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Sample records for choriocarcinoma

  1. Primary pulmonary choriocarcinoma

    Science.gov (United States)

    Snoj, Ziga; Kocijancic, Igor

    2017-01-01

    Abstract Background The aim of the study was to establish whether there are different clinical entities of primary pulmonary choriocarcinoma (PPC) that deserve different diagnostic approach and the most optimal treatment. Patients and methods A systematic review with PubMed search was conducted to identify studies that reported cases of PPC. The eligibility criteria were histological diagnosis of pulmonary choriocarcinoma and thorough examination of the reproductive organs to exclude potential primary choriocarcinoma in the gonads. Furthermore, to illustrate the review we additionally present a patient referred at our institution. Results 55 cases (17 men) were included in the review with a median age of 34 years. Women with the history of gestational event showed better survival outcome than women without the history of gestational event. Patients treated with combined modality treatment (surgery and chemotherapy) survived longer than the patients without combined modality treatment. Furthermore, multivariate analysis of prognostic factors showed that the combined modality treatment had independent prognostic significance. Size of the tumour showed significant prognostic influence in univariate and multivariate analysis. Conclusions PPC is an extreme rarity with variable clinical characteristics and outcome. It is important to capture and treat patients in the early stages of the disease. Women with the history of gestational event may show better survival, therefore genetic examination could help us to predict patient’s prognosis. Surgery followed by adjuvant chemotherapy appears to represent the best treatment for PPC.

  2. [Choriocarcinoma causing a pulmonary embolus.

    DEFF Research Database (Denmark)

    Theliade, J.E.; Skovby, A.M.; Kirk, V.;

    2008-01-01

    that was histologically compatible with a choriocarcinoma. Trophoblast tumors are rare, but unspecific symptoms from lungs, liver, kidney or brain warrant control of S-hCG in women, even when pregnancy has not been recognized or menopause has been reached Udgivelsesdato: 2008/1/28...

  3. Developing retroperitoneal anaplastic carcinoma with choriocarcinoma focus after ovarian non-gestastional choriocarcinoma: Case report

    OpenAIRE

    2012-01-01

    Introduction. Choriocarcinoma is a malignant form of gestational trophoblastic neoplasm (GTN). It is a rare event but also a curable malignancy. In the majority of instancies it developes after any gestational event. In some cases it developes as non-gestational extrauterine malignancy. Prognosis of choriocarcinoma is poor when invasion and metastases appear early and spread fast. This form of choriocarcinoma can lead to incurable and letal outcome. Case report. We presented a 20-year-o...

  4. Solitary infantile choriocarcinoma of the liver: MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Hoef, Marianne van der; Willi, Ulrich V.; Huisman, Thierry A.G.M. [University Children' s Hospital Zurich, Department of Diagnostic Imaging, Zurich (Switzerland); Niggli, Felix K. [University Children' s Hospital Zurich, Department of Paediatrics, Zurich (Switzerland)

    2004-10-01

    Infantile hepatic choriocarcinoma is a rare, highly malignant germ-cell tumour believed to result from a choriocarcinoma of the placenta that spreads to the child. Most infants present with a characteristic clinical picture of anaemia, hepatomegaly and precocious puberty. Imaging findings, including conventional MRI, may be non-specific. To improve the accuracy of diagnosis, we present the imaging findings of contrast-enhanced dynamic MRI in a 4.5-month-old boy with infantile hepatic choriocarcinoma. (orig.)

  5. Abnormal Presentation of Choriocarcinoma and Literature Review

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    Yousefi, Zohreh; Mottaghi, Mansorhe; Rezaei, Alireza; Ghasemian, Sedighe

    2016-01-01

    Introduction Gestational trophoblastic neoplasms have highly been malignant potential, which usually occurred in child-bearing age women. Unusual feature of this malignancy would be rare, it was important to take in mind the possibility of GTN in different manifestation. Based on the above mentioned, the aim of this presentation would be the management and outcome of a case series of choriocarcinoma patients with abnormal manifestation. Case Presentation We have presented four patients, first who initially manifestation with signs of septic shock, the second case with severe gastrointestinal hemorrhage, the third case with postpartum infection and the forth case was a postmenopausal bleeding patient. Conclusions In case of metastatic choriocarcinoma with precise history, accurate diagnosis and appropriate treatment have led us to curable results. PMID:27482332

  6. Developing retroperitoneal anaplastic carcinoma with choriocarcinoma focus after ovarian non-gestastional choriocarcinoma: Case report

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    Nikolić Branka

    2012-01-01

    Full Text Available Introduction. Choriocarcinoma is a malignant form of gestational trophoblastic neoplasm (GTN. It is a rare event but also a curable malignancy. In the majority of instancies it developes after any gestational event. In some cases it developes as non-gestational extrauterine malignancy. Prognosis of choriocarcinoma is poor when invasion and metastases appear early and spread fast. This form of choriocarcinoma can lead to incurable and letal outcome. Case report. We presented a 20-year-old patient with abdominal and retroperitoneal malignancy - anaplastic carcinoma combined with choriocarcinoma metastases in. Tumor developed three months after left adnexectomy which had been done because of adnexal tumor. Choriocarcinoma was immunohistochemicaly confirmed in adnexal masses. Two courses of chemotherapy, metotrexate + folic acid (MTX+FA regimen, were administrated. The initial serum beta human chorionic gonadotropin level stayed unknown as well as the last one after the treatment. The patient came from the other country and was hospitalized because of pelvic and abdominal pain and palpable abdominal masses in hypogastrium with progressive anemia. The human chorionic gonadotropin level was 38 mIU/L. Tumor biopsy was done and choriocarcinoma metastases were immunohistochemicaly confirmed with predominant anaplastic carcinoma. Five day course of MTX + cyclophosphamide regimen was administrated and the patient was prepared for operative treatment. Relaparotomy was perforemed and tumor completely exceeded. Tumor mass mostly developed retroperitonely and partialy in abdominal cavity infiltrating intestinal wall with rupture of sigmoid colon. Anaplastic carcinoma, with large fields of necrosis and bleeding, was confirmed after histological examination. Immunohistochemical examination excluded choriocarcinoma in tumor mass. After 20 blood units transfusion, one course of chemotherapy and tumor excision, the patient left hospital on the 9th postoperative day

  7. Radioimmunodetection of human choriocarcinoma xenograft in nude mouse

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To study the efficiency of radioimmuno-detection in locating the xenograft of human chorio-carcinoma in nude mouse. Methods: Radioimmuno-detection was performed using cocktail antibodies of 131I-labeled mouse anti-human chorionic gonadotropin monoclonal antibodies to locate the xenograft of human choriocarcinoma in nude mouse. Radioactivity in different tissues was measured and the tumor/non-tumor ratio was calculated. Normal mouse IgG was used as control IgG. Results: The accumulation of radioactivity in the xenograft area could be recognized as early as 24 h after the injection of the radiolabelled antibodies. 72-96 h after the injection, the xenograft could be clearly shown. The minimal shown xenograft was 0.8 cm in diameter. The tumor/non-tumor ratio increased with the time and was obviously higher than that in control group. Conclusion: Radioimmunodetection can efficiently locate human choriocarcinoma xenograft in nude mouse.

  8. Infantile and Maternal Choriocarcinoma: A Case Report and Review of Literature

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    Ziba Mosayebi

    2016-12-01

    Full Text Available Background: Choriocarcinoma is a rare highly malignant trophoblastic neoplasm. It can be preceded by any form of gestation including a complete or a partial mole, miscarriage and normal pregnancy. Simultaneous intraplacental choriocarcinoma involving both mother and infant is extremely rare. Hepatomegaly, anemia, elevated ßHCG is the diagnostic triad. Here we report a 6 weeks old Afghan girl infant with intraplacental choriocarcinoma presented by severe anemia and widespread multiple metastatic lesions in liver, lung and brain with an elevated level of ßHCG . According to rarity of the disease, rapid progression and the high mortality rate with delay in diagnosis and intervation , choriocarcinoma should be one of the differential diagnosis in severe infantile and maternal anemia without any antecedent reason. According to highly vascular and friable nature of tumor, biopsy can be dangerous for diagnosis. As choriocarcinoma secrets ßHCG, measurement of serum ßHCG is the most common method used to diagnose choriocarcinoma

  9. ECTOPIC CHORIOCARCINOMA IN A PRETEEN IN OGBOMOSO, SOUTH-WEST NIGERIA. A CASE REPORT

    OpenAIRE

    Olumuyiwa Ogunlaja A; Gbemi Ano-Edward H.; Akintunde Fehintola O; Michael Alao A; Olufemi Awotunde T; Idowu Ogunlaja P; Olurotimi Aaron; Ajibola Idowu; Funmito Fehintola O; Matthew Bojuwoye O; Sunday Oladeji A; Matthew Lasisi E

    2016-01-01

    Ectopic Choriocarcinoma is an extremely rare occurrence. The case of ectopic choriocarcinoma discussed here involved a 12 year old girl who presented with lower abdominal pain and dizziness following a short period of amenorrhea after attaining menarche. Aprovisional diagnosis of ruptured ectopic gestation was made based on the clinical evaluation and patient had emergency laparotomy. Histopathology report revealed a choriocarcinoma of the ovary. Patient defaulted on subsequent follow up care...

  10. Primary choriocarcinoma in the anterior mediastinum in a man:a case report and review of the literatures

    Institute of Scientific and Technical Information of China (English)

    沈华浩; 张根生; 徐峰

    2004-01-01

    @@ Primary mediastinal choriocarcinoma in men is exceedingly rare and is thought to be unresponsive to treatment. We review the literatures and report a case of male primary choriocarcinoma in the anterior mediastinum.

  11. ECTOPIC CHORIOCARCINOMA IN A PRETEEN IN OGBOMOSO, SOUTH-WEST NIGERIA. A CASE REPORT

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    Olumuyiwa Ogunlaja A

    2016-12-01

    Full Text Available Ectopic Choriocarcinoma is an extremely rare occurrence. The case of ectopic choriocarcinoma discussed here involved a 12 year old girl who presented with lower abdominal pain and dizziness following a short period of amenorrhea after attaining menarche. Aprovisional diagnosis of ruptured ectopic gestation was made based on the clinical evaluation and patient had emergency laparotomy. Histopathology report revealed a choriocarcinoma of the ovary. Patient defaulted on subsequent follow up care. This case is presented as an eye opener on the need to also focus on the reproductive health challenges, early sex education in preteen and rare occurrence of the disease amongst the Pre-teenage groups. It is also important to deal with the possibility of a non gestational choriocarcinoma of the ovary which has a worse prognosis.

  12. Massive fetomaternal hemorrhage caused by an intraplacental choriocarcinoma: a case report

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    Henningsen, Anna-Karina Aaris; Maroun, Lisa Leth; Havsteen, Hanne

    2010-01-01

    Background. Intraplacental choriocarcinoma is a rare but highly malignant trophoblastic neoplasm. When found near term the risk of maternal metastasis is high because of the late diagnosis. Case. We describe a case of an intraplacental choriocarcinoma diagnosed postpartum after a near-term delive...... choriocarcinoma 3 cm in diameter. The tumor had infiltrated the maternal basal plate. Conclusion. Fetomaternal bleeding is a rare form of presentation of choriocarcinoma but its presence should always warrant detailed examination of placenta, mother, and infant....... of a severely anemic infant. A fetomaternal hemorrhage resulted in a hemoglobin concentration in the infant of only 2,1 g/dL. Neither mother nor child showed signs of metastatic disease. The macroscopic examination showed a hydropic placenta weighing more than 1 kilogram. Microscopy showed an intraplacental...

  13. [Fatal amnioinfusion with previous choriocarcinoma in a parturient woman].

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    Hrgović, Z; Bukovic, D; Mrcela, M; Hrgović, I; Siebzehnrübl, E; Karelovic, D

    2004-04-01

    The case of 36-year-old tercipare is described who developed choriocharcinoma in a previous pregnancy. During the first term labour the patient developed cardiac arrest, so reanimation and sectio cesarea was performed. A male new-born was delivered in good condition, but even after intensive therapy and reanimation occurred death of parturient woman with picture of disseminate intravascular coagulopathia (DIK). On autopsy and on histology there was no sign of malignant disease, so it was not possible to connect previous choricarcinoma with amniotic fluid embolism. Maybe was place of choriocarcinoma "locus minoris resistentiae" which later resulted with failure in placentation what was hard to prove. On autopsy we found embolia of lung with a microthrombosis of terminal circulation with punctiformis bleeding in mucous, what stands for DIK.

  14. Primary vulvovaginal choriocarcinoma: a case report of unusual presentation and literature review

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    Ushashree Das

    2013-06-01

    Full Text Available Only one case of primary extra uterine vaginal choriocarcinoma and one case of primary vulvar choriocarcinoma have been reported in literature. This is a case of 27 year old lady who presented with a 10cm × 7cm× 5cm vulvar mass with pain abdomen since 1 month, to the Gynecologic oncology outpatient. The mass was smooth, hard and fixed to underlying structures. Multiple bilateral inguinal lymph nodes were enlarged. Vulvar biopsy with Immunohistochemistry proved it to be choriocarcinoma. CT scan thorax, abdomen and pelvis showed multiple bilateral lung metastases, empty uterine cavity and normal sized uterus with a vaginal mass extending up to introitus encasing urethra and anal canal with multiple enlarged pelvic & inguinal lymph nodes. Final diagnosis of Primary Vulvovaginal choriocarcinoma FIGO stage III and WHO score-12 was made. Multidrug chemotherapy with Etoposide, Methotrexate, Actinomycin-D, Folinic Acid, Cyclophosphamide and Vincristine (EMA-CO was started then shifted to Etoposide, Methotrexate, Actinomycin-D, Folinic Acid and Cisplatin (EMA-EP regimen followed by Paclitaxel & Carboplatin, because of poor response. Patient’s βHCG became 1.57IU/L with resolution of all lesions after 5 three weekly cycles of Paclitaxel & Carboplatin. Now she is planned for three more cycles of chemotherapy. This case highlights another atypical presentation of choriocarcinoma. [Int J Reprod Contracept Obstet Gynecol 2013; 2(3.000: 470-472

  15. Choroidal metastases in testicular choriocarcinoma, successful treatment with chemo- and radiotherapy: a case report

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    Guber Ivo

    2011-12-01

    Full Text Available Abstract Background Choriocarcinoma is a very rare cause of ocular metastasis. Only 18 male patients have been reported on, 4 of whom survived, but with significant loss of vision. Case presentation A 26-year-old Caucasian man, suffering from testicular choriocarcinoma with pulmonary, cerebral, renal, hepatic and osseous metastases, underwent left radical orchiectomy. While being treated with chemotherapy, he presented with loss of vision in the left eye. Ophthalmoscopy revealed bilateral non-pigmented, hemorrhagic choroidal tumours, compatible with secondary lesions. Continued chemotherapy and stereotactic radiotherapy of the skull and spine lead to full remission with excellent vision, after more than 4 years of follow up. Conclusion Testicular choriocarcinoma is an exceptional cause of choroidal metastasis, potentially asymptomatic and with specific clinical features. Radiotherapy can complement radical orchiectomy and chemotherapy, to achieve full remission and maintain good vision.

  16. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

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    Seyda Gunduz

    2012-07-01

    Full Text Available Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein.

  17. Coexistence of Gastric Adenocarcinoma and Choriocarcinoma: Complete Response to Trastuzumab and Chemotherapy

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    Gunduz, Seyda; Elpek, Gulsum Ozlem; Uysal, Mukremin; Goksu, Sema Sezgin; Tatli, Murat; Arslan, Deniz; Coskun, Hasan Senol; Bozcuk, Hakan; Savas, Burhan; Ozdogan, Mustafa

    2012-01-01

    Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gonadotropin and overexpression of the cErbB2 proto-oncogene. Staging revealed multiple metastases in the liver. A complete response was obtained with a combination of trastuzumab and chemotherapy. The diagnosis of gastric choriocarcinomas without pathological examination is difficult due to their rare occurrence. A complete response can be obtained with trastuzumab in the treatment of cases with overexpression of the cErbB2 protein. PMID:23525369

  18. Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

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    Xie L

    2016-11-01

    Full Text Available Lisha Xie,1,* Tiancen Zhao,1,2,* Jing Cai,1 You Su,1 Zehua Wang,1 Weihong Dong1 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 2Department of Obstetrics and Gynecology, Central Hospital of Wuhan, Wuhan, China *These authors contributed equally to this work Objective: The objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX in human choriocarcinoma cells regarding DNA damage response. Methods: Two choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot. Results: Remarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63 but not in MTX-resistant cancer cells (A2780 and Hela after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53. Conclusion: The MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma. Keywords: choriocarcinoma, chemotherapy hypersensitivity, DNA double-strand break, RAD51, p53

  19. Cutaneous metastasis of testicular choriocarcinoma, diagnosed by fine-needle aspiration cytology: A rare case report and review of the literature

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    Bita Geramizadeh

    2012-01-01

    Full Text Available Skin metastasis of testicular choriocarcinoma is very rare. Until now about nine cases have been reported in the English literature; however, only one of them has been diagnosed by fine-needle aspiration (FNA cytology. Herein, we report our experience with FNA cytology diagnosis of a metastatic testicular choriocarcinoma to the skin of chin. The combination of highly atypical mononuclear cells (cytotrophoblasts and multinucleated malignant cells (syncytiotrophoblasts are characteristic of metastatic tumor in a known case of choriocarcinoma of testis.

  20. Primary pulmonary choriocarcinoma after human chorionic gonadotropin normalization following hydatidiform mole

    DEFF Research Database (Denmark)

    Maestá, Izildinha; Leite, Fábio Vicente; Michelin, Odair Carlito

    2010-01-01

    BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response to chemo......BACKGROUND: Primary pulmonary choriocarcinoma (PPC) is rare and frequently leads to death. CASES: Two young patients presented with previous molar pregnancy and spontaneous serum human chorionic gonadotropin (hCG) normalization. Patient 1 was referred to our center after partial response...... 3 years after diagnosis. Patient 2 presented with persistently high hCG, though the affected organ was not identified. Chemotherapy was unsuccessful. Patient reevaluation showed an isolated pulmonary mass. Pulmonary lobectomy was performed; 2 weeks later, hCG was normal and consolidation with 2...

  1. Gastric choriocarcinoma admixed with an α-fetoprotein-producing adenocarcinoma and separated adenocarcinoma

    Institute of Scientific and Technical Information of China (English)

    Bang Wool Eom; So-Youn Jung; Hongman Yoon; Myeong-Cherl Kook; Keun Won Ryu; Jun Ho Lee; Young-Woo Kim

    2009-01-01

    We report a case of gastric choriocarcinoma admixed with an α-fetoprotein (AFP)-producing adenocarcinoma .A 70-year-old man was hospitalized for gastric cancer that was detected during screening by esophagogastroduodenoscopy (EGD). Initial laboratory data showed the increased serum level of AFP and EGD revealed a 5-cm ulcerofungating mass in the greater curvature of the gastric antrum.The patient underwent radical subtotal gastrectomy with D2 lymph node dissection and Billroth Ⅱ gastrojejunostomy. Histopathological evaluation confirmed double primary gastric cancer: gastric choriocarcinoma admixed with an AFP-producing adenocarcinoma and separated adenocarcinoma. At 2 wk postoperatively, his human chorionic gonadotropin and AFP levels had reduced and six cycles of adjuvant chemotherapy were initiated. No recurrence or distant metastasis was observed at 4 years postoperatively.

  2. Combined choriocarcinoma,neuroendocrine cell carcinoma and tubular adenocarcinoma in the stomach

    Institute of Scientific and Technical Information of China (English)

    Yasumitsu Hirano; Takuo Hara; Hiroshi Nozawa; Kaeko Oyama; Naohiro Ohta; Kenji Omura; Go Watanabe; Hideki Niwa

    2008-01-01

    We described a patient with adenocarcinoma of the stomach combined with choriocarcinoma and neuroendocrine cell carcinoma.An 85-year-old man visited our hospital because of appetite loss.Gastric fiborscopy revealed a large tumor occupying the cardial region and anterior wall of the gastric body.The patient underwent total gastrectomy with lymphnode dissection and partial resection of the liver.Choriocarcinoma,small cell carcinoma and tubular adenocarcinoma existed in the gastric tumor.The choriocarcinomatous foci contained cells positive for beta-subunit of human chorionic gonadotropin (B-hCG) and human placental lactogen mainly in syncytiotrophoblastic cells.The small cell carcinomatous loci contained cells positive for synaptophysin,neuron-specific enolase (NSF),and chromogranin A.The prognosis for gastric adenocarcinoma with choriocarcinoma and neuroendocrine cell carcinoma is exceedingly poor.This patient died about 2 mo after the first complaint from hepatic failure.This is the first reported case of gastric cancer with these three pathological features.

  3. Coriocarcinoma primário do colo uterino Primary choriocarcinoma of the uterine cervix

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    Maria Fernanda Moreira Ferraz

    2003-06-01

    Full Text Available Coriocarcinomas geralmente ocorrem no corpo uterino durante o período reprodutivo. Raramente podem acontecer alterações de localização e de idade de acometimento. Coriocarcinomas primários do colo uterino são extremamente raros, geralmente ocorrem no pós-parto de seis meses a dois anos e se apresentam com sangramento por via vaginal. Existem três teorias para o desenvolvimento dos coriocarcinomas no colo uterino: 1 a paciente ter tido uma gestação cervical que sofreu transformação maligna; 2 que o coriocarcinoma da cérvice seja uma metástase de um tumor primário do corpo que desapareceu; 3 que seu desenvolvimento seja devido ao transporte de células coriônicas da gestação precedente como êmbolos, os quais ficaram latentes e posteriormente sofreram transformação maligna. A terapêutica preconizada é a realização de histerectomia com manutenção dos anexos e posterior quimioterapia. Relatamos o caso de uma mulher de 34 anos que, seis meses após parto normal, iniciou com sangramento vaginal. O exame especular mostrou massa vegetante e hemorrágica do colo uterino e a dosagem de gonadotrofina coriônica humana fração b (b-HCG revelou altos níveis sangüíneos. O exame histopatológico mostrou uma neoplasia maligna composta por sincício e citotrofoblasto malignos comprometendo apenas o colo uterino. Nosso caso é um coriocarcinoma ectópico e acreditamos que seu desenvolvimento no colo uterino seja devido ao transporte de células coriônicas da gravidez precedente que sofreram posterior transformação maligna.Choriocarcinomas usually occur within the body of the uterus during reproductive years. On rare occasions they may occur abnormally in relation to place and time. Primary choriocarcinomas of the uterine cervix are extremely rare. They usually occur in a latent period of six months to two years after the preceding pregnancy, and present with disfunctional vaginal bleeding. Theoretically, there are three

  4. Plasmodium falciparum parasites expressing pregnancy-specific variant surface antigens adhere strongly to the choriocarcinoma cell line BeWo

    DEFF Research Database (Denmark)

    Haase, Rikke N; Megnekou, Rosette; Lundquist, Maja;

    2006-01-01

    Placenta-sequestering Plasmodium falciparum parasites causing pregnancy-associated malaria express pregnancy-specific variant surface antigens (VSA(PAM)). We report here that VSA(PAM)-expressing patient isolates adhere strongly to the choriocarcinoma cell line BeWo and that the BeWo line can...

  5. [Metastatic choriocarcinoma associated with Wunderlich syndrome: case report and literature review].

    Science.gov (United States)

    Ojendiz-Nava, Roberto Carlos; Niebla-Cárdenas, Danniela; Hernández-Flores, Sara Elia; Audifred-Salomón, Jorge Román; Morales-Leyte, Ana Lilia

    2015-03-01

    Choriocarcinoma is a rare condition, with an incidence of 1 in 30 to 40,000 pregnancies in the United States and Europe. In Mexico it is reported in 1 in 10,000 pregnancies. Wunderlich syndrome is a spontaneous perirenal hematoma, a very rare entity. This paper reports the case of a young patient with a history of molar pregnancy one year prior to admission, valuation due to fainting, generalized headache, spontaneous pain in the right flank and data of hypovolemic shock. Computed tomography reported right perirenal hematoma, normal uterus, two annexes with data of tecaluteinic cysts, beta human chorionic gonadotropin greater than 200,000 IU/mL. Patient was stabilized with crystalloid, blood products and right adrenal artery embolization. It was corroborated the brain, mediastinum and abdomen metastases. She was sent to a third level hospital, starting holocraneal radiotherapy, she had retroperitoneal bleeding and died a week later.

  6. Gestational Choriocarcinoma Presenting with Lacrimal Gland Metastasis: A First Reported Case

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    Naushad A. B. Ahamed

    2015-01-01

    Full Text Available Background. Gestational choriocarcinoma (GC is a recognized clinicopathological subtype of gestational trophoblastic neoplasia that usually metastasizes hematogenously to highly vascular organs like the lung, liver, and brain. However, orbital metastasis to the choroid and lacrimal gland is a rare occurrence. Case Presentation. A 21-year-old female presented with headache and left orbital swelling one year after resection of a complete hydatidiform mole followed by adjuvant methotrexate chemotherapy. A metastatic imaging screening revealed multiple metastases in the lungs, brain, and adrenal gland, in addition to the choroid and lacrimal gland. Based on her modified WHO risk factors scoring she was started on chemotherapy and whole brain radiotherapy, which resulted in a complete response. At two-year follow-up, serum b-HCG level was with normal limits; imaging surveillance was uneventful. Conclusion. We present the first case of lacrimal gland metastasis in a young girl from GC relapse.

  7. "Term delivery following successful treatment of choriocarcinoma with brain metastases, (a case report"

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    F. Behnamfar

    2006-08-01

    Full Text Available Background: Cerebral metastases from choriocarcinoma are poor prognostic indicator of outcome in both the World Health Organization and FIGO classification systems. Although gestational trophoblastic neoplasia has become the most curable gynecological malignancy, failure rate among “high-risk” patients is still high despite the use of aggressive multidrug regimens. case: A 27 year old woman (G4P2Ab1 presented with hemiplegia due to brain metastases of choriocarcinoma one year after spontaneous abortion. She underwent craniotomy and was treated with nine courses of multiple agent etoposide, methotrexate, actinomycin-etoposide and cisplatinum (EMA-EP regimen combined with whole brain irradiation. She delivered a term healthy child two years after termination of treatment. Conclusion: Multiagent EMA-EP chemotherapy and whole brain irradiation with craniotomy in selected patients preserves fertility and may improve a patient overall prognosis. Methods: In a descriptive study from February to April 2005, two hundred sixty six consecutive pregnant women referring to a university hospital were asked to answer a questionnaire containing questions their sexual status and some demographic data. In 122 cases the answers of the spouses was collected also. The answers were compared in divided groups according to age range, duration of marriage, parity and educational status. Results: Fifty five percent of men and fifty eight percent of women had a negative attitude about sexual relations during pregnancy, and 60% of men and 75% of women presented incorrect knowledge about sexuality during pregnancy. Main reasons for decreased sexual relations in pregnancy were mentioned to be dysparaunia, and the fear of trauma to the baby, abortion, membrane rapture, preterm labor and infection. Conclusion: As couples’ knowledge and attitudes about sexuality affect their general sexual behavior during pregnancy it is crucial to provide proper consultation regarding

  8. Metastatic choriocarcinoma induced separate simultaneous intracerebral haemorrhages: a very rare occurrence and its novel association with Klinefelter syndrome.

    Science.gov (United States)

    Joret, Maximilian Olavi; Starke, Robert M; Scotter, John; Heppner, Peter

    2015-11-12

    Non-traumatic separate simultaneous intracerebral haemorrhages (SSIHs) are rare. Relevant aetiologies are diverse and their diagnosis challenging. We report a unique case of SSIH in an 18-year-old male with a background of previously undiagnosed testicular choriocarcinoma and Klinefelter syndrome. The patient was admitted to Auckland City Hospital with headaches, drowsiness and vomiting. A CT scan revealed SSIH in a background of tumorous lesions. His β human chorionic gonadotropin titre was elevated at 355 000 IU/L. The SSIH and the associated tumorous lesions were acutely surgically resected and the patient started on bleomycin, etoposide and cisplatin combination chemotherapy with excellent results. In this article, we underline choriocarcinoma as a rare aetiology of SSIH and present an example of the clinical presentation, investigation and management of this very rare pathological entity.

  9. Coriocarcinoma: um estudo de caso Coriocarcinoma: un estudio de caso Choriocarcinoma: a case study

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    Pollyana Alves Silva

    2010-02-01

    Full Text Available O presente estudo objetivou descrever o caso de uma cliente portadora de coriocarcinoma gestacional e a assistência de enfermagem necessária a esta condição. A partir de informações constantes do prontuário médico e de anamnese e exame físico realizados em visita domiciliária, formularam-se diagnósticos e intervenções de enfermagem embasados na literatura. Foram identificados diagnósticos referentes aos períodos perioperatório e de tratamento quimioterápico. Além dos diagnósticos referidos, foi possível identificar outros relativos ao período pós-tratamento da cliente. O processo de enfermagem mostrou-se efetivo para a assistência qualificada à cliente com coriocarcinoma.El presente estudio objetivó describir el caso de una cliente portadora de coriocarcinoma gestacional y la asistencia de enfermería necesaria a esta condición. A partir de informaciones constantes del prontuario médico y de anamnese y examen físico realizados en visita domiciliaria, se formularon diagnósticos e intervenciones de enfermería embasados en la literatura. Fueron identificados diagnósticos referentes a los períodos periquirúrgico y de tratamiento quimioterápico. Además de los diagnósticos referidos, fue posible identificar otros relativos al período pos-tratamiento de la cliente. El proceso de enfermeria se mostro efectivo para la asistencia calificada a la cliente con coriocarcinoma.The present study aimed at describing the case of a client bearer for gestational choriocarcinoma and the nursing assistance needed for this condition. From information contained in the medical history and of anamnesis and physical examination made in a home visit, made up diagnoses and inteventions of nursing based in literature. Diagnoses have been identified related to the periods perioperative and chemotherapy treatment. In addition to these diagnoses, it was possible to identify others on the post-treatment period of client. The process of

  10. A rare case of arteriovenous malformation following hysterectomy in a case of choriocarcinoma

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    Suchitra R

    2015-10-01

    Full Text Available A uterine arteriovenous malformation (AVM is a rare cause of uterine bleeding. It may have varied presentations ranging from being completely asymptomatic; to features of congestive heart failure, to vaginal bleeding which may at times life be threatening. Clinical findings in such cases are often un-reliable; requiring a high index of suspicion to make the diagnosis. We report a case of a 46-year-old lady who presented with heavy vaginal bleeding. She has undergone hysterectomy with a histopathology of choriocarcinoma one and half months back. She has received chemotherapy and 8 fractions of radiotherapy for the same. AVM was diagnosed following a CT angiogram and was managed by embolization. We also discuss in brief about this uncommon but serious condition which the radiologist/gynaecologist may encounter in their practice. AV Malformation is a rare but potentially life-threatening cause of vaginal bleeding which must be kept in the differential diagnosis of sudden and massive vaginal bleeding. It requires a high index of clinical suspicion. Despite its rarity, early recognition of an AVM is imperative to enable timely diagnosis and intervention. [Int J Reprod Contracept Obstet Gynecol 2015; 4(5.000: 1561-1564

  11. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage

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    Koji Komori

    2016-05-01

    Full Text Available A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient’s abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient’s condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations.

