Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trophoblastic disease is usually related to pregnancy and occurs in about 1 in 1300 pregnancies in Western countries. Since the advent of methotrexate therapy, trophoblastic tumors have become one of the most curable malignancies. Trophoblastic disease can develop independently of gestation, but this is very rare. We report the unusual case of a 58-year-old woman who had a metastatic choriocarcinoma 6 years after menopause and 29 years after her last pregnancy. The tumor proved to be primarily resistant to monochemotherapy and developed chemoresistance to three different polychemotherapeutic regimens. Eleven months after the diagnosis of uterine choriocarcinoma the patient died from advanced metastatic disease.
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PMID:Metastatic choriocarcinoma in a postmenopausal woman. 864 28

A 28-year-old Caucasian woman who had a missed abortion was subsequently found to have a partial hydatidiform mole. Despite twice repeated suction and evacuation of the uterus, her serum beta-human chorionic gonadotropin levels remained persistently elevated. Angiography demonstrated a large vascular uterine tumour and two small metastases in the liver. The patients was classified as having gestational trophoblastic disease stage IV. She responded well to multiagent chemotherapy. The role of imaging in the section of gestational trophoblastic disease is discussed.
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PMID:Clinics in diagnostic imaging (9). Gestational trophoblastic disease with liver metastases. 878 25

High-risk metastatic gestational trophoblastic disease (GTD) in patients who have failed primary chemotherapy has a very poor prognosis. About 25% of women with high-risk metastatic disease become refractory to EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide and vincristine) and fall to achieve a complete remission. Currently, there is no standard salvage chemotherapeutic regime for EMA-CO failure. Paclitaxel, a taxane analog extracted from the bark of the western yew (Taxus brevlfolla), has shown antitumor activity in a variety of cancer cell lines. High in vivo efficacy was confirmed in phase II trials, especially for breast and epithelial ovarian cancer patients. Recently, two in vitro studies have shown that paclitaxel is a highly effective antineoplastic agent in choriocarcinoma cell lines. We present the first clinical report of a serologic remission with high-dose paclitaxel (250 mg/m2 i.v. infusion over 24 h every 3 weeks) of a highly refractory GTD in a patient who developed brain metastasis after multiple combined chemotherapeutic regimens. The patient tolerated paclitaxel with granulocyte colony stimulating factor support very well. The remission with paclitaxel in this patient confirms its preclinical activity in high-risk, refractory GTD.
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PMID:Remission of refractory gestational trophoblastic disease with high-dose paclitaxel. 886 14

An observational study on the role of Doppler sonography in the assessment of patients with malignant trophoblastic disease was performed in an Oncology Unit of a University teaching hospital. A total of 32 consecutive patients referred for chemotherapy were recruited. Twenty-three non-pregnant and 18 women in the first trimester of pregnancy acted as controls. The patients were prospectively followed-up for 2 years. It was found that the uterine arterial resistance index and pulsatility index in patients who required chemotherapy were significantly lower when compared with the non-pregnant and pregnant controls; (Student t-test; P < 0.001 and P < 0.01, respectively). Stepwise regression analysis of beta-hCG titres on uterine artery resistance index showed significant correlation, after controlling for uterine volume (adjusted multiple R = 0.71, P < 0.00001). There were, however, no significant independent associations between the initial uterine artery resistance index and the need for chemotherapy, number of courses of chemotherapy required, duration required for the beta-hCG titre to return to normal, presence of metastatic disease, or the subsequent development of drug resistance or relapse. It was concluded that uterine arterial Doppler indices are significantly correlated with trophoblastic activity (beta-hCG titres) in malignant trophoblastic disease. However, their role in the prediction of subsequent tumour behaviour need to be assessed in larger series.
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PMID:The role of Doppler sonography in assessment of malignant trophoblastic disease. 888 94

