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Sample records for choriocarcinoma

  1. Choriocarcinoma presenting with thyrotoxicosis

    OpenAIRE

    Sotello, David; Rivas, Ana Marcella; Test, Victor J.; Lado-Abeal, Joaquin

    2016-01-01

    We describe a 26-year-old man with metastatic choriocarcinoma who presented with hyperthyroidism associated with elevated β-human chorionic gonadotropin (B-HCG) and respiratory failure secondary to diffuse lung metastasis. After the first cycle of chemotherapy, the concentration of B-HCG dramatically decreased and the patient became euthyroid, allowing us to discontinue antithyroid medications. The patient's hyperthyroidism was caused by stimulation of the thyroid gland by high B-HCG levels, ...

  2. Choriocarcinoma presenting with thyrotoxicosis.

    Science.gov (United States)

    Sotello, David; Rivas, Ana Marcella; Test, Victor J; Lado-Abeal, Joaquin

    2016-01-01

    We describe a 26-year-old man with metastatic choriocarcinoma who presented with hyperthyroidism associated with elevated β-human chorionic gonadotropin (B-HCG) and respiratory failure secondary to diffuse lung metastasis. After the first cycle of chemotherapy, the concentration of B-HCG dramatically decreased and the patient became euthyroid, allowing us to discontinue antithyroid medications. The patient's hyperthyroidism was caused by stimulation of the thyroid gland by high B-HCG levels, as shown by the marked improvement of the patient's thyroid function panel after chemotherapy. PMID:26722165

  3. Epigenetic Therapy in Human Choriocarcinoma

    International Nuclear Information System (INIS)

    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

  4. [Choriocarcinoma causing a pulmonary embolus.

    DEFF Research Database (Denmark)

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

    2008-01-01

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

  5. Primary Nongestational Choriocarcinoma of the Ovary

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    AMM Shariful Alam; Syeda Nurjahan Bhuiyan; Md Rashid Un Nabi

    2014-01-01

    Pure primary ovarian choriocarcinoma is an extremely rare and aggressive tumor. It can be of gestational or nongestational in origin. The gestational type can arise from an ovarian pregnancy or can be of metastatic origin from uterine choriocarcinoma. The nongestational type is a very rare germ cell neoplasm. It is important to distinguish between two types of choriocarcinomas as nongestational origin is highly malignant and has worse prognosis than gestational type. But it is very difficult ...

  6. Primary Nongestational Choriocarcinoma of the Ovary

    Directory of Open Access Journals (Sweden)

    AMM Shariful Alam

    2014-01-01

    Full Text Available Pure primary ovarian choriocarcinoma is an extremely rare and aggressive tumor. It can be of gestational or nongestational in origin. The gestational type can arise from an ovarian pregnancy or can be of metastatic origin from uterine choriocarcinoma. The nongestational type is a very rare germ cell neoplasm. It is important to distinguish between two types of choriocarcinomas as nongestational origin is highly malignant and has worse prognosis than gestational type. But it is very difficult to differentiate by routine histological examination. Nongestational choriocarcinoma has been found to be resistant to single agent chemotherapy. It occurs usually around 13 years of age and is mainly confined to females under 20. Here we report a case of primary pure nongestational choriocarcinoma of the ovary in an unmarried girl of 14 years, diagnosed in 2001 and treated successfully with surgery and combination chemotherapy and remained disease-free till last reporting in September 2013.

  7. Mediastinal Choriocarcinoma Masquerading as Relapsed Hodgkin Lymphoma

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    Lam, Selay; Rizkalla, Kamilia; Hsia, Cyrus C.

    2011-01-01

    Primary mediastinal choriocarcinoma is a rare extragonadal germ cell malignancy. We describe the first case of a patient who developed mediastinal choriocarcinoma after treatment for Hodgkin lymphoma (HL). A 25-year-old man with classic HL, nodular sclerosis subtype, underwent treatment with splenectomy followed by radiation therapy. Unfortunately, his disease relapsed with a paraspinal mass, and he was subsequently treated with MOPP (mechlorethamine, Oncovin, procarbazine, and prednisone) al...

  8. Metastatic choriocarcinoma in an infant: imaging appearance

    International Nuclear Information System (INIS)

    Metastatic choriocarcinoma is unusual in infancy and considered to be due to metastases from the placenta. Only fifteen cases have been previously reported. We present an unusual case of hepatic, pulmonary, and axillary lymph node metastases from choriocarcinoma in a 3-month-old female. Several of the lesions had large vascular channels identified by computed tomography and sonography with color and duplex Doppler. (orig.)

  9. Metastatic choriocarcinoma in the small bowel: a case report

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    Zohreh Yousefi

    2014-08-01

    Conclusion: In abnormal postpartum hemorrhage, we should consider the possibility of choriocarcinoma. Although, it is important to note rare manifestations of metastatic choriocarcinoma of small bowel in massive gastrointestinal hemorrhage.

  10. Occult choriocarcinoma: Detection using radiolabeled monoclonal antibodies

    International Nuclear Information System (INIS)

    Occult choriocarcinoma, manifested only by an elevated B-hCG level, can be a difficult management problem. The authors evaluated the ability of I-131-labeled 5F9.3, a murine monoclonal antibody reactive with choriocarcinomas but not hCG, to detect foci of choriocarcinoma in five patients referred with elevated B-hCG levels but in whom the location of residual disease was uncertain. I-131 5F9.3, 0.5-1.0 mCi, was injected intravenously in each patient and images with dynamic background subtraction of TcHSA were obtained at later time points. In four patients chest studies were true positive (confirmed surgically in all), the chest CT scans in these patients had been interpreted as not definitely showing active disease. In the fifth patient no abnormal focus of uptake was seen and subsequent B-hCG levels normalized. In two of the patients with chest lesions, foci of abdominal uptake were seen that were not due to tumor. One of these patients had a partial small bowel obstruction; the other appeared to have a false-positive study. I-131 5F9.3 is a promising agent for the detection of occult choriocarcinomas

  11. 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.)

  12. Abnormal Presentation of Choriocarcinoma and Literature Review

    Science.gov (United States)

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

    2016-01-01

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

  13. FBI-1 and choriocarcinoma cell proliferation

    OpenAIRE

    Cheung, Man-keung; 張文強

    2013-01-01

    Gestational trophoblastic disease (GTD) includes a spectrum of diseases that involve abnormal growth of trophoblastic cells inside the uterus. It can range from benign hydatidiform moles (HM) to frankly malignant choriocarcinoma, placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumour (ETT).GTD are considered curable if the patient is correctly diagnosed and receive appropriate treatment during the early stage of the disease. About 15% -30% of hydatidiform moles will...

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

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    Nikolić Branka

    2012-01-01

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

  15. Pure choriocarcinoma of ovary diagnosed by fine needle aspiration cytology

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    Naniwadekar M

    2009-07-01

    Full Text Available Pure ovarian choriocarcinoma is extremely rare and can develop as a germ cell tumor or as a metastasis from uterine or tubal gestational choriocarcinoma or rarely from an ovarian pregnancy. The cytomorphologic findings have been reported previously in different sites. However, this is the first case of pure ovarian choriocarcinoma diagnosed on cytology to the best of our knowledge. The distinction between a gestational and nongestational choriocarcinoma is difficult. A 19-year-old female patient presented with an irregular per-vaginal bleeding and a mass in lower abdomen. Fine needle aspiration cytology smears of the mass were hypocellular and showed large, multinucleated giant cells and malignant mononucleated cells. Background was hemorrhagic. Serum β hCG level was 3,80,000 mIU/ml. A diagnosis of choriocarcinoma was offered which was later confirmed by histopathology. The diagnosis of choriocarcinoma on fine needle aspiration cytology is based on the presence of large, multinucleated giant cells and malignant mononucleated cells. A high index of suspicion should be maintained and estimation of serum β hCG plays a key role in supporting the diagnosis.

  16. Radioimmunodetection of human choriocarcinoma xenograft in nude mouse

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

  17. CT evaluation of choriocarcinoma with brain metastases

    International Nuclear Information System (INIS)

    It is well established that the computed tomography(CT) is an essential part not only in screening primary brain tumors, but also in staging known malignancy. This paper reports various CT findings demonstrated in 12 cases of choriocarcinoma with brain metastasis. The CT findings such as the number, location and density of the metastatic lesions, the degree of brain edema, mass effect and effect of contrast enhancement are reviewed as well as the episode of stroke syndrome and survival duration after neurologic symptom attacks. The results were as follows: 1. The of these cases showed solitary metastatic lesion and remaining 2 cases were multiple lesions. 2. One was isodense density and the others were hemorrhagic increased density by CT. 3. All of these showed mass effect to the surrounding structures along with moderate to marked brain edema. 4. The position of the metastatic lesion were located at the supratentorially in all cases. Most of them were at the unilateral frontal or parietal area or both of them. One which noted multiple metastatic foci showed at the bilateral occipital regions. 5. Nine cases showed ring enhancement after contrast infusion. One which noted isodense density on the noninfusion scan showed also ring enhancement after contrast infusion. 6. Nine cases showed positive stroke syndrome. One of them was performed emergency craniotomy. The remaining 3 cases noted progressive neurologic symptoms. 7. Two cases were noted only brain metastasis but the others also had various degree of pulmonary metastasis and 2 of latter had hepatic metastasis, too. 8. Most of the cases were treated with CHAMOCA regimen, and one of them was taken whole brain irradiation (3000 rads/2 weeks). Another on case revealed marked regression of not only metastatic brain lesion but the pulmonary lesion after the 8th course of CHAMOCA regimen and still alive for over 460 days

  18. CT evaluation of choriocarcinoma with brain metastases

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    Yoon, Sei Chul; Kim, Choon Yul; Kwon, Hyung Chul; Bahk, Young Whee; Kim, Seung Jo [Catholic Medical College, Seoul (Korea, Republic of)

    1984-03-15

    It is well established that the computed tomography(CT) is an essential part not only in screening primary brain tumors, but also in staging known malignancy. This paper reports various CT findings demonstrated in 12 cases of choriocarcinoma with brain metastasis. The CT findings such as the number, location and density of the metastatic lesions, the degree of brain edema, mass effect and effect of contrast enhancement are reviewed as well as the episode of stroke syndrome and survival duration after neurologic symptom attacks. The results were as follows: 1. The of these cases showed solitary metastatic lesion and remaining 2 cases were multiple lesions. 2. One was isodense density and the others were hemorrhagic increased density by CT. 3. All of these showed mass effect to the surrounding structures along with moderate to marked brain edema. 4. The position of the metastatic lesion were located at the supratentorially in all cases. Most of them were at the unilateral frontal or parietal area or both of them. One which noted multiple metastatic foci showed at the bilateral occipital regions. 5. Nine cases showed ring enhancement after contrast infusion. One which noted isodense density on the noninfusion scan showed also ring enhancement after contrast infusion. 6. Nine cases showed positive stroke syndrome. One of them was performed emergency craniotomy. The remaining 3 cases noted progressive neurologic symptoms. 7. Two cases were noted only brain metastasis but the others also had various degree of pulmonary metastasis and 2 of latter had hepatic metastasis, too. 8. Most of the cases were treated with CHAMOCA regimen, and one of them was taken whole brain irradiation (3000 rads/2 weeks). Another on case revealed marked regression of not only metastatic brain lesion but the pulmonary lesion after the 8th course of CHAMOCA regimen and still alive for over 460 days.

  19. The uterine choriocarcinoma in postmenopausal women: specificities of diagnosis and treatment

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    Kaabia, Ons; Meddeb, Sawsen; Rhim, Mohamed Salah; Bibi, Mohamed; Khairi, Hedi

    2014-01-01

    Choriocarcinoma is a gestational trophoblastic tumor that mainly affects women of childbearing age. Cases of choriocarcinoma in postmenopausal women are exceptional. Through an observation and literature review, we propose to study the specific diagnosis and treatment features of this tumor in menopausal women. We report the observation of a pure uterine choriocarcinoma, which occurred in post-menopause. The diagnosis was made on the analysis of surgical specimens confirmed by measurement of ...

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

    Institute of Scientific and Technical Information of China (English)

    沈华浩; 张根生; 徐峰

    2004-01-01

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

  1. Unusual gestational choriocarcinoma arising in an interstitial pregnancy

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    Sawsen Meddeb; Mohamed Salah Rhim; Wissal Zarrouk; Mohamed Bibi; Mohamed Tahar Yacoubi; Hedi Khairi

    2014-01-01

    INTRODUCTION: Choriocarcinoma is a highly malignant trophoblastic neoplasm. Its association with ectopic pregnancy is very rare and usually with aggressive behavior. PRESENTATION OF CASE: We report a new case arising in an interstitial pregnancy occurring in a 46-year-old woman. The patient was admitted for severe pelvic pain and abundant metrorrhagia. One month ago, she had had a laparoscopic resection of an interstitial pregnancy subsequent to failure of chemotherapy by methotrexate. The...

  2. Atypical presentation of uterine choriocarcinoma a case report with review of literature

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    Rajshree Dayanand Katke

    2015-01-01

    Full Text Available Gestational trophoblastic diseases include complete and partial molar pregnancy, invasive mole, placental site trophoblastic tumor, and choriocarcinoma. Gestational choriocarcinoma is one of the most malignant form of a group of tumors. Although choriocarcinoma has a very high propensity to metastasize to various sites including brain it also has a very high cure rate. Our study represents the case of choriocarcinoma developed after primary invasive mole which was treated successfully with combined surgical and medical management. We now present a course of gestational trophoblastic disease transforming from benign to a malignant condition in due course of management. We are presenting a case of a 26-year-old female who came to us with molar pregnancy which turned out be invasive mole on histopathological examination and converted into choriocarcinoma in due course of treatment even after methotrexate chemotherapy.

  3. A pure non-gestational ovarian choriocarcinoma with delayed solitary brain metastases: Case report and review of the literature.

    Science.gov (United States)

    Rao, K V L Narasinga; Konar, Subhas; Gangadharan, Jagathlal; Vikas, V; Sampath, S

    2015-01-01

    Choriocarcinoma is the most malignant tumour of gestational trophoblastic origin. Most ovarian choriocarcinomas are gestational in origin and usually metastasize to the ovary from uterine or tubal choriocarcinoma. Non gestational choriocarcinoma (NGOC) of the ovary is exceedingly rare and usually seen along with other germ cell tumors. Non gestational choriocarcinoma has been found to be resistant to single-agent chemotherapy and has a worse prognosis than gestational choriocarcinoma. We are reporting long term follow up of published rare case of pure non gestational ovarian choriocarcinoma (NGOC) with concurrent metastases to the spleen and adrenal glands, who developed a delayed solitary brain metastases, two years after completion of primary treatment. Surgery along with triple agent chemotherapy and radiotherapy was found to give good remission in this aggressive disease. PMID:26752905

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

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    GUNDUZ, SEYDA; Elpek, Gulsum Ozlem; Uysal, Mukremin; Goksu, Sema Sezgin; Tatli, Murat; Arslan, Deniz; Coskun, Hasan Senol; BOZCUK, Hakan; Savas, Burhan; Ozdogan, Mustafa

    2012-01-01

    Gastric choriocarcinoma is a rare neoplasm and usually accompanies gastric adenocarcinoma. The prognosis is poor due to the aggressive course of the disease. A 57-year-old female patient with weight loss and abdominal pain was examined. The patient was operated following the examination, and pathological analysis revealed the presence of a gastric adenocarcinoma associated with choriocarcinoma. Immunohistochemical analysis showed a positive reaction with antibodies to beta-human chorionic gon...

  5. [Chemotherapy-sensitive uterine choriocarcinoma: a case report].

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    Dimitrakova, E; Pekhlivanov, B; Milchev, N

    2009-01-01

    We report a case of uterine choriocarcinoma in a 42-year-old female presenting with abdominal pain, uterus enlargement, high serum levels of beta human chorionic gonadotropin (b-hCG) and a positive pregnancy test on two separate occasions. At laparatomy, blood and clots were observed in the abdomen, an enlarged uterus with tumor infiltrates in the uterus, appendix, bladder and plica vesico-uterina. Follwing hysterectomy and bilateral oophoorectomy, the patient received chemotherapy and was followed for two years. No tumor recurrences were observed and the b-hCG levels returned to normal. In conclusion, the condition responds favorably the chemotherapy and recurrences are rate when there are no metastases to the liver or the brain. PMID:20198788

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

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    Ushashree Das

    2013-06-01

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

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

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    Guber Ivo

    2011-12-01

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

  8. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  10. 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.

  11. Ectopic pregnancy with associated gestational choriocarcinoma in a California sea lion (Zalophus californianus).

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    Fravel, Vanessa A; Lowenstine, Linda J; Koehne, Amanda

    2016-07-01

    A wild-born, captive-reared, 14 yr old, primiparous female California sea lion Zalophus californianus presented for anorexia of 14 d duration and abdominal distention. Routine complete blood cell count revealed leukocytosis with a neutrophilia, and serum chemistry revealed hypoalbumenemia and hyponatremia. Treatment with broad spectrum antibiotics and non-steroidal anti-inflammatories were started, but the animal continued to decline. Abdominal radiographs revealed a mature mineralized fetal skull and spine in the caudal abdomen and abdominal ultrasound revealed ascites but could not confirm the fetus. The patient was taken to surgery where a full term fetus was found outside of the uterus but within the fetal membranes, representing a secondary ectopic pregnancy. The patient passed away during surgery and was taken to necropsy. Gross necropsy revealed a diffuse peritonitis with yellow deposits over the serosal surfaces of the abdominal organs. The uterus appeared intact grossly and the ovaries appeared abnormal. The mesenteric, renal, and sub-lumbar nodes were enlarged and edematous. Histopathology revealed choriocarcinoma in the right uterine horn with evidence of chronic uterine rupture and protrusion of the placental tissue into the abdomen. The choriocarcinoma had metastasized locally as well as to the liver, spleen and lung. Choriocarcinoma is a highly malignant trophoblastic neoplasm that is rare in domestic animals. This case represents, to the authors' knowledge, the first report of gestational choriocarcinoma causing secondary ectopic pregnancy in a California sea lion and presents questions regarding pregnancy monitoring and management in a population of captive, minimally trained California sea lions.

