない. また, 報告例の多くは, すでに骨, 肝, 肺など多臓器に転移を伴った症例が多く, 女性生殖器への転移の形で初再発をきたした例はきわめてまれである. 今回われわれは, 根治術後3年を経た後, 女性生殖器へのびまん性転移の形で初再発をきたした早期乳癌の1例を経験した. 局在性腫瘤を伴わないびまん性転移の場合, 画像検査による診断は困難であり, その診断には腫瘍マーカーの測定とともに細胞診が有用であった. この症例は乳癌既往症例における初再発を知るうえで婦人科細胞診を含む積極的な検索が必要であることを示唆する興味深い症例と思われた.

過去3年間において当科を受診した妊婦2972例に対して綿棒または湿綿球にて子宮頸部擦過細胞診を実施した.結果はclass III aが16例 (0.54%), class III bが4例 (0.13%), class IVが2例 (0.07%) であった.当科ではこのような細胞診異常を呈した妊婦については極力円錐切除を回避するよう心がけており, 細胞診やコルポスコープで進行癌を示唆する所見がない場合は, 円錐切除を敢えて行っていない.初回細胞診にてclass IVを呈した2例は狙い組織診にて1例はcarcinoma in situ (CIS), 1例はsevere dysplasiaであった.2例とも円錐切除は実施せず, 保存的に経過観察を行ったところ, いずれも細胞診上はclass IVを持続した.この2例は産後の子宮全摘, 円錐切除により, 組織学的にCISであった.また, 今回の検討期間中には進行癌を示唆する症例は認められなかった.当科の管理方針は妊娠中の円錐切除に起因するさまざまな合併症を回避できる点において有用であるが, 浸潤癌におけるunder diagnosisの危険性については今後症例を重ね検討する必要があると思われた.

We measured cord blood levels of calcium-regulating hormones and osteocalcin in 34 premature infants of various gestational ages. 1,25(OH)2D levels were low in mid-gestation and increased with advancing gestation. Parathyroid hormone levels were low, and calcitonin levels were high in mid-gestation. Both of them declined with advancing gestation. Osteocalcin levels were high in mid-gestation. They increased from 22 weeks through 27 weeks of gestational age, and decreased thereafter. Circulating osteocalcin is considered as a clinical marker of bone turnover. However, cord blood osteocalcin decreased between 27 and 36 weeks of gestation during which period calcium accumulation by the fetus increases. Therefore, cord blood osteocalcin does not appear to reflect fetal bone formation.

The effects of D,L-buthionine-S, R-sulphoximine (BSO) on the cellular glutathione (GSH) levels and cis-diamminedichloroplatinum (II) (CDDP) sensitivity of human ovarian cancer cell lines (HRA, KK and MH) with different sensitivity to CDDP were examined. HRA cells were derived from ascites of a patient with serous cystadenocarcinoma of the ovary who responded well to CDDP-based combination chemotherapy. KK and MH cells were also established from ascites of a patient with clear cell carcinoma of the ovary and with serous cystadenocarcinoma of the ovary, respectively who did not respond to CDDP-based combination chemotherapy. The KK and MH cell lines showed 2.93- and 7.80-fold higher resistance to CDDP in vitro than HRA cells, respectively and had also cross-resistance to its analogues. Although GSH levels in the CDDP sensitive HRA cells were 33.4 nmol/10(7) cells, the CDDP resistant KK and MH cells showed 5.61-and 10.48-fold higher GSH levels, respectively. The higher the GSH levels the more rapid depletion of the cellular GSH by BSO occurred. Cystine, a component of GSH, resulted in an increase of the cellular GSH in these cell lines. When the cellular GSH levels were changed by BSO or cystine, changes of the IC50 to CDDP and its analogues of the CDDP resistant KK and MH cells correlated with those of the cellular GSH levels while the IC50 values of the CDDP sensitive HRA cells remained unchanged. In addition, when these resistant cell lines (but not HRA cells) were incubated with CDDP, the cellular GSH levels markedly increased. From these results, we conclude that GSH may have a role in the mechanisms of intrinsic resistance to CDDP and its analogues of the KK and MH cell lines.

A 44-year-old woman with stage IV non-Hodgkin's lymphoma (NHL) of the left ovary is described. She had an extended hysterectomy and bilateral salpingo-ophorectomy and thereafter received six courses of combination chemotherapy (cyclophosphamide, adriamycin, vincristine and predonisolone; CHOP). The patient is well with no evidence of recurrence at 12 months after surgery. The literature on primary ovarian lymphoma is reviewed.

