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)

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

Patients with metastasising carcinoma of the uterine cervix or recurrent disease, in whom local treatment as surgery or radiotherapy has failed, are still an unsolved problem. Platinum-based multi-agent chemotherapies achieve overall response rates up to 60%, but side effects are serious and so far no survival benefit has been proven. Recent publications report on a synergistic effect of combination therapy using 13-cis-retinoic acid and interferon alpha-2 a in the treatment of squamous cell carcinoma of the cervix. In a pilot study we include 6 patients with locally recurrent or metastasising squamous cell carcinomas, five of the uterine cervix, one of the vulva. The systemic therapy consisted of-orally administered 13-cis-retinoic acid (80 mg q. d.) and subcutaneously injected interferon alpha-2 a (6 x 10(6) I.E. q. d.). All patients were primarily treated by surgical and/or radiation therapy. In each case chemotherapy had been either already performed or rejected by the patient. Median duration of treatment was 52 days, median survival time 107 days. Out of 6 patients 3 experienced progression of disease uninfluenced by therapy. One patient with multiple subcutaneous lymph node metastases showed mixed response for a short period of 3 weeks before progression and eventual death. One patient had no change or disease for 13 months with subsequent progression and eventual death after 22 months. One patient could not be evaluated for an allergic reaction after only 15 days of treatment. Other side effects were "flu-like symptoms", skin irritations, conjunctivitis sicca and chileitis, all WHO 1-2. Overall toxicity must be rated low compared to standard chemotherapy, but is not negligible. In our study the positive reports in literature concerning the treatment of primary advanced cervical cancer and recurrent advanced carcinoma of the skin could not be reproduced. This might be due to the small number of cases, which is a common problem in immunotherapeutic studies. Moreover, very unfavourable patient selection criteria in our study compared to primarily untreated patients may also have contributed to different response rates. However, in our opinion the tested regimen cannot be considered sufficiently effective in patients suffering from pretreated, recurrent squamous cell carcinoma of the cervix or vulva.
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PMID:[13-cis retinoic acid and interferon-alfa-2a as palliative therapy in pretreated, recurrent squamous epithelial carcinoma of the cervix uteri and vulva]. 903 64

To determine the effects of neoadjuvant chemotherapy (NAC) in the management of cervical carcinoma Stage IB2 (tumor diameter > 4 cm), we reviewed 52 surgically treated patients diagnosed between January 1987 and December 1993. There were 20 patients treated with preoperative neoadjuvant chemotherapy and 32 treated by primary radical hysterectomy. Mean tumor diameter was significantly larger in the neoadjuvant, compared with the primary surgery group (6.5 +/- 1.8 vs 5.4 +/- 0.7, P = 0.003). In the NAC group, 5 of 20 patients were treated with three courses of cisplatin, methotrexate, and bleomycin every 21 days, whereas 15 of 20 patients received three courses of cisplatin, vincristine, and bleomycin every 10 days. Postoperative adjuvant therapy consisting of either radiation or chemotherapy was employed in 13/20 patients (65%) in the NAC group and 20/32 patients (63%) in the primary surgical group. At a median follow-up of 52.5 months, 4/20 patients (20%) in the NAC group recurred vs 11/32 (34%) in the primary surgery group. The overall response rate to NAC was 90%, with 2/20 complete clinical responders and 16/20 partial responders. High-risk pathologic factors were less commonly observed in the NAC group when compared with the primary surgical group with the incidence of nodal metastases, positive vascular space involvement, undiagnosed parametrial disease, and > or = 75% depth of invasion observed in 10.0% vs 37.5%, 20.0% vs 46.9%, 0.0% vs 15.6%, and 30.0% vs 68.8%, respectively. No differences were noted in operative time or blood loss. Cox proportional-hazards analysis indicated that the most significant prognostic factor was depth of invasion. Although the patients who received neoadjuvant chemotherapy had significantly larger tumors at baseline, their 5-year survival rate was slightly higher than that of the primary surgery group (80.0% vs 68.7%, P = 0.162). Patients receiving neoadjuvant chemotherapy, despite having significantly larger pretreatment tumors, had fewer high-risk pathologic factors, postoperatively. Although this was a small, nonrandomized study, the relative improvement in pathologic response and long-term outcome associated with neoadjuvant chemotherapy was encouraging. This highlights the need for a prospective randomized clinical trial to establish whether neoadjuvant chemotherapy can significantly improve the long-term outcome of women with Stage IB2 squamous cell carcinoma of the cervix.
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PMID:Neoadjuvant chemotherapy in stage IB2 squamous cell carcinoma of the cervix. 915 50

Only 19 cases of metastases at the cannula insertion site after laparoscopy for gynecological malignancy have been reported in the literature. One case has been diagnosed with cervical squamous cell carcinoma, whereas the others have been diagnosed with ovarian cancer and borderline ovarian tumor. We present a novel case of laparoscopy-site abdominal wall metastasis from endometrial cancer after laparoscopic-assisted vaginal hysterectomy (LAVH). The 56-year-old female patient exhibited metastases of an abdominal wall trocar site and a perineal site after undergoing LAVH and laparoscopic-assisted (LA) bilateral pelvic lymph node sampling as well as LA para-aortic lymph node sampling for treating endometrial carcinoma, surgical staging IIIC, G3. The interval between the surgical extirpation of endometrial carcinoma and diagnosis of the tumor recurrence was 6 months, suggesting that overmanipulation of the diseased organ during laparoscopic surgery may have resulted in tumor spillage, intraperitoneal dissemination, and wound contamination. Although this procedure has been proven beneficial to patients with benign disease or early-stage gynecologic malignancies, laparoscopic-assisted vaginal hysterectomy may not be efficacious to eradicate advanced gynecological malignancy.
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PMID:Port site metastasis after laparoscopic-assisted vaginal hysterectomy for endometrial cancer: possible mechanisms and prevention. 969 97