  12. 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...

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  14. Choriocarcinoma with negative urinary and serum beta human chorionic gonadotropin (β HCG : A case report

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    Mehra Reeti

    2005-12-01

    Full Text Available This was a rare case where a patient presented clinically as a case of post abortal sepsis and ultrasound showing the picture of an intramural degenerating fibroid. Her serum and urine both were negative for b human chorionic gonadotropin (bHCG. Patient succumbed to choriocarcinoma 1 month later. Failure to detect urinary and serum bHCG lead to maternal mortality due to the choriocarcinoma. The failure to detect, certain degradation products of HCG which may predominate in gestational trophoblastic neoplasia, by many common HCG testing kits lead to the error of diagnosis. Only 3 of the 7 common commercial serum HCG tests appropriately detects nicked HCG and its free bHCG, DPC immulite assay, being the most sensitive method. Though of rare occurrence, this awareness is important for diagnosis and follow-up of gestational trophoblastic neoplasia and could have been life saving in our case.

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Maria Fernanda Moreira Ferraz

    2003-06-01

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

  17. 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...

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

    Science.gov (United States)

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

    2015-03-01

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

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

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    Naushad A. B. Ahamed

    2015-01-01

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

  20. Effective component from verbena officinalis L. inhibits proliferation and induces apoptosis of human choriocarcinoma JAR cells

    Institute of Scientific and Technical Information of China (English)

    Xu Shan; Chen Qi; Xu Chang-fen

    2005-01-01

    Objective: To examine the action of the effective component, 4'-methylether -scutellarein, from Verbena officinalis L. (VOL) on the proliferation and apoptosis of human choriocarcinoma JAR cells.Methods: Cell proliferation was measured by MTT [3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrasodium bromide, MTT] assay and the incorporation of tritiated thymidine (3H-TdR). Apoptosis of cell was evaluated by flow cytometry (FCM) and the characteristic apoptotic DNA ladder by agarose gel electrophoresis, and the morphological changes of apoptotic JAR cells were observed under fluorescence microscopy and electron microscopy (EM). Expressions of apoptosis proteins, poly (ADP-ribose) polymerase (PARP) and caspase-3, -8, and -9 were determined with Western blot.Results: The effective component from VOL inhibited the proliferation of JAR cells in a dose- and time-dependent manner. The treated cell cycle was arrested in S phase and an apoptotic peak was found in S phase using FCM analysis. A typical DNA ladder appeared in the treatment group when analyzed by agarose gel electrophoresis. Using fluorescence microscopy, the percentage of apoptotic cell was 0.9%, 6%, and 14% after treatments of 10, 20, and 40 mg·L-1 of the effective component, respectively, for 48 h. Typical apoptotic changes, such as condensed chromatin and presence of apoptotic bodies, were observed under EM. Treatment with effective component for 48 h and 72 h also induced protein expression of PARP and caspase-3, -8, and -9 as seen by Western blot.Conclusions: The effective component from VOL inhibits cell proliferation and induces apoptosis in human choriocarcinoma JAR cells.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Clinicopathological analysis of non-gestational ovarian choriocarcinoma: Report of two cases and review of the literature

    OpenAIRE

    Wang, Qiong; Guo, Chao; ZOU, LINGFENG; Wang, Yun; Song, Xin; Ma, Yaqi; Liu, Aijun

    2016-01-01

    The aim of the present study was to analyze the clinicopathological features of two cases of non-gestational ovarian choriocarcinoma (NGCO). The histopathological, immunohistochemical and clinical features of two cases of NGCO in the left ovaries of two 13 year-old female patients were investigated and the relevant literature was reviewed. In both cases, the tumor masses exhibited cribriform, papillary and nested cellular growth patterns, and hemorrhage and necrosis were evident. In case one,...

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

    Directory of Open Access Journals (Sweden)

    Pollyana Alves Silva

    2010-02-01

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

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

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    Koji Komori

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Wan Yu Luk

    2013-01-01

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

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

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    Suchitra R

    2015-10-01

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

  8. 妊娠绒毛膜癌肺转移的诊治进展%Progress of the Diagnosis and Treatment of Pulmonary Metastasis of Gestational Choriocarcinoma

    Institute of Scientific and Technical Information of China (English)

    马冬捷

    2011-01-01

    Gestational choriocarcinoma is the most common gestational trophoblastic neoplasia. It is prone to hematogenous metastasis, most commonly to the lungs. With the advent and development of chemotherapy, choriocarcinoma has become a curable tumor. However, patients with drug-resistant and recurrent choriocarcinoma are difficult to treat, even with the management of pulmonary metastasis. Resorting to surgery is also a tough decision given the challenges of identify-ing the appropriate surgical indication and timing. This review discusses the basic principles of management as well as recent advances in the diagnosis and treatment of patients with pulmonary metastasis of gestational choriocarcinoma.%妊娠绒毛膜癌(简称绒癌)是最常见的妊娠滋养细胞肿瘤,极易发生血行转移,常出现肺转移.自一系列有效化疗药物用于绒癌治疗之后,绒癌已成为可治愈的恶性肿瘤之一,但耐药及复发仍是治疗失败的主要原因,特别是肺转移灶的处理.如何掌握手术指征和时机成为治疗难点.本文就绒癌肺转移的诊断、化疗、手术指征及时机、手术方式等治疗进展进行综述.

  9. Apigenin Reduces Survival of Choriocarcinoma Cells by Inducing Apoptosis via the PI3K/AKT and ERK1/2 MAPK Pathways.

    Science.gov (United States)

    Lim, Whasun; Park, Sunwoo; Bazer, Fuller W; Song, Gwonhwa

    2016-12-01

    Apigenin is a flavonoid found in parsley, onions, oranges, tea, chamomile, wheat, and sprouts. It has a variety of biological properties including anti-oxidant, anti-mutagenic, anti-carcinogenic, anti-inflammatory, anti-proliferative, and anti-spasmodic effects. Based on epidemiological and case-control studies, apigenin is regarded as a novel chemotherapeutic agent against various cancer types. However, little is known about the effects of apigenin on choriocarcinoma cells. Therefore, we investigated the anti-cancer effects of apigenin on choriocarcinoma cells (JAR and JEG3) in the present study. Apigenin reduced viability and migratory properties, increased apoptosis, and suppressed mitochondrial membrane potential in both the JAR and JEG3 cells. In addition, apigenin predominantly decreased phosphorylation of AKT, P70RSK, and S6 whereas the phosphorylation of ERK1/2 and P90RSK was increased by apigenin treatment of JAR and JEG3 cells in a dose-dependent manner. Moreover, treatment of JAR and JEG3 cells with both apigenin and pharmacological inhibitors of PI3K/AKT (LY294002) and ERK1/2 (U0126) revealed synergistic anti-proliferative effects. Collectively, these results indicated that the apigenin is an invaluable chemopreventive agent that inhibits progression and metastasis of choriocarcinoma cells through regulation of PI3K/AKT and ERK1/2 MAPK signal transduction mechanism. J. Cell. Physiol. 231: 2690-2699, 2016. © 2016 Wiley Periodicals, Inc. PMID:26970256

  10. 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-PA-inhibitor...... for the removal of u-PA after its complex formation with a specific inhibitor. The data suggest a novel mechanism by which receptor-mediated endocytosis is initiated by the binding of a secondary ligand. Full text...

  11. 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.

  12. 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.

  13. Clinical Study and Literature Review of Intracranial Metastases of Choriocarcinoma%鞘内注射甲氨蝶呤治疗绒毛膜细胞癌脑转移9例疗效分析

    Institute of Scientific and Technical Information of China (English)

    邱家玲; 武立菊; 陈小祥

    2014-01-01

    Objective To explore the curative efficacy of intrathecal methotrexate chemotherapy for patients with in -tracranial metastases of choriocarcinoma .Methods Retrospectively reviewed 9 brain metastases choriocarcinoma patients who re-ceived intrathecal methotrexate combined with multiagent systemic chemotherapy in our hospital .Results Remission rate was 88.9 % and 5-year survival rate of these cases was 44.4%,side effects were tolerable .Conclusion Intrathecal methotrexate chemotherapy is effective and safety for patients with intracranial metastases of choriocarcinoma .%目的:探讨鞘内注射甲氨喋呤治疗绒毛膜细胞癌脑转移的疗效。方法回顾性分析9例经鞘内注射甲氨喋呤联合静脉化学治疗绒毛膜细胞癌脑转移的疗效和副作用。结果鞘内注射甲氨喋呤治疗绒毛膜细胞癌脑转移客观缓解率为88.9%,5年生存率为44.4%,不良反应轻。结论鞘内注射甲氨喋呤治疗绒毛膜细胞癌颅内转移安全、有效。

  14. FBI-1 Is Overexpressed in Gestational Trophoblastic Disease and Promotes Tumor Growth and Cell Aggressiveness of Choriocarcinoma via PI3K/Akt Signaling.

    Science.gov (United States)

    Mak, Victor C Y; Wong, Oscar G W; Siu, Michelle K Y; Wong, Esther S Y; Ng, Wai-Yan; Wong, Richard W C; Chan, Ka-Kui; Ngan, Hextan Y S; Cheung, Annie N Y

    2015-07-01

    Human placental trophoblasts can be considered pseudomalignant, with tightly controlled proliferation, apoptosis, and invasiveness. Gestational trophoblastic disease (GTD) represents a family of heterogeneous trophoblastic lesions with aberrant apoptotic and proliferative activities and dysregulation of cell signaling pathways. We characterize the oncogenic effects of factor that binds to the inducer of short transcripts of HIV-1 [FBI-1, alias POZ and Krüppel erythroid myeloid ontogenic factor (POKEMON)/ZBTB7A] in GTD and its role in promoting cell aggressiveness in vitro and tumor growth in vivo. IHC studies showed increased nuclear expression of FBI-1, including hydatidiform moles, choriocarcinoma (CCA), and placental site trophoblastic tumor, in GTD. In JAR and JEG-3 CCA cells, ectopic FBI-1 expression opposed apoptosis through repression of proapoptotic genes (eg, BAK1, FAS, and CASP8). FBI-1 overexpression also promoted Akt activation, as indicated by Akt-pS473 phosphorylation. FBI-1 overexpression promoted mobility and invasiveness of JEG-3 and JAR, but not in the presence of the phosphoinositide 3-kinase inhibitor LY294002. These findings suggest that FBI-1 could promote cell migration and invasion via phosphoinositide 3-kinase/Akt signaling. In vivo, nude mice injected with CCA cells with stable FBI-1 knockdown demonstrated reduced tumor growth compared with that in control groups. These findings suggest that FBI-1 is clinically associated with the progression of, and may be a therapeutic target in, GTD, owing to its diverse oncogenic effects on dysregulated trophoblasts. PMID:26093985

  15. A Case Report of Gastric Primary Choriocarcinoma with Multiple Organs Metastasis and Relaled Literature Review%胃原发性绒毛膜癌伴多脏器转移一例报告并文献复习

    Institute of Scientific and Technical Information of China (English)

    底建敏; 王健; 杨艳瑞; 徐杰

    2016-01-01

    Objective To provide reference for clinical treatment by detecting the growth characteristics of thegastric pri-mary choriocarcinoma with multiple organs metastasis. Methods A case diagnosed as gastric primary choriocarcinoma was retro-spective analyzed and related literatures were reviewed. Results The patient wad admitted for irregular vaginal bleeding for 6+months. Urine pregnancy test was positive (+) at a local hospital, pelvic color doppler ultrasound examination indicated no gesta-tional sac. In our hospital the checkedck blood humen chorionic gonadotropin (β-hCG) increased obviously, after the test, the chest, abdomen, pelvic CT examinations, and liver biopsy and immunohistochemical, gastroscope biopsy and diagnostic curettage (endometrium of menstrual period) were performed and the patient was diagnosed withgastric primary choriocarcinoma. The patient lived nearly eight months after chemotherapy and biological treatment and died of multi-organs failure. Conclusion Gastric primary choriocarcinoma is rare, with high malignant degree and fast tumor progress, and early distant metastases. It has poor prognosis.%目的 探讨胃原发性绒毛膜癌(绒癌)伴多脏器转移患者肿瘤的生长特点,为临床治疗提供参考.方法 对胃原发性绒癌1例的临床资料进行回顾性分析并复习相关文献.结果 本例因阴道不规则出血6+个月入院.在当地医院查尿妊娠试验(+),行盆腔彩色多普勒超声(彩超)检查提示未见妊娠囊.后在我院查血绒毛膜促性腺激素(β-hCG)明显升高,结合胸部、腹部、盆腔CT检查及肝穿刺活检、免疫组织化学、胃镜活检及诊断性刮宫(月经期子宫内膜),明确诊断为胃原发性绒癌,予化疗及生物治疗,存活近8个月出现多脏器功能衰竭,家属放弃治疗后死亡.结论 胃原发性绒癌临床较为少见,恶性程度高,肿瘤进展迅速,早期多已出现远处转移,监测血清β-hCG水平可评价治疗效果,但预后一般较差.

  16. Postoperative ectopic pregnancy with choriocarcinoma of brain metastases(a report of 1 case and review of literature)%异位妊娠术后绒癌脑转移1例并文献复习

    Institute of Scientific and Technical Information of China (English)

    刘东媛; 曾小君; 孙彦辉; 汪向红; 刘妮英; 范妮娜; 王丹; 张红波; 陈小奇; 穆林森; 张锦

    2014-01-01

    Objective To report one case of postoperative ectopic pregnancy with choriocarcinoma of brain metastases and rexiew the literature .Methods Combined with gynecological ,neurological,pathology and imaging examination the results clearly confirmed choriocarcinoma .By undergone emergency ectopic pregnancy laparoscopic surgery to remove the lesion Oviduct and Gestational sac ,the postoperative pathology showed normal embryos .The follow up from 6 to 12 months showed a case was diagnosed brain metastases by craniotomy and pathological reports showed as choriocarcinoma .Lumbar puncture methotrexate chemotherapy , dehydration , hormones and other symptomatic treatment were underwent .Results The patients ’ symptoms improved and no recurrent lesions were followed up for 6 months.Conclusions The postoperative ectopic pregnancy with choriocarcinoma of brain metastases occurrs in childbearing women age with atypical clinical manifestations and high misdiagnosis . Chemotherapy combined therapy may improve symptoms in postoperative .%目的:报告1例异位妊娠术后绒癌脑转移瘤的病例并回顾文献。方法通过妇科及神经系统检查,病理及影像学结果确诊绒癌。急诊行腹腔镜下异位妊娠手术,切除孕囊及病变侧输卵管,术后病理示正常胚胎。术后随访6~12个月1例发生脑转移,予以开颅手术,病理报告绒癌。术后腰穿甲氨蝶呤化疗、脱水、激素等对症治疗。结果患者术后症状改善,随访6个月未见病变复发。结论异位妊娠术后发生绒癌脑转移瘤可见于育龄妇女,临床表现不典型,误诊率高。术后化疗为主的综合治疗可改善患者症状。

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

    Science.gov (United States)

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

    2008-03-01

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

  18. Effect of hepatitis B virus infection on trophoblast cell line (HTR-8/SVneo) and choriocarcinoma cell line (JEG3) is linked to CD133-2 (AC141) expression.

    Science.gov (United States)

    Cui, Hong; Chen, Jing; Na, Quan

    2016-01-01

    Mother-to-infant transmission of hepatitis B virus (HBV) plays an important role in the chronic carrier state in China. In our studies, the response of trophoblast cell and choriocarcinoma cell to HBV infection regarding the expression of CD133-2 (AC141) was evaluated. Western blot and RT-PCR showed that a high level of CD133-2 protein and mRNA in HTR-8/SVneo cells, but a low level in JEG-3 cells. Lower proliferation and mobility, and higher apoptosis were observed in HTR-8/SVneo cells and JEG-3-CD133-2(+) cells after HBV infection than those in HTR-8-CD133-2(-) cells and JEG-3 cells. Our main finding is that CD133-negative cells (HTR-8-CD133-2(-) and JEG-3) are prone to HBV infection. In the last, our data indicated that the activation of Smad signaling pathway and the induction of epithelial-mesenchymal transition (EMT) in CD133-negative cells after HBV infection. In summary, our study demonstrated that CD133 is a key factor that mediated HBV infection to trophoblast cell and choriocarcinoma cell. PMID:27508045

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

    Directory of Open Access Journals (Sweden)

    Teresa de Jesus Jhayya

    1999-12-01

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

  20. 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)

    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

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

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  2. Choriocarcinoma syndrome を来した性腺外胚細胞腫瘍に対してModified BEP レジメンによる導入化学療法が奏効した1例

    OpenAIRE

    大島, 純平; 植村, 元秀; 加藤, 大悟; 永原, 啓; 木内, 寛; 辻村, 晃; 野々村, 祝夫

    2014-01-01

    We present a case study of a 46-year-old man with extra gonadal germ cell tumor with multiple lung metastases and very high levels (324, 100 mIU/ml) of the tumor marker human chorionic gonadotropin (hCG). He underwent chemotherapy with VP-16, ifosfamide and cisplatinum regimen, but on day 2, he noticed strong dyspnea. A chest X-ray showed bilateral infiltration of the lungs, and he was diagnosed with acute respiratory distress syndrome (ARDS) from choriocarcinoma syndrome. After ARDS improved...

