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Sample records for choriocarcinoma

  1. Postpartum choriocarcinoma

    International Nuclear Information System (INIS)

    Sirichand, P.; Das, C.M.; Hassan, N.

    2006-01-01

    Choriocarcinoma, following term pregnancy, is a rare form of gestational trophoblastic disease. The usual presentation is with persistent primary or secondary postpartum hemorrhage, the diagnosis is often delayed because of failure to recognize this mode of presentation of the disease. Early diagnosis is important because this rare condition is potentially curable with appropriate chemotherapy. A case of postpartum choriocarcinoma, following a term pregnancy is reported that was successfully treated with methotrexate therapy and surgery. (author)

  2. Choriocarcinoma of the Stomach

    International Nuclear Information System (INIS)

    Lee, Dong Ho; Ko, Young Tae; Lim, Jae Hee

    1987-01-01

    Choriocarcinoma is considered to be a malignant tumor of the trophoblast originating within the uterus. But it may be rarely encountered in the stomach. We have experienced a case of extragonadal choriocarcinoma arising from the stomach and present its ultrasonographic findings

  3. Gestational Trophoblastic Disease -Choriocarcinoma

    International Nuclear Information System (INIS)

    Bozik, M.

    2011-01-01

    Gestational trophoblastic tumors are a group of a diseases from the benign hydatidiform mole, through the invasive mole to the highly malignant form of a choriocarcinoma. Choriocarcinoma is a rare tumor and it is the most malignant and aggressive neoplasm of all the gestational trophoblastic diseases. It grows rapidly and metastasizes to the lung, liver, and, less frequently, to the brain. The author presents the case of a 26-year-old woman who is indicated to the CT examination for suspected brain tumor based on the previous examinations. The patient was diagnosed with metastatic choriocarcinoma to the brain, kidney and adrenal gland on the basis of an anamnesis by her husband, a high value of beta-hCG and a gynecological examination. (author)

  4. Epigenetic Therapy in Human Choriocarcinoma

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    Hisashi Narahara

    2010-09-01

    Full Text Available Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and promotion of tumorigenesis in choriocarcinomas, novel compounds endowed with a histone deacetylase (HDAC inhibitory activity are an attractive therapeutic approach. HDAC inhibitors (HDACIs were able to mediate inhibition of cell growth, cell cycle arrest, apoptosis, and the expression of genes related to the malignant phenotype in choriocarcinoma cell lines. In this review, we discuss the biologic and therapeutic effects of HDACIs in treating choriocarcinoma, with a special focus on preclinical studies.

  5. [Fetomaternal transfusion and diagnosis of gestational choriocarcinoma].

    Science.gov (United States)

    Emin, L; Izard, A; Schiavone, S; Kermanach, P; Deramecourt, M; Duclusaud, A; Gertych, W; Girard, S

    2015-03-01

    Choriocarcinoma is a rare but agressive malignant trophoblastic neoplasm. Fetomaternal transfusion can be the first sign of choriocarcinoma. We describe two cases of gestational choriocarinoma whose first manifestation was a fetomaternal transfusion. Fetomaternal transfusion is a rare demonstration of choriocarcinoma but its diagnosis must lead to a placenta examination with specific research of choriocarcinoma. The more the therapeutic care is precise, the better is the forecast. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  6. [Choriocarcinoma causing a pulmonary embolus.

    DEFF Research Database (Denmark)

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

    2008-01-01

    A 32 year-old women experienced dyspnea and thoracic pain that persisted with variable intensity over a course of eight months until acute worsening necessitated admission. A CT scan demonstrated a central pulmonary embolus. Subsequent surgical embolectomy produced a grained substance that was hi...... 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...

  7. Solitary infantile choriocarcinoma of the liver: MRI findings

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    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.)

  8. Incidental placental choriocarcinoma in a term pregnancy: a case report

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    Chung Christopher

    2008-10-01

    Full Text Available Abstract Introduction Gestational choriocarcinoma occurs in 1 in 40,000 pregnancies. Of all forms of gestational choriocarcinoma, placental choriocarcinoma is the most rare. Maternal choriocarcinoma is usually diagnosed in symptomatic patients with metastases. The incidental finding of a choriocarcinoma confined to the placenta with no evidence of dissemination to the mother, or infant is the least common scenario. Case presentation The patient is an 18 year-old Gravida 1 Para 1 African American female who delivered a viable 3641 g female infant at 39 weeks gestation. Her pregnancy course was complicated by gestational hypertension during the third trimester. Her placenta revealed intraplacental choriocarcinoma. She was then followed closely by the Gynecologic Oncology service with a weekly serum beta human chorionic gonadotropin value. Beta human chorionic gonadotropin values dropped from 3070 mIU/ml to less than 2 mIU/ml two months post partum. No chemotherapy was initiated. Metastasis was ruled out by chest x-ray and whole body computed tomography scan. To date, both mother and baby are well. Conclusion Due to the potential fatal outcome of placental choriocarcinoma, careful evaluation of both mother and infant after the diagnosis is made is important. The incidence of placental choriocarcinoma may actually be higher than expected since it is not routine practice to send placentas for pathological evaluation after a normal spontaneous delivery. The obstetrician, pathologist, and pediatrician should have an increased awareness of placental choriocarcinoma and its manifestations.

  9. A Rare Case of Metastatic Choriocarcinoma of Lung Origin

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    Parth Rali

    2017-01-01

    Full Text Available Choriocarcinoma is part of the spectrum of gestational trophoblastic disease that occurs in women of reproductive age. Although the most common metastatic site of choriocarcinoma is the lung, primary pulmonary choriocarcinoma is rare. To diagnose primary pulmonary choriocarcinoma, the patient should have no previous gynecologic malignancy, have elevated human chorionic gonadotropin, and have pathological confirmation of the disease excluding gonadal primary site of the tumor. Due to the paucity of data, there are no guidelines for treatment. Prognosis of this malignancy is extremely poor. We report a rare case of metastatic primary lung choriocarcinoma in a 69-year-old postmenopausal woman who was treated with combination of surgery, chemotherapy, and radiation. The patient had a good outcome and is doing well after 1-year follow-up.

  10. Massive hemoptysis as a rare presentation of metastatic choriocarcinoma

    International Nuclear Information System (INIS)

    Husain, S.J.; Zubairi, A.B.S.; Yunus, A.; Jamil, S.

    2006-01-01

    Choriocarcinoma is an uncommon but rapidly invasive and widely metastasizing tumor. Lung is the commonest organ of spread, usually presenting as mild hemoptysis and chest pain in a patient with a recent miscarriage or known molar pregnancy. One such case of a 25 years old woman is reported who did not have any history of recent pregnancy or miscarriage and presented with a life-threatening massive hemoptysis. She responded well to therapy once the diagnosis of metastatic choriocarcinoma was established. (author)

  11. Embolization for hemorrhage of liver metastases from choriocarcinoma

    NARCIS (Netherlands)

    Lok, C. A. R.; Reekers, J. A.; Westermann, A. M.; van der Velden, J.

    2005-01-01

    Background. Because gestational trophoblastic disease (GTD) is highly sensitive to chemotherapy, life-threatening hemorrhage from metastases can occur especially early after starting therapy. Cases. Two cases of post-term choriocarcinoma with liver metastases complicated by profuse life-threatening

  12. Metastatic Choriocarcinoma Following Live Birth – A Rare Presentation

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    Joya Sree Roy

    2011-09-01

    Full Text Available Choriocarcinoma is the most malignant tumor of gestational trophoblastic neoplasia. Post-partum choriocarcinoma is an infrequent event with poor prognosis. The diagnosis is usually delayed due to failure to recognize the mode of presentation of this disease. Being a rare occurrence, limited data is available regarding its clinical features. We present a 24 years old women with parity one delivered by caesarean section indicated for premature rupture of membrane with fetal distress at 39 wks of pregnancy. Frequent episodes of heavy vaginal bleeding had started 28 days following C/S. For this, she had H/O uterine evacuatin twice within 5 days interval. Biopsy report of second curettage showed choriocarcinoma. On admission to Dhaka Medical College Hospital (DMCH, the pretreatment Human Chorionic Gonadotrophin (βhCG level was >200000.0 IU/L, uterine mass of about 18 wks pregnancy size & X-Ray chest showed segmental consolidation in left mid zone of lung. After consultation with oncologist Etoposide, Methotrexate, Dactinomycin, Cyclophosphamide & Vincristine (EMACO therapy was started but before completion of her proposed cycles, she developed a live threatening condition which was managed very urgently and meticulously. Now the patient is under regular monitoring. Key words: GTD; Choriocarcinoma DOI: http://dx.doi.org/10.3329/bsmmuj.v4i2.8642 BSMMU J 2011; 4(2:116-118

  13. Infantile choriocarcinoma: a case report with MRI, angiography and bone scintigraphy

    International Nuclear Information System (INIS)

    Sashi, R.; Sato, K.; Hirano, H.; Tomura, N.; Watarai, J.; Ishida, A.; Morita, M.

    1996-01-01

    Infantile and maternal choriocarcinoma is a very rare disease. We report a case with the characteristic clinical features of infantile choriocarcinoma: developing anemia, hemorrhagic liver tumors, rapid progression to death and maternal choriocarcinoma. Bone scintigraphy showed increased uptake by the liver tumors. In this case there were two possible primary sites: the placenta of this pregnancy and a hydatidiform mole that had been present 2 years previously. (orig.). With 1 fig

  14. Choriocarcinoma as cause of pulmonary embolism: Presentation of a case

    International Nuclear Information System (INIS)

    Medina Gonzalez, Maria Elena; Rodriguez Reyna, Juan Carlos; Nip Fabero, Olga J

    2009-01-01

    This is the case of a 21 years old, black, female patient admitted at the Teaching Territorial Hospital of Cardenas 'Dr Julio M Aristegui Villamil' presenting breathlessness, dry cough, without expectoration, no fever and affection of the general status. She died a week after the admission in a picture of arrhythmia . The conclusion of the necropsy was pulmonary thromboembolism of tumor origin (choriocarcinoma) in both pulmonary arteries

  15. Colorectal choriocarcinoma in a patient with probable Lynch syndrome

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    Viktor Hendrik Koelzer

    2016-11-01

    Full Text Available Background: Personalized therapy of colorectal cancer (CRC is influenced by morphological, molecular and host-related factors. Here we report the comprehensive clinicopathological and molecular analysis of a pure extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentation: A 61 year old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan (XELOXIRI and bevacizumab. Molecular phenotyping identified loss of the mismatch-repair (MMR protein PMS2, microsatellite instability, a lack of MLH1 promoter methylation and lack of of BRAF mutation suggestive of Lynch-Syndrome. Targeted next generation sequencing revealed an Ataxia Telangiectasia Mutated (ATM p.P604S missense mutation. A bleomycin, etoposide and cisplatin (BEP treatment protocol targeting germ-cell neoplasia lead to disease remission and prolonged survival of 34 months.Conclusions: Comprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.Key words: Colorectal cancer, choriocarcinoma, histopathology, prognostic factors, Lynch syndrome, microsatellite instability, ataxia telangiectasia mutated, molecular pathology, next generation sequencing, personalized medicine

  16. Origin of choriocarcinoma in previous molar pregnancy proved by DNA analysis

    International Nuclear Information System (INIS)

    Vojtassak, J.; Repiska, V.; Konecna, B.; Zajac, V.; Korbel, M.; Danihel, L.

    1996-01-01

    A 17-year old woman had in a short time period (seven months) a very exciting reproduction history. Molar pregnancy in December 1993, choriocarcinoma in January 1994 and induced abortion in June 1994. DNA analysis proved the origin of the choriocarcinoma in the previous molar pregnancy. (author)

  17. EXTRAGONADAL CHORIOCARCINOMA OF THE COLON – INCIDENCE, DIAGNOSIS, AND TREATMENT - A CASE REPORT

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    Sergey Dimitrov Iliev

    2018-04-01

    Full Text Available Choriocarcinoma is a malignant trophoblastic cancer. It could be gestational and non-gestational. The primary extragonadal choriocarcinoma of the colon is an exceptionally rare tumor. There are only 12 cases of this tumor described in the literature. Only four of these 12 cases are pure primary choriocarcinomas of the colon. In the other eight cases, there is an adenocarcinoma with a choriocarcinoma component. In that reason, rare case like this is advisable to be reported. Case presentation The purpose of this report was to systematize the existing information about the frequency, diagnosis, and treatment of primary choriocarcinoma of the colon and to present our experience with diagnostic and therapeutic approaches to this exceptionally rare and not well-known tumor. Primary extragonadal choriocarcinoma is most frequently found in the retroperitoneal space, mediastinum, pituitary gland and, very rarely, in the gastrointestinal tract. The stomach is the most frequent localization in the gastrointestinal tract. In our case, an extended right hemicolectomy was performed according to the principles of oncologic resection. Chemotherapy for gonadal choriocarcinoma was started. At present - four months after the surgical intervention, the Bulgarian patient does not show progression of the disease and is in good general health. Conclusion There is still no algorithm for treatment of primary choriocarcinoma of the colon because this is an extremely rare tumor. The behavior in this type of tumors remains a challenge for clinicians.

  18. Spontaneous acute subdural hematoma as an initial presentation of choriocarcinoma: A case report

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    Rocque Brandon G

    2008-06-01

    Full Text Available Abstract Introduction Diverse sequelae of central nervous system metastasis of choriocarcinoma have been reported, including infarction, intra or extra axial hemorrhages, aneurysm formation and carotid-cavernous fistula. Here we report a case of subdural hematoma as the first presentation of choriocarcinoma. Case presentation The patient is a 34-year-old woman whose initial presentation of widely metastatic choriocarcinoma was an acute subdural hematoma, requiring decompressive craniectomy. Histopathologic examination of the tissue showed no evidence of choriocarcinoma, but the patient was found to have diffuse metastatic disease and cerebrospinal fluid indices highly suggestive of intracranial metastasis. Conclusion Choriocarcinoma frequently metastasizes intracranially. We review the diverse possible manifestations of this process. In addition, the cerebrospinal fluid:serum beta-human chorionic gonadotropin ratio is an important factor in diagnosing these cases. Finally, the role of the neurosurgeon is discussed.

  19. Primary choriocarcinoma of the colon: a case report and review of the literature

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    Jiang Lun

    2013-01-01

    Full Text Available Abstract Choriocarcinoma usually arises in the uterus and gonads. Primary choriocarcinoma (PCC in an extragenital organ is rare. When it occurs in the gastrointestinal tract, the stomach is the most common site. Only 12 cases of PCC of the colon have been reported in the world literature. Most cases were associated with adenocarcinoma. We report the case of a 36-year-old man with PCC of the colon and review the clinical characteristics of previously documented cases.

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

    Science.gov (United States)

    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.

  1. Receptor-mediated endocytosis of trichosanthin in choriocarcinoma cells

    International Nuclear Information System (INIS)

    Chan, W.Y.; Huang Hai; Tam, S.-C.

    2003-01-01

    Trichosanthin (TCS) is a ribosome inactivating protein (RIP). It is generally believed that its many biological activities act through inhibition of ribosomes resulting in a decrease in protein synthesis. It has been hypothesized that the rate of entry of TCS into cells to reach ribosomes is an important factor in determining its biological activity. To prove this hypothesis, we have mapped out and compared the intracellular routing of TCS in two cell lines, namely the choriocarcinoma JAR cell line, which is known to be highly sensitive to the toxic effects of TCS, and the hepatoma H35 cell line, to which TCS shows minimal toxicity. Results from laser scanning confocal microscopy indicated that fluorescein isothiocyanate labeled TCS quickly accumulated inside JAR cells within 4 h of incubation while only a low level of fluorescent signals was detected in H35 cells during the same period of time. When TCS was conjugated with gold particles (Au) and its intracellular locations were traced with a transmission electron microscope, it was found that most of TCS were bound to coated pits on the JAR cell surface and were rapidly internalized within an hour. By 4 h, TCS reached almost every cytoplasmic region including ribosomes, and the JAR cell began to degenerate. In H35 cells, however, the binding of TCS to coated pits was not observed, but instead, a small amount of TCS was found to penetrate the cell non-specifically by direct diffusion across the cell membrane. Our observations suggest that most of TCS enter JAR cells via a specific receptor mediated pathway, which allows a swift transport of TCS across the membrane and a rapid accumulation of intracellular TCS, while in H35 cells, TCS takes a slow and non-specific route. The receptor-mediated uptake together with the specific intracellular routing of TCS may partly account for the differential vulnerability of the choriocarcinoma cell line towards the toxicity of TCS

  2. Dickkopf-1 induced apoptosis in human placental choriocarcinoma is independent of canonical Wnt signaling

    International Nuclear Information System (INIS)

    Peng Sha; Miao Chenglin; Li Jing; Fan Xiujun; Cao Yujing; Duan Enkui

    2006-01-01

    Placental choriocarcinoma, a reproductive system carcinoma in women, has about 0.81% occurrence frequency in China, which leads to over 90% lethality due to indistinct pathogenesis and the absence of efficient therapeutic treatment. In the present study, using immunostaining and reverse transcription PCR, we reported that Dickkopf-1 (Dkk-1) is prominently expressed in human cytotrophoblast (CTB) cell, but absent in the human placental choriocarcinoma cell line JAR and JEG3, implicating an unknown correlation between Dkk-1 and carcinogenesis of placental choriocarcinoma. Further, through exogenous introduction of Dkk-1, we found repressed proliferation in JAR and JEG3, induced apoptosis in JAR, and discovered significant tumor suppression effects of Dkk-1 in placental choriocarcinoma. Moreover we found that this function of Dkk-1 is achieved through c-Jun N-terminal kinase (JNK), whereas the canonical Wnt pathway may not have a great role. This discovery is not symphonic to previous functional understanding of Dkk-1, a canonical Wnt signaling antagonist. Together, our data indicate the possible correlation between Dkk-1 and human placental choriocarcinoma and suggest potential applications of Dkk-1 in treatment of human placental choriocarcinomas

  3. 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.