Effects of antineoplastic prostaglandins (PG) on human ovarian cancer cell growth were examined by using HR cells derived from ascites of a patient with serous cystadenocarcinoma of the ovary. With regard to inhibition of cancer cell proliferation in vitro, the effects of delta 7-PGA1 was most marked, followed by that of delta 12-PGJ2, PGJ2 and PGD2. When antineoplastic prostaglandins were administered to nude mice bearing HR cells, tumor growth in groups treated with PGJ2 and delta 12-PGJ2 alone was significantly inhibited 63 days after tumor inoculation, compared to that in an untreated group. Consequently, a significant prolongation of median survival was obtained with delta 12-PGJ2, compared to that in untreated groups and in groups with cisplatin alone. In addition, when prostaglandins were administered together with cisplatin, adjuvant inhibitory effects on the tumor growth were obtained 35, 56 and 63 days after tumor inoculation. Subsequently a significant prolongation of median survival was observed when cisplatin was combined with PGD2 or delta 7-PGA1, compared to the results in groups treated with PGD2 alone, delta 7-PGA1 alone or cisplatin alone. Combination of PGJ2 or delta 12-PGJ2 and cisplatin resulted in a significant decrease of hematocrit and body weight 63 days after tumor inoculation, suggesting a deterioration of the median survival. These results suggest that combination of PGD2 or delta 7-PGA1 with cisplatin may be of clinical use for ovarian cancer resistant to cisplatin.

Between January 1, 1979, and September 30, 1990, a total of 1,886 patients in the National Defense Medical College Hospital, a self-referred population, had a hysterectomy because of signs and symptoms presumably resulting from uterine myomas. After hysterectomy with presumed benign disease, a histologic diagnosis of leiomyosarcoma was made in 7 patients (0.37%). Preoperative diagnosis of leiomyosarcoma was not made in any of the 7 patients. However, serum lactate dehydrogenase levels were abnormally elevated in 3 of them, and degenerative changes were found within the tumor by ultrasonography in 5 of them. Furthermore, increased lactate dehydrogenase levels and degenerative changes within the tumor were found in 3 of the patients whose tumors had 10 or more mitoses per 10 high-power fields. The prognosis for the leiomyosarcomas with increased mitotic rates is very poor. Therefore, a degenerative change within the uterine mass and an increased lactate dehydrogenase level, when present, should suggest the diagnosis of leiomyosarcoma.

To study the correlation between stress urinary incontinence (SUI) and the mobility and funneling of the bladder neck (BN) by observation of pre- and postoperative course by perineal ultrasound (PUS).We investigated 123 cases that underwent reconstructive surgery for pelvic organ prolapse (POP). We prospectively checked bladder neck mobility (BNM) during the Valsalva maneuver and funneling of the BN at rest by PUS. We defined the width multiplied by the depth of the funnel-like profile of the BN as the funneling index (FI). We checked BNM, FI, and the presence of SUI just before the operation, and we checked the postoperative course of BNM and SUI.When BNM was ≥10 mm before surgery, the odds ratio for accompanying SUI was 2.68 relative to BNM10 mm (p = 0.031). When FI was ≥150 before surgery, the odds ratio for accompanying SUI was 4.12 relative to FI150 (p = 0.004). Although postoperative BNM values were significantly improved immediately after surgery, they gradually increased within 2 years. Among the cases with preoperative SUI, the recurrence rate was significantly higher in the patients whose FI was150 (p = 0.019).Our results yielded by PUS suggested that larger BNM and FI values were the causative factors of SUI. PUS may be beneficial for selecting a suitable surgical procedure for POP, and it may also be helpful for assessing surgical efficacy.

We measured serum concentrations of calcium-regulating hormones and osteocalcin in 20 women longitudinally throughout pregnancy, 1,25-Dihydroxyvitamin D levels were high early in pregnancy and increased with advancing gestation. Parathyroid hormone and osteocalcin levels were low in early pregnancy. They declined toward the middle of pregnancy, but increased in late pregnancy. The serum osteocalcin level correlated with the parathyroid hormone level. The synthesis of osteocalcin by osteoblasts is stimulated by the action of 1,25-dihydroxyvitamin D, and serum osteocalcin levels are also related to the levels of parathyroid hormone. During early and mid pregnancy, the stimulatory effect of 1,25-dihydroxyvitamin D on the synthesis of osteocalcin may be overridden by the inhibitory effect of declining parathyroid hormone levels. The increase in osteocalcin level in late pregnancy may be a consequence of increasing levels of both parathyroid hormone and 1,25-dihydroxyvitamin D.