  12. Recovery from Choriocarcinoma Syndrome Associated with a Metastatic Extragonadal Germ Cell Tumor Hemorrhage

    Science.gov (United States)

    Komori, Koji; Takahari, Daisuke; Kimura, Kenya; Kinoshita, Takashi; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuichi; Uemura, Norihisa; Natsume, Seiji; Kawakami, Jiro; Iwata, Yoshinori; Tsutsuyama, Masayuki; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Ouchi, Akira; Shimizu, Yasuhiro

    2016-01-01

    A germ cell tumor is the most common form of malignancy in early male life, and can be classified as either seminomatous or nonseminomatous. Choriocarcinoma, comprised of nonseminomatous germ cells, is the most aggressive type of germ cell tumor and characteristically metastasizes to the retroperitoneal lymph nodes and less frequently to the lungs, liver, bone or brain [Shibuya et al., 2009;48: 551–554]. A 56-year-old man was admitted to another hospital complaining of abdominal distension. Symptoms included anorexia, vomiting, and diarrhea. The patient was diagnosed with an extragonadal germ cell tumor and referred to our hospital to receive chemotherapy. The day after admission, the patient's abdominal distension gradually worsened. An emergency operation revealed venous hemorrhage from the surface of a metastatic extragonadal germ cell tumor between the ligament of Treitz and the inferior mesenteric vein in a horizontal position. Hemostatic treatment was performed with 4-0 proline thread attached to a medicated cotton sponge, rather than using a simple proline thread, and the closure area was manually compressed. Chemotherapy was initiated on postoperative day 10. A metastatic extragonadal germ cell tumor that causes massive hemorrhage and gastrointestinal hemorrhage is very rare, and represents a life-threatening emergency. If the patient's condition carries a substantial risk of bleeding to death, it may be worthwhile to attempt abdominal operations. PMID:27403124

  13. A Fibroid or Cancer? A Rare Case of Mixed Choriocarcinoma and Epithelioid Trophoblastic Tumour

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    Wan Yu Luk

    2013-01-01

    Full Text Available Background. Gestational trophoblastic disease (GTD is a rare complication of pregnancy which is characterised by abnormal growth of the trophoblasts at the placental site. It is categorised into benign and malignant forms, which include hydatidiform moles (HMs and gestational trophoblastic neoplasia (GTN, respectively. A mixed choriocarcinoma (CC and epithelioid trophoblastic tumour (ETT is an extremely rare subgroup of GTN, which is a highly curable but aggressive form of malignancy. Case. We report a case of mixed CC and ETT in a 41-year-old patient who presented with a 2-year history of menorrhagia and fibroid uterus in the absence of previous history of molar pregnancy. She had a 12-year interval between the antecedent pregnancy and presentation. She was treated with intensive regimen of adjuvant chemotherapy, etoposide, methotrexate, and actinomycin-D with etoposide and cisplatin (EMA-EP. She has remained disease free for more than 5 years. Conclusion. This case highlights the importance of considering GTN as one of the differential diagnoses value of β-HCG in patients presented with menorrhagia and growing fibroids.

  14. The choriocarcinoma cell line BeWo: syncytial fusion and expression of syncytium-specific proteins.

    Science.gov (United States)

    Orendi, Kristina; Gauster, Martin; Moser, Gerit; Meiri, Hamutal; Huppertz, Berthold

    2010-11-01

    Fusion of the trophoblast-derived choriocarcinoma cell line BeWo can be triggered by forskolin. BeWo cells are regularly used as a cell culture model to mimic in vivo syncytialisation of placental villous trophoblast. The β subunit of human chorionic gonadotropin (CGB), placental alkaline phosphatase as well as placental protein 13 (PP13, LGALS13) are exclusively expressed in the syncytiotrophoblast of the human placenta, and CGB is commonly used as a marker of syncytial differentiation. Here we tested the hypothesis that syncytial fusion precedes CGB and LGALS13 expression in trophoblast-derived BeWo cells. BeWo cells were cultured for 48 h in the presence or absence of forskolin and varying concentrations of H-89, a protein kinase A inhibitor that interferes with the forskolin-mediated pathway of syncytial fusion. LGALS13 and CGB expression were quantified by DELFIA and real-time PCR. Cell fusion was determined by morphological analysis and cell counting after immunofluorescence staining. In forskolin-stimulated BeWo cells that were hindered to fuse by treatment with H-89, levels of CGB protein expression were not altered, while LGALS13 protein and mRNA expression decreased significantly to control levels without forskolin. The LGALS13 protein expression data coincided with a significant decrease in syncytial fusion, while CGB protein expression was unaffected by rates of cell fusion and proliferation. We postulate that CGB protein expression is not necessarily linked to syncytial fusion, and thus CGB should be used with great caution as a marker of BeWo cell fusion.

  15. Comparative distribution study of /sup 111/In-labelled DTPA and TTHA monoclonal antibody conjugates in a choriocarcinoma xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Buckley, R.G.; Barnett, P.; Searle, F.; Pedley, R.; Boden, J.A.

    1986-11-01

    Conjugates of the chelating agents DTPA and TTHA with a monoclonal anti-HCG were prepared. The tissue distribution of the /sup 111/In-Labelled conjugates and also /sup 111/In-citrate was studied in mice bearing human choriocarcinoma xenografts. The antibody conjugates both gave high liver and spleen radionuclide accumulation. Elevated femur levels were observed for the TTHA conjugate and /sup 111/In-citrate. Generally the DTPA conjugate showed the highest tumor-tissue ratios, although its tumor/blood ratio was lower than the other two materials. The results infer that the DTPA conjugate has the greatest utility as an imaging agent but that it would require a background subtraction technique.

  16. The human leukocyte antigen G promotes trophoblast fusion and β-hCG production through the Erk1/2 pathway in human choriocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ji-meng [School of Medicine, Nankai University, Tianjin 300071 (China); State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hong-xi [Department of Obstetrics and Gynecology, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038 (China); Wang, Li [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Gao, Zhi-ying, E-mail: gaozy301@yahoo.com.cn [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China); Yao, Yuan-qing, E-mail: yqyao@126.com [Department of Obstetrics and Gynecology, General Hospital of Chinese People’s Liberation Army, Beijing 100853 (China)

    2013-05-10

    Highlights: •HLA-G expression promotes BeWo cells fusion and fusogenic gene expression. •HLA-G is capable of inducing β-hCG production in human choriocarcinoma cell lines. •Up-regulation of β-hCG production by HLA-G is mediated via the Erk1/2 pathway. -- Abstract: The human leukocyte antigen G (HLA-G) is expressed on the fetal–maternal interface and plays a role in protecting fetal-derived trophoblasts from the maternal immune response, allowing trophoblasts to invade the uterus. However, HLA-G also possesses immune suppressing-independent functions. We found that HLA-G expressing BeWo choriocarcinoma cells increased cell–cell fusion compared to control BeWo cells under forskolin treatment. Regardless of forskolin treatment, the expression of fusogenic gene mRNAs, including syncytin-1, the transcription factor glial cell missing 1 (Gcm1), and beta human chorionic gonadotropin (β-hCG) were elevated. HLA-G up-regulates β-hCG production in human choriocarcinoma cells because HLA-G knockdown in JEG-3 cells induces a dramatic decrease in β-hCG compared with control cells. The defect in β-hCG production in HLA-G knocked-down cells could not be completely overcome by stimulating hCG production through increasing intracellular cAMP levels. HLA-G expressing cells have increased phosphorylation levels for extracellular signal-regulated kinase1/2 (Erk1/2) in BeWo cells. The Erk1/2 pathway is inactivated after the inhibition of HLA-G expression in JEG-3 cells. Finally, Erk1/2 inhibition was able to suppress the increased hCG production induced by HLA-G expression. Together, these data suggest novel roles for HLA-G in regulating β-hCG production via the modulation of the Erk1/2 pathway and by inducing trophoblast cell fusion.

  17. Concurrent development of testicular seminoma and choriocarcinoma of the superior mediastinum, presented as cervical mass: a case report and implications about pathogenesis of germ-cell tumours

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    Bamias Aristotelis

    2006-11-01

    Full Text Available Abstract Background Synchronous presentation of more than one germ cell tumours of different histology in the same patient is considered to be very rare. In these cases of multiple germ cell tumours, strong theoretical and clinical data suggest an underlying common pathogenetic mechanism concerning genetic instability or abnormalities during the pluripotent embryonic differentiation and maturation of the germ cell. Case presentation A 25 year-old young man presented with an enlarging, slightly painful left cervical mass. Despite the initial disorientation of the diagnosis to a possible thyroid disorder, the patient underwent complete surgical resection of the mass revealing mediastinal choriocarcinoma. Subsequent ultrasound of the scrotum indicated the presence of a small lobular node in the upper pole of the left testicle and the patient underwent radical left inguinal orchiectomy disclosing a typical seminoma. Based on these results, the patient received 4 cycles of Bleomycin, Etoposide and Platinum chemotherapy experiencing only mild toxicity and resulting in complete ongoing clinical and biochemical remission. Conclusion The pathogenesis of concurrent germ cell tumours in the same patient remains an area of controversy. Although the genetic instability of the pluripotent germ cell offers an adequate explanation, the possibility of metastasis from the primary, less differentiated tumour to a distant location as a more mature subtype cannot be excluded. Possible development of a metastatic site of different histology and thus biological behaviour (e.g choriocarcinoma should be anticipated. Furthermore, urologists, pathologists and medical oncologists should be meticulous in the original pathological diagnosis in these patients, since there is a significant frequency of germ cell tumours with mixed or overlapping histological elements with diverse potential of evolution and differentiation.

  18. Expression of matrix metallo-proteinase-28 in human nor-mal cytotrophoblast cells and a choriocarcinoma cell line,JEG-3

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    There are striking similiarities present between the behavior of invasive placental cells and that of invasive cancer cells. Matrix metalioproteinases (MMPs) are one of the most important mediators. MMP-28, the new member ofMMPs, was sequenced and identified recently. Expression of MMP-28 mRNA and protein in the cytotrophoblast cells anda choriocarcinoma cell line, JEG-3 cell, was conducted by zymography, RT-PCR and Northern blot. There is MMP-28mRNA expression in both the cytotrophoblast cells and JEG-3 cells by RT-PCR. The activity of MMP-28 in cytotrophoblast cells was significantly weaker than that in JEG-3 (P < 0.01) by zymography. Furthermore, mRNA expression of MMP-28 was significantly stronger (P < 0.001) in JEG-3than in human cytotrophoblast cells in a time-dependent way by Northern Blot. Our results suggest that MMP-28 may play a role in some of the tissue-remodeling events associated with normal pregnancy and tumor progression.``

  19. Progesterone receptor (PR) isoforms PRA and PRB differentially regulate expression of the breast cancer resistance protein in human placental choriocarcinoma BeWo cells.

    Science.gov (United States)

    Wang, Honggang; Lee, Eun-Woo; Zhou, Lin; Leung, Peter C K; Ross, Douglas D; Unadkat, Jashvant D; Mao, Qingcheng

    2008-03-01

    Breast cancer resistance protein (BCRP) plays a significant role in drug disposition and in conferring multidrug resistance in cancer cells. Previous studies have shown that steroid hormones such as 17beta-estradiol and progesterone can affect BCRP expression in cancer cells. In this study, we investigated the molecular mechanism by which BCRP expression in human placental choriocarcinoma BeWo cells is regulated by progesterone. Transfection of the progesterone receptor (PR) isoforms PRA and PRB resulted in a similarly increased expression of PRA and PRB, respectively. However, progesterone significantly increased BCRP expression and activity only in PRB-transfected cells. This stimulatory effect of progesterone was abrogated by the PR antagonist mifepristone (RU-486). Consistently, transcriptional activity of the BCRP promoter was induced 2- to 6-fold by 10(-8) to 10(-5) M progesterone in PRB-transfected cells. Progesterone had little effect on BCRP expression and activity and transcriptional activity of the BCRP promoter in PRA-transfected cells; however, cotransfection of PRA and PRB significantly decreased the progesterone-response compared with that in cells transfected with only PRB. Mutations in a novel progesterone response element (PRE) identified between -243 to -115 bp of the BCRP promoter region significantly attenuated the progesterone-response in PRB-transfected cells, and deletion of the PRE nearly completely abrogated the progesterone effect. Specific binding of both PRA and PRB to the BCRP promoter through the identified PRE was confirmed using the electrophoretic mobility shift assay. Collectively, progesterone induces BCRP expression in BeWo cells via PRB but not PRA. PRA represses the PRB activity. Thus, PRA and PRB differentially regulate BCRP expression in BeWo cells.

  20. Embolia pulmonar decorrente de coriocarcinoma metastático com apresentação atípica Pulmonary embolism resulting from metastatic choriocarcinoma with atypical presentation: report of a case

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    Teresa de Jesus Jhayya

    1999-12-01

    Full Text Available É apresentado o caso de uma paciente de 36 anos, com coriocarcinoma metastático pulmonar com apresentação clínica e radiológica atípica. O achado de hipertensão pulmonar indicou a possibilidade de tromboembolia pulmonar; todavia, o diagnóstico definitivo e causa da embolia pulmonar foram dados na autópsia. Discutem-se as formas de apresentação das metástases do coriocarcinoma, sua repercussão e o período de latência que pode existir até evidenciar a neoplasia.A case is presented of a 36 year-old woman, with metastatic lung choriocarcinoma with atypical clinical and radiological presentation. The finding of pulmonary hypertension indicated the possibility of pulmonary thromboembolism, still, the definitive diagnosis and cause of pulmonary embolism were done in the autopsy. The authors discuss the manners of choriocarcinoma metastasis presentation, its repercussions and the latent period which may exist until it presents evidence of neoplasm.

  1. Clinical study of partial mole or choriocarcinoma with co-existing fetus%妊娠合并部分性葡萄胎或绒癌临床研究

    Institute of Scientific and Technical Information of China (English)

    赵湘婉; 李娟清

    2010-01-01

    目的 通过对妊娠合并部分性葡萄胎或绒癌病例的报道和分析,以引起临床重视.方法 回顾性分析妊娠合并部分性葡萄胎或绒癌7例的临床资料及相关辅助检查(β-hCG检测和超声),7例患者年龄平均28岁.所有病例均经手术和病理予以确诊.结果 妊娠合并部分性葡萄胎共5例,母均存活,胎儿仅存活1例,为孕32周者;妊娠合并绒癌者共2例,母均死亡,婴儿1例死亡,1例存活,2年后失访.结论 近年本类疾病有增多趋势,应引起遗传学、生殖医学、妇科肿瘤、围产医学和病理学等重视.%Objective To evaluate the rare entity of partial mole or choriocarcinoma with co-existing fetus.Methods A total of 7 cases of partial mole or choriocarcinoma with co-existing fetus were selected to collect clinical profiles and perform auxiliary examinations such as serum β-hCG and sonography.The data were analyzed retrospectively and all cases confirmed by surgery and histopathological diagnosis.Results There were 5 cases of partial moles with co-existing fetus.All patients stayed alive at follow-up.However,only 1 fetus delivered at 32-week gestation survived.All patients of choriocarcinoma with co-existing fetus died.Among them,1 newborn died and another one lost follow-up after 2 years.Conclusion Recently the rate of gestational trophoblastic disease with co-existing fetus is rising.It is quite important that the professionals of genetics,reproductive medicine,gynecological oncology,perinatal medicine and pathology should pay more attention to this emerging disease.

  2. Primary choriocarcinoma of uterine cervix treated by uterine artery drug pouring and embolism:one case report%子宫动脉药物灌注及栓塞治疗原发性宫颈绒癌一例

    Institute of Scientific and Technical Information of China (English)

    Yan Wang; Haiyang Jiang; Shaoguang Wang; Xuan Wang; Zhiyun Song

    2009-01-01

    Primary choriocarcinoma of the uterine cervix (PCC) is an extremely rare disease. The conventional treatment of PCC is a combination of hysterectomy and chemotherapy. We present one rare case proved by cervical biopsy. The patient was an 36-year-old Chinese woman with irregular vaginal bleeding for 60 days. A cervical tumoral mass was seen in the pel-vic examination and biopsy revealed active hyperplasia of trophoblastic cell, Because of massive vaginal haemorThage, the patient accepted uterine artery drug pouring and embolism emergently. This management had gained a satisfactory effect. Thus, Uterine artery drug pouring and embolism is one new and effective weapon for PCC, which can preserve the patient's productive abUity.

  3. Quantification of new antiepileptic drugs by liquid chromatography/electrospray ionization tandem mass spectrometry and its application to cellular uptake experiment using human placental choriocarcinoma BeWo cells.

    Science.gov (United States)

    Furugen, Ayako; Kobayashi, Masaki; Nishimura, Ayako; Takamura, Shigeo; Narumi, Katsuya; Yamada, Takehiro; Iseki, Ken

    2015-10-01

    A method for quantification of new antiepileptic drugs, including lamotrigine (LTG), levetiracetam (LEV), gabapentin (GBP), and topiramate (TPM), in cellular samples, using liquid chromatography/electrospray ionization tandem mass spectrometry was developed to better understand the membrane transport mechanisms of these drugs. Cell lysate was deproteinized by methanol containing LEV-d3 as an internal standard (IS). Chromatographic separation was performed on a C18 column using gradient elution with methanol-water-formic acid (10:90:0.1, v/v/v) and methanol-formic acid (100:0.1, v/v). Analytes were detected in positive ion electrospray mode with selected reaction monitoring (SRM). This method was applicable for a linear range of 5 to 500pmol for LTG; 5 to 1000pmol for LEV; 10 to 10,000pmol for GBP; and 5 to 5000pmol for TPM. The intra-day precision, inter-day precision, and accuracy data were assessed and found to be acceptable. This developed and validated method was then successfully applied to the investigation of uptake of the new antiepileptic drugs in placental choriocarcinoma BeWo cells. The intracellular concentration of these drugs in BeWo cells, accumulating over 30min at 37°C was in the order of GBP>LTG>LEV≈TPM. Furthermore, the uptake of GBP at 4°C was much lower than that at 37°C. The uptake of GBP was saturated at high concentrations. The kinetic parameters calculated for GBP uptake in BeWo cells were determined as Km of 105.4±6.4μM and Vmax at 8153±348pmol/mg protein/min. The novel method described here should enable investigators to elucidate the transport mechanisms of these antiepileptic drugs in BeWo cells.

  4. Extra gonadal non-seminomatous germ cell tumour and PET-T.D.M. with {sup 18}F-F.D.G.: about one case of primitive retroperitoneal choriocarcinoma; Tumeurs germinales non seminomateuses extragonadiques et TEP-TDM au F-18 FDG: a propos d'un cas de choriocarcinome retroperitoneal primitif

    Energy Technology Data Exchange (ETDEWEB)

    Cimarelli, S.; Deshayes, E.; Mognetti, T.; Desuzinges, C. [Service de medecine nucleaire, centre Leon-Berard, Lyon, (France); Biron, P. [departement d' oncologie, centre Leon-Berard, Lyon, (France); Rivoire, M. [departement de chirurgie, centre Leon-Berard, Lyon, (France); Giammarile, F. [service de medecine nucleaire, hopital Lyon-Sud, (France)

    2009-05-15

    The non-seminomatous germinal tumors represent 60% of the germinal tumors, the most frequent cancer for young men.The positron computed tomography/computed tomography (PET/T.D.M.) with {sup 18}F fluorodeoxyglucose seems full of promises for the initial evaluation and the early evaluation of chemotherapy. for this type of tumor. In 1 to 5% of cases these tumors are extra gonadal. We present the case of a twenty three years old man with a retroperitoneal primitive choriocarcinoma with numerous metastases for whom the metabolic imaging was useful. We discuss the interest of this examination in this rare pathology. For the extra gonadal non-seminomatous germinal tumors the PET-F.D.G. seems bring information useful for the determination of the viable character of a post-chemotherapy residual mass, especially when the anatomical imaging show results discordant with the clinico biological data. (N.C.)

  5. A CASE OF MAMMARY METASTASIS FROM CHORIOCARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    @@ A 25 years old female was hospitalized because a mass had been found in the right breast more than 5 months and progressively enlarged after delivery for 3 months. 5 months before, a bean-sized nodule found by the patient in her right breast asymptommatically.

  6. Unusual gestational choriocarcinoma arising in an interstitial pregnancy

    Directory of Open Access Journals (Sweden)

    Sawsen Meddeb

    2014-01-01

    CONCLUSION: The current trend of the treatment of ectopic pregnancy by conservative surgery requires adequate monitoring of βhCG and careful examination of pathologic specimens to avoid misdiagnosis of ectopic gestational trophoblastic disease.

  7. "Hysteroscopic ablation of Choriocarcinoma in a patient resistant to chemotherapy "

    Directory of Open Access Journals (Sweden)

    Ghazizadeh S

    2000-09-01

    Full Text Available Gestational Trophoblastic Neoplasia ( GTN is one of the most common gynecologic tumors in our country. Despite development of effective chemotherapy: some cases remain resistant and if there is only focus of tumor, resection would be indicated.We present a young woman with stage 1 persistant GTN showing no response to chemotherapy. Transvaginal sonograpy revealed trophoblastic tissue in the uterus. Metastatic work up was negative. Tumor was resected by hyteroresectoscopy, and there was no need for subsequent chemotherapy, BHCG remained negative after 26 months of follow up.

  8. Massive fetomaternal hemorrhage caused by an intraplacental choriocarcinoma: a case report

    DEFF Research Database (Denmark)

    Henningsen, Anna-Karina Aaris; Maroun, Lisa Leth; Havsteen, Hanne;

    2010-01-01

    of a severely anemic infant. A fetomaternal hemorrhage resulted in a hemoglobin concentration in the infant of only 2,1 g/dL. Neither mother nor child showed signs of metastatic disease. The macroscopic examination showed a hydropic placenta weighing more than 1 kilogram. Microscopy showed an intraplacental...

  9. Walker Prize Lecture, 1977. Choriocarcinoma: can we afford to cure cancer.

    Science.gov (United States)

    Bagshawe, K D

    1978-01-01

    The way the management of patients with trophoblastic tumours has depended on the acquisition of new knowledge and new drugs is demonstrated. Emphasis is put on the ability to detect early disease by biochemical markers and on the ability to define on a multifactorial basis the resistance potential of the tumours. This provides a basis for stratification of treatment and the use of prophylactic chemotherapy to prevent cerebral metastases in certain patients. Although chemotherapy is often intensive and prolonged, there has so far been little evidence of long-term effects and many women have had normal pregnancies subsequently, but the limitations of present data are discussed. The difficulties of matching available resources to society's needs in the cancer field make it necessary to consider whether such treatment is unjustifiably expensive. It is shown that for these tumours early diagnosis not only proves effective in therapeutic terms but provides substantial financial savings. It is suggested that screening programmes for cancer cannot be accepted or rejected on principle. In judging them on their individual merits it is appropriate to anticipate interaction between earlier diagnosis and more effective drug treatment.

  10. Expression of serum amyloid A4 in human trophoblast-like choriocarcinoma cell lines and human first trimester/term trophoblast cells

    Science.gov (United States)

    Rossmann, C.; Hammer, A.; Koyani, C.N.; Kovacevic, A.; Siwetz, M.; Desoye, G.; Poehlmann, T.G.; Markert, U.R.; Huppertz, B.; Sattler, W.; Malle, E.

    2014-01-01

    Trophoblast invasion into uterine tissues represents a hallmark of first trimester placental development. As expression of serum amyloid A4 (SAA4) occurs in tumorigenic and invasive tissues we here investigated whether SAA4 is present in trophoblast-like human AC1-M59/Jeg-3 cells and trophoblast preparations of human first trimester and term placenta. SAA4 mRNA was expressed in non-stimulated and cytokine-treated AC1-M59/Jeg-3 cells. In purified trophoblast cells SAA4 mRNA expression was upregulated at weeks 10 and 12 of pregnancy. Western-blot and immunohistochemical staining of first trimester placental tissue revealed pronounced SAA4 expression in invasive trophoblast cells indicating a potential role of SAA4 during invasion. PMID:24951172

  11. Intraplacentaert koriokarcinom

    DEFF Research Database (Denmark)

    Rørne, Ditte Josefine; Kirschner, Benny

    2010-01-01

    Choriocarcinoma is found in 1/20,000-40,000 pregnancies. The disease typically presents with symptomatic metastases. We present a case of incidentally discovered intraplacental choriocarcinoma. A gravida 7 at 35 + 4 weeks' gestation presented because of abdominal pain and decreased foetal movemen....... An acute Caesarean was performed with the delivery of a hypotonic, anaemic girl with an Apgar score of 0/1. Choriocarcinoma typically presents as yellow areas, resembling intraplacental infarction. Consequently, the incidence is probably higher than presumed....

  12. The HLA-G*0105N null allele induces cell surface expression of HLA-E molecule and promotes CD94/NKG2A-mediated recognition in JAR choriocarcinoma cell line.

    Science.gov (United States)

    Sala, Frédéric G; Del Moral, Pierre-Marie; Pizzato, Nathalie; Legrand-Abravanel, Florence; Le Bouteiller, Philippe; Lenfant, Françoise

    2004-12-01

    HLA-G is a non-classical HLA class Ib molecule primarily expressed in trophoblast cells, and is thought to play a key role in the induction of materno-fetal tolerance during pregnancy. In addition, the HLA-G gene provides a suitable leader sequence peptide capable of binding to HLA-E. However, the existence of placentas homozygous for the HLA-G*0105N null allele suggests that HLA-G1 might not be essential for fetal survival. To investigate whether expression of the HLA-G*0105N allele supports HLA-E cell surface expression, we transfected the HLA-G*0105N gene into JAR trophoblast cells. Flow cytometry analysis showed that HLA-G*0105N-transfected cells express surface HLA-E to a similar extent as the unmutated HLA-G gene, whereas HLA-G1 cell surface expression was undetectable. Using the NKL cell line in a standard (51)Cr release assay, the HLA-E molecules were found to inhibit natural killer lysis, through a mechanism partially dependent on CD94/NKG2A-mediated recognition.

  13. DNA Analysis in Samples From Younger Patients With Germ Cell Tumors and Their Parents or Siblings

    Science.gov (United States)

    2016-10-05

    Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Embryonal Carcinoma; Testicular Seminoma; Testicular Teratoma; Testicular Yolk Sac Tumor

  14. Epithelioid trophoblastic tumor of the uterus: a report of three cases

    Institute of Scientific and Technical Information of China (English)

    LIU Qi; SHI Qun-li; ZHANG Jian-min; LI Yan; DU Yi-ming; SHEN Shi-ming; MA Heng-hui; MENG Kui

    2007-01-01

    @@ Epithelioid trophoblastic tumor(ETT)of the uterus is a rare tumor introduced recently,which is distinct from placental site trophoblastic tumor (PSTT) and choriocarcinoma with the histological appearance of resembling low-grade squamous cell carcinomas.

  15. Cervical poorly differentiated adenocarcinoma with dominant choriocarcinomatous pattern: A case report

    Directory of Open Access Journals (Sweden)

    Nikolić Branka

    2015-01-01

    Full Text Available Introduction. Gestational trophoblastic neoplasm (GTN, choriocarcinoma in coexistence with primary cervical adenocarcinoma, is a rare event not easy to diagnose. Choriocarcinoma is a malignant form of GTN but curable if metastases do not appear early and spread fast. Case report. We presented choriocarcinoma in coexistence with primary cervical adenocarcinoma in a 48-year-old patient who had radical hysterectomy because of confirmed cervical carcinoma (Dg: Carcinoma porto vaginalis uteri FIGO st I B1. Histological findings confirmed cervical choriocarcinoma with extensive vascular invasion and apoptosis but GTN choriocarcinoma was finally confirmed after immunohystochemical examinations. Preoperative serum human gonadotropine (beta hCG level stayed unknown. This patient did not have any pregnancy-like symptoms before the operation. The first beta hCG monitoring was done two months after the operation and found negative. According to the final diagnosis the decision of Consilium for Malignant Diseases was that this patient needed serum hCG monitoring as well as treatment with chemotherapy for high-risk GTN and consequent irradiation for adenocarcinoma. Conclusion. The early and proper diagnosis of nonmetastatic choriocarcinoma of nongestational origine in coexistence with cervical carcinoma is curable and can have good prognosis.

  16. Hemoptysis and hemoperitoneum due to metastatic gestational choriocarcinma: bronchial artery embolization and superselective splenic artery embolization: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Tae Beom; Park, Byung Ho; Yoon, Seong Kuk; Kim, Chan Sung; Lee, Jin Hwa; Oh, Jong Young [Donga University School of Medicine, Pusan (Korea, Republic of); Seong, Chang Kyu; Kim, Yong Joo; Kim, Young Hwan [Kyungpook National University School of Medicine, Daegu (Korea, Republic of)

    2003-01-01

    Gestational choriocarcinoma is easily disseminated hematogenously and its hypervascular nature places the patient at risk of significant hemorrhage both at the sites of metastatic lesion and in the uterus. In addition, its tends to give rise to pseudoaneurysm formation. Treatment of the condition by percutaneous embolization has been reported in several published articles, and hemoperitoneum secondary to rupture of splenic metastasis of gestational choriocarcinoma has also been reported, as has angiographic embolization. Hemoptysis resulting from pulmonary metastasis and treatment by means of embolization of the bronchial artery have not been reported, however. In this article, we describe a case of hemoptysis and hemoperitoneum due to pulmonary and splenic metastasis of gestational choriocarcinoma. Treatment of the condition involved embolization of the bronchial artery and superselective embolization of the splenic artery.

