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)

This report describes a novel method of immunochemotherapy; the active immunization to the drug 5-fluorouracil (5-FU) with enhanced antitumor activity resulting from its subsequent systemic administration. Two metastasizing carcinomas in the Fischer strain (F344) rat have been used: a chemically induced bladder carcinoma (FBCa) and a spontaneous mammary adenocarcinoma (MACa). Both tumors grow rapidly and result in 100% mortality within 10 wk of implantation. Neither tumor is sensitive to systemic 5-FU alone. Intradermal sensitization to 5-FU before FBCa tumor implantation, followed by 5-FU administered systemically, resulted in significant tumor regression and improvement in survival with eradication of all tumor and cure in 20% of animals. A similar antitumor effect was observed with the MACa. A comparable drug effect was observed when methotrexate sensitization was given before FBCa implantation followed by systemic MTX. Specificity to the sensitizing drug was demonstrated by the lack of effect of sensitization with either 5-FU or MTX unless followed by systemic therapy with the requisite sensitizing agent. Sensitization to 5-FU has also been assessed after FBCa implantation followed by resection of the local tumor. Resection was performed after distant tumor metastases had occurred, and was followed by systemic 5-FU therapy. Whereas tumor resection alone failed to cure any animal, sensitization to 5-FU increased cure rate fourfold over animals receiving systemic 5-FU alone. Antibody to 5-FU in the sera of sensitized animals has been suggested by an immunoenzymatic staining technique and its specificity confirmed in a radioimmunoassay. It is postulated that a combination of the systemic agent and the antibody elicited to it by sensitization produces the significant antitumor effect observed. The antitumor effect observed with this new approach to immunochemotherapy warrants further experimental and clinical study.
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PMID:Sensitization to low dose 5-fluorouracil. Subsequent enhancement of its systemic antitumor effect in the rat. 710 95

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

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

Sequential chemotherapy with methotrexate and 5-fluorouracil (MTX/5-FU) for advanced gastric cancer was given 29 patients. The procedure consisted of weekly MTX 100 mg/m2 (i.v.) followed three hours later by 5-FU 600 mg/m2 (i.v.) with leucovorin rescue on each of the following two days. Nine of 28 patients (32.1%) showed partial response to this treatment. Response rates were 28.6% in the 21 cases with poorly differentiated adenocarcinoma and 42.9% in the 7 cases with well- or moderately-differentiated adenocarcinoma. This procedure was especially effective for primary lesions (PR 9/20: 45%) and lymphnode metastases (CR 4 + PR 4, 8/17: 47.1%). Side effects were mild leukopenia and G-I symptoms such as nausea, diarrhea and loss of appetite, except in 1 patient who died of severe myelosuppression with sepsis. We concluded that sequential MTX/5-FU therapy is fairly effective and the adjuvant chemotherapy of choice for advanced or recurrent gastric cancer with not only poorly differentiated adenocarcinoma but also well- or moderately-differentiated adenocarcinoma.
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PMID:[Sequential chemotherapy with methotrexate and 5-fluorouracil for advanced gastric cancer]. 953 Mar 60

We report here on treatment results of consecutive CCLSG NHL studies (NHL855, 1985-1989; NHL890, 1989-1996). The NHL855 protocol consisted of an induction phase of five drugs (VCR, PRD, CPM, DXR, and high-dose MTX) and a maintenance phase of 7 drugs. The probabilities of EFS at 7 years were 78% (SE, 10%) for the patients with localized disease, and 38% (SE, 7%) for those with advanced disease. In the NHL 890 protocol, the patients were assigned to two different treatment groups according to their histology and received different consolidation therapy; non-lymphoblastic subtype was treated almost identically to NHL855 while LASP and VP-16 were newly added for the lymphoblastic subtype. The 7-year EFS improved to 91% (SE, 6%) for localized disease, and 61% (SE, 6%) for advanced disease. A remarkable improvement was particularly evident for lymphoblastic type with mediastinal mass. Optional trial of high-dose sequential chemotherapy and peripheral blood progenitor cell auto grafting resulted in an unfavorable outcome. The 7-year EFS according to main histological subgroups were as follows: 84% (10%) for large cell type, 67% (11%) for Burkitt's-type, 58% (10%) for lymphoblastic type. Secondary cancer occurred in two of the 163 patients studied. Both patients were AML (M0/M4) and MLL rearrangement was detected in the M4 case.
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PMID:[Treatment of children with non-Hodgkin's lymphoma with CCLSG NHL 855/890 protocols long-term outcome and incidence of secondary malignancies]. 959 95

A novel monoclonal antibody has been developed that reacts strongly with human prostatic cancer, especially tumors of high grade. This antibody (7E11C-5) is currently in Phase 3 trials as an imaging agent for metastatic disease. We have cloned the gene that encodes the antigen that is recognized by the 7E11C-5 monoclonal antibody and have designated this unique protein prostate-specific membrane (PSM) antigen. PSM antigen is a putative class II transmembranous glycoprotein exhibiting a molecular size of Mr 94,000. Functionally, class II membrane proteins serve as transport or binding proteins or have hydrolytic activity. Preliminary studies have demonstrated binding of pteroylmonoglutamate (folate) to membrane fractions that also cross-reacted with the PSM monoclonal antibody. We observed substantial carboxypeptidase activity as folate hydrolase associated with PSM antigen. The purpose of our study was to demonstrate that human prostatic carcinoma cells expressing PSM antigen exhibit folate hydrolase activity using methotrexate triglutamate (MTXGlu3) and pteroylpentaglutamate (PteGlu5) as substrates. Isolated membrane fractions from four human prostate cancer cell lines (LNCaP, PC-3, TSU-Prl, and Duke-145) were examined for folate hydrolase activity using capillary electrophoresis. After timed incubations at various pH ranges and in the presence and absence of thiol reagents, separation of pteroyl(glutamate)n derivatives was achieved with an electrolyte of sodium borate and SDS, while absorbance was monitored at 300 nm. The results demonstrate clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3. The membrane-bound enzyme is an exopeptidase, because it progressively liberates glutamates from MTXGlu3 and PteGlu5 with accumulation of MTX and PteGlu1, respectively. The semipurified enzyme has a broad activity from pH 2.5 to 9.5 and exhibits activity maxima at pH 5 and 8. Enzymatic activity is maintained in the presence of reduced glutathione, homocysteine, and p-hydroxymercuribenzoate (0.05-0.5 mm) but was inhibited weakly by DTT (>/=0.2 mm). By contrast to LNCaP cell membranes, membranes isolated from other human prostate adenocarcinoma cells (PC-3, Duke-145, and TSU-Pr1) did not exhibit comparable hydrolase activity, nor did they react with 7E11-C5 monoclonal antibody. After transfection of PC-3 cells with a full-length 2.65-kb PSM cDNA subcloned into a pREP7 eukaryotic expression vector, non-PSM antigen-expressing PC-3 cells developed immunoreactivity to 7E11-C5 monoclonal antibody and demonstrated folate hydrolase activities and optimum pH activity profiles identical to those of LNCaP cells. The membrane-bound enzymes from both LNCaP- and PC-3-transfected cells also have a capacity to hydrolyze an alpha-linked glutamyl moiety from N-acetyl-alpha-aspartylglutamate. We have identified that PSM antigen is a pteroyl poly-gamma-glutamyl carboxypeptidase (folate hydrolase) and is expressed strongly in human prostate cancer. Cancer cells that express this enzyme are resistant to methotrexate therapy. Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance.
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PMID:Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells. 981 19


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