The mechanism of cis-diamminedichloroplatinum (II) (CDDP) resistance was examined by using a CDDP-resistant (KFr) cell line established by continuous exposure of KF cells (derived from serous cystadenocarcinoma of the ovary) to escalating doses of CDDP. When KFr cells were incubated with 66.7 microM CDDP, the uptake of CDDP was significantly inhibited and the cellular content in the KFr cells was about a half of that in KF cells after incubation for 4 h. When the KF or KFr cells were incubated for 4 h with 100 microM CDDP, the release pattern of CDDP from KFr cells was similar to that from KF cells. In addition, the DNA histogram of both KF and KFr cells revealed that KF cells seemed to contain two clones of cell population and the KFr cells may have been selected by exposure to CDDP. At 3 h after intraperitoneal administration of 0.5 mg of CDDP per mouse to nude mice with KF or KFr tumor, the CDDP content in the KFr tumor was significantly lower than that in the KF tumor. In contrast, at 6 or 9 h after CDDP administration the CDDP content in the KFr tumor was significantly higher than that in the KF tumor. Furthermore, the KFr cells had cross-resistance to various CDDP analogues including carboplatin. It was shown that cellular uptakes of two CDDP analogues into KFr cells were significantly lower than those into KF cells.

Comparison was made between lymphocyte subsets in peripheral blood from patients with benign ovarian tumor and those with advanced ovarian carcinoma. In addition, changes of lymphocyte subsets of patients with ovarian carcinoma before and after operation were also examined. The percentage and absolute number of CD3-/HLA-DR+ (B cells) in peripheral blood from patients with advanced ovarian carcinoma were significantly lower than values from patients with benign ovarian tumor, whereas both percentage and absolute number of CD3-/HLA-DR- (null cells) cells in patients with advanced ovarian carcinoma were significantly higher. Although there was no significant difference in natural killer (NK) cell subsets (CD57+ CD16- and CD57+ CD16+ cells) between patients with benign ovarian tumor and ovarian carcinoma, the percentage and absolute number of CD57-/CD16+ (highly differentiated NK cells) cells in patients with ovarian carcinoma were significantly higher than those in patients with benign ovarian tumor. Both the absolute number and percentage of CD3+/HLA-DR+ (activated T cells) cells in ovarian cancer patients with minimal residual tumors after operation were significantly increased, compared to the levels before operation, while the values in the patients with large residual tumors were significantly decreased. In addition, the percentage and absolute number of CD3-/HLA-DR- (null cells) cells in the patients with minimal residual tumors were significantly decreased after operation, while values in the patients with large residual tumors remained unchanged before and after operation. The patients with minimal residual tumors after operation were characterized by a significant increase in the percentage of CD57- CD16+ (highly differentiated NK cells) cells. On the other hand, in the patients with large residual tumors no change of the NK cell subsets was observed before and after operation.

To obtain further insight into the role of endogenous dopamine on the adenohypophyseal hormones secretion in normal women, responses of the adenohypophyseal hormones to a dopamine antagonist, metoclopramide, were evaluated in 7 normal women during the early follicular, late follicular and mid-luteal phases of the menstrual cycle. PRL increments following metoclopramide were similar in all phases. During the early and late follicular phases, metoclopramide induced no significant change in circulating LH levels. However, a significant rise in serum LH was observed following metoclopramide during the mid-luteal phase. No significant changes in serum FSH levels were observed after metoclopramide during any of the 3 phases of the cycle. Following metolopramide, serum TSH levels significantly rose in all phases. TSH increments following metoclopramide were significantly lower in the mid-luteal phase than in the early follicular phase. These results suggest that the modulatory effect of endogenous dopamine on adenohypophyseal hormones secretion is variable and selective throughout the normal menstrual cycle.

Female perineal structures located around the perineal body were histologically examined using semiserial sections obtained from 15 elderly female cadavers. The smooth muscle content of the perineal body was greater in multiparous women. The connective tissue of the perineal body extended inferolaterally and provided a fibromuscular mass that was 10-30 mm long mediolaterally and 3-15 mm long superoinferiorly. The lateral extension (LEX) of the perineal body occupies a space that is surrounded by the vestibular bulb, internal anal sphincter, and levator ani slings. The LEX did not directly connect to the ischiopubic bony rami but did connect indirectly via the vestibular bulb and ischiocavernosus. Thus, the LEX appears to play a critical role for maintaining the topographical relationship between the vagina and the rectum. The surgical approximation of bilateral LEX instead of levator ani may be of key importance when doing a perineorrhaphy. As pudendal nerve branches run along the inferior margin of the LEX, a mediolateral episiotomy may not be the best option.