  17. Pathogenesis of Testicular Germ Cell Tumors from a Developmental Point of View

    NARCIS (Netherlands)

    K. Biermann (Katharina)

    2010-01-01

    textabstractCurrent classification systems of human germ cell tumors (GCTs) are based on histological composition. In the group of nonseminomas, different variants of teratoma (somatic differentiation), yolk sac tumor and choriocarcinoma (extra-embryonic differentiation), are recognized, as well as

  18. PARTIAL HYDATIDIFORM MOLE WITH A LIVE FETUS: A RARE ENTITY

    Directory of Open Access Journals (Sweden)

    Mounika Reddy

    2015-07-01

    Full Text Available BACKGROUND : Gestational trophoblastic neoplasia (GTN represents a spectrum of premalignant and malignant diseases that occur after abnormal fertilization. [ 1 ] GTN includes complete hydatidiform mole (CHM, partial hydatidiform mole (PHM, invasive mole, choriocarcinoma, and placental - site trophoblastic tumor (PSTT. CHM and PHM together account for 80% of all cases of GTN.

  19. Gestational trophoblastic diseases - clinical guidelines for diagnosis, treatment, follow-up, and counselling

    DEFF Research Database (Denmark)

    Niemann, Isa; Vejerslev, Lars O; Froeding, Ligita Paskeviciute

    2015-01-01

    line chemotherapy is BEP or EP, alternatively EMA-CO (B). Choriocarcinoma is primarily treated with chemotherapy. Hysterectomy and/or resection of metastases are possible treatments (A). Placental site trophoblastic tumour (PSTT) and epithelioid trophoblastic tumour (ETT) are primarily treated...

  20. Kinetics of silica nanoparticles in the human placenta

    DEFF Research Database (Denmark)

    Poulsen, Marie Sønnegaard; Mose, Tina; Maroun, Lisa Leth;

    2015-01-01

    choriocarcinoma cell line and the ex vivo perfused human placenta. Nanotoxicity in BeWo cells was examined by the MTT assay which demonstrated decreased cell viability at concentrations >100 µg/mL. In the placental perfusion experiments, antipyrine crossed the placenta rapidly, with a foetal:maternal ratio of 0...

  1. MR imaging of gestational trophoblastic tumors

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin Bum; Ha, Hyun Kwon; Kim, Hak Hee; Lee, Eun Ja; Lee, Jae Hee; Song, Ha Hun; Kim, Taek Geun; Ro, Sang Chun; Jee, Mi Kyung; Chung, Jae Geun [Catholic University Medical College, Seoul (Korea, Republic of)

    1994-09-15

    To evaluate the MR findings of gestational trophoblastic tumor(GTT) in correlation with pathological results. Nine patients who confirmed the diagnosis (four choriocarcinomas and five invasive moles) constituted the basis of our study. Pathologic specimens were taken from the tumors corresponding to the regions of interest on MR images The MR images were analyzed in respect of the morphology and signal intensity of the tumors, uterine and adnexal vascularity, and the adnexal lesion. The MR findings of four choriocarcinomas were well-defined, hemorrhagic masses with central necrosis; the masses were hyperintense on T1-weighted images. In contrast, the five invasive moles showed irregular and permeative masses with densely enhanced solid components and tiny cystic lesion. The trophoblstic proliferation, coagulation necrosis, and molar villi had variable signal intensities on T1- and T2-weighted images. Our results suggest that MR imaging is a promising tool for noninvasive morphologic analysis of GTTS.

  2. Internalization of Trichosanthin via Different Endocytic Mechanisms

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fan; SUI Senfang

    2005-01-01

    Trichosanthin (TCS) is a plant toxin with ribosome-inactivating activity. TCS can be internalized by the host cells and then attacks the ribosomes resulting in cell death. However, the manner for endocytic uptake of TCS is not well understood. The present work investigates the endocytosis pathway of TCS in human choriocarcinoma cells. The different endocytic mechanisms are interfered by potassium depletion, cholesterol-extraction/addition, or treatments of various drugs. The experiments detect their effects on the TCS-uptake. The results show that a large portion of the TCS can be internalized by clathrin-dependent, as well as by clathrin-independent but cholesterol-dependent endocytosis in human choriocarcinoma cells.

  3. 妊娠滋养细胞疾病基础研究进展

    Institute of Scientific and Technical Information of China (English)

    冯苗; 王自能

    2003-01-01

    @@ 妊娠滋养细胞疾病(gestational trophoblashc disease,GTD)是一组来源于胎盘绒毛滋养细胞的疾病,包括葡萄胎(hy-datidiform mole,HM)、侵蚀性葡萄胎(inrasive hydatidiform mole,IHM)、绒癌(choriocarcinoma,CCA)和一类少见的胎盘部位滋养细胞肿瘤.

  4. MR imaging of gestational trophoblastic tumor: role of gadolinium enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Si Young; Byun, Jae Young; Kim, Bum Su; Yun, Young Hyun; Mun, Kyung Mi; Park, Kyung Sin; Kim, Byung Kee; Bae, Seog Nyeon; Shinn, Kyung Sub

    1997-12-01

    The purpose of this study is to investigate the role of gadolinium enhanced MR imaging in the evaluation of gestational trophoblastic tumors (invasive mole and choriocarcinoma). Pre-enhanced T1-and T2-weighted images and gadolinium enhanced T1-weighted images of 34 gestational trophoblastic tumors (15 choriocarcinomas, 19 invasive moles) were retrospectively evaluated and enhancement patterns were analyzed. Morphologica differences and structural characteristics were analyzed by the evaluation of tumor margin, patterns of hemorrhagic necroses, the development of intratumoral vascularity, and molar villi. Graded scores of MR findings between pre- and gadolinium enhanced images were based on the following criteria : 1) visualization of tumor margin 2) distinction between tumor necrosis and zone of trophoblastic proliferation ; and 3) molar villi. Statistical differences between graded scores of pre- and post-enhanced images were analyzed. Gadolinium enhanced MR imaging was helpful for the visualization of tumor characteristics in gestational trophoblastic tumors and in differential diagnosis between invasive mole and choriocarcinoma. (author). 16 refs., 4 tabs., 4 figs.

  5. Usefulness of magnetic resonance imaging (MRI) in the detection of the lesions of gestational trophoblastic disease; Comparison with computed tomography and digital subtraction angiography

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Satoshi; Akahori, Taiichiro; Mochizuki, Matsuto; Kono, Michio (Kobe Univ. (Japan). School of Medicine)

    1992-02-01

    Twenty patients with gestational trophoblastic disease (GTN) were examined by magnetic resonance imaging (MRI), computed tomography (CT) and digital subtraction angiography (DSA), to evaluate their usefulness in the diagnosis of the disease. The lesions of hydatidiform mole were mainly composed of molar vesicles, dilated vessels and hemorrhage which were depicted as small round high intensity lesions on the T2-weighted images and as tree-like low intensity lesions and high or low intensity lesions of various shapes in the T1-, T2-weighted images. These MRI findings closely corresponded to the histopathological findings. On the other hand, CT findings obtained with hydatidiform mole were characterized by filling defects or a small round low density area on contrast enhanced images. The detection ratio for intramural lesions of invasive mole and choriocarcinoma by MRI was 83% (5/6), while that by CT was 50% (3/6). The obliteration of the junctional zone and interruption of the myometrium observed in MRI were significant signs suggesting intramural invasion of the disease. In fact, these signs in MRI were observed in all of the six cases of invasive mole or choriocarcinoma examined. In conclusion, MRI is a powerful means for the determining the intramural invasive mole and choriocarcinoma. Thus more accurate diagnosis of GTN will be obtained with the combined use of MRI and DSA. (author).

  6. A 15-year-old female with amenorrhea, abdominal distention, and elevated human chorionic gonadotropin: pregnancy, right? Not so fast….

    Science.gov (United States)

    Aggarwal, Arun; Ocon, Anthony J; Nibhanipudi, Kumara

    2012-10-01

    Nongestational choriocarcinoma, a rare ovarian tumor, may present in young women with amenorrhea, abdominal distention, and elevated urine human chorionic gonadotropin (hCG), all of which may be mistaken for pregnancy. A 15-year-old Hispanic female, who reported no sexual activity, presented with 6 months of amenorrhea, abdominal pain, and progressive abdominal distension. Initially, suspicion of pregnancy was considered. Physical examination was significant for abdominal distension, but no uterine fundus or fetal anatomy could be palpated, and auscultation did not reveal any fetal heart sounds or bruits. Laboratory values showed elevated urine hCG, cancer antigen 125, and cancer antigen 19.9 levels but normal serum hCG level and was inconsistent with pregnancy. Computed tomographic scans revealed a large abdominal heterogeneous mass and pleural effusions. Salpingo-oophorectomy with total omentectomy and inversion appendectomy removed a 21 × 20.5 × 16.5-cm tumor. Pathological testing determined it to be a nongestational choriocarcinoma. This rare tumor is more common in the pediatric adolescent population than in adults. Surgical resection and chemotherapy often result in a positive prognosis. In female adolescent patients presenting with elevated hCG level, amenorrhea, and abdominal distention, choriocarcinoma should be considered, especially in those with no history of sexual activity or before menarche.

  7. [From human andro- and parthenogenesis (hydatidiform moles and benign ovarian teratomas) to cancer].

    Science.gov (United States)

    Coullin, P

    2005-01-01

    Genomic imprinting is a process that appeared in mammals. This phenomenon blocks the normal development of parthenogenic and androgenic conceptuses, that is to say benign ovarian teratomas and hydatidiform moles respectively. Pathological modifications of these conceptuses depend on whether the chromosomes come from the mother or father. These pathologies are associated with an accidental anomaly during gametogenesis and/or fertilizing. These reproductive anomalies are sporadic and some familial cases may exist suggesting a genetic control of such diseases. The human andro- and parthenogenetic conceptuses, but more frequently the moles, may be invasive (choriocarcinoma). An imbalance of the imprinting genes may initiate the deregulation of other genes, including oncogenes and anti-oncogenes, which can explain the cancerous modification. Immunological and environmental factors must be also considered (presence of the only paternal chromosomes in the choriocarcinoma). Numerous works on this subject are published and some recent important discoveries underline the roles of genes HOX, Tim P3, E-cad and p-16, and the recurrent chromosome anomalies 7q21+and 8p21- in the mole to choriocarcinoma processing. Although these phenomena are complex and heterogeneous, the andro- and parthenogenote conceptuses are particularly interesting models with which to understand developmental disorders and cancerous progression.

  8. Spontaneous reproductive pathology in female guinea pigs.

    Science.gov (United States)

    Veiga-Parga, Tamara; La Perle, Krista M D; Newman, Shelley J

    2016-11-01

    Reproductive pathology of domestic guinea pigs is underreported to date. To provide a comprehensive review of uterine disease in guinea pigs, we performed a retrospective study of the pathology archives of the University of Tennessee, College of Veterinary Medicine. By histology, 13 of 37 uterine lesions in 23 animals were neoplastic; the other 24 nonneoplastic lesions included cystic endometrial hyperplasia (16 of 24), endometrial hemorrhage (3 of 24), pyometra (2 of 24), polyp (2 of 24), and mucometra (1 of 24). The most common guinea pig uterine neoplasms were uterine leiomyomas (6 of 13), followed by adenomas (3 of 13) and leiomyosarcomas (1 of 13). Other neoplasms included anaplastic tumors of unknown origin (2 of 13) and choriocarcinoma (1 of 13). Both anaplastic tumors and the choriocarcinoma were positive for vimentin. The choriocarcinoma was positive for HSD83B1, indicating a trophoblastic origin and its final diagnosis. All were negative for cytokeratin and smooth muscle. In multiple animals, more than 1 tumor or lesion was reported. Estrogen receptor and progesterone receptor expression was nearly 100% in uterine neoplasms. Nearly all animals for which data were available had cystic rete ovarii (18 of 19); the animal with no cystic rete ovarii had paraovarian cysts. In our study, female pet guinea pigs had a tendency to develop cystic endometrial hyperplasia and uterine neoplasia. Factors for the development of these lesions could be cystic rete ovarii, hormone dysregulation, and/or age. Other factors could contribute to the development of uterine lesions. As in other species, early ovariohysterectomy could decrease the prevalence of uterine lesions.

  9. The biological function of hyperglycosylated hCG

    Institute of Scientific and Technical Information of China (English)

    Laurence A Cole; Stephen A Butler

    2012-01-01

    Objective:Hyperglycosylated human chorionic gonadotropin(hCG) is a variant of hCG made by cytotrophoblast cell.Here we examine the role of hyperglycosylated hCG in placenta growth and invasion.Methods:JEG-3 choriocarcinoma cells and term cytotrophoblast monolayer culture were prepared.The effect of supplemental hyperglycosylated hCG and hCG was investigated. Growth of these cells was examined by increase incell number.Invasion was investigated using Matrigel basement membrane cells.The proportion of cell invadingMatrigel was determined. Results:Term cytotrophoblast cell andJEG-3 choriocarcinoma cells grew to5427±834 cells (109%) and7114±553 cells(142%).With the supplementation of hyperglycosylated hCG, they grew significantly wider to7633±177 cells(142%) and10315±1477 cells(206%).With the supplementation of hCG they diminished to4227±769 cells(78%) and5620±657 cells(79%).Term cytotrophoblast cell andJEG-3 choriocarcinoma cells penetratedMatigel membranes to(40.0±10.0)% and(46.0±9.8)%.Hyperglycosylated hCG significantly enhanced penetration to(76.0±13.0)% and(84.0±6.6)%. hCG diminished penetration to(32.0±9.1)% and(32.0±4.5)%.Conclusions:Hyperglycosylated hCG enhances both cytotrophoblast growth and cytotrophoblast cell invasion. hCG minimally suppresses growth and invasion.

  10. Recent advances in understanding the etiology and pathogenesis of pediatric germ cell tumors

    DEFF Research Database (Denmark)

    Mosbech, Christiane Hammershaimb; Rechnitzer, Catherine; Brok, Jesper S;

    2014-01-01

    Pediatric germ cell tumors (GCTs) are rare neoplasms arising predominantly in the gonads and sacrococcygeal, mediastinal, and intracranial localizations. In this article, we review current knowledge of pathogenesis of pediatric GCTs, which differs from adult/adolescent GCTs. One distinctive feature...... transcription factors OCT-3/4, NANOG, and AP-2γ in germinomas/seminomas/dysgerminomas is consistent with retaining a germ cell phenotype. Teratomas, in contrast, develop through a pathway of aberrant somatic differentiation of immature germ cells, and the yolk sac tumors and choriocarcinomas result from...... of pathogenesis of these fascinating tumors....

  11. Carcinosarcoma with choriocarcinomatous and osteosarcomatous differentiation in a patient with juvenile polyposis syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Parra-Medina

    2015-09-01

    Full Text Available Juvenile polyposis syndrome (JPS is an infrequent autosomal dominant hereditary predisposition to the occurrence of hamartomatous polyps in the colon and rectum. We describe the case of a 12-year-old boy with JPS associated with an abdominal tumor. Histological sections of the abdominal tumor showed components of adenocarcinoma, osteosarcoma, and choriocarcinoma. Immunohistochemistry was AE1/AE3, CK7, HCG and SALL4 positive. Juvenile polyposis syndrome patients are at increased risk of colorectal adenocarcinoma. However, we present a case of an adenocarcinoma associated with other unusual components. This association has not been reported before.

  12. Measurement of Cu/Zn SOD in placenta, cultured cells, various fetal tissues, decidua and semen by ELISA.

    Science.gov (United States)

    Ali Akbar, S; Nicolaides, K H; Brown, P R

    1998-07-01

    The concentration of copper/zinc-containing superoxide dismutase (Cu/Zn SOD) was measured in placental villous tissues (8-20 weeks' gestation), decidual tissues, cultured cells from chorionic villi and amniotic fluid cells, various fetal tissues (8-11 weeks' gestation), spermatozoa, seminal plasma and ovarian follicular fluid using a sensitive enzyme-linked immunosorbent assay (ELISA). The isoenzyme was expressed in all samples expect ovarian follicular fluid. Cu/Zn SOD was also detected in hydatidiform mole and choriocarcinoma. In placental villous tissues the concentration of the enzyme increased with gestation between 8 and 20 weeks of pregnancy (n = 69, r = 0.34, P < 0.005).

  13. Invasive mole presenting as pain abdomen

    Directory of Open Access Journals (Sweden)

    Swati Singh

    2013-06-01

    Full Text Available Gestational trophoblastic neoplasms (GTN are proliferative as well as degenerative disorders of placental elements and include complete or partial mole (90%, invasive mole (5.8%, choriocarcinoma (1-2% and placental site tumor (1-2%. 15% of complete mole can develop into invasive mole. Very rarely (2-4% partial mole can develop into invasive one presenting with features of incomplete abortion, mixed abortion and sometimes as obstetric emergencies like intraperitoneal hemorrhage. So, proper diagnosis and timely intervention can prevent mortality and reduce the morbidity of the patients. [Int J Reprod Contracept Obstet Gynecol 2013; 2(3.000: 480-481

  14. Solubilization of proteins: the importance of lysis buffer choice.

    Science.gov (United States)

    Peach, Mandy; Marsh, Noelle; Miskiewicz, Ewa I; MacPhee, Daniel J

    2015-01-01

    The efficient extraction of proteins of interest from cells and tissues is not always straightforward. Here we demonstrate the differences in extraction of the focal adhesion protein Kindlin-2 from choriocarcinoma cells using NP-40 and RIPA lysis buffer. Furthermore, we demonstrate the use of a more denaturing urea/thiourea lysis buffer for solubilization, by comparing its effectiveness for solubilization of small heat-shock proteins from smooth muscle with the often utilized RIPA lysis buffer. Overall, the results demonstrate the importance of establishing the optimal lysis buffer for specific protein solubilization within the experimental workflow.

  15. Lack of a Y-Chromosomal Complement in the Majority of Gestational Trophoblastic Neoplasms

    Directory of Open Access Journals (Sweden)

    Kai Lee Yap

    2010-01-01

    Full Text Available Gestational trophoblastic neoplasms (GTNs are a rare group of neoplastic diseases composed of choriocarcinomas, placental site trophoblastic tumors (PSTTs and epithelioid trophoblastic tumors (ETTs. Since these tumors are derivatives of fetal trophoblastic tissue, approximately 50% of GTN cases are expected to originate from a male conceptus and carry a Y-chromosomal complement according to a balanced sex ratio. To investigate this hypothesis, we carried out a comprehensive analysis by genotyping a relatively large sample size of 51 GTN cases using three independent sex chromosome genetic markers; Amelogenin, Protein Kinase and Zinc Finger have X and Y homologues that are distinguishable by their PCR product size. We found that all cases contained the X-chromosomal complement while only five (10% of 51 tumors harbored the Y-chromosomal complement. Specifically, Y-chromosomal signals were detected in one (5% of 19 choriocarcinomas, one (7% of 15 PSTTs and three (18% of 17 ETTs. The histopathological features of those with a Y-chromosome were similar to those without. Our results demonstrate the presence of a Y-chromosomal complement in GTNs, albeit a low 10% of cases. This shortfall of Y-chromosomal complements in GTNs may reinforce the notion that the majority of GTNs are derived from previous molar gestations.

  16. Expression of epidermal growth factor and its receptor in gestational trophoblastic diseases

    Institute of Scientific and Technical Information of China (English)

    LI Ning; YUAN Yu-kang; LIU Hui-xi

    2005-01-01

    Objective: To determine whether epidermal growth factor (EGF) and its receptor have any possible correlation with etiology of gestational trophoblastic diseases. Methods: Avidin-biotin immunoperoxidase techniques with polyclonal antibodies against EGF, EGFR were used to examine 53 cases of GTD, including complete hydatidiform mole(16),invasive mole(20),gestational choriocarcinoma(17).Results:EGF was mainly localized on syncytiotrophoblasts (ST), and was found less on cytotrophoblasts. Cytologic localization of EGFR showed the similar results. The positive rate of EGF and EGFR were 0.625, 0.813 in hydatidiform mole, 0.405, 0.450 in invasive mole and 0.118, 0.235 in gestational choriocarcinoma. There was significant difference of EGF or EGFR among hydatidiform mole group and other groups, respectively (P<0.05). Conclusion:The cellular levels of EGF and EGFR decreased gradually in the development of GTD. It implied that the autocrine and paracrine mechanism may play an important role on the proliferation and differentiation of trophoblast cells and the disorder of the system may lead to GTD malignant transformation.

  17. Trend of Complete Hydatidiform Mole

    Directory of Open Access Journals (Sweden)

    K Thapa

    2010-03-01

    Full Text Available INTRODUCTION: Complete Hydatidiform mole is one of the most frequent abnormal pregnancies. This review studies the trend of complete mole in Paropakar Maternity and Women's hospital and clinical ability to detect it. METHODS: This is a retrospective study of 504 cases of complete hydatidiform mole recorded at Paropakar maternity and women's hospital, Kathmandu, during 2058-2065 B.S. Medical records were reviewed and incidence, clinical presentation and method of diagnosis were studied. RESULTS: During the study period, there were 13,9117 births and 504 complete moles, 12 partial moles, 48 persistent gestational tumours, six choriocarcinoma and four invasive moles recorded in the hospital. The incidence of complete mole was one per 276 births. It was prevalent among women younger than 29 years (80% and among the primigravidae (36.7%. More than 90% women presented in the first half of their pregnancy and vaginal bleeding was the main complaint (68.3%. Suction evacuation, dilation and evacuation followed by sharp curettage and abdominal hysterectomy were performed in 80.6%, 17.6% and 1.2% of the women respectively. Persistent mole and choriocarcinoma developed in 9.5% and 0.4% respectively. CONCLUSIONS: Complete mole has the highest incidence. It affects mostly younger women and presents with vaginal bleeding most of the time, usually in the first half of their pregnancy. Keywords: complete hydatidiform mole, gestational trophoblastic disease, persistent gestational tumours.

  18. Expression of c-erbB2 in Gestational Trophoblastic Disease and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    王玉霞; 曹阳; 孙永玉

    2002-01-01

    Summary: In order to explore a potential indicator of predicting the occurrence and development of gestational trophoblastic tumor, the expression of c-erbB2 oncogene in human normal placenta, hyda tidiform mole and choriocarcinoma was investigated. The expression of c-erbB2 was detected im munohistochemically by monoclonal antibody against the gene on the formalin-fixed paraffin sections of 21 hydatidiform moles, 21 invasive moles, 20 choriocarcinomas and 30 normal placentas. Results showed that the expression level of c-erbB2 was significantly higher in gestational trophoblastic tumor than in hydatidiform mole and normal placenta of midterm and term pregnancy (P<0. 05), while there was no significant difference between patients with gestational trophoblastic tumor of stage Ⅲ ,Ⅳ and those of stage Ⅰ , Ⅱ . It was demonstrated that overexpression of c-erbB2 may closely associ ated with malignant transformation of hydatidiform mole, not only providing important insight into pathogenesis of gestational trophoblastic tumor, but also having an important significance for the ear-ly diagnosis and early treatment of gestational trophoblastic tumor.

  19. [AgNOR of gastational trophoblastic tumors and its clinical significance].

    Science.gov (United States)

    Yang, B L

    1993-07-01

    A total of 120 paraffin-embedded gestational trophoblastic tumor tissue blocks was selected and divided into 5 groups: (1) 20 cases of normal chorionic villi. (2) 40 cases of hydatidiform mole with no malignant change during a following-up period of at least two years. (3) 40 cases of hydatidiform mole which developed into invasive mole or choriocarcinoma. (4) 10 cases of invasive mole. (5) 10 cases of choriocarcinoma. Nucleolar organizer regions (NORs) was Ag-stained and AgNOR dots were counted using the Plotion's method. The result showed that there was significant difference between group 1 and group 2 (P < 0.005), group 2 and group 3 (P < 0.001), group 3 and group 4 (P < 0.05). Taking the AgNOR count 4.00 as a standard, 75% of the cases in group 2 (mean = 2.730) was below this standard. The study suggested that with the increase of malignancy of trophoblastic tumor, the AgNOR count increased correspondingly. A quantitative study of AgNOR might be a useful measure to detect the early malignant change of hydatidiform mole.

  20. Hydatidiform molar pregnancy in Malaysian women: a histopathological study from the University Hospital, Kuala Lumpur.

    Science.gov (United States)

    Cheah, P L; Looi, L M; Sivanesaratnam, V

    1993-06-01

    A review of gestational trophoblastic disease diagnosed at the Department of Pathology, University Hospital, Kuala Lumpur from January 1989 to December 1990 using established histological criteria showed 25 complete hydatidiform moles (CHM), 11 partial hydatidiform moles (PHM), 1 invasive mole and 2 choriocarcinoma. The ages of the patients with CHM ranged from 21 to 43 years (mean = 28.5 years) and PHM 20 to 33 years (mean = 27.5 years). The invasive mole occurred in a 42-year-old Malay woman. The two patients with choriocarcinoma were both Chinese and 41 and 46-years old respectively. During the same period, 1,062 non-molar abortions and 13,115 births, inclusive of livebirths and stillbirths were recorded at the University Hospital. The incidence rate of hydatidiform moles was thus estimated to be 1:384 pregnancies. PHM constituted 30% of all molar pregnancies. Hydatidiform moles occurred among the Malays, Chinese and Indians at the rate of 2.43, 2.66 and 3.29 per 1,000 pregnancies respectively. It appears that hydatidiform molar pregnancy has the highest prevalence among the Indians, a finding similar to an earlier Singapore study.

  1. Radiology of gestational trophoblastic neoplasia

    Energy Technology Data Exchange (ETDEWEB)

    Allen, S.D. [Department of Radiology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London (United Kingdom); Lim, A.K. [Department of Radiology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London (United Kingdom); Seckl, M.J. [Department of Medical Oncology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London (United Kingdom); Blunt, D.M. [Department of Radiology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London (United Kingdom); Mitchell, A.W. [Department of Radiology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London (United Kingdom)]. E-mail: amitchell@hhnt.org

    2006-04-15

    Gestational trophoblastic neoplasia (GTN) encompasses a broad spectrum of placental lesions from the pre-malignant hydatidiform mole (complete and partial) through to the malignant invasive mole, choriocarcinoma and rare placental site trophoblastic tumour (PSTT). Ultrasound remains the radiological investigation of choice for initial diagnosis, and it can also predict invasive and recurrent disease. Magnetic resonance imaging is of invaluable use in assessing extra-uterine tumour spread, tumour vascularity, and overall staging. Positron emission tomography and computed tomography undoubtedly have a role in recurrent and metastatic disease, while angiography has a place in disease and complication management. This review will describe the relevant pathophysiology and natural history of GTN, and the use of imaging techniques in the diagnosis and management of these conditions.

  2. Effects of Nutrition Relevant Mixtures of Phytoestrogens on Steroidogenesis, Aromatase, Estrogen, and Androgen Activity

    DEFF Research Database (Denmark)

    Taxvig, Camilla; Engell-Kofoed, Anders Elleby; Sonne-Hansen, Katrine;

    2010-01-01

    Phytoestrogens (PEs) are naturally occurring plant components produced in a large range of plants. They can induce biologic responses in vertebrates by mimicking or modulating the action or production of endogenous hormones. This study examined mixtures of 12 food relevant PEs for effects...... on steroid hormone production, aromatase activity, estrogenic activity, and for interaction with the androgen receptor. The results show that a mixture of all tested PEs increased estradiol production and decreased testosterone production in H295R human adrenal corticocarcinoma cells, indicating an induced...... aromatase activity. Furthermore, exposure of the H295R cells to isoflavonoids caused a decrease in testosterone production, and various mixtures of PEs significantly stimulated MCF-7 human breast adenocarcinoma cell growth and induced aromatase activity in JEG-3 choriocarcinoma cells. The estrogenic effect...

  3. Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery.

    Science.gov (United States)

    Viola-Villegas, Nerissa; Rabideau, Amy E; Bartholomä, Mark; Zubieta, Jon; Doyle, Robert P

    2009-08-27

    The intrinsic factor (IF) vitamin B(12) ileum anchored receptor, cubilin, mediates endocytotic uptake of the IF complex of vitamin B(12) to the blood serum. This receptor was targeted for the selective delivery and accumulation of a new bioprobe, a B(12) conjugate of rhenium 2, in the cubilin expressing placental choriocarcinoma BeWo cell line. Competitive uptake and cytotoxicity assays of 2 were investigated and interactions with nuclear DNA explored. In addition, the mechanism of internalization of 2 was confirmed to proceed in an IF-cubilin mediated fashion via siRNA transfection experiments. These studies show the great potential of cubilin as a new target for the delivery of B(12) based conjugates for cancer diagnostics and/or treatment.

  4. COLOR DOPPLER ULTRASOUND IN EVALUATION OF SCROTAL LESIONS

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    Desai Sanjay

    2015-11-01

    Full Text Available : Color Doppler ultrasound is a non-invasive, non-ionising and rapid method for scrotal examination. The present study is carried out to evaluate clinically suspected cases of scrotal lesions, the sensitivity, specificity of color doppler. MATERIAL AND METHODS: This prospective study comprises 120 patients of different age groups with clinical suspicion of scrotal lesions. Color doppler ultrasound was done with 7.5MHz transducer. RESULTS: Of the total 120 cases, benign conditions 111 (92.5% is more common than malignant 9 (7.5%. In benign group commonest diagnoses were hydrocele, epididymo-orchitis, varicocele and epididymal cyst. In malignant group teratocarcinoma, choriocarcinoma, seminoma, lymphoma, embryonal cell carcinoma, yolk sac tumor with teratocarcinoma. The sensitivity for diagnosing extratesticular lesions was 83.14% and for testicular lesions 88.57%. CONCLUSION: Color doppler ultrasound is helpful in differentiating extratesticular and intratesticular lesions. It should be performed in all patients with suspected scrotal lesions

  5. Genetics and Epigenetics of Recurrent Hydatidiform Moles: Basic Science and Genetic Counselling.

    Science.gov (United States)

    Nguyen, Ngoc Minh Phuong; Slim, Rima

    2014-01-01

    Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal hyperproliferation of trophoblastic cells, which derive from the trophectoderm, the outer layer of the blastocyst that would normally develop into the placenta during pregnancy. GTDs encompass hydatidiform mole (HM) (complete and partial), invasive mole, gestational choriocarcinoma, placental-site trophoblastic tumor, and epithelioid trophoblastic tumor. Of these, the most common is HM, and it is the only one that has been reported to recur in the same patients from independent pregnancies, which indicates the patients' genetic predisposition. In addition, HM is the only GTD that segregates in families according to Mendel's laws of heredity, which made it possible to use rare familial cases of recurrent HMs (RHMs) to identify two maternal-effect genes, NLRP7 and KHDC3L, responsible for this condition. Here, we recapitulate current knowledge about RHMs and conclude with the role and benefits of testing patients for mutations in the known genes.