  3. 功能蛋白O-GlcNAc糖基化修饰调控绒毛膜癌细胞的转移%O-GlcNAcylation of Functional Protein Regulates Human Choriocarcinoma Cells Migration

    Institute of Scientific and Technical Information of China (English)

    屈茹楠; 琚娜娜; 吴明军; 赵德璋; 王应雄; 杨竹; 于超

    2013-01-01

    为研究氧连接N-乙酰葡萄糖胺(O-linked N-acetylglucosamine,O-GlcNAc)糖基化修饰调控人绒毛膜癌细胞(JAR)迁移的分子机制,首先采用siRNA和酶特异性抑制剂作用细胞,构建O-GlcNAc修饰总蛋白低表达和高表达的细胞模型;利用Transwell方法及黏附实验比较细胞迁移及与血管内皮细胞黏附能力的变化;并通过免疫共沉淀技术检测重要的功能蛋白β-catenin的O-GlcNAc程度,从而分析蛋白转录翻译后调控对肿瘤细胞迁移影响的分子机制.结果表明,增加JAR细胞中O-GIcNAc修饰水平可促进细胞迁移及与血管内皮细胞的黏附活性,且O-GlcNAc修饰作用的靶蛋白β-catenin的糖基化水平也显著增加.当下调细胞中O-GlcNAc蛋白修饰水平,其迁移及黏附能力随之下降.表明O-GlcNAc修饰参与了绒毛膜癌细胞转移的调控.%To investigate the molecular mechanisms involved in human choriocarcinoma cells (JAR)migration regulated by O-GlcNAc glycosylation,cell models expressing different O-GlcNAcylation levels were established by siRNA interference or OGA inhibitor.Transwell assay and adhesion assay were used to examine JAR cell migration ability and adhesion to EA.hy926 cells.Meanwhile,the O-GlcNAcylation level of β-catenin was detected by immunoprecipitation.The results indicated O-GlcNAcylation enhances the JAR cell migration and adhesion to endothelial cells in vitro.Moreover,the O-GlcNAcylation of β-catenin but not the protenin level increased apparently.The migration and adhesion ability were obviously declined in JAR cells with O-GlcNAcylation down-regulation.These findings suggest that O-GlcNAcylation is involved in the regulation of tumor cell migration.

  4. 男性胃原发性绒毛膜癌一例并文献复习%Primary gastric choriocarcinoma in male patients:A case report and literature review

    Institute of Scientific and Technical Information of China (English)

    骆莉莉; 王欣; 张颖; 常滋毓; 杨丽丽

    2014-01-01

    Objective:To investigate the pathogenetic factors,differential diagnosis and treatment regimen for the primary gastric choriocarcinoma in male patients.Methods:Immunohistochemical technique was used to detect the clinical picture and pathological properties in one case of primary gastric chorio-carcinoma,and related literatures were reviewed.Results:Microscopically,the tumor presented with its partial cells analogou to cytotrophoblasts and syncy-tiotrophoblasts,and other cells were low-differentiated adenocarcinoma.Immunohistochemistry findings revealed positive expression of CK and CK7 for the tumor cells,HCG for the syncytiotrophoblasts,and EMA and CEA for the adenocarcinoma.Treatments were associated with surgery and chemotherapy,yet the patient died 6 months later due to lung metastasis and mutiple organs failure .Conclusion:Primary gastric choriocarcionma is a rare case in males with highest malignancy,which makes difficult treatment and poor prognosis,though its therapy regimen currently relies on integrated options.%目的:探讨男性胃原发性绒毛膜癌的发病因素,诊断、鉴别诊断及治疗方案。方法:对1例男性胃原发性绒毛膜癌病例进行临床表现、病理学特点、免疫组化检测,并进行相关文献复习。结果:镜下显示部分瘤细胞似细胞滋养层细胞和合体滋养层细胞;部分瘤细胞为低分化腺癌细胞。免疫组化示肿瘤细胞CK、CK7表达阳性;合体滋养细胞HCG表达阳性;腺癌细胞EMA、CEA表达阳性。采用手术加化疗的综合治疗,6个月后患者因肺转移,多脏器功能衰竭死亡。结论:发生于男性胃原发性绒毛膜癌极其罕见,恶性程度高,治疗难度大,以综合治疗为主,预后差。

  5. Unusual gestational choriocarcinoma arising in an interstitial pregnancy

    Directory of Open Access Journals (Sweden)

    Sawsen Meddeb

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ghazizadeh S

    2000-09-01

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

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

    Science.gov (United States)

    Bagshawe, K. D.

    1978-01-01

    The way the management of patients with trophoblastic tumours has depended on the acquisition of new knowledge and new drugs is demonstrated. Emphasis is put on the ability to detect early disease by biochemical markers and on the ability to define on a multifactorial basis the resistance potential of the tumours. This provides a basis for stratification of treatment and the use of prophylactic chemotherapy to prevent cerebral metastases in certain patients. Although chemotherapy is often intensive and prolonged, there has so far been little evidence of long-term effects and many women have had normal pregnancies subsequently, but the limitations of present data are discussed. The difficulties of matching available resources to society's needs in the cancer field make it necessary to consider whether such treatment is unjustifiably expensive. It is shown that for these tumours early diagnosis not only proves effective in therapeutic terms but provides substantial financial savings. It is suggested that screening programmes for cancer cannot be accepted or rejected on principle. In judging them on their individual merits it is appropriate to anticipate interaction between earlier diagnosis and more effective drug treatment. PMID:626471

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

    Science.gov (United States)

    Bagshawe, K D

    1978-01-01

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

  9. 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...

  10. Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Ren, S.G.; Braunstein, G.D. (Univ. of California School of Medicine, Los Angeles (USA))

    1991-03-01

    Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells. This study was performed to examine whether insulin also regulates the production of hCG by this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96, and 53 mg/L, respectively. Time-course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media. Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the presence of insulin and (35S)methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable (35S)methionine-hCG secreted into the medium than the control cultures (P less than 0.05). During this time period, human placental lactogen release and total trichloroacetice acid-precipitable (35S)methionine protein were not increased. The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation. Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells.

  11. Insulin stimulates synthesis and release of human chorionic gonadotropin by choriocarcinoma cell lines

    International Nuclear Information System (INIS)

    Recent studies have shown that insulin regulates placental lactogen, progesterone, and estrogen production from human trophoblast cells. This study was performed to examine whether insulin also regulates the production of hCG by this type of cell. After 24-36 h of preincubation, JEG-3 and JAR cells (2-3 x 10(5) cells/ml.well) or human term trophoblast cells (1 x 10(6) cells/ml.well) were exposed to the test hormone in serum-free Dulbecco's Modified Eagle's Medium for 24-96 h. Secretion of hCG from JEG-3 cells was stimulated by human insulin, human proinsulin, or porcine insulin in a dose-dependent manner, with lowest effective doses of 6.7, 96, and 53 mg/L, respectively. Time-course studies showed that hCG secretion peaked at 72-96 h with insulin exposure; in contrast, no decernable peak was seen without insulin in serum-free media. Exposure of JEG-3 cells for 24 h to 209 mg/liter insulin stimulated hCG synthesis, with 40 +/- 3% more immunoreactive intracellular hCG (P less than 0.05). Cells grown in the presence of insulin and [35S]methionine had 47 +/- 21% more labeled intracellular hCG and 56 +/- 13% more immunoprecipitable [35S]methionine-hCG secreted into the medium than the control cultures (P less than 0.05). During this time period, human placental lactogen release and total trichloroacetice acid-precipitable [35S]methionine protein were not increased. The insulin-induced stimulation of hCG synthesis was inhibited by cycloheximide. Additionally, insulin did not significantly affect total intracellular protein during 24-96 h of incubation. Insulin also increased hCG release from JAR cells, but not from human term trophoblast cells. A mouse monoclonal antibody to the IGF-I receptor inhibited the stimulation of insulin in JEG-3 cells

  12. Calcium-dependent trichosanthin-induced generation of reactive oxygen species involved in apoptosis of human choriocarcinoma cells

    Science.gov (United States)

    Zhang, Chunyang; Ma, Hui; Chen, Die Yan

    2001-04-01

    The type-I ribosome-inactivating protein trichosanthin (TCS) has a broad spectrum of biological and pharmacological activities, including abortifacient, anti-tumor and anti-HIV. We found for the first time that TCS induced production of reactive oxygen species (ROS) in JAR cells by using fluorescent probe 2',7'-dichlorofluorescin diacetate with confocal laser scanning microscopy. TCS-induced ROS showed dependence on the increase in intracellular calcium and on the presence of extracellular calcium. The production of ROS increased rapidly after the application of TCS, which paralleled TCS-indued increase in intracellular calcium monitored using fluo 3-AM, suggesting that TCS-induced ROS might mediate by the increase in intracellular Ca2PLU concentration. Simultaneous observation of the nuclear morphological changes and production of ROS in JAR cells with two-photon laser scanning microscopy and confocal laser scanning microscopy revealed that ROS involved in the apoptosis of JAR cells, which was confirmed by that antioxidant (alpha) -tocopherol prevented TCS-induced ROS formation and cell death. The finding that calcium-dependent TCS-induced ROS involved in the apoptosis of JAR cells might provide new insight into the anti-tumor and anti-HIV mechanism of TCS.

  13. Impact of Axis of GHRH and GHRH Receptor on Cell Viability and Apoptosis of the Placental Choriocarcinoma Cell Line.

    Science.gov (United States)

    Liu, A-X; Zhang, D; Zhu, Y-M; Gao, H-J; Jiang, J-Y; Hu, X-L; Lv, P-P; Leung, P C K; Huang, H-F

    2016-01-01

    Although GHRH and GHRH-R are recognized as key factors in placental development, little is known about the mechanism(s) of the regulation in trophoblastic cells during placental development. The objective of this study is to determine the potential relationship between the expression levels of GHRH-R and the placental and JEG-3 cell function. Furthermore, we aim to investigate the downstream pathways of GHRH/GHRH-R axis in the control of the JEG-3 cell viability and apoptosis. In this study, we detected the expression pattern of GHRH-R in human chorionic villous tissues and JEG-3 cell. Then, we evaluated the effects of GHRH/GHRH-R and the downstream pathways by using GHRH antagonist (JMR-132) on JEG-3 cell. Our present study found the expressions of GHRH-R in placental villous tissues and JEG-3 cell, and the expression levels of GHRH-R was significantly lower in villous tissues of early pregnancy loss when compared to normal controls. JMR-132 inhibited cellular viability and induced apoptosis in JEG-3 cell in a time and dosedependent manners through activation of caspase-3, p38, and p53, as well as inhibition of phosphorylation of Akt. Interestingly, ER stress markers such as GRP78, ubiquitinated proteins and phospho-eIF2α were significantly increased in JEG-3 cell after being treated with JMR-132. Conversely, pretreated with salubrinal (a selective inhibition of protein phosphatase 1-mediated eIF2α dephosphorylation), JEG-3 cells were rescued from JMR-132-mediated cell growth inhibition, and abolished JMR-132-induced cleaved caspase-3, CHOP, phospho-p53, and ubiquitinated proteins accumulation. Knockdown of endogenous GHRH-R significantly abolished the JMR-132-induced cleaved caspase-3 and activation of p38. In conclusion, our results, for the first time, demonstrated the expression levels of GHRH-R were closely related to the placental function. Inhibition of GHRH-R by using GHRH antagonist in JEG-3 cell may reduce cell viability and induce apoptosis through inactivation of Akt and ER stress via phosphorylation of eIF2α. These observations have enriched our understanding on the function of GHRH/GHRH-R axis and the downstream pathways in the control of the placental development. The Most Important Aspect of the Paper: Our present study for the first time provided evidences that GHRH and GHRH-R loops involve in JEG-3 cell viability and apoptosis through Akt and eIF2α pathways. PMID:26917260

  14. Combination Chemotherapy in Treating Young Patients With Recurrent or Resistant Malignant Germ Cell Tumors

    Science.gov (United States)

    2016-04-12

    Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Ovarian Germ Cell Tumor; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular Embryonal Carcinoma and Yolk Sac Tumor; Testicular Yolk Sac Tumor

  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. Standard-Dose Combination Chemotherapy or High-Dose Combination Chemotherapy and Stem Cell Transplant in Treating Patients With Relapsed or Refractory Germ Cell Tumors

    Science.gov (United States)

    2016-07-26

    Germ Cell Tumor; Teratoma; Choriocarcinoma; Germinoma; Mixed Germ Cell Tumor; Yolk Sac Tumor; Childhood Teratoma; Malignant Germ Cell Neoplasm; Extragonadal Seminoma; Non-seminomatous Germ Cell Tumor; Seminoma

  17. 马鞭草提取液C部位对人绒毛膜癌JAR细胞增殖的影响%Inhibitory Effects of the Part C in Alcohol Extract of Verbena Officinalis on Human Choriocarcinoma JAR Cell Line

    Institute of Scientific and Technical Information of China (English)

    张立平; 罗莉; 王家俊; 徐昌芬

    2004-01-01

    目的:探讨马鞭草(Verbena officinalis)提取液C部位对人绒毛膜癌JAR细胞增殖的影响.方法:通过相差显微镜观察活细胞贴壁程度、细胞形态改变;MTT法测定不同浓度C部位在不同时段对JAR细胞的增殖抑制率,结果用方差分析进行统计学检验:流式细胞仪检测细胞阻滞周期.结果:马鞭草C部位可引起细胞数目减少并萎缩;细胞增殖抑制率随着时间的延长和浓度的增加逐渐增大,72 h的40 mg/ml剂量组抑制最明显,抑制率为65%;流式细胞仪检测结果显示阻滞周期在G2/M期之间.结论:马鞭草提取液C部位对人绒毛膜癌JAR细胞增殖有明显抑制作用,其作用机制有待进一步探索.

  18. 马鞭草诱导人绒毛膜癌JAR细胞凋亡作用观察%OBSERVATION ON THE INHIBITION EFFECT OF VERBENA OFFICINALIS ON HUMA CHORIOCARCINOMA JAR CELLS

    Institute of Scientific and Technical Information of China (English)

    张立平; 徐昌芬

    2009-01-01

    [目的]探讨马鞭草C部位对人绒癌JAR细胞抑制作用机理. [方法]通过相差显微镜观察活细胞贴壁程度、细胞形态改变;荧光显微镜观察细胞形态学变化;透射电镜观察细胞超微结构变化;琼脂糖凝胶电泳观察用药后细胞DNA断裂情况;流式细胞仪检测细胞凋亡情况. [结果]马鞭草C部位可引起细胞数目减少并萎缩;荧光显微镜下观察到典型凋亡细胞的形态学特征;电镜下见到明显的凋亡小体;琼脂糖凝胶电泳出现"阶梯状条带";流式细胞仪检测发现用药后出现明显的凋亡峰. [结论]马鞭草C部位对人绒癌JAR细胞抑制作用机理是诱导其凋亡.

  19. Tamoxifen Modulates the Expression of Complement Inhibitory Proteins on Chorio-carcinoma Cell Line JAR%它莫西芬对绒毛膜癌细胞株JAR补体调节蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    辛云碧; 陈松华; 归绥琪; 葛锡锐

    2003-01-01

    为探索抗肿瘤药物Tamoxifen对绒毛膜癌细胞株JAR表面补体调节蛋白表达的影响,实验以绒毛膜癌细胞株JAR为研究对象,用流式细胞术和RT-PCR分别检测Tamoxifen作用前后JAR细胞补体调节蛋白在蛋白质和mRNA水平的表达.结果显示:在10-6M Tamoxifen作用3 d后,JAR细胞补体调节蛋白DAF和CD59的蛋白质表达水平明显降低,而MCP无明显改变;在10-6M Tamoxifen作用24 h后,JAR细胞DAF和CD59 mRNA表达水平分别降低88%和60%.提示Tamoxifen可能通过降低DAF和CD59的表达,提高肿瘤细胞对宿主补体攻击的敏感性.

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

    Science.gov (United States)

    2016-04-07

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

  1. An unusual case of pulmonary embolism.

    Science.gov (United States)

    Khakural, Prabhat; Shrestha, Kajan R; Sapkota, Ranjan; Shrestha, Uttam K

    2015-01-01

    Pulmonary embolism carries a significant morbidity and mortality. Metastatic choriocarcinoma presenting as pulmonary embolism is a rare event. Here, we report a case of a 25-year-lady with a history of worsening shortness of breath for 4 months who was treated as a case of pneumonia and tuberculosis. Owing to the worsening condition, she had a contrast enhanced computed tomography (CECT) chest done and was diagnosed to have pulmonary embolism. She underwent pulmonary embolectomy. The histopathological examination of the embolus revealed it to be metastatic choriocarcinoma. She showed a good response to chemotherapy. Metastatic choriocarcinoma should be considered as a differential diagnosis in females presenting with pulmonary embolism. PMID:25687445

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

    Institute of Scientific and Technical Information of China (English)

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

    2007-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nikolić Branka

    2015-01-01

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

  4. The Studies on the Part C of Verbena Officinalis-induced Human Choriocarcinoma JAR Cells Apoptosis and Its Molecular Mechanism in vitro%马鞭草C部位诱导人绒毛膜癌JAR细胞凋亡分子机制研究

    Institute of Scientific and Technical Information of China (English)

    张立平; 夏邦亮; 罗莉; 徐昌芬

    2005-01-01

    目的:探讨马鞭草C部位诱导人绒毛膜癌JAR细胞凋亡的分子机制.方法:流式细胞仪检测细胞周期;Western-blot及RT-PCR检测Fas/Fasl蛋白及基因的表达.结果:药物作用后细胞被不同程度阻滞于G2/M期,并伴有G0/G1期比例下降;Fasl蛋白表达降低,Fas在C部位作用前后均无表达;Fasl mRNA转录呈下降趋势.结论:马鞭草C部位将人绒毛膜癌JAR细胞阻滞在G2/M期,并诱导其凋亡,其作用机制可能与Fasl的表达下调有关.

