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)

A number of papers have been published on the clinical correlation of the expression of the 67 kDa laminin binding protein (LBP) with the metastatic potential of solid tumors. Both mRNA and protein expression levels have been reported, but both the relationship between them and the molecular nature of the 67 kDa surface product remain unclear. We have utilized a homotypic overexpression system to investigate the cell surface presentation of the 67 kDa LBP and the contribution of this protein to the invasive phenotype of cultured cell lines. We report here that the cellular mRNA levels do not directly reflect the levels of the 67 kDa LBP observed on the cell surface in this overexpression system. Methotrexate amplification of transfected plasmids expressing the 67 kDa LBP leads to an initial elevation of both the LBP mRNA and surface protein levels. This is accompanied by an altered, more flattened, cell morphology. Later, apparent adaptation of the cells to methotrexate is accompanied by a down-regulation of the surface expression of the protein. mRNA levels, however, remain elevated. A nine amino acid sequence, CDPGYIGSR (peptide 11), within the beta chain of laminin 1 has been identified as a probable binding domain for the 67 kDa LBP. Previous studies have identified a region of the 67 kDa LBP which may be involved in laminin interaction, although not necessarily via the peptide 11 domain. We have identified a second site within the amino acid coding sequence of the 67 kDa LBP which also shows biological activity both in vitro and in vivo. A peptide with this sequence, LBP residues 205-229, binds laminin-1 in a peptide 11 inhibitable manner. The receptor-derived peptide modulates invasion of basement membrane matrix in vitro and inhibits experimental lung colony formation when injected along with B16BL6 mouse melanoma cells. However, pretreatment of the melanoma cells with the peptide enhances lung colony formation. Thus, the interaction of the 67 kDa LBP with basement membrane matrix appears to involve a complex series of events including multiple adhesive sites and tight regulation of cell surface expression.
Clin Exp Metastasis 1995 Sep
PMID:Control pathways of the 67 kDa laminin binding protein: surface expression and activity of a new ligand binding domain. 764 20

Cancer of the penis is the rarest male genital tract tumour, accounting for only 1% of all cancers in men. It is highly lymphophilic. Complex diagnostic problems are posed by both the primary tumour and lymph nodes. The prognosis depends on the degree of lymphatic spread. This cancer occurs in uncircumcised men with poor personal hygiene. The diagnosis is based on biopsy of all persistent lesions on the glans. In every case, treatment requires complete removal of the prepuce. Small noninvasive cancers can be treated by application of radioactive iridium wire. Inguinal lymph node biopsy is performed on a palpable node. Small cancers with lymph node involvement requires extensive inguinal lymph node dissection. Adjuvant irradiation is only indicated when the tumour has extended beyond the lymph node capsule. Cancer invading the corpora cavernosa has a poor prognosis (T3). It justifies large amputation of the penis with perineal urethrostomy and extensive lymph node dissection in the presence of positive nodes. Advanced cancers with unresectable lymph nodes (inguinal and iliac) and/or metastases (pulmonary) require combination chemotherapy with MTX-cisplatin-bleomycin.
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PMID:[Cancer of the penis. 1989]. 789 18

Far-advanced gastric carcinoma of the stomach remains a lethal disease, showing a particularly poor prognosis in the patients with linitis plastica type. Considering the high potential for biological malignancies, we attempted preoperative induction (neoadjuvant) chemotherapy against far-advanced cancer associated with distant metastases. Anticancer drugs used in this study were FAM or sequential MTX/5-FU. Neoadjuvant chemotherapy was carried out on 24 patients prior to surgery. The response to chemotherapy showed shrinking of massive nodal involvement in 50% (5/10) and complete disappearance of malignant ascites in 87.5% (7/8). The morphological improvement of primary gastric lesions was obtained in 9 out of 24 cases (37.5%). In 15 cases (68.2%) total gastrectomy was done with extended lymph node dissection. In one of 9 cases showing marked improvement, no viable cancer cells were seen in whole stomach associated with multiple foci of granulomatous lesions of regional nodes after 3 cycles of MTX/5-FU. Disease-free survival of neoadjuvant group showed a significant prolongation of its median survival of 14 months, compared to that of 4-6 months in the surgery alone group. Our result leads to the conclusion that the patients whose tumor was effectively destroyed by neoadjuvant chemotherapy had a good prognosis.
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PMID:[Neoadjuvant chemotherapy for far-advanced gastric carcinoma]. 812 83

An advanced gastric cancer patient with multiple retroperitoneal lymph node metastases and bone metastases was treated with sequential MTX and 5-FU. Complete response was obtained against both gastric primary lesion and retroperitoneal lymph nodes observed endoscopically and by computed tomography. Partial response was obtained against bone metastases observed by bone scintigraphy. Side effects of the chemotherapy were not observed.
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PMID:[A case of nonresectable gastric cancer treated by sequential methotrexate and 5-fluorouracil]. 829 4