  4. Primary ovary choriocarcinoma: individual DNA polymorphic analysis as a strategy to confirm diagnosis and treatment

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    Fernando Nalesso

    2013-04-01

    Full Text Available Primary choriocarcinoma of the ovary is rare. Furthermore, this tumor can arise from gestational tissue or pure germ cells of the ovary, with the latter resulting in non-gestational choriocarcinoma. While the clinical characteristics and histology of both tumor types are identical, differentiation of these tumors is necessary for effective treatment. One strategy for the differentiation of these tumors types is to assay for the presence of paternal DNA. Accordingly, in the present case, a patient with primary choriocarcinoma of the ovary with a non-gestational origin was confirmed by DNA analysis. The patient subsequently exhibited an excellent response to chemotherapy, and following surgery, achieved complete remission. A pathological analysis of surgical specimens further confirmed the absence of tumor.

  5. Testicular choriocarcinoma with cutaneous metastasis in a 19-year-old man.

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    Toberer, Ferdinand; Enk, Alexander; Hartschuh, Wolfgang; Grüllich, Carsten

    2018-07-01

    A 19-year-old man suffering from testicular choriocarcinoma presented to the dermatology department with a cutaneous metastasis on his head. This metastasis was the first sign of disease that led to medical consultation. Histopathology revealed cytotrophoblasts and syncytiotrophoblasts, the later expressing human chorionic gonadotropin antigen. Whole body computed tomography showed multiple metastases of the brain, lung, liver, bone, paraaortic lymph nodes and left uvea; the primary was found in the left testicle. Despite neurosurgical intervention and chemotherapy the patient died 9 days after the biopsy of the cutaneous metastasis. Cutaneous metastases of testicular choriocarcinoma are exceptionally rare, with fewer than a dozen cases reported in the English-language literature. The present case highlights that testicular choriocarcinoma metastatic to the skin should be included in the differential of cutaneous scalp tumors. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Suppression of choriocarcinoma invasion and metastasis following blockade of BDNF/TrkB signaling

    International Nuclear Information System (INIS)

    Kawamura, Kazuhiro; Kawamura, Nanami; Okamoto, Naoki; Manabe, Motomu

    2013-01-01

    Brain-derived neurotrophic factor (BDNF) acts through its cognate receptor tyrosine kinase-B (TrkB) to regulate diverse physiological functions in reproductive and other tissues. In normal and malignant trophoblastic cells, the BDNF/TrkB signaling promotes cell growth. Due to the highly malignant nature of choriocarcinoma, we investigated possible involvement of this system in choriocarcinoma cell invasion and metastasis. We demonstrated that treatment of cultured choriocarcinoma cells, known to express both BDNF and TrkB, with a soluble TrkB ectodomain or a Trk receptor inhibitor K252a suppressed cell invasion accompanied with decreased expression of matrix metalloproteinase-2, a cell invasion marker. In vivo studies using a tumor xenograft model in athymic nude mice further showed inhibition of cell invasion from tumors to surrounding tissues following the suppression of endogenous TrkB signaling. For an in vivo model of choriocarcinoma metastasis, we performed intravenous injections of JAR cells expressing firefly luciferase into severe combined immunodeficiency (SCID) mice. Treatment with K252a inhibited metastasis of tumors to distant organs. In vivo K252a treatment also suppressed metastatic tumor growth as reflected by decreased cell proliferation and increased apoptosis and caspases-3/7 activities, together with reduced tissue levels of a tumor marker, human chorionic gonadotropin-β. In vivo suppression of TrkB signaling also led to decreased expression of angiogenic markers in metastatic tumor, including cluster of differentiation 31 and vascular endothelial growth factor A. Our findings suggested essential autocrine/paracrine roles of the BDNF/TrkB signaling system in choriocarcinoma invasion and metastasis. Inhibition of this signaling could serve as the basis to develop a novel therapy for patients with choriocarcinoma

  7. 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...

  8. 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

  9. Spontaneous renal hemorrhage secondary to choriocarcinoma in a man with congenital hypospadias and cryptorchidism: a case report and literature review.

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    Li, Yi; Chen, Gang; Chen, Han; Wen, Shuang; Xiong, Chao-Yu; Yang, Zi-Yi; Zhu, Yun-Xiao; Jeffreys, Nathan

    2018-05-08

    Choriocarcinoma is a rare malignant germ-cell tumour, most commonly found in adult women. It infrequently presents as spontaneous renal haemorrhage (SRH). Genital malformation and SRH secondary to choriocarcinoma has previously been only reported in females. We present what we believe to be the first case of a male patient with genital malformation (hypospadias and cryptorchidism) and SRH at presentation of choriocarcinoma. A 25-year-old man presented to the department with intense pain in the right flank region and lower back. Initial investigations showed spontaneous renal haemorrhage, for which an emergency partial nephrectomy was performed. Clinical, radiological, and pathological investigations suggested a diagnosis of testicular choriocarcinoma with metastases to the right kidney, both lungs, and brain. Initial treatment was with a chemotherapy regimen of cisplatin, etoposide and bleomycin and whole brain radiotherapy; however, 6 months after diagnosis the patient developed liver metastasis, after which time the BEP protocol was switched to ITP with oral apatinib. Despite best efforts, the liver and lung metastasis continued to grow and a decision was made to discontinue active treatment and provide only palliative care until the patient passed away. Choriocarcinoma is a difficult cancer to diagnose pre-operatively. In male patients with early metastasis, prognosis may be much poorer than in the commoner gestational choriocarcinoma. A multidisciplinary with comprehensive post-surgical intervention is of great importance in the treatment of these patients.

  10. Gestational Tubal Choriocarcinoma Presenting as a Pregnancy of Unknown Location following Ovarian Induction

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    Lawrence Hsu Lin

    2018-01-01

    Full Text Available The management of pregnancy of unknown location (PUL can be a challenging situation, since it can present as several different conditions. Here we describe a rare case of gestational choriocarcinoma arising in the fallopian tube after ovarian induction in an infertile patient. The patient received clomiphene for ovarian induction and had rising levels of human chorionic gonadotropin (hCG over nine months without sign of pregnancy. After referral to our center, the patient was diagnosed with a paraovarian tumor, which revealed a gestational choriocarcinoma arising in the fallopian tube; the final diagnosis was supported by pathological and cytogenomic analysis. Malignancies, such as gestational trophoblastic disease, should be in the differential diagnosis of PUL; the early recognition of these conditions is key for the proper treatment and favorable outcome.

  11. Serum-SP/sub 1/-pregnancy-specific-. beta. -glycoprotein in choriocarcinoma and other neoplastic disease

    Energy Technology Data Exchange (ETDEWEB)

    Searle, F; Leake, B A; Bagshawe, K D; Dent, J [Charing Cross Group of Hospitals, London (UK)

    1978-03-18

    A radioimmunoassay for a placental glycoprotein, ..beta../sub 1/SP/sub 1/, capable of detecting 2 ..mu..g/l of the glycoprotein in serum was used to measure concentrations of ..beta../sub 1/SP/sub 1/ in patients with choriocarcinoma, teratoma, colonic cancer, breast cancer, and ovarian cancer. Twelve out of 94 (13%) healthy men and healthy non-pregnant women had detectable serum-..beta../sub 1/SP/sub 1/ concentrations. Concentrations up to 50,000 ..mu..g/l were found in the sera of patients with hydatidiform mole, invasive mole, choriocarcinoma, and malignant teratoma. ..beta../sub 1/-glycoprotein concentrations were generally much lower than corresponding concentrations of chorionic gonadotrophin which is the most reliable marker for trophoblastic tumors. In a few cases, however, ..beta../sub 1/-glycoprotein measurements may be useful in the detection of minimal residual tumor. The slightly raised values found in some patients with carcinoma of the colon, breast, or ovary seem unlikely to be useful for diagnostic purposes or for monitoring the course of these cancers.

  12. "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

  13. Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress.

    Science.gov (United States)

    Yang, Changwon; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

    2017-07-28

    Myricetin is a bioactive compound found in a variety of vegetables and fruits, and its anti-cancer effects are well known. In this study, we confirmed that myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3) and also promoted apoptosis and regulated cell cycle progression in a dose-dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In addition, we found that ROS production, lipid peroxidation, glutathione depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca 2+ release from the endoplasmic reticulum associated with modulation of ER stress in JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic antiproliferative effects with current chemotherapeutics, etoposide and cisplatin, on choriocarcinoma cells. Collectively, results of the present study provide strong evidence for the potential of myricetin to be an effective therapeutic for the prevention of human placental choriocarcinomas. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Paraneoplastic limbic encephalitis in a patient with extragonadal choriocarcinoma--significance of onconeural antibodies.

    Science.gov (United States)

    Szkandera, Joanna; Ploner, Ferdin; Bauernhofer, Thomas; Kasparek, Anne-Katrin; Payer, Franz; Balic, Marija; Knechtel, Gudrun; Gerger, Armin; Gallè, Günter; Samonigg, Hellmut; Hofmann, Günter

    2010-01-01

    Paraneoplastic limbic or brainstem encephalitis is considered to be an autoimmune-mediated disorder of the nervous system associated with different types of cancer including germ cell tumors. We report on a 31-year-old patient presenting with eye motility dysfunction, dysarthrophonia, lethargy, depression, slow mentation, disorientation, dysgraphia, and retarded motion sequence. Neurologic tests, brain imaging, and blood chemistry tests failed to determine the cause of the symptoms. Further examinations including ultrasound of the abdomen led to the detection of a retroperitoneal mass. The biopsy of this mass showed fractions of a choriocarcinoma. The patient underwent curative chemotherapy, but although the cancer therapy was successful, the neurologic disorders did not improve. Concurrent examination for anti-Ma2 antibodies in the serum was positive and confirmed the paraneoplastic origin of these symptoms. Patients with symptoms of limbic or brainstem encephalitis, especially young men, should be tested for anti-Ma2 antibodies in the serum to elucidate their origin. The detection of these antibodies supports the diagnosis of a paraneoplastic syndrome, and may lead to the earlier identification of an otherwise hidden extragonadal germ cell tumor. Copyright © 2010 S. Karger AG, Basel.

  15. MicroRNA-34a is a tumor suppressor in choriocarcinoma via regulation of Delta-like1

    International Nuclear Information System (INIS)

    Pang, Ronald TK; Leung, Carmen ON; Lee, Cheuk-Lun; Lam, Kevin KW; Ye, Tian-Min; Chiu, Philip CN; Yeung, William SB

    2013-01-01

    Choriocarcinoma is a gestational trophoblastic tumor which causes high mortality if left untreated. MicroRNAs (miRNAs) are small non protein-coding RNAs which inhibit target gene expression. The role of miRNAs in choriocarcinoma, however, is not well understood. In this study, we examined the effect of miR-34a in choriocarcinoma. MiR-34a was either inhibited or ectopically expressed transiently in two choriocarcinoma cell lines (BeWo and JEG-3) respectively. Its actions on cell invasion, proliferation and colony formation at low cell density were examined. The miR-34a putative target Notch ligand Delta-like 1 (DLL1) was identified by adoption of different approaches including: in-silico analysis, functional luciferase assay and western blotting. Real-time quantitative polymerase chain reaction was used to quantify changes in the expression of matrix proteinase in the treated cells. To nullify the effect of miR-34a ectopic expression, we activated Notch signaling through force-expression of the Notch intracellular domain in the miR-34a force-expressed cells. In addition, we studied the importance of DLL1 in BeWo cell invasion through ligand stimulation and antibody inhibition. Furthermore, the induction in tumor formation of miR-34a-inhibited BeWo cells in SCID mice was investigated. Transient miR-34a force-expression significantly suppressed cell proliferation and invasion in BeWo and JEG-3 cells. In silicon miRNA target prediction, luciferase functional assays and Western blotting analysis demonstrated that miR-34a regulated DLL1 expression in both cell lines. Although force-expression of miR-34a suppressed the expression of DLL1 and NOTCH1, the extent of suppression was higher in DLL1 than NOTCH1 in both cell lines. MiR-34a-mediated DLL1 suppression led to reduced matrix metallopeptidase 9 and urokinase-type plasminogen activator expression. The effect of miR-34a on cell invasion was partially nullified by Notch signaling activation. DLL1 ligand stimulated while

  16. Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

    Science.gov (United States)

    Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

    2016-01-01

    Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Non-Gestational Choriocarcinoma with Widespread Metastases Presenting with Type 1 Respiratory Failure in a 39-Year-Old Female: Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Louisa Stockton

    2018-03-01

    Full Text Available Introduction: Non-gestational choriocarcinoma (NGCC is an extremely rare cancer. We report a case presenting in extremis. Case Report: A 39-year-old woman presented with type 1 respiratory failure with a 1-month history of breathlessness. Computed tomography (CT revealed widespread metastatic disease involving the lungs, liver, pancreas, and breast. Serum β-human chorionic gonadotropin was markedly raised. Over 72 h, she deteriorated and was started on high-flow nasal cannula to facilitate discussions and for comfort. Histology from a breast biopsy suggested a choriocarcinoma, and she was commenced on etoposide and cisplatin. Unfortunately she continued to deteriorate and died on day 11 of admission. Molecular genotyping received post-mortem confirmed non-gestational choriocarcinomatous differentiation within a high-grade tumour. Discussion: NGCC carries a worse prognosis compared with gestational choriocarcinoma and is historically less chemosensitive. However, differentiation between these two diagnoses is challenging due to a lack of immuno-histochemical differences. The NGCC in this case was likely to have originated in the lung due to a 12-cm mass in the lingula, and extensive emphysema on CT. Primary pulmonary choriocarcinoma has a rapidly fatal course in the majority of patients. Conclusion: This is the only case to our knowledge of NGCC presenting in extremis, where an accurate diagnosis was not achieved pre-mortem. This also demonstrates the merit of non-invasive ventilation within palliation to facilitate communication and comfort.

  18. 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...... be used to efficiently select for VSA(PAM) expression in vitro....

  19. Induction of apoptosis in human choriocarcinoma cell lines by treatment with 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone (vesnarinone).

    Science.gov (United States)

    Isaka, Keiichi; Fujito, Atsuya; Sagawa, Yasukazu; Yudate, Tamaki; Nishi, Hirotaka; Ito, Hiroe; Takayama, Masaomi

    2002-01-01

    Induction of apoptosis is an attractive strategy in cancer therapy but it clinical practice is not yet sufficient in choriocarcinoma. The quinolinone derivative, vesnarinone, is a novel inotropic agent used for treating congestive heart failure and may also have a potential anticancer activity. It induces apoptosis and differentiation in some tumor cell lines. We examined the antitumor effect of vesnarinone in eight cell lines established from human choriocarcinoma and hydatidiform mole using MTT assay and also analyzed the nuclear fragmentation of tumor cells by DNA electrophoresis assay. Vesnarinone inhibited the proliferation of choriocarcinoma cell lines in a dose-dependent manner and induced DNA fragmentation in cells. However, the BM cell line prepared by subcultivation from hydatidiform mole showed no growth suppression or DNA fragmentation in response to vesnarinone. On the other hand, PCR-SSCP analysis and direct DNA sequencing have shown that a human choriocarcinoma cell line, SCH, has a mutant p53 gene at codon 249. When SCH cells were treated with vesnarinone cellular proliferation was significantly inhibited. Vesnarinone suppressed the proliferation of all choriocarcinoma cell lines and induced apoptosis, regardless of the existence of p53 mutation. In addition, it has been found by RT-PCR that expression of c-Myc mRNA is upregulated by treating choriocarcinoma cells with vesnarinone. The finding suggests that vesnarinone might induce expression of c-Myc gene in choriocarcinoma cells, the product of which may be associated with the inhibition of cell growth and induce apoptosis. These results suggest that vesnarinone is a useful reagent for the treatment of choriocarcinoma.

  20. Ascorbic acid transported by sodium-dependent vitamin C transporter 2 stimulates steroidogenesis in human choriocarcinoma cells.

    Science.gov (United States)

    Wu, Ximei; Iguchi, Takuma; Itoh, Norio; Okamoto, Kousuke; Takagi, Tatsuya; Tanaka, Keiichi; Nakanishi, Tsuyoshi

    2008-01-01

    Reduced vitamin C [ascorbic acid (AA)], which is taken up into cells by sodium-dependent vitamin C transporter (SVCT) 1 and 2, is believed to be important for hormone synthesis, but its role in generating placental steroids needed to maintain pregnancy and fetal development is not clear. To determine the steroidogenic effect of AA and the role of SVCT2 in AA-induced steroidogenesis, we tested the effects of AA treatment and SVCT2 knockdown on steroidogenesis in human choriocarcinoma cell lines. AA treatment of JEG-3, BeWo, and JAR cells for 48-h dose dependently increased progesterone and estradiol levels. In JEG-3 cells, AA increased the mRNA expression of P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase, key enzymes for steroidogenesis. Stable knockdown of SVCT2 in JEG-3 cells by retrovirally mediated RNA interference decreased the maximal velocity of AA uptake by approximately 50%, but apparent affinity values were not affected. SVCT2 knockdown in JEG-3 cells significantly suppressed the AA-induced mRNA expression of placental P450 cholesterol side-chain cleavage enzyme, 3beta-hydroxysteroid dehydrogenase type 1, and aromatase. This suppression of the AA-induced mRNA expression of steroidogenic enzymes subsequently decreased progesterone and estradiol production. In addition, inhibition of MAPK kinase-ERK signaling, which is a major pathway for AA-regulated gene expression, failed to affect AA-induced steroidogenesis. Our observations indicate that SVCT2-mediated AA uptake into cells is necessary for AA-induced steroidogenesis in human choriocarcinoma cell, but MAPK kinase-ERK signaling is not involved in AA-induced steroidogenesis.

