Malignant lymphoma of the vagina successfully treated with rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone.

PURPOSE: Primary malignant lymphoma of the vagina is extremely rare. The most common histologic subtype is diffuse large B-cell lymphoma (DLBCL). We report a case of vaginal DLBCL successfully treated with chemotherapy consisting of rituximab, adryamicin, cyclophosphamide, vincristine sulfate, and prednisolone (R-CHOP), followed by pelvic irradiation. CASE: A 44-year-old Japanese woman was admitted complaining of atypical genital bleeding and puruloid vaginal discharge. Gynecological examination showed an ulceration of the vaginal wall and a hard mass the size of a goose egg beneath the left vaginal wall, which had infiltrated to the left pelvic wall. The pathological diagnosis based on a punch biopsy taken from the vaginal tumor was non-Hodgkin's lymphoma. Based on immunohistochemical study, the tumor was subclassified as activated B-cell type DLBCL. The patient was diagnosed with Ann Arbor Stage IEA DLBCL and Stage III vaginal cancer, according to the International Federation of Gynecologists and Obstetricians (FIGO) classification system. She was successfully treated by six courses of R-CHOP, followed by radiation therapy. The patient is well without evidence of disease 13 months following the initial treatment. CONCLUSION: Little attention has been paid to the use of rituximab in addition to conventional chemotherapy and the importance of clinical and morphological subgrouping of DLBCL arising in the vagina. The present case indicates that the effects of rituximab on the prognosis of vaginal DLBCL must be evaluated, and that clinical use of immunophenotypic subgrouping should be considered for vaginal DLBCL.

Villoglandular papillary adenocarcinoma of the uterine cervix diagnosed during pregnancy.

Villoglandular papillary adenocarcinoma (VPA) is a very rare subtype of adenocarcinoma of the uterine cervix but a well recognized variant of cervical adenocarcinoma with a favorable prognosis generally occurring in women of child-bearing age. Only five cases of VPA and pregnancy have been reported. Herein, we report a case of VPA diagnosed during pregnancy and this patient delivered a healthy baby. A successful pregnancy can be completed in patients with VPA without lymph-vascular invasion, when treated conservatively. This management is particularly desirable in young women to preserve reproductive capability.

Distribution and species composition of juvenile and adult scombropids (Teleostei, Scombropidae) in Japanese coastal waters.

Two scombropid fishes, Scombrops boops and Scombrops gilberti, are closely related and commercially important species in Japan. These species are often confused in commercial markets because of their morphological similarity. In this study, scombropid specimens collected from various Japanese coastal waters were subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis and phylogenetic analysis of the 16S rRNA gene in mitochondrial DNA. These analyses showed that all the scombropid specimens collected from localities in the Sea of Japan were identified as S. boops, whereas those from the Pacific Ocean included two species, S. boops and S. gilberti. Almost all juvenile (<200 mm standard body length, S(L)) S. gilberti originated from the Pacific coastal waters of the northern Japan, whereas adults (>400 mm S(L)) were found only in deep water off the Izu Peninsula to the Izu Islands. This suggests that S. gilberti might migrate extensively during its life cycle. In addition, differences in the number of specimens and the distribution between the two species suggest that S. gilberti is less abundant than S. boops in Japanese waters.

Primary mucinous adenocarcinoma of the vagina.

PURPOSE: Primary mucinous adenocarcinoma of the vagina is a rare disease which is characterized by aggressiveness and poor prognosis because of its rapid growth and recurrence, its frequent distant metastases, and its relative resistance to conventional treatment modalities including surgery, radiotherapy, and chemotherapy. We report a case of advanced stage primary mucinous adenocarcinoma of the vagina that showed a highly aggressive course and resistance to combination chemotherapy with paclitaxel and carboplatin. CASE: A 46-year-old multigravid Japanese woman was admitted to our hospital to be treated for Stage IVb primary mucinous adenocarcinoma of the vagina. She had no history of in utero exposure to diethylstilbestrol. She was treated by two courses of neoadjuvant chemotherapy with tri-weekly paclitaxel and carboplatin, which were not effective. Subsequently, total pelvic exenteration with pelvic lymphadenectomy was performed. However, the disease progressed rapidly and the patient died five months after the initial treatment. CONCLUSION: Because of its rarity, little is known about the behavior of primary mucinous adenocarcinoma of the vagina. Additional data about patients with this rare tumor should be collected and analyzed in an attempt to elucidate its prognostic factors, characteristics, optimal treatment, and outcome.