Objective. To investigate whether somatic mutations in cell cycle checkpoint genes, TP53 and p21 , are involved in the development of ovarian cancer with or without BRCA1 germline mutation. Methods. We analyzed somatic genetic alterations of TP53 and p21 in 46 ovarian cancer patients with BRCA1 germline mutations and 93 sporadic patients, using direct sequencing for the entire coding sequences in TP53 and p21 . Results. TP53 somatic mutations were detected in 25 of the 46 BRCA1 cases and 40 of the 93 sporadic cases (54.3% vs. 43.0%). In contrast, p21 somatic mutations were detected in 1 of the 46 BRCA1 cases and 2 of the 93 sporadic cases (2.2% vs. 2.2%). TP53 mutations in sporadic cases more frequently occurred in exons 6–11 than those in cases with germline BRCA1 mutations (84.4% vs. 56.3%: P = 0.013). The proportion of sporadic cases with TP53 mutations in non-serous tumors (e.g. endometrioid, clear cell, or mucinous) was significantly lower than that in serous tumors (18.5% vs. 53.0%: P = 0.0038). However, there was no significant difference between the proportion of BRCA1 cases with TP53 mutation in non-serous and in serous tumors (37.5% vs. 57.9%). Conclusions. Our results suggest that somatic mutation of TP53 plays less of a role in the carcinogenesis of sporadic non-serous tumors than in that of sporadic serous tumors or BRCA1 -related tumors. Furthermore, p21 somatic mutation appears to be less involved in the development of ovarian cancer than TP53 somatic mutation.

Oxytocin (OT) has been detected in mammalian granulosa-luteal cells during the early stages. The purpose of this study was to explore gene expressions of OT and OT receptor (OTR) in human cumulus cells. Cumulus cells enclosing a mature oocyte were obtained from 6 women undergoing clinical in vitro fertilization and embryo transfer programs. OT and OTR gene expressions were investigated by employing reverse transcription polymerase chain reaction and reverse transcription polymerase chain reaction/single-strand conformation polymorphism methods. OT gene expression in the cumulus cells was positive in 5 women and weakly positive in the remaining patient. The structure of OT mRNA in the cumulus cells was equivalent to that in human hypothalamus. OTR gene expression was also observed in the cumulus cells. This study is the first to describe the simultaneous expression of both OT and OTR genes in human cumulus cells. It is suggested that local OT plays some important roles in fertility through modification of the micro-environment around the oocyte.

We investigated the relationship between interleukin-6 (IL-6) levels and subset profiles of T lymphocyte (T-cell) and macrophage in peritoneal fluid (PF) with or without endometriosis (EM). IL-6 levels in PF with EM were significantly higher than those without EM. IL-6 producing cells with EM were analyzed in each activated mature T-cell (CD3+CD69+) and macrophage (CD14+) were 0.5 and 3.5%, respectively, whereas it was mostly negative in those without EM. Cytotoxic T-cell (CD8+CD11b-) profiles in PF with EM were also quiet different from those without EM. Cellular immunity in the peripheral blood did not change during the course of IVF-ET cycles, although plasma levels of ovarian steroid hormones significantly increased comparing with that in normal ovarian cycles. Cytotoxic T-cell type 1 (Tc1) profiles might be useful predictive values in the pregnancy outcome for infertile patients with EM.

To define the involvement of p16/CDKN2 and p15/MTS2 tumor-suppressor genes for response to chemotherapy in primary epithelial ovarian cancer, we analyzed alterations of the gene in 45 patients who were treated with primary cytoreductive surgery followed by 6 courses of cis-diamminedichloroplatinum (II) (cisplatin)-based combination chemotherapy. Homozygous deletion of p16/CDKN2 and p15/MTS2 genes was found in 8 (18%) and 15 (33%) cases, respectively. Response to the chemotherapy was confirmed by finding at second surgery after the chemotherapy in 26 patients, resulting in 17 responders and 9 nonresponders. The abundance of gene deletion in nonresponders (56%) was significantly higher (p = 0.0463) when compared to that in responders (18%). Moreover, the deletion of genes was a significant poor prognostic factor (p = 0.0441) in advanced ovarian cancer. These results suggest that deletion of p16/CDKN2 and/or p15/MTS2 is a potential indicator for poor chemotherapy response and adverse prognosis in ovarian cancer patients. © 2002 Wiley-Liss, Inc.