  1. Recurrent hydatidiform mole: A case report of six consecutive molar pregnancies complicated by choriocarcinoma, and review of the literature

    Directory of Open Access Journals (Sweden)

    Ahlam A Al-Ghamdi

    2011-01-01

    Full Text Available Hydatidiform mole (HM is the most common form of gestational trophoblastic neoplasia. Recurrence of HM is extremely rare. Here, we report the case of a patient with six consecutive partial HMs without normal pregnancy. A 42-year-old lady who was referred to us at King Fahad Hospital of the University, Al Khobar, initially as a case of 26-year-old with persistent trophoblastic disease after three recurrent molar pregnancies that were confirmed histologically in the referring hospital. She underwent evacuation and curettage and was followed up by serial β-human chorionic gonadotropin levels, and did not require chemotherapy. She then had three more molar pregnancies in 1995, 1996, and 2004; all molar pregnancies were evacuated by suction curettage at her base hospital, but in the last event, she complained of shortness of breath and abdominal pain. Diagnostic workup in our hospital confirmed choriocarcinoma, for which she received multiple regimen chemotherapy and was cured. Unfortunately, she lately presented with symptoms suggestive of premature menopause.

  2. Antagonism of EG-VEGF Receptors as Targeted Therapy for Choriocarcinoma Progression In Vitro and In Vivo.

    Science.gov (United States)

    Traboulsi, Wael; Sergent, Frédéric; Boufettal, Houssine; Brouillet, Sophie; Slim, Rima; Hoffmann, Pascale; Benlahfid, Mohammed; Zhou, Qun Y; Balboni, Gianfranco; Onnis, Valentina; Bolze, Pierre A; Salomon, Aude; Sauthier, Philippe; Mallet, François; Aboussaouira, Touria; Feige, Jean J; Benharouga, Mohamed; Alfaidy, Nadia

    2017-11-15

    Purpose: Choriocarcinoma (CC) is the most malignant gestational trophoblastic disease that often develops from complete hydatidiform moles (CHM). Neither the mechanism of CC development nor its progression is yet characterized. We recently identified endocrine gland-derived vascular endothelial growth factor (EG-VEGF) as a novel key placental growth factor that controls trophoblast proliferation and invasion. EG-VEGF acts via two receptors, PROKR1 and PROKR2. Here, we demonstrate that EG-VEGF receptors can be targeted for CC therapy. Experimental Design: Three approaches were used: (i) a clinical investigation comparing circulating EG-VEGF in control ( n = 20) and in distinctive CHM ( n = 38) and CC ( n = 9) cohorts, (ii) an in vitro study investigating EG-VEGF effects on the CC cell line JEG3, and (iii) an in vivo study including the development of a novel CC mouse model, through a direct injection of JEG3-luciferase into the placenta of gravid SCID-mice. Results: Both placental and circulating EG-VEGF levels were increased in CHM and CC (×5) patients. EG-VEGF increased JEG3 proliferation, migration, and invasion in two-dimensional (2D) and three-dimensional (3D) culture systems. JEG3 injection in the placenta caused CC development with large metastases compared with their injection into the uterine horn. Treatment of the animal model with EG-VEGF receptor's antagonists significantly reduced tumor development and progression and preserved pregnancy. Antibody-array and immunohistological analyses further deciphered the mechanism of the antagonist's actions. Conclusions: Our work describes a novel preclinical animal model of CC and presents evidence that EG-VEGF receptors can be targeted for CC therapy. This may provide safe and less toxic therapeutic options compared with the currently used multi-agent chemotherapies. Clin Cancer Res; 23(22); 7130-40. ©2017 AACR . ©2017 American Association for Cancer Research.

  3. Incidental primary mediastinal choriocarcinoma diagnosed by endobronchial ultrasound-guided fine needle aspiration in a patient presenting with transient ischemic attack and stroke.

    Science.gov (United States)

    Francischetti, Ivo M B; Cajigas, Antonio; Suhrland, Mark; Farinhas, Joaquim M; Khader, Samer

    2017-08-01

    We describe a case of a 41-year old male patient with no significant prior medical history who presents with symptoms of Transient Ischemic Attack and stroke. Magnetic Resonance Imaging (MRI) of the brain identified areas of ischemia in the left side, and angiography showed occlusion of the left Medial Cerebral Artery (MCA). Cardiac Transthoracic Echocardiogram (TTE) for stroke evaluation incidentally noted a mediastinal abnormality leading to cancer work-up. Computer Tomography (CT) and 18 F-fluorodeoxyglucose (FDG) PET-CT scan of the chest incidentally revealed an avid 6 cm paraesophagial/subcarinal mass. Further diagnostic work-up with endoscopic and endobronchial ultra sound (EBUS)-guided fine needle aspiration (FNA) of the mass yielded a cytology diagnosis of Germ Cell Tumor (GCT), with choriocarcinoma component. Additionally, high plasma levels of β-human chorionic gonadotrophin (β-HCG) were detected with no evidence of testicular tumor. This exceedingly rare presentation for a primary mediastinal choriocarcinoma underscores the importance of complete investigation of young patients presenting with neurological symptoms compatible with ischemic events. Diagn. Cytopathol. 2017;45:738-743. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Preimplantation Factor (PIF Promotes HLA-G, -E, -F, -C Expression in JEG-3 Choriocarcinoma Cells and Endogenous Progesterone Activity

    Directory of Open Access Journals (Sweden)

    Miya Soukaina Hakam

    2017-10-01

    Full Text Available Background/Aims: Pregnancy success requires mandatory maternal tolerance of the semi/ allogeneic embryo involving embryo-derived signals. Expression levels of PreImplantation Factor (PIF, a novel peptide secreted by viable embryos, correlate with embryo development, and its early detection in circulation correlates with a favourable pregnancy outcome. PIF enhances endometrial receptivity to promote embryo implantation. Via the p53 pathway, it increases trophoblast invasion, improving cell survival / immune privilege. PIF also reduces spontaneous and LPS-induced foetal death in immune naïve murine model. We examined PIF effect on gene expression of human leukocyte antigen (HLA-G, -E -F and –C and the influence of PIF on local progesterone activity in JEG-3 choriocarcinoma cells. Methods: PIF and progesterone (P4 effects on JEG-3 cells surface and intracellular HLA molecules was tested using monoclonal antibodies, flow cytometry, and Western blotting. PIF and IL17 effects on P4 and cytokines secretion was determined by ELISA. PIF and P4 effects on JEG-3 cells proteome was examined using 2D gel staining followed by spot analysis, mass spectrometry and bioinformatic analysis. Results: In cytotrophoblastic JEG-3 cells PIF increased intracellular expression of HLA-G, HLA-F, HLA-E and HLA-C and surface expression of HLA-G, HLA-E and HLA-C in dose and time dependent manner. In case of HLA-E, -F results were confirmed also by Western blot. Proteome analysis confirmed an increase in HLA-G, pro-tolerance FOXP3+ regulatory T cells (Tregs, coagulation factors and complement regulator. In contrast, PIF reduced PRDX2 and HSP70s to negate oxidative stress and protein misfolding. PIF enhanced local progesterone activity, increasing steroid secretion and the receptor protein. It also promoted the secretion of the Th1/Th2 cytokines (IL-10, IL-1β, IL-8, GM-CSF and TGF-β1, resulting in improved maternal signalling. Conclusion: PIF can generate a pro

  5. 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.

  6. Benzo(a)pyrene induced cell cycle arrest and apoptosis in human choriocarcinoma cancer cells through reactive oxygen species-induced endoplasmic reticulum-stress pathway.

    Science.gov (United States)

    Kim, Soo-Min; Lee, Hae-Miru; Hwang, Kyung-A; Choi, Kyung-Chul

    2017-09-01

    Cigarette smoke (CS) contains over 60 well established carcinogens. In this study, we examined the effects of benzo(a)pyrene (B(a)P), a main CS component, on the viability and apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cell lines. An MTT assay confirmed that B(a)P decreased the cell viability of JEG-3 and BeWo cells in a dose-dependent manner. Additionally, Western blot (WB) assay revealed that protein expression of cyclin D and cyclin E decreased, while protein expression of p21 and p27 was increased in response to B(a)P treatment for 48 h. The changes in reactive oxygen species (ROS) levels in JEG-3 and BeWo cells exposed to B(a)P were also measured by a dichlorofluorescein diacetate (DCF-DA) assay, which revealed that ROS levels increased in response to B(a)P treatment for 48 h. WB assay also confirmed that each B(a)P treatment of JEG-3 and BeWo cells for 4 h promoted the expression of phosphorylated eukaryotic initiation factor 2 alpha protein (p-eIF2α) and C/EBP homologous protein (CHOP), which are known to be involved in ROS-mediated endoplasmic reticulum stress (ER-stress) related apoptosis. Overall, the protein expression of Bax (a pro-apoptosis marker) increased, while the expression of Bcl-xl (an anti-apoptotic marker) decreased and the number of apoptotic cells increased in response to B(a)P treatment for 48 h. Taken together, these results suggest that B(a)P has the potential to induce apoptosis of JEG-3 and BeWo human choriocarcinoma cancer cells by increasing the ROS level and simultaneously activating ER-stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. 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

    Directory of Open Access Journals (Sweden)

    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.

  8. Lysosomal degradation of receptor-bound urokinase-type plasminogen activator is enhanced by its inhibitors in human trophoblastic choriocarcinoma cells

    DEFF Research Database (Denmark)

    Jensen, Poul Henning; Christensen, Erik Ilsø; Ebbesen, P.

    1990-01-01

    We have studied the effect of plasminogen activator inhibitors PAI-1 and PAI-2 on the binding of urokinase-type plasminogen activator (u-PA) to its receptor in the human choriocarcinoma cell line JAR. With 125I-labeled ligands in whole-cell binding assays, both uncomplexed u-PA and u......, with the highest density of grains over the membrane at cell-cell interphases, but, after incubation at 37 degrees C, 17 and 27% of the grains for u-PA and u-PA-PAI-1 complexes, respectively, appeared over lysosomal-like bodies. These findings suggest that the u-PA receptor possesses a clearance function......-PA-inhibitor complexes bound to the receptor with a Kd of approximately 100 pM at 4 degrees C. Transferring the cells to 37 degrees C led to degradation to amino acids of up to 50% of the cell-bound u-PA-inhibitor complexes, whereas the degradation of uncomplexed u-PA was 15%; the remaining ligand was recovered...

  9. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells

    International Nuclear Information System (INIS)

    Ritvos, O.; Ranta, T.; Jalkanen, J.; Suikkari, A.M.; Voutilainen, R.; Bohn, H.; Rutanen, E.M.

    1988-01-01

    The placenta expresses genes for insulin-like growth factors (IGFs) and possesses IGF-receptors, suggesting that placental growth is regulated by IGFs in an autocrine manner. We have previously shown that human decidua, but not placenta, synthesizes and secretes a 34 K IGF-binding protein (34 K IGF-BP) called placental protein 12. We now used human choriocarcinoma JEG-3 cell monolayer cultures and recombinant (Thr59)IGF-I as a model to study whether the decidual 34 K IGF-BP is able to modulate the receptor binding and biological activity of IGFs in trophoblasts. JEG-3 cells, which possess type I IGF receptors, were unable to produce IGF-BPs. Purified 34 K IGF-BP specifically bound [125I]iodo-(Thr59)IGF-I. Multiplication-stimulating activity had 2.5% the potency of (Thr59)IGF-I, and insulin had no effect on the binding of [125I] iodo-(Thr59)IGF-I. 34 K IGF-BP inhibited the binding of [125I] iodo-(Thr59)IGF-I to JEG-3 monolayers in a concentration-dependent manner by forming with the tracer a soluble complex that could not bind to the cell surface as demonstrated by competitive binding and cross-linking experiments. After incubating the cell monolayers with [125I]iodo-(Thr59)IGF-I in the presence of purified binding protein, followed by cross-linking, no affinity labeled bands were seen on autoradiography. In contrast, an intensely labeled band at 40 K was detected when the incubation medium was analyzed, suggesting that (Thr59)IGF-I and 34 K IGF-BP formed a complex in a 1:1 molar ratio. Also, 34 K IGF-BP inhibited both basal and IGF-I-stimulated uptake of alpha-[3H]aminoisobutyric acid in JEG-3 cells. RNA analysis revealed that IGF-II is expressed in JEG-3 cells

  10. [Choriocarcinoma causing a pulmonary embolus.

    DEFF Research Database (Denmark)

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

    2008-01-01

    A 32 year-old women experienced dyspnea and thoracic pain that persisted with variable intensity over a course of eight months until acute worsening necessitated admission. A CT scan demonstrated a central pulmonary embolus. Subsequent surgical embolectomy produced a grained substance that was hi...

  11. CASE REPORT A recurrent gestational choriocarcinoma case ...

    African Journals Online (AJOL)

    Admin

    molar pregnancy (Luna Russo et al., 2015). To our knowledge recurrence resulting in rupture 14 month following a live pregnancy is an extremely rare event. Management of gestational trophoblastic disease in our setup poses multiple challenges as seen in this particular case. Serum β-HCG follow up for these patients ...

  12. CASE REPORT A recurrent gestational choriocarcinoma case ...

    African Journals Online (AJOL)

    Admin

    malignant form with significant cure rate and minimal sequela if treated adequately and ... pregnancy test as an alternative follow up for serum β-HCG. .... intraoperative may suggest a form of avascular necrosis of the entire uterine wall.

  13. 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...

  14. CYTOGENETIC ANALYSIS OF THE MATURE TERATOMA AND THE CHORIOCARCINOMA COMPONENT OF A TESTICULAR MIXED NONSEMINOMATOUS GERM-CELL TUMOR

    NARCIS (Netherlands)

    DEGRAAFF, WE; OOSTERHUIS, JW; DEJONG, B; VANECHTENARENDS, J; WIERSEMABUIST, J; KOOPS, HS; SLEIJFER, DT

    1992-01-01

    We karyotyped two histologically distinct components with different metastatic behavior of a testicular nonseminomatous germ cell tumor. The two components showed an almost identical chromosomal pattern. These almost identical karyotypes of the two components with different metastatic potential

  15. 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....

  16. 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

  17. Browse Title Index

    African Journals Online (AJOL)

    Items 201 - 250 of 312 ... Vol 24, No 2 (2009), Medicinal properties of fractionated .... Vol 31, No 2 (2016), Repeated acute oral exposure to cannabis sativa ... (Hhm) Using Jar Human Choriocarcinoma Cancer Cell Line As A Model, Abstract PDF.

  18. A five - year review of gestational trophoblastic diseases in Port ...

    African Journals Online (AJOL)

    Methods: A retrospective analysis of women treated for gestational ... persistent trophoblastic disease while 8(21.1%) had chemotherapy for choriocarcinoma. ... as well as proper counseling of patients treated on the benefits of follow up visits.

  19. Kou et al., Afr J Tradit Complement Altern Med. (2013) 10(3):512 ...

    African Journals Online (AJOL)

    AJTCAM

    Medical University, 3Department of Hematology, First Affiliated Hospital of Xinxiang Medical ... inhibitory effect of Verbena officinalis extract on human choriocarcinoma JAR cells and its ... All mice were provided with enough water and food,.

  20. Cervical poorly differentiated adenocarcinoma with dominant choriocarcinomatous pattern--A case report.

    Science.gov (United States)

    Nikolić, Branka; Ćurković, Aleksandar; Dikić, Svetlana Dragojević; Mitrović, Ana; Kuzmanović, Igor; Arandjelović, Aleksandra; Stanković, Goran

    2015-07-01

    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. 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: Carcinomaporo 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. The early and proper diagnosis of nonmetastatic choriocarcinoma of nongestational origine in coexistence with cervical carcinoma is curable and can have good prognosis.

  1. An unusual presentation of testicular tumor

    International Nuclear Information System (INIS)

    Amin, M.U.; Rahan, T.; Haq, A.U.; Aftab, P.

    2006-01-01

    A case of testicular choriocarcinoma is reported in which blood mixed stools and haemoptysis were the presenting manifestations as the patient never told about the testicular swelling to his parents. Orchidectomy was performed but the patient presented again with massive hematemesis due to gastric perforation secondary to gastric metastasis. The size of the testis at diagnosis was approximately 12 x 7cm. This was also unusual as testicular choriocarcinoma presents as a small mass. The patient eventually died of the complications within one month of diagnosis. (author)

  2. Pattern of gynaecological cancers in Ghana | Nkyekyer | East African ...

    African Journals Online (AJOL)

    Subjects: Cases of gynaecological cancers seen in a fifty two month period. Results: Cervical cancer was the commonest, constituting about 57.8% of gynaecological cancers. Ovarian cancer, endometrial cancer, choriocarcinoma and vulval carcinoma followed in that order. The mean age and parity for cervical carcinoma ...

  3. Childhood Liver Cancer Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Childhood liver cancer has two major histologic subgroups: hepatoblastoma and hepatocellular carcinoma. Less common histologies are undifferentiated embryonal sarcoma of the liver, infantile choriocarcinoma, and vascular liver tumors. Get detailed information about newly diagnosed and recurrent childhood liver cancers including tumor biology, presentation, prognosis, staging, and treatment in this summary for clinicians.

