• [Metastatic and hemorrhagic brain arteriovenous fistulae due to a choriocarcinoma. Case report]

• Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin.

• Massive feto-maternal hemorrhage: an early presentation of women with gestational choriocarcinoma.

• Elevated hCG and a high proportion of hCGbeta in serum preceding the diagnosis of trophoblastic disease by seven months.

• The relationship between expression of c-ras, c-erbB-2, nm23, and p53 gene products and development of trophoblastic tumor and their

• Gestational trophoblastic disease.

• [Hemoptysis in a previously healthy woman in late pregnancy]

• Restoration of TGF-beta regulation of plasminogen activator inhibitor-1 in Smad3-restituted human choriocarcinoma cells.

• Is lack of response to single-agent chemotherapy in gestational trophoblastic disease associated with dose scheduling or chemotherapy

1
UI - 11972150
AU - Fadli M; Lmejjati M; Amarti A; El Hassani MR; El Abbadi N; Bellakhdar F
TI - [Metastatic and hemorrhagic brain arteriovenous fistulae due to a choriocarcinoma. Case report]
SO - Neurochirurgie 2002 Feb;48(1):39-43
AD - Service de Neurochirurgie (Pr Bellakhdar), CHU Ibn Sina, BP 8056 Rabat-Nations Unies, Rabat, Maroc, Spain.
Brain metastasis of choriocarinoma is uncommon. These tumors develop in women of childbearing age and commonly produce signs and symptoms of subarachnoid hemorrhage, intracerebral hemorrhage, or brain tumor. Diagnosis can be established by histologic study of operative swabs and bioassay of the patient's blood, urine and cerebrospinal fluid for chorionic gonadotropin. This condition is highly chemo- and radiosensitive. We report the case of a 36-year-old woman with intracranial neoplastic fistulae. Rupture occurred 3 days after spontaneous abortion at 3 months of pregnancy. The patient presented with hemiplegia, aphasia and unclear consciousness. Left fronto-parietal hematoma was diagnosed on the CT scan, and cerebral angiography showed an arteriovenous intracranial fistulae. The hematoma and angioma were surgically removed successfully. The histological examination showed a metastatic choriocarcinoma. Surgery was followed by chemotherapy and radiotherapy. After 6 years of follow-up, complete remission has been obtained.

2
UI - 12090984
AU - Sebire NJ; Foskett M; Paradinas FJ; Fisher RA; Francis RJ; Short D;
TI - Newlands ES; Seckl MJ Outcome of twin pregnancies with complete hydatidiform mole and healthy co-twin.
SO - Lancet 2002 Jun 22;359(9324):2165-6
AD - Trophoblastic Disease Unit, Department of Histopathology, Imperial College School of Medicine at Charing Cross Hospital, London W6 8RF, UK.
We assessed 77 twin pregnancies, comprising complete hydatidiform mole (CHM) and healthy co-twin, to ascertain the risks to the mother and baby of continuing the pregnancy, versus termination. 24 women with histologically confirmed CHM and healthy co-twin pregnancies decided to have a termination. 53 women continued with their pregnancies, though two had to have terminations because of severe pre-eclampsia, and 23 spontaneously aborted (<24 weeks' gestation). 28 pregnancies lasted 24 weeks or more, resulting in 20 livebirths. Chemotherapy to eliminate persistent gestational trophoblastic disease (pGTD) was required in three of 19 women (16%; 95% CI 3-39) who terminated their pregnancies in the first trimester, and in 12 of 58 (21%; 95% CI 11-33%) who continued their pregnancies. CHM and healthy co-twin pregnancies have a high risk of spontaneous abortion, but about 40% result in livebirths, without significantly increasing the risk of pGTD.

3
UI - 12047317
AU - Lam CM; Wong SF; Lee KW; Ho LC; Yu VS
TI - Massive feto-maternal hemorrhage: an early presentation of women with gestational choriocarcinoma.
SO - Acta Obstet Gynecol Scand 2002 Jun;81(6):573-6
AD - Department of Obstetrics and Gynecology, Princess Margaret Hospital, Hong Kong.

4
UI - 12066956
AU - Vartiainen J; Alfthan H; Lehtovirta P; Stenman UH
TI - Elevated hCG and a high proportion of hCGbeta in serum preceding the diagnosis of trophoblastic disease by seven months.
SO - BJOG 2002 May;109(5):589-90
AD - Department of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland.

5
UI - 12051871
AU - Yang X; Zhang Z; Jia C; Li J; Yin L; Jiang S
TI - The relationship between expression of c-ras, c-erbB-2, nm23, and p53 gene products and development of trophoblastic tumor and their predictive significance for the malignant transformation of complete hydatidiform mole.
SO - Gynecol Oncol 2002 Jun;85(3):438-44
AD - Department of Obstetrics and Gynecology, Qilu Hospital, Jinan, People's Republic of China.
OBJECTIVE: The aims of this retrospective study by means of immunohistochemical staining were (1) to study the expression of c-ras, c-erbB-2, p53, and nm23 gene products in complete hydatidiform moles that progress to gestational trophoblastic tumor and in those that remit spontaneously after evacuation, and (2) to estimate the predictive value of the expression of these four gene products in malignant transformation of complete hydatidiform mole. METHODS: Clinical data of patients with complete hydatidiform mole were obtained by retrospective chart review. Formalin-fixed paraffin sections of 50 cases of complete mole that progressed to gestational tumor and 32 cases of complete mole that remitted spontaneously were studied immunohistochemically for c-ras, c-erbB-2, p53, and nm23 proteins. The prognostic value of the proteins for the malignant transformation of complete mole was analyzed by multiple logistic regression and stepwise logistic estimation. Sections of 30 cases of invasive mole and 19 cases of choriocarcinoma were also immunohistologically studied for expression of the proteins. RESULTS: Expression of c-erbB-2 and p53 gene products was significantly increased and expression of nm23 and c-ras products was remarkably decreased in complete hydatidiform moles that progressed into postmolar tumor compared with those that remitted spontaneously after evacuation. There was no significant difference in the expression of the four genes in invasive mole and in choriocarcinoma. A logistic estimation model for predicting malignant transformation of complete mole was established based on the expression of gene products. When the expression of four gene products was used, the predictive sensitivity of the regression model was 86.0%, and the specificity was 75.0%. The positive predictive value was 84.3%, the negative predictive value was 77.4%. Logistic stepwise regression analysis showed that the altered expression of c-erbB-2 and nm23 products had strong predictive value, while the expression of c-ras and p53 products had no significant predictive value for the malignant transformation of complete mole. CONCLUSION: The altered expression of c-ras, c-erbB-2, nm23, and p53 gene products may be important in the pathogenesis of gestational trophoblastic tumor. The decreased expression of nm23 protein and increased expression of c-erbB-2 protein are strong predictors for the malignant transformation of complete mole.