  6. Placental Sequestration of Plasmodium falciparum Malaria Parasites Is Mediated by the Interaction Between VAR2CSA and Chondroitin Sulfate A on Syndecan-1

    DEFF Research Database (Denmark)

    Ayres Pereira, Marina; Mandel Clausen, Thomas; Pehrson, Caroline;

    2016-01-01

    During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans......-down experiments using placental extracts from whole placenta or syncytiotrophoblast microvillous cell membranes showed three distinct CSPGs available for VAR2CSA adherence. Further examination of these three CSPGs by immunofluorescence and proximity ligation assays showed that syndecan-1 is the main receptor...... for VAR2CSA mediated placental adherence. We further show that the commonly used placental choriocarcinoma cell line, BeWo, express a different set of proteoglycans than those present on placental syncytiotrophoblast and may not be the most biologically relevant model to study placental malaria. Syncytial...

  7. Vorinostat and Temozolomide in Treating Young Patients With Relapsed or Refractory Primary Brain Tumors or Spinal Cord Tumors

    Science.gov (United States)

    2013-05-01

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Embryonal Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Extra-adrenal Paraganglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma

  8. Invasive mole: a rare cause of postmenopausal bleeding

    Directory of Open Access Journals (Sweden)

    Mamour Guèye

    2013-06-01

    Full Text Available Gestational trophoblastic disease (GTD describes a number of gynaecological tumours that originate in the trophoblast layer, including hydatidiform mole (complete or partial, placental site trophoblastic tumour, choriocarcinoma and invasive mole. Invasive moles are responsible of most cases of localized gestational trophoblastic neoplasia (GTN. Invasive mole is a condition where a molar pregnancy, such as a partial hydatidiform mole or complete hydatidiform mole, invades the wall of the uterus. It is an extremely rare condition. As GTN is not considered in the differential diagnosis of postmenopausal uterine malignancies, its preoperative diagnosis is challenging. We report a case of invasive hydatidiform mole in a postmenopausal woman discovered in a context of postmenopausal bleeding. She underwent hysterectomy and followed up till her beta hCG levels were within normal limits. The patient is in complete remission in the first postoperative year. [Int J Reprod Contracept Obstet Gynecol 2013; 2(3.000: 451-453

  9. Current Chemotherapeutic Management of Patients with Gestational Trophoblastic Neoplasia

    Directory of Open Access Journals (Sweden)

    Taymaa May

    2011-01-01

    Full Text Available Gestational trophoblastic neoplasia (GTN describes a heterogeneous group of interrelated lesions that arise from abnormal proliferation of placental trophoblasts. GTN lesions are histologically distinct, malignant lesions that include invasive hydatidiform mole, choriocarcinoma, placental site trophoblastic tumor (PSTT and epithelioid trophoblastic tumor (ETT. GTN tumors are generally highly responsive to chemotherapy. Early stage GTN disease is often cured with single-agent chemotherapy. In contrast, advanced stage disease requires multiagent combination chemotherapeutic regimens to achieve a cure. Various adjuvant surgical procedures can be helpful to treat women with GTN. Patients require careful followup after completing treatment and recurrent disease should be aggressively managed. Women with a history of GTN are at increased risk of subsequent GTN, hence future pregnancies require careful monitoring to ensure normal gestational development. This article will review the workup, management and followup of women with all stages of GTN as well as with recurrent disease.

  10. Neurocritical care complications of pregnancy and puerperum.

    Science.gov (United States)

    Frontera, Jennifer A; Ahmed, Wamda

    2014-12-01

    Neurocritical care complications of pregnancy and puerperum such as preeclampsia/eclampsia, hemolysis, elevated liver enzymes, low platelets syndrome, thrombotic thrombocytopenic purpura, seizures, ischemic and hemorrhagic stroke, postpartum angiopathy, cerebral sinus thrombosis, amniotic fluid emboli, choriocarcinoma, and acute fatty liver of pregnancy are rare but can be devastating. These conditions can present a challenge to physicians because pregnancy is a unique physiologic state, most therapeutic options available in the intensive care unit were not studied in pregnant patients, and in many situations, physicians need to deliver care to both the mother and the fetus, simultaneously. Timely recognition and management of critical neurologic complications of pregnancy/puerperum can be life saving for both the mother and fetus.

  11. Preeclampsia-like symptoms induced in mice by fetoplacental expression of STOX1 are reversed by aspirin treatment.

    Science.gov (United States)

    Doridot, Ludivine; Passet, Bruno; Méhats, Céline; Rigourd, Virginie; Barbaux, Sandrine; Ducat, Aurélien; Mondon, Françoise; Vilotte, Marthe; Castille, Johann; Breuiller-Fouché, Michelle; Daniel, Nathalie; le Provost, Fabienne; Bauchet, Anne-Laure; Baudrie, Véronique; Hertig, Alexandre; Buffat, Christophe; Simeoni, Umberto; Germain, Guy; Vilotte, Jean-Luc; Vaiman, Daniel

    2013-03-01

    Preeclampsia (PE) is a common human-specific pregnancy disorder defined by hypertension and proteinuria during gestation and responsible for maternal and fetal morbimortality. STOX1, encoding a transcription factor, was the first gene associated with PE as identified by positional cloning approaches. Its overexpression in choriocarcinoma cells mimics the transcriptional consequences of PE in the human placenta. Here, we created transgenic mouse strains overexpressing human STOX1. Wild-type female mice crossed with transgenic male mice reproduce accurately the symptoms of severe PE: gestational hypertension, proteinuria, and elevated plasma levels of soluble fms-like tyrosine kinase 1 and soluble endoglin. Placental and kidney histology were altered. Symptoms were prevented or alleviated by aspirin treatment. STOX1-overexpressing mice constitute a unique model for studying PE, allow testing therapeutic approaches, and assessing the long-term effects of the preeclamptic syndrome.

  12. Recent advances in molecular and cell biology of testicular germ-cell tumors.

    Science.gov (United States)

    Chieffi, Paolo

    2014-01-01

    Testicular germ-cell tumors (TGCTs) are the most frequent solid malignant tumors in men 20-40 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs comprise two major histologic groups: seminomas and nonseminomas germ-cell tumors (NSGCTs). NSGCTs can be further divided into embryonal, carcinoma, Teratoma, yolk sac tumor, and choriocarcinoma. Seminomas and NSGCTs present significant differences in clinical features, therapy, and prognosis, and both show characteristics of the primordial germ cells. Many discovered biomarkers including OCT3/4, SOX2, SOX17, HMGA1, Nek2, GPR30, Aurora-B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups and could represent useful novel molecular targets for antineoplastic strategies. More insight into the pathogenesis of TGCTs is likely to improve disease management not only to better treatment of these tumors but also to a better understanding of stem cells and oncogenesis.

  13. Endocrine disrupting potentials of Bisphenol A, Bisphenol A dimethacrylate, 4-n-Nonyl-phenol and 4-Octylphenol assessed in cell model systems for effects on the estrogen-, androgen-, aryl hydrocarbon-receptor and aromatase activity

    DEFF Research Database (Denmark)

    Bonefeld-Jørgensen, Eva Cecilie; Long, Manhai; Hofmeister, Marlene V;

    used as surfactants. We have investigated the effect in vitro of these four plasticizers in four cell culture model systems.The estrogenic potencies were analyzed using the stable ERE-luciferase transfected cell line MVLN measuring the relative estrogen receptor (ER) transactivated luciferase units...... in the conversion of androgens to estrogens in an array of cells, were assessed in the human choriocarcinoma JEG-3 cells using the classical [3H]2O assay. Trans-activation of the Aryl hydrocarbon receptor (AhR) was determined in the mouse hepatoma Hepa1.12cR cell line, stable transfected by an AhR-CALUX construct...... determining RLU. All four compounds elicited a response in each of the four bioassays. Thus, our in vitro data clearly indicates that the four tested plasticizers have ED potentials and that such effects can be mediated via several cellular pathway systems including the estrogen- and the androgen hormones...

  14. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

    Science.gov (United States)

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang

    2014-01-01

    Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

  15. Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines

    Directory of Open Access Journals (Sweden)

    Feix Sonja

    2010-10-01

    Full Text Available Abstract Background Matrix metalloproteinases (MMPs are involved in the degradation of protein components of the extracellular matrix and thus play an important role in tumor invasion and metastasis. Their expression is related to the progression of gynecological cancers (e.g. endometrial, cervical or ovarian carcinoma. In this study we investigated the expression pattern of the 23 MMPs, currently known in humans, in different gynecological cancer cell lines. Methods In total, cell lines from three endometrium carcinomas (Ishikawa, HEC-1-A, AN3 CA, three cervical carcinomas (HeLa, Caski, SiHa, three chorioncarcinomas (JEG, JAR, BeWo, two ovarian cancers (BG-1, OAW-42 and one teratocarcinoma (PA-1 were examined. The expression of MMPs was analyzed by RT-PCR, Western blot and gelatin zymography. Results We demonstrated that the cell lines examined can constitutively express a wide variety of MMPs on mRNA and protein level. While MMP-2, -11, -14 and -24 were widely expressed, no expression was seen for MMP-12, -16, -20, -25, -26, -27 in any of the cell lines. A broad range of 16 MMPs could be found in the PA1 cells and thus this cell line could be used as a positive control for general MMP experiments. While the three cervical cancer cell lines expressed 10-14 different MMPs, the median expression in endometrial and choriocarcinoma cells was 7 different enzymes. The two investigated ovarian cancer cell lines showed a distinctive difference in the number of expressed MMPs (2 vs. 10. Conclusions Ishikawa, Caski, OAW-42 and BeWo cell lines could be the best choice for all future experiments on MMP regulation and their role in endometrial, cervical, ovarian or choriocarcinoma development, whereas the teratocarcinoma cell line PA1 could be used as a positive control for general MMP experiments.

  16. Therapy and prognosis of testicular carcinomas in relation to TNM classification

    Energy Technology Data Exchange (ETDEWEB)

    Batata, M.A.; Chu, F.C.H.; Hilaris, B.S.; Papantoniou, P.A.; Whitmore, W.F. Jr.; Golbey, R.B.

    1982-08-01

    Eight-hundred and thirty-one patients with testicular carcinomas, either teratocarcinoma (405), embryonal carcinoma (406) or pure choriocarcinoma (20), treated mainly at our center from 1950 to 1976, were clinicopathologically staged according to the TNM Classification. The cancer was confined to the body of testis alone (T/sub 1/N/sub 0/M/sub 0/) or extended to paratesticular structures (T/sub 2-4/N/sub 0/M/sub 0/) in 37% of all patients. Para-aortic lymph nodes were found involved (N/sub 1-3/) in 33% and juxtaregional lymph nodes (N/sub 4/) in 9% of patients; distant metastases were detected initially in the lung alone (M/sub 1/) and other distant organs (M/sub 2/) in 21% of the patients. Postorchiectomy treatment was retroperitoneal lymphadenectomy with or without regional-juxtaregional irradiation and systemic chemotherapy in 470 patients; the other 361 patients received external irradiation and/or adjuvant chemotherapy. Survival determined at 5 years was 58% in teratocarcinoma cases, 41% in embryonal carcinoma cases and 0% in pure choriocarcinoma cases. Rates of 5-year survival according to the TNM staging were 81% for T/sub 1/N/sub 0/M/sub 0/ tumors, 58% for T/sub 2-4/N/sub 0/M/sub 0/ tumors, 44% for N/sub 1-3/M/sub 0/ tumors, 33% for N/sub 4/M/sub 0/ tumors and 10% for N/sub 0-4/M/sub 1 or 2/ tumors.

  17. Cannabidiol changes P-gp and BCRP expression in trophoblast cell lines

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    Valeria Feinshtein

    2013-09-01

    Full Text Available Objectives. Marijuana is the most commonly used illicit drug during pregnancy. Due to high lipophilicity, cannabinoids can easily penetrate physiological barriers like the human placenta and jeopardize the developing fetus. We evaluated the impact of cannabidiol (CBD, a major non-psychoactive cannabinoid, on P-glycoprotein (P-gp and Breast Cancer Resistance Protein (BCRP expression, and P-gp function in a placental model, BeWo and Jar choriocarcinoma cell lines (using P-gp induced MCF7 cells (MCF7/P-gp for comparison. Study design. Following the establishment of the basal expression of these transporters in the membrane fraction of all three cell lines, P-gp and BCRP protein and mRNA levels were determined following chronic (24–72 h exposure to CBD, by Western Blot and qPCR. CBD impact on P-gp efflux function was examined by uptake of specific P-gp fluorescent substrates (calcein-AM, DiOC2(3 and rhodamine123(rh123. Cyclosporine A (CsA served as a positive control. Results. Chronic exposure to CBD resulted in significant changes in the protein and mRNA levels of both transporters. While P-gp was down-regulated, BCRP levels were up-regulated in the choriocarcinoma cell lines. CBD had a remarkably different influence on P-gp and BCRP expression in MCF7/P-gp cells, demonstrating that these are cell type specific effects. P-gp dependent efflux (of calcein, DiOC2(3 and rh123 was inhibited upon short-term exposure to CBD. Conclusions. Our study shows that CBD might alter P-gp and BCRP expression in the human placenta, and inhibit P-gp efflux function. We conclude that marijuana use during pregnancy may reduce placental protective functions and change its morphological and physiological characteristics.

  18. Gene expression arrays reveal a rapid return to normal homeostasis in immunologically-challenged trophoblast-like JAR cells.

    Science.gov (United States)

    Jarvis, James N; Dozmorov, Igor; Jiang, Kaiyu; Chen, Yanmin; Frank, Mark Barton; Cadwell, Craig; Turner, Sean; Centola, Michael

    2004-04-01

    The immunologic adaptations of pregnancy have come under increasing scrutiny in the past 15 years. Existing experimental evidence clearly demonstrates that placental trophoblasts play an important role in regulating immunologic/inflammatory responses at the maternal-fetal interface. We used a well-developed gene expression array to examine in greater detail the physiologic response of trophoblast-like choriocarcinoma cells to a model immunologic 'challenge.' We co-cultured PHA-activated or resting peripheral blood mononuclear cells (PBMC) with the human choriocarcinoma cell line JAR for time periods ranging from 2 to 18 h. Messenger RNA expression in the JAR cells was then assessed using a 21,329-gene microarray and novel biostatistical analyses that we have previously published. Patterns of differential gene expression were assessed using a commercial pathway analysis software program. Differences in gene expression between JAR cells cultured with activated PBMC (experimental samples) and JAR cells cultured with resting PBMC (control samples) were seen only at the 2h time point. That is, multiple genes were transcribed in JAR cells in response to activated PBMC, but expression levels of the genes had all returned to baseline by 6h. Molecular modeling demonstrated that the differentially expressed genes were largely associated with cell growth and differentiation. This model was confirmed by noting a two-fold increase in CD10/neutral endopeptidase expression (a marker for cell differentiation) in JAR cells incubated with media from activated PBMC compared with JAR cells incubated with resting PBMC. These findings support the hypothesis that there is a delicate immunologic milieu at the maternal-fetal interface that must be maintained. Immunologic/inflammatory challenge at the maternal-fetal interface is compensated by cellular mechanisms that work to reduce inflammation and rapidly restore immunologic balance.

  19. Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms.

    Directory of Open Access Journals (Sweden)

    Helen N Jones

    Full Text Available Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor -1 (hIGF-1 in the placenta corrects fetal weight deficits in mouse, rat, and rabbit models of intrauterine growth restriction without changes in placental weight. The underlying mechanisms of this effect have not been elucidated. To investigate the effect of intra-placental IGF-1 over-expression on placental function we examined glucose transporter expression and localization in both a mouse model of IUGR and a model of human trophoblast, the BeWo Choriocarcinoma cell line.At gestational day 18, animals were divided into four groups; sham-operated controls, uterine artery branch ligation (UABL, UABL+Ad-hIGF-1 (10(8 PFU, UABL+Ad-LacZ (10(8 PFU. At gestational day 20, pups and placentas were harvested by C-section. For human studies, BeWo choriocarcinoma cells were grown in F12 complete medium +10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 hours. MOIs of 10∶1 and 100∶1 were utilized. The RNA, protein expression and localization of glucose transporters GLUT1, 3, 8, and 9 were analyzed by RT-PCR, Western blot and immunohistochemistry.In both the mouse placenta and BeWo, GLUT1 regulation was linked to altered protein localization. GLUT3, localized to the mouse fetal endothelial cells, was reduced in placental insufficiency but maintained with Ad-I GF-1 treatment. Interestingly, GLUT8 expression was reduced in the UABL placenta but up-regulated following Ad-IGF-1 in both mouse and human systems. GLUT9 expression in the mouse was increased by Ad-IGF-1 but this was not reflected in the BeWo, where Ad-IGF-1 caused moderate membrane relocalization.Enhanced GLUT isoform transporter expression and relocalization to the membrane may be an important mechanism in Ad-hIGF-1mediated correction of placental insufficiency.

  20. MR imaging findings of pineal germinoma: focus on differential diagnosis from other germ cell tumors

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    Kim, Hyun Jin; Lee, Ho Kyu; Kim, Jae Kyun; Shin, Ji Hoon; Choi, Choong Gon; Lee, Myung Jun; Ham, Soo Youn; Lee, Jong Hwa; Suh, Dae Chul [Ulsan Univ. College of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    To determine the characteristic MR imaging findings of pineal germinoma, and differential diagnosis from other germ cell tumors. MR images of patients with histopathologically proven pineal germinoma(n=3D14) and other pineal germ cell tumors(n=3D10) were retrospectively analyzed with regard to size, signal intensity and homogeneity, enhancing features, cyst formation, and multiplicity of lesions. Other pineal germ cell tumors were the mixed germ cell tumors (n=3D4), malignant teratomas (n=3D3), choriocarcinoma(n=3D1), embryonal carcinoma(n=3D1), and endodermal sinus tumor(n=3D1). Tumor markers were evaluated. On T1-weighted images, germinomas showed homogeneous(86%) or iso signal intensity (93%), while other germ cell tumors showed inhomogeneous(70%) or iso signal intensity(70%). On T2-weighted images, germinomas showed homogeneous(64%) or iso signal intensity(57%), while other germ cell tumors showed inhomogeneous(70%) or high signal intensity(80%). On Gd-DTPA enhanced images, germinomas showed homogeneous (93%) or strong enhancement (64%), while other germ cell tumors showed homogeneous(60%) or strong enhancement (70%). Cyst formation was noted in ten Patients (71%) with germinoma and in six (60%) with other germ cell tumors. Invasion on surrounding structures was seen in 11 patients (79%) with germinoma and in five (50%) with other germ cell tumors. Lesions were multiple in three patients(21%) with germinoma. Thirteen of 14 patients with germinoma had normal serum {alpha}-FP(tetoprotein) and {beta}-HCG(human chononic gonafotrophin) levels. Two of four patients with mixed germ cell tumors had elevated serum {beta}-FP and {alpha}-HCG levels; in the ther two, elevated serum {alpha}-FP or {beta}-HCG levels were noted. In the malignant teratoma and embryonal carcinoma patients, serum {alpha}-FP and {beta}-HCG levels were normal. The patient with choriocarcinoma had an elevated serum {beta}-HCG level. On T1W1, the only significant differential point (p<0.01) between

  1. Therapy and prognosis of testicular carcinomas in relation to TNM classification.

    Science.gov (United States)

    Batata, M A; Chu, F C; Hilaris, B S; Papantoniou, P A; Whitmore, W F; Golbey, R B

    1982-08-01

    Eight-hundred and thirty-one patients with testicular carcinomas, either teratocarcinoma (405), embryonal carcinoma (406) or pure choriocarcinoma (20), treated mainly at our center from 1950 to 1976, were clinicopathologically staged according to the TNM Classification. The cancer was confined to the body of testis alone (T1 N0 M0) or extended to paratesticular structures (T2-4 N0 M0) in 37% of all patients. Para-aortic lymph nodes were found involved (N1-3) in 33% and juxtaregional lymph nodes (N4) in 9% of patients; distant metastases were detected initially in the lung alone (M1) and other distant organs (M2) in 21% of the patients. Postorchiectomy treatment was retroperitoneal lymphadenectomy with or without regional-juxtaregional irradiation and systemic chemotherapy in 470 patients; the other 361 patients received external irradiation and/or adjuvant chemotherapy. Survival determined at 5 years was 58% in teratocarcinoma cases, 41% in embryonal carcinoma cases and 0% in pure choriocarcinoma cases. Rates of 5-year survival according to the TNM staging were 81% for T1 N0 M0 tumors, 58% for T2-4 N0 M0 tumors, 44% for N1-3 M0 tumors, 33% for N4 M0 tumors and 10% for N0-4 M1 or 2 tumors. In patients who underwent lymphadenectomy with or without external irradiation, the 5-year survival rates with and without adjuvant chemotherapy, respectively, were 96% and 86% for T1 N0 M0 tumors, 100% and 60% for T2-4 N0 M0 tumors, 66% and 42% for N1-3 M0 tumors, 54% and 40% for N4 M0 tumors and 38% and 0% for N0-4 M1 tumors. In patients treated by external irradiation alone or following lymphadenectomy the rates of 5-year survival with versus without adjuvant chemotherapy were 100% versus 66% for T1-4 N0 M0 tumors, 44% versus 18% for N1-3 M0 tumors, 41% versus 22% for N4 M0 tumors and 3% versus 4% for N0-4 M1-2 tumors.

  2. [Two Cases of Germ Cell Tumors with Hyperthyroidism Due to High Serum hCGLevels].

    Science.gov (United States)

    Chihara, Ichiro; Nitta, Satoshi; Kimura, Tomokazu; Kandori, Shuya; Kawahara, Takashi; Waku, Natsui; Kojima, Takahiro; Joraku, Akira; Miyazaki, Jun; Iwasaki, Hitoshi; Suzuki, Hiroaki; Kawai, Koji; Nishiyama, Hiroyuki

    2016-09-01

    We reported two cases of hyperthyroidism that developed during induction chemotherapy for advanced germ cell tumors with high serum human chorionic gonadotropin (hCG) levels. Case 1 : An 18-year-old man with mediastinal choriocarcinoma complained of tachycardia and tremor. His pretreatment serum hCG level was 1.37 million mIU/ml. The free thyroxine (fT4) level measured on day 2 of the first course of bleomycin, etoposide and cisplatin (BEP) was elevated to 7.8 ng/dl (<1.7 ng/dl), whereasthe thyroidstimulating hormone (TSH) level was undetectable. We diagnosed the patient with hyperthyroidism and started oral propranolol and thiamazole. Subsequently, his tachycardia and tremor disappeared. On day 12 of the first course of BEP, his hCG level decreased to less than 50,000 mIU/ml. Also, his fT4 level returned to the normal range. Case 2 : A 29-year-old man presented with a left scrotal mass. He was diagnosed with non-seminoma testicular cancer (embryonal carcinoma and choriocarcinoma) with multiple lung, liver and lymph node metastases. On the admission day, his serum hCG and fT4 levels were high ; 3.23 million mIU/ml and 2.2 ng/dl, respectively. The TSH level was low at 0.011 mIU/ml. On day 3 of the first course of BEP, his hCG and fT4 levels increased to 4.5 million mIU/ml and 3.0 ng/dl, respectively. He complained of tachycardia, tremor and hyperhydrosis. He was started on propranolol and potassium iodide. After the treatment, histachycardia, tremor and hyperhidrosisdis appeared. HisfT4 level normalized on day 17 of the first course of BEP. The TSH-like activity of hCG is considered to be responsible for paraneoplastic hyperthyroidism among germ cell cancer patients with high hCG levels. To our knowledge, thisisthe first report of such a case in Japan. However, thisphenomenon isnot rare among patients with extremely high hCG levels. Therefore, we should be careful of these patients.

  3. Investigation of Risk Factors, Stage and Outcome in Patients with Gestational Trophoblastic Disease since 2001 to 2011 in Iran-Yazd

    Science.gov (United States)

    Karimi-Zarchi, Mojgan; Mortazavizadeh, Mohammad Reza; Soltani-Gerdefaramrzi, Malihe; Rouhi, Mitra; Yazdian-Anari, Pouria; Ahmadiyeh, Mohammad Hosain

    2015-01-01

    Background and Aim: Gestational trophoblastic disease (GTN) is one of the high-risk forms of pregnancy that requires a lot of attention in terms of research studies, considering its incidence and the importance of the disease in advanced form. The aim of this study was to investigate the risk factors and clinical procedure of patients with gestational trophoblastic disease from 2001 to 2002. Method of Study: This is a retrospective descriptive study, which was carried out on 150 patients with trophoblastic disease. These patients’ files were obtained from Shohadaye Kargar and Shahid Sadoughi hospitals and women’s oncology offices of Yazd city. The patients were contacted one by one and their disease situation was determined. The data obtained were recorded in a questionnaire and analyzed by SPSS software. Result: The results indicated that the average age of the patients was 27.65 ± 8.22 with variations in age ranging from 15 to 35 year. In addition, majorities were in the age group of 20 to 40 years. 43.2 percent of the women were affected during their first gestation. 4% had molar gestation record, and 9.4% had positive family record. Mean time of survival was 93.38 ± 0.62 months (MIN ± SE), and only one died owing to chemotherapy complication. Vaginal bleeding (90%) was the most common symptom. 54.6 percent of the disease had complete mole, 30% had incomplete mole, 8.6% had invasive mole, 4.6% had choriocarcinoma and 2% had placenta site trophoblastic tumor (PSTT). Among the patients studied, 28.7% were benign in GTN group while 71.3 % were malignant in the GTN group. The malignant patients were divided into three groups per risk, and 41.2% were in the high-risk group. There was theca-lutein cyst in 54% of the patients, which had a significant relationship with the disease risk of persistent GTN. Conclusion: Choriocarcinoma and invasive mole is the most malignant pathology. There was significant relationship between disease interval and the beginning of

  4. Effects of nutrition relevant mixtures of phytoestrogens on steroidogenesis, aromatase, estrogen, and androgen activity.

    Science.gov (United States)

    Taxvig, Camilla; Elleby, Anders; Sonne-Hansen, Katrine; Bonefeld-Jørgensen, Eva C; Vinggaard, Anne Marie; Lykkesfeldt, Anne E; Nellemann, Christine

    2010-01-01

    Phytoestrogens (PEs) are naturally occurring plant components produced in a large range of plants. They can induce biologic responses in vertebrates by mimicking or modulating the action or production of endogenous hormones. This study examined mixtures of 12 food relevant PEs for effects on steroid hormone production, aromatase activity, estrogenic activity, and for interaction with the androgen receptor. The results show that a mixture of all tested PEs increased estradiol production and decreased testosterone production in H295R human adrenal corticocarcinoma cells, indicating an induced aromatase activity. Furthermore, exposure of the H295R cells to isoflavonoids caused a decrease in testosterone production, and various mixtures of PEs significantly stimulated MCF-7 human breast adenocarcinoma cell growth and induced aromatase activity in JEG-3 choriocarcinoma cells. The estrogenic effect in the MCF7 cells of the isoflavonoid mixture and coumestrol was supported by an observed increase in progesterone receptor protein expression as well as a decreased ERalpha expression. Overall, the results support that nutrition-relevant concentrations of PEs both alone and in mixtures possess various endocrine disrupting effects, all of which need to be considered when assessing the effects on human health.

  5. The first trimester human trophoblast cell line ACH-3P: A novel tool to study autocrine/paracrine regulatory loops of human trophoblast subpopulations – TNF-α stimulates MMP15 expression

    Directory of Open Access Journals (Sweden)

    Knöfler Martin

    2007-12-01

    Full Text Available Abstract Background The trophoblast compartment of the placenta comprises various subpopulations with distinct functions. They interact among each other by secreted signals thus forming autocrine or paracrine regulatory loops. We established a first trimester trophoblast cell line (ACH-3P by fusion of primary human first trimester trophoblasts (week 12 of gestation with a human choriocarcinoma cell line (AC1-1. Results Expression of trophoblast markers (cytokeratin-7, integrins, matrix metalloproteinases, invasion abilities and transcriptome of ACH-3P closely resembled primary trophoblasts. Morphology, cytogenetics and doubling time was similar to the parental AC1-1 cells. The different subpopulations of trophoblasts e.g., villous and extravillous trophoblasts also exist in ACH-3P cells and can be immuno-separated by HLA-G surface expression. HLA-G positive ACH-3P display pseudopodia and a stronger expression of extravillous trophoblast markers. Higher expression of insulin-like growth factor II receptor and human chorionic gonadotropin represents the basis for the known autocrine stimulation of extravillous trophoblasts. Conclusion We conclude that ACH-3P represent a tool to investigate interaction of syngeneic trophoblast subpopulations. These cells are particularly suited for studies into autocrine and paracrine regulation of various aspects of trophoblast function. As an example a novel effect of TNF-α on matrix metalloproteinase 15 in HLA-G positive ACH-3P and explants was found.

  6. A novel feeder-free culture system for human pluripotent stem cell culture and induced pluripotent stem cell derivation.

    Directory of Open Access Journals (Sweden)

    Sanna Vuoristo

    Full Text Available Correct interactions with extracellular matrix are essential to human pluripotent stem cells (hPSC to maintain their pluripotent self-renewal capacity during in vitro culture. hPSCs secrete laminin 511/521, one of the most important functional basement membrane components, and they can be maintained on human laminin 511 and 521 in defined culture conditions. However, large-scale production of purified or recombinant laminin 511 and 521 is difficult and expensive. Here we have tested whether a commonly available human choriocarcinoma cell line, JAR, which produces high quantities of laminins, supports the growth of undifferentiated hPSCs. We were able to maintain several human pluripotent stem cell lines on decellularized matrix produced by JAR cells using a defined culture medium. The JAR matrix also supported targeted differentiation of the cells into neuronal and hepatic directions. Importantly, we were able to derive new human induced pluripotent stem cell (hiPSC lines on JAR matrix and show that adhesion of the early hiPSC colonies to JAR matrix is more efficient than to matrigel. In summary, JAR matrix provides a cost-effective and easy-to-prepare alternative for human pluripotent stem cell culture and differentiation. In addition, this matrix is ideal for the efficient generation of new hiPSC lines.