  4. 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...

  5. Detergent insolubility of alkaline phosphatase during biosynthetic transport and endocytosis. Role of cholesterol

    NARCIS (Netherlands)

    Cerneus, D. P.; Ueffing, E.; Posthuma, G.; Strous, G. J.; van der Ende, A.

    1993-01-01

    Alkaline phosphatase is anchored to the outer leaflet of the plasma membrane by a covalently attached glycosyl-phosphatidylinositol anchor. We have studied the biosynthetic transport and endocytosis of alkaline phosphatase in the choriocarcinoma cell line BeWo, which endogenously expresses this

  6. Untitled

    African Journals Online (AJOL)

    recognized by Hippocrates and was carefully described in the sixth century by Actues of Amida, who was the first to use the term hydatid. However, it was not until 1903 that Marchand identified uterine choriocarcinoma as a chorionic malignancy rather than a uterine malignancy arising in the decidua (2). Though gestational.

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

    NARCIS (Netherlands)

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

    1987-01-01

    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

  8. Role of Axumin PET Scan in Germ Cell Tumor

    Science.gov (United States)

    2018-05-01

    Testis Cancer; Germ Cell Tumor; Testicular Cancer; Germ Cell Tumor of Testis; Germ Cell Tumor, Testicular, Childhood; Testicular Neoplasms; Testicular Germ Cell Tumor; Testicular Yolk Sac Tumor; Testicular Choriocarcinoma; Testicular Diseases; Germ Cell Cancer Metastatic; Germ Cell Neoplasm of Retroperitoneum; Germ Cell Cancer, Nos

  9. TropJrnal Vol 30 No 1 for PDF

    African Journals Online (AJOL)

    Mr Olusoji

    all gynaecological tumours are shown in table 2. Squamous cell carcinoma was the most common cancer of the cervix (93.4%). Choriocarcinoma accounted for the largest proportion of uterine cancers (53.8%) while epithelial tumours were the most common type of ovarian cancer. (61.3%) with serous cyst adenocarcinoma.

  10. Thyrotoxicosis in pregnancy:: A case report

    OpenAIRE

    Kamath, Bola R; Rao, Kamla J; Mayadunne, Adikari AK

    2001-01-01

    There are various causes of hyperthyroidism in pregnancy such as Graves’ disease and gestational thyrotoxicosis. The thyroid stimulation results from the excessive levels of circulating human chorionic gonadotropin (hCG) produced by the trophoblastic tissue in both hydatidiform moles and choriocarcinoma. We present a pregnant patient with hydatidiform mole who presented with hyperthyroidism that resolved after evacuation of the mole.

  11. Kinderen met hyperthyreoïdie door verhoogd hCG

    NARCIS (Netherlands)

    Jöbsis, Jasper J.; van Trotsenburg, A. S. Paul; Merks, Johannes H. M.; Kamp, Gerdine A.

    2014-01-01

    We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking

  12. In vitro placental model optimization for nanoparticle transport studies

    DEFF Research Database (Denmark)

    Cartwright, Laura; Poulsen, Marie Sønnegaard; Nielsen, Hanne Mørck

    2012-01-01

    Background: 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...... 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...

  13. Monoclonal antibodies against pregnancy-specific β1-glycoprotein (SP1) in immunohistochemistry and radioimmunoassay

    International Nuclear Information System (INIS)

    Wahlstroem, T.; Heikinheimo, M.

    1983-01-01

    Monoclonal mouse antibodies against pregnancy-specific beta-1-glycoprotein (SP 1 ) have been studied for their suitability in immunoperoxidase staining and radioimmunoassay methodologies. These antibodies were useful in staining normal placentas, hydatidiform moles, invasive moles and choriocarcinomas. They showed good specificity, with minimal background staining, and will thus be superior to conventional polyclonal antisera in immunohistochemistry. However, the presently tested monoclonal anti-SP 1 antibodies were found not to be suitable for radioimmunoassay. (Auth.)

  14. Combined prednisolone and pirfenidone in bleomycin-induced lung disease

    Directory of Open Access Journals (Sweden)

    Preyas J Vaidya

    2016-01-01

    Full Text Available Bleomycin is a cytostatic drug commonly employed in the treatment of Hodgkin's disease, seminomas, and choriocarcinoma. Bleomycin may induce a chronic pulmonary inflammation that may progress to fibrosis. So far, only corticosteroids have been used in the treatment of bleomycin-induced lung disease with variable results. Pirfenidone is an antifibrotic drug that has been approved for the treatment of idiopathic pulmonary fibrosis. We report two cases of bleomycin-induced lung disease treated successfully with pirfenidone and oral corticosteroids.

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

    International Nuclear Information System (INIS)

    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.

    1997-01-01

    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

  16. A case report of treating a high-risk gestational trophoblastic disease (GTD

    Directory of Open Access Journals (Sweden)

    Zhi Hao Liew

    2017-12-01

    Full Text Available Background: GTD developing after a normal pregnancy is reported in 25% of patients and it is usually choriocarcinoma. It occurs in approximately 5 per 100,000 pregnancies in Southeast Asia. Case: A 34 year-old Malay lady, gravida 4 para 4+0 presented with vaginal bleeding in two weeks after the delivery of her fourth child who was born as full term through LSCS. She admitted to hospital and underwent Suction and curettage. The histopathology came back as choriocarcinoma. On post-op day 7, she developed massive hemoperitoneum due to uterine perforation caused by tumour rupture. Therefore, total abdominal hysterectomy was performed. Post-surgery serum beta hCG was 209,320 IU/L. Thyroid function test was normal. Histopathology examination revealed choriocarcinoma at the fundus with haemorrhagic necrotic areas, infiltrating myometrial wall and right fallopian tube stump with serosal breach. CT imaging showed normal brain and multiple bilateral lung nodules in upper and lower lobes. She was given first cycle of EMA-CO (Etoposide, Methotrexate, Actinomycin D, Vincristine, Cyclophosphamid in view of high-risk choriocarcinoma with lungs metastasis, stage III with WHO prognostic scoring 11. Her pre-chemotherapy beta hCG was 263,753 IU/L which gradually went down and became less than 0.1 after cycle-5. CT scan was also normal. After that, another two more cycles of chemotherapy were proceeded. Therefore, she has completed seven cycles of chemotherapy in March 2016. She has been monitored under oncology follow-up for one year. Monthly βhCG was always normal until now without signs and symptoms of recurrence. Conclusion: Generally, high-risk GTDs are resistant to single agent chemotherapy and multiple chemotherapy regimens are necessary. Although this patient is a case of choriocarcinoma having high risk features, such as antecedent full-term pregnancy and pre-treatment beta-hCG of 263,753 IU/L (more than 100,000, she gained complete remission after seven

  17. 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. © 2016 The Author(s).

  18. FEMALE GENITAL TRACT CANCERS IN SAGAMU, SOUTHWEST, NIGERIA.

    Science.gov (United States)

    Adefuye, P O; Adefuye, B O; Oluwole, A A

    2014-11-01

    To describe pattern of female genital tract cancers seen at Olabisi Onabanjo University Teaching Hospital (OOUTH), Sagamu, Nigeria. This is a retrospective review of all cases of female genital tract cancers managed at the Gynaecology department of OOUTH, Sagamu, Nigeria. OOUTH is a tertiary health institution of the State's university and it takes referrals from within and outside the State. Case records of all female genital tract cancers managed between January 2004 and December 2013 were retrieved and analysed using SPSS version 16.0. There were 2059 women treated forvarious gynaecologic conditions, 179 (8.7%) were cases of female genital tract cancers and 161 records were available for analysis. Cervical cancer constituted the commonest (51.6%), followed by ovarian (35.4%), endometrial (9.9%), and choriocarcinoma (1.9%). There were no cases of vaginal and fallopian tube cancers. The lowest mean age was found in choriocarcinoma (36.60 ± 4.50 years) and highest in vulvar cancer (70.00 ± 2.82 years). The mean ages for cervical, endometrial and ovarian cancers were (51.98 ± 12.39), (65.38 ± 7.24), and (54.42 ± 10.51) years respectively. Similarly the least mean parity was found in choriocarcinoma (2.33 ± 1.52), and the highest in vulvar cancer (6.00 ± 1.44). The mean parity for cervical, endometrial, and ovarian were (4.10 ± 1.49),(3.06 ± 1.48), and (3.72 ± 1.68) respectively. These differences are statistically significant, age; F = 7.61, p < 0.0001, and parity; F = 3.27, p= 0.013. Incidence of cervical, endometrial, and ovarian cancers remain high and presentations are at late stages. There is a need to improve on cervical cancer screening, and for the attending physicians to improve on their indices of suspicions as regards endometrial and ovarian cancers.

  19. Rare Presentation of Metastatic Cystic Trophoblastic Tumor in a Patient Without Prior Chemotherapy

    Directory of Open Access Journals (Sweden)

    Michael L. Wang

    2017-07-01

    Full Text Available Cystic trophoblastic tumor (CTT is a rare testicular germ cell tumor (GCT predominantly seen in post-chemotherapy patients. It is prognostically similar to teratoma and requires no additional chemotherapy in the absence of a nonteratomatous GCT component. We report a case of metastatic CTT in a patient with primary testicular teratoma without prior chemotherapy. Retroperitoneal lymph node metastases contained teratoma, embryonal carcinoma, and CTT. The CTT was β-hCG positive and SALL4 negative by immunohistochemistry (IHC. CTT can arise in metastatic testicular GCT in treatment naïve patients. An important differential diagnosis is choriocarcinoma due to treatment implications, and SALL4 IHC may help.

  20. Application of pregnancy specific β1 glycoprotein-radioimmunoassay (SP1-ria) in obstetrics and gynecology

    International Nuclear Information System (INIS)

    Zhang Weiyuan

    1988-01-01

    Serum SP 1 values of 395 patients were determined by radioimmunoassay. It was found that SP 1 was apparently absent from the blood of normal men and nonpregnant women, increased with gestational stage in pregnant women, and was highest in late pregnancy. In high-risk pregnancy, SP 1 was lower than normal pregnamey group (PC0.01) could also be detected in ectopic pregnancy. In patients with benign and malignant hydatidiform mole, and choriocarcinoma, AP 1 level decreased with malignant degree. The authors suggest that measurement of SP 1 levels is a valuable index for monitoring high-risk pregnancy, diagnosing ectopic pregnancy and following-up trophoblastic cell diseases

  1. [Children with hyperthyroidism due to elevated hCG levels].

    Science.gov (United States)

    Jöbsis, Jasper J; van Trotsenburg, A S Paul; Merks, Johannes H M; Kamp, Gerdine A

    2014-01-01

    We describe two children with hyperthyroidism secondary to elevated hCG levels: one patient with gestational trophoblastic disease and one patient with choriocarcinoma. hCG resembles other glycoproteins that can lead to hyperthyroidism through TSH receptor activation. Also, through its LH-mimicking effect, hCG can induce high oestradiol levels, resulting in stormy pubertal development. False negative hCG tests due to the high-dose hook effect may complicate the diagnostic process. In patients with antibody-negative thyrotoxicosis, the diagnosis of hCG-induced hyperthyroidism must be considered.

  2. Long-term unmaintained remissions after agressive multidisciplinary treatment of advanced non-seminomatous testicular germ cell tumors.

    Science.gov (United States)

    Carey, R W; Weitzman, S A; Wilkins, E W; Chu, A M; Prout, G R

    1977-10-01

    Five patients with disseminated non-seminomatous testicular germ cell tumors are described. These patients have been clinically free of disease for 25 to more than 99 months and may be cured, since the interval after last treatment ranges from 13 to more than 76 months. Two patients, including 1 with pure choriocarcinoma, represent chemotherapeutic successes. In 3 patients the advantages of an individualized, multidisciplinary approach with surgery, radiotherapy and chemotherapy are shown. The benefits of continued aggressive treatment using residual therapeutic modalities despite prior failure with other therapy are documented.

  3. 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.

  4. 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.

  5. Effectivity of pazopanib treatment in orthotopic models of human testicular germ cell tumors

    International Nuclear Information System (INIS)

    Juliachs, Mercè; Viñals, Francesc; Vidal, August; Muro, Xavier Garcia del; Piulats, Josep M; Condom, Enric; Casanovas, Oriol; Graupera, Mariona; Germà, Jose R; Villanueva, Alberto

    2013-01-01

    Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies

  6. 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.

  7. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  8. Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

    International Nuclear Information System (INIS)

    Dhanda, S.; Ramani, S.; Dhanda, S.; Ramani, S.; Thakur, M.

    2014-01-01

    Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial), invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI) is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extra uterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT), and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography) and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity. 1. Introduction Gestational trophoblastic disease (GTD) refers to an abnormal trophoblastic proliferation composed of a broad spectrum of lesions ranging from benign, albeit pre malignant hydatiform mole (complete and partial), through to the aggressive invasive mole, choriocarcinoma

  9. Malignant primary germ-cell tumor of the brain: case report

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh (Kobe Municipal Central Hospital (Japan))

    1983-04-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported. The first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe. Total removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule. Histological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma. Primary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma. In this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy.

  10. Formulación de metotrexato 50 mg solución inyectable Formulation of metotrexate 50 mg injectable solution

    Directory of Open Access Journals (Sweden)

    Armando Gato del Monte

    2006-08-01

    Full Text Available El metotrexato es un antimetabolito que se agrupa entre los antagonistas del ácido fólico, para el tratamiento de cariocarcinoma gestacional, cariocarcinoma destructivo y lunar hidatiforme, leucemia linfocítica aguda, profilaxis y tratamiento de leucemias meníngeas y terapia de mantenimiento en combinación con otros agentes quimioterapéuticos en diferentes tumores sólidos y linfomas no Hogkin, así como en artritis y psoriasis. Para desarrollar este producto se elaboraron los ensayos preliminares en la etapa de preformulación, se determinaron las características organolépticas, el pH y la concentración del principio activo. Mediante estos estudios se logró obtener una formulación de metotrexato 50 mg solución inyectable con características adecuadas, estable física, química, biológica y microbiológicamente. La formulación que se obtuvo se escaló industrialmente, la cual se envasó en bulbos que cumplen satisfactoriamente con los parámetros de calidad establecidos. Mediante el estudio de estabilidad realizado a estos lotes se comprobaron los parámetros de calidad al producto terminado, que aparecen en la Farmacopea de los Estados Unidos 26 (USP. Se le estableció al medicamento una fecha de vencimiento de 2 años bajo las condiciones de temperatura controlada de 2-8 °C y protegido de la luzMetotrexate is an antimetabolite that groups itslef among the folic acid antagonists for the treatment of gestational choriocarcinoma, destructive choriocarcinoma, lunar hydatidiform choriocarcinoma, acute lymphocytic leukemia, prophylaxis and treatment of meningeal leukemias and maintenance therapy combined with other chemotherapeutic agents in different solid tumors and non-Hodgkin lymphomas, as well as in arthritis and psoriasis. To develop this product, preliminary trials were made in the preformulation stage, and the organoleptic characteristics, pH, and the active principle concentration were determined. By these studies, it was

  11. Progranulin shows cytoprotective effects on trophoblast cells in vitro but does not antagonize TNF-α-induced apoptosis.

    Science.gov (United States)

    Stubert, Johannes; Waldmann, Kathrin; Dieterich, Max; Richter, Dagmar-Ulrike; Briese, Volker

    2014-11-01

    The glycoprotein progranulin directly binds to TNF-receptors and thereby can antagonize the inflammatory effects of TNF-α. Here we analyzed the impact of both cytokines on cytotoxicity and viability of trophoblast cells. Isolated villous first trimester human trophoblast cells and the human choriocarcinoma cell line BeWo were treated with recombinant human progranulin and TNF-α. Analyses were performed by LDH- and MTT-assay and measurement of caspase-8-activity. Progranulin treatment showed some cytoprotective effects on isolated trophoblast cells. However, TNF-α-induced apoptosis was not antagonized by addition of progranulin. Effects were similar, but more pronounced in BeWo cells. The cytoprotective activity of progranulin on trophoblast cells in vitro was only weak and of doubtful biologic relevance. It was not able to antagonize TNF-α. Future studies should focus on possible paracrine activities of progranulin.

  12. A Label-Free and Ultrasensitive Immunosensor for Detection of Human Chorionic Gonadotrophin Based on Graphene FETs.

    Science.gov (United States)

    Islam, Kamrul; Suhail, Ahmed; Pan, Genhua

    2017-07-12

    We report on a label-free immunosensor based on graphene field effect transistors (G-FETs) for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG), as an indicator of pregnancy and related disorders, such as actopic pregnancy, choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was non-covalently anchored onto the graphene channel in order to retain the sp² lattice. The G-FET transfer characteristics showed repeatable and reliable responses in all surface modifying steps using a direct current (DC) readout system. The hCG concentration gradient showed a detection limit of ~1 pg·mL -1 . The proposed method facilitates the cost-effective and viable production of graphene point-of-care devices for clinical diagnosis.