Salmonella enterica serovar Typhi in Japan, 2001-2006: emergence of high-level fluoroquinolone-resistant strains.

The phage types and antimicrobial susceptibilities of 226 isolates of Salmonella enterica serovar Typhi from imported cases in Japan between 2001 and 2006 were investigated. Most (93.8%) had travelled to Asian countries, particularly South East Asia. Twenty-one phage types were identified with E1 (30.5%), UVS (15.9%) and B1 (9.3%) being the most common. The frequency of multidrug-resistant strains reached 37.0% in 2006 with phage types E1 and E9 predominating. Almost half (48.2%) of the isolates were resistant to nalidixic acid and two isolates displayed high-level fluoroquinolone resistance. Three mutations, two in gyrA and one in parC, were identified in both isolates.

A successful pregnancy and delivery after resectoscopic surgery for early invasive endometrial cancer.

Among young women, the incidence of uterine corpus cancer is increasing. Most young women can not preserve fertility because simple total hysterectomy with bilateral salpingo-oophorectomy is the standard method for early endometrial cancer so far. We present a case of early endometrial adenocarcinoma which succeeded in pregnancy and delivery after resectoscopic surgery. Following a circumferential resection of the lesion including the mucosa and muscle layer under resectoscopic guidance, the patient became pregnant by means of in vitro fertilization-embyo transfer with hormone replenishment. She underwent cesarean section at 33 weeks and five days of gestation and had a healthy baby. Resectscopic surgery can help to preserve fertility among young women who have early invasive endometrial cancer.

Primary malignant melanoma of the vagina.

Malignant melanoma originating in the vagina is considered extremely rare and has a very poor prognosis. We report a case of a 70-year-old woman with primary malignant melanoma of the vagina, and discuss the importance of prognostic factors and the efficacy of adjuvant chemotherapy.

Bowel obstruction due to endometriosis in the rectovaginal septum.

It is very rare that endometriotic lesions in the rectovaginal septum cause ileus. We report a case of bowel obstruction due to endometriotic lesions in the rectovaginal septum in a 22-year-old woman whose barium enema presented with apple-core-like findings. Diagnostic and treatment modalities were discussed. Preoperative and postoperative gonadotropin-releasing hormone analog and aromatase inhibitor therapy promote relief of clinical symptoms, a reduction of tumor volume and a better approach to radical surgery.

Beta-hydroxyisovalerylshikonin induces apoptosis and G0/G1 cell-cycle arrest of endometriotic stromal cells: a preliminary in vitro study.

BACKGROUND: Most of the current medical treatments for endometriosis aim to down-regulate the estrogen activity. However, a high recurrence rate after medical treatments has been the most significant problem. Beta-hydroxyisovalerylshikonin (beta-HIVS) is an ATP non-competitive inhibitor of protein-tyrosine kinases and is considered an apoptosis-inducing agent. The aim of this study is to evaluate the effects of beta-HIVS on the proliferation, cell cycle and apoptosis of endometriotic stromal cells. METHODS: We investigated the effects of beta-HIVS on cultured ovarian endometriotic cyst stromal cells (ECSC) by a modified methylthiazoletetrazolium (MTT) assay, a 5-bromo-2'-deoxyuridine (BrdU) incorporation assay and internucleosomal DNA fragmentation assays. The effect of beta-HIVS on the cell cycle of ECSC was determined by flow cytometry. The expression of apoptosis-related molecules was examined in ECSC using western blot analysis. RESULTS: Beta-HIVS significantly inhibited the proliferation and DNA synthesis of ECSC and induced apoptosis and G0/G1 phase cell-cycle arrest of these cells. Down-regulation of the B-cell lymphoma/leukaemia-2 (Bcl-2) expression with the activation of caspase-3, caspase-8 and caspase-9 was observed in ECSC after beta-HIVS treatment. CONCLUSIONS: These results suggest that beta-HIVS induces apoptosis of ECSC by suppressing anti-apoptotic proteins. Although our present findings are preliminary, beta-HIVS could potentially be a therapeutic agent for the treatment of endometriosis.