  5. Blockage in G2/M Phase and Induction Apoptosis on Human Choriocarcinoma JAR Cells by Verbena Officinalis C%马鞭草C部位使人绒癌JAR细胞阻滞于G2/M期并诱导细胞凋亡

    Institute of Scientific and Technical Information of China (English)

    王家俊; 罗莉; 张立平; 徐昌芬

    2004-01-01

    目的:观察马鞭草C部位(Verbena officinalis C)对人绒癌JAR细胞周期分布和凋亡的影响,探讨其诱导凋亡机制.方法:采用MTT比色法测定马鞭草C部位对JAR细胞增殖的影响;流式细胞仪检测其对JAR细胞周期分布和细胞凋亡的影响:RT-PCR检测药物作用前后Bax和Bcl-2 mRNA表达变化.结果:马鞭草C部位抑制绒癌JAR细胞增殖,并呈明显时间和剂量效应关系.流式细胞仪结果显示,与对照组比较,40g/L马鞭草C部位处理48 h后,使JAR细胞G2/M期增加154.3%,S期比例降低41.6%;JAR细胞凋亡率增加6.74倍.不同剂量马鞭草C部位处理JAR细胞48 h后,Bax表达水平增加,Bcl-2表达水平下降,并呈剂量依赖性.结论:马鞭草C部位阻滞绒癌JAR细胞于G2/M期,通过改变Bax和Bcl-2表达,诱导JAR细胞凋亡.

  6. An Analysis of Methotrexate Combined with Etopside and Cisplatin in the Treatment for 20 Cases with Chemorefractory Choriocarcinoma%甲氨蝶呤联合足叶乙甙、顺铂治疗绒毛膜癌耐药病例20例分析

    Institute of Scientific and Technical Information of China (English)

    吴谋喜; 石向红

    2007-01-01

    回顾性分析足叶乙甙、甲氨蝶呤、顺铂(EMP)方案治疗20例绒毛膜癌耐药病例的临床疗效及毒副反应.20例经平均6.5个疗程化疗,12例完全缓解(60%),5例部分缓解(25%),3例无效(15%),有效率85%(x2=15.06,P<0.01).完全缓解后复发率为8.3%.

  7. 5-杂氮脱氧胞苷对JEG-3细胞及印迹基因H19效应的初步研究%The expression of imprinted gene H19 and the demethylation effect of 5-aza-2'deoxycytidine in a choriocarcinoma cell line

    Institute of Scientific and Technical Information of China (English)

    卢林杉; 李力; 俞丽丽; 易萍; 李平; 陈星云; 刘苹; 周元国

    2008-01-01

    目的:研究甲基化酶抑制剂5-杂氮脱氧胞苷(5-aza-2'-deoxycytidine,ADC)对人绒毛膜上皮癌细胞株JEG-3细胞的生物学作用,观察JEG-3细胞H19表达变化与滋养细胞增殖、分化和侵袭等行为的相关性,从表观遗传学角度探讨滋养细胞侵袭行为的调控.方法:应用MTY法检测不同浓度5-杂氮脱氧胞苷在不同时相下对JEG-3细胞增殖的影响.体外小室迁移实验观察5-杂氮脱氧胞苷对JEG-3细胞迁移的影响.荧光定量RTPCR检测5-杂氮脱氧胞苷作用下JEG-3细胞H19 mRNA表达的变化.结果:5-杂氮脱氧胞苷对JEG-3细胞增殖起抑制作用,在一定范围内与时间和剂量呈正相关.经100μmol/L 5-杂氮脱氧胞苷作用24h后的JEG-3细胞迁移能力明显受限,迁移细胞数较对照组差异显著(P<0.01).经5-杂氮脱氧胞苷作用后JEG-3细胞中H19 mRNA表达增高,在一定范围内与时间和剂量呈正相关.结论:甲基化酶抑制剂5-杂氮脱氧胞苷可致H19 mR-NA过量表达,并进一步抑制滋养细胞的增殖和迁移能力.H19印迹基因表达上调与滋养细胞增殖抑制和迁移能力降低有关.

  8. 双光子及共聚焦激光扫描显微术研究天花粉蛋白对人绒癌细胞的作用机制%Studying the Effect of Trichosanthin on Choriocarcinoma Cells with both Two-photon and Confocal Laser Scanning Microscopy*

    Institute of Scientific and Technical Information of China (English)

    张春阳; 贡宜萱; 马辉; 安成才; 陈瓞延

    2001-01-01

    天花粉蛋白(trichosanthin,TCS)是从中草药栝楼根中提取的一种核糖体失活蛋白,具有抗肿瘤和抗HIV功能.应用双光子及共聚焦激光扫描显微术结合特异性荧光探针Hoechst 33342、2',7'-二氯荧光黄双乙酸酯(DCFH-DA)、Indo-1和Fluo 3-AM,首次同时观察了TCS诱导人绒癌细胞(JAR细胞)凋亡过程中活性氧自由基(ROS)和细胞内钙离子浓度([Ca2+]i)的变化,实验结果表明TCS引起的[Ca2+]i升高和ROS形成参与了TCS诱导的JAR细胞凋亡,并且ROS形成和[Ca2+]i升高有关.共聚焦激光扫描显微术的研究结果表明,[Ca2+]i升高不是导致ROS形成的主要原因,TCS诱导产生的ROS可能是通过TCS与JAR细胞膜表面受体作用介导的.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-01-01

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

  10. Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

    Science.gov (United States)

    2013-03-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Myelodysplastic Syndromes; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Disseminated Neuroblastoma; Malignant Neoplasm; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Mixed Germ Cell Tumor; Ovarian Monodermal and Highly Specialized Teratoma; Ovarian Polyembryoma; Ovarian Yolk Sac Tumor; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Seminoma; Testicular Choriocarcinoma and Teratoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular

  11. Primary Gastric Chorioadenocarcinoma.

    Science.gov (United States)

    Baraka, Bahaaeldin A; Al Kharusi, Suad S; Al Bahrani, Bassim J; Bhathagar, Gunmala

    2016-09-01

    Primary gastric chorioadenocarcinoma (PGC) is a rare and rapidly invasive tumor. Choriocarcinoma is usually known to be of endometrial origin and gestational; however, it has been reported in other extragenital organs, such as the gall bladder, prostate, lung, liver, and the gastrointestinal tract. Human chorionic gonadotropin related neoplasms of the stomach are seldom discussed in the literature. We report a case of PGC in a 56-year-old man treated with a standard non-gestational choriocarcinoma chemotherapy regimen, EMA/CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), with a complete response and good tolerability. PMID:27602194

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    aromatase activity. Furthermore, exposure of the H295R cells to isoflavonoids caused a decrease in testosterone production, and various mixtures of PEs significantly stimulated MCF-7 human breast adenocarcinoma cell growth and induced aromatase activity in JEG-3 choriocarcinoma cells. The estrogenic effect...

  13. Cytogenetics of a malignant ovarian germ-cell tumor

    NARCIS (Netherlands)

    van Echten, J; van Doorn, LC; van der Linden, HC; van der Veen, AY; de Jong, B

    1998-01-01

    Cytogenetic investigation of a malignant ovarian tumor diagnosed as a mixed germ-cell tumor, composed of extensive choriocarcinoma and foci of yolk-sac tumor, revealed a highly abnormal chromosomal pattern. We found a chromosome number in the hypertriploid/hypotetraploid range, and several clonal st

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

    Directory of Open Access Journals (Sweden)

    Mounika Reddy

    2015-07-01

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

  15. MR imaging of gestational trophoblastic tumors

    Energy Technology Data Exchange (ETDEWEB)

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

    1994-09-15

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

  16. Internalization of Trichosanthin via Different Endocytic Mechanisms

    Institute of Scientific and Technical Information of China (English)

    ZHANG Fan; SUI Senfang

    2005-01-01

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

  17. Nuclear factor I acts as a transcription factor on the MMTV promoter but competes with steroid hormone receptors for DNA binding.

    OpenAIRE

    Brüggemeier, U; Rogge, L.; Winnacker, E L; Beato, M

    1990-01-01

    Several steroid hormones induce transcription of the mouse mammary tumor virus (MMTV) promoter, through an interaction of their respective receptors with the hormone responsive elements (HREs) in the long terminal repeat (LTR) region. The molecular mechanism underlying transcriptional activation is not known, but binding of nuclear factor I (NFI) to a site adjacent to the HRE appears to be required for efficient transcription of the MMTV promoter. In JEG-3 choriocarcinoma cells the MMTV promo...

  18. MEA療法が奏功した難治性非セミノーマ精巣腫瘍の1例

    OpenAIRE

    永井, 康晴; 南, 高文; 伊丹, 祥隆; 小林, 泰之; 清水, 信貴; 山本, 豊; 林, 泰司; 野澤, 昌弘; 吉村, 一宏; 石井, 徳味; 植村, 天受

    2013-01-01

    We experienced a case of testicular cancer that was successfully treated by salvage chemotherapy comprised of methotrexate, actinomycin D and etoposide (MEA). A 25-year-old man was admitted to our hospital with a diagnosis of stage III B2 (JUA classification) testicular cancer. The patient had multiple lung metastases, and underwent a left orchiectomy. A histopathological examination revealed a choriocarcinoma, embryonal carcinoma, mature teratoma, and a yolk sac tumor. Tumor marker levels we...

  19. 妊娠滋养细胞疾病基础研究进展

    Institute of Scientific and Technical Information of China (English)

    冯苗; 王自能

    2003-01-01

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

  20. Malignant ovarian tumours in childhood in Britain, 1962-78.

    OpenAIRE

    La Vecchia, C; Morris, H. B.; Draper, G J

    1983-01-01

    The files of the Childhood Cancer Research Group and of the Oxford Survey of Childhood Cancers were scrutinized for all the ovarian neoplasms registered in England, Scotland and Wales in children under age 15 years throughout the period 1962-78. Among 172 cases confirmed as malignant ovarian tumours, 145 (84%) were tumours of germ cell origin (54 dysgerminomas, 36 malignant teratomas, 26 endodermal sinus tumours, 4 embryonal carcinomas, 2 pure choriocarcinomas, 20 mixed germ cell neoplasms, 3...

  1. Mapping of domains in human laminin using monoclonal antibodies: localization of the neurite-promoting site

    OpenAIRE

    1986-01-01

    Monoclonal antibodies were made against a truncated form of human laminin isolated from placenta. 12 antibodies were isolated and characterized. All antibodies stained basement membranes in placenta and immunoprecipitated laminin from media of cultured choriocarcinoma cells. Three antibodies, 3E5, 4C7, and 4E10, partially blocked the neurite-promoting activity of laminin. Addition of a second antibody, goat anti-mouse IgG, caused more complete blocking of the activity. Two of the blocking ant...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-12-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1992-02-01

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

  4. The biological function of hyperglycosylated hCG

    Institute of Scientific and Technical Information of China (English)

    Laurence A Cole; Stephen A Butler

    2012-01-01

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

  5. In vitro placental model optimization for nanoparticle transport studies

    DEFF Research Database (Denmark)

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

    2012-01-01

    ’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...

  6. In vitro placental model optimization for nanoparticle transport studies

    DEFF Research Database (Denmark)

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

    2012-01-01

    '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...

  7. Invasive mole presenting as pain abdomen

    Directory of Open Access Journals (Sweden)

    Swati Singh

    2013-06-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

  9. Surgery and Combination Chemotherapy in Treating Children With Extracranial Germ Cell Tumors

    Science.gov (United States)

    2016-05-06

    Childhood Embryonal Tumor; Childhood Extracranial Germ Cell Tumor; Childhood Extragonadal Germ Cell Tumor; Childhood Malignant Ovarian Germ Cell Tumor; Childhood Malignant Testicular Germ Cell Tumor; Childhood Teratoma; Ovarian Embryonal Carcinoma; Ovarian Yolk Sac Tumor; Stage II Malignant Testicular Germ Cell Tumor; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Ovarian Germ Cell Tumor; Stage III Malignant Testicular Germ Cell Tumor; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Germ Cell Tumor; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma

  10. 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.

  11. Imaging features of thoracic metastases from gynecologic neoplasms.

    Science.gov (United States)

    Martínez-Jiménez, Santiago; Rosado-de-Christenson, Melissa L; Walker, Christopher M; Kunin, Jeffery R; Betancourt, Sonia L; Shoup, Brenda L; Pettavel, Paul P

    2014-10-01

    Gynecologic malignancies are a heterogeneous group of common neoplasms and represent the fourth most common malignancy in women. Thoracic metastases exhibit various imaging patterns and are usually associated with locally invasive primary neoplasms with intra-abdominal spread. However, thoracic involvement may also occur many months to years after initial diagnosis or as an isolated finding in patients without evidence of intra-abdominal neoplastic involvement. Thoracic metastases from endometrial carcinoma typically manifest as pulmonary nodules and lymphadenopathy. Thoracic metastases from ovarian cancer often manifest with small pleural effusions and subtle pleural nodules. Thoracic metastases to the lungs, lymph nodes, and pleura may also exhibit calcification and mimic granulomatous disease. Metastases from fallopian tube carcinomas exhibit imaging features identical to those of ovarian cancers. Most cervical cancers are of squamous histology, and while solid pulmonary metastases are more common, cavitary metastases occur with some frequency. Metastatic choriocarcinoma to the lung characteristically manifests with solid pulmonary nodules. Some pulmonary metastases from gynecologic malignancies exhibit characteristic features such as cavitation (in squamous cell cervical cancer) and the "halo" sign (in hemorrhagic metastatic choriocarcinoma) at computed tomography (CT). However, metastases from common gynecologic malignancies may be subtle and indolent and may mimic benign conditions such as intrapulmonary lymph nodes and remote granulomatous disease. Therefore, radiologists should consider the presence of locoregional disease as well as elevated tumor marker levels when interpreting imaging studies because subtle imaging findings may represent metastatic disease. Positron emission tomography/CT may be helpful in identifying early locoregional and distant tumor spread. PMID:25310428

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

    Institute of Scientific and Technical Information of China (English)

    王玉霞; 曹阳; 孙永玉

    2002-01-01

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

  13. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    1993-06-01

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

  16. ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor.

    Science.gov (United States)

    Xiao, Guang-Qian; Li, Faqian; Unger, Pamela D; Katerji, Hani; Yang, Qi; McMahon, Loralee; Burstein, David E

    2016-06-01

    Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor. PMID:26916077

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

    Science.gov (United States)

    2013-05-01

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

  18. Clinical efficacy of superselective arterial embolization in the treatment of hemorrhage from malignant gestational trophoblastic tumor

    Institute of Scientific and Technical Information of China (English)

    Geng Shuo; Wan Xi-run; Xiang Yang; Feng Feng-zhi; Yang Xiu-yu; Li Xiao-guang; Liu Wei; Yang Ning

    2010-01-01

    Objective: To evaluate the efficacy of superselective arterial embolization in controlling hemorrhage from malignant gestational trophoblastic tumor. Methods: From February 1990 to January 2008, 44 patients with hemorrhage from malignant gestational trophoblastic tumor (including 29 cases of choriocarcinoma and 15 cases of invasive mole) were treated with superselective arterial embolization. The hemorrhage sites included uterus (40 cases), cervical metastasis (1 case) and vaginal metastasis (3 cases).Results: In 41 cases (93.2 %), superselective arterial embolization successfully controlled the hemorrhage. Hysterectomy was performed in the 3 failed cases and uterine perforation was revealed by laparotomy. Five patients had normal term delivery after successful superselective arterial embolization and chemotherapy, and two patients are now in the healthy second trimester of pregnancy.Conclusion: Superselective arterial embolization can effectively control the hemorrhage from malignant gestational trophoblastic tumor.

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

    Science.gov (United States)

    Nguyen, Ngoc Minh Phuong; Slim, Rima

    2014-01-01

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

  20. 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.

  1. Invasive mole: a rare cause of postmenopausal bleeding

    Directory of Open Access Journals (Sweden)

    Mamour Guèye

    2013-06-01

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

  2. Current Chemotherapeutic Management of Patients with Gestational Trophoblastic Neoplasia

    Directory of Open Access Journals (Sweden)

    Taymaa May

    2011-01-01

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

  3. Radiology of gestational trophoblastic neoplasia

    Energy Technology Data Exchange (ETDEWEB)

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

    2006-04-15

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

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

    Science.gov (United States)

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

    2013-03-01

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

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

    Directory of Open Access Journals (Sweden)

    Feix Sonja

    2010-10-01

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

  6. So-called intracranial germ cell tumours: personal experiences and a theory of their pathogenesis.

    Science.gov (United States)

    Sano, K; Matsutani, M; Seto, T

    1989-06-01

    We investigated 110 cases of intracranial germ cell tumours (up to the end of 1986), 56% of which showed monotypic histological patterns and 44% were shown to be mixed tumours. All these cases underwent surgery followed by radiation and/or chemotherapy. All cases of choriocarcinoma and embryonal carcinoma died within 2 yr: cases of endodermal sinus tumour also showed poor results (4 yr survival rate was 12.5%). Mature teratoma had a 5 yr survival rate (5YSR) and a 10 yr survival rate (10YSR) of 78.3% each: immature teratoma showed a 5YSR of 44.9%. Two-cell pattern tumours (PTC) showed a 5YSR of 85.8% and a 10YSR of 82.4%. They (PTC) can be divided into two groups (i) germinoma and (ii) pinealoma of pineal parenchyma origin (pineocytoma with lymphocytic infiltration) on the basis of the difference in the tumour cell-stroma relationship and also placental alkaline phosphatase stain. In the pineal region, 70% of PTC belonged to the category of pinealoma and in the suprasellar region, 92% of PTC were germinoma. Germinoma showed a 5YSR of 91.4% and a 10YSR of 91.4%, whereas those of the pinealoma were 78.2% and 68.4% respectively. This suggests that the biological characteristics of germinoma and pinealoma may be different. All these results may bring into question the validity of the germ cell theory, since germinoma, which should be the most undifferentiated according to the theory, was the most benign and choriocarcinoma and endodermal sinus tumour, which should be the most differentiated, were the most malignant in the follow-up study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2569683

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

    Science.gov (United States)

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang

    2014-01-01

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

  8. The molecular role of connexin 43 in human trophoblast cell fusion.

    Science.gov (United States)

    Dunk, Caroline E; Gellhaus, Alexandra; Drewlo, Sascha; Baczyk, Dora; Pötgens, Andy J G; Winterhager, Elke; Kingdom, John C P; Lye, Steven J

    2012-04-01

    Connexin expression and gap junctional intercellular communication (GJIC) mediated by connexin 43 (Cx43)/gap junction A1 (GJA1) are required for cytotrophoblast fusion into the syncytium, the outer functional layer of the human placenta. Cx43 also impacts intracellular signaling through protein-protein interactions. The transcription factor GCM1 and its downstream target ERVW-1/SYNCYTIN-1 are key players in trophoblast fusion and exert their actions through the ERVW-1 receptor SLC1A5/ASCT-2/RDR/ATB(0). To investigate the molecular role of the Cx43 protein and its interaction with this fusogenic pathway, we utilized stable Cx43-transfected cell lines established from the choriocarcinoma cell line Jeg3: wild-type Jeg3, alphahCG/Cx43 (constitutive Cx43 expression), JpUHD/Cx43 (doxycyclin-inducible Cx43 expression), or JpUHD/trCx43 (doxycyclin-inducible Cx43 carboxyterminal deleted). We hypothesized that truncation of Cx43 at its C-terminus would inhibit trophoblast fusion and protein interaction with either ERVW-1 or SLC1A5. In the alphahCG/Cx43 and JpUHD/Cx43 lines, stimulation with cAMP caused 1) increase in GJA1 mRNA levels, 2) increase in percentage of fused cells, and 3) downregulation of SLC1A5 expression. Cell fusion was inhibited by GJIC blockade using carbenoxylone. Neither Jeg3, which express low levels of Cx43, nor the JpUHD/trCx43 cell line demonstrated cell fusion or downregulation of SLC1A5. However, GCM1 and ERVW-1 mRNAs were upregulated by cAMP treatment in both Jeg3 and all Cx43 cell lines. Silencing of GCM1 prevented the induction of GJA1 mRNA by forskolin in BeWo choriocarcinoma cells, demonstrating that GCM1 is upstream of Cx43. All cell lines and first-trimester villous explants also demonstrated coimmunoprecipitation of SLC1A5 and phosphorylated Cx43. Importantly, SLC1A5 and Cx43 gap junction plaques colocalized in situ to areas of fusing cytotrophoblast, as demonstrated by the loss of E-cadherin staining in the plasma membrane in first

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

    Science.gov (United States)

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

    2015-01-01

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

  10. Regulation of amino acid transporters by adenoviral-mediated human insulin-like growth factor-1 in a mouse model of placental insufficiency in vivo and the human trophoblast line BeWo in vitro

    Science.gov (United States)

    Jones, H.; Crombleholme, T.; Habli, M.