  13. Efficacy of transcatheter uterine artery embolization for treating emergency hemorrhage obstetrics and gynecology

    International Nuclear Information System (INIS)

    Li Hongwei

    2011-01-01

    Objective: To evaluate the efficacy of selective iliac artery embolization (TAE) or uterine artery embolization (UAE) for treatment of emergency hemorrhage in obstetrics and gynecology. Methods: Selective bilateral TAE or UAE were performed on 59 patients with acute cervical hemorrhage from postpartum hemorrhage (30), cervical cancer (16), endometrial cancer (8), and choriocarcinoma (5). Gelfoam particles were used in postpartum hemorrhage; chemotherapeutics and Iodipin suspension were used in malignancy. Results: Bleeding was stopped completely in all 59 patients with TAE or UAE procedure time of 30-50 minutes (mean: 42.17±4.78 minutes). There were no serious complications. Conclusion: TAE or UAE are effective for treating emergency hemorrhage in obstetrics and gynecology. (authors)

  14. Cannonball lung metastases as a presenting feature of ectopic hCG expression

    Directory of Open Access Journals (Sweden)

    Rong-Hsin Yang

    2016-08-01

    Full Text Available Cannonball metastases refer to well-defined spherical nodules scattered over both lungs, being a classical presentation of hematogenous tumor spreading. Striking progression of lung metastases without established primary malignancy can raise a diagnostic challenge. We herein report three cases with cannonball metastases at initial presentation. Two patients ended up having a choriocarcinoma but no awareness of the presence of primary tumors, and the third had abrupt lung metastases of endometrial cancer while she was being asymptomatic. Relentless progression was illustrated by clinical and radiographic changes. Ectopic expression of human chorionic gonadotropin (hCG would seemingly go some way responsible for fulminant cancer spreading associated with poor prognosis in our patients. The goal of this presentation is to raise awareness of ectopic hCG expression in patients presenting with similar astonishing scenarios.

  15. A Label-Free and Ultrasensitive Immunosensor for Detection of Human Chorionic Gonadotrophin Based on Graphene FETs

    Directory of Open Access Journals (Sweden)

    Kamrul Islam

    2017-07-01

    Full Text Available We report on a label-free immunosensor based on graphene field effect transistors (G-FETs for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG, as an indicator of pregnancy and related disorders, such as actopic pregnancy, choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was non-covalently anchored onto the graphene channel in order to retain the sp2 lattice. The G-FET transfer characteristics showed repeatable and reliable responses in all surface modifying steps using a direct current (DC readout system. The hCG concentration gradient showed a detection limit of ~1 pg·mL−1. The proposed method facilitates the cost-effective and viable production of graphene point-of-care devices for clinical diagnosis.

  16. A transplant recipient with a mixed germ-cell ovarian tumor

    Directory of Open Access Journals (Sweden)

    Ketata Hafed

    2008-01-01

    Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

  17. Intracranial germ-cell tumors

    International Nuclear Information System (INIS)

    Baker, L.L.; Kollias, S.S.; Cogen, P.H.; Barkovich, A.J.

    1991-01-01

    This paper reports on the MR characteristics together with the clinical and histologic features of cerebral germ-cell tumors were investigated to augment data regarding this rare, diverse class of neoplasms. Germinomas were homogeneous or heterogeneous masses, predominantly isointense to normal brain on T1-weighted images, and hyperintense and heterogeneous on T2-weighted images; three showed adjacent brain edema. Enhancement was prominent, either homogeneous or heterogeneous. One had spinal drop metastases. Teratomas, more common in young patients, were more heterogeneous than germinomas on T1-weighted and T2-weighted images. Five showed hyper- and hypointense foci on T1-weighted images that corresponded to fat and calcium, respectively, at CT. Teratomas did not enhance or enhanced heterogeneously. Two had intratumoral hemorrhage; there were no metastases. Both patients with choriocarcinoma had hemorrhagic masses

  18. 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...

  19. Objective Ki-67 Index Quantification In Non-Breast Tumors – Preliminary Data In Timisoara, Romania

    Directory of Open Access Journals (Sweden)

    A. Vaduva

    2016-06-01

    Proper image segmentation was identified on 25 cases. The best segmentation was obtained in lymphoid and central nervous system (CNS tumors. Lower Ki-67 values than the ones manually reported were identified in 16/25 cases (64%. Interestingly, digital quantification showed all 7 lymphoid cases to have a lower Ki-67 index than manually reported, while 6/9 CNS had higher Ki67 indices using automation processing. Valid digital quantification was not possible on skin, cervical and urothelial tumors, as regions of interest could not be defined to restrain the area to be evaluated.   Conclusion: Our preliminary study shows that ImmunoRatio plugin for Fiji in combination with IrfanView preprocessing are free, easy to use and powerful tools to obtain an objective Ki-67 index in non-mammary tumors: CNS, lymphoid, soft tissue, neuroendocrine tumors, choriocarcinomas and malignant melanomas.  

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

    International Nuclear Information System (INIS)

    Schröpfer, Andrea; Kammerer, Ulrike; Kapp, Michaela; Dietl, Johannes; Feix, Sonja; Anacker, Jelena

    2010-01-01

    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. 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. 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). 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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signalling

    Directory of Open Access Journals (Sweden)

    Martin eKnöfler

    2013-09-01

    Full Text Available Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signalling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signalling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β-catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signalling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signalling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β-catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signalling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodelling. Moreover, changes in Wnt signalling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signalling in physiological and abnormal

  3. 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.

  4. Clinical significance of three-dimensional sonohysterography

    International Nuclear Information System (INIS)

    Lee, Eun Hye; Lee, Mi Hwa; Lee, Chan; Kim, Jong Wook; Shin, Myung Choel

    1999-01-01

    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.

  5. 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.

  6. 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.)

  7. Modulation of Human Serotonin Transporter Expression by 5-HTTLPR in Colon Cells

    Directory of Open Access Journals (Sweden)

    Tewin Tencomnao

    2011-10-01

    Full Text Available Serotonin (5-HT is a monoamine neurotransmitter and plays important roles in several of the human body’s systems. Known as a primary target for psychoactive drug development, the 5-HT transporter (5-HTT, SERT plays a critical role in the regulation of serotonergic function by reuptaking 5-HT. The allelic variation of 5-HTT expression is caused by functional gene promoter polymorphism with two principal variant alleles, 5-HTT gene-linked polymorphic region (5-HTTLPR. It has been demonstrated that 5-HTTLPR is associated with numerous neuropsychiatric disorders. The functional roles of 5-HTTLPR have been reported in human choriocarcinoma (JAR, lymphoblast and raphe cells. To date, the significance of 5-HTTLPR in gastrointestinal tract-derived cells has never been elucidated. Thus, the impact of 5-HTTLPR on 5-HTT transcription was studied in SW480 human colon carcinoma cells, which were shown to express 5-HTT. We found 42-bp fragment in long (L allele as compared to short (S allele, and this allelic difference resulted in 2-fold higher transcriptional efficiency of L allele (P < 0.05 as demonstrated using a functional reporter gene assay. Nevertheless, the transcriptional effect of estrogen and glucocorticoid on 5-HTT expression via 5-HTTLPR was not found in this cell line. Our study was the first to demonstrate the molecular role of this allelic variation in gastrointestinal tract cells.

  8. A Study of Patients with Primary Mediastinal Germ Cell Tumors Treated Using Multimodal Therapy

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    Yutaro Tanaka

    2017-01-01

    Full Text Available Objectives. Primary mediastinal germ cell tumors (PMGCTs are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. Methods. We examined 6 patients (median age: 25 years, range: 19–27 years with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8–84 months. Results. Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP or etoposide and cisplatin (EP. One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. Conclusions. Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

  9. Diagnostic value of different tumor markers, our experience

    International Nuclear Information System (INIS)

    Pervez, T.; Anwar, S.

    2000-01-01

    Variety of tumor markers with varying sensitivity and specificity are used for diagnosis of different malignancies. This study was done to determine the diagnostic value of different tumor markers in our patients with various malignancies. Out of 235 patients studied, 162 were suffering from malignant and 73 from benign diseases. Among these 84 were positive for tumor markers. Out of these positive tumor markers, 75 were suffering from malignancy. Tumor marker analyzed were ca-15-3, ca-125, BETA-HCG, CEA, PSA and alpha-FP depending upon the type of the disease these cases presented. Analysis of the results revealed that different tumor markers had sensitivity varying from 76.9-95.8% and specificity varying form 75-90.9%. CA-125 was observed to be the most specific and sensitive tumor marker for ovarian tumors followed by alpha-FP for hepatocellular tumors and CEA for gastrointestinal tumors. Similarly, PSA for prostate cancers, beta-HCG for choriocarcinoma and CA-15-3 for breast cancer. It is concluded that all the tumor markers have a variable diagnostic value, which cannot be relied upon independently, without other tests added to increase diagnostic value. (author)

  10. Minimally-aggressive gestational trophoblastic neoplasms.

    Science.gov (United States)

    Cole, Laurence A

    2012-04-01

    We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Proportion hyperglycosylated hCG: a new test for discriminating gestational trophoblastic diseases.

    Science.gov (United States)

    Cole, Laurence A

    2014-11-01

    Hyperglycosylated human chorionic gonadotropin (hCG) is a variant of hCG with large oligosaccharide side chains. Although hCG is produced by syncytiotrophoblast cells, hyperglycosylated hCG marks cytotrophoblast cell. Hyperglycosylated hCG signals placental implantation. Total hCG in serum and urine is measured by the Siemens Immulite hCG pregnancy test; the result is in milli-international unit per milliliter. Hyperglycosylated hCG is determined by the B152 microtiter plate assay; the result is in nanogram per milliliter. Hyperglycosylated hCG results can be converted to milli-international unit per milliliter equivalents by multiplying by 11. The test measures proportion hyperglycosylated hCG, hyperglycosylated hCG / total hCG. Proportion hyperglycosylated hCG marks cases intent on developing persistent hydatidiform mole (68% detection at 17% false detection). Proportion hyperglycosylated hCG also marks persistent hydatidiform mole (100% detection at 5.1% false detection). Proportion hyperglycosylated hCG distinguishes choriocarcinoma and gestational trophoblastic neoplasm cases, absolutely discriminating aggressive cases and minimally aggressive cases. Proportion hyperglycosylated hCG identifies quiescent gestational trophoblastic disease cases. It recognizes quiescent cases that become persistent disease (100% detection at 0% false positive). Proportion hyperglycosylated hCG is an invaluable test for discriminating gestational trophoblastic diseases.

  12. Toxicity of diuron in human cancer cells.

    Science.gov (United States)

    Huovinen, Marjo; Loikkanen, Jarkko; Naarala, Jonne; Vähäkangas, Kirsi

    2015-10-01

    Diuron is a substituted phenylurea used as a herbicide to control broadleaf and grass weeds and as a biocidal antifouling agent. Diuron is carcinogenic in rat urinary bladder and toxic to the reproductive system of oysters, sea urchins and lizards. The few studies carried out in human cells do not include the genotoxicity of diuron. We have investigated the toxicity of diuron in human breast adenocarcinoma (MCF-7) and human placental choriocarcinoma (BeWo) cells. The production of reactive oxygen species (ROS) was statistically significantly increased in both cell lines but only at the highest 200 μM concentration. Diuron clearly reduced the viability of BeWo, but not MCF-7 cells. The relative cell number was decreased in both cell lines indicative of inhibition of cell proliferation. In the Comet assay, diuron increased DNA fragmentation in MCF-7 but not in BeWo cells. The expressions of p53 protein, a marker for cell stress, and p21 protein, a transcriptional target of p53, were increased, but only in MCF-7 cells. In conclusion, our results suggest that diuron is cytotoxic and potentially genotoxic in a tissue-specific manner and that ROS play a role in its toxicity. Thus, exposure to diuron may exert harmful effects on fetal development and damage human health. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. 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.

  14. CT findings of solitary intracranial metastasis

    International Nuclear Information System (INIS)

    Suh, Dae Chul; Lee, Kyung Soo; Chang, Kee Hyun

    1987-01-01

    The authors retrospectively reviewed and analyzed CT scans of fifty patients with solitary intracranial lesion selected from 118 patients who had been confirmed to have intracranial metastasis from 1979 to 1985. The results were as follows: 1. The most common primary tumors with solitary metastasis, in order of frequency, were lung cancer, breast cancer, choriocarcinoma, colon cancer, lymphoma and others. 2. Precontrast scans obtained in 35 cases showed cystic very low density in 20%, slightly low density in 9%, isodensity in 20%, high density in 51% when he densities of the lesions were compared with that of the normal brain tissue. 3. After contrast enhancement 43 out of 50 showed one of 4 patterns of enhancement. Homogeneous enhancement without necrosis were found in 26%, homogeneous enhancement with necrosis in 18%, ring-enhancement in 26% and irregular enhancement in 16%. No enhancement was found in 14%. 4. The locations of the metastatic lesions were intra axial in 45 and extra axial in 5. Among the intra axial lesions, the parietal lobe was the most common location. Extra axial metastases were epidural, calvarial and leptomeningeal. 5. Degrees of surrounding edema were mild in 32%, moderate in 19% and severe in 49%

  15. Translation of LINE-1 DNA elements in vitro and in human cells

    International Nuclear Information System (INIS)

    Leibold, D.M.; Swergold, G.D.; Thayer, R.E.; Singer, M.F.; Fanning, T.G.; Dombroski, B.A.

    1990-01-01

    The LINE-1(L1) family of interspread DNA sequences found throughout the human genome (L1 Homo sapiens, L1Hs) includes active transposable elements. Current models for the mechanism of transposition involve reverse transcription of an RNA intermediate and utilization of element-encoded proteins. The authors report that an antiserum against the polypeptide encoded by the L1Hs 5' open reading frame (ORF1) detects, in human cells, an endogenous ORF1 protein as well as the ORG1 product of an appropriate transfecting recombinant vector. The endogenous polypeptide is most abundant in teratocarcinoma and choriocarcinoma cells, among those cell lines tested; it appears to be a single species of ∼38 kDa. In contrast, RNAs synthesized in vitro from cDNAs representing full-length, polyadenylylated cytoplasmic L1Hs RNA yield, upon in vitro translation, ORF1 products of slightly different sizes. This is consistent with the fact that the various cDNAs are different and represent transcription of different genomic L1Hs elements. In vitro studies additionally suggest that translation of ORF1 is initiated at the first AUG codon. Finally, in no case was an ORF1-ORF2 fusion protein detected

  16. 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.

  17. Cancer incidence in the population of Nagasaki city 30 years after atomic bombing

    International Nuclear Information System (INIS)

    Okuyama, Shinichi; Mishina, Hitoshi

    1988-01-01

    In order to attest the evolutionary hypothesis of non-epithelial-epithelial tumor shift (Okuyama and Mishina 1986), the published cancer incidence data for the population of Nagasaki City during the period of 1973-1977 was studied along with appropriate control populations of Fukuoka City, and Miyagi and Osaka prefectures. Significant increments of non-epithelial tumors including leukemias, and epithelial tumors such as cervical cancers and choriocarcinomas were observed. An inference was made to the post-atomic bomb radiation carcinogenesis that different organ systems responded to that irradiation with different oncogenic patterns: Neoplasms of the pre-vertebral organs (non-epithelial organ systems) were the first to react and tapered long (curve type I); Tumors of the vertebral but pre-mammalian (those of the digestive tract, respiratory and thyroid) could have formed two separate peaks, one for the early and high dosage and the other for the late and low dosage (II); With breast cancer or the mammalian symbol tumor, there was a single peak reflecting the cohort of reproductives (III). The evolutionary and phylogenetic progression could have taken place from I through III. Thus, cancer incidence analysis may be helpful in deciphering the atomic bomb radiation carcinogenesis. (author)

  18. 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.)

  19. Uncommon mucosal metastases to the stomach

    Directory of Open Access Journals (Sweden)

    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.

  20. Cell surface fucosylation does not affect development of colon tumors in mice with germline Smad3 mutation

    Science.gov (United States)

    Domino, Steven E.; Karnak, David M.; Hurd, Elizabeth A.

    2006-01-01

    Background/Aims: Neoplasia-related alterations in cell surface α(1,2)fucosylated glycans have been reported in multiple tumors including colon, pancreas, endometrium, cervix, bladder, lung, and choriocarcinoma. Spontaneous colorectal tumors from mice with a germline null mutation of transforming growth factor-β signaling gene Smad3 (Madh3) were tested for α(1,2)fucosylated glycan expression. Methods: Ulex Europaeus Agglutinin-I lectin staining, fucosyltransferase gene northern blot analysis, and a cross of mutant mice with Fut2 and Smad3 germline mutations were performed. Results: Spontaneous colorectal tumors from Smad3 (-/-) homozygous null mice were found to express α(1,2)fucosylated glycans in an abnormal pattern compared to adjacent nonneoplastic colon. Northern blot analysis of α(1,2)fucosyltransferase genes Fut1 and Fut2 revealed that Fut2, but not Fut1, steady-state mRNA levels were significantly increased in tumors relative to adjacent normal colonic mucosa. Mutant mice with a Fut2-inactivating germline mutation were crossed with Smad3 targeted mice. In Smad3 (-/-)/Fut2 (-/-) double knock-out mice, UEA-I lectin staining was eliminated from colon and colon tumors, however, the number and size of tumors present by 24 weeks of age did not vary regardless of the Fut2 genotype. Conclusions: In this model of colorectal cancer, cell surface α(1,2)fucosylation does not affect development of colon tumors. PMID:17264540

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

    Science.gov (United States)

    Mao, Yang; Resende, Mafalda; Daugaard, Mads; Riis Kristensen, Anders; Damm, Peter; G. Theander, Thor; R. Hansson, Stefan; Salanti, Ali

    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 (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location. VAR2CSA pull-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 fusion of the BeWo cells, triggered by forskolin treatment, caused an increased expression of placental CS-modified syndecan-1. In line with this, we show that rVAR2 binding to placental CS impairs syndecan-1-related Src signaling in forskolin treated BeWo cells, but not in untreated cells. PMID:27556547

  2. Expression of a fms-related oncogene in carcinogen-induced neoplastic epithelial cells

    International Nuclear Information System (INIS)

    Walker, C.; Nettesheim, P.; Barrett, J.C.; Gilmer, T.M.