  7. Kinetics of gold nanoparticles in the human placenta.

    Science.gov (United States)

    Myllynen, Päivi K; Loughran, Michael J; Howard, C Vyvyan; Sormunen, Raija; Walsh, Adrian A; Vähäkangas, Kirsi H

    2008-10-01

    We studied the transfer of PEGylated gold nanoparticles through perfused human placenta. In 'once-through' perfusions using 15 and 30nm nanoparticles both maternal and fetal outflows were collected. Recirculating perfusions using 10 or 15nm nanoparticles lasted 6h. The gold concentration in samples was analysed on ICP-MS. The reference compound antipyrine crossed the placenta rapidly, as expected. In open perfusions nanoparticles were detected in maternal but not in fetal outflow, suggesting the lack of placental transfer. During 6h re-circulating perfusions, no particles were detected in fetal circulation. Using transmission electron microscopy (TEM) and silver enhancement, nanoparticles could be visualized in the placental tissue mainly in the trophoblastic cell layer. In in vitro experiments, nanoparticles were taken up by BeWo choriocarcinoma cells and retained inside the cells for an extended period of 48h. In conclusion, PEGylated gold nanoparticles of the size 10-30nm did not cross the perfused human placenta in detectable amounts into the fetal circulation within 6h. Whether PEGylated gold nanoparticles eventually are able to cross placenta and whether nanoparticles affect placental functions needs to be further studied.

  8. Pathologies of the uterine endometrial cavity: usual and unusual manifestations and pitfalls on magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Mayumi; Matsuzaki, Kenji; Yoshida, Shusaku; Nishitani, Hiromu [University of Tokushima, Department of Radiology, Tokushima (Japan); Uehara, Hisanori [University of Tokushima, Department of Molecular and Environmental Pathology, Tokushima (Japan); Shimazu, Hideki [Oe Kyoudo Hospital, Department of Radiology (Japan)

    2005-11-01

    The endometrial cavity may demonstrate various imaging manifestations such as normal, reactive, inflammatory, and benign and malignant neoplasms. We evaluated usual and unusual magnetic resonance imaging (MRI) findings of the uterine endometrial cavity, and described the diagnostic clues to differential diagnoses. Surgically proven pathologies of the uterine endometrial cavity were evaluated retrospectively with pathologic correlation. The pathologies included benign endometrial neoplasms such as endometrial hyperplasia and polyp, malignant endometrial neoplasms such as endometrial carcinoma and carcinosarcoma, endometrial-myometrial neoplasm such as endometrial stromal sarcoma, pregnancy-related lesions in the endometrial cavity such as gestational trophoblastic diseases (hydatidiform mole, invasive mole and choriocarcinoma) and placental polyp, myometrial lesions simulating endometrial lesions such as submucosal leiomyoma and some adenomyosis, endometrial neoplasms simulating myometrial lesions such as adenomyomatous polyp and endometrial lesions arising in the hemicavity of a septate/bicornate uterus, and fluid collections in the uterine cavity (hydro/hemato/pyometra). It is important to recognize various imaging findings in these diseases, in order to make a correct preoperative diagnosis. (orig.)

  9. THE ROLE OF HYSTERECTOMY IN THE THERAPY OF GESTATIONAL TROPHOBLASTIC TUMOR

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective.To evaluate the role of hysterectomy for patients with gestational trophoblastic tumor.Methods.We retrospectively analyzed 68 cases of gestational trophoblastic neoplasia treated by hysterectomy from 1985~1997 at PUMC hospital. Thirty-eight cases were diagnosed of choriocarcinoma and 30 were invasive mole.Results.Twenty-three elder patients who didn't desire to preserve fertility were selected for hysterectomy after shorter courses of chemotherapy, 22 of them had a complete remission(95.6%), the total aver-age courses of chemotherapy was 4.2. Of twenty-seven chemorefractory cases who were suspected of a refractory isolated lesion in the uterus, delayed hysterectomy as an adjunct to chemotherapy was performed, 20 of them got a complete remission(74.1%), the total average courses of chemotherapy were 9.4. Emergency hysterectomy is indicated in 18 patients with uterine perforation or life-threatening hemorrhage, 17 cases had a complete remission(94.4%), the total average courses of chemotherapy were 7.6.Conclusion.Although the development of effective chemotherapy has resulted in improved survival of patients with gestational trophoblastic tumor, hysterectomy remains an important adjuncts in the treatment of a selected subset of patients; in order to operate more completely and prevent recurrence, it's better to perform extended hysterectomy for the indicated patients.

  10. Cryptorchidism and testicular cancer.

    Science.gov (United States)

    Batata, M A; Whitmore, W F; Chu, F C; Hilaris, B S; Loh, J; Grabstald, H; Golbey, R

    1980-09-01

    An analysis of 125 patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor treated at our hospital from 1934 to 1975 is presented. Cryptorchidism was corrected ipsilaterally or contralaterally in 83 patients with intrascrotal testis cancer when they were from 4 to 42 years old, either spontaneously (21 patients), by orchiopexy (51 patients) or by hormonal therapy (11 patients). Forty-two cryptorchid patients (uncorrected cases) presented with either ipsilateral inguinal (24 patients), abdominal (14 patients) or contralateral intrascrotal tumors (4 patients). Tumor histologic types on orchiectomy were pure seminoma in 54 patients, embryonal carcinoma in 35, teratocarcinoma in 33 and pure choriocarcinoma in 3. The 5-year survival rates were 60 per cent for the corrected cases and 63 per cent for the uncorrected cases according to cryptorchid state, and they were 78 per cent in patients with pure seminoma and 48 per cent in patients with other germinomas according to histologic type. The majority (58 of 73) of 5-year survivors received regional lymphatic irradiation, in 39 patients with pure seminoma, and/or systemic chemotherapy, in 19 patients with germinal carcinomas, with or without regional lymphadenectomy.

  11. Testicular cancer in cryptorchids.

    Science.gov (United States)

    Batata, M A; Chu, F C; Hilaris, B S; Whitmore, W F; Golbey, R B

    1982-03-01

    One-hundred thirty-seven patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor were treated at our hospital from 1934 to 1976. Cryptorchidism was corrected ipsilaterally or contralaterally in 93 patients with intrascrotal testis cancer when they were from 2 to 42 years old, either spontaneously (24 patients), by orchiopexy (58 patients), or by hormonal therapy (11 patients). Forty-four cryptorchid patients (uncorrected cases) had either ipsilateral inguinal (24 patients), or abdominal (14 patients), or contralateral intrascrotal tumors (six patients). Tumor histologic types on orchiectomy were pure seminoma in 56 patients, embryonal carcinoma in 41, teratocarcinoma in 37, and pure choriocarcinoma in 3. The five-year survival rates were similar in the corrected (61%) and uncorrected (63%) cases, and they were higher in patients with pure seminoma (79%) than in patients with germinal carcinomas (50%). The majority (64 of 80) of five-year survivors received regional lymphatic irradiation in 41 patients with pure seminoma and/or systemic chemotherapy in 23 patients with other germinomas. Since the testicular tumors that developed despite correction of the cryptorchid state were predominantly (72%) germinal carcinomas, unilateral cryptorchidism, which usually is associated with testicular atrophy, should be treated by orchiectomy instead of orchiopexy to prevent ipsilateral carcinogenesis. Cryptorchid patients with testicles that descended late should be observed periodically, especially after the 20-year latent period, for early detection of cancer.

  12. Overexpressed ubiquitin ligase Cullin7 in breast cancer promotes cell proliferation and invasion via down-regulating p53

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Hongsheng [Department of Histology and Embryology, Guangdong Medical College, Dongguan 523808, Guangdong (China); Wu, Fenping [The 7th People’s Hospital of Chengdu, Chengdu 610041, Sichuan (China); Wang, Yan [The Second School of Clinical Medicine, Guangdong Medical College, Dongguan 523808, Guangdong (China); Yan, Chong [School of Pharmacy, Guangdong Medical College, Dongguan 523808, Guangdong (China); Su, Wenmei, E-mail: wenmeisutg@126.com [Oncology of Affiliated Hospital Guangdong Medical College, Zhanjiang 524000, Guangdong (China)

    2014-08-08

    Highlights: • Cullin7 is overexpressed in human breast cancer samples. • Cullin7 stimulated proliferation and invasion of breast cancer cells. • Inhibition of p53 contributes to Cullin7-induced proliferation and invasion. - Abstract: Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in breast cancer carcinogenesis remains unclear. In this study, we compared Cullin7 protein levels in breast cancer tissues with normal breast tissues and identified significantly higher expression of Cullin7 protein in breast cancer specimens. By overexpressing Cullin7 in breast cancer cells HCC1937, we found that Cullin7 could promote cell growth and invasion in vitro. In contrast, the cell growth and invasion was inhibited by silencing Cullin7 in breast cancer cell BT474. Moreover, we demonstrated that Cullin7 promoted breast cancer cell proliferation and invasion via down-regulating p53 expression. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in breast cancer and may be a potential therapeutic target for breast cancer management.

  13. [Genetics of hydatidiform moles].

    Science.gov (United States)

    Brackertz, M

    1983-07-01

    Newer genetic investigations show that the complete or classical hydatidiform mole has in over 90% of the cases a diploid female set of chromosomes which is exclusively of paternal origin. The 23 X sperm genom is doubled and the nucleus of the ovocyte is degenerated. In contradistinction the nucleus of the ovocyte persists in partial moles. The normal ontogenesis is also disturbed by a preponderance of paternal genetic material. By melting of 2 instead of 1 paternal germ cell (Dispermia) the genom of partial moles is to 1/3 of maternal and to 2/3 of paternal origin. The triploid set of chromosomes shows usually 69xxy. Whereas the potential of malignancy of partial moles is low a choriocarcinoma results from 2 to 10% of the complete moles. Responsible maybe recessive hereditary mutations of growth controlling genes, which are present in complete moles in a homozygote form due to the doubling of a single paternal set of chromosomes. Total absence of the growth controlling loci of these genes maternally permits an unhibited expression of the growth controlling paternal genes.

  14. Differential transferrin expression in placentae from normal and abnormal pregnancies: a pilot study

    Directory of Open Access Journals (Sweden)

    Bukovsky Antonin

    2008-07-01

    Full Text Available Abstract Background The placenta is an important site for iron metabolism in humans. It transfers iron from the mother to the fetus. One of the major iron transport proteins is transferrin, which is a blood plasma protein crucial for iron uptake. Its localization and expression may be one of the markers to distinguish placental dysfunction. Methods In the experimental study we used antibody preparation, mass spectrometric analysis, biochemical and immunocytochemical methods for characterization of transferrin expression on the human choriocarcinoma cell line JAR (JAR cells, placental lysates, and cryostat sections. Newly designed monoclonal antibody TRO-tf-01 to human transferrin was applied on human placentae from normal (n = 3 and abnormal (n = 9 pregnancies. Results Variations of transferrin expression were detected in villous syncytiotrophoblast, which is in direct contact with maternal blood. In placentae from normal pregnancies, the expression of transferrin in the syncytium was significantly lower (p Conclusion These observations suggest that in the case of abnormal pregnancies, the fetus may require higher levels of transferrin in order to prevent iron depletion due to the stress from the placental dysfunction.

  15. Acquired uterine vascular malformations: radiological and clinical outcome after transcatheter embolotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Maleux, Geert; Heye, Sam; Wilms, Guy [University Hospitals Gasthuisberg, Department of Radiology, Leuven (Belgium); Timmerman, Dirk [University Hospitals Gasthuisberg, Department of Obstetrics and Gynecology, Leuven (Belgium)

    2006-02-01

    The purpose of this retrospective study is to assess the radiological and clinical outcome of transcatheter embolization of acquired uterine vascular malformations in patients presenting with secondary postpartum or postabortion vaginal hemorrhage. In a cohort of 17 patients (mean age: 29.7 years; standard deviation: 4.23; range: 25-38 years) 18 embolization procedures were performed. Angiography demonstrated a uterine parenchymal hyperemia with normal drainage into the large pelvic veins (''low-flow uterine vascular malformation'') in 83% (n=15) or a direct arteriovenous fistula (''high-flow uterine vascular malformation'') in 17% (n=3). Clinically, in all patients the bleeding stopped after embolization but in 1 patient early recurrence of hemorrhage occurred and was treated by hysterectomy. Pathological analysis revealed a choriocarcinoma. During follow-up (mean time period: 18.8 months; range: 1-36 months) 6 patients became pregnant and delivered a healthy child. Transcatheter embolization of the uterine arteries, using microparticles, is safe and highly effective in the treatment of a bleeding acquired uterine vascular malformation. In case of clinical failure, an underlying neoplastic disease should be considered. Future pregnancy is still possible after embolization. (orig.)

  16. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  17. B-esterase determination and organophosphate insecticide inhibitory effects in JEG-3 trophoblasts.

    Science.gov (United States)

    Espinoza, Marlon; Rivero Osimani, Valeria; Sánchez, Victoria; Rosenbaum, Enrique; Guiñazú, Natalia

    2016-04-01

    The placenta and trophoblasts express several B-esterases. This family includes acethylcholinesterase (AChE), carboxylesterase (CES) and butyrylcholinesterase (BChE), which are important targets of organophosphate insecticide (OP) toxicity. To better understand OP effects on trophoblasts, B-esterase basal activity and kinetic behavior were studied in JEG-3 choriocarcinoma cell cultures. Effects of the OP azinphos-methyl (Am) and chlorpyrifos (Cp) on cellular enzyme activity were also evaluated. JEG-3 cells showed measurable activity levels of AChE and CES, while BChE was undetected. Recorded Km for AChE and CES were 0.33 and 0.26 mM respectively. Native gel electrophoresis and RT-PCR analysis demonstrated CES1 and CES2 isoform expression. Cells exposed for 4 and 24 h to the OP Am or Cp, showed a differential CES and AChE inhibition profiles. Am inhibited CES and AChE at 4 h treatment while Cp showed the highest inhibition profile at 24 h. Interestingly, both insecticides differentially affected CES1 and CES2 activities. Results demonstrated that JEG-3 trophoblasts express AChE, CES1 and CES2. B-esterase enzymes were inhibited by in vitro OP exposure, indicating that JEG-3 cells metabolization capabilities include phase I enzymes, able to bioactivate OP. In addition, since CES enzymes are important for medicinal drug activation/deactivation, OP exposure may interfere with trophoblast CES metabolization, probably being relevant in a co-exposure scenario during pregnancy.

  18. PPAR-γ Regulates Trophoblast Differentiation in the BeWo Cell Model

    Directory of Open Access Journals (Sweden)

    Khrystyna Levytska

    2014-01-01

    Full Text Available Common pregnancy complications, such as severe preeclampsia and intrauterine growth restriction, disrupt pregnancy progression and impair maternal and fetal wellbeing. Placentas from such pregnancies exhibit lesions principally within the syncytiotrophoblast (SCT, a layer in direct contact with maternal blood. In humans and mice, glial cell missing-1 (GCM-1 promotes differentiation of underlying cytotrophoblast cells into the outer SCT layer. GCM-1 may be regulated by the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-γ; in mice, PPAR-γ promotes labyrinthine trophoblast differentiation via Gcm-1, and, as we previously demonstrated, PPAR-γ activation ameliorates disease features in rat model of preeclampsia. Here, we aimed to characterize the baseline activity of PPAR-γ in the human choriocarcinoma BeWo cell line that mimics SCT formation in vitro and modulate PPAR-γ activity to study its effects on cell proliferation versus differentiation. We report a novel negative autoregulatory mechanism between PPAR-γ activity and expression and show that blocking PPAR-γ activity induces cell proliferation at the expense of differentiation, while these remain unaltered following treatment with the agonist rosiglitazone. Gaining a deeper understanding of the role and activity of PPAR-γ in placental physiology will offer new avenues for the development of secondary prevention and/or treatment options for placentally-mediated pregnancy complications.

  19. The CK1 family: contribution to cellular stress response and its role in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Uwe eKnippschild

    2014-05-01

    Full Text Available Members of the highly conserved and ubiquitously expressed pleiotropic CK1 family play major regulatory roles in many cellular processes including DNA-processing and repair, proliferation, cytoskeleton dynamics, vesicular trafficking, apoptosis, and cell differentiation. As a consequence of cellular stress conditions, interaction of CK1 with the mitotic spindle is manifold increased pointing to regulatory functions at the mitotic checkpoint. Furthermore, CK1 is able to alter the activity of key regulatory proteins and signal integration molecules and is tightly connected to the regulation of β-catenin, p53- and MDM2-specific functions and degradation. Considering the importance of CK1 for accurate cell division and regulation of tumor suppressor functions it is not surprising that mutations and alterations in the expression and/or activity of CK1 isoforms are often detected in various tumor entities including cancer of the kidney, choriocarcinomas, breast carcinomas, oral cancer, adenocarcinomas of the pancreas, and ovarian cancer. Therefore, effort has enormously increased (i to understand the regulation of CK1 and its involvement in tumorigenesis- and tumor progression-related signal transduction pathways and (ii to develop CK1-specific inhibitors for the use in personalized therapy concepts. In this review we summarize the current knowledge regarding the regulation, functions, and interactions of CK1 family members with cellular proteins playing central roles in cellular stress-responses and carcinogenesis.

  20. Clinical significance of three-dimensional sonohysterography

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Hye; Lee, Mi Hwa; Lee, Chan; Kim, Jong Wook; Shin, Myung Choel [Pochon Cha University College of Medicine, Pochon (Korea, Republic of)

    1999-12-15

    To evaluate the usefulness of three dimensional sonohysterography (3D SHG) in the evaluation of uterine endometrial and submucosal lesions in comparison with conventional two-dimensional sonohysterography (2D SHG). Our series consisted of 26 patients (mean aged 41 years) who complained of uterine bleeding, menorrhagia, or dysmenorrhea. 2D SHG was performed, and then 3D SHG was done after the volume mode was switched on. Simultaneous display of three perpendicular two-dimensional planes and surface rendering of findings on particular section were obtained. We analyzed whether the endometrium was thickened or not, and the location, size, shape, echogenicity, posterior shadowing, and echogenic rim of the focal lesion. The results were compared with the pathologic findings or MRI. There were submucosal myomas (n=12), intramural myomas (n=2), endometrial polyps (n=7), placental polyp (n=1), and normal endometrial cavities (n=4) on SHG. Nineteen cases were confirmed by pathologic findings or MRI. The results were correlated in 89% (17/19) of the cases. We misdiagnosed 2 cases: focal endometrial hyperplasia and choriocarcinoma were misdiagnosed as endometrial polyp and placental polyp, respectively. Imaging diagnoses were same in the techniques. Comparing with 2D SHG, 3D SHG provided a subjective display of pathologic findings and an additional information about spatial relationship between focal lesion and surroundings.

  1. Histopathological study of endometrium in cases of abnormal uterine bleeding

    Directory of Open Access Journals (Sweden)

    Saroj A. Bolde

    2014-08-01

    Full Text Available Background: Abnormal uterine bleeding is one of the commonest complaints in women and when it occurs without organic lesions like tumor, inflammation, it is called as dysfunctional uterine bleeding. Aim of current study was to find out the histopathological pattern of endometrium in Abnormal Uterine Bleeding (AUB also to study organic causes of AUB. Methods: Specimens received as endometrial curettage and hysterectomy specimens were studied followed by correlation of histopathology with age and clinical presentation. Results: The patients were mainly from the age group of 30-49 years (74.24%. The most common menstrual disorder was menorrhagia (46.86%. In dysfunctional uterine bleeding the most common histological pattern of endometrium includes proliferative endometrium (22.8% followed by endometrial hyperplasia (19.40%, atrophic endometrium (7.16%, secretory endometrium (5.97%, irregular shedding [1.80%], irregular ripening (1.20% and anovulatory endometrium (0.59%. Organic lesions encountered in AUB cases were leiomyoma (17.92%, endometrial polyp (1.79%, endometrial carcinoma (1.50%, endometriosis (0.59% and choriocarcinoma (0.29%. Conclusion: It is important to know the histological pattern of the endometrium like proliferative endometrium, endometrial hyperplasia, atrophic endometrium, secretory endometrium, irregular ripening and shredding and organic lesions in patients diagnosed as AUB in different age groups since recognition of these conditions will help and will avoid further complications. [Int J Res Med Sci 2014; 2(4.000: 1378-1381

  2. Design, Synthesis, Anticancer Pharmacology of Actinomycin D Analogues: 5,5' -MeSer2-ActD and 5,5' -MeAla2-ActD

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@ Introduction Actinomycin D (ActD, Figure 1.), containing a planar phenoxazone ring and two cyclic pentapeptides, is one of the most intensely studied anticancer drugs and currently used to treat highly malignant tumors, such as Wilms' tumor and gestational choriocarcinoma. Although ActD possesses high antitumor activities, its clinical usefulness is limited by its extreme cytotoxicity. Thus, if the structure of ActD can be modified to reduce its cytotoxicity while retaining its activity, such an analogue would be a better antitumor drug. On the basis of X-ray crystal structures of the complexes between ActD and DNA[1], and our work [2], we designed and totally synthesized two ActD analogs 8a-b iii which both of the (L)-N-methyl-valine residues of ActD were replaced with LN-MeAla and L-N-MeSer, respectively. The anticancer pharmacology of the two analogs were examined. The result shows that the toxicity of the two analogs are higher than ActD and the antitumoe activity are lower than ActD, too.

  3. Design, Synthesis, Anticancer Pharmacology of Actinomycin D Analogues: 5,5' -MeSer2-ActD and 5,5' -MeAla2-ActD

    Institute of Scientific and Technical Information of China (English)

    NI; JingMan

    2001-01-01

    Introduction  Actinomycin D (ActD, Figure 1.), containing a planar phenoxazone ring and two cyclic pentapeptides, is one of the most intensely studied anticancer drugs and currently used to treat highly malignant tumors, such as Wilms' tumor and gestational choriocarcinoma. Although ActD possesses high antitumor activities, its clinical usefulness is limited by its extreme cytotoxicity. Thus, if the structure of ActD can be modified to reduce its cytotoxicity while retaining its activity, such an analogue would be a better antitumor drug. On the basis of X-ray crystal structures of the complexes between ActD and DNA[1], and our work [2], we designed and totally synthesized two ActD analogs 8a-b iii which both of the (L)-N-methyl-valine residues of ActD were replaced with LN-MeAla and L-N-MeSer, respectively. The anticancer pharmacology of the two analogs were examined. The result shows that the toxicity of the two analogs are higher than ActD and the antitumoe activity are lower than ActD, too.  ……

  4. Inhibin alpha gene expression in human trophoblasts is regulated by interactions between TFAP2 and cAMP signaling pathways.

    Science.gov (United States)

    Depoix, Christophe L; Debiève, Frédéric; Hubinont, Corinne

    2014-11-01

    Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3',5'-adenosine monophosphate (AMP)-response element (CRE) found in a region of the promoter that is homologous to the human INHA promoter. We previously found that during in vitro cytotrophoblast differentiation, human INHA gene expression was regulated by TFAP2A via association with an AP-2 site located upstream of this CRE. The aim of this study was to evaluate if the human INHA gene was also regulated by cAMP in trophoblasts, and to investigate the possible crosstalk between TFAP2 and cAMP signaling pathways in the regulation of INHA gene expression. Treatment with cAMP or forskolin increased INHA mRNA expression by 7- and 2-fold in primary cytotrophoblasts and choriocarcinoma-derived BeWo cells, respectively. Treatment with the protein kinase A inhibitor H-89 reduced forskolin-induced luciferase activity by ∼40% in BeWo cells transfected with an INHA promoter-driven luciferase reporter vector. TFAP2 overexpression increased basal luciferase activity, whereas the dominant repressor KCREB abolished it. Surprisingly, mutation of the CRE also eliminated the TFAP2-induced transcription, although TFAP2 overexpression was still able to increase forskolin-induced luciferase activity when the AP-2 binding site, but not the CRE site, was mutated. Thus, INHA gene expression is upregulated by cAMP via CRE in human trophoblasts, and TFAP2 regulates this expression by interacting with CRE.

  5. Overtreatment and inadequate therapy of gestational trophoblastic neoplasms%妊娠滋养细胞肿瘤治疗中的过度与不足

    Institute of Scientific and Technical Information of China (English)

    赵峻; 向阳

    2011-01-01

    妊娠滋养细胞肿瘤(GTN)包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤,虽然总体治愈率达90%以上,但治疗不当的问题仍然存在.文章从化疗方案的选择、化疗副反应的处理、停止化疗的时机、手术的指征及价值等几方面阐述在临床上存在的对GTN患者治疗的过度与不足.%Gestational trophoblastic neoplasm includes invasive mole, choriocarcinoma, placenta] site trophoblastic tumor and epithelial trophoblastic tumor. There is still inappropriate therapy of GTN in the clinic although the cure rate of GTN is above 90%. This article expounds both overtreatment and inadequate therapy of GTN patients on instituting appropriate regimen,management of adverse reaction of chemotherapy, indications of termination of therapy and value of surgical management.

  6. 滋养细胞肿瘤患者再妊娠相关问题%Gestational trophoblastic neoplasms and successor pregnancies

    Institute of Scientific and Technical Information of China (English)

    赵峻; 向阳

    2013-01-01

    妊娠滋养细胞肿瘤(GTN)包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤.由于GTN多发生于育龄妇女,治疗的同时保留患者的生育功能显得尤为重要.文章详细阐述了保留生育功能治疗GTN的方法(包括化疗、栓塞治疗、保守性手术、放疗等)及其对生育功能的影响,并对治疗后再妊娠的结局进行了阐述.%Gestational trophoblastic neoplasm includes invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelial trophoblastic tumor. Fertility sparing therapy for these patients is especially important because these diseases often involve reproductive aged women. This article expounds fertility sparing therapy for GTN including chemotherapy, embolotherapy, conservative surgery, and radiotherapy. The outcome of successor pregnancies after fertility sparing therapy is reviewed as well.

  7. Fertility sparing therapy on gestational trophoblastic neoplasms%妊娠滋养细胞肿瘤保留生育功能的治疗

    Institute of Scientific and Technical Information of China (English)

    赵峻; 向阳

    2012-01-01

    妊娠滋养细胞肿瘤(gestational trophoblastic neoplasms,GTN)包括侵蚀性葡萄胎、绒毛膜癌、胎盘部位滋养细胞肿瘤和上皮样滋养细胞肿瘤.由于GTN多发生于育龄妇女,治疗的同时保留患者的生育功能显得尤为重要.本文详细阐述了保留生育功能治疗GTN的方法,如化疗、栓塞治疗、保守性手术、放疗等,并总结了治疗后的妊娠结局.%ence to.- XIANG Yang E-mail: xiangyang65&gmail. com [Abstract] Gestational trophoblastic neoplasm includes invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelial trophoblastic tumor. Fertility sparing therapy for these patients is especially important because these diseases often involve reproductive aged women. This article expounds fertility sparing therapy for GTN including chemotherapy, embolotherapy, conservative surgery, and radiotherapy. The outcome of future pregnancies after fertility sparing therapy is reviewed as well.

  8. Pancreaticoduodenectomy for metastatic tumors to the periampullary region.

    Science.gov (United States)

    Medina-Franco, H; Halpern, N B; Aldrete, J S

    1999-01-01

    Although operative resection of metastatic lesions to the liver, lung, and brain has proved to be useful, only recently have there been a few reports of pancreaticoduodenectomies in selected cases of metastases to the periampullary region. In this report we present four cases of proven metastatic disease to the periampullary region in which the lesions were treated by pancreaticoduodenectomy. Metastatic tumors corresponded to a melanoma of unknown primary site, choriocarcinoma, high-grade liposarcoma of the leg, and a small cell cancer of the lung. All four patients survived the operation and had no major complications. Two patients died of recurrence of their tumors, 6 and 63 months, respectively, after operation; the other two patients are alive 21 and 12 months, respectively, after operation. It can be inferred from this small but documented experience, as well as a review of the literature, that pancreaticoduodenectomy for metastatic disease can be considered in selected patients, as long as this operation is performed by experienced surgeons who have achieved minimal or no morbidity and mortality with it.

  9. Dynamic change of Adamalysin 19 (ADAM19) in human placentas and its effects on cell invasion and adhesion in human trophoblastic cells

    Institute of Scientific and Technical Information of China (English)

    SANG; QingXiang; Amy

    2009-01-01

    Human ADAM19 is a recently identified member of the ADAM family.It is highly expressed in human placentas,but its dynamic change and function at the human feto-maternal interface during placentation remain to be elucidated.In this present study,the spatial and temporal expression and cellular localization of ADAM19 in normal human placentas were first demonstrated,and the effects of ADAM19 on trophoblast cell adhesion and invasion were further investigated by using a human choriocarcinoma cell line(JEG-3) as an in vitro model.The data demonstrated that ADAM19 was widely distributed in villous cytotrophoblast cells,syncytiotrophoblast cells,column trophoblasts,and villous capillary endothelial cells during early pregnancy.The mRNA and protein level of ADAM19 in placentas was high at gestational weeks 8-9,but diminished significantly at mid-and term pregnancy.In JEG-3 cells,the overexpression of ADAM19 led to diminished cell invasion,as well as increases in cell adhesiveness and the expression of E-cadherin,with no changes in β-catenin expression observed.These data indicate that ADAM19 may participate in the coordinated regulation of human trophoblast cell behaviors during the process of placentation.

  10. Hystera Ektomia: not always called for

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    Manvi Jindal

    2013-08-01

    Full Text Available Unsympathetic hysterectomies have seen a rising trend in India in the recent times, the unsuspecting folks being pushed into surgeries wrongly citing the austerity of the illness. We highlight a case of a 26 year old female patient with post-partum bleeding per vaginum for 6 months, who was initially treated conservatively at several hospitals. Later, histopathologically proven to be a case of Choriocarcinoma (WHO Stage I with FIGO prognostic score of 5, was hysterectomized hastily overlooking the reports and the patient discharged without further intervention. Few months later the patient presented with brain and lungs metastases. Had the patient been properly evaluated and treated appropriately initially, surgery was not indicated. Instead the patient was callously operated upon and histopathological report not followed which resulted in patient developing distant metastases (WHO Stage IV with FIGO prognostic score of 17. Unwarranted and unevaluated hysterectomies should be checked by appropriately evaluating the extent of the disease. [Int J Reprod Contracept Obstet Gynecol 2013; 2(4.000: 708-710

  11. Ischemic Stroke during Pregnancy and Puerperium

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    Elisabetta Del Zotto

    2011-01-01

    Full Text Available Ischemic stroke during pregnancy and puerperium represents a rare occurrence but it could be a serious and stressful event for mothers, infants, and also families. Whenever it does occur, many concerns arise about the safety of the mother and the fetus in relation to common diagnostic tests and therapies leading to a more conservative approach. The physiological adaptations in the cardiovascular system and in the coagulability that accompany the pregnant state, which are more significant around delivery and in the postpartum period, likely contribute to increasing the risk of an ischemic stroke. Most of the causes of an ischemic stroke in the young may also occur in pregnant patients. Despite this, there are specific conditions related to pregnancy which may be considered when assessing this particular group of patients such as pre-eclampsia-eclampsia, choriocarcinoma, peripartum cardiomiopathy, amniotic fluid embolization, and postpartum cerebral angiopathy. This article will consider several questions related to pregnancy-associated ischemic stroke, dwelling on epidemiological and specific etiological aspects, diagnostic issue concerning the use of neuroimaging, and the related potential risks to the embryo and fetus. Therapeutic issues surrounding the use of anticoagulant and antiplatelets agents will be discussed along with the few available reports regarding the use of thrombolytic therapy during pregnancy.