The phase I trial in breast cancer conducted by Peters et al. defined a regimen of high-dose chemotherapy consisting of cyclophosphamide, cisplatinum and BCNU (CPA/cDDP/BCNU). In chemotherapy-resistant metastatic disease, 23% of patients achieved complete remission followed by early relapse. In a phase II study, 53% of stage IV patients with no prior treatment achieved complete response (CR) with 16% progression-free at five to nine years post-transplant. Chemically debulking with an Adriamycin, 5FU, and Methotrexate regimen (AFM) to minimal tumor burden achieved 68% CR, with approximately 20% disease-free patients at 36 months. Other high dose chemotherapy regimens have been developed, again demonstrating in stage IV patients complete remissions in excess of 65% and progression-free survival rates of 20-30%.
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PMID:Positive selection and ex vivo expansion of hematopoietic progenitors as autografts for high-dose chemotherapy, potential importance in patients with bone metastases. 885 28

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

A case of poorly differentiated adenocarcinoma of the small bowel with extensive lymph node metastases is herein presented, which responded to methotrexate/5-fluorouracil (MTX/5-FU) sequential therapy. The lymph node metastases disappeared completely after 10 months of treatment. After recurrence, combination therapy with radiation, hyperthermia, and cisplatinum were also effective in reducing the degree of nodal swelling while still allowing the patient to maintain her accustomed lifestyle for a prolonged period of time. Further multi-institutional studies are still needed, however, to fully assess this new therapeutic regimen for small bowel cancers.
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PMID:Small intestinal cancer with extensive lymph node metastases showing complete remission by methotrexate/5-fluorouracil sequential therapy: report of a case. 903 2

Sequential MTX/5-FU therapy (intravenous route) is powerful chemotherapy especially for poorly differentiated adenocarcinoma of the stomach and its peritoneal metastases. The authors had proposed the idea of intraperitoneal sequential MTX/5-FU chemotherapy for potential peritoneal metastases and micrometastases from advanced gastric carcinoma. This experimental study was planned to confirm this experimentally. Peritoneal seeding model of nude mice was made by the intraperitoneal inoculation of human gastric cancer cell line MKN-45. Control group (n = 5) had no treatment. The intraperitoneal (i.p.) group and intravenous (i.v.) group underwent the treatments on the 7th, 14th, and 21st day after cell implantation. Experimental chemotherapies consisted of intraperitoneal injection of MTX (15 mg/kg, 1.5 ml saline) and 5-FU (50 mg/kg, 1.0 ml saline) for i.p. group and intravenous injection of MTX (15 mg/kg, 0.2 ml saline) and 5-FU (50 mg/kg, 0.2 ml saline) for i.v. group. Interval time between MTX and 5-FU administration was 2 hours. On the 35th day after the cell implantation necropsies were performed. Counting of peritoneal metastatic nodules revealed the number of nodules of control group. (14.2 +/- 6.7) > i.v. group (5.3 +/- 4.1) > i.p. group (0.41 +/- 0.7) (p < 0.05). Weight of omental tumors showed Control group (0.246 +/- 0.136 g) > i.v. group (0.140 +/- 0.068 g) > i.p. group (0.051 +/- 0.017 g) (i.v.-i.p., p < 0.01). The mouse body weight decrease less in the i.p. group than in the i.v. group (p < 0.05) throughout this experiment. The results of this experiment demonstrated intraperitoneal sequential MTX/5-FU therapy was more effective than intravenous sequential MTX/5-FU therapy for potential peritoneal seeding and peritoneal micrometastases from the gastric cancer. Moreover, the side effect of intraperitoneal administration was milder than by the intravenous route.
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PMID:[Experimental study on intraperitoneal sequential MTX/5-FU therapy for peritoneal seeding in comparison with intravenous administration]. 938 24

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

During the last three decades numerous randomized trials have been conducted in head and neck squamous cell carcinoma. The issue of pre- vs post-operative radiotherapy in advanced cancers was settled in the late 70s in favour of the latter approach and new fractionation schemes are currently being investigated, with no definite answers as yet. There is no uniform policy regarding the problem of elective neck dissection in early stage anterior oral cavity carcinoma. Often some chemotherapeutic regimen is involved in clinical trials in an attempt to improve on the standard of surgery and radiotherapy. Neoadjuvant chemotherapy has never been proven to benefit patients with advanced squamous cell carcinoma of the head and neck despite being able to decrease the rate of distant metastases. Chemotherapy given prior to or simultaneously with definite radiotherapy seems to offer the best chances for preserving vital organs, such as the larynx. Methotrexate is still the least toxic and most potent drug in recurrent or metastatic disease. The chemoprotective effect of low-dose isotretinoin on multiple primaries in the head and neck has yet to be evaluated.
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PMID:Messages from completed randomized trials in head and neck cancer. 948 14


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