    1987-01-01

    Following carcinogen exposure in vitro, normal rat tracheal epithelial cells are transformed in a multistage process in which the cultured cells become immortal and ultimately, neoplastic. Five cell lines derived from tumors produced by neoplastically transformed rat tracheal epithelial cells were examined for the expression of 11 cellular oncogenes previously implicated in pulmonary or epithelial carcinogenesis. RNA homologous to fms was expressed at a level 5-19 times higher than normal tracheal epithelial cells in three of five of the tumor-derived lines. All three lines expressing high levels of fms-related RNA gave rise to invasive tumors of epithelial origin when injected into nude mice. Increased expression of the fms-related mRNA was not due to gene amplification, and no gene rearrangement was detected by Southern analyses. RNA blot analysis using a 3' v-fms probe detected a 9.5-kilobase message in the three tumor-derived lines, whereas both normal rat aveolar macrophages and the human choriocarcinoma line BeWo expressed a fms transcript of ≅ 4 kilobases. The authors conclude from these data that the gene expressed as a 9.5-kilobase transcript in these neoplastic epithelial cells is a member of a fms-related gene family but may be distinct from the gene that encodes the macrophage colony-stimulating factor (CSF-1) receptor

  3. Nontraumatic spontaneous rupture of the kidney : etiology and CT findings

    International Nuclear Information System (INIS)

    Heo, Tae Haeng; Jeon, Hae Jeong; Shin, Hyun Joon; Kim, Bo Hyun; Cho, Kyoung Sik; Kim, Young Hwa; Kim, Seung Hyup; Park, Churl Min

    1997-01-01

    To evaluate the usefulness of CT scanning in determining the etiology of spontaneous rupture of the kidney We retrospectively analyzed the CT findings of spontaneous rupture of the kidney in eleven patients, Four were male and seven were female, and they were aged between 20 and 71 (mean, 46.6) years. Both pre- and post-contrast enhanced CT scanning was performed in all patients. Spontaneous renal rupture was induced in seven cases by neoplasms (three angiomyolipomas, three renal cell carcinomas, and one metastatic choriocarcinoma), in three cases by infection or inflammation (acute and chronic pyelonephritis, and renal abscess), and in one, by renal cyst. Common CT findings of rupture of the kidney were the accumulation of high density fluid in the perirenal and anterior pararenal space, and inhomogeneous irregular low density of renal parenchyma and the rupture site. Angiomyolipoma showed fat and an angiomatous component in the lesion, while acute and chronic pyelonephrities revealed thinning of the renal parenchyma and an irregular renal outline. Renal cell carcinoma showed a dense soft tissue mass in the parenchyma. Well-defined, round low-density lesions were noted in the case of renal cyst and renal abscess. CT is very useful in diagnosing and determining the etiology of non-traumatic spontaneous rupture of the kidney and plays an important role in the evaluation of emergency cases

  4. Primary Germ Cell Tumors of the Mediastinum: 10 Years of Experience in a Tertiary Teaching Hospital

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    Chih-Jen Yang

    2005-09-01

    Full Text Available Germ cell tumors occur mostly in the gonad. Extragonadal germ cell tumors are rare, and most occur in the retroperitoneum and mediastinum. Primary mediastinal germ cell tumors are often found in the anterior portion of the mediastinum and include teratomas and non-teratomatous tumors. Non-teratomatous tumors include seminomas and malignant non-seminomatous germ cell tumors (MNSGCTs. MNSGCTs include yolk sac tumors, choriocarcinomas, embryonal carcinomas, and mixed type germ cell tumors. Teratomas are the most common germ cell tumors of the mediastinum, and seminomas are the most common non-teratomatous germ cell tumors of the mediastinum. Cases of primary mediastinal MNSGCT reported in the literature are rare. In this report, we review all primary mediastinal germ cell tumors from a 10-year period at the Chung-Ho Memorial Hospital of Kaohsiung Medical University. A total of 14 cases were reviewed, including 11 patients with mature teratomas, two with yolk sac tumors, and one with seminoma. We discuss the differences in clinical presentation, histopathologic characteristics, treatment, and prognosis.

  5. Gestational Trophoblastic Disease: A Multimodality Imaging Approach with Impact on Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Sunita Dhanda

    2014-01-01

    Full Text Available Gestational trophoblastic disease is a condition of uncertain etiology, comprised of hydatiform mole (complete and partial, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. It arises from abnormal proliferation of trophoblastic tissue. Early diagnosis of gestational trophoblastic disease and its potential complications is important for timely and successful management of the condition with preservation of fertility. Initial diagnosis is based on a multimodality approach: encompassing clinical features, serial quantitative β-hCG titers, and pelvic ultrasonography. Pelvic magnetic resonance imaging (MRI is sometimes used as a problem-solving tool to assess the depth of myometrial invasion and extrauterine disease spread in equivocal and complicated cases. Chest radiography, body computed tomography (CT, and brain MRI have been recommended as investigative tools for overall disease staging. Angiography has a role in management of disease complications and metastases. Efficacy of PET (positron emission tomography and PET/CT in the evaluation of recurrent or metastatic disease has not been adequately investigated yet. This paper discusses the imaging features of gestational trophoblastic disease on various imaging modalities and the role of different imaging techniques in the diagnosis and management of this entity.

  6. Cyclic AMP regulation of the human glycoprotein hormone α-subunit gene is mediated by an 18-base-pair element

    International Nuclear Information System (INIS)

    Silver, B.J.; Bokar, J.A.; Virgin, J.B.; Vallen, E.A.; Milsted, A.; Nilson, J.H.

    1987-01-01

    cAMP regulates transcription of the gene encoding the α-subunit of human chorionic gonadotropin (hCG) in the choriocarcinoma cells (BeWo). To define the sequences required for regulation by cAMP, the authors inserted fragments from the 5' flanking region of the α-subunit gene into a test vector containing the simian virus 40 early promoter (devoid of its enhancer) linked to the bacterial chloramphenicol acetyltransferase (CAT) gene. Results from transient expression assays in BeWo cells indicated that a 1500-base-pair (bp) fragment conferred cAMP responsiveness on the CAT gene regardless of position or orientation of the insert relative to the viral promoter. A subfragment extending from position -169 to position -100 had the same effect on cAMP-induced expression. Furthermore, the entire stimulatory effect could be achieved with an 18-bp synthetic oligodeoxynucleotide corresponding to a direct repeat between position -146 and -111. In the absence of cAMP, the α-subunit 5' flanking sequence also enhanced transcription from the simian virus 40 early promoter. They localized this enhancer activity to the same -169/-100 fragment containing the cAMP response element. The 18-bp element alone, however, had no effect on basal expression. Thus, this short DNA sequence serves as a cAMP response element and also functions independently of other promoter-regulatory elements located in the 5' flanking sequence of the α-subunit gene

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

    International Nuclear Information System (INIS)

    Guo, Hongsheng; Wu, Fenping; Wang, Yan; Yan, Chong; Su, Wenmei

    2014-01-01

    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

  8. 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.

  9. HTR8/SVneo cells display trophoblast progenitor cell-like characteristics indicative of self-renewal, repopulation activity, and expression of "stemness-" associated transcription factors.

    Science.gov (United States)

    Weber, Maja; Knoefler, Ilka; Schleussner, Ekkehard; Markert, Udo R; Fitzgerald, Justine S

    2013-01-01

    JEG3 is a choriocarcinoma--and HTR8/SVneo a transformed extravillous trophoblast--cell line often used to model the physiologically invasive extravillous trophoblast. Past studies suggest that these cell lines possess some stem or progenitor cell characteristics. Aim was to study whether these cells fulfill minimum criteria used to identify stem-like (progenitor) cells. In summary, we found that the expression profile of HTR8/SVneo (CDX2+, NOTCH1+, SOX2+, NANOG+, and OCT-) is distinct from JEG3 (CDX2+ and NOTCH1+) as seen only in human-serum blocked immunocytochemistry. This correlates with HTR8/SVneo's self-renewal capacities, as made visible via spheroid formation and multi-passagability in hanging drops protocols paralleling those used to maintain embryoid bodies. JEG3 displayed only low propensity to form and reform spheroids. HTR8/SVneo spheroids migrated to cover and seemingly repopulate human chorionic villi during confrontation cultures with placental explants in hanging drops. We conclude that HTR8/SVneo spheroid cells possess progenitor cell traits that are probably attained through corruption of "stemness-" associated transcription factor networks. Furthermore, trophoblastic cells are highly prone to unspecific binding, which is resistant to conventional blocking methods, but which can be alleviated through blockage with human serum.

  10. The human luteinizing hormone receptor gene promoter: activation by Sp1 and Sp3 and inhibitory regulation.

    Science.gov (United States)

    Geng, Y; Tsai-Morris, C H; Zhang, Y; Dufau, M L

    1999-09-24

    To understand the transcriptional mechanism(s) of human LH receptor (LHR) gene expression, we have identified the dominant functional cis-elements that regulate the activity of the promoter domain (-1 to -176 bp from ATG). Mutagenesis demonstrated that the promoter activity was dependent on two Sp1 domains (-79 bp, -120 bp) in a transformed normal placental cell (PLC) and the choriocarcinoma JAR cell. Both elements interacted with endogenous Sp1 and Sp3 factors but not with Sp2 or Sp4. In Drosophila SL2 cells, the promoter was activated by either Sp1 or Sp3. An ERE half-site (EREhs) at -174 bp was inhibitory (by 100%), but was unresponsive to estradiol and did not bind the estrogen receptor or orphan receptors ERR1 and SF-1. The 5' upstream sequence (-177 to -2056 bp) inhibited promoter activity in PLC by 60%, but only minimally in JAR cells. Activation of the human LHR promoter through Sp1/3 factors is negatively regulated through EREhs and upstream sequences to exert control of gene expression. Copyright 1999 Academic Press.

  11. 3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

    International Nuclear Information System (INIS)

    Collier, Abby C.; Helliwell, Rachel J.A.; Keelan, Jeffrey A.; Paxton, James W.; Mitchell, Murray D.; Tingle, Malcolm D.

    2003-01-01

    The anti-HIV drug 3'-azido-3'-deoxythymidine (AZT) is the drug of choice for preventing maternal-fetal HIV transmission during pregnancy. Our aim was to assess the cytotoxic effects of AZT on human placenta in vitro. The mechanisms of AZT-induced effects were investigated using JEG-3 choriocarcinoma cells and primary explant cultures from term and first-trimester human placentas. Cytotoxicity measures included trypan blue exclusion, MTT, and reactive oxygen species (ROS) assays. Apoptosis was measured with an antibody specific to cleaved caspase-3 and by rescue of cells by the general caspase inhibitor Boc-D-FMK. The effect of AZT on the activities of glutathione-S-transferase, β-glucuronidase, UDP-glucuronosyl transferase, cytochrome P450 (CYP) 1A, and CYP reductase (CYPR) in the placenta was assessed using biochemical assays and immunoblotting. AZT increased ROS levels, decreased cellular proliferation rates, was toxic to mitochondria, and initiated cell death by a caspase-dependent mechanism in the human placenta in vitro. In the absence of serum, the effects of AZT were amplified in all the models used. AZT also increased the amounts of activity of GST, β-glucuronidase, and CYP1A, whereas UGT and CYPR were decreased. We conclude that AZT causes apoptosis in the placenta and alters metabolizing enzymes in human placental cells. These findings have implications for the safe administration of AZT in pregnancy with respect to the maintenance of integrity of the maternal-fetal barrier

  12. Pst I restriction fragment length polymorphism of the human placental alkaline phosphatase gene in normal placentae and tumors

    International Nuclear Information System (INIS)

    Tsavaler, L.; Penhallow, R.C.; Kam, W.; Sussman, H.H.

    1987-01-01

    The structure of the human placental alkaline phosphatase gene from normal term placentae was studied by restriction enzyme digestion and Southern blot analysis using a cDNA probe to the gene for the placental enzyme. The DNA digests fall into three distinct patterns based on the presence and intensity of an extra 1.1-kilobase Pst I Band. The extra 1.1-kilobase band is present in 9 of 27 placenta samples, and in 1 of these samples the extra band is present at double intensity. No polymorphism was revealed by digestion with restriction enzymes EcoRI, Sma I, BamHI, or Sac I. The extra Pst I-digestion site may lie in a noncoding region of the gene because no correlation was observed between the restriction fragment length polymorphism and the common placental alkaline phosphatase alleles identified by starch gel electrophoresis. In addition, because placental alkaline phosphatase is frequently re-expressed in neoplasms, the authors examined tissue from ovarian, testicular, and endometrial tumors and from BeWo choriocarcinoma cells in culture. The Pst I-DNA digestion patterns from these cells and tissues were identical to those seen in the normal ovary and term placentae. The consistent reproducible digestion patterns seen in DNA from normal and tumor tissue indicate that a major gene rearrangement is not the basis for the ectopic expression of placental alkaline phosphatase in neoplasia

  13. Adult testicular cancer: Two decades of Saudi national data.

    Science.gov (United States)

    Abomelha, Mohammed

    2017-01-01

    There is a paucity of data regarding testicular cancer among Saudis as well as the nonexistent of published national data. Furthermore, a substantial increase of the incidence of testicular cancer among Saudis was lately noted. The aim of the study is to determine the trends and patterns of testicular cancer among adult Saudis using national data over a period of 20 years. The national database of the Saudi Cancer Registry (SCR) on testicular cancer over the last two decades was studied including epidemiological and histological patterns. The 1004 cases of testicular cancer among adult Saudis reported by the SCR will be the subject of this study. From 1994 to 2013, 1004 cases of testicular cancer among adult Saudis were reported to the SCR, with a steadily significant increase in incidence rate reaching an annual rate of 94 cases in 2013. Age of the patients ranged 15-93 years with a mean of 34.5 years. The most affected age group was 20-34 years, where 51% of all testicular cancer accumulated. Around 85% of testicular cancer is germ cell tumors, while paratesticular and gonadal stromal tumors represent 15%. Of all testicular cancer, seminomas were seen in 40.7%, nonseminomas in 44.6%. Notably, 70.4% of the cases in the first decade were seminomas, while in the second decade 65.9% of the cases were nonseminomas. The subtypes of the nonseminomas were a mixed tumor in 51.6%, embryonal carcinoma in 19.9%, yolk sac tumor in 12.3%, germinomas in 6.7%, teratomas in 6%, and choriocarcinomas in 3.6%. Lymphomas (34.7%) and rhabdomyosarcomas (23.6%) are on the top of the paratesticular tumor group. The Surveillance Epidemiology and End Results summary stage of seminomas was localized in 61.6%, regional in 19.8%, and distant in 12.6%, while of nonseminomas was 48%, 15.5%, and 28.5%, respectively. Localized and distant status of seminomas improved over the studied period by 12% and 4% respectively, while this trend was not seen in nonseminomas. The incidence rate is on rising

  14. Metastatic tumor of the pancreas: helical CT findings

    International Nuclear Information System (INIS)

    Lee, Soon Jin; Lee, Won Jae; Lim, Hyo Keun; Kim, Seung Hoon; Kim, Kyeong Ah; Choi, Sang Hee; Jang, Hyun Jung; Lee, Ji Yeon

    2000-01-01

    To analyze the helical computed tomographic (CT) findings of distant metastatic tumors to the pancreas and to determine the differential points between these and primary pamcreatic carcinomas. We sruveyed 22 patients with metastatic tumor of the pancreas, proven on the basis of clinical and pathological findings. Seventeen patients were men, and five were women, and their ages ranged between 36 and 83 years. Their primary conditions were lung cancer (n=3D15), rectal cancer (n=3D2), melanoma of the foot, chondrosarcoma of the sacrum, cervical cancer, leiomyosarcoma of the uterus, and extragonadal choriocarcinoma of the mediastinum. We retrospectively reviewed the abdominal helical CT findings, analysing the number, location, size and attenuation of masses, as well as secondary change, which included dilatation of the pancreatic and biliary ducts and invasion of peripancreatic tissue or vessels. We also evaluated the differential findings of primary pancreatic cancer. Sixteen patients had a solitary focal mass, while in five, two masses were present. Among the 22 patients, low-density nodular masses were present in 21; in the other, in whom multiple metastasis from chondrosarcoma had occurred, there was dense calcification. The size of metastatic masses varied, ranging from 0.6 to 6 cm in diameter. The pancreatic duct proximal to the mass was dilated in ten cases, while the bile duct was dilated in six. The metastatic masses masses demonstrated no peripancreatic or vascular invasion, though they showed a discrete margin and contour bulging. Single metastasis to the pancreas was most common, and metastatic masses had a discrete margin, with contour bulging. There was no peripancreatic or vascular invasion. If the metastasis involved a single low-attenuated mass, however, with pancreatic or biliary dilatation, it was difficult to differentiate this from primary pancreatic cancer. (author)

  15. Placental Aromatase Is Deficient in Placental Ischemia and Preeclampsia.

    Directory of Open Access Journals (Sweden)

    Alejandra Perez-Sepulveda

    Full Text Available Preeclampsia is a maternal hypertensive disorder with uncertain etiology and a leading cause of maternal and fetal mortality worldwide, causing nearly 40% of premature births delivered before 35 weeks of gestation. The first stage of preeclampsia is characterized by reduction of utero-placental blood flow which is reflected in high blood pressure and proteinuria during the second half of pregnancy. In human placenta androgens derived from the maternal and fetal adrenal glands are converted into estrogens by the enzymatic action of placental aromatase. This implies that alterations in placental steroidogenesis and, subsequently, in the functionality or bioavailability of placental aromatase may be mechanistically involved in the pathophysiology of PE.Serum samples were collected at 32-36 weeks of gestation and placenta biopsies were collected at time of delivery from PE patients (n = 16 and pregnant controls (n = 32. The effect of oxygen tension on placental cells was assessed by incubation JEG-3 cells under 1% and 8% O2 for different time periods, Timed-mated, pregnant New Zealand white rabbits (n = 6 were used to establish an in vivo model of placental ischemia (achieved by ligature of uteroplacental vessels. Aromatase content and estrogens and androgens concentrations were measured.The protein and mRNA content of placental aromatase significantly diminished in placentae obtained from preeclamptic patients compared to controls. Similarly, the circulating concentrations of 17-β-estradiol/testosterone and estrone/androstenedione were reduced in preeclamptic patients vs. controls. These data are consistent with a concomitant decrease in aromatase activity. Aromatase content was reduced in response to low oxygen tension in the choriocarcinoma JEG-3 cell line and in rabbit placentae in response to partial ligation of uterine spiral arteries, suggesting that reduced placental aromatase activity in preeclamptic patients may be associated with chronic

  16. 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

  17. Online combination of reversed-phase/reversed-phase and porous graphitic carbon liquid chromatography for multicomponent separation of proteomics and glycoproteomics samples.