    2014-01-01

    Previous work in our laboratory demonstrated that over-expression of human insulin-like growth factor-11 (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 amino acid transporter expression and localization in both a mouse model of placental Insufficiency (PI) and a model of human trophoblast, the BeWo Choriocarcinoma cell line. For in vitro human studies, BeWo Choriocarcinoma cells were maintained in F12 complete medium + 10%FBS. Cells were incubated in serum-free control media ± Ad-IGF-1 or Ad-LacZ for 48 h. MOIs of 10:1 and 100:1 were utilized. In BeWo, transfection efficiency was 100% at an MOI of 100:1 and Ad-IGF-1 significantly increased IGF-1 secretion, proliferation and invasion but reduced apoptosis compared to controls. In vitro, amino acid uptake was increased following Ad-IGF-1 treatment and associated with significantly increased RNA expression of SNAT1, 2, LAT1 and 4F2hc. Only SNAT2 protein expression was increased but LAT1 showed relocalization from a perinuclear location to the cytoplasm and cell membrane. For in vivo studies, timed-pregnant animals were divided into four groups on day 18; sham-operated controls, uterine artery branch ligation (UABL), UABL + Ad-hIGF-1 (108 PFU), UABL + Ad-LacZ (108 PFU). At gestational day 20, pups and placentas were harvested by C-section. Only LAT1 mRNA expression changed, showing that a reduced expression of the transporter levels in the PI model could be partially rectified with Ad-hIGF1 treatment. At the protein level, System L was reduced in PI but remained at control levels following Ad-hIGF1. The System A isoforms were differentially regulated with SNAT2 expression diminished but SNAT1 increased in PI and Ad-hIGF1 groups. Enhanced

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1998-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Uwe eKnippschild

    2014-05-01

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

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

    Science.gov (United States)

    2014-11-04

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

  14. Contributions of phosphorylation to regulation of OCTN2 uptake of carnitine are minimal in BeWo cells.

    Science.gov (United States)

    Rytting, Erik; Audus, Kenneth L

    2008-02-01

    Physiological functions of organic cation transporters (OCTs) in the placenta include transporting essential nutrients from the maternal to fetal circulations. OCTN2 transports carnitine with high affinity, and the transport of several drugs has also been shown to be mediated by this transporter. In this work, the role of phosphorylation and dephosphorylation mechanisms in regulating OCTN2 was investigated by observing the effects of various activators and inhibitors of kinases and phosphatases on the uptake of carnitine in BeWo cells, a human choriocarcinoma trophoblast cell line frequently used as an in vitro model of the rate-limiting barrier for maternal-fetal exchange. Preincubation with genistein resulted in significant increases in both alkaline phosphatase (ALP) activity and carnitine uptake. Levamisole, an ALP inhibitor, caused a more substantial decrease in carnitine uptake than expected from its corresponding decrease in ALP activity. It was determined that levamisole competitively inhibits carnitine uptake, with a K(i) value of 1.01+/-0.05mM, and this effect has a greater role in decreasing carnitine uptake than any indirect effects of ALP inhibition upon OCTN2 function. Progesterone also competitively inhibited carnitine uptake (K(i)=48.6+/-5.0muM), but had no effect on ALP activity in BeWo cells. PMID:17977516

  15. 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.

  16. 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)

    Ayres Pereira, Marina; Mandel Clausen, Thomas; Pehrson, Caroline; Mao, Yang; Resende, Mafalda; Daugaard, Mads; Riis Kristensen, Anders; Spliid, Charlotte; Mathiesen, Line; E Knudsen, Lisbeth; Damm, Peter; G Theander, Thor; R Hansson, Stefan; A Nielsen, Morten; Salanti, Ali

    2016-08-01

    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

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

    Science.gov (United States)

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

    2015-10-01

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

  18. Ischemic Stroke during Pregnancy and Puerperium

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Betri Enrico

    2009-09-01

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

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

    Institute of Scientific and Technical Information of China (English)

    SANG; QingXiang; Amy

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    NI; JingMan

    2001-01-01

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

  2. 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.)

  3. 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

  4. Six cases of malignant germ-cell tumors (grade 4). Comparison with germinoma (grade 2, 3) on CT

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, M.; Machida, T.; Maehara, T. (Tokyo Univ. (Japan). Faculty of Medicine)

    1981-08-01

    The CT patterns of six malignant germ-cell tumors other than germinomas (one embryonal carcinoma, one choriocarcinoma, one yolk sac tumor, and three immature teratomas) were compared with those of 12 germinomas (ten suprasellar, one pineal, and one basal ganglia). The effects of irradiation and the changes in the concentration of serum ..cap alpha..-fetoprotein (AFP) and human chorionic gonadotropin (HCG) were compared by means of serial studies. 1. Pre-contrast CT Four of the six (67%) malignant germ-cell tumors showed isodense masses with irregular margins that contained calcified dots and small necrotic cavities. All 12 germinomas showed round, high-density masses with smooth margins without necrotic cavities. The suprasellar germinomas showed no calcification on CT. 2. Post-contrast CT Both malignant germ-cell tumors and germinomas showed a strong enhancement after contrast administration. 3. Change in size after irradiation Malignant germ-cell tumors did not show a decrease in size after radiotherapy (20 - 40 Gy), although the necrotic cavities enlarged in three out of four tumors. Germinomas were highly radiosensitive and showed a remarkable change in size on follow-up CT after irradiation. 4. Serum AFP and HCG The concentrations of serum AFP and/or HCG before therapy were abnormally high in five malignant germ-cell tumors. In three out of four patients, the concentration of serum AFP was normalized, but in one patient the concentration of AFP increased even after irradiation.

  5. Effectiveness of gefitinib in combination with methotrexate in the treatment of ectopic pregnancy

    Directory of Open Access Journals (Sweden)

    Capmas P

    2015-07-01

    Full Text Available Perrine Capmas,1 Hervé Fernandez21Inserm, Centre of Research in Epidemiology and Population Health (CESP, 2Department of Gynecology, Bicetre Hospital, GHU Sud, AP-HP, Le Kremlin Bicêtre, FranceAbstract: Medical management for ectopic pregnancy is subject to substantial variations with different protocols and various routes of administration. Regardless the protocol used, methotrexate is currently the medical treatment of choice for ectopic pregnancy. The risk of a rescue surgery is a main concern. Recently, some studies suggested combining gefitinib and methotrexate to improve medical treatment and to decrease the need for reinjection and for additional surgery. Gefitinib is an orally administered EGF receptor-tyrosine kinase inhibitor. For tubal ectopic pregnancy, median recovery time was shorter after combination treatment with gefitinib and methotrexate. Toxicity reported with combination treatment was acneiform rash in 67% of cases and diarrhea in 42%. They were always transient and are known side effects of gefitinib previously described in lung cancer. These preliminary results are very promising but need to be explored further before wide distribution. For ectopic pregnancy, combining treatment seems to be interesting but results of the first randomized trial have to be evaluated first. For other indications, such as non-tubal ectopic pregnancy or choriocarcinoma, randomized studies are needed before wide use of the combination in current practice.Keywords: toxicity, efficacy, EGF receptor-tyrosine kinase inhibitor, non-tubal ectopic pregnancy

  6. Mixed malignant germ cell tumor of ovary

    Directory of Open Access Journals (Sweden)

    Sviračević Branko

    2011-01-01

    Full Text Available Introduction. Malignant tumours of ovary germ epithelium are very rare and account for about 2-5% of all ovarian tumours of germ origin. In adolescent patients under 20 years of age diagnosed to have ovarian tumour, these tumours originate from germ cells in about 70% of cases. Depending on the stage of the disease, medical treatment and age, the death rate ranges from 25% to 84%. A special group of germ tumours are mixed germ cells tumours built of two or more different types of germ tumours. Case report. This paper gives a diagnostic-therapeutic procedure and the clinical picture with the course and outcome of the decease in a nineteen-year old patient with a mixed malignant germ tumour (dysgerminoma, choriocarcinoma, immature teratoma found in one of the ovaries. It also deals with the appearance and development, some characteristics and histological build of the tumours diagnosed in this case. Conclusion. Malignant tumours of ovary germ epithelium are very rare and develop in female population under 30 years of age. They are characterized by a high degree of malignity. They are resistant to cytostatic treatment, they spread very quickly with the lethal outcome. The course of the disease is not characteristic and is usually masked under some other acute gynaecological disease. The definitive diagnosis is made after laparotomy and pathohistological analysis of the tumour tissue.

  7. CpG methylation suppresses transcriptional activity of human syncytin-1 in non-placental tissues

    International Nuclear Information System (INIS)

    Syncytin-1 is a captive envelope glycoprotein encoded by one of human endogenous retroviruses W. It is expressed exclusively in the placental trophoblast where it participates in cell-to-cell fusion during differentiation of syncytiotrophobast. In other tissues, however, syncytin-1 expression must be kept in check because inadvertent cell fusion might be dangerous for tissue organization and integrity. We describe here an inverse correlation between CpG methylation of syncytin-1 5' long terminal repeat and its expression. Hypomethylation of the syncytin-1 5' long terminal repeat in the placenta and in the choriocarcinoma-derived cell line BeWo was detected. However, other analyzed primary cells and cell lines non-expressing syncytin-1 contain proviruses heavily methylated in this sequence. CpG methylation of syncytin-1 is resistant to the effect of the demethylating agent 5-azacytidine. The inhibitory role of CpG methylation is further confirmed by transient transfection of in-vitro-methylated syncytin-1 promoter-driven reporter construct. Altogether, we conclude that CpG methylation plays a principal role in the transcriptional suppression of syncytin-1 in non-placental tissues, and, in contrast, demethylation of the syncytin-1 promoter in trophoblast is a prerequisite for its expression and differentiation of multinucleated syncytiotrophoblast

  8. 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.

  9. Clinical significance of three-dimensional sonohysterography

    International Nuclear Information System (INIS)

    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.

  10. [A case of a nonseminomatous germ cell tumor responding to MEA therapy].

    Science.gov (United States)

    Nagai, Yasuharu; Minami, Takafumi; Itami, Yoshitaka; Kobayashi, Yasuyuki; Shimizu, Nobutaka; Yamamoto, Yutaka; Hayashi, Taiji; Nozawa, Masahiro; Yoshimura, Kazuhiro; Ishii, Tokumi; Uemura, Hirotugu

    2013-10-01

    We experienced a case of testicular cancer that was successfully treated by salvage chemotherapy comprised of methotrexate, actinomycin D and etoposide (MEA). A 25-year-old man was admitted to our hospital with a diagnosis of stage III B2 (JUA classification) testicular cancer. The patient had multiple lung metastases, and underwent a left orchiectomy. A histopathological examination revealed a choriocarcinoma, embryonal carcinoma, mature teratoma, and a yolk sac tumor. Tumor marker levels were elevated ; human chorionic gonadotropin β was 46 mIU/ml and alpha fetoprotein was 437 ng/ml. Although he was treated post-operatively with two courses of bleomycin, etoposide and cisplatin therapy, four courses of high-dose carboplatin, etoposide and iphosphamide (VIP) therapy, and two courses of CPT-11+ cisplatin therapy, tumor maker levels remained elevated and lung metastases were stable. Accordingly, he received three courses of MEA therapy. MEA therapy is regimen used to treat gestational trophoblastic neoplasia. After MEA therapy, levels of the tumor markers normalized. He then underwent a partial resection of lung and enucleation of lung metastasis by the video assisted thoracoscopic surgery method. Histopathological examination of the lung metastasis revealed only necrotic tissue. Tumor recurrence has not been observed in the 14 months since the MEA therapy. PMID:24262714

  11. Diagnostic value of different tumor markers, our experience

    International Nuclear Information System (INIS)

    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)

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

    Institute of Scientific and Technical Information of China (English)

    赵峻; 向阳

    2011-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    赵峻; 向阳

    2013-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    赵峻; 向阳

    2012-01-01

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

  15. A critical examination of the foundations of immunotherapy for cancer.

    Science.gov (United States)

    Hewitt, H B

    1979-07-01

    It is argued that immunotherapy (IMTH) for cancer, as well as the theory of cancer immunogenicity on which it rests, derives no secure foundation either from clinical observations or from experimental study of valid animal tumour models. Discouraging clinical observations include: the long history of failure of IMTH; the rejection of IMTH for choriocarcinoma--a true allograft in the patient; the extreme rarity of spontaneous regression, and progressive discrediting of the theory of immunosurveillance; the high frequency of nodal metastasis; and the failure to demonstrate a tumour-specific antigen in man. The great majority of animal tumours used for experimental studies of IMTH display artefactual immunogenicity associated with their mode of induction or conditions of transplantation and cannot be accepted as valid models of clinical cancer. The author reviews his total failure to demonstrate immunogenicity or successful IMTH using a wide range of animal tumours from which known laboratory artefacts have been strictly excluded. The inordinate promotion of tumour immunology and IMTH in recent years is attributed to unfortunate sociological influences encouraging premature assertion of clinical relevance from experimental research. PMID:572751

  16. 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.

  17. 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.

  18. Dose-dependent and cell type-specific cell death and proliferation following in vitro exposure to radial extracorporeal shock waves.

    Science.gov (United States)

    Hochstrasser, Tanja; Frank, Hans-Georg; Schmitz, Christoph

    2016-01-01

    Radial extracorporeal shock wave (rESW) therapy is widely used in musculoskeletal disorders and wound repair. However, the mechanisms of action are still largely unknown. The current study compared the effects of rESWs on two cell types. Human fetal foreskin fibroblasts (HFFF2) and human placental choriocarcinoma cell line JEG-3 were exposed to 0, 100, 200, 500 or 5000 rESWs generated with a Swiss DolorClast device (2.5 bar, 1 Hz). FACS analysis immediately after rESW exposure showed that initially, rESWs rather induced mechanical cell destruction than regulated or programmed cell death. Cell damage was nearly negated by reducing cavitation. Furthermore, cell viability decreased progressively with higher numbers of rESWs. Exposure to rESWs had no impact on growth potential of JEG-3 cells, but dose-dependently increased growth potential of HFFF2 cells. Cultivation of cells that were initially exposed to sham-rESWs in conditioned media increased the growth potential of HFFF2 cells, nevertheless, an even stronger effect was achieved by direct exposure to rESWs. Additionally, cell cycle distribution analysis demonstrated a shift in proportion from G0/G1 to G2/M phase in HFFF2 cells, but not in JEG-3 cells. These data demonstrate that rESWs leads to initial and subsequent dose-dependent and cell type-specific effects in vitro. PMID:27477873

  19. A new approach combining LC-MS and multivariate statistical analysis for revealing changes in histone modification levels.

