Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercalcemia with adult T-cell leukemia (ATL) is chiefly caused by an excessive production by tumor cells of parathyroid hormone-related protein (PTHrP). We have previously reported hypercalcemic patients with solid tumors to excrete a large amount of the C-terminal fragments of PTHrP (C-PTHrP) into their urine. To elucidate whether PTHrP production correlates with or predicts the development of hypercalcemia, we studied the urinary excretion of C-PTHrP in 36 ATL patients. The urinary excretion of C-PTHrP was in the normal range (< 0.40 nmol equivalent to PTHrP (109-141)/g creatinine) in HTLV-1-positive carriers (n 3), ATL patients in complete remission (n 2) and chronic type ATL patients (n 2). It was marginally increased in seven patients in partial remission, and gradually increased as the disease progressed. In 20 patients who died without or with hypercalcemia, it was increased to 1.98 +/- 0.69 (n 9) and 7.6 +/- 2.1 nmol/g creatinine (mean +/- SD, n 11, P < 0.01), respectively. Urinary C-PTHrP excretion was significantly correlated with serum calcium and LDH levels as well as with CD25-positive cells in the peripheral blood. In four patients whose urinary excretion had been serially determined, it increased prior to the development of hypercalcemia. The findings suggest the urinary excretion of C-PTHrP to be of use as a predictor of the development of hypercalcemia in ATL patients. In ATL patients whose urinary excretion of C-PTHrP is progressively increasing, the serum calcium concentration should be carefully monitored to prevent hypercalcemic crisis.
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PMID:Urinary excretion of parathyroid hormone-related protein as a predictor of hypercalcemia in patients with adult T-cell leukemia. 146 94

Isolated mitochondria from highly glycolytic Ehrlich and AS30-D tumor cells have a 12.4- and a 2.3-fold higher cholesterol level, respectively, than that of rat liver mitochondria. The passive proton permeability of Ehrlich and AS30-D tumor inner membrane mitochondria is, respectively, 4- and 1.4-fold lower than that of rat liver mitochondrial membrane. This feature is accompanied by a lower proton leak current in tumor mitochondria. A 3.5-fold cholesterol enrichment of rat liver mitochondria decreases their passive proton permeability by a factor of 2, thus establishing a direct relationship between the cholesterol contents of mitochondrial membranes and the passive proton permeability. Creatine kinase activity is present in the cytosol of these cells and is mostly represented by the BB isoform. Since AS30-D tumor cells' treatment with the creatine analogue beta-guanidinopropionic acid decreases their life span and viability, creatinine kinase is an indispensable enzyme entering a main energy distribution pathway starting from mitochondrial ATP, through glycolysis and creatine phosphorylation, to satisfy the large energy demands of tumor cell division.
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PMID:Low mitochondrial proton leak due to high membrane cholesterol content and cytosolic creatine kinase as two features of the deviant bioenergetics of Ehrlich and AS30-D tumor cells. 151 50

Basic studies on intra-arterial hyperthermic treatment (1AHT) were conducted in rabbits implanted with VX2 tumor inside the thigh. For the purpose of determining the best temperature, saline added Adriamycin (ADM) (2 mg/body) that heated up to a predetermined objective temperature was injected. At 3 days after administration, the intratumor concentration of ADM (ITCA) and blood laboratory data were obtained. ITCA of the 53 degrees C group (1.13 +/- 0.41 micrograms/g) was significantly higher than those in the 23 degrees C group. In the 58 degrees C group, BUN, CPK, and creatinine were elevated. These data suggested that the best temperature of IAHT was about 53 degrees C. The treated rabbits were divided into 4 groups (heated saline added ADM, heated saline, non-heated saline added ADM, control) and the tumor growth rates after IAHT were investigated. The tumor size of the groups treated by heated saline was inhibited compared with that in the other two groups. There was no elevation of intratumor temperature in spite of IAHT. At 2 days after the IAHT, patho logically there were vacuolar degeneration in the arterial endothelial cells near the tumor, and narrowing of involved artery. These results suggest that the antitumor effect by IAHT is related with blood supply without hyperthermic effect.
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PMID:[Basic studies of intra-arterial hyperthermic treatment]. 153 Mar 27