  12. Translocation of positively and negatively charged polystyrene nanoparticles in an in vitro placental model.

    Science.gov (United States)

    Kloet, Samantha K; Walczak, Agata P; Louisse, Jochem; van den Berg, Hans H J; Bouwmeester, Hans; Tromp, Peter; Fokkink, Remco G; Rietjens, Ivonne M C M

    2015-10-01

    To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell layer that separates an apical from a basolateral compartment. PS-NPs were characterized with respect to size, surface charge, morphology and protein corona. Translocation of PS-NPs was not related to PS-NP charge. Two PS-NPs were translocated across the BeWo transwell model to a lower extent than amoxicillin, a model compound known to be translocated over the placental barrier to only a limited extent, whereas one PS-NP showed a slightly higher translocation. Studies on the effect of transporter inhibitors on the translocation of the PS-NPs indicated that their translocation was not mediated by known transporters and mainly dependent on passive diffusion. It is concluded that the BeWo b30 model can be used as an efficient method to get an initial qualitative impression about the capacity of NPs to translocate across the placental barrier and set priorities in further in vivo studies on translocation of NPs to the fetus.

  13. Smooth muscle tumor of the placenta - an entrapped maternal leiomyoma: a case report

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    Murtoniemi Katja

    2009-06-01

    Full Text Available Abstract Introduction Neoplasms of the placenta are uncommon. Tumors arising from the placental tissue include two distinct histological types: the benign vascular tumor, chorangioma, and very rarely, choriocarcinoma. Benign leiomyomas, in contrast, are very common tumors of the uterine wall and occur in 0.1% to 12.5% of all pregnant women. However, the incorporation of uterine leiomyoma into the placenta is exceptional and raises the question of its origin. This case is possibly the first report on this kind of a placental tumor which has been examined using both immunohistochemistry and chromosome analysis. Case presentation A 34-year-old G4P3 Caucasian woman was followed up antenatally because of a stillbirth in her previous pregnancy. At 36 weeks' gestation, a hypoechoic, 3.6 × 4.2 cm rounded mass was noted within the placenta on ultrasound examination. Histologically, the tumor was a benign leiomyoma and this finding was supported by immunohistochemistry. The newborn infant was male. Chromosomes of the neoplasm were studied by the fluorescence in situ hybridization technique and the tumor was found to carry XX chromosomes. Conclusion A rare benign smooth muscle neoplasm involving the placental parenchyma is presented. The tumor was a uterine leiomyoma of maternal origin, which had become entrapped by the placenta. This case report is of interest to the clinical specialty of obstetrics and gynecology and will advance our knowledge of the etiology of placental tumors.

  14. Uncommon mucosal metastases to the stomach

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    Kanthan R

    2009-08-01

    Full Text Available Abstract Background Metastases to the stomach from an extra-gastric neoplasm are an unusual event, identified in less than 2% of cancer patients at autopsy. The stomach may be involved by hematogenous spread from a distant primary (most commonly breast, melanoma or lung, or by contiguous spread from an adjacent malignancy, such as the pancreas, esophagus and gallbladder. These latter sites may also involve the stomach via lymphatic or haematogenous spread. We present three cases of secondary gastric malignancy. Methods/Results The first is a 19-year-old male who received a diagnosis of testicular choriocarcinoma in September 2004. Metastatic malignancy was demonstrated in the stomach after partial gastrectomy was performed to control gastric hemorrhage. The second is a 75-year-old male, generally well, who was diagnosed with adenocarcinoma of the lung in September 2005. Poorly differentiated adenocarcinoma of the lung was demonstrated in a subsequent biopsy of "gastric polyps". The third is an 85-year-old man with no known history of malignancy who presented for evaluation of iron deficiency anemia by endoscopy in February 2006. Biopsies of the colonic and gastric mucosa demonstrated moderately differentiated invasive colonic adenocarcinoma with metastatic deposits in the stomach. Conclusion While the accurate recognition of these lesions at endoscopy is fraught with difficulty, pathological awareness of such uncommon metastases in the gastric mucosa is essential for accurate diagnosis and optimal patient management.

  15. Chromosome territories, X;Y translocation and Premature Ovarian Failure: is there a relationship?

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    Betri Enrico

    2009-09-01

    Full Text Available Abstract Background Premature ovarian failure (POF is a secondary hypergonadotrophic amenorrhea occurring before the age of 40 and affecting 1-3% of females. Chromosome anomalies account for 6-8% of POF cases, but only few cases are associated with translocations involving X and Y chromosomes. This study shows the cytogenetic and molecular analysis of a POF patient came to our attention as she developed a left ovary choriocarcinoma at the age of 10 and at 14 years of age she presented secondary amenorrhea with elevated levels of gonadotropins. Results Breakpoint position on X and Y chromosomes was investigated using Fluorescent In Situ Hybridisation (FISH with a panel of specific BAC probes, microsatellite analysis and evaluation of copy number changes and loss of heterozigosity by Affymetrix® GeneChip platform (Santa Clara, CA, USA. Patient's karyotype resulted 46, X, der(Yt(X;Y(q13.1;q11.223. X inactivation study was assessed by RBA banding and showed preferential inactivation of derivative chromosome. The reciprocal spatial disposition of sexual chromosome territories was investigated using whole chromosome painting and centromeres probes: patient's results didn't show a significant difference in comparison to normal controls. Conclusion The peculiar clinical case come to our attention highlighted the complexity of POF aetiology and of the translocation event, even if our results seem to exclude any effect on nuclear organisation. POF phenotype could be partially explained by skewed X chromosome inactivation that influences gene expression.

  16. Iron metabolism in BeWo chorion carcinoma cells. Transferrin-mediated uptake and release of iron.

    Science.gov (United States)

    van der Ende, A; du Maine, A; Simmons, C F; Schwartz, A L; Strous, G J

    1987-06-25

    Growing human choriocarcinoma BeWo b24 cells contain 1.5 X 10(6) functional cell surface transferrin binding sites and 2.0 X 10(6) intracellular binding sites. These cells rapidly accumulate iron at a rate of 360,000 iron atoms/min/cell. During iron uptake the transferrin and its receptor recycle at least each 19 min. The accumulated iron is released from the BeWo cells at a considerable rate. The time required to release 50% of previously accumulated iron into the extracellular medium is 30 h. This release process is cell line-specific as HeLa cells release very little if any iron. The release of iron by BeWo cells is stimulated by exogenous chelators such as apotransferrin, diethylenetriaminepenta-acetic acid, desferral, and apolactoferrin. The time required to release 50% of the previously accumulated iron into medium supplemented with chelator is 15 h. In the absence of added chelators iron is released as a low molecular weight complex, whereas in the presence of chelator the iron is found complexed to the chelator. Uptake of iron is inhibited by 250 microM primaquine or 2.5 microM monensin. However, the release of iron is not inhibited by these drugs. Intracellular iron is stored bound to ferritin. A model for the release of iron by BeWo cells and its implication for transplacental iron transport is discussed.

  17. Vorinostat and Bortezomib in Treating Young Patients With Refractory or Recurrent Solid Tumors, Including Central Nervous System Tumors and Lymphoma

    Science.gov (United States)

    2013-07-01

    Childhood Burkitt Lymphoma; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germ Cell Tumor; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Medulloepithelioma; Childhood Meningioma; Childhood Mixed Glioma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Childhood Oligodendroglioma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific

  18. Photodynamic therapy in gastrointestinal cancer: a realistic option?

    Science.gov (United States)

    Barr, H

    2000-02-01

    Photodynamic therapy is now a useful and practical option of the local treatment of gastrointestinal cancers. There is increasing screening and surveillance of patients at risk of oesophageal and gastric cancers. The early detection of disease is often unhelpful if an elderly or frail patient needs to be subjected to radical resectional surgery. Photodynamic therapy can eradicate and cure early mucosal disease following a single endoscopic treatment. If the disease is more advanced good local control and palliation is often possible. Overall, palliation can often be achieved using simpler methods which are highly effective and not associated with the problems of prolonged photosensitisation. It is rapidly becoming clear that the ideal indication is for the treatment of dysplastic lesions in the oesophagus associated with columnar-lined oesophagus (Barrett's oesophagus). In these circumstances a heterogeneous field change often with multifocal dysplasia or cancer can be widely eradicated. Similar areas of squamous dysplasia in the upper oesophagus can be treated. At present a major complication of stricture formation is associated with the use of some photosensitisers. The treatment of cancer at the ampulla of Vater and choriocarcinoma is also proving very effective. The treatment can be performed at endoscopy and is well tolerated and safe.

  19. Notch signalling in placental development and gestational diseases.

    Science.gov (United States)

    Haider, S; Pollheimer, J; Knöfler, M

    2017-01-16

    Activation of Notch signalling upon cell-cell contact of neighbouring cells controls a plethora of cellular processes such as stem cell maintenance, cell lineage determination, cell proliferation, and survival. Accumulating evidence suggests that the pathway also critically regulates these events during placental development and differentiation. Herein, we summarize our present knowledge about Notch signalling in murine and human placentation and discuss its potential role in the pathophysiology of gestational disorders. Studies in mice suggest that Notch controls trophectoderm formation, decidualization, placental branching morphogenesis and endovascular trophoblast invasion. In humans, the particular signalling cascade promotes formation of the extravillous trophoblast lineage and regulates trophoblast proliferation, survival and differentiation. Expression patterns as well as functional analyses indicate distinct roles of Notch receptors in different trophoblast subtypes. Altered effects of Notch signalling have been detected in choriocarcinoma cells, consistent with its role in cancer development and progression. Moreover, deregulation of Notch signalling components were observed in pregnancy disorders such as preeclampsia and fetal growth restriction. In summary, Notch plays fundamental roles in different developmental processes of the placenta. Abnormal signalling through this pathway could contribute to the pathogenesis of gestational diseases with aberrant placentation and trophoblast function.

  20. Prognosis of gestational trophoblast neoplasia accidentally diagnosed by laparoscopy for a presumed ectopic pregnancy%疑似异位妊娠腹腔镜手术后意外诊断的妊娠滋养细胞肿瘤患者的预后

    Institute of Scientific and Technical Information of China (English)

    郭琦; 冯凤芝; 向阳; 万希润; 任彤

    2016-01-01

    目的:研究因疑似异位妊娠而进行腹腔镜手术中意外发现的妊娠滋养细胞肿瘤( GTN)患者的预后。方法回顾性分析了自2009年1月至2013年12月期间,11例因疑似异位妊娠在北京协和医院接受腹腔镜手术,而术后意外发现为GTN患者的临床资料。结果因疑似异位妊娠进行腹腔镜探查术,而术后病理诊断为GTN的患者有11例,包括5例胎盘部位滋养细胞肿瘤(PSTT),5例绒毛膜癌及1例异位妊娠性绒癌。在术后1~9 d内[均值(1.9±1.6) d],11例患者中9例进行了氟尿嘧啶(5-FuDR)为基础的联合药物化疗,2例进行了EMA/CO方案化疗。另外,3例患者在化疗后进行全子宫切除的辅助治疗。中位随访时间为48个月(16~72个月),所有随访患者都达到了血清学完全缓解(SCR),只有1例PSTT患者出现了复发,而复发后经过补救化疗,再次获得SCR。结论尽管有些GTN的临床特点类似异位妊娠,经腹腔镜探查手术明确诊断后,通过化疗,仍能获得极好的预后。%Objective: To investigate the prognosis of gestational trophoblast neoplasia ( GTN) diagnosed incidentally by laparoscopy for a presumed ectopic pregnancy. Methods: Clinical data of the patients with GTN diagnosed incidentally after laparoscopy for a presumed ectopic pregnancy in Peking Union Medical College Hospital from Jan 2009 to Dec 2013 were analyzed retrospectively. Results: Eleven patients were diagnosed as GTN based on postoperative pathology after laparoscopic lesion resection for a presumed ectopic pregnancy,including 5 patients with trophoblastic tumor ( PSTT) at placenta site,5 patients with choriocarcinoma and 1 patient with ectopic gestational choriocarcinoma. Of 11 patients, 9 patients received floxuridine (5-FuDR)-based multidrug chemotherapy and 2 received EMA/CO chemotherapy within 1-6 days [mean (1. 9±1. 6) days)] after surgery. In addition,3 patients underwent adjuvant hysterectomy combined with chemotherapy. The follow

  1. Primary gastric chorioadenocarcinoma: a needle in a haystack

    Directory of Open Access Journals (Sweden)

    Teresa G. Hayes

    2011-04-01

    Full Text Available Primary gastric chorioadenocarcinoma (PGC is an exceedingly rare neoplasm which is often misdiagnosed as gastric adenocarcinoma at presentation. A markedly elevated serum beta human chorionic gonadotrophin (Beta HCG level is a characteristic feature of this tumor. A 44 year old white male presented with generalized abdominal pain and fullness, tarry black stools and weight loss of 3 months duration. Medical work-up including imaging with CT scans revealed the presence of a gastric mass and multiple liver metastases. Tumor markers were significant for a Beta HCG of 23717.5 MIU/ML. Scrotal ultrasound did not show the presence of a testicular mass. Upper GI endoscopy with biopsy was positive for a poorly differentiated adenocarcinoma with Beta HCG staining on immunohistochemistry. The patient was diagnosed with metastatic PGC. He received four cycles of chemotherapy with Bleomycin, Etoposide and Cisplatinum. At the end of the fourth cycle, Beta HCG was 23 MIU/ML. CT scan for restaging, however showed an increase in the size of the metastatic lesions. The patient subsequently became profoundly pancytopenic, developed disseminated intravascular coagulation (DIC and expired 12 months after initial presentation. PGC genetically and morphologically represents an adenocarcinoma and a choriocarcinoma. The significance of an elevated serum Beta HCG is controversial and it may have a role in evaluating response to treatment and tumor recurrence. Curative resection, appropriate chemotherapy and the absence of metastatic lesions is associated with improved survival. Hence, a high index of suspicion must be maintained to diagnose this tumor correctly at presentation and tailor therapy accordingly.

  2. Human placental expression of SLIT/ROBO signaling cues: effects of preeclampsia and hypoxia.

    Science.gov (United States)

    Liao, Wu-Xiang; Laurent, Louise C; Agent, Sally; Hodges, Jennifer; Chen, Dong-Bao

    2012-04-01

    Preeclampsia is characterized by dysfunctional endothelium and impaired angiogenesis. Recent studies suggest that the neuronal guidance SLIT/ROBO system regulates tumor angiogenesis. This study investigated if SLIT and ROBO are differentially expressed in healthy term and preeclamptic placentas and if hypoxia regulates SLIT and ROBO expression in placental trophoblast and endothelial cells. Total RNA and protein were extracted from placental tissues of healthy term (n = 5) and preeclamptic (n = 6) pregnancies and used for SLIT/ROBO expression analyses with reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative-PCR, and immunoblotting. Paraffin-embedded tissues were processed to localize SLIT/ROBO proteins in placental villi by immunohistochemistry. BeWo choriocarcinoma cells and human umbilical vein endothelial cells (HUVEC) were treated with 2% or 10% oxygen or the hypoxia mimetic deferoxamine mesylate (100 μM) to test if hypoxia regulates SLIT/ROBO expression. SLIT2, SLIT3, ROBO1, and ROBO4 mRNA and proteins were detected in the placenta. SLIT2 and ROBO1 proteins localized in the syncytiotrophoblast, and SLIT3, ROBO1, and ROBO4 in capillary endothelium of the placental villi. Levels of ROBO1 and ROBO4 as well as sFLT1 (soluble fms-like tyrosine kinase-1) proteins were significantly greater in preeclamptic placentas compared to normal controls. Hypoxia significantly increased both mRNA and protein levels of SLIT2 in BeWo cells and of SLIT3, ROBO1, and ROBB4 in HUVEC. Thus, trophoblast and endothelial coexpression of SLIT/ROBO suggests an autocrine/paracrine regulatory system for regulating placental function. Differential expression of SLITs and ROBOs in healthy term and preeclamptic placentas and hypoxia regulation of their expressions in placental cells implicate a potential pathophysiological role for this system in preeclampsia.

  3. En Bloc Resection of Solitary Functional Secreting Spinal Metastasis.

    Science.gov (United States)

    Goodwin, C Rory; Clarke, Michelle J; Gokaslan, Ziya L; Fisher, Charles; Laufer, Ilya; Weber, Michael H; Sciubba, Daniel M

    2016-05-01

    Study Design Literature review. Objective Functional secretory tumors metastatic to the spine can secrete hormones, growth factors, peptides, and/or molecules into the systemic circulation that cause distinct syndromes, clinically symptomatic effects, and/or additional morbidity and mortality. En bloc resection has a limited role in metastatic spine disease due to the current paradigm that systemic burden usually determines morbidity and mortality. Our objective is to review the literature for studies focused on en bloc resection of functionally active spinal metastasis as the primary indication. Methods A review of the PubMed literature was performed to identify studies focused on functional secreting metastatic tumors to the spinal column. We identified five cases of patients undergoing en bloc resection of spinal metastases from functional secreting tumors. Results The primary histologies of these spinal metastases were pheochromocytoma, carcinoid tumor, choriocarcinoma, and a fibroblast growth factor 23-secreting phosphaturic mesenchymal tumor. Although studies of en bloc resection for these rare tumor subtypes are confined to case reports, this surgical treatment option resulted in metabolic cures and decreased clinical symptoms postoperatively for patients diagnosed with solitary functional secretory spinal metastasis. Conclusion Although the ability to formulate comprehensive conclusions is limited, case reports demonstrate that en bloc resection may be considered as a potential surgical option for the treatment of patients diagnosed with solitary functional secretory spinal metastatic tumors. Future prospective investigations into clinical outcomes should be conducted comparing intralesional resection and en bloc resection for patients diagnosed with solitary functional secretory spinal metastasis.

  4. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity.

    Science.gov (United States)

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [(3)H](2)O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks.

  5. Currently used pesticides and their mixtures affect the function of sex hormone receptors and aromatase enzyme activity

    Energy Technology Data Exchange (ETDEWEB)

    Kjeldsen, Lisbeth Stigaard; Ghisari, Mandana; Bonefeld-Jørgensen, Eva Cecilie, E-mail: ebj@mil.au.dk

    2013-10-15

    The endocrine-disrupting potential of pesticides is of health concern, since they are found ubiquitously in the environment and in food items. We investigated in vitro effects on estrogen receptor (ER) and androgen receptor (AR) transactivity, and aromatase enzyme activity, of the following pesticides: 2-methyl-4-chlorophenoxyacetic acid (MCPA), terbuthylazine, iodosulfuron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, chlormequat chloride, bitertanol, propiconazole, prothioconazole, mancozeb, cypermethrin, tau fluvalinate, malathion and the metabolite ethylene thiourea (ETU). The pesticides were analyzed alone and in selected mixtures. Effects of the pesticides on ER and AR function were assessed in human breast carcinoma MVLN cells and hamster ovary CHO-K1 cells, respectively, using luciferase reporter gene assays. Effects on aromatase enzyme activity were analyzed in human choriocarcinoma JEG-3 cells, employing the classical [{sup 3}H]{sub 2}O method. Five pesticides (terbuthylazine, propiconazole, prothioconazole, cypermethrin and malathion) weakly induced the ER transactivity, and three pesticides (bitertanol, propiconazole and mancozeb) antagonized the AR activity in a concentration-dependent manner. Three pesticides (terbuthylazine, propiconazole and prothioconazole) weakly induced the aromatase activity. In addition, two mixtures, consisting of three pesticides (bitertanol, propiconazole, cypermethrin) and five pesticides (terbuthylazine, bitertanol, propiconazole, cypermethrin, malathion), respectively, induced the ER transactivity and aromatase activity, and additively antagonized the AR transactivity. In conclusion, our data suggest that currently used pesticides possess endocrine-disrupting potential in vitro which can be mediated via ER, AR and aromatase activities. The observed mixture effects emphasize the importance of considering the combined action of pesticides in order to assure proper estimations of related health effect risks

  6. MRI diagnosis and differential diagnosis of pineal region tumors%松果体区肿瘤的MRI诊断与鉴别诊断

    Institute of Scientific and Technical Information of China (English)

    岑家定

    2013-01-01

    Objective To discuss the MRI diagnosis and differential diagnosis of pineal region tumors. Methods Retrospected and analysed 28 cases of pineal region tumors diagnosed with MRI data. Results 8 cases of germ cell tumor, glioma with teratoma in 5 cases, 2 cases of meningioma, 4 cases of choriocarcinoma, neuroblastoma, pinealoblastoma, arachnoid cyst and skin itching cyst in 1 cases. The diagnostic results showed that only rely on the MRI signal was difficult to accurately diagnose,combined with clinical data was still needed. Conclusion MRI examination could accurately display the pineal region tumor morphology and location, diagnosis and differential diagnosis could be combined with the source to determine the tumor tissue, effectively improved the accuracy diagnosis and differential diagnosis.%  目的探讨松果体区肿瘤的MRI诊断与鉴别诊断。方法回顾分析28例松果体区肿瘤患者MRI诊断资料。结果生殖细胞瘤8例,胶质瘤及畸胎瘤各5例,脑膜瘤2例,绒毛膜癌4例,神经母细胞瘤、松果体母细胞瘤、蛛网膜囊肿及皮痒囊肿各1例。诊断结果显示,仅依靠MRI信号难以准确诊断,还需结合临床资料,有助于准确诊断。结论 MRI检查能够准确显示松果体区肿瘤的形态以及位置,诊断与鉴别诊断可以结合肿瘤的组织学来源确定,有效提高诊断以及鉴别诊断的准确性。

  7. Evaluation of SF-1 expression in testicular germ cell tumors: a tissue microarray study of 127 cases.

    Science.gov (United States)

    Sangoi, Ankur R; McKenney, Jesse K; Brooks, James D; Higgins, John P

    2013-07-01

    Differentiating testicular germ cell tumors from sex-cord stromal tumors can be difficult in certain cases because of overlapping morphologic features and/or an absence of clinically apparent hormonal symptoms. Immunohistochemistry may be needed as an ancillary diagnostic tool in this differential diagnostic setting. Steroidogenic factor-1 (SF-1) is a nuclear transcription factor controlling steroidogenesis and is expressed in developing Sertoli and Leydig cells. Although 1 recent study has reported SF-1 nuclear immunoreactivity in testicular sex-cord stromal tumors, the specificity for this marker in germ cell tumors has not been evaluated. After encountering several problematic cases (including some on testicular biopsy), we sought to determine the diagnostic specificity of SF-1 in a large series of germ cell tumors. Nuclear immunohistochemical expression of SF-1 was evaluated in 127 germ cell tumors using tissue microarray technology with 23 non-germ cell tumor tissues as positive internal controls. No nuclear SF-1 expression was identified in any of the 127 germ cell tumors [including choriocarcinoma (3), embryonal carcinoma (25), epidermal inclusion cyst (1), intratubular germ cell neoplasia unclassified (4), seminoma (72), spermatocytic seminoma (2), teratoma (8), and yolk sac tumor (12)]. All 23 non-germ cell tumor tissues showed strong nuclear SF-1 expression in Sertoli and/or Leydig cells [including testicular atrophy (10), cryptorchidism (2), normal testis (4), hypospermatogenesis (1), immature testis (1), intratubular large cell calcifying Sertoli cell tumor (1), Leydig cell tumor (3), and Sertoli only (1)]. This study documents the absence of SF-1 expression in testicular germ cell tumors and supports its specificity for sex-cord stromal lesions in this diagnostic context.

  8. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    Science.gov (United States)

    2016-08-24

    Acinar Cell Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bladder Adenocarcinoma; Bronchioloalveolar Carcinoma; Cervical Adenocarcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Endometrial Adenocarcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Giant Cell Carcinoma; Intestinal Neuroendocrine Carcinoma; Intrahepatic Cholangiocarcinoma; Lung Carcinoid Tumor; Lung Sarcomatoid Carcinoma; Major Salivary Gland Carcinoma; Malignant Odontogenic Neoplasm; Malignant Peripheral Nerve Sheath Tumor; Malignant Skin Neoplasm; Malignant Testicular Sex Cord-Stromal Tumor; Metastatic Malignant Neoplasm of Unknown Primary Origin; Mixed Mesodermal (Mullerian) Tumor; Mucinous Adenocarcinoma; Mucinous Cystadenocarcinoma; Nasal Cavity Adenocarcinoma; Nasal Cavity Carcinoma; Nasopharyngeal Carcinoma; Nasopharyngeal Papillary Adenocarcinoma; Nasopharyngeal Undifferentiated Carcinoma; Oral Cavity Carcinoma; Oropharyngeal Undifferentiated Carcinoma; Ovarian Adenocarcinoma; Ovarian Germ Cell Tumor; Ovarian Mucinous Adenocarcinoma; Ovarian Squamous Cell Carcinoma; Pancreatic Acinar Cell Carcinoma; Pancreatic Neuroendocrine Carcinoma; Paraganglioma; Paranasal Sinus Adenocarcinoma; Paranasal Sinus Carcinoma; Parathyroid Gland Carcinoma; Pituitary Gland Carcinoma; Placental Choriocarcinoma; Placental-Site Gestational Trophoblastic Tumor; Primary Peritoneal High Grade Serous Adenocarcinoma; Pseudomyxoma Peritonei; Scrotal Squamous Cell Carcinoma; Seminal Vesicle Adenocarcinoma; Seminoma; Serous Cystadenocarcinoma; Small Intestinal Adenocarcinoma; Small Intestinal Squamous

  9. Development of a model for functional studies of ABCG2 (breast cancer resistance protein) efflux employing a standard BeWo clone (B24).

    Science.gov (United States)

    Crowe, Andrew; Keelan, Jeffrey A

    2012-10-01

    Human choriocarcinoma-derived BeWo cells express high levels of breast cancer resistance protein (BCRP/ABCG2) with no functional P-glycoprotein (P-gp) (ABCB1) activity, making them a potential model to study bidirectional ABCG2-mediated drug transport. However, the original BeWo clone (B24) available to researchers does not form confluent monolayers with tight junctions required by the model. Our aim was to adapt culture conditions to attempt to generate confluent BeWo monolayers for drug transport studies using the standard B24 clone. BeWo cells (B24; American Type Culture collection [ATCC]) were cultured in six-well plates or polycarbonate millicell inserts in a number of media formulations, growth supplements, and basement membrane substitutes. Cells were examined for confluence by microscopy, and transepithelial electrical resistance (TEER) was measured daily; monolayer permeability was assessed when TEER had stabilized. Optimal growth rates were achieved in culture conditions consisting of Medium 199 (M199) supplemented with epidermal growth factor (EGF; 20 ng/mL), vitamin supplements, and 10% fetal calf serum (FCS) with collagen coating. A TEER of 170 Ω in 0.6 cm(2) inserts was achieved 2 weeks after seeding under optimal conditions. The cell-impermeable diffusion marker 5(6) carboxy-2,7dichlorodihydrofluorescein (C-DCDHF) had a permeability coefficient of 3.5×10(-6) cm/s, indicative of minimal paracellular permeability. ABCG2 expression, as determined by immunoblotting, remained unaffected by confluency. In conclusion, we describe culture conditions for the B24 BeWo clone that facilitate the formation of monolayers with tighter junctions and reduced paracellular transport compared to previously published models. These growth conditions provide a good model of ABCG2-mediated drug transport in a human placental cell line.

  10. A profile of cases of gestational trophoblastic neoplasia at a large tertiary centre in dubai.

    Science.gov (United States)

    Rangwala, Tasneem H; Badawi, Faiza

    2011-01-01

    Objectives. To study (1) the prevalence of different types of gestational trophoblastic neoplasia (GTN) in the local and nonlocal population of women at Al Wasl Hospital, a tertiary level referral centre for northern Emirates, (2) the safety of cervical preparation before uterine evacuation, (3) the role of repeat uterine evacuation in curing these cases, and (4) the percentage of cases ultimately requiring chemotherapy. Material and Methods. Retrospective analysis of case records of 35 women with diagnosis of gestational trophoblastic neoplasia were managed in the Department of Obstetrics and Gynecology at Al Wasl Hospital, over a 2-year period between January 2007 to December 2008. Results. 35 cases of gestational trophoblastic neoplasia were seen in a 2-year period (January 2007 to December 2008) at Al Wasl Hospital, with 7000 deliveries per year, prevalence being 1 in 400 live births. 60% cases were local Arabs. Histopathology revealed complete mole in 13 cases, partial mole in 17 cases, hydropic degeneration of villi in 4 cases, and no identifiable tissue in 1 case. No cases of choriocarcinoma or placental site trophoblastic tumour were seen during the study period. 34% cases received cervical preparation with prostaglandins prior to surgical curettage. Complications were minor. 62% were cured by primary suction curettage, 12% after second (repeat) uterine evacuation, and 25% needed single drug chemotherapy. 8% cases defaulted after primary evacuation and were lost to followup. Conclusions. Prevalence of GTN in the local Arab population is similar to other Asian populations. The majority of cases are cured by simple suction uterine curettage. Cervical preparation with prostaglandins should be done in selected cases to avoid perforation during evacuation. Second (repeat) uterine evacuation can be curative in some cases with strict selection criteria and avoid the need for chemotherapy. Regional registry of cases is needed to estimate the true incidence of this

  11. Epidermal growth factor-like domain 7 promotes migration and invasion of human trophoblast cells through activation of MAPK, PI3K and NOTCH signaling pathways.