    Science.gov (United States)

    Bilgraer, Raphaël; Gillet, Sylvie; Gil, Sophie; Evain-Brion, Danièle; Laprévote, Olivier

    2014-11-01

    While acting upon chromatin compaction, histone post-translational modifications (PTMs) are involved in modulating gene expression through histone-DNA affinity and protein-protein interactions. These dynamic and environment-sensitive modifications are constitutive of the histone code that reflects the transient transcriptional state of the chromatin. Here we describe a global screening approach for revealing epigenetic disruption at the histone level. This original approach enables fast and reliable relative abundance comparison of histone PTMs and variants in human cells within a single LC-MS experiment. As a proof of concept, we exposed BeWo human choriocarcinoma cells to sodium butyrate (SB), a universal histone deacetylase (HDAC) inhibitor. Histone acid-extracts (n = 45) equally representing 3 distinct classes, Control, 1 mM and 2.5 mM SB, were analysed using ultra-performance liquid chromatography coupled with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-QTOF-MS). Multivariate statistics allowed us to discriminate control from treated samples based on differences in their mass spectral profiles. Several acetylated and methylated forms of core histones emerged as markers of sodium butyrate treatment. Indeed, this untargeted histonomic approach could be a useful exploratory tool in many cases of xenobiotic exposure when histone code disruption is suspected. PMID:25167371

  20. Anticancer chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1988-10-01

    Despite troubled beginnings, anticancer chemotherapy has made significant contribution to the control of cancer in man, particularly within the last two decades. Early conceptual observations awakened the scientific community to the potentials of cancer chemotherapy. There are now more than 50 agents that are active in causing regression of clinical cancer. Chemotherapy's major conceptual contributions are two-fold. First, there is now proof that patients with overt metastatic disease can be cured, and second, to provide a strategy for control of occult metastases. In man, chemotherapy has resulted in normal life expectancy for some patients who have several types of metastatic cancers, including choriocarcinoma, Burkitt's lymphomas, Wilm's tumor, acute lymphocytic leukemia, Hodgkins disease, diffuse histiocytic lymphoma and others. Anticancer chemotherapy in Veterinary medicine has evolved from the use of single agents, which produce only limited remissions, to the concept of combination chemotherapy. Three basic principles underline the design of combination chemotherapy protocols; the fraction of tumor cell killed by one drug is independent of the fraction killed by another drug; drugs with different mechanisms of action should be chosen so that the antitumor effects will be additive; and since different classes of drugs have different toxicities the toxic effects will not be additive.

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

    Institute of Scientific and Technical Information of China (English)

    NI JingMan; YANG XiaoWu; JIA ZhengPing; PAN XingFu; WANG Rui

    2001-01-01

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

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

    Science.gov (United States)

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

    2015-10-01

    To obtain insight in translocation of nanoparticles across the placental barrier, translocation was studied for one positively and two negatively charged polystyrene nanoparticles (PS-NPs) of similar size in an in vitro model. The model consisted of BeWo b30 cells, derived from a human choriocarcinoma grown on a transwell insert forming a cell layer that separates an apical from a basolateral compartment. PS-NPs were characterized with respect to size, surface charge, morphology and protein corona. Translocation of PS-NPs was not related to PS-NP charge. Two PS-NPs were translocated across the BeWo transwell model to a lower extent than amoxicillin, a model compound known to be translocated over the placental barrier to only a limited extent, whereas one PS-NP showed a slightly higher translocation. Studies on the effect of transporter inhibitors on the translocation of the PS-NPs indicated that their translocation was not mediated by known transporters and mainly dependent on passive diffusion. It is concluded that the BeWo b30 model can be used as an efficient method to get an initial qualitative impression about the capacity of NPs to translocate across the placental barrier and set priorities in further in vivo studies on translocation of NPs to the fetus. PMID:26145586

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

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

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

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

    International Nuclear Information System (INIS)

    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

  5. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    Science.gov (United States)

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

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

    Directory of Open Access Journals (Sweden)

    Saroj A. Bolde

    2014-08-01

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

  7. 3'-Azido-3'-deoxythymidine (AZT) induces apoptosis and alters metabolic enzyme activity in human placenta

    International Nuclear Information System (INIS)

    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

  8. Pulmonary medicine and palliative care.

    Science.gov (United States)

    Tucakovic, M; Bascom, R; Bascom, P B

    2001-04-01

    Gynaecological malignancies affect the respiratory system both directly and indirectly. Malignant pleural effusion is a poor prognostic factor: management options include repeated thoracentesis, chemical pleurodesis, symptomatic relief of dyspnoea with oxygen and morphine, and external drainage. Parenchymal metastases are typically multifocal and respond to chemotherapy, with a limited role for pulmonary metastatectomy. Pulmonary tumour embolism is frequently associated with lymphangitic carcinomatosis, and is most common in choriocarcinoma. Thromboembolic disease, associated with the hypercoagulable state of cancer, is treated with anticoagulation. Inferior vena cava filter placement is indicated when anticoagulation cannot be given, or when emboli recur despite adequate anticoagulation. Palliative care has a major role for respiratory symptoms of gynaecological malignancies. Treatable causes of dyspnoea include bronchospasm, fluid overload and retained secretions. Opiates are effective at relieving dyspnoea associated with effusions, metatases, and lymphangitic tumour spread. Non-pharmacological therapies include energy conservation, home redesign, and dyspnoea relief strategies, including pursed lip breathing, relaxation, oxygen, circulation of air with a fan, and attention to spiritual suffering. Identification and treatment of gastroesophageal reflux, sinusitis, and asthma can improve many patients' coughs. Chest wall pain responds to local radiotherapy, nerve blocks or systemic analgesia. Case examples illustrate ways to address quality of life issues. PMID:11358403

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

    Science.gov (United States)

    2013-07-01

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

  10. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  11. A rare case of combined placental site trophoblastic tumour with mature cystic teratoma and mixed germ cell tumour in the testis.

    Science.gov (United States)

    Leow, Wei Qiang; Loh, Hwai Liang Alwin; Lee, Lui Shiong; Goh, Chin Hong Ronald

    2015-08-01

    A 20-year-old male presented with persistent right testicular pain. Following ultrasound detection of testicular nodules and biopsy for intraoperative consultation which yielded germ cell tumour, he underwent radical orchidectomy. A predominantly whitish cyst and a lobulated, variegated nodule were identified. Histology showed a mature cystic teratoma with a focus of infiltrative epithelioid cells containing eosinophilic cytoplasm and pleomorphic nuclei, invading ectatic vessel wall associated with fibrinoid change. These cells were positive for cytokeratin, human placental lactogen and inhibin, while negative for Melan-A, p63 and alpha-fetoprotein, consistent with placental site trophoblastic tumor (PSTT). The variegated nodule was a mixed germ cell tumour composed of embryonal carcinoma and immature teratoma. Aside from choriocarcinoma, primary trophoblastic tumors such as PSTT, which are derived from intermediate trophoblasts, are extremely rare in the testis. Aside from a case of pure testicular PSTT, 2 other cases have been described in association with germ cell tumour, of which one is a mature teratoma with PSTT that demonstrated gain of chromosome 12p. The other presented with PSTT in retroperitoneal recurrence of a testicular mixed germ cell tumour. We discussed the features of this tumour in the testis and important differentials in its diagnosis.

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

    Institute of Scientific and Technical Information of China (English)

    郭琦; 冯凤芝; 向阳; 万希润; 任彤

    2016-01-01

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

  13. 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.

  14. 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.

  15. Involvement of GATA transcription factors in the regulation of endogenous bovine interferon-tau gene transcription.

    Science.gov (United States)

    Bai, Hanako; Sakurai, Toshihiro; Kim, Min-Su; Muroi, Yoshikage; Ideta, Atsushi; Aoyagi, Yoshito; Nakajima, Hiromi; Takahashi, Masashi; Nagaoka, Kentaro; Imakawa, Kazuhiko

    2009-12-01

    Expression of interferon-tau (IFNT), necessary for pregnancy establishment in ruminant ungulates, is regulated in a temporal and spatial manner. However, molecular mechanisms by which IFNT gene transcription is regulated in this manner have not been firmly established. In this study, DNA microarray/RT-PCR analysis between bovine trophoblast CT-1 and Mardin-Darby bovine kidney (MDBK) cells was initially performed, finding that transcription factors GATA2, GATA3, and GATA6 mRNAs were specific to CT-1 cells. These mRNAs were also found in Days 17, 20, and 22 (Day 0 = day of estrus) bovine conceptuses. In examining other bovine cell lines, ovary cumulus granulosa (oCG) and ear fibroblast (EF) cells, GATA2 and GATA3, but not GATA6, were found specific to the bovine trophoblast cells. In transient transfection analyses using the upstream region (-631 to +59 bp) of bovine IFNT gene (bIFNT, IFN-tau-c1), over-expression of GATA2/GATA3 did not affect the transcription of bIFNT-reporter construct in human choriocarcinoma JEG3 cells. Transfection of GATA2, GATA3, ETS2, and/or CDX2, however, was effective in the up-regulation of the bIFNT construct transfected into bovine oCG and EF cells. One Point mutation studies revealed that among six potential GATA binding sites located on the upstream region of the bIFNT gene, the one next to ETS2 site exhibited reduced luciferase activity. In CT-1 cells, endogenous bIFNT gene transcription was up-regulated by over-expression of GATA2 or GATA3, but down-regulated by siRNA specific to GATA2 mRNA. These data suggest that GATA2/3 is involved in trophoblast-specific regulation of bIFNT gene transcription. PMID:19598245

  16. 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)

    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

  17. 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

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

    Science.gov (United States)

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

    2013-07-01

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

  19. Endometrial carcinoma in elderly women.

    Science.gov (United States)

    Hoffman, K; Nekhlyudov, L; Deligdisch, L

    1995-08-01

    Endometrial carcinoma remains the most common invasive gynecologic malignancy. Increased longevity is associated with an increased incidence of endometrial carcinoma (EC) in elderly women. While recent studies have looked at aging and its relation to ovarian, breast, and cervical cancer, few have focused on EC in the growing elderly population. This study analyzed 35 histologic specimens of EC in women 75-92 years of age. Findings revealed that only 23% of the tumors were Stage I, G1. The majority (77%) were deeply invasive or of advanced stage (IC-IV). These were G2, G3, or "virulent" types of nonendometrioid EC (undifferentiated, clear cell, uterine serous papillary, and squamous cell carcinoma). Fifty-seven percent of tumors were endometrioid, of which 9% were mixed, including a rare case of nongestational choriocarcinoma. The nonendometrioid tumors, compared to the endometrioid types, were more often high-stage tumors with vascular invasion. They were also more often associated with atrophic (vs hyperplastic) uninvolved endometrium. Clinical risk factors (nulliparity, obesity, estrogen replacement therapy) were assessed and correlated with the histologic findings. It was shown that tumors in the elderly were less likely to be estrogen-related. It was concluded that EC in this age group is more aggressive, histologically less differentiated, and often nonendometrioid compared with EC in the general population. The increased virulence of EC in the elderly may be related to the tumor's independence from hormonal factors, to the poorly understood but well-known diminished immunologic defense against cancer in general in elderly patients, and/or to the belated diagnosis of the disease in this population. PMID:7622105

  20. Discovery and diagnostic value of a novel oncofetal protein: glypican 3.

    Science.gov (United States)

    Wang, Sean K; Zynger, Debra L; Hes, Ondrej; Yang, Ximing J

    2014-11-01

    Glypican 3 is a membrane-bound heparan sulfate proteoglycan, which has recently been identified as a marker for liver cancer and germ cell malignancies. Individuals with loss-of-function mutations for the glypican 3 gene exhibit Simpson-Golabi-Behmel syndrome, a rare X-linked overgrowth disorder. Expression of glypican 3 mRNA and protein is normally silenced in most adult organs and may reappear during malignant transformation. In the past few years, immunohistochemical and molecular characteristics of glypican 3 in hepatocellular carcinoma have been elucidated. More recently, glypican 3 has been emerging as a new diagnostic marker for germ cell tumors and especially testicular and ovarian yolk sac tumors. However, in other tumors such as renal cell carcinomas, squamous cell carcinomas, and melanomas, studies disagree on the level of glypican 3 expression. Finally, there is the controversial notion of glypican 3 as a tumor suppressor gene. In this review article, we update current knowledge on glypican 3 expression in normal and neoplastic tissues, evaluate its utility as a tumor marker in clinical practice, and explore its role as a novel oncofetal protein with clinical implications. Our focus is on the diagnostic value of glypican 3 in germ cell tumors and other neoplasms in addition to hepatocellular carcinoma. In conclusion, glypican 3 has been proven to be a useful immunohistochemical marker in distinguishing yolk sac tumors, choriocarcinomas, and Wilms tumors from other malignancies histologically mimicking these primitive tumors. Clinically, we recommend that glypican 3 be used as part of a panel of markers in subtyping testicular germ cell tumors. PMID:25299314

  1. Organ transplantation from deceased donors with cancer: is it safe?

    Directory of Open Access Journals (Sweden)

    Nalesnik MA

    2011-08-01

    Full Text Available Michael A Nalesnik1, Michael G Ison21Division of Transplantation and Hepatic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Pittsburg, PA, USA; 2Divisions of Infectious Diseases and Organ Transplantation, Northwestern University Feinberg School of Medicine, Chicago, IL, USAAbstract: The availability of donor organs continues to be insufficient to meet the needs of patients actively waiting for transplant. Consequently, there is continuing pressure to increase the donor organ pool while simultaneously assuring safety for the recipient population. The complication of donor malignancy transmission has been documented almost from the beginning of transplantation, and continues to be a concern today. The anecdotal nature of case reports and compiled series ensures that clinical decisions related to organ use from donors with malignancy will of necessity continue to be made on the basis of low-level evidence. Despite this limitation, the literature indicates that not all donor neoplasms have the same risk for transmission to the recipient, and it is necessary to consider the specific malignancy affecting the donor, as well as the condition of the recipient, before a decision is made to transplant or discard a given organ. Published cases suggest that certain forms of neoplasia, such as melanoma, choriocarcinoma, sarcoma, small cell carcinoma, or metastatic carcinomas serve as strong contraindications to organ donation. In contrast, considerable experience exists to suggest that certain tumors of the central nervous system, small subclinical prostate carcinomas, or small renal cell carcinomas resected prior to transplant, among other tumors, should not in themselves disqualify an individual from donating organs in the appropriate circumstance. This review presents the case for considering organ transplantation in the setting of certain donor malignancies and discusses factors to be weighed in such decisions. Additionally

  2. Nivolumab and Ipilimumab in Treating Patients With Rare Tumors

    Science.gov (United States)

    2016-08-24

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

  3. 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.

  4. Estrogens and human papilloma virus oncogenes regulate human ether-à-go-go-1 potassium channel expression.

    Science.gov (United States)

    Díaz, Lorenza; Ceja-Ochoa, Irais; Restrepo-Angulo, Iván; Larrea, Fernando; Avila-Chávez, Euclides; García-Becerra, Rocío; Borja-Cacho, Elizabeth; Barrera, David; Ahumada, Elías; Gariglio, Patricio; Alvarez-Rios, Elizabeth; Ocadiz-Delgado, Rodolfo; Garcia-Villa, Enrique; Hernández-Gallegos, Elizabeth; Camacho-Arroyo, Ignacio; Morales, Angélica; Ordaz-Rosado, David; García-Latorre, Ethel; Escamilla, Juan; Sánchez-Peña, Luz Carmen; Saqui-Salces, Milena; Gamboa-Dominguez, Armando; Vera, Eunice; Uribe-Ramírez, Marisela; Murbartián, Janet; Ortiz, Cindy Sharon; Rivera-Guevara, Claudia; De Vizcaya-Ruiz, Andrea; Camacho, Javier

    2009-04-15

    Ether-à-go-go-1 (Eag1) potassium channels are potential tools for detection and therapy of numerous cancers. Here, we show human Eag1 (hEag1) regulation by cancer-associated factors. We studied hEag1 gene expression and its regulation by estradiol, antiestrogens, and human papillomavirus (HPV) oncogenes (E6/E7). Primary cultures from normal placentas and cervical cancer tissues; tumor cell lines from cervix, choriocarcinoma, keratinocytes, and lung; and normal cell lines from vascular endothelium, keratinocytes, and lung were used. Reverse transcription-PCR (RT-PCR) experiments and Southern blot analysis showed Eag1 expression in all of the cancer cell types, normal trophoblasts, and vascular endothelium, in contrast to normal keratinocytes and lung cells. Estradiol and antiestrogens regulated Eag1 in a cell type-dependent manner. Real-time RT-PCR experiments in HeLa cells showed that Eag1 estrogenic regulation was strongly associated with the expression of estrogen receptor-alpha. Eag1 protein was detected by monoclonal antibodies in normal placenta and placental blood vessels. Patch-clamp recordings in normal trophoblasts treated with estradiol exhibited potassium currents resembling Eag1 channel activity. Eag1 gene expression in keratinocytes depended either on cellular immortalization or the presence of HPV oncogenes. Eag1 protein was found in keratinocytes transfected with E6/E7 HPV oncogenes. Cell proliferation of E6/E7 keratinocytes was decreased by Eag1 antibodies inhibiting channel activity and by the nonspecific Eag1 inhibitors imipramine and astemizole; the latter also increased apoptosis. Our results propose novel oncogenic mechanisms of estrogen/antiestrogen use and HPV infection. We also suggest Eag1 as an early indicator of cell proliferation leading to malignancies and a therapeutic target at early stages of cellular hyperproliferation. PMID:19351862

  5. 妊娠滋养细胞疾病的研究进展

    Institute of Scientific and Technical Information of China (English)

    王红

    2007-01-01

    妊娠滋养细胞疾病(gestaional trophoblastic diseas,GTD)是包括葡萄胎(hydatidiform mole HM)、侵蚀性葡萄胎(invasive hydatidiform mole,IHM)、绒癌(choriocarcinoma CCA)和少见类型的胎盘部位滋养细胞肿瘤等一组来源于胎盘绒毛滋养细胞的疾病。除HM以外其它滋养细胞疾病又称滋养细胞肿瘤(gestationaltro Dhoblatic tumor,GTT)。经过几十年的努力,对滋养细胞的分子生物学、遗传学、发病机理及潜在恶性的探讨以及在治疗学上都有了明显的进展。20世纪后期基因组学的快速发展,使人们深入地了解了滋养细胞的发生、发展规律。但是对于滋养细胞疾病的发病机理及其发展和预后,至今仍缺乏具有说服力的解释。本文对近年来有关妊娠滋养细胞疾病的研究状况做一综述。

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

    International Nuclear Information System (INIS)

    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 [3H]2O 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. - Highlights:

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

    Directory of Open Access Journals (Sweden)

    Mitra M Gilani

    2013-01-01

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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    Jiale Qin

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

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

    Science.gov (United States)

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

    2012-06-01

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

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

    Science.gov (United States)

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

    2013-10-15

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

  12. 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

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

    Science.gov (United States)

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

    2016-05-01

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

  14. 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.