Complete response to radiation therapy in a patient with chemotherapy-resistant ovarian clear cell adenocarcinoma.

Recurrent ovarian cancer after front-line chemotherapy is incurable. In most institutions, chemotherapy is continued as salvage therapy after primary chemotherapy failure and despite the fact that long-term survival and complete responses are infrequent. Radiation therapy for patients with recurrent ovarian cancer has often been done with palliative intent. A patient with ovarian clear cell adenocarcinoma received irradiation with palliative intent to the whole pelvis after chemotherapy (paclitaxel, carboplatin, and irinotecan) produced no effect. Although she developed a rectovaginal fistula due to cancer invasion during radiation therapy. One year and half after the therapy, she is still alive with no evidence of disease. In an effort to maximize salvage potential and quality of life while minimizing toxicity, selected patients with ovarian cancer should be treated with radiation therapy directed to residual or recurrent sites.

Significance of fractionated irradiation for the biological therapeutic gain of carbon ions.

It is well established that the RBE (relative biological effectiveness) for cell killing depends on LET (linear energy transfer), and that a maximum RBE is observed at approximately 150 keV.micron-1. However, the therapeutic gain depends on the ratio of the RBEs for the effects on the cancer cell population and the effects on normal tissues. The RBE of a given radiation quality depends not only on LET but also on dose, biological system and effect, and irradiation conditions. There is no data available to answer the question: which LET is suitable to improve the biological therapeutic gain of carbon ions? Here, three different LET values of 290 MeV/u carbon ions were selected, and the relative biological effectiveness was compared between tumour-growth retardation and skin damage using a murine transplantable tumour. Larger RBE values for tumours after than the skin type were obtained when carbon ions of intermediate LET were delivered daily for 2 to 5 fractions. The biological therapeutic gain would be high for the carbon ion SOBP if the number of fractions were correctly selected in clinical trials.

c-Ets1 is a promising marker in epithelial ovarian cancer.

c-Ets1 controls the expression of some genes involved in extracellular matrix remodeling. To elucidate the involvement of c-Ets1 in epithelial ovarian carcinogenesis, we investigated the role of the proto-oncogene c-ets1 in the regulation of physiological processes such as cell proliferation, differentiation, and tumor invasion. Using fluorescent immunohistochemistry, we analyzed serial frozen sections for c-Ets1 protein expression in 26 patients with ovarian epithelial carcinoma, 10 patients with benign cystadenoma of the ovary, and 10 premenopausal patients with normal ovaries. We analyzed the relationship between the percentage of c-Ets1 stained cells in a patient and characteristics of the patient including histological classification, clinical stage, histological grade, and clinical outcome. c-Ets1 was not detected in any cases of benign ovarian cystadenoma. Most of the c-Ets1 proteins were found in the cytoplasm and some in the nucleus of epithelial ovarian cancer tissues. Moreover, c-Ets1 was strongly expressed in the head portion of papillary cancer tissues that had invaded the stroma. c-Ets1 expression was significantly associated with clinical stage (p<0.01), histological grade (p<0.01), and clinical outcome (p<0.01). Survival data were available for all patients and univariate Cox regression analysis showed that c-Ets1 expression was significantly associated with a poor prognosis (p<0.05). Our results demonstrate that c-Ets1 expression in epithelial ovarian cancer correlates to the malignant potential of the tumor.

Expression of cathepsin L in normal endometrium and endometrial cancer.