    Science.gov (United States)

    Lam, Maggie P Y; Lau, Edward; Siu, S O; Ng, Dominic C M; Kong, Ricky P W; Chiu, Philip C N; Yeung, William S B; Lo, Clive; Chu, Ivan K

    2011-11-01

    In this paper, we describe an online combination of reversed-phase/reversed-phase (RP-RP) and porous graphitic carbon (PGC) liquid chromatography (LC) for multicomponent analysis of proteomics and glycoproteomics samples. The online RP-RP portion of this system provides comprehensive 2-D peptide separation based on sequence hydrophobicity at pH 2 and 10. Hydrophilic components (e.g. glycans, glycopeptides) that are not retained by RP are automatically diverted downstream to a PGC column for further trapping and separation. Furthermore, the RP-RP/PGC system can provide simultaneous extension of the hydropathy range and peak capacity for analysis. Using an 11-protein mixture, we found that the system could efficiently separate native peptides and released N-glycans from a single sample. We evaluated the applicability of the system to the analysis of complex biological samples using 25 μg of the lysate of a human choriocarcinoma cell line (BeWo), confidently identifying a total of 1449 proteins from a single experiment and up to 1909 distinct proteins from technical triplicates. The PGC fraction increased the sequence coverage through the inclusion of additional hydrophilic sequences that accounted for up to 6.9% of the total identified peptides from the BeWo lysate, with apparent preference for the detection of hydrophilic motifs and proteins. In addition, RP-RP/PGC is applicable to the analysis of complex glycomics samples, as demonstrated by our analysis of a concanavalin A-extracted glycoproteome from human serum; in total, 134 potentially N-glycosylated serum proteins, 151 possible N-glycosylation sites, and more than 40 possible N-glycan structures recognized by concanavalin A were simultaneously detected. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. ABCG2/BCRP decreases the transfer of a food-born chemical carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in perfused term human placenta.

    Science.gov (United States)

    Myllynen, Päivi; Kummu, Maria; Kangas, Tiina; Ilves, Mika; Immonen, Elina; Rysä, Jaana; Pirilä, Rauna; Lastumäki, Anni; Vähäkangas, Kirsi H

    2008-10-15

    We have studied the role of ATP binding cassette (ABC) transporters in fetal exposure to carcinogens using 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) a known substrate for ABC transporters as a model compound. In perfusion of human term placenta, transfer of (14)C-PhIP (2 microM) through the placenta resulted in fetal-to-maternal concentration ratio (FM ratio) of 0.72+/-0.09 at 6 h. The specific ABCG2 inhibitor KO143 increased the transfer of (14)C-PhIP from maternal to fetal circulation (FM ratio 0.90+/-0.08 at 6 h, p<0.05) while the ABCC1/ABCC2 inhibitor probenecid had no effect (FM ratio at 6 h 0.75+/-0.10, p=0.84). There was a negative correlation between the expression of ABCG2 protein in perfused tissue and the FM ratio of (14)C-PhIP (R=-0.81, p<0.01) at the end of the perfusion. The expression of ABCC2 protein did not correlate with FM ratio of PhIP (R: -0.11, p=0.76). In addition, PhIP induced the expression of ABC transporters in BeWo cells at mRNA level. In conclusion, our data indicates that ABCG2 decreases placental transfer of (14)C-PhIP in perfused human placenta. Also, PhIP may modify ABC transporter expression in choriocarcinoma cells.

  19. Sera of patients with recurrent miscarriages containing anti-trophoblast antibodies (ATAB) reduce hCG and progesterone production in trophoblast cells in vitro.

    Science.gov (United States)

    von Schönfeldt, Viktoria; Rogenhofer, Nina; Ruf, Katharina; Thaler, Christian J; Jeschke, Udo

    2016-09-01

    Reproductive failure including RM has been suggested to correlate with antibodies that cross react with HLA-negative syncytiotrophoblasts and we have reported that 17% of women with 2 or more miscarriages and 34% of women with 3 or more miscarriages express anti-trophoblast antibodies (ATAB). Until now, the mechanism, how ATAB interfere with pregnancy success is not known. HCG and progesterone both play fundamental roles in supporting human pregnancy. Therefore we investigated the effects of sera of RM patients containing ATAB on the hCG and progesterone production of cells of the choriocarcinoma cell line JEG-3. In vitro study to investigate effects of patient sera with and without ATAB on hCG and progesterone secretion of JEG-3 cells. The presence of ATAB was detected as described earlier. Effects of sera from ATAB positive and ATAB negative RM patients on hCG and progesterone secretion by JEG-3 cells were analysed 12 and 24h after plating. Sera of women without pregnancy pathologies served as controls. Sera of ATAB-positive RM patients significantly inhibit hCG secretion of JEG-3 cells for 12h after plating compared to sera of healthy controls (p=0.019) and significantly reduce progesterone production for 12h (p=0.046) and 24h (p=0.027) of co-culture. Sera of ATAB-negative RM patient show no significant effect on progesterone secretion. Inhibition of hCG and progesterone production might point to a mechanism, how ATAB interfere with early pregnancies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. Expression of the vascular endothelial growth factor receptor neuropilin-1 at the human embryo-maternal interface.

    Science.gov (United States)

    Baston-Buest, Dunja M; Porn, Anne C; Schanz, Andrea; Kruessel, Jan-S; Janni, Wolfgang; Hess, Alexandra P

    2011-02-01

    Angiogenesis is required for successful implantation of the invading blastocyst. Vascular endothelial growth factor (VEGF) is an important key player in angiogenesis and vascular remodeling during the implantation process. Besides its well-characterized receptors VEGFR1 and VEGFR2, neuropilin-1 (NRP-1) has been shown to play an additional role in the signaling process of angiogenesis in human endometrium during the menstrual cycle, as a co-receptor of VEGF. These findings led to the hypothesis that NRP-1 might play a role in the vascular remodeling process during embryo implantation and the establishment of a pregnancy. NRP-1 mRNA transcript and protein expression were investigated in human choriocarcinoma cell lines (JEG-3, Jar and BeWo) aiming to evaluate the expression of NRP-1 in vitro, as well as in human decidua of all three trimesters of pregnancy, by western blot analysis (three samples of each trimester of pregnancy). The localization of NRP-1 in human decidua of all three trimesters of pregnancy was analyzed by immunohistochemistry (five samples of each trimester of pregnancy). NRP-1 transcript and protein were expressed in all cell lines examined. Corresponding to the analysis of human tissue by western blot and the localization by immunohistochemistry, NRP-1 protein higher expressed in samples of early pregnancy in comparison to the end of pregnancy. NRP-1 was expressed in the decidua, villi and invading cytotrophoblast of all samples investigated. This is the first study clearly showing the expression of NRP-1 in human decidua and trophoblast, suggesting an important role for the VEGF co-receptor NRP-1 besides the established receptor VEGFR2 at the embryo-maternal interface during embryonic implantation and placentation. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  1. Live cell imaging of in vitro human trophoblast syncytialization.

    Science.gov (United States)

    Wang, Rui; Dang, Yan-Li; Zheng, Ru; Li, Yue; Li, Weiwei; Lu, Xiaoyin; Wang, Li-Juan; Zhu, Cheng; Lin, Hai-Yan; Wang, Hongmei

    2014-06-01

    Human trophoblast syncytialization, a process of cell-cell fusion, is one of the most important yet least understood events during placental development. Investigating the fusion process in a placenta in vivo is very challenging given the complexity of this process. Application of primary cultured cytotrophoblast cells isolated from term placentas and BeWo cells derived from human choriocarcinoma formulates a biphasic strategy to achieve the mechanism of trophoblast cell fusion, as the former can spontaneously fuse to form the multinucleated syncytium and the latter is capable of fusing under the treatment of forskolin (FSK). Live-cell imaging is a powerful tool that is widely used to investigate many physiological or pathological processes in various animal models or humans; however, to our knowledge, the mechanism of trophoblast cell fusion has not been reported using a live- cell imaging manner. In this study, a live-cell imaging system was used to delineate the fusion process of primary term cytotrophoblast cells and BeWo cells. By using live staining with Hoechst 33342 or cytoplasmic dyes or by stably transfecting enhanced green fluorescent protein (EGFP) and DsRed2-Nuc reporter plasmids, we observed finger-like protrusions on the cell membranes of fusion partners before fusion and the exchange of cytoplasmic contents during fusion. In summary, this study provides the first video recording of the process of trophoblast syncytialization. Furthermore, the various live-cell imaging systems used in this study will help to yield molecular insights into the syncytialization process during placental development. © 2014 by the Society for the Study of Reproduction, Inc.

  2. Studies Using an in Vitro Model Show Evidence of Involvement of Epithelial-Mesenchymal Transition of Human Endometrial Epithelial Cells in Human Embryo Implantation*

    Science.gov (United States)

    Uchida, Hiroshi; Maruyama, Tetsuo; Nishikawa-Uchida, Sayaka; Oda, Hideyuki; Miyazaki, Kaoru; Yamasaki, Akiko; Yoshimura, Yasunori

    2012-01-01

    Human embryo implantation is a critical multistep process consisting of embryo apposition/adhesion, followed by penetration and invasion. Through embryo penetration, the endometrial epithelial cell barrier is disrupted and remodeled by an unknown mechanism. We have previously developed an in vitro model for human embryo implantation employing the human choriocarcinoma cell line JAR and the human endometrial adenocarcinoma cell line Ishikawa. Using this model we have shown that stimulation with ovarian steroid hormones (17β-estradiol and progesterone, E2P4) and suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, enhances the attachment and adhesion of JAR spheroids to Ishikawa. In the present study we showed that the attachment and adhesion of JAR spheroids and treatment with E2P4 or SAHA individually induce the epithelial-mesenchymal transition (EMT) in Ishikawa cells. This was evident by up-regulation of N-cadherin and vimentin, a mesenchymal cell marker, and concomitant down-regulation of E-cadherin in Ishikawa cells. Stimulation with E2P4 or SAHA accelerated Ishikawa cell motility, increased JAR spheroid outgrowth, and enhanced the unique redistribution of N-cadherin, which was most prominent in proximity to the adhered spheroids. Moreover, an N-cadherin functional blocking antibody attenuated all events but not JAR spheroid adhesion. These results collectively provide evidence suggesting that E2P4- and implanting embryo-induced EMT of endometrial epithelial cells may play a pivotal role in the subsequent processes of human embryo implantation with functional control of N-cadherin. PMID:22174415

  3. Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I.

    Directory of Open Access Journals (Sweden)

    Marc U Baumann

    Full Text Available Glucose transport to the fetus across the placenta takes place via glucose transporters in the opposing faces of the barrier layer, the microvillous and basal membranes of the syncytiotrophoblast. While basal membrane content of the GLUT1 glucose transporter appears to be the rate-limiting step in transplacental transport, the factors regulating transporter expression and activity are largely unknown. In view of the many studies showing an association between IGF-I and fetal growth, we investigated the effects of IGF-I on placental glucose transport and GLUT1 transporter expression. Treatment of BeWo choriocarcinoma cells with IGF-I increased cellular GLUT1 protein. There was increased basolateral (but not microvillous uptake of glucose and increased transepithelial transport of glucose across the BeWo monolayer. Primary syncytial cells treated with IGF-I also demonstrated an increase in GLUT1 protein. Term placental explants treated with IGF-I showed an increase in syncytial basal membrane GLUT1 but microvillous membrane GLUT1 was not affected. The placental dual perfusion model was used to assess the effects of fetally perfused IGF-I on transplacental glucose transport and syncytial GLUT1 content. In control perfusions there was a decrease in transplacental glucose transport over the course of the perfusion, whereas in tissues perfused with IGF-I through the fetal circulation there was no change. Syncytial basal membranes from IGF-I perfused tissues showed an increase in GLUT1 content. These results demonstrate that IGF-I, whether acting via microvillous or basal membrane receptors, increases the basal membrane content of GLUT1 and up-regulates basal membrane transport of glucose, leading to increased transepithelial glucose transport. These observations provide a partial explanation for the mechanism by which IGF-I controls nutrient supply in the regulation of fetal growth.

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

    International Nuclear Information System (INIS)

    Gorrochategui, Eva; Pérez-Albaladejo, Elisabet; Casas, Josefina; Lacorte, Sílvia; Porte, Cinta

    2014-01-01

    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

  5. Let-7i-Induced Atg4B Suppression Is Essential for Autophagy of Placental Trophoblast in Preeclampsia.

    Science.gov (United States)

    Xu, Yinyan; Huang, Xinyan; Xie, Juan; Chen, Yanni; Fu, Jing; Wang, Li

    2017-09-01

    Autophagy, identified as type II programmed cell death, has already been known to be involved in the pathophysiology of preeclampsia (PE), which is a gestational disease with high morbidity. The present study aims to investigate the functional role of let-7i, a miRNA, in trophoblastic autophagy. Placental tissue used in this study was collected from patients with severe preeclampsia (SPE) or normal pregnant women. A decreased level of let-7i was found in placenta of SPE. In addition, autophagic vacuoles were observed in SPE and the expression of microtubule associated protein 1 light chain 3 (LC3) II/I was elevated. In vitro, let-7i mimics suppressed the autophagic activities in human HTR-8/SVneo trophoblast cell line (HTR-8) and human placental choriocarcinoma cell line JEG-3, whereas let-7i inhibitor enhanced the activities. As a potential target of let-7i, autophagy-related 4B cysteine peptidase (Atg4B) had an increased expression level in SPE. As expected, the increased expression of Atg4B was negatively regulated by let-7i using dual luciferase reporter assay. Furthermore, these trophoblast-like cells transfected with the let-7i mimic or inhibitors resulted in a significant change of Atg4B in both mRNA and protein level. More importantly, Atg4B overexpression could partly reverse let-7i mimic-reduced LC3II/I levels; whereas Atg4B silencing partly attenuated let-7i inhibitor-induced the level of LC3II/I expression. Taken together, these findings suggest that let-7i is able to regulate autophagic activity via regulating Atg4B expression, which might contribute to the pathogenesis of PE. J. Cell. Physiol. 232: 2581-2589, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. 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

  7. 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.

  8. 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.

  9. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    Science.gov (United States)

    2018-05-14

    Acinar Cell Carcinoma; Adenoid Cystic Carcinoma; Adrenal Cortex Carcinoma; Adrenal Gland Pheochromocytoma; Anal Canal Neuroendocrine Carcinoma; Anal Canal Undifferentiated Carcinoma; Appendix Mucinous Adenocarcinoma; Bartholin Gland Transitional Cell Carcinoma; Bladder Adenocarcinoma; Cervical Adenocarcinoma; Cholangiocarcinoma; Chordoma; Colorectal Squamous Cell Carcinoma; Desmoid-Type Fibromatosis; Endometrial Transitional Cell Carcinoma; Endometrioid Adenocarcinoma; Esophageal Neuroendocrine Carcinoma; Esophageal Undifferentiated Carcinoma; Extrahepatic Bile Duct Carcinoma; Fallopian Tube Adenocarcinoma; Fallopian Tube Transitional Cell Carcinoma; Fibromyxoid Tumor; Gastric Neuroendocrine Carcinoma; Gastric Squamous Cell Carcinoma; Gastrointestinal Stromal Tumor; 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 Testicular Sex Cord-Stromal Tumor; Metaplastic Breast Carcinoma; Metastatic Malignant Neoplasm of Unknown Primary Origin; Minimally Invasive Lung Adenocarcinoma; 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; Ovarian Transitional 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

  10. Outcomes of malignant ovarian germ-cell tumors treated in Chiang Mai University Hospital over a nine year period.

    Science.gov (United States)

    Neeyalavira, Vithida; Suprasert, Prapaporn

    2014-01-01

    Malignant ovarian germ cell tumors (MOGCT) are rare neoplasms that most frequently occur in women at a young reproductive age. There have been limited data regarding this disease from Southeast Asian countries. We therefore conducted a retrospective study to analyze the clinical characteristics and the treatment outcomes of MOGCT treated at our institute between January, 2003 and December, 2012. Seventy-six patients were recruited from this period with the mean age of 21.6 years and 11.8% were pre-puberty. The two most common symptoms were pelvic mass and pelvic pain. Two-thirds of the studied patients presented at an early stage. The most common histology was immature teratoma (34.2%) followed by endodermal sinus tumor (28.9%), dysgerminoma (25%), mixed type (10.5%) and choriocarcinoma (1.3%). Over 80% of these patients received fertility sparing surgery and about 70% received adjuvant chemotherapy with the complete response rate at 73.3% and partial response at 11.1%. The most frequent chemotherapy was BEP regimen (bleomycin, etoposide, cisplatin). With the mean follow up time at 56.0 months, 12 patients (15.8%) developed recurrence and only an advanced stage was the independent prognostic factor. The ten year progression free survival (PFS) and overall survival rate of our study were 81.9% and 86.2%, respectively. In conclusion, MOGCT often occurs at a young age. Treatment with fertility sparing operations and adjuvant chemotherapy with a BEP regimen showed a good outcome. An advanced stage is a significant prognostic factor for recurrence.