  15. Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport.

    Science.gov (United States)

    Wittmaack, F M; Gåfvels, M E; Bronner, M; Matsuo, H; McCrae, K R; Tomaszewski, J E; Robinson, S L; Strickland, D K; Strauss, J F

    1995-01-01

    The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest member of the low density lipoprotein receptor (LDLR) family. Very little is known about VLDLR localization and regulation. Immunohistochemical analysis of human placenta with a specific polyclonal antibody detected VLDLR in syncytiotrophoblast and intermediate trophoblast cells. VLDLR transcripts were also localized in these cells by in situ hybridization histochemistry. In addition, VLDLR messenger RNA (mRNA) was detected in villous core endothelial cells and cells appearing to be Hofbauer cells. Northern blot analysis of placenta revealed a 2.6-fold increase in VLDLR mRNA at term compared to that in the first trimester. The regulation of VLDLR expression was studied in JEG-3 and BeWo choriocarcinoma cells, two trophoblast-derived cell lines. Treatment of these cells with 8-bromo-cAMP caused a profound suppression of VLDLR message, whereas LDLR transcripts were increased. Incubation of JEG-3 cells with 25-hydroxycholesterol did not lead to sterol negative feedback on VLDLR gene expression, unlike LDLR mRNA, which declined markedly. Insulin (200 mg/L) up-regulated VLDLR message in JEG-3 cells 2-fold, as did the fibrate hypolipidemic drug, clofibric acid. We conclude that 1) VLDLR is expressed in human placental trophoblast cells in a pattern consistent with a role in placental lipid transport; 2) VLDLR expression is high at term relative to that in the first trimester; and 3) the trophoblast VLDLR is subject to down-regulation by cAMP and up-regulation by insulin and fibrate hypolipidemic drugs. PMID:7828550

  16. Trophoblast expression dynamics of the tumor suppressor gene gastrokine 2.

    Science.gov (United States)

    Fahlbusch, Fabian B; Ruebner, Matthias; Huebner, Hanna; Volkert, Gudrun; Bartunik, Hannah; Winterfeld, Ilona; Hartner, Andrea; Menendez-Castro, Carlos; Noegel, Stephanie C; Marek, Ines; Wachter, David; Schneider-Stock, Regine; Beckmann, Matthias W; Kehl, Sven; Rascher, Wolfgang

    2015-09-01

    Gastrokines (GKNs) were originally described as stomach-specific tumor suppressor genes. Recently, we identified GKN1 in extravillous trophoblasts (EVT) of human placenta. GKN1 treatment reduced the migration of the trophoblast cell line JEG-3. GKN2 is known to inhibit the proliferation, migration and invasion of gastric cancer cells and may interact with GKN1. Recently, GKN2 was detected in the placental yolk sac of mice. We therefore aimed to further characterize placental GKN2 expression. By immunohistochemistry, healthy first-trimester placenta showed ubiquitous staining for GKN2 at its early gestational stage. At later gestational stages, a more differentiated expression pattern in EVT and villous cytotrophoblasts became evident. In healthy third-trimester placenta, only EVT retained strong GKN2 immunoreactivity. In contrast, HELLP placentas showed a tendency of increased levels of GKN2 expression with a more prominent GKN2 staining in their syncytiotrophoblast. Choriocarcinoma cell lines did not express GKN2. Besides its trophoblastic expression, we found human GKN2 in fibrotic villi, in amniotic membrane and umbilical cord. GKN2 co-localized with smooth muscle actin in villous myofibroblasts and with HLA-G and GKN1 in EVT. In the rodent placenta, GKN2 was specifically located in the spongiotrophoblast layer. Thus, the gestational age-dependent and compartment-specific expression pattern of GKN2 points to a role for placental development. The syncytial expression of GKN2 in HELLP placentas might represent a reduced state of functional differentiation of the syncytiotrophoblast. Moreover, the specific GKN2 expression in the rodent spongiotrophoblast layer (equivalent to human EVT) might suggest an important role in EVT physiology. PMID:26070363

  17. Studies on Quantum Dots-labeled Trichosanthin%量子点标记天花粉蛋白的研究

    Institute of Scientific and Technical Information of China (English)

    张春阳; 马辉; 丁尧; 金雷; 陈瓞延; 苗琦; 聂书明

    2001-01-01

    Semiconductor quantum dots were used for the first time to label trichosanthin.The absorption spectrum,fluorescent spectrum and enzymatic activity of quantum dots-labeled trichosanthin were studied in this paper.The absorbane of QDs-TCS varied to a less extent with wavelength in the range of 400-600 nm.The fluorescent spectrum of QDs-TCS underwent a blue-shift in the emission peak,but the intrinsic spectral width was unchanged.No changes were found in the enzymatic activity of QDs-TCS in comparison with trichosanthin.Distribution of QDs-TCS within human choriocarcinoma cells was simultaneously observed with two-photon laser scanning microscopy and confocal laser scanning microscopy.The results indicated that QDs-TCS could enter the cytoplasm across the membrane and aggregated around the nuleolus.%将半导体量子点应用于标记天花粉蛋白,研究了量子点标记天花粉蛋白的吸收光谱、荧光光谱和酶活性变化.与游离的QDs相比,QDs-TCS的吸收光谱在400~600 nm范围内不发生明显变化;QDs-TCS的发射光谱发生蓝移,但发射半宽不变;标记上QDs后TCS的酶活性没有发生改变.利用双光子激发扫描荧光显微镜和激光共聚焦显微镜同时观察QDs-TcS在人绒癌细胞内的分布发现,QDs-TCS能够跨膜进入细胞,并在细胞核周围呈聚集分布.

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

    Science.gov (United States)

    Rangwala, Tasneem H; Badawi, Faiza

    2011-01-01

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

  19. Triethylenetetramine modulates polyamine and energy metabolism and inhibits cancer cell proliferation.

    Science.gov (United States)

    Hyvönen, Mervi T; Ucal, Sebahat; Pasanen, Markku; Peräniemi, Sirpa; Weisell, Janne; Khomutov, Maxim; Khomutov, Alex R; Vepsäläinen, Jouko; Alhonen, Leena; Keinänen, Tuomo A

    2016-05-15

    Polyamine metabolism is an attractive anticancer drug target, since polyamines are absolutely required for cellular proliferation, and increased levels of polyamines and their biosynthetic enzyme ornithine decarboxylase (ODC) are associated with cancer. Triethylenetetramine (TETA) is a charge-deficient isosteric analogue of the polyamine spermidine (Spd) and a Cu(II)-chelating compound used for the treatment of Wilson's disease, and it has been implicated as a potential anticancer therapeutic drug. In the present study, we studied the effects of TETA in comparison with two other Cu(II)-chelators, D-penicillamine (PA) and tetrathiomolybdate (TTM), on polyamine metabolism in DU145 prostate carcinoma, MCF-7 breast carcinoma and JEG-3 choriocarcinoma cells. TETA induced antizyme, down-regulated ODC and inhibited [(14)C] Spd uptake. Moreover, it completely prevented α-difluoromethylornithine (DFMO)-induced increase in [(14)C] Spd uptake, and inhibited [(14)C] putrescine (Put) uptake and ODC activity in vivo Seven-day treatment of DU145 cells with TETA caused growth cessation by reducing intracellular polyamine levels and suppressing the formation of hypusinated eukaryotic translation initiation factor 5A (eIF5A). TETA or its N-acetylated metabolites also inhibited spermine (Spm), diamine and semicarbazide-sensitive amine oxidases and decreased the level of intracellular reactive oxygen species. Moreover, TETA inhibited the utilization of Put as energy source via the tricarboxylic acid (TCA) cycle, as indicated by decreased production of (14)CO2 from [(14)C] Put. These results indicate that TETA attacks multiple proven anticancer drug targets not attributed to copper chelation, which warrants further studies to reveal its potential in cancer chemoprevention and cure. PMID:27001865

  20. Comprehensive Immunohistochemical Study of Programmed Cell Death Ligand 1 (PD-L1): Analysis in 5536 Cases Revealed Consistent Expression in Trophoblastic Tumors.

    Science.gov (United States)

    Inaguma, Shingo; Wang, Zengfeng; Lasota, Jerzy; Sarlomo-Rikala, Maarit; McCue, Peter A; Ikeda, Hiroshi; Miettinen, Markku

    2016-08-01

    Programmed cell death 1/programmed cell death ligand (PD-1/PD-Ls) axis is crucial for the modulation of immune responses and self-tolerance. Also, aberrant PD-L1 expression on the tumor cells or tumor-associated inflammatory cells accelerates immune evasion of tumor cells. In the past decade, PD-1/PD-L immune checkpoint inhibitors were introduced to cancer treatment trials and, in some cases, showed significant anticancer effects. PD-L1 immunohistochemical staining is considered a potential predictor of clinical response to PD-1/PD-L immune checkpoint inhibitor treatment. However, immunohistochemical data on PD-L1 expression in different types of cancer especially rare entities remain incomplete. In this study, PD-L1 expression was immunohistochemically analyzed in 5536 tumors including germ cell, epithelial, mesenchymal, melanocytic/neuroectodermal, and lymphohematopoietic tumors, as well as in a set of human normal tissues including a fetus. Immunohistochemical analysis was performed with E1L3N rabbit monoclonal antibody and Leica Bond Max automation using multitumor blocks containing up to 70 tumor samples. PD-L1 was constitutively and strongly expressed in placental trophoblasts as well as choriocarcinomas and trophoblastic components of germ cell tumors. Also, the neoplastic cells of classical Hodgkin lymphoma, anaplastic large cell lymphoma, schwannoma, thymoma, and squamous cell carcinoma of various sites frequently expressed PD-L1. In gastrointestinal adenocarcinomas, PD-L1-expression was associated with EBER positivity and mismatch-repair deficiency. In addition, PD-L1 was variably expressed in non-neoplastic macrophages and dendritic cells. PD-L1 immunohistochemistry may have some role in the immunophenotypic differential diagnosis of tumors and pinpointing potential candidates for anti-PD-1/PD-L immune checkpoint therapy. PMID:27158757

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

    Science.gov (United States)

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

    2003-02-01

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

  2. 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

  3. Leptin is an anti-apoptotic effector in placental cells involving p53 downregulation.

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    Ayelén Rayen Toro

    Full Text Available Leptin, a peripheral signal synthetized by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. We have previously demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work, we aimed to study the molecular mechanisms that mediate the survival effect of leptin in placenta. We used the human placenta choriocarcinoma BeWo and first trimester Swan-71 cell lines, as well as human placental explants. We tested the late phase of apoptosis, triggered by serum deprivation, by studying the activation of Caspase-3 and DNA fragmentation. Recombinant human leptin added to BeWo cell line and human placental explants, showed a decrease on Caspase-3 activation. These effects were dose dependent. Maximal effect was achieved at 250 ng leptin/ml. Moreover, inhibition of endogenous leptin expression with 2 µM of an antisense oligonucleotide, reversed Caspase-3 diminution. We also found that the cleavage of Poly [ADP-ribose] polymerase-1 (PARP-1 was diminished in the presence of leptin. We analyzed the presence of low DNA fragments, products from apoptotic DNA cleavage. Placental explants cultivated in the absence of serum in the culture media increased the apoptotic cleavage of DNA and this effect was prevented by the addition of 100 ng leptin/ml. Taken together these results reinforce the survival effect exerted by leptin on placental cells. To improve the understanding of leptin mechanism in regulating the process of apoptosis we determined the expression of different intermediaries in the apoptosis cascade. We found that under serum deprivation conditions, leptin increased the anti-apoptotic BCL-2 protein expression, while downregulated the pro-apoptotic BAX and BID proteins expression in Swan-71 cells and placental explants. In both models leptin augmented BCL-2/BAX ratio. Moreover we have demonstrated that p53, one of the key cell cycle

  4. Human chorionic gonadotropin: Different glycoforms and biological activity depending on its source of production.

    Science.gov (United States)

    Fournier, Thierry

    2016-06-01

    Human chorionic gonadotropin (hCG) is the first hormonal message from the placenta to the mother. It is detectable in maternal blood two days after implantation and behaves like a super LH agonist stimulating progesterone secretion by the corpus luteum. In addition to maintaining the production of progesterone until the placenta itself produces it, hCG also has a role in myometrial quiescence and local immune tolerance. Specific to humans, hCG is a complex glycoprotein composed of two highly glycosylated subunits. The α-subunit is identical to the pituitary gonadotropin hormones (LH, FSH, TSH), contains two N-glycosylation sites, and is encoded by a single gene (CGA). By contrast, the β-subunits are distinct for each hormones and confer both receptor and biological specificity, although LH and hCG bind to the same receptor (LH/CG-R). The hCG ß-subunit is encoded by a cluster of genes (CGB) and contains two sites of N-glycosylation and four sites of O-glycosylation. The hCG glycosylation state varies with the stage of pregnancy, its source of production and in the pathology. It is well established that hCG is mainly secreted into maternal blood, where it peaks at 8-10weeks of gestation (WG), by the syncytiotrophoblast (ST), which represents the endocrine tissue of the human placenta. The invasive extravillous trophoblast (iEVT) also secretes hCG, and in particular hyperglycosylated forms of hCG (hCG-H) also produced by choriocarcinoma cells. In maternal blood, hCG-H is elevated during early first trimester corresponding to the trophoblastic cell invasion process and then decreases. In addition to its endocrine role, hCG has autocrine and paracrine roles. It promotes formation of the ST and angiogenesis through LH/CG-R but has no effect on trophoblast invasion in vitro. By contrast, hCG-H stimulates trophoblast invasion and angiogenesis by interacting with the TGFß receptor in a LH/CG-R independent signalling pathway. hCG is largely used in antenatal screening

  5. 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

  6. Residual tumor after the salvage surgery is the major risk factors for primary treatment failure in malignant ovarian germ cell tumors: A retrospective study of single institution

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    Park Jong Sup

    2011-10-01

    Full Text Available Abstract Background Malignant ovarian germ cell tumors are rare, and knowledge of their prognostic factors is limited, with little available randomized data. This study was conducted to evaluate the clinicopathologic characteristics of malignant ovarian germ cell tumors and to determine the association of their prognostic factors to primary treatment failure. Methods The medical records of 57 patients with stages I to IV malignant ovarian germ cell tumor were retrospectively reviewed, and their clinicopathologic and treatment-related data were collected and analyzed. Results The median age at the diagnosis was 23.3 years (range: 8-65 years, and the median follow-up period was 108 months (range: 48-205 months. The histological types of the tumors were immature teratoma (n = 24, dysgerminoma (n = 20, endodermal sinus tumor (n = 8, mixed germ cell tumor (n = 4, and choriocarcinoma (n = 1. 66.7% of the patients had stage I disease; 5.2%, stage II; 26.3%, stage III; and 1.8%, stage IV. After the initial surgery, 49 patients (86% received cisplatin-based chemotherapy. The five-year survival rate was 96.5%. There were six primary treatment failures, with two of the patients dying of the disease, and the median time to the recurrence was 8 months. The histological diagnosis (P P = 0.0052, elevation of beta-hCG (P = 0.0134, operation methods (P = 0.0006, and residual tumor after the salvage surgery (P P = 0.0011, Hazard ratio = 29.046, 95% Confidence interval 3.832-220.181. Conclusion Most malignant ovarian germ cell tumors have excellent prognoses with primary treatment, and good reproductive outcomes can be expected. Because primary treatment failure is associated with the residual disease after the salvage surgery, knowledge of the presence or absence of this risk factor may be helpful in risk stratification and individualization of adjuvant therapy in malignant ovarian germ cell tumors. Further large-scale prospective studies to confirm these results

  7. The clinic analysis of resistant and high - risk malignant gestational trophoblastic tumor in 20 cases%耐药及高危恶性滋养细胞肿瘤20例临床分析

    Institute of Scientific and Technical Information of China (English)

    郭兴来; 梅新宽; 钱和生; 史洪武; 亓兵

    2011-01-01

    目的 观察EMA/CO方案治疗耐药及高危妊娠恶性滋养细胞肿瘤的疗效及毒副反应.方法2007年2月至2010年2月,采用EMA/CO方案治疗耐药及高危妊娠恶性滋养细胞肿瘤20例,其中初治患者18例,耐药患者1例,复发患者1例.结果该方案治疗20例妊娠恶性滋养细胞肿瘤患者,16例完全缓解,总完全缓解率为80%.其中,侵蚀性葡萄胎的完全缓解率为88.89%,绒癌为72.73%,初治性妊娠恶性滋养细胞肿瘤为88.89%.毒副反应主要为Ⅰ-Ⅱ度恶心、呕吐和骨髓抑制.结论EMA/CO方案是治疗耐药和高危滋养细胞肿瘤的有效方案,疗效好,毒副反应较轻,可以作为首选方案,患者易接受,值得临床推广.%Objective Observation of EM A / CO regimen in the treatment resistant and high - risk malignant gestational tropho-blastic tumor efficacy and toxiciry. Methods February 2007 to February 2010, with EMA / CO regimen in the treatment resistant and high - risk malignant gestational trophoblastic tumor in 20 cases, of which 18 cases of newly diagnosed patients, patients with drug resistance in 1 case, 1 case of recurrent patients. Results The 20 patients in the treatment of malignant gestational trophoblastic tumor patients, 16 had complete remission, complete remission rate of 80% of the total. Including invasive mole in the complete remission rate of 88.89% , chorio-carcinoma of the complete remission rate of 72.73% , initial treatment of malignant gestational trophoblastic tumor complete remission rate of 88. 89%. The major side effect is I - II nausea, vomiting and bone marrow suppression. Conclusion EMA / CO treatment program is a high - risk gestational trophoblastic tumor resistant and effective program, good efficacy, less side effects, can serve as a preferred option, easily accepted by patients, deserves further study.