Cutaneous metastases of gestational trophoblastic disease are extremely uncommon. A patient with metastatic, poor prognosis disease and a large metastatic lesion on her left fifth digit is presented. The clinical course and complete response to EMACO chemotherapy are outlined. The presence of metastatic disease in a reproductive-age woman requires consideration of gestational trophoblastic disease in the differential diagnosis.
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PMID:Gestational trophoblastic disease presenting as a large metastasis to the finger. 889 81

Methotrexate produced the first remission in leukemia and the first cure of a solid tumor, choriocarcinoma. Methotrexate tightly binds to dihydrofolate reductase (DHFR), blocking the reduction of dihydrofolate to tetrahydrofolic acid, the active form of folic acid. Methotrexate also directly inhibits the folate-dependent enzymes of de novo purine and thymidylate synthesis. Resistance to methotrexate may develop as a result of elevated DHFR activity or defective transport of methotrexate into malignant cells. Increased DHFR enzyme levels may also result from amplification of the DHFR gene, which is now clinically significant in selected patients. Methotrexate is an active drug in the first-line treatment of gestational trophoblastic disease (GTD) and in metastatic squamous cell carcinoma of the cervix. Since the introduction of methotrexate chemotherapy for malignant GTD, most hospitals have reported almost 100% cure rates for patients with nonmetastatic disease using single-agent regimens. Patients with low-risk metastatic disease have been treated with methotrexate and folinic acid and over 50% complete remission rates have been reported. Patients with metastatic GTD who had one or more high-risk factors benefited from initial multiagent chemotherapy, rather than waiting for acquisition of drug-resistance to single-agent therapy to start multiagent treatment. Using multiagent combination chemotherapy such as MAC (methotrexate, actinomycin D, cyclophosphamide) or EMA-CO (etoposide, methotrexate, actinomycin D and cyclophosphamide, vincristine), most investigators have reported remission in approximately 60 to 80% of patients with high-risk metastatic GTD. Although the role of chemotherapy in carcinoma of the cervix has been limited for several reasons, trial of combination chemotherapy including methotrexate has been reported. However, it is still impossible to draw definite conclusions as to whether methotrexate combined with another clearly active drug may yield a superior response rate and survival.
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PMID:[Methotrexate in gynecologic oncology]. 897 93

The placental site trophoblastic tumor (PSTT) is the rarest form of trophoblastic disease and shows a wide spectrum of symptoms. A 32-year-old women is presented with PSTT after abruptio in the 7th week of gestation which was initially misdiagnosed as cervical carcinoma on cervical punch biopsy. Therefore, a radical Wertheim-Held hysterectomy was done. The uterus showed a small tumor restricted to the cavum with no cervical infiltration, resembling in all histologic and immunohistochemical features a PSTT. The pelvic lymph nodes showed no metastases. There was no nephrotic syndrome. The patient showed no evidence of disease fourteen months after hysterectomy.
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PMID:Placental site trophoblastic tumor (PSTT) initially misdiagnosed as cervical carcinoma. 919 8

Trophoblasts are derived from the normal placenta, and they infiltrate into the endometrium and the maternal blood vessels under strict control but, unlike malignant cells, never metastasize. To understand the proliferative characteristics of trophoblasts and its related disorders, we assessed telomerase activity in chorionic villi obtained from 27 normal individuals, 9 hydatidiform moles, and 2 choriocarcinomas. Telomerase activity was detected in 13/27 (48%) normal chorionic villi samples. The detectability and the level of telomerase activity depended on gestational age; 8/10 (80%) villi samples in the first trimester (relative telomerase activity; 1.77 +/- 1.37), whereas 2/8 (25%) villi samples in the second trimester (0.78 +/- 1.52) and 3/9 (33%) in the third trimester (0.28 +/- 0.43) had telomerase activity. Telomerase activity of normal chorionic villi in the first trimester was higher than that of the third trimester (P = 0.0251). In contrast, all mole samples had increased telomerase activity compared to normal villi (3.17 +/- 2.81, P = 0.0152). Thus, a relationship may exist among cell proliferation, telomerase activity, and progression to trophoblastic disease.
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PMID:Comparison of telomerase activity in normal chorionic villi to trophoblastic diseases. 945 90