  11. 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.

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

    International Nuclear Information System (INIS)

    Blazquez, Alba G.; Briz, Oscar; Gonzalez-Sanchez, Ester; Perez, Maria J.; Ghanem, Carolina I.; Marin, Jose J.G.

    2014-01-01

    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

  13. Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion

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    Goldman Shlomit

    2009-11-01

    Full Text Available Abstract Background We have previously shown that Matrix metalloproteinase (MMP -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts. Methods The effect of Forskolin (PKA on MMP-2 expression was assessed by Northern Blot and RT-PCR. Possible transcription factors binding to consensus MMP-2 promoter sequences in response to Forskolin, were detected by EMSA binding assay and their expression assessed by western blot analysis. Antisense transfection of relevant transcription factors was performed and the inhibitory effect assessed on MMP-2 expression (RT-PCR, secretion (zymography and trophoblast invasiveness (transwell migration assay. Results We found that Forskolin increased MMP-2 mRNA in JAR cells within 24 hours, and induced binding to p53, Ets, C/EBP and AP-2. Transcription factors Ets-2, phospho- p53, C/EBP epsilon, C/EBP lambda and AP-2 alpha bound to their respective binding sequences in response to Forskolin and the expressions of these transcription factors were all elevated in Forskolin- treated cells. Inhibition of Ets-2 and p53 reduced MMP-2 expression, secretion and invasiveness of Forskolin treated cells. Conclusion MMP-2 is regulated by PKA through several binding sites and transcription factors including Ets-2, p53, C/EBP, C/EBP lambda and AP-2 alpha. Ets-2 and p53 mediate cAMP- induced trophoblast invasiveness, through regulation of MMP-2.

  14. 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.

  15. Headache and pregnancy: a systematic review.

    Science.gov (United States)

    Negro, A; Delaruelle, Z; Ivanova, T A; Khan, S; Ornello, R; Raffaelli, B; Terrin, A; Reuter, U; Mitsikostas, D D

    2017-10-19

    This systematic review summarizes the existing data on headache and pregnancy with a scope on clinical headache phenotypes, treatment of headaches in pregnancy and effects of headache medications on the child during pregnancy and breastfeeding, headache related complications, and diagnostics of headache in pregnancy. Headache during pregnancy can be both primary and secondary, and in the last case can be a symptom of a life-threatening condition. The most common secondary headaches are stroke, cerebral venous thrombosis, subarachnoid hemorrhage, pituitary tumor, choriocarcinoma, eclampsia, preeclampsia, idiopathic intracranial hypertension, and reversible cerebral vasoconstriction syndrome. Migraine is a risk factor for pregnancy complications, particularly vascular events. Data regarding other primary headache conditions are still scarce. Early diagnostics of the disease manifested by headache is important for mother and fetus life. It is especially important to identify "red flag symptoms" suggesting that headache is a symptom of a serious disease. In order to exclude a secondary headache additional studies can be necessary: electroencephalography, ultrasound of the vessels of the head and neck, brain MRI and MR angiography with contrast ophthalmoscopy and lumbar puncture. During pregnancy and breastfeeding the preferred therapeutic strategy for the treatment of primary headaches should always be a non-pharmacological one. Treatment should not be postponed as an undermanaged headache can lead to stress, sleep deprivation, depression and poor nutritional intake that in turn can have negative consequences for both mother and baby. Therefore, if non-pharmacological interventions seem inadequate, a well-considered choice should be made concerning the use of medication, taking into account all the benefits and possible risks.

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. [Complete hydatiforme mole in Morocco: epidemiological and clinical study].

    Science.gov (United States)

    Boufettal, H; Coullin, P; Mahdaoui, S; Noun, M; Hermas, S; Samouh, N

    2011-09-01

    Complete hydatidiform moles (CHM) are a real public health problem, especially in the "southern countries" and Asia, because of their impact on the female reproduction and the risk to progression to either invasive mole or choriocarcinoma. We collected the cases of CHM referred to our department over a period of ten years (2000 to 2009). We will present our results, emphasize the modalities of diagnosis, treatment and evolution, with a review of literature. During this study, we identified 254 cases of CHM, and recorded 57,987 births and 1627 abortions. Their incidence was 0.43% of pregnancies. The mean age of our patients is 25 years old (16 to 55). Relative risk observed was much increased among women under 20 years old (×6.8) and those over 40 years old (×15). Both of nulliparous and primiparous patients represented 52.3% of the cohort. Eighty-five percent of patients belonged to an agricultural environment associated with a low socio-economic status. Uterine bleeding was the most common symptom accounting for 93.7%. Toxic syndrome was present in 18.5% of patients. Physical examination showed a highly increased uterine size in 85% of cases associated with lateral uterine mass in 25% of cases. The diagnosis was suspected using ultrasonography in all cases associated with an elevated level of plasmatic β-human chorionic gonadotrophin (βhCG). All cases were confirmed histologically. Treatment used was endo-uterine aspiration in all cases. Recurrence of CHM was documented in 25 patients or 9.4%. Neoplasic progression was observed for 6.3% of cases. All of them have evolved into remission with chemotherapy. CHM continue to be a public health problem in Morocco, their incidence is among the highest ones. In fact, this studied population corresponds to the lowest socio-economic status and generally described as population at risk. It is subject to drastic weather's conditions causing loss of fresh products. Extreme ages and degree of parity are also risk factors

  20. 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

  1. In vitro placental model optimization for nanoparticle transport studies

    Directory of Open Access Journals (Sweden)

    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

  2. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis.

    Science.gov (United States)

    Chen, Dong-Bao; Feng, Lin; Hodges, Jennifer K; Lechuga, Thomas J; Zhang, Honghai

    2017-09-01

    Endogenous hydrogen sulfide (H2S), mainly synthesized by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH), has been implicated in regulating placental angiogenesis; however, the underlying mechanisms are unknown. This study was to test a hypothesis that trophoblasts synthesize H2S to promote placental angiogenesis. Human choriocarcinoma-derived BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only. The H2S producing ability of BeWo cells was significantly inhibited by either inhibitors of CBS (carboxymethyl hydroxylamine hemihydrochloride, CHH) or CTH (β-cyano-L-alanine, BCA) and that in HTR-8/SVneo cells was inhibited by CHH only. H2S donors stimulated cell proliferation, migration, and tube formation in ovine placental artery endothelial cells (oFPAECs) as effectively as vascular endothelial growth factor. Co-culture with BeWo and HTR-8/SVneo cells stimulated oFPAEC migration, which was inhibited by CHH or BCA in BeWo but CHH only in HTR-8/SVneo cells. Primary human villous trophoblasts (HVT) were more potent than trophoblast cell lines in stimulating oFPAEC migration that was inhibited by CHH and CHH/BCA combination in accordance with its H2S synthesizing activity linked to CBS and CTH expression patterns. H2S donors activated endothelial nitric oxide synthase (NOS3), v-AKT murine thymoma viral oncogene homolog 1 (AKT1), and extracellular signal-activated kinase 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) in oFPAECs. H2S donor-induced NOS3 activation was blocked by AKT1 but not MAPK3/1 inhibition. In keeping with our previous studies showing a crucial role of AKT1, MAPK3/1, and NOS3/NO in placental angiogenesis, these data show that trophoblast-derived endogenous H2S stimulates placental angiogenesis, involving activation of AKT1, NOS3/NO, and MAPK3/1. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study

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

    Directory of Open Access Journals (Sweden)

    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

  4. Roles of microRNA-34a in the pathogenesis of placenta accreta.

    Science.gov (United States)

    Umemura, Kota; Ishioka, Shin-Ichi; Endo, Toshiaki; Ezaka, Yoshiaki; Takahashi, Madoka; Saito, Tsuyoshi

    2013-01-01

    MicroRNA-34a (miR-34a) is associated with invasion and metastasis of various cancers. The trophoblastic cells of placenta accreta invade into the myometrium in a similar way to the invasion of cancers. We studied the roles of miR-34a in the pathogenesis of placenta accreta. The human choriocarcinoma cell line JAR was used for in vitro experiments as a model of trophoblasts, and placental tissues from the operative specimen of patients with or without placenta accreta were used for experiments in vivo. Morpholino antisense oligomer against miR-34a (miR-34a Morpho/AS) was added to JAR, and the expression of miR-34a and plasminogen activator inhibitor-1 (PAI-1) was determined by real time PCR. The effects of antisense, interleukin (IL)-6 and IL-8 in the process of invasion were studied with an invasion assay. Expression of miR-34a in vivo was studied with the use of fluorescent in situ hybridization (FISH). Expression of miR-34a was inhibited by 65% with the administration of antisense, and a slight increase in miR-34a expression was observed with the addition of IL-6 and IL-8. PAI-1 expression decreased with the addition of IL-6 and IL-8, and increased with the administration of antisense. There was an increase in invasive capacity through the inhibition of miR-34a expression. Strong FISH expression of miR-34a was observed in trophoblast cells of non-placenta accreta, and a clear decrease in miR-34a expression was observed in those of placenta accreta. Expression of miR-34a was downregulated in placenta accreta. In vitro experiments also showed that the invasive potential of JAR increased by suppressing miR-34a, probably through the expression of PAI-1. © 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.

  5. Mercury toxicokinetics of the healthy human term placenta involve amino acid transporters and ABC transporters

    International Nuclear Information System (INIS)

    Straka, Elisabeth; Ellinger, Isabella; Balthasar, Christina; Scheinast, Matthias; Schatz, Jasmin; Szattler, Tamara; Bleichert, Sonja; Saleh, Leila; Knöfler, Martin; Zeisler, Harald; Hengstschläger, Markus; Rosner, Margit; Salzer, Hans; Gundacker, Claudia

    2016-01-01

    Highlights: • It is known that MeHg is able to pass the placenta and to affect fetal brain development. • Uptake and efflux transporters were examined in human primary trophoblast cells and BeWo cells. • Involvement in mercury transfer was assessed by measurement of cellular mercury content upon siRNA mediated gene knockdown. • Localization of transporters was determined by immunofluorescence microscopy. • LAT1 and rBAT at the apical membrane of the syncytiotrophoblast (STB) are involved in MeHg uptake. • MRP1 located at basal membrane of STB mediates mercury efflux. - Abstract: Background: The capacity of the human placenta to handle exogenous stressors is poorly understood. The heavy metal mercury is well-known to pass the placenta and to affect brain development. An active transport across the placenta has been assumed. The underlying mechanisms however are virtually unknown. Objectives: Uptake and efflux transporters (17 candidate proteins) assumed to play a key role in placental mercury transfer were examined for expression, localization and function in human primary trophoblast cells and the trophoblast-derived choriocarcinoma cell line BeWo. Methods: To prove involvement of the transporters, we used small interfering RNA (siRNA) and exposed cells to methylmercury (MeHg). Total mercury contents of cells were analyzed by Cold vapor-atomic fluorescence spectrometry (CV-AFS). Localization of the proteins in human term placenta sections was determined via immunofluorescence microscopy. Results: We found the amino acid transporter subunits L-type amino acid transporter (LAT)1 and rBAT (related to b 0,+ type amino acid transporter) as well as the efflux transporter multidrug resistance associated protein (MRP)1 to be involved in mercury kinetics of trophoblast cells (t-test P < 0.05). Conclusion: The amino acid transporters located at the apical side of the syncytiotrophoblast (STB) manage uptake of MeHg. Mercury conjugated to glutathione (GSH) is

  6. Involvement of the DNA mismatch repair system in cisplatin sensitivity of testicular germ cell tumours.

    Science.gov (United States)

    Rudolph, Christiane; Melau, Cecilie; Nielsen, John E; Vile Jensen, Kristina; Liu, Dekang; Pena-Diaz, Javier; Rajpert-De Meyts, Ewa; Rasmussen, Lene Juel; Jørgensen, Anne

    2017-08-01

    Testicular germ cell tumours (TGCT) are highly sensitive to cisplatin-based chemotherapy, but patients with tumours containing differentiated teratoma components are less responsive to this treatment. The cisplatin sensitivity in TGCT has previously been linked to the embryonic phenotype in the majority of tumours, although the underlying mechanism largely remains to be elucidated. The aim of this study was to investigate the role of the DNA mismatch repair (MMR) system in the cisplatin sensitivity of TGCT. The expression pattern of key MMR proteins, including MSH2, MSH6, MLH1 and PMS2, were investigated during testis development and in the pathogenesis of TGCT, including germ cell neoplasia in situ (GCNIS). The TGCT-derived cell line NTera2 was differentiated using retinoic acid (10 μM, 6 days) after which MMR protein expression and activity, as well as cisplatin sensitivity, were investigated in both undifferentiated and differentiated cells. Finally, the expression of MSH2 was knocked down by siRNA in NTera2 cells after which the effect on cisplatin sensitivity was examined. MMR proteins were expressed in proliferating cells in the testes, while in malignant germ cells MMR protein expression was found to coincide with the expression of the pluripotency factor OCT4, with no or low expression in the more differentiated yolk sac tumours, choriocarcinomas and teratomas. In differentiated NTera2 cells we found a significantly (p cisplatin sensitivity, compared to undifferentiated NTera2 cells. Also, we found that partial knockdown of MSH2 expression in undifferentiated NTera2 cells resulted in a significantly (p cisplatin sensitivity. This study reports, for the first time, expression of the MMR system in fetal gonocytes, from which GCNIS cells are derived. Our findings in primary TGCT specimens and TGCT-derived cells suggest that a reduced sensitivity to cisplatin in differentiated TGCT components could result from a reduced expression of MMR proteins, in

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

    International Nuclear Information System (INIS)

    Zeng Zhizhen; O'Brien, Julie A.; Lemaire, Wei; O'Malley, Stacey S.; Miller, Patricia J.; Zhao Zhijian; Wallace, Michael A.; Raab, Conrad; Lindsley, Craig W.; Sur, Cyrille; Williams, David L.

    2008-01-01

    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 [ 35 S](S)-2-amino-4-chloro-N-(1-(4-phenyl-1-(propylsulfonyl)piperidin-4-yl) ethyl)benzamide ([ 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 [ 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 d =1.9 nM), selective, GlyT1 inhibitor that, when radiolabeled with [ 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 [ 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 positron emission

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

    Science.gov (United States)

    Meng, Yao; Liu, Shuangfeng; Li, Juan; Meng, Yanfa; Zhao, Xiaojun

    2012-01-01

    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 (mPEG)(2)-Lys-NHS (20 kDa). 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 (PEG)ylated 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 virus-1. Furthermore, both PEGylated proteins showed about 60%-70% antitumor and antivirus activities, and at the same time decreased 50%-70% immunogenicity when compared with their unmodified counterparts. α-MMC and MAP30 obtained from this novel purification strategy can meet the requirement of a large amount of samples for research. Their chemical modification can solve the problem of strong immunogenicity and meanwhile preserve moderate activities. All these findings suggest the potential application of PEGylated α-MMC and PEGylated MAP30 as antitumor and antivirus agents. According to these results, PEGylated RIPs can be constructed with

  9. Formas moleculares da gonadotrofina coriônica humana: características, ensaios e uso clínico Molecular forms of human chorionic gonadotropin: characteristics, assays and clinical use

    Directory of Open Access Journals (Sweden)

    Sebastião Freitas de Medeiros

    2006-04-01

    aplicação mais universal destes marcadores hormonais.The human chorionic gonadotropin (hCG results from a non-covalent linkage of two subunits, alpha (alphahCG and beta (betahCG, separately synthesized by normal trophoblastic tissue, hydatiform mole, choriocarcinoma, pituitary cells, and tumoral tissues of different histologic types. The peptide chain and its further glycosylation in the secretory cell involves the complex action of different enzymes. This complexity results in the secretion of heterogeneous molecular forms. The different molecules might be found in serum, urine and amniotic fluid of pregnant women; serum, urine, and vesicles of patients with hydatiform mole or choriocarcinoma and in other biological fluids of normal non-pregnant women and men or patients with different embryonary types of cancer. Both the intact hCG molecule and its free subunits and the hyperglycosylated (H-hCG, nicked (N-hCG and core fragment of betahCG (CF- betahCG variant forms have relevant clinical use. Depending on the prevalent molecular form or the proportion of the variant form to the intact hCG in a determined clinical situation the measurement of a specific molecule is chosen. This review analyzes the clinical use of hCG and its related molecules in the early detection of ectopic pregnancy or patients with higher risk of abortion, in the identification of an embryo or fetus with chromosomal abnormalities, and in the evaluation of risk for preeclampsia or fetal growth restriction. The review also examines the use of hCG and variant forms as tumor markers. It is concluded that it is useful to measure hCG and/or related molecules in clinical practice, but difficulties in developing and achievement of more sensitive and specific new assays limit their use.

  10. 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