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

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    Cappa Stella

    2008-07-01

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

  9. DAPT抑制妊娠滋养细胞肿瘤Notch信号通路对细胞增殖和EMT影响的研究%A study on the role of notch signaling pathway in gestational trophoblastic tumor.

    Institute of Scientific and Technical Information of China (English)

    周园园; 薛艳; 田泉; 安瑞芳

    2015-01-01

    Objective:To study the significance of Notch signaling pathway in the de-velopment of gestational trophoblastic tumor and the relationship between EMT. Methods:The choriocarcinoma cell lines JAR and JEG-3 were treated with gamma-secretase inhibitor ( DAPT) . Using MTT assay to examine the activity of the two cell lines and evaluate the infulu-ence on the proliferation in JAR and JEG-3 cells of DAPT. qPCR was performed to assess mR-NA expression of Notch1. In addition,EMT related protein E-cadherin was detected by Western blot. Results:DAPT could inhibit JEG-3 cells and JAR cells growth,down-regulate the expres-sion of Notch1 mRNA,and up-regulate the expression of E-cadherin in JAR cells. Conclusions:Notch sigaling pathway and EMT may be associated with the development of gestational tropho-blastic tumor. DAPT may be a potential target of new therapeutic investigation in gestational trophoblastic tumor.%目的:探讨Notch信号通路在人妊娠滋养细胞肿瘤发生发展过程中的重要作用,及其与EMT之间的关系. 方法:采用γ-分泌酶抑制剂DAPT处理JAR和JEG-3两种人绒毛膜癌细胞株,MTT法检测两种细胞株的增殖情况,qPCR法检测Notch1 mRNA表达. Western blot法检测DAPT阻断Notch信号通路后JAR细胞中EMT相关蛋白E-cad的表达情况. 结果:DAPT能抑制JEG-3、JAR细胞生长,10μmol/L和15μmol/L DAPT作用48 h开始分别抑制JEG-3和JAR细胞生长( P0. 05);JAR细胞中,10μmol/L和15μmol/L DAPT作用组中Notch1 mRNA表达下调,两组比较差异有统计学意义( P<0 . 05 ). DAPT能上调JAR细胞中E-cad表达. 结论:Notch信号通路和EMT与妊娠滋养细胞肿瘤的发生发展有关;γ-分泌酶抑制剂DAPT或可成为妊娠滋养细胞肿瘤治疗的一个新靶点.

  10. Outcome of patients with stage II and III nonseminomatous germ cell tumors: Results of a single center

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    Ataergin S

    2007-01-01

    Full Text Available Background: The prognostic factors in nonseminomatous germ cell tumors have been mainly derived from the analysis of stage I tumors. Aims: The aim of this study was to evaluate some prognostic factors and the outcome of patients with stage II and III nonseminomatous germ cell tumors according to risk groups treated between 1993 and 2002. Settings and Design: Patients were retrospectively classified as good, intermediate and poor risk groups according to International Germ Cell Cancer Consensus Group. Materials and Methods: Biopsy specimens of 58 patients with stage II and III nonseminomatous germ cell tumors were analyzed by means of tumor histopathology, primary localization site of the tumor, relapse sites, initial serum tumor marker levels, the presence of persistent serum tumor marker elevation and the patients′ outcome. Statistical Analysis :0 Kruskall Wallis test and Mann-Whitney U test were used to determine the differences between the groups. Kaplan-Meier method was used for survival analysis and log rank test was used to compare the survival probabilities of groups. Cox proportional hazard analysis was used to determine the prognostic factors in univariate and multivariate analysis. Results: Five-year overall and disease-free survival rates were calculated as 85% and 75% in stage II; 44% and 29% in stage III cases, respectively. Fifty-seven percent of patients were classified in good risk, 9% in intermediate risk and 27% in poor risk groups. Five-year overall survival rates were 97%, 75% and 7% ( P < 0.001 and disease-free survival rates were 83%, 34% and 7% ( P < 0.001 in good, intermediate and poor risk groups, respectively. Analysis of the prognostic factors revealed that the localization site of the primary tumor ( P < 0.001, the initial stage of disease ( P < 0.001, the initial serum AFP level (p: 0.001, the initial β -HCG level (p: 0.0048, the presence of yolk sac and choriocarcinoma components in tumor (p: 0.003 and p: 0

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

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    Kala Mrinalini

    2005-12-01

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

  12. 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

  13. Liganded thyroid hormone receptor inhibits phorbol 12-O-tetradecanoate-13-acetate-induced enhancer activity via firefly luciferase cDNA.

    Directory of Open Access Journals (Sweden)

    Hiroko Misawa

    Full Text Available Thyroid hormone receptor (TR belongs to the nuclear hormone receptor (NHR superfamily and regulates the transcription of its target genes in a thyroid hormone (T3-dependent manner. While the detail of transcriptional activation by T3 (positive regulation has been clarified, the mechanism of T3-dependent repression (negative regulation remains to be determined. In addition to naturally occurring negative regulations typically found for the thyrotropin β gene, T3-bound TR (T3/TR is known to cause artificial negative regulation in reporter assays with cultured cells. For example, T3/TR inhibits the transcriptional activity of the reporter plasmids harboring AP-1 site derived from pUC/pBR322-related plasmid (pUC/AP-1. Artificial negative regulation has also been suggested in the reporter assay with firefly luciferase (FFL gene. However, identification of the DNA sequence of the FFL gene using deletion analysis was not performed because negative regulation was evaluated by measuring the enzymatic activity of FFL protein. Thus, there remains the possibility that the inhibition by T3 is mediated via a DNA sequence other than FFL cDNA, for instance, pUC/AP-1 site in plasmid backbone. To investigate the function of FFL cDNA as a transcriptional regulatory sequence, we generated pBL-FFL-CAT5 by ligating FFL cDNA in the 5' upstream region to heterologous thymidine kinase promoter in pBL-CAT5, a chloramphenicol acetyl transferase (CAT-based reporter gene, which lacks pUC/AP-1 site. In kidney-derived CV1 and choriocarcinoma-derived JEG3 cells, pBL-FFL-CAT5, but not pBL-CAT5, was strongly activated by a protein kinase C activator, phorbol 12-O-tetradecanoate-13-acetate (TPA. TPA-induced activity of pBL-FFL-CAT5 was negatively regulated by T3/TR. Mutation of nt. 626/640 in FFL cDNA attenuated the TPA-induced activation and concomitantly abolished the T3-dependent repression. Our data demonstrate that FFL cDNA sequence mediates the TPA-induced transcriptional

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

    Institute of Scientific and Technical Information of China (English)

    肖罡; 方陆雄; 邱炳辉; 漆松涛

    2011-01-01

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

  15. 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

  16. 混合性生殖细胞瘤的64层螺旋CT诊断及病理表现%Diagnosis of mixed germ cell tumor by 64-slice spiral CT and pathological manifestations

    Institute of Scientific and Technical Information of China (English)

    朱刚明; 谭琦碹; 钟胜; 李兆勇; 付东

    2011-01-01

    目的:探讨64层螺旋CT对混合性生殖细胞瘤的诊断价值.方法:回顾性分析7例经病理证实的混合性生殖细胞瘤的CT平扫及两期增强表现、病理标本及切片特征.结果:7例病灶3例位于卵巢,3例位于前纵隔.1例位于睾丸;其中3例边界清楚;各病灶密度不均匀,内见囊变、坏死区,1例可见脂肪及钙化:增强扫描静脉期较动脉期强化明显,均呈不均匀强化.病理结果2例卵黄囊瘤与成熟畸胎瘸混合型.2例卵黄囊瘤与未成熟畸胎瘤混合型.1例卵黄囊瘤、胚胎性癌、畸胎瘤混合型,1例绒癌与无性细胞癌混合型,1例精原细胞瘤、胚胎性癌、滋养细胞成分混合型.结论:64层螺旋CT对混合性生殖细胞瘤的诊断虽无特异性,但在一定程度上为肿瘤良恶性判断、临床分期提供十分重要的依据.%Objective:To investigate the diagnostic value of mixed germ cell tumor by 64 -slice spiral CT. Methods: The plain CT and two-phase enhanced CT scanning and pathological specimens of 7 cases of the tumor confirmed by pathology were retrospectively studied. Results: 3 cases were found in ovarian and 3 cases in anterior mediastinum and 1 case in testis. 3 lesions were clear boundary, with fat and calcification in 1 lesion. All the lesions were uneven density and the cystic or necrotic area could be found. Venous phase enhancement was significantly higher than other phase, showed inhomogc-neous enhance. Pathological findings: induded 2 cases of yolk sac tumor and mature teratoma mixed. 2 cases of yolk sac tumor and immature teratoma mixed, 1 case of yolk sac tumor embryonal carcinoma and teratoma mixed. 1 case of chorio-carcinoma and asexual cell carcinoma mixed, and 1 case of seminoma embryonal carcinoma and trophoblastic ingredients mixed. Conclusion: Although there is no specific by 64-slice spiral CT. To a certain degree.it can determine the benign or malignant tumor and give the important prop for clinical staging.

  17. 低危型妊娠滋养细胞肿瘤耐药高危因素探讨%Investigation the high-risk factors of drug resistance in low-risk gestational trophoblastic neoplasia

    Institute of Scientific and Technical Information of China (English)

    杨焯; 钱建华

    2011-01-01

    Objective To investigate the related high-risk factors of drug resistance in low-risk gestational trophoblastic neoplasia(GTN). Methods 452 cases of low-risk GTN patients admitted in Women's Hospital of Zhejiang University between Jan 2000 and Jan 2010 were analyzed retrospectively. According to drug resistance or not, they are divided into drug resistant group(86 cases) and non-drug resistant group(366 cases). Results The incidence of drug resistance is 19. 03%. High serous hCG level before initial chemotherapy ( especially greater than 10 000 U/L) , lung metastases in several places, distant metastasis, large lesion in uterine are apt to develop drug resistance; Drug resistance happens in choriocarcinomas more easily than invasive hydatidiform moles; In addition, serious side effects of chemotherapy, insufficient course and dose of treatment for sensitive to chemotherapy drugs, long interval time between two courses are also prone to be resistant. However, there are no difference in age, clinical stages, previous pregnancy properties, chemotherapy drugs and the way to administration, interval time between last pregnancy and initial chemotherapy ( P > 0. 05). Conclusion Chemotherapy regimens should be individualized. Combined drugs should to be administered reasonably to high-risk group as early as possible. Also, we should pay attention to comprehensive treatment such as surgery. Only in this way, we can reduce the rate of drug resistance and improve the curative effect.%目的 探讨低危型妊娠滋养细胞肿瘤耐药的相关高危因素.方法 收集2000年1月至2010年1月浙江大学附属妇产科医院收治的452例低危型妊娠滋养细胞肿瘤患者的资料,根据耐药与否分为耐药组(86例)和非耐药组(366例)进行回顾性分析.结果 耐药发生率为19.03%.初始化疗前高HCG值(尤其是血HCG值>10000U/L)者、肺部有多处转移灶、有远处转移、子宫大病灶者易发生耐药.绒癌较侵蚀性葡萄胎易发

  18. Clinical Characteristics Analysis of 291 Cases of Gestaional Trophoblastie Neoplasia%妊娠滋养细胞肿瘤291例临床特征分析

    Institute of Scientific and Technical Information of China (English)

    张烨; 薛艳; 刘腾; 张勇华; 安瑞芳

    2012-01-01

    Objective:To analyze the development of Ivasive hydatkfrform mole (IHM) and choriocarcino-ma (CC) in the past 15 years. Methods:A retrospective analysis were performed in 221 IHM patients and 77 CC patients treated in our hospital between December 1994 and December 2009. Patients were assigned into groups by each 5-year,and the clinical characteristics were compared among groups. Results:In the past 15 years,there is no significant difference in the morbidity in either IHM or CC,while the average age of patients increased significantly (IHM:P=0.001, P = 0.040;CC:P=0.050, P=0.015). The propotion of patients o-ver 40 year-old in 2005 -2009 group was significantly higher than those in 1994 ~ 1999 and 2000~2004 groups (IHM:P=0. 003,P=0.050;CC:P=0. 040,P=0. 010). The number of patient without clinical manifestations in IHM also increased gradually( P = 0. 002,P = 0. 018,P=0. 001). There is no significant difference in CC (P>0.05). Conclusions: In the past 15 years,The average age of patients increased significantly. The number of patient over 40 years increased,and the number of patients without clinical manifestations in IHM also increased gradually.%目的:了解15年妊娠滋养细胞肿瘤(GTN)临床特征的变化趋势,以提高对本病的认识.方法:回顾性分析西安交通大学医学院第一附属医院1994年12月至2009年12月收治的291例GTN患者的临床资料,其中侵蚀性葡萄胎(IHM)221例及绒毛膜癌(CC)70例.以每5年为一个阶段分组,对其临床特征进行比较分析.结果:15年间IHM及CC的发生率无明显变化.IHM及CC患者的发病平均年龄在15年中均有所上升,2005 ~ 2009年组的年龄分布明显高于1994 ~1999年组和2000~2004年组(IHM:P =0.001,P=0.040;CC:P =0.050,P=0.015),特别是年龄>40岁患者,2005 ~ 2009年组所占比例也明显高于1994~1999年组和2000 ~ 2004年组(IHM:P =0.003,P=0.050;CC:P =0.040,P=0.010).IHM及CC患者中无症状患者比例均有所上升;IHM

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

    Institute of Scientific and Technical Information of China (English)

    徐洁; 薛艳; 曾宪玲; 安瑞芳

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    梁劲荃; 赵或明; 梁睿; 主改霞; 孙润琴

    2001-01-01

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

  1. Gonadoblastoma and hepatoid and endometrioid-like yolk sac tumor: an update.

    Science.gov (United States)

    Ulbright, Thomas M

    2014-07-01

    liver involvement permitted its distinction in most cases. More recently this variant has been found to occasionally produce bile in canalicular-like structures and to stain strongly for both SALL4 and glypican 3, 2 recently described markers of yolk sac tumor. Recognition of hepatoid yolk sac tumor was followed by the description of a potential mimic, primary ovarian hepatoid carcinoma, which, however, occurred in a significantly older patient population and was occasionally associated with surface epithelial neoplasia. The endometrioid-like variant of yolk sac tumor simulated primary endometrioid adenocarcinoma. It can be suspected on routine stains because of primitive appearing nuclei, frequent subnuclear vacuoles, and in some cases association with more usual yolk sac tumor. Its recognition is now facilitated by a panel of immunohistochemical stains that are often expressed differentially in these 2 neoplasms--endometrioid-like yolk sac tumor: positive for SALL4, glypican 3, and α-fetoprotein; endometrioid adenocarcinoma: positive for cytokeratin 7 and epithelial membrane antigen. Finally, Dr Scully contributed one of the first cases in the literature of yet another nuance in the complicated world of yolk sac neoplasia, namely the development of some tumors on the background of a surface epithelial neoplasm. This is analogous to the more common development of choriocarcinoma from carcinoma and, in the case of yolk sac tumor, diagnosis is aided clinically by the usual older age of the patient and nature of the associated neoplasia. PMID:24901396

  2. 缺氧对胎盘滋养层细胞细胞周期和凋亡的影响%Effects of hypoxia on cell cycle and apoptosis of cultured trophoblastic cells

    Institute of Scientific and Technical Information of China (English)

    赵海君; 张园; 高玲玲; 高超; 崔毓桂; 刘嘉茵

    2012-01-01

    目的 观察缺氧时滋养层细胞细胞周期及凋亡变化.方法 体外培养胎盘绒毛膜癌滋养层细胞株(BeWo细胞),二氯化钴(CoCl2)处理模拟化学缺氧.噻唑蓝法测定不同浓度(0、125、250、500μmol/L)CoCl2作用不同时相(6、12、24 h)后细胞活力;流式细胞术检测250 μmol/L CoCl2处理细胞不同时间(6、12、24 h)后细胞周期和凋亡改变.结果 125 μmol/L CoCl2对细胞活力无明显影响(P>0.05);250μmol/L CoCl2作用时细胞活力呈下降趋势(P>0.05);500μmol/L CoCl2处理6、12、24 h后细胞活力均有明显下降(P<0.01).250 μmol/L CoCl2诱导构建滋养层细胞缺氧模型.250μmol/L CoCl2作用12、24 h后,G2/M期细胞比例增多(分别为0.24±0.13和0.31±0.01)(P<0.05或P<0.01).250 μmol/L CoCl2作用细胞24 h后细胞凋亡呈增加趋势(P>0.05).结论 成功构建了滋养层细胞体外缺氧培养模型.缺氧诱导滋养层细胞周期向G2/M期进展,增加细胞凋亡.%To observe the changes of the cell cycle and apoptosis induced by hypoxia in Be Wo cell line in vitro. Methods The choriocarcinoma trophoblast cell line Be Wo cells were treated with cobalt chloride (C0CI2) to mimic a hypoxia culture model in vitro. After exposured to CoCl2 of different concentrations (0,125,250,500 jumol/L) for 6,12 and 24 h, respectively, the cell viability was examined by MTT assay. After exposured to 250 jumol/L C0CI2 for 6,12,24 h,the cell cycle and apoptosis rate were detected by flow cytometry. Results There was no significant difference in cell vitality cultured with CoQ2 of 125 jumol/L(P>0. 05). After treated with 250 μmol/L CoCI2, the cell vitality displayed a downward trend(P>0, 05). While co-cultured with 500 ponol/L CoCl2 for 6,12 and 24 h, the cell viability decreased significantly(P0. 05). Conclusion A suitable cell hypoxia model in vitro has been successfully established in trophoblast cells. Hypoxia promotes trophoblast cell cycle into G2/M phase and the apoptosis in

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

    Institute of Scientific and Technical Information of China (English)

    李娜; 曲芃芃

    2014-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    于海林; 奚美丽; 李俊; 鹿欣

    2015-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

    李晓川; 冯凤芝; 向阳; 万希润; 任彤; 杨隽钧

    2015-01-01

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