Choriocarcinoma arising in the placenta, or intraplacental choriocarcinoma, has seldom been reported, particularly in the absence of maternal metastases. Reluctance to diagnose choriocarcinoma in the presence of chorionic villi can delay diagnosis; however, timely diagnosis of choriocarcinoma is prognostically important, both for the mother and infant. We report the clinicopathologic findings in five mothers and infants in whom choriocarcinoma was identified in the placenta. None of the mothers had a history of gestational trophoblastic disease in previous pregnancies. Three placentas were similar with a single small lesion grossly suggesting a small infarct; microscopically these consisted of infarcted areas surrounded by choriocarcinoma. These three mothers were unusual in that none had metastatic choriocarcinoma; two were treated with chemotherapy and remained disease-free; the third was lost to follow-up shortly following delivery. The remaining two mothers had known pulmonary metastases at time of delivery. One of these latter two placentas contained a large marginal lesion microscopically identified as choriocarcinoma. The fifth placenta had rare microscopic foci of choriocarcinoma, and sheets of necrotic choriocarcinoma were identified in "blood clot" submitted with the placenta. In four of the five cases the choriocarcinoma appeared to be arising from otherwise normal chorionic villi, and in no case was there invasion of the villous stroma. All of the infants survived, and none had evidence of choriocarcinoma. These cases support the concept that choriocarcinoma associated with otherwise normal pregnancy arises in the placenta and may be more common than reported.
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PMID:Intraplacental choriocarcinoma associated with viable pregnancy: pathologic features and implications for the mother and infant. 968 62

The point mutations occurring in codons 12 and 13 of Ki-ras in 78 patients with colorectal carcinoma (31 Dukes' A and B, 21 Dukes' C, and 26 Dukes' D) have been determined by allele-specific oligonucleotide hybridization and sequencing. Duplicate samples of invasive primary carcinoma, adjacent normal tissue, and available lymph node and liver metastases from the same patients were microdissected from paraffin sections. There were no differences in the mutation rate between primary carcinomas and secondary deposits: 26 of 78 (33 per cent) primary carcinomas, 10 of 32 (31 per cent) lymph node metastases, and 10 of 26 (38 per cent) liver metastases. Multiple sampling revealed frequent heterogeneity within carcinomas: 9 of 26 primaries with Ki-ras mutations also contained areas of carcinoma with only the wild-type gene, implying that Ki-ras mutation, even when present in a colonic carcinoma, may not have been necessary for establishing the malignant phenotype. Also, 2 of 26 (8 per cent) Dukes' D patients had a mutation in their primary carcinoma but none in liver metastases and 6 of 47 (13 per cent) Dukes' C and D patients had mutations in liver or lymph node metastases but none in the primary carcinoma. Such heterogeneity may modify the effectiveness of novel therapies targeting mutant Ki-ras function, such as farnesyltransferase inhibition. Mutation of codon 12 from GGT (glycine) to GTT (valine) was more prevalent in primary and metastatic deposits of Dukes' C/D carcinomas (P = 0.01) than in primary carcinomas from Dukes' A/B patients. Mutations of codon 12 to GAT, AGT, GCT and codon 13 GGC to GAC were also found, but no correlation with carcinoma aggressiveness was apparent. Follow-up of 71/78 patients (up to 12 years) revealed decreased overall survival (P = 0.001) in patients with the GGT to GTT transversion in codon 12, even when the analysis was restricted to Dukes' D cases, supporting the suggestion that this mutation may confer a more aggressive phenotype in colorectal carcinoma.
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PMID:Heterogeneity of mutant versus wild-type Ki-ras in primary and metastatic colorectal carcinomas, and association of codon-12 valine with early mortality. 971 38


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