6
UI - 12057055
AU - Schorge JO; Goldstein DP; Bernstein MR; Berkowitz RS
TI - Gestational trophoblastic disease.
SO - Curr Treat Options Oncol 2000 Jun;1(2):169-75
AD - Division of Gynecologic Oncology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Patients diagnosed with molar pregnancy are treated by either suction curettage or hysterectomy, depending on their desire to preserve fertility. We use single-agent chemotherapy, preferably methotrexate, to treat low- or moderate-risk persistent trophoblastic tumors. High-risk patients who have metastatic disease are treated primarily with combination chemotherapy and, as indicated, adjuvant radiotherapy or surgery. We perform a hysterectomy in all cases of placental-site trophoblastic tumors; combination chemotherapy is used if there is evidence of metastatic disease.

7
UI - 12077881
AU - Sjovall S
TI - [Hemoptysis in a previously healthy woman in late pregnancy]
SO - Duodecim 2000;116(24):2780-2
AD - Satakunnan keskussairaala, teho-osasto Sairaalantie 3 28500 Pori. sari.sjovall@satshp.fi

8
UI - 12074587
AU - Xu G; Chakraborty C; Lala PK
TI - Restoration of TGF-beta regulation of plasminogen activator inhibitor-1 in Smad3-restituted human choriocarcinoma cells.
SO - Biochem Biophys Res Commun 2002 Jun 28;294(5):1079-86
AD - Departments of Anatomy and Cell Biology, The University of Western Ontario, London, Ont., Canada N6A 5C1.
Proliferation, migration, and invasiveness of the normal placental extravillous trophoblast (EVT) cells are negatively regulated by transforming growth factor-beta (TGF-beta), whereas malignant EVT (JAR and JEG-3 choriocarcinoma) cells are resistant to TGF-beta. These malignant cells were found to have lost the expression of Smad3. Present study examined whether Smad3 restitution in JAR cells could restore TGF-beta response. We produced a stable Smad3 cDNA-transfected clone (JAR-smad3/c) which exhibited further upregulation of Smad3 in the presence of TGF-beta1. Since anti-invasive effects of TGF-beta in the normal EVT cells were shown to be mediated in part by plasminogen activator inhibitor-1 (PAI-1) and urokinase-type plasminogen activator (uPA), we compared the expression of PAI-1 and uPA in the normal EVT, JAR, and JAR-smad3/c cells in the presence or absence of TGF-beta1. The basal levels of PAI-1 mRNA and secreted PAI-1 and uPA proteins were found to be very low in JAR and JAR-smad3/c cells, as compared to the normal EVT cells. However, TGF-beta1 upregulated PAI-1 and downregulated uPA in JAR-smad3/c cells, but not in JAR cells. Thus, resistance of choriocarcinoma cells to anti-invasive effects of TGF-beta may, at least in part, be due to loss of Smad3 expression.

9
UI - 11925117
AU - Kohorn EI
TI - Is lack of response to single-agent chemotherapy in gestational trophoblastic disease associated with dose scheduling or chemotherapy resistance?
SO - Gynecol Oncol 2002 Apr;85(1):36-9
AD - Yale Trophoblast Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA. ernest.kohorn@yale.edu
OBJECTIVE: The aim of this study was to determine whether in the management of low-risk gestational trophoblastic neoplasia (GTN) the administration of 5-day courses of 12 microg/kg actinomycin D is effective following the failure of 1.25 mg/m(2) "pulsed" actinomycin D. METHODS: Patients with low-risk GTN who failed to respond to 1.25 mg/m(2) pulsed actinomycin were switched to the 5-day course of 12 microg/kg actinomycin. RESULTS: Patients with low-risk GTN who failed to respond to pulsed actinomycin were changed to the same chemotherapy agent, actinomycin D, given as a 5-day course at 12 microg/kg. Four of the five responded and one required methotrexate to achieve remission. CONCLUSIONS: Pulsed biweekly actinomycin and pulsed weekly methotrexate have been shown to have a higher failure rate than the 5-day regimens of the same medications. This study demonstrates that failure of pulsed actinomycin may be successfully treated by a 5-day course of the same medication. It appears that with the pulsed regimens cytotoxic exposure of trophoblastic cells to the medication is too brief and the 5-day course permits more cells to be in cycle. It is suggested that, following failure of a pulsed regimen, the patient is given the same chemotherapy as a 5-day course, rather than switching from actinomycin to methotrexate or vice versa. This conserves options for chemotherapy in GTN.

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