    Science.gov (United States)

    Massimiani, M; Vecchione, L; Piccirilli, D; Spitalieri, P; Amati, F; Salvi, S; Ferrazzani, S; Stuhlmann, H; Campagnolo, L

    2015-05-01

    Epidermal growth factor-like domain 7 (Egfl7) is a gene that encodes a partially secreted protein and whose expression is largely restricted to the endothelia. We recently reported that EGFL7 is also expressed by trophoblast cells in mouse and human placentas. Here, we investigated the molecular pathways that are regulated by EGFL7 in trophoblast cells. Stable EGFL7 overexpression in a Jeg3 human choriocarcinoma cell line resulted in significantly increased cell migration and invasiveness, while cell proliferation was unaffected. Analysis of mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways showed that EGFL7 promotes Jeg3 cell motility by activating both pathways. We show that EGFL7 activates the epidermal growth factor receptor (EGFR) in Jeg3 cells, resulting in downstream activation of extracellular regulated kinases (ERKs). In addition, we provide evidence that EGFL7-triggered migration of Jeg3 cells involves activation of NOTCH signaling. EGFL7 and NOTCH1 are co-expressed in Jeg3 cells, and blocking of NOTCH activation abrogates enhanced migration of Jeg3 cells overexpressing EGFL7. We also demonstrate that signaling through EGFR and NOTCH converged to mediate EGFL7 effects. Reduction of endogenous EGFL7 expression in Jeg3 cells significantly decreased cell migration. We further confirmed that EGFL7 stimulates cell migration by using primary human first trimester trophoblast (PTB) cells overexpressing EGFL7. In conclusion, our data suggest that in trophoblast cells, EGFL7 regulates cell migration and invasion by activating multiple signaling pathways. Our results provide a possible explanation for the correlation between reduced expression of EGFL7 and inadequate trophoblast invasion observed in placentopathies.

  12. Endothelin-1 induces endoplasmic reticulum stress by activating the PLC-IP(3) pathway: implications for placental pathophysiology in preeclampsia.

    Science.gov (United States)

    Jain, Arjun; Olovsson, Matts; Burton, Graham J; Yung, Hong-wa

    2012-06-01

    Recent evidence implicates placental endoplasmic reticulum (ER) stress in the pathophysiological characteristics of preeclampsia. Herein, we investigate whether endothelin (ET)-1, which induces Ca(2+) release from the ER, can induce placental ER stress. Loss of ER Ca(2+) homeostasis impairs post-translational modification of proteins, triggering ER stress-response pathways. IHC confirmed the presence of both ET-1 and its receptors in the syncytiotrophoblast. Protein levels and immunoreactivity of ET-1 and the endothelin B receptor (ETBR) were increased in preeclamptic samples compared with normotensive controls. JEG-3 and BeWo choriocarcinoma cells treated with ET-1 displayed an increase in ER stress markers. ET-1 induced phospho-activation of the ETBR. Treating cells with BQ788, an ETBR antagonist, or small-interfering RNA knockdown of the receptor inhibited induction of ER stress. ET-1 also stimulated p-phospholipase C (PLC)γ1 levels. By using inhibitors of PLC activation, U73122, and the inositol 1,4,5-triphosphate (IP(3)) receptor, xestospongin-C, we demonstrated that ET-1 induces ER stress via the PLC-IP(3) pathway. Furthermore, ET-1 levels increased in the syncytiotrophoblast of explants from normal placentas after hypoxia-reoxygenation in vitro. Conditioned medium from hypoxia-reoxygenation explants also contained higher ET-1 levels, which induced ER stress in JEG-3 cells that was abolished by an ET-1-neutralizing antibody. Collectively, the data show that ET-1 induced ER stress in trophoblasts via the ETBR and initiation of signaling through the PLC-IP(3) pathway, with the potential for autocrine stimulation.

  13. Embelin-Induced Apoptosis of Human Prostate Cancer Cells Is Mediated through Modulation of Akt and β-Catenin Signaling.

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    Nahee Park

    Full Text Available There is increasing evidence that embelin, an active component of Embelia ribes, induces apoptosis in human cancer cells, but the detailed mechanisms are still unclear. Here, we have investigated the effect of embelin on the growth of human prostate cancer cells. Embelin strongly inhibited cell growth especially in human prostate cancer cell lines, including PC3, DU145, LNCaP-LN3 and normal prostate epithelial cell, RWPE-1 compared to breast cancer (MDA-MB-231, MCF-7, and T47D, hepatoma (HepG2, Hep3B, and HuH-7, or choriocarcinoma (JEG-3. We observed that embelin induced apoptosis of PC3 cells in a time-dependent manner correlated with decreased expression of Bcl-2, Bcl-xL, and Mcl-1, increased translocation of Bax into mitochondria, and a reduction in the mitochondrial membrane potential. Furthermore, embelin induced voltage-dependent anion channel (VDAC 1 expression and oligomerization, which may promote cytochrome c and AIF release. Because embelin was able to inhibit Akt activation and cyclooxygenase-2 expression, the effects on Wnt/ β-catenin signaling were determined. Embelin activated glycogen synthase kinase (GSK-3β by preventing phosphorylation and suppressed β-catenin expression. Attenuation of β-catenin-mediated TCF transcriptional activity and gene transcription, such as cyclin D1, c-myc, and matrix metalloproteinase (MMP-7, were shown in embelin-treated cells. The changes in β-catenin levels in response to embelin were blocked by lithium chloride, a GSK-3 inhibitor, indicating that embelin may decrease β-catenin expression via GSK-3β activation. Furthermore, exposure of PC3 cells to embelin resulted in a significant decrease in cell migration and invasion. In conclusion, these findings suggest that inhibition of Akt signaling and activation of GSK-3β partially contributes to the pro-apoptotic effect of embelin in prostate cancer cells.

  14. Expression patterns of maspin and mutant p53 are associated with the development of gestational trophoblastic neoplasia.

    Science.gov (United States)

    Sun, Pengming; Wu, Qibin; Ruan, Guanyu; Zheng, Xiu; Song, Yiyi; Zhun, Jianfan; Wu, Lixiang; Gotlieb, Walter H

    2016-11-01

    Gestational trophoblastic disease (GTD) is a group of conditions that originate from the abnormal proliferation of trophoblastic cells. GTDs encompass hydatidiform moles (HMs) and gestational trophoblastic neoplasia (GTN). GTNs are a group of malignant diseases that require chemotherapy, or more aggressive treatment. There is a requirement for more tumor markers to predict the development of GTN from HMs. The current study evaluated the expression of maspin and tumor protein p53 (p53) in GTD, and their role in predicting the development of GTN. Expression of maspin and mutant p53 (m-p53) was detected by immunohistochemistry in 48 normal first trimester placentas, matched for gestational age to 49 HMs that regressed, 39 malignant HMs and 11 invasive moles or choriocarcinomas. Spearman's rank correlation analysis and logistic regression were performed on the expression patterns of maspin and m-p53, and on the clinical prognostic factors in GTD. Compared with normal placenta levels, the expression levels of maspin were decreased, whereas the expression levels of m-p53 were increased in GTDs (Pp53 in complete and partial HMs were not significantly different (P>0.05). In HMs, maspin expression was inversely correlated with serum β human chorionic gonadotropin, uterine size and diameter of theca-lutein cysts; however, m-p53 expression demonstrated a positive correlation with these factors (all Pp53 expression was significantly higher in patients with an advanced FIGO stages (FIGO stage ≥III) compared with patients in early stages (FIGO stage ≤II; 87.9 vs. 58.8%; P=0.019). The combination of maspin negative expression with m-p53 positive expression had an 84% specificity value, 76% positive predictive value and 70% negative predictive value for the development of GTN. In conclusion, maspin-negative and m-p53-positive expression is associated with the development of GTN in HMs.

  15. The WHO score predicts treatment outcome in low risk gestational trophoblastic neoplasia patients treated with weekly intramuscular methotrexate

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    Mitra M Gilani

    2013-01-01

    Full Text Available Background: Gestational trophoblastic neoplasia (GTN includes a spectrum of disease ranging from hydatidifrom mole to choriocarcinoma. Low risk GTN is defined as persistent molar pregnancy with a WHO score lower than seven. The optimal chemotherapeutic regimen still remains controversial. Aim: The objectives of this study was to determine efficacy and safety of weekly intramuscular methotrexte in the treatment of low risk gestational trophoblastic neoplasia.(LRGTN and also identify prognostic factors associated with treatment failure, necessitating second line chemotherapy. Materials and Methods: Sixty-six women with LRGTN from 2001 to 2009 were treated with weekly intramuscular methotrexate at 40mg/m 2 as first line therapy.Monitoring of treatment was done with weekly checking of βhCG level. Three consecutive negative βhCG measurements showed complete response. After first negative βhCG measurement, one additional dose was administered for consolidation. Results: Of 66 patients, who started the treatment five continued their treatment in other medical centres and were excluded from final analysis for treatment evaluation, and seven discontinued first line therapy because of hepatotoxicity. Of the remaining 54, complete remission occurred in 43 (79.6% and eleven were resistant to first line therapy. Mean WHO score prior to starting chemotherapy was significantly different between two groups of response and resistance according to our data. Change of treatment to second line Actinomycin-D was necessary in eigtheen cases because of resistance to first line in eleven and liver enzyme elevation in seven patients. Sixteen of these 18 responded to Actinomycin-D as second line and one needed hysterectomy for complete response. One patient received multiagent chemotherapy for complete remission. Conclusion: We recommend this effective and safe method of chemotherapy for women with LRGTN. According to our data, lower mean WHO score predicts a better

  16. The Gestational Trophoblastic Diseases: A Ten Year Retrospective Study

    Directory of Open Access Journals (Sweden)

    Razieh Mohammadjafari

    2010-01-01

    Full Text Available Background: Gestational trophoblastic disease (GTD defines a heterogenenous group ofinterrelated lesions that arise from the trophoblastic epithelium of the placenta. There are severalhistologically distinct types of GTD: hydatiform mole (complete or partial, persistant/invasivegestational trophoblastic neoplasia (GTN, choriocarcinoma and placenta site trophoblastictumors. The aim of this study was to determine the frequency and risk factors of GTD amongwomen admitted to Imam Khomeini Hospital in Ahvaz, Iran.Materials and Methods: This was a cross-sectional study conducted at Imam KhomeiniHospital in Ahvaz, Iran. All hospital records related to GTD (132 from 1996 until 2006 werereviewed. Demographic and histo-pathologic characteristics were extracted. Chi-square andFisher-exact tests were used to analyze all variables. P ≤ 0.05 was considered statisticallysignificant. SPSS, version 11 was used for statistical analysis.Results: The mean age of patients was 27.6 years. Most patients who presented with GTDwere of ages 18-35 years (71.3%. There was no relationship between age and hydatiformmole during the reproductive years. There were 28 (18.9% patients over the age 40, of which18 (15.90% of these had a complete hydatiform mole. Within this group, 9 (6.8% changedto a persistent mole. There was a significant relationship between age over 40 and completemole (p<0.02. The percentage of patients with blood groups A and O was the same (37.9%.There was a significant relationship between blood groups (O+ and A+ and complete mole(p<0.05.Conclusion: The most common age range for hydatiform mole was 18-35 years. Women overthe age of 40 had a more complete hydatiform mole, which is similar to the other countries.Age and blood group are two risk factors for hydatiform mole.

  17. A well-circumscribed border with peripheral Doppler signal in sonographic image distinguishes epithelioid trophoblastic tumor from other gestational trophoblastic neoplasms.

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    Jiale Qin

    Full Text Available As epithelioid trophoblastic tumor (ETT shares similar clinical features with other gestational trophoblastic neoplasms (GTNs, it is likely to be clinically misdiagnosed and subsequently treated in an improper way. This study aimed to identify the sonographic features of ETT that are distinct from other GTNs, including placental site trophoblastic tumor (PSTT and invasive mole/choriocarcinoma (IM/CC. Here, we retrospectively analyzed ultrasound images of 12 patients with ETT in comparison with those of 21 patients with PSTT and 24 patients with IM/CC. The results showed that maximal diameter and hemodynamic parameters were not significantly different among ETT, PSTT and IM/CC (P>0.05. However, a well-circumscribed border with hypoechogenic halo was identified in the gray-scale sonogram in all 12 cases of ETT, while only in 1 out of 21 cases of PSTT and 1 out of 16 cases of IM/CC (P<0.001 for ETT vs. PSTT or IM/CC. Moreover, a peripheral pattern of Doppler signals was observed in 11 out of 12 ETT lesions, showing relatively more Doppler signal spots around the tumor border than within the boundary, while a non-peripheral pattern of Doppler signals in all 21 PSTT cases and 14 out of 16 IM/CC cases: with minimal, moderate or remarkable signal spots within the tumor, but not along the tumor (P<0.001 for ETT vs. PSTT or IM/CC. These distinct sonographic features of ETT correlated with histopathologic observations, such as expansive growth pattern and vascular morphology. Thus, we draw the conclusions that the well-circumscribed border with peripheral Doppler signal may serve as a reliable sonographic feature to discriminate ETT from other types of GTNs. With further validation in a larger patient set in our ongoing multi-center study, this finding will be potentially developed into a non-invasive pre-operative GTN subtyping method for ETT.

  18. The effect of acetaminophen on the expression of BCRP in trophoblast cells impairs the placental barrier to bile acids during maternal cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Blazquez, Alba G., E-mail: albamgb@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Briz, Oscar, E-mail: obriz@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Gonzalez-Sanchez, Ester, E-mail: u60343@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); Perez, Maria J., E-mail: mjperez@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); University Hospital of Salamanca, IECSCYL-IBSAL, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain); Ghanem, Carolina I., E-mail: cghanem@ffyb.uba.ar [Instituto de Investigaciones Farmacologicas, Facultad de Farmacia y Bioquimica, CONICET, Universidad de Buenos Aires, Buenos Aires (Argentina); Marin, Jose J.G., E-mail: jjgmarin@usal.es [Laboratory of Experimental Hepatology and Drug Targeting (HEVEFARM), IBSAL, University of Salamanca, Salamanca (Spain); CIBERehd, Instituto de Salud Carlos III, Madrid (Spain)

    2014-05-15

    Acetaminophen is used as first-choice drug for pain relief during pregnancy. Here we have investigated the effect of acetaminophen at subtoxic doses on the expression of ABC export pumps in trophoblast cells and its functional repercussion on the placental barrier during maternal cholestasis. The incubation of human choriocarcinoma cells (JAr, JEG-3 and BeWo) with acetaminophen for 48 h resulted in no significant changes in the expression and/or activity of MDR1 and MRPs. In contrast, in JEG-3 cells, BCRP mRNA, protein, and transport activity were reduced. In rat placenta, collected at term, acetaminophen administration for the last three days of pregnancy resulted in enhanced mRNA, but not protein, levels of Mrp1 and Bcrp. In fact, a decrease in Bcrp protein was found. Using in situ perfused rat placenta, a reduction in the Bcrp-dependent fetal-to-maternal bile acid transport after treating the dams with acetaminophen was found. Complete biliary obstruction in pregnant rats induced a significant bile acid accumulation in fetal serum and tissues, which was further enhanced when the mothers were treated with acetaminophen. This drug induced increased ROS production in JEG-3 cells and decreased the total glutathione content in rat placenta. Moreover, the NRF2 pathway was activated in JEG-3 cells as shown by an increase in nuclear NRF2 levels and an up-regulation of NRF2 target genes, NQO1 and HMOX-1, which was not observed in rat placenta. In conclusion, acetaminophen induces in placenta oxidative stress and a down-regulation of BCRP/Bcrp, which may impair the placental barrier to bile acids during maternal cholestasis. - Highlights: • Acetaminophen induces changes in placental BCRP expression in vitro. • This drug reduces the ability of placental cells to export BCRP substrates. • Acetaminophen induces changes in Bcrp expression in rat placenta. • Placental barrier to bile acids is impaired in rats treated with this drug.

  19. Biological functions of hCG and hCG-related molecules

    Directory of Open Access Journals (Sweden)

    Cole Laurence A

    2010-08-01

    Full Text Available Abstract Background hCG is a term referring to 4 independent molecules, each produced by separate cells and each having completely separate functions. These are hCG produced by villous syncytiotrophoblast cells, hyperglycosylated hCG produced by cytotrophoblast cells, free beta-subunit made by multiple primary non-trophoblastic malignancies, and pituitary hCG made by the gonadotrope cells of the anterior pituitary. Results and discussion hCG has numerous functions. hCG promotes progesterone production by corpus luteal cells; promotes angiogenesis in uterine vasculature; promoted the fusion of cytotrophoblast cell and differentiation to make syncytiotrophoblast cells; causes the blockage of any immune or macrophage action by mother on foreign invading placental cells; causes uterine growth parallel to fetal growth; suppresses any myometrial contractions during the course of pregnancy; causes growth and differentiation of the umbilical cord; signals the endometrium about forthcoming implantation; acts on receptor in mother's brain causing hyperemesis gravidarum, and seemingly promotes growth of fetal organs during pregnancy. Hyperglycosylated hCG functions to promote growth of cytotrophoblast cells and invasion by these cells, as occurs in implantation of pregnancy, and growth and invasion by choriocarcinoma cells. hCG free beta-subunit is produced by numerous non-trophoblastic malignancies of different primaries. The detection of free beta-subunit in these malignancies is generally considered a sign of poor prognosis. The free beta-subunit blocks apoptosis in cancer cells and promotes the growth and malignancy of the cancer. Pituitary hCG is a sulfated variant of hCG produced at low levels during the menstrual cycle. Pituitary hCG seems to mimic luteinizing hormone actions during the menstrual cycle.

  20. Perfluorinated chemicals: Differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells

    Energy Technology Data Exchange (ETDEWEB)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Casas, Josefina [Department of Biomedicinal Chemistry, IQAC–CSIC, 08034 Barcelona, Catalonia (Spain); Lacorte, Sílvia, E-mail: slbqam@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain); Porte, Cinta, E-mail: cinta.porte@cid.csic.es [Department of Environmental Chemistry, IDAEA–CSIC, 08034 Barcelona, Catalonia (Spain)

    2014-06-01

    The cytotoxicity of eight perfluorinated chemicals (PFCs), namely, perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDoA), perfluorobutanesulfonate (PFBS), perfluorohexanesulfonate (PFHxS) and perfluorooctanesulfonate (PFOS) was assessed in the human placental choriocarcinoma cell line JEG-3. Only the long chain PFCs – PFOS, PFDoA, PFNA, PFOA – showed significant cytotoxicity in JEG-3 cells with EC50 values in the range of 107 to 647 μM. The observed cytotoxicity was to some extent related to a higher uptake of the longer chain PFCs by cells (PFDoA > PFOS ≫ PFNA > PFOA > PFHxA). Moreover, this work evidences a high potential of PFOS, PFOA and PFBS to act as aromatase inhibitors in placental cells with IC50s in the range of 57–80 μM, the inhibitory effect of PFBS being particularly important despite the rather low uptake of the compound by cells. Finally, exposure of JEG-3 cells to a mixture of the eight PFCs (0.6 μM each) led to a relative increase (up to 3.4-fold) of several lipid classes, including phosphatidylcholines (PCs), plasmalogen PC and lyso plasmalogen PC, which suggests an interference of PFCs with membrane lipids. Overall, this work highlights the ability of the PFC mixture to alter cellular lipid pattern at concentrations well below those that generate toxicity, and the potential of the short chain PFBS, often considered a safe substitute of PFOS, to significantly inhibit aromatase activity in placental cells. - Highlights: • Eight perfluorinated chemicals of different chain lengths have been selected. • Long chain ones – PFOS, PFDoA, PFNA, PFOA – were cytotoxic in placenta cells. • The uptake of long chain perfluorinated chemicals by cells was comparatively higher. • PFOS, PFOA and the short chain PFBS significantly inhibited aromatase activity. • A mixture of perfluorinated chemicals significantly altered placenta cell

  1. In vitro and in vivo models for the evaluation of new inhibitors of human steroid sulfatase, devoid of residual estrogenic activity.

    Science.gov (United States)

    Shields-Botella, J; Bonnet, P; Duc, I; Duranti, E; Meschi, S; Cardinali, S; Prouheze, P; Chaigneau, A M; Duranti, V; Gribaudo, S; Rivière, A; Mengual, L; Carniato, D; Cecchet, L; Lafay, J; Rondot, B; Sandri, J; Pascal, J C; Delansorne, R

    2003-02-01

    The goal of our research project is to develop a new class of orally active drugs, estrone sulfatase inhibitors, for the treatment of estrogen-dependent (receptor positive) breast cancer. Several compounds were synthesized and their pharmacological potencies explored. Based on encouraging preliminary results, three of them, TX 1299, TX 1492 and TX 1506 were further studied in vitro as well as in vivo. They proved to be strong inhibitors of estrone sulfatase when measured on the whole human JEG-3 choriocarcinoma and MCF-7 breast cancer cells and their IC(50)s found to be in the range of known standard inhibitors. Their residual estrogenic activity was checked as negative in the test of induction of alkaline phosphatase (APase) activity in whole human endometrial adenocarcinoma Ishikawa cells. In addition, their effect on aromatase activity in JEG-3 cells was also examined, since the goal of inhibiting both sulfatase and aromatase activities appears very attractive. However, it has been unsuccessful so far. Then, in vivo potencies of TX 1299, the lead compound in our chemical series, were evaluated in comparison with 6,6,7-COUMATE, a non-steroidal standard, in two different rat models and by oral route. First, the absence of any residual estrogenic activity for these compounds was checked in the uterotrophic model in prepubescent female rats. Second, antiuterotrophic activity in adult ovariectomized rat supplemented with estrone sulfate (E(1)S), showed that both compounds were potent inhibitors, the power of TX 1299 relative to 6,6,7-COUMATE being around 80%. This assay was combined with uterine sulfatase level determination and confirmed the complete inhibition of this enzyme within the target organ. Preliminary studies indicated that other non-steroid compounds in the Théramex series were potent in vitro and in vivo inhibitors of estrone sulfatase in rats and further studies are in progress.

  2. Robot - assisted laparoscopic retroperitoneal lymph node dissection in testicular tumor

    Science.gov (United States)

    Torricelli, Fabio C. M.; Jardim, Denis; Guglielmetti, Giuliano B.; Patel, Vipul; Coelho, Rafael F.

    2017-01-01

    ABSTRACT Introduction and objective Retroperitoneal lymph node dissection (RPLND) is indicated for patients with non-seminomatous germ cell tumor (NSGCT) with residual disease after chemotherapy. Although the gold standard approach is still the open surgery, few cases of robot-assisted laparoscopic RPLND have been described. Herein, we aim to present the surgical technique for robot-assisted laparoscopic RPLND. Patient and method A 30 year-old asymptomatic man presented with left testicular swelling for 2 months. Physical examination revealed an enlarged and hard left testis. Alpha-fetoprotein (>1000ng/mL) and beta-HCG (>24.000U/L) were increased. Beta-HCG increased to >112.000U/L in less than one month. The patient underwent a left orchiectomy. Pathological examination showed a mixed NSGCT (50% embryonal carcinoma; 30% teratoma; 10% yolk sac; 10% choriocarcinoma). Computed tomography scan revealed a large tumor mass close to the left renal hilum (10x4x4cm) and others enlarged paracaval and paraortic lymph nodes (T2N3M1S3-stage III). Patient was submitted to 4 cycles of BEP with satisfactory response. Residual mass was suggestive of teratoma. Based on these findings, he was submitted to a robot-assisted RPLND. Results RPLND was uneventfully performed. Operative time was 3.5 hours. Blood loss was minimal, and there were no intra- or postoperative complications. The patient was discharged from hospital in the 1st postoperative day. Pathological examination showed a pure teratoma. After 6 months of follow-up, patient is asymptomatic with an alpha-fetoprotein of 2.9ng/mL and an undetectable beta-HCG. Conclusion Robot-assisted laparoscopic RPLND is a feasible procedure with acceptable morbidity even for post chemotherapy patients when performed by an experienced surgeon.

  3. Trypanosoma cruzi (Chagas' disease agent reduces HIV-1 replication in human placenta

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    Cappa Stella

    2008-07-01

    Full Text Available Abstract Background Several factors determine the risk of HIV mother-to-child transmission (MTCT, such as coinfections in placentas from HIV-1 positive mothers with other pathogens. Chagas' disease is one of the most endemic zoonoses in Latin America, caused by the protozoan Trypanosoma cruzi. The purpose of the study was to determine whether T. cruzi modifies HIV infection of the placenta at the tissue or cellular level. Results Simple and double infections were carried out on a placental histoculture system (chorionic villi isolated from term placentas from HIV and Chagas negative mothers and on the choriocarcinoma BeWo cell line. Trypomastigotes of T. cruzi (VD lethal strain, either purified from mouse blood or from Vero cell cultures, 24 h-supernatants of blood and cellular trypomastigotes, and the VSV-G pseudotyped HIV-1 reporter virus were used for the coinfections. Viral transduction was evaluated by quantification of luciferase activity. Coinfection with whole trypomastigotes, either from mouse blood or from cell cultures, decreased viral pseudotype luciferase activity in placental histocultures. Similar results were obtained from BeWo cells. Supernatants of stimulated histocultures were used for the simultaneous determination of 29 cytokines and chemokines with the Luminex technology. In histocultures infected with trypomastigotes, as well as in coinfected tissues, IL-6, IL-8, IP-10 and MCP-1 production was significantly lower than in controls or HIV-1 transducted tissue. A similar decrease was observed in histocultures treated with 24 h-supernatants of blood trypomastigotes, but not in coinfected tissues. Conclusion Our results demonstrated that the presence of an intracellular pathogen, such as T. cruzi, is able to impair HIV-1 transduction in an in vitro system of human placental histoculture. Direct effects of the parasite on cellular structures as well as on cellular/viral proteins essential for HIV-1 replication might influence

  4. Effect of nomegestrol acetate on estrogen biosynthesis and transformation in MCF-7 and T47-D breast cancer cells.

    Science.gov (United States)

    Shields-Botella, J; Chetrite, G; Meschi, S; Pasqualini, J R

    2005-01-01

    androstenedione to E(1) in the aromatase-rich choriocarcinoma cell line JEG-3. In conclusion, the inhibitory effect provoked by NOMAC on the enzymes involved in the biosynthesis of E(2) (sulfatase and 17HSD pathways) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive E(1)S, can open attractive perspectives for future clinical trials.