OBJECTIVE: To evaluate the expression of cathepsin L in normal endometrium and endometrial adenocarcinoma. STUDY DESIGN: Tissue from eight cases of G1 and eight of G2 endometrioid adenocarcinoma, and 15 normal endometrial specimens were examined by immunohistochemistry. RESULTS: In the normal endometrium, cathepsin L was expressed in a few cell layers of the apical part of the glandular epithelium throughout the menstrual cycle. In the carcinomas, there was an inverse correlation between the grade of tumor and the cathepsin L expression. CONCLUSION: Cathepsin L expression may cease during endometrial carcinogenesis and its expression may be less important in tumor progression than it is in tumors of other tissues.

Atypical polypoid adenomyoma in a patient with hyperprolactinemia.

We report a case of an atypical polypoid adenomyoma in a patient with hyperprolactinemia. A 23-year-old Japanese woman was admitted complaining of atypical genital bleeding. Specula examination revealed a walnut-size polypoid mass extruding from the cervix. The patient was oligomenorrheac, and endocrine analysis showed hyperprolactinemia. Transvaginal ultrasonography and magnetic resonance imaging revealed an endometrial polypoid mass (4 x 3 x 3 cm) arising from the lower segment of the uterine corpus. The pathologic diagnosis of the tumor after polypectomy was atypical polypoid adenomyoma. It is suggested that ovarian dysfunction caused by hyperprolactinemia may be involved in the pathogenesis of atypical polypoid adenomyoma in the present case.

Polo-like kinase (PLK) expression in endometrial carcinoma.

Polo-like kinase (PLK) is a cell cycle-regulated, cyclin-independent serine/threonine protein kinase. Recent reports have shown a critical role for PLK during tumorigenesis. To explore whether PLK plays a general role as a tumor marker of endometrial carcinomas, we examined the expression of PLK mRNA and protein in endometrial carcinomas and normal endometrium, and analyzed the relationship between PLK protein expression and malignant potential. We found that PLK mRNA was expressed in all specimens from endometrial carcinoma patients using RT-PCR methods, although some specimens from normal endometria were negative. Immunohistochemically, most of the PLK was found in the cytoplasm (around the nucleus), and partly in the nucleus of endometrial carcinoma glands and also secreted tissues from endometrial carcinoma glands. PLK was expressed at the basement membrane of carcinoma glands and partly expressed in the head portion of papillary carcinoma tissues. There was a significant correlation between percentages of PLK-positive cells and histological grade of endometrial carcinoma (P<0.0001). However, the expression of proliferating cell nuclear antigen and Ki-67 was independent of PLK expression. Moreover, we noted that PLK is strongly expressed in invading carcinoma cells. PLK expression could reflect the degree of malignancy and proliferation in endometrial carcinoma. Thus, in addition to being of diagnostic value, modulation of PLK activity in the tumors by chemotherapeutic agents or gene therapy may prove to be of therapeutic value.

Ca2+-images of smooth muscle cells and endothelial cells in one confocal plane in femoral artery segments of the rat.

Simultaneous recording of Ca2+-images in one confocal plane from vascular smooth muscle cells (SMCs) and endothelial cells (ECs) of an intact rat femoral artery segment was performed using indo-1 and a confocal microscope. During application of 10 microM acetylcholine (ACh), elevation and oscillation of intracellular Ca2+ concentration ([Ca2+]i) were observed in ECs but not in SMCs. Sequential conduction of Ca2+ oscillation from an EC to the neighboring ECs in one longitudinal direction was often observed in the presence of ACh. On the other hand, the activation of voltage-dependent Ca2+ channels by external 30 mM K+ resulted in the elevation of [Ca2+]i only in SMCs. When 10 microM ACh was added in the presence of 30 mM K+, it was observed in one confocal plane that [Ca2+]i in ECs and SMCs was almost simultaneously increased and decreased, respectively. The simultaneous recording method in this intact preparation will provide a line of valuable information about the interactions between SMCs and ECs, based on spatio-temporal analyses of absolute values of [Ca2+]i in individual cells.

Expression of receptor tyrosine kinase EphB4 and its ligand ephrin-B2 is associated with malignant potential in endometrial cancer.