Background: We have previously reported that paclitaxel (taxol) results in cisplatin sensitization to human ovarian cancer cells with cisplatin resistance in vitro. This study was designed to determine effects of taxol and its combination with cisplatin on growth of cisplatin-sensitive cell line (KF28) and the cisplatin-resistant counterpart (KFr13) in nude mice. Methods: From 14 days after tumor inoculation treatment was initiated. Taxol (3 mg/kg) and cisplatin (2 mg/kg) were administered i.p. once a week for 5 weeks. Results: In nude mice bearing cisplatin-sensitive cells (KF28), taxol followed by cisplatin and cisplatin plus taxol inhibited significantly (P < 0.05) the tumor growth rate compared with that in nude mice treated with cisplatin alone or taxol alone and cisplatin followed by taxol. On the other hand, in nude mice bearing cisplatin-resistant KFr13 cells, treatment with taxol alone inhibited completely the tumor growth rate, whereas no schedule-dependent interaction of taxol with cisplatin was observed. Conclusion: These results suggest that treatment with taxol alone may be superior to combination of taxol with cisplatin in patients with cisplatin-resistant ovarian carcinoma.

Although clear cell carcinoma of the ovary is considered to be a tumor with poor prognosis, the clinical characteristics has not been defined. The aim of this study was to evaluate the response of clear cell carcinoma of the ovary to first and second-line chemotherapy and explore effective chemotherapy. Fifty-three patients with clear cell carcinoma of the ovary were enrolled between 1988 and 1997 at our department. Since taxol was not available in Japan at that time, cisplatin-based combination chemotherapy has been exclusively used as a standard first-line chemotherapy. Retrospective analyses of clinical characteristics and the response to first or second-line chemotherapy were performed. Median age was 52 years (range 27-71 years). Tumors were 34% (18/53) stage I, 19% (5/53) stage II, 38% (20/53) stage III, and 9% (5/53) stage IV. All patients with I or II stage disease had optimal cytoreduction. Out of 25 patients with III or IV stage disease 20% (5/25) had negative residual tumor, 36% (9/25) had2 cm residual tumor, and 44% (11/25) had/=2 cm residual tumor. All patients received postoperative platinum-based chemotherapy. Of 23 patients with measurable residual tumor 8.7% (2/23) completely and 13% (3/23) partially responded to first-line chemotherapy consisting of cisplatin, adriamycin and cyclophosphamide (CAP) or cisplatin and cyclophosphamide (CP) by CT scan or second look laparotomy. Presence of endometriosis was 55% (29/53) but was not a prognostic factor. Although overall response rate of ovarian clear cell carcinoma to first-line chemotherapy by CAP or CP was about 22%, EP or EJ consisting of etoposide and cisplatin or carboplatin used as a second-line chemotherapy showed 29% response rate, while CPT-P consisting of CPT-11 and cisplatin showed 40% response rate. Clear cell carcinomas were frequently present at early stage, with association of endometriosis and with poor overall prognosis. Although patients with advanced ovarian clear cell carcinoma seemed to have better response to CPT-P than conventional platinum-based chemotherapy, further studies are required with larger number of patients to draw firm conclusions.

Ginsenoside Rh2 (Rh2), isolated from an ethanol extract of the processed root of Panax ginseng CA Meyer, inhibits the growth of B16 melanoma cells. This study was designed to evaluate the ability of Rh2 to inhibit growth of human ovarian cancer cells (HRA) in vitro and in nude mouse. Rh2 inhibited proliferations of various established human ovarian cancer cell lines in a dose-dependent manner between 10 and 60 microM in vitro and induced apoptosis at around the IC50 dose. When HRA cells were inoculated s.c. into the right flank of nude mice, all mice formed a palpable tumor within 14 days. Although i.p. administration of Rh2 alone hardly inhibited the tumor growth, when Rh2 was combined with cis-diamminedichloroplatinum(II) (CDDP) the tumor growth was significantly inhibited, compared to treatment with CDDP alone. When mice were treated p.o. with Rh2 daily (but not weekly), the tumor growth was significantly (P

The aim of this study was to determine prognostic factors of patients with advanced ovarian carcinoma who were not successfully cytoreduced at first surgery. Twenty patients with incomplete initial cytoreduction surgery (12 patients with stage IIIc and 8 patients with stage IV), were analyzed for prognostic factors. The survival time of 13 patients with second reduction surgery (SRS) was significantly (P