A phase II clinical study of 254-S, a new anticancer platinum complex for gastrointestinal cancers, was conducted by the 254-S Gastrointestinal Cancer Study Group consisting of 16 institutions. 254-S was administered at 100 mg/m2 by intravenous drip infusion. This administration was repeated at 4-week intervals. The cases in which 254-S could be administered at least two times were regarded as complete cases evaluable for tumor response; of 75 cases registered, 53 were complete cases (29 cases with esophageal cancer, 12 with stomach cancer and 12 with colon cancer). As a result, 15 partial responses (PR) were obtained in the 29 patients with esophageal cancer and 1 PR from the 12 patients with stomach cancer, for a 51.7% and 8.3% response rate, respectively. 5 PR (55.6%) were obtained in 9 esophageal cancer patients with prior chemotherapy, including 2 PR in 4 patients previously treated with cisplatin. Major toxic effects observed were hematotoxicity including thrombocytopenia (59.0%), leukopenia (68.9%) and anemia (57.4%) and gastrointestinal toxicity such as nausea and vomiting (63.9%) and anorexia (41.0%); since grade 3 or 4 thrombocytopenia was observed with an incidence of 27.9%, careful monitoring seems to be required during the treatment with this product. Abnormal parameter changes on renal function included elevations of BUN (18.0%) and serum creatinine (9.8%). Based on these results, it was concluded that 254-S is a useful anticancer agent for the treatment of esophageal cancer.
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PMID:[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for gastrointestinal cancers. 254-S Gastrointestinal Cancer Study Group]. 155 98

DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion-toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies.
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PMID:Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor. 158 7

A phase II clinical study of 254-S, a new anticancer platinum complex, for cervical cancer was conducted by the 254-S Cervical Cancer Study Group consisting of 10 institutions. 254-S was administered at 80 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals, in principle. Forty of 45 patients registered, were eligible and 38 were evaluable for tumor response (complete cases). Complete response (CR) and partial response (PR) were obtained in 4 (10.5%) and 9 patients (23.7%), respectively, for a 34.2% response rate. Against squamous cell carcinoma, a 38.2% response rate (4 CR and 9 PR in 34 patients) was obtained. The response rate obtained in patients with no prior chemotherapy was 40.0% (2 CR and 8 PR in 25 patients), while that in patients with prior chemotherapy was 23.1% (2 CR and 1 PR in 13 patients). Major toxic effects observed were hematotoxicity, including thrombocytopenia (35.1%), leukopenia (73.0%), anemia (75.7%), gastrointestinal toxicity such as nausea and vomiting (83.8%) and anorexia (83.8%). Nephrotoxicity observed was in the form of an elevation of serum creatinine with an incidence of 2.7% and a decrease in creatinine clearance with an incidence of 21.7%. In comparison with the results obtained in the phase II clinical study for gynecological cancers in which 254-S was administered at 100 mg/m2, the response rate obtained in this study was slightly lower but thrombocytopenia and leukopenia observed were less frequent and milder. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of cervical cancer.
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PMID:[A phase II clinical study of cis-diammine glycolato platinum, 254-S, for cervical cancer of the uterus]. 160 66

The clinical course of 138 children who underwent unilateral nephrectomy and had a normal contralateral kidney at the time of nephrectomy was reviewed. The diagnosis leading to nephrectomy included obstructive uropathy in 46% of the cases, reflux or pyelonephritis in 30%, Wilms tumor in 15%, hypertension in 4%, dysplastic kidney in 2% and trauma in 2%. Mean age at nephrectomy was 7.3 years and median followup was 24.7 years. Of the 138 patients 121 (88%) are well and 17 died, including 14 secondary to metastatic Wilms tumor and 1 of renal failure. Survival of nonWilms tumor patients was similar to that of an age-matched control group. In 30 patients 24-hour creatinine clearance and 24-hour urinary protein excretion were measured. Proteinuria (greater than 150 mg./24 hours) was found in 8 of the 30 patients (27%) (p less than 0.001), renal insufficiency developed in 9 (30%) (p less than 0.0001) and hypertension occurred in 10% (p greater than 0.10). Children with an acquired solitary kidney are at increased risk for proteinuria and renal insufficiency.
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PMID:Prognosis of children with solitary kidney after unilateral nephrectomy. 164 May 59