  5. Targeting the active site of the placental isozyme of alkaline phosphatase by phage-displayed scFv antibodies selected by a specific uncompetitive inhibitor

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    Kala Mrinalini

    2005-12-01

    Full Text Available Abstract Background The isozymes of alkaline phosphatase, the tissue non-specific, intestinal and placental, have similar properties and a high degree of identity. The placental isozyme (PLAP is an oncofetal antigen expressed in several malignancies including choriocarcinoma, seminoma and ovarian carcinoma. We had earlier attempted to isolate PLAP-specific scFv from a synthetic human immunoglobulin library but were unable to do so, presumably because of the similarity between the isozymes. In this work, we have employed a PLAP-specific uncompetitive inhibitor, L-Phe-Gly-Gly, to select isozyme specific scFvs. An uncompetitive inhibitor binds to the enzyme in the presence of substrate and stabilizes the enzyme-substrate complex. Several uncompetitive inhibitors have varying degrees of isozyme specificity for human alkaline phosphatase isozymes. A specific uncompetitive inhibitor would be able to unmask conformational differences between the otherwise very similar molecules. Also, such inhibitors would be directed to regions at/close to the active site of the enzyme. In this work, the library was first incubated with PLAP and the bound clones then eluted by incubation with L-Phe-Gly-Gly along with the substrate, para-nitro phenyl phosphate (pNPP. The scFvs were then studied with regard to the biochemical modulation of their binding, isozyme specificity and effect on enzyme activity. Results Of 13 clones studied initially, the binding of 9 was inhibited by L-Phe-Gly-Gly (with pNPP and 2 clones were inhibited by pNPP alone. Two clones had absolute and 2 clones had partial specificity to PLAP. Two clones were cross-reactive with only one other isozyme. Three scFv clones, having an accessible His6-tag, were purified and studied for their modulation of enzyme activity. All the three scFvs inhibited PLAP activity with the kinetics of competitive inhibition. Cell ELISA could demonstrate binding of the specific scFvs to the cell surface expressed PLAP

  6. New discoveries on the biology and detection of human chorionic gonadotropin

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    Cole Laurence A

    2009-01-01

    Full Text Available Abstract Human chorionic gonadotropin (hCG is a glycoprotein hormone comprising 2 subunits, alpha and beta joined non covalently. While similar in structure to luteinizing hormone (LH, hCG exists in multiple hormonal and non-endocrine agents, rather than as a single molecule like LH and the other glycoprotein hormones. These are regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG. For 88 years regular hCG has been known as a promoter of corpus luteal progesterone production, even though this function only explains 3 weeks of a full gestations production of regular hCG. Research in recent years has explained the full gestational production by demonstration of critical functions in trophoblast differentiation and in fetal nutrition through myometrial spiral artery angiogenesis. While regular hCG is made by fused villous syncytiotrophoblast cells, extravillous invasive cytotrophoblast cells make the variant hyperglycosylated hCG. This variant is an autocrine factor, acting on extravillous invasive cytotrophoblast cells to initiate and control invasion as occurs at implantation of pregnancy and the establishment of hemochorial placentation, and malignancy as occurs in invasive hydatidiform mole and choriocarcinoma. Hyperglycosylated hCG inhibits apoptosis in extravillous invasive cytotrophoblast cells promoting cell invasion, growth and malignancy. Other non-trophoblastic malignancies retro-differentiate and produce a hyperglycosylated free beta-subunit of hCG (hCG free beta. This has been shown to be an autocrine factor antagonizing apoptosis furthering cancer cell growth and malignancy. New applications have been demonstrated for total hCG measurements and detection of the 3 hCG variants in pregnancy detection, monitoring pregnancy outcome, determining risk for Down syndrome fetus, predicting preeclampsia, detecting pituitary hCG, detecting and managing gestational trophoblastic diseases, diagnosing quiescent

  7. A novel radioligand for glycine transporter 1: characterization and use in autoradiographic and in vivo brain occupancy studies

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Zhizhen [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)], E-mail: zhizhen_zeng@merck.com; O' Brien, Julie A. [Sleep and Psychiatric Disorders, Merck Research Laboratories, West Point, PA 19486 (United States); Lemaire, Wei [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); O' Malley, Stacey S.; Miller, Patricia J. [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States); Zhao Zhijian [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); Wallace, Michael A. [Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065 (United States); Raab, Conrad [Drug Metabolism, Merck Research Laboratories, West Point, PA 19486 (United States); Lindsley, Craig W. [Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486 (United States); Departments of Pharmacology and Chemistry, Vanderbilt University, Nashville, TN 37232 (United States); Sur, Cyrille; Williams, David L. [Imaging, Merck Research Laboratories, West Point, PA 19486 (United States)

    2008-04-15

    Introduction: In an effort to develop agents to test the NMDA hypofunction hypothesis of schizophrenia, benchmark compounds from a program to discover potent, selective, competitive glycine transporter 1 (GlyT1) inhibitors were radiolabeled in order to further study the detailed pharmacology of these inhibitors and the distribution of GlyT1 in brain. We here report the in vitro characterization of [{sup 35}S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl) ethyl)benzamide ([{sup 35}S]ACPPB), a radiotracer developed from a potent and selective non-sarcosine-derived GlyT1 inhibitor, its use in autoradiographic studies to localize (S)-2-amino-6-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl)ethyl) benzamide (ACPPB) binding sites in rat and rhesus brain and for in vivo occupancy assays of competitive GlyT1 inhibitors. Methods: Functional potencies of unlabeled compounds were characterized by [{sup 14}C]glycine uptake into JAR (human placental choriocarcinoma) cells and synaptosomes. Radioligand binding studies were performed with tissue homogenates. Autoradiographic studies were performed on tissue slices. Results: ACPPB is a potent (K{sub d}=1.9 nM), selective, GlyT1 inhibitor that, when radiolabeled with [{sup 35}S], is a well-behaved radioligand with low nondisplaceable binding. Autoradiographic studies of rat and rhesus brain slices with this ligand showed that specific binding sites were plentiful and nonhomogeneously distributed, with high levels of binding in the brainstem, cerebellar white matter, thalamus, cortical white matter and spinal cord gray matter. In vivo studies demonstrate displaceable binding of [{sup 35}S]ACPPB in rat brain tissues following iv administration of this radioligand. Conclusions: This is the first report of detailed anatomical localization of GlyT1 using direct radioligand binding, and the first demonstration that an in vivo occupancy assay is feasible, suggesting that it may also be feasible to develop

  8. In vitro placental model optimization for nanoparticle transport studies

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    Cartwright L

    2012-01-01

    Full Text Available Laura Cartwright1, Marie Sønnegaard Poulsen2, Hanne Mørck Nielsen3, Giulio Pojana4, Lisbeth E Knudsen2, Margaret Saunders1, Erik Rytting2,51Bristol Initiative for Research of Child Health (BIRCH, Biophysics Research Unit, St Michael's Hospital, UH Bristol NHS Foundation Trust, Bristol, UK; 2University of Copenhagen, Faculty of Health Sciences, Department of Public Health, 3University of Copenhagen, Faculty of Pharmaceutical Sciences, Department of Pharmaceutics and Analytical Chemistry, Copenhagen, Denmark; 4Department of Environmental Sciences, Informatics and Statistics, University Ca' Foscari Venice, Venice, Italy; 5Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Texas, USABackground: Advances in biomedical nanotechnology raise hopes in patient populations but may also raise questions regarding biodistribution and biocompatibility, especially during pregnancy. Special consideration must be given to the placenta as a biological barrier because a pregnant woman's exposure to nanoparticles could have significant effects on the fetus developing in the womb. Therefore, the purpose of this study is to optimize an in vitro model for characterizing the transport of nanoparticles across human placental trophoblast cells.Methods: The growth of BeWo (clone b30 human placental choriocarcinoma cells for nanoparticle transport studies was characterized in terms of optimized Transwell® insert type and pore size, the investigation of barrier properties by transmission electron microscopy, tight junction staining, transepithelial electrical resistance, and fluorescein sodium transport. Following the determination of nontoxic concentrations of fluorescent polystyrene nanoparticles, the cellular uptake and transport of 50 nm and 100 nm diameter particles was measured using the in vitro BeWo cell model.Results: Particle size measurements, fluorescence readings, and confocal microscopy indicated both cellular uptake of

  9. Modulating drug resistance by targeting BCRP/ABCG2 using retrovirus-mediated RNA interference.

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    Ni Xie

    Full Text Available The BCRP/ABCG2 transporter, which mediates drug resistance in many types of cells, depends on energy provided by ATP hydrolysis. Here, a retrovirus encoding a shRNA targeting the ATP-binding domain of this protein was used to screen for highly efficient agents that could reverse drug resistance and improve cell sensitivity to drugs, thus laying the foundation for further studies and applications.To target the ATP-binding domain of BCRP/ABCG2, pLenti6/BCRPsi shRNA recombinant retroviruses, with 20 bp target sequences starting from the 270th, 745th and 939th bps of the 6th exon, were constructed and packaged. The pLenti6/BCRPsi retroviruses (V-BCRPi that conferred significant knockdown effects were screened using a drug-sensitivity experiment and flow cytometry. The human choriocarcinoma cell line JAR, which highly expresses endogenous BCRP/ABCG2, was injected under the dorsal skin of a hairless mouse to initiate a JAR cytoma. After injecting V-BCRPi-infected JAR tumor cells into the dorsal skin of hairless mice, BCRP/ABCG2 expression in the tumor tissue was determined using immunohistochemistry, fluorescent quantitative RT-PCR and Western blot analyses. After intraperitoneal injection of BCRP/ABCG2-tolerant 5-FU, the tumor volume, weight change, and apoptosis rate of the tumor tissue were determined using in situ hybridization. V-BCRPi increased the sensitivity of the tumor histiocytes to 5-FU and improved the cell apoptosis-promoting effects of 5-FU in the tumor.The goal of the in vivo and in vitro studies was to screen for an RNA interference recombinant retrovirus capable of stably targeting the ATP-binding domain of BCRP/ABCG2 (V-BCRPi to inhibit its function. A new method to improve the chemo-sensitivity of breast cancer and other tumor cells was discovered, and this method could be used for gene therapy and functional studies of malignant tumors.

  10. Steroidal inhibitors as chemical probes of the active site of aromatase.

    Science.gov (United States)

    Brueggemeir, R W; Moh, P P; Ebrahimian, S; Darby, M V

    1993-03-01

    Androstenedione analogs containing 7 alpha-substituents have proven to be potent inhibitors of aromatase in human placental microsomes, in MCF-7 mammary cell cultures, and in JAr choriocarcinoma cells. Recent investigations have focused on the use of mechanism-based inhibitors, such as 7 alpha-substituted 1,4-androstadienediones, to biochemically probe the active site of aromatase. Inhibition kinetics were determined under initial velocity conditions using purified human placental cytochrome P450arom protein in a reconstituted system. Derivatives of 1,4-androstadiene-3,17-dione and 1,4,6-androstatriene-3,17-dione exhibited high affinity in the purified enzyme system. 7 alpha-(4'-Amino)phenylthio-1,4-androstadiene-3,17-dione, abbreviated 7 alpha-APTADD, demonstrated rapid time-dependent, first-order inactivation of reconstituted aromatase activity only in the presence of NADPH. The apparent Kinact for 7 alpha-APTADD is 11.8 nM, the first-order rate of inactivation is 2.72 x 10(-3) sec-1, and the half-time of inactivation at infinite inhibitor concentration is 4.25 min. The values for the rate constant and half-time of inactivation are similar to those observed in the placental microsomal assay system. Further studies were performed with radioiodinated 7 alpha-(4'-iodo)phenylthio-1,4-androstadienedione, 7 alpha-IPTADD, and the reconstituted aromatase system. Incubations with [125I] 7 alpha-IPTADD were followed by protein precipitation, solvent extraction, and column chromatography. Analysis of the isolated cytochrome P450arom by gel electrophoresis and autoradiography demonstrated the presence of only one radioactive band, which corresponded to the protein staining band for cytochrome P450arom. HPLC radiochromatographic analysis of the isolated cytochrome P450aroM confirmed the presence of only one radioactive peak coeluting with the u.v. peak for cytochrome P450arom. Peptide mapping analysis by reverse-phase HPLC of digested inhibitor-cytochrome P450arom complex

  11. Autophagy in the human placenta throughout gestation.

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    Tai-Ho Hung

    Full Text Available BACKGROUND: Autophagy has been reported to be essential for pre-implantation development and embryo survival. However, its role in placental development and regulation of autophagy during pregnancy remain unclear. The aims of this study were to (1 study autophagy by characterizing changes in levels of beclin-1, DRAM, and LC3B in human placenta throughout gestation; (2 determine whether autophagy is involved in regulation of trophoblast invasion in JEG-3 cells (a choriocarcinoma cell line; (3 examine the effects of reduced oxygen and glucose on the autophagic changes; and (4 investigate the effect of reoxygenation and supplementation of glucose after oxygen-glucose deprivation (OGD on the autophagic changes in primary cytotrophoblasts obtained from normal term pregnancy. METHODOLOGY/PRINCIPAL FINDINGS: An analysis of 40 placental samples representing different gestational stages showed (1 no significant differences in beclin-1, DRAM, and LC3B-II levels in placentas between early and mid-gestation, and late gestation with vaginal delivery; (2 placentas from late gestation with cesarean section had lower levels of LC3B-II compared to early and mid-gestation, and late gestation with vaginal delivery; levels of DRAM were also lower compared to placentas from early and mid-gestation; and (3 using explant cultures, villous tissues from early and late gestation had similar rates of autophagic flux under physiological oxygen concentrations. Knockdown of BECN1, DRAM, and LC3B had no effects on viability and invasion activity of JEG-3 cells. On the other hand, OGD caused a significant increase in the levels of LC3B-II in primary cytotrophoblasts, while re-supplementation of oxygen and glucose reduced these changes. Furthermore, there were differential changes in levels of beclin-1, DRAM, and LC3B-II in response to changes in oxygen and glucose levels. CONCLUSIONS/SIGNIFICANCE: Our results indicate that autophagy is involved in development of the human

  12. RISK FACTORS FOR GESTATIONAL TROPHOBLASTIC NEOPLASIA: A CASE CONTROL STUDY IN A TERTIARY HOSPITAL

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    Hema Sreedharan Nair

    2016-10-01

    Full Text Available BACKGROUND Gestational trophoblastic disease is a spectrum of proliferative abnormalities of the trophoblast. GTD represents a benign form of the disease while GTN is the malignant often metastatic lesion. 75-80 per cent of patients initially diagnosed as GTD will follow a benign course after dilatation and curettage. 15-20 per cent develop locally invasive disease and 3-5 per cent develop metastatic lesions. The study aims to assess the proportion of gestational trophoblastic neoplasia among women with gestational trophoblastic disease and identify the risk factors for chemotherapy in gestational trophoblastic neoplasia. MATERIALS AND METHODS This is a case-control study conducted in a tertiary hospital during a 5-year period. Cases are gestational trophoblastic neoplasia diagnosed by either rising beta-HCG levels or plateauing beta-HCG levels or by histological evidence of choriocarcinoma. Controls are cases of gestational trophoblastic disease post evacuation with normal HCG regression at 8 weeks. There were 306 controls and 57 cases. RESULTS Tabulated and analysed using SPSS package. Of the 363 patients of gestational trophoblastic disease, 57 (15.7% needed chemotherapy. 98.2% belonged to the age group of 20-35 years. 63% had gestational age of more than 12 weeks, 56.1% had pre-evacuation HCG of more than 40,000. 15.7% needed combination therapy. CONCLUSION 1. 83.1% of patients belonged to age group of 20-30 years. 2. Blood group distribution of patients with gestational trophoblastic disease did not show any significance. 3. 15.7% of total patients were diagnosed to have gestational trophoblastic neoplasia that necessitated chemotherapy. 4. When uterine size was more than 12 weeks, a statistically significant number of patients needed chemotherapy compared to non-chemotherapy group. 5. When BHCG values were more than 40,000, a statistically significant number of patients needed chemotherapy. 6. A risk score of seven or more was found to

  13. 松果体区肿瘤的MRI表现与其病理学对照研究%Relationship of manifestations of pineal region tumors on MRI with their pathology

    Institute of Scientific and Technical Information of China (English)

    邱炳辉; 肖罡; 莫益萍; 邱晓瑜; 方陆雄; 漆松涛

    2011-01-01

    Objectives To study the manifestations of differently pathological pineal region tumors on MRI and evaluate the MRI value to their diagnosis. Method The pathological data of 131 cases of pineal region tumors, which were removed by microsurgery from January, 1999 to January, 2009, were compared with their manifestations on preoperative MRI. Results Of 131 cases of pineal region rumors, 21 were germinomas, 18 teratomas, 6 choriocarcinomas, 2 embryonal careinomas, 1 endodermal sinus tumor, 12 mixed germ cell tumors, 27 neuroepithelial rumors, 17 pineal parenchymal cell tumors, 14 menigiomas and 13 other tumors. The enhancement of all the lesions which differed in degree on MRI was observed in 60 cases of the germ cell tumors, of which, 39 had little cystic components and 21 did not. There were typical butterfly signs on MRI in 5 cases of germinomas and typical honeycomb-like appearance on MRI in 13 cases of teratomas. MRI showed that there was hemorrhage in 5 of 6 cases of choriocarcinomas. There were clear bounds and strong and homogeneous enhancement on MRI in 14 cases of meningiomas, of which, 6 had the thickening of the adjacent dura and 8 did not. There were significantly different manifestation on MRI among 17 cases of pineal parenchymal cell tumors, 27 cases of neuroepithelial tissue rumors, and 13 cases of the others tumors in the pineal regions. Conclusions The manifestations of the pineal region tumors on MRI were related to their pathological type. Some manifestations of the part pineal region tumors on MRI were highly special, but the MRI sensitivity to the diagnosis of the pineal region tumors was low. It is still difficult to discriminate the accurate pathological quality of the pineal region tumors by MRI.%目的 探讨不同病理性质的松果体区肿瘤MRI表现,评价其临床诊断价值.方法 回顾性分析1999年1月至2009年1月经开颅手术治疗的131例松果体区肿瘤患者的MRI及病理学资料,并进行对比分析.结果 这131

  14. p16 Cyclin D1在妊娠滋养细胞疾病组织中 的表达及意义%Expression of pi6 and Cyclin D1 in the tissues of gestational trophoblastic diseases and its significance

    Institute of Scientific and Technical Information of China (English)

    梁劲荃; 赵或明; 梁睿; 主改霞; 孙润琴

    2001-01-01

    Objective To detect the significance of p16 and CyclinD1 in the tumorigenesis of trophoblastic tumors.Methods Immunohistochemical SP method was used to detect the p16 and CyclinD1 gene expression in the tissues of 49 cases of trophoblastic diseases ( the primary curretage tissues of moles 32 cases, invasive moles 12 cases and choriocarcinoma 5 cases ) and 4 cases of normal chorion of early gestation. Results The expression of p16 and CyclinD1 was respectively all positive and all negative in the chorion of early gestation. When the moles that didn′t transform to malignancy, the moles that did transform and the trophoblasfic tumors were detected,a descending tendency of p16 expression was found ,while the expression of CyclinD1 showed an ascending tendency. The positive rate of p16 expression was significantly different between the following groups: the moles transforming malignantly later and the moles that didnt transform,the moles that didnt transform and the invasive moles( P 0.05). Conclusions The absent expression of the cell cycle regulating gene pi6 and the excessive expression of cyclinD1 may play a key role in the malignant transformation of trophocyte and in the development of invasive moles. Detection of p16 and Cyclin D1 expression in the primary curretage tissues of moles may be of great value in assessing the prognosis of moles.%目的探讨p16、CyclinD1基因在滋养细胞肿瘤发生方面的意义。方法用免疫组化SP法,对49例滋养细胞疾病组织(葡萄胎首次清宫标本32例,侵蚀性葡萄胎及绒癌子宫标本分别为12例和5例)和4例早孕正常绒毛组织中p16和CyclinD1进行检测。结果在早孕绒毛组织中,pi6和CyclinD1表达分别为全部阳性和全部阴性。在不恶变葡萄胎、以后发生恶变的葡萄胎和滋养细胞肿瘤中p16表达呈下降趋势,CyclinD1表达呈上升趋势。p16和CyclinD1表达阳性率在不恶变葡萄胎与以后发生恶变的葡萄胎组间、在不恶变

  15. Pathological features and origin of primary pineal mixed germ cell tumors%原发性松果体区混合性生殖细胞肿瘤病理特点及其起源探讨

    Institute of Scientific and Technical Information of China (English)

    肖罡; 方陆雄; 邱炳辉; 漆松涛

    2011-01-01

    choriocarcinoma component, 7 showed yolk sac tumor component, and 3 showed rhabdomyoma component. Germinoma components were found on the tumor margin in 7 specimens, and intermingled germinoma and other components were found in 10 specimens. Conclusion Pineal mixed germ cell tumor originates from the residue germ cells around the pineal gland, and most likely evolves from single primordial germ cells.

  16. Preparation of an antitumor and antivirus agent: chemical modification of α-MMC and MAP30 from Momordica Charantia L. with covalent conjugation of polyethyelene glycol

    Directory of Open Access Journals (Sweden)

    Meng Y

    2012-06-01

    Full Text Available Yao Meng,1,2 Shuangfeng Liu,1 Juan Li,3 Yanfa Meng,3 Xiaojun Zhao2,41School of Medical Laboratory Science, Chengdu Medical College, Chengdu, China; 2West China Hospital Laboratory of Nanomedicine and Institute for Nanobiomedical Technology and Membrane Biology, Sichuan University, Chengdu, China; 3Key Laboratory of Bio-resources and Eco-environment Ministry of Education/Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, College of Life Science, Sichuan University, Chengdu, China; 4Center for Biomedical Engineering, Massachusetts Institute of Technology, Cambridge, MA, USABackground: Alpha-momorcharin (α-MMC and momordica anti-HIV protein (MAP30 derived from Momordica charantia L. have been confirmed to possess antitumor and antivirus activities due to their RNA-N-glycosidase activity. However, strong immunogenicity and short plasma half-life limit their clinical application. To solve this problem, the two proteins were modified with (mPEG2-Lys-NHS (20 kDa.Methodology/principal findings: In this article, a novel purification strategy for the two main type I ribosome-inactivating proteins (RIPs, α-MMC and MAP30, was successfully developed for laboratory-scale preparation. Using this dramatic method, 200 mg of α-MMC and about 120 mg of MAP30 was obtained in only one purification process from 200 g of Momordica charantia seeds. The homogeneity and some other properties of the two proteins were assessed by gradient SDS-PAGE, electrospray ionization quadruple mass spectrometry, and N-terminal sequence analysis as well as Western blot. Two polyethylene glycol (PEGylated proteins were synthesized and purified. Homogeneous mono-, di-, or tri-PEGylated proteins were characterized by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The analysis of antitumor and antivirus activities indicated that the serial PEGylated RIPs preserved moderate activities on JAR choriocarcinoma cells and herpes simplex

  17. 妊娠滋养细胞疾病中EMT相关蛋白CK19和N-cad表达的研究%The expression of epithelial to mesenchymal transition associated protein of CK19 and N-cad in gestational trophoblastic disease

    Institute of Scientific and Technical Information of China (English)

    徐洁; 薛艳; 曾宪玲; 安瑞芳

    2014-01-01

    目的:探讨上皮细胞向间质转化(EMT)相关蛋白细胞角蛋白19(CK19)和神经钙黏蛋白( N-cad)在妊娠滋养细胞疾病发生、发展中的作用。方法:采用免疫组化S-P法检测了41例正常早孕绒毛( NP)、31例葡萄胎( HM)、32例妊娠滋养细胞肿瘤( GTN)[26例侵蚀性葡萄胎(IM)+6例绒癌(CCA)]中CK19和N-cad的定位及表达情况。结果:NP组中CK19和N-cad蛋白相对表达均显著高于HM、GTN组(P<0.05),HM组显著高于GTN组(P<0.05)。 CK19与N-cad的表达无相关性(r=0.202,P=0.268)。结论:伴随着滋养细胞恶性程度的升高,CK19和N-cad表达逐渐降低,提示EMT可能与滋养细胞的恶性转化有关。%Objective:To explore the role of epithelial to mesenchymal transition (EMT) associated protein of Cytokeratin 19 (CK19) and N-cadherin (N-cad) in oncogenesis, development of gestational trophoblastic disease ( GTD) . Methods:CK19 and N-cad were de-tected Immunohistochemically in paraffin-embedded tissue of 41 cases of normal placenta ( NP) ,31 cases of hydatidiform mole ( HM ) , 32 cases of gestational trophoblastic neoplasia ( GTN ) [ 26 cases of invasive hydatidiform mole ( IM ) and 6 cases of choriocarcinoma (CCA)]. Results:In NP,HM and GTN,the median mean density of CK19 was (7. 62±5. 54) ×10-2,(4. 76±3. 33)×10-2,(3. 20±3. 84)×10-2,respectively,the median mean density of N-cad was (10.6±8.39)×10-2,(4.15±4.19)×10-2,(2.28±3.05)×10-2,respectively. There were significant differences between NP and HM,GTN (P<0. 05),and between HM and GTN ( P<0 . 05 ) . There was no correlation between CK19 and N-cad ( r=0 . 202 , P=0 . 268 ) . Con-clusions:The expressions of CK19 and N-cad decrease with the increase of tropohblast malig-nancy which indicate that CK19 and N-cad may involve in the events of malignant transforma-tion of trophocytes,and EMT may play an important role in the malignant progression of GTD.

  18. Histological features of tumor-bearing tissues formed by human fibroblasts after reprograming by Piwil2%P iwil2重编程人成纤维细胞成瘤组织的组织学特征

    Institute of Scientific and Technical Information of China (English)

    曾广平; 吴鑫; 何大维; 扶溢瑶; 刘星; 张德迎; 林涛; 魏光辉

    2015-01-01

    Objective To observe the histological features of tumor⁃bearing tissues formed by human fibroblasts after reprograming by spermatogonial stem cell self⁃renewal key regulating gene Piwil2 ( Piwil2⁃iCSC) . Methods Piwil2⁃iCSC tumor spheroids⁃like colonies were selected for tumor formation assay in four nude mice. Pathological features of Piwil2⁃iCSC tumors were observed by histology. Stem cell markers and common triploblastic markers were detected by reverse transcriptase⁃polymerase chain reaction ( RT⁃PCR ) assay and immunohistochemistry. Germ cell tumor markers were detected by immunohistochemical examination. Results Two weeks after inoculation, subcutaneous tumors were formed in all the four nude mice with a tumor formation rate of 100%. In the Piwil2⁃iCSC tumor tissues, Piwil2⁃GFP+ cells showed high⁃density nuclear expression and were widely observed in DAPI⁃stained sections. Numerous mitotic figure of the neoplastic cells were seen (> 10 cells/field of vision under high magnification) in HE⁃stained sections. Enlarged abnormal cell nuclei were observed. RT⁃PCR assay showed that Piwil2⁃iCSC tumors still expressed Piwil2 and some self⁃renewal and pluripotent markers of stem cells and some markers of triploblastic differentiation. Immunohistochemical staining showed that the tumors expressed stem cell markers, triploblastic markers and germ cell tumor markers AFP and HCG. Conclusions Piwil2⁃iCSC tumors are probably undifferentiated embryonic small cell carcinoma, most likely to be immature teratoma, mixed with yolk sac tumor and choriocarcinoma components. It can be used as a useful model for the research of origin or genesis mechanism of cancer stem cells and the treatment of relevant tumors.%目的:观察生殖干细胞自我更新关键调节基因Piwil2重编程人包皮成纤维细胞获得的肿瘤干细胞( Piwil2⁃iCSC)体内成瘤组织的组织学特征。方法挑选Piwil2⁃iCSC肿瘤球样克隆细胞进行裸

  19. Expression of Cyclin E and Its Related Proteins in Gestational Trophoblastic Disease%滋养细胞疾病中Cyclin E及其相关蛋白的表达

    Institute of Scientific and Technical Information of China (English)

    李娜; 曲芃芃

    2014-01-01

    目的:探讨细胞周期蛋白E(Cyclin E)、细胞周期蛋白依赖激酶2(CDK-2)、P27KIP1和P21WAF1/CIP1在正常胎盘组织、葡萄胎和滋养细胞肿瘤(gestational trophoblastic neoplasia,GTN)组织中的表达,研究上述指标表达水平的相关性以及与妊娠滋养细胞疾病(gestational trophoblastic disease,GTD)的关系。方法:采用链霉素-过氧化物酶免疫组化方法检测30例正常胎盘组织、38例葡萄胎组织和9例GTN组织(侵蚀性葡萄胎8例,绒癌1例)中Cyclin E、CDK-2、P27KIP1和P21WAF1/CIP1的表达,分析其与GTD发生发展及预后的关系。结果:①Cyclin E、CDK-2在葡萄胎和GTN组织中的表达高于正常胎盘组织(P<0.01);P27KIP1和P21WAF1/CIP1在GTN组织中的表达低于葡萄胎和正常胎盘组织(P<0.05), P27KIP1和P21WAF1/CIP1在发生恶性转变的葡萄胎组织中的表达低于未发生恶变者(P<0.05)。②Cyclin E与P27KIP1、P21WAF1/CIP1的表达呈负相关(P<0.05);Cyclin E与CDK-2的表达呈正相关(P<0.05);P27KIP1与P21WAF1/CIP1的表达呈正相关(P<0.05)。CDK-2表达随P27KIP1和P21WAF1/CIP1的表达降低呈增高趋势,但差异无统计学意义(P>0.05)。结论:Cyclin E/CDK-2复合物及其抑制蛋白P27KIP1和P21WAF1/CIP1的异常表达参与了GTN的发生发展;P27KIP1和P21WAF1/CIP1可能成为预测葡萄胎恶变的有效标记物。%Objective: To investigate the expression of Cyclin E,CDK-2 and their inhibitors P27KIP1 and P21WAF1/CIP1 in gestational trophoblastic disease (GTD). Methods:Expression of the above indexes were determined immunohistochemically by specific antibodies for these proteins on formalin-fixed paraffin sections of 30 of normal placenta tissues ,38 of hydatidiform moles and 9 of gestational trophoblastic neoplasms (GTN), including 8 invasive moles and 1 choriocarcinoma. Results:①The expression of Cyclin E and CDK-2 in GTD was significantly

  20. 高危型妊娠滋养细胞肿瘤的评估与治疗%Evaluation and management of high-risk gestational trophoblastic neoplasm

    Institute of Scientific and Technical Information of China (English)

    于海林; 奚美丽; 李俊; 鹿欣

    2015-01-01

    for high-risk patients is still 70% to 80% as a result of drug resistance and disease recurrence. This study aimed to evaluate the clinical characteristics and outcome of patients with high-risk GTN.Methods:The clinical records of patients with high-risk GTN treated in Obstetrics and Gynecology Hospital of Fudan University from Jan. 2003 to Jan. 2013 were analyzed and reviewed retrospectively from the aspect of different treatment.Results:Fifty-one patients with high-risk GTN were admitted to this hospital. Among 51 high-risk GTN patients, 46 patients were evaluated retrospectively and 5 patients were excluded for incomplete treatments. Of the 46 patients with high-risk GTN, 27 patients were treated by chemotherapy alone, 19 patients received chemotherapy and adjuvant surgical therapy. Forty-four patients received EMA-CO (VP-16+Act-D+MTX/VCR+CTX) as a ifrst-line chemotherapy, 81.82% (36/44) had complete remission and 8 patients developed resistance to EMA-CO. EMA-EP (VP-16+Act-D+MTX/VP-16+cisplatin) was used as second-line chemotherapy for the 8 patients resistant to EMA-CO, 6 patients (2 underwent adjuvant surgical therapy) achieved remission and 2 patients died as a result of drug-resistance and disease progression. For the remaining 2 patients, one was treated by 5-FU+KSM and pulmonary resection, and the other was treated by MTX for misdiagnosis as ectopic pregnancy and then converted to EMA-CO for the pathological diagnosis of choriocarcinoma after surgery. Both of them achieved complete remission. Ultimately, 95.65% (44/46)patients achieved complete remission. Among the 19 patients who underwent adjuvant surgical therapy, 94.70% (18/19) patients achieved complete remission after chemotherapy and adjuvant surgery, and the remaining one patient died of disease progression.Conclusion:Standard combination chemotherapy is crucial in the treatment of high-risk GTN. The role of adjuvant surgery in the management of high-risk GTN should not be underestimated.

  1. Value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia cases with uterine mass%腹腔镜手术在以宫体占位为主的可疑妊娠滋养细胞肿瘤诊断中的价值

    Institute of Scientific and Technical Information of China (English)

    李晓川; 冯凤芝; 向阳; 万希润; 任彤; 杨隽钧

    2015-01-01

    Objective To evaluate the value of laparoscopic surgery in the diagnosis of suspected gestational trophoblastic neoplasia (GTN) cases with uterine mass.Methods The clinical characteristics of patients underwent laparoscopic surgery for a suspected diagnosis of GTN with uterine mass in Peking Union Medical College Hospital from November 2009 to November 2014 were retrospectively reviewed and analyzed.GTN and other pregnant-related disease were definitely diagnosed by pathological findings.The prognoses of the GTN cases were also investigated.Results Sixty-two patients with a suspected diagnosis of GTN with uterine mass were studied.Among them,17 cases were definitely diagnosed as GTN,including 8 choriocarcinoma,5 invasive mole and 4 placental site trophoblastic tumor(PSTT).The other 45 cases were diagnosed as benign pregnancy-related diseases,including 29 cornual pregnancy,6 cesarean scar pregnancy,5 placenta accreta,4 intramural uterine pregnancy and 1 exaggerated placental site.There were no significantly differences between the two groups in average age,preoperative value or tendency of β-hCG,and location or size of lesions (P>0.05).More GTN patients showed a history of hydatidiform mole [5/17 vs 4% (2/45),P>0.05],and more patients with benign pregnancy-related disease showed a history of cesarean section [38% (17/45) vs 1/17,P>0.05].No serious perioperative complication was found in these patients received laparoscopic surgery.All GTN patients achieved complete remission by chemotherapy later.Except for 1 case loss,no recurrence was found in 11 low-risk stage Ⅰ cases with an average follow-up period of 11-66 months,1 high-risk stage Ⅰ case with a follow-up period of 61 months and 4 cases PSTT with a follow-up period of 13-66 months.Conclusions There were some atypical GTN cases with uterine mass,which were difficult to be differentiated from benign pregnancy-related diseases according to the clinical characteristics.Laparoscopic surgery with a