Clinically evident cardiac metastases from malignant neoplasms are uncommon, occurring most commonly in association with lung and breast carcinoma, lymphoma, leukemia and melanoma. The vast majority, over 90%, present with pericardial involvement. Squamous cell carcinomas of the cervix rarely produce cardiac metastases, with endomyocardia metastases being particularly rare. Three patients are reported who presented with primary squamous cell carcinoma of the cervix and developed this pattern of metastasis, one of whom was diagnosed at endomyocardial biopsy and the other two at autopsy. The paucity of such cases in the literature emphasizes the uniqueness of this phenomenon.
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PMID:Cardiac metastasis from primary cervical squamous cell carcinoma: three case reports and a review of the literature. 928 43

Gestational choriocarcinoma (CCA) is a well-defined tumor, but there may be a surprising variation in its morphologic appearance. A 33-year-old woman with term-pregnancy six months before presented with dysfunctional bleedings that lasted about five weeks. Cervical punch biopsy and currettage revealed a polymorphic tumor which was initially diagnosed as poorly differentiated squamous cell cancer of the cervix. Methotrexat monochemotherapy was performed after histology definitely revealed CCA on the radical abdominal hysterectomy-specimen (Wertheim-Meigs). Immediately after HE, the patient developed diffuse pulmonary metastases and died of respiratory insufficiency after two courses of MTX-therapy. The autopsy confirmed metastatic CCA. The second patient, a 48-year-old women with pregnancy 24 years before, was initially treated with radical HE after misdiagnosis of cervical currettage as squamous cell cancer of the uterine cervix. The patient showed complete remission after two courses of medium risk-protocol and seven courses of high risk-protocol (CHAMOCA). All cervical curettage specimens which did not show typical squamous cell cancer. even in older women, were suspicious of CCA. CCA often shows degenerative changes or predominantly intermediate or cytotrophoblastic cellular elements. To detect the cells of most diagnostic value in CCA, the syncytiotrophoblastic elements, HCG-immunohistochemistry may be helpful.
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PMID:Postpartal gestational choriocarcinoma fatally misdiagnosed as squamous cell cancer of the uterine cervix. 944 76

Metastases to the female breast are rare and those to the male breast are even rarer. Differentiating primary from metastatic breast carcinoma is important for rational therapy and avoidance of unnecessary radical surgery. Data on five women and two men with metastases to the breast are presented here. The primary tumours in these seven cases were as follows: three bronchogenic carcinoma and one each from papillary adenocarcinoma of the ovary, adenocarcinoma of the colon, squamous cell carcinoma of the nasal cavity and squamous cell carcinoma of the cervix. In both men (who had primary lung carcinoma), mammograms showed dense glandular tissue occupying nearly the entire breast. All five women had multiple nodules. Two of these cases were unilateral and three were bilateral. The metastatic nodules were round, with slightly irregular or ill-defined margins and calcification in the single case from metastatic papillary adenocarcinoma of the ovary. Ultrasonograms demonstrated well-circumscribed low-echoic masses in all cases. In a patient with known extramammary malignancy and a breast mass, mammograms and ultrasonograms should be undertaken to exclude a primary breast carcinoma and for proper management.
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PMID:Metastatic carcinoma to the male and female breast. 950 97

Mutant p53 is frequently detected in endometrial and ovarian carcinoma, but it is rare in cervical cancers. Previous reports focused on cervical squamous cell carcinoma, whereas cervical adenocarcinoma was given little attention. We searched for p53 gene mutations in 74 primary cervical adenocarcinomas with known human papillomavirus (HPV) status. Our aim was to evaluate the prevalence of p53 mutations and to investigate their possible role as an independent prognostic factor. We found mutations in 13.5% with a high rate of G:C --> A:T transitions as observed in endometrial adenocarcinoma. As p53 mutations are more frequently detected in malignancies of high grade, high stage, and large size, this molecular event seems to play a role in the progression rather than in the induction of cervical adenocarcinoma. In our series, patients with HPV-negative tumors and patients with mutated neoplasms, irrespective of HPV infection, had a shorter survival. Yet the absence of HPV infection and presence of p53 mutations are not independent risk factors for tumor-related death after adjustment for clinicopathological confounders. The only significant and independent predictors of survival are age of patient, stage of disease, tumor grade, and presence of lymph node metastases.
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PMID:Analysis and clinical implications of p53 gene mutations and human papillomavirus type 16 and 18 infection in primary adenocarcinoma of the uterine cervix. 954 66

Intramedullary spinal metastases are rare and prior to the availability of MRI were seldom diagnosed antemortem. Lung and breast carcinoma are the most common primary sources. Cervical carcinoma is the least likely source of intramedullary spinal metastases. A case of intramedullary spinal metastases is described in a 29-year-old woman with squamous cell carcinoma of the cervix.
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PMID:Intramedullary spinal metastasis from carcinoma of the cervix. 1034 97

A 40-year-old woman was diagnosed as having stage II squamous cell cervical carcinoma and managed with radiotherapy. Three months after treatment, she presented with features suggestive of an advanced ovarian tumour including gross abdominal swelling, bilateral ovarian tumours, multiple tumour seedlings in the abdominal cavity and ascites. There was also pleural effusion. Operative findings revealed widespread intra-abdominal metastases whose histology, contrary to expectations, showed squamous cell carcinoma of cervical origin. Distant metastases from squamous cell carcinoma of the cervix are rare. A high index of suspicion is necessary to detect this unusual mode of presentation.
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PMID:Squamous cell carcinoma of the cervix simulating an advanced malignancy of the ovaries. 1045 47


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