The protein kinases includes many oncogenes and growth-factor receptors, as well as genes that are involved in cell cycle regulation. EphB4 receptors are a subfamily of receptor tyrosine kinases that are activated by ephrin-B2 ligands and are thought to play an important role in the development and oncogenesis of various tissues. However, very little experimental evidence exists to support this hypothesis. To elucidate the involvement of EphB4 and ephrin-B2 in endometrial carcinogenesis, we used fluorescent immunohistochemistry to analyze serial frozen sections of 20 endometrial carcinomas and 20 normal endometria for EphB4 and ephrin-B2 protein expression. We analyzed the relationship between the patient's characteristics and the percentages of EphB4- and ephrin-B2-stained cells. EphB4 expression was significantly associated with histological grade (p < 0.001) and certain clinical stages. Ephrin-B2 Expression was significantly associated with the presence of invasion to > 1/2 myometrium (p = 0.002). Our results demonstrate that increased EphB4 and ephrin-B2 expression may reflect or induce in endometrial carcinomas increased potential for growth and tumorigenicity. Furthermore, these results suggest that EphB4 receptor kinase may modulate the biological behavior of endometrial carcinomas through autocrine and/or paracrine activation, which is caused by ephrin-B2 ligands that are expressed in the same or neighbouring cells by immunohistochemistry.

Id1 expression is associated with histological grade and invasive behavior in endometrial carcinoma.

Basic helix-loop-helix (bHLH) DNA-binding proteins have been reported to regulate tissue-specific transcription of cellular differentiation within multiple cell lineages. The Id family of helix-loop-helix proteins does not possess a basic DNA-binding domain and functions as a negative regulator of bHLH proteins by forming high-affinity heterodimers with bHLH proteins. Id proteins were originally characterized as inhibitors of DNA binding and cell differentiation. Thus, overexpression of Id proteins correlates with cell proliferation and arrested differentiation in many cell lineages. To elucidate the involvement of Id1 in endometrial carcinogenesis, we analyzed serial frozen sections for Id1 protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. We analyzed the relationship between the percentages of Id1-stained cells and the patient's characteristics, including histological grade, clinical stage, presence of invasion to >1/2 myometrium, and clinical outcome. In normal endometria, Id1 was not detected in either the proliferative or the secretory phase. There was, however, abundant Id1 immunoreactivity in the endometrial carcinoma cells. Moreover, Id1 was strongly expressed in the inflammatory cells. Scoring on the basis of the percentage of positive cells indicated that Id1 expression is significantly associated with histological grade (P<0.05) and the presence of invasion to >1/2 myometrium (P<0.05). Our results demonstrate that increased Id1 expression in endometrial carcinoma correlates with the malignant potential of this tumor.

Dose--response of initial G2-chromatid breaks induced in normal human fibroblasts by heavy ions.

PURPOSE: To investigate initial chromatid breaks in prematurely condensed G2 chromosomes following exposure to heavy ions of different LET. MATERIAL AND METHODS: Exponentially growing human fibroblast cells AG1522 were irradiated with gamma-rays, energetic carbon (13 keV/ microm, 80 keV/microm), silicon (55 keV/microm) and iron (140 keV/microm, 185keV/microm, 440keV/microm) ions. Chromosomes were prematurely condensed using calyculin-A. Initial chromatid-type and isochromatid breaks in G2 cells were scored. RESULTS: The dose response curves for total chromatid breaks were linear regardless of radiation type. The relative biological effectiveness (RBE) showed a LET-dependent increase, peaking around 2.7 at 55-80keV/microm and decreasing at higher LET. The dose response curves for isochromatid-type breaks were linear for high-LET radiations, but linear-quadratic for gamma-rays and 13 keV/microm carbon ions. The RBE for the induction of isochromatid breaks obtained from linear components increased rapidly between 13keV/microm (about 7) and 80keV/microm carbon (about 71), and decreased gradually until 440 keV/microm iron ions (about 66). CONCLUSIONS: High-LET radiations are more effective at inducing isochromatid breaks, while low-LET radiations are more effective at inducing chromatid-type breaks. The densely ionizing track structures of heavy ions and the proximity of sister chromatids in G2 cells result in an increase in isochromatid breaks.