In this pilot study of metastatic melanoma, interleukin-2 (IL-2) and cisplatin (CDDP) chemotherapy were combined using an alternating schedule designed to explore potential synergism between these modalities. Bolus IL-2 was given at a dose of 600,000 IU/kg intravenously (IV) every 8 hours, days 1 to 5 and 15 to 19, followed by high-dose CDDP administered by two different regimens: (A) 135 to 150 mg/m2 IV bolus over 30 minutes with the chemoprotectant WR-2721 910 mg/m2 or (B) 50 mg/m2 IV over 2 hours every day for 3 days. The trial design allowed an assessment of response to each phase of therapy. Among 27 assessable patients, there were 10 (37%) overall responses, including three (11%) complete responses (CRs) with durations of 9, 16, and 30+ months. Tumor regression was noted in seven patients (partial response [PR], four; minor response [MR], three; response rate [RR], four of 27 [15%]) after IL-2 administration and in 14 patients (PR, 12; MR, two; RR, 12 of 27 [44%]) after CDDP treatment, demonstrating noncrossresistance between the components of the regimen. Major PRs (greater than 90% reduction of tumor burden) or CRs were only seen in patients responding to IL-2. Toxicity during IL-2 therapy was typical for high-dose IL-2 protocols and was reversible. Among the first 20 patients treated with CDDP regimen A, there were eight episodes of grade IV nephrotoxicity (creatinine level greater than 5.0 mg/dL), including three of six patients treated with an initial CDDP dose of 135 mg/m2. This side effect was more frequent among patients with liver metastasis (P less than .05, Fisher's exact test). No significant nephrotoxicity was noted in seven patients treated on regimen B. Although ototoxicity was frequent, minimal bone marrow and neurologic toxicity was noted. There were no treatment-related deaths. This combination showed at least additive activity against melanoma, and the more protracted CDDP schedule was well tolerated. This regimen may serve as a model for future combined immunotherapy and chemotherapy trials in metastatic melanoma.
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PMID:Interleukin-2 and high-dose cisplatin in patients with metastatic melanoma: a pilot study. 165 88

Chemotherapy is the only effective method of treating unresectable hepatoblastoma. Most protocols require the administration of multiple highly toxic agents. We evaluated the ability of single-agent high-dose cis-platinum (HD-CDDP) to shrink unresectable primary hepatoblastoma to allow resection. Seven children aged 11 to 72 months had unresectable hepatoblastoma based on size and location. Initial alpha-fetoprotein (AFP) levels were between 4,900 and 1,840,000 ng/mL (mean, 555,900 ng/mL). Chest computed tomography (CT) scans obtained before beginning HD-CDDP therapy showed multiple or bilateral lung masses in 3 patients. Chemotherapy for each of the 7 children consisted of only HD-CDDP, 150 mg/m2, at 3-week intervals. HD-CDDP was stopped and prompt resection performed when AFP levels ceased to decline significantly (n = 4; mean nadir, 18,600); the corrected creatinine clearance decreased below 60 mL/min (n = 2); or, in one case, significant hemorrhage occurred within the tumor. Therefore, the number of HD-CDDP doses given preoperatively varied between 1 and 7 (mean, 3). No children required dialysis. Tumor cells in the bone marrow of one child disappeared completely after one dose of HD-CDDP. Follow-up CT scans showed complete resolution of the pulmonary metastases in 2 children, a partial response in the third, and a marked reduction of primary tumors to resectable sizes. Six children underwent tumor excision with adequate margins; parents of the seventh child refused permission for surgery. There were 2 operative deaths, 3 deaths due to local or distant disease, and 2 patients survived (postoperative follow-up, 22 and 14 months).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marked response to preoperative high-dose cis-platinum in children with unresectable hepatoblastoma. 165 88

A Wilms' tumor in a 4 year old girl did not diminish under preoperative chemotherapy following SIOP 9/GPO study guidelines. Surgery revealed an anaplastic (high grade) nephroblastoma infiltrating pancreas, transverse colon, and diaphragm. During postoperative treatment with ifosfamide, vincristine, actinomycin D, and doxorubicin, there was massive tumor growth per continuitatem in chest and abdomen within 6 weeks. Following a French study for relapsed Wilms' tumor, we gave 160 mg/m2 carboplatin and 100 mg/m2 etoposide on 5 consecutive days. After only one cycle, the tumor showed already remarkable regress. We applied six cycles of carboplatin/etoposide and a abdominal radiation. At the end of therapy, the patient was in complete remission. Side effects of chemotherapy were severe bone marrow aplasia and a moderate and reversible decrease of creatinine clearance. The combination of carboplatin and etoposide is a promising therapy in Wilms' tumor resistant to classic nephroblastoma drugs like vincristine, doxorubicin, and actinomycin D.
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PMID:[Complete remission of a highly malignant, progressive under therapy Wilm's tumor using the combination carboplatin and etoposide (VP 16)]. 166 16


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