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)

Clinicopathological analysis was performed in 19 patients diagnosed clinically with malignant histiocytosis. Ultimately, 9 patients died and 10 are still alive. All 19 had fever of unknown origin. Among the 10 surviving patients, 6 recovered with only supportive therapy such as antibiotic treatment. One recovered with steroid therapy and 2 with VP (vincristine and prednisolone) therapy. Complications due to immunodeficiency were detected in one surviving patient and 2 who died. All 9 patients who died had anemia, and 8 had thrombocytopenia. However, among survivors, only one had anemia and only 2 had thrombocytopenia. Chromosomal abnormality was detected in one patient who died. Histiocytic cells were classified morphologically into 3 types: immature, intermediate and mature. In 4 patients who died, histiocytic cells were immature, but in 4 others mature histiocytic cells were detected. In 5 of the 10 surviving patients, histiocytic cells were of the immature type. Immuno-histochemical analysis of the origin of histiocytic cells in 8 deceased patients showed T-zone histiocytes in one, T cells in one, monocyte phagocytic system (MPS) in 5, and histiocytes of unknown origin in one. Thus, malignant histiocytosis is a heterogenous entity including reactive histiocytic disorder, lymphocytic neoplasm and true histiocytic neoplasm. In histiocyte proliferative disorders, red blood cell counts and platelet counts are useful for assessing prognosis, while cytological findings only confuse this evaluation.
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PMID:[Evaluation of clinical features, cytopathological findings and prognosis of histiocyte proliferative disorders]. 140 58

Carboplatin represents an ideal candidate for dose optimization in individual patients. The excellent correlations between renal function and carboplatin total body clearance and between carboplatin area under the plasma concentration by time curve (AUC) and thrombocytopenia allow calculation of carboplatin dosages that simultaneously minimize the likelihood of toxicity and maximize the amount of drug that can be delivered. Current studies are defining the essential relationship between carboplatin AUC and the likelihood of achieving a therapeutic response in various tumor types. These quantitative relationships between carboplatin AUC and thrombocytopenia and AUC and response should be the foundation for the intelligent use of carboplatin as an individual agent and for the intelligent assessment of the beneficial or adverse effects of other agents when combined with carboplatin.
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PMID:Utility of individualized carboplatin dosing alone and in combination regimens. 141 24

Kaposi's sarcoma (KS) is the most common tumor among HIV-infected individuals, but its involvement in the gastrointestinal tract was reported long before the AIDS epidemic. Although most cases of gastrointestinal KS are asymptomatic, advanced lesions may occasionally result in a severe and life-threatening hemorrhage that requires immediate treatment. At the NYU Medical Center, we have seen three AIDS patients present with severe upper tract bleeding (> 8 U/48 h) from KS lesions of the antrum, fundus, and duodenum. The last patient was also bleeding from an ulcerated rectal KS lesion. Because all three patients had a coexisting thrombocytopenia (platelets < 50,000/mm3) and were poor operative risks, injection sclerotherapy was performed. All four KS lesions stopped bleeding, and three out of the four lesions decreased in size. To our knowledge, this is the first report of successfully using sclerotherapy to treat severe hemorrhage due to gastrointestinal KS.
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PMID:Severe hemorrhage caused by gastrointestinal Kaposi's syndrome in patients with the acquired immunodeficiency syndrome: treatment with endoscopic injection sclerotherapy. 141 7

Bleeding problems in the cancer patient may result from the effects of the tumor on hemostatic mechanisms or from the treatment of the tumor by cytotoxic and other agents. Among the tumor-related bleeding problems are disseminated intravascular coagulation, primary fibrinolysis, thrombocytopenia, acquired platelet dysfunction, and circulating inhibitors or anticoagulants. Disseminated intravascular coagulation in most solid tumors is associated with hypercoagulability, whereas in acute promyelocytic leukemia bleeding is the most common presentation. Treatment-related bleeding disorders include the common problem of thrombocytopenia secondary to myelosuppressive chemotherapy as well as the interesting microangiopathic hemolytic anemia syndrome associated with mitomycin C and other agents.
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PMID:Bleeding problems in the cancer patient. 145 14

Recombinant interleukin-2 (IL-2) produces clinical responses in approximately 20% of adult patients with renal cell carcinoma and melanoma, with both high-dose bolus and continuous infusion regimens. Because of the lower toxicity of continuous infusion, we elected to investigate in a Phase I trial a 5-day continuous infusion repeated for three weeks in children with malignancies refractory to standard therapy. Nineteen children with solid tumors and eight children with hematologic malignancies were entered into the study. The maximum tolerated dose was 3 x 10(6) U/m2/day, with dose-limiting toxicities occurring in five of seven patients treated at the 5 x 10(6) U/m2/day dose level. Dose-limiting toxicities included hypotension, hyperbilirubinemia, thrombocytopenia, pulmonary/pleural effusion, and nephrotoxicity. Serum IL-2 levels were detectable at the higher dose levels and were comparable to those observed in adult patients. Hematologic changes at the higher dose levels included rebound lymphocytosis occurring within 48 h of discontinuation of IL-2, eosinophilia, and decreased platelet counts. No objective responses to therapy were seen. We have identified a dose and schedule of administration for IL-2 in pediatric patients that can be given without intensive care unit support. Pediatric Phase II trials examining the anti-tumor activity of IL-2 given by this schedule are in progress.
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PMID:A phase I study of interleukin-2 in children with cancer. 145 95

CI-973, a platinum(II) derivative with a 2-methyl-1,4-butanediamine carrier ligand, has activity in cisplatin-resistant tumor models in vitro and in vivo. In a Phase I pharmacokinetic study, 31 patients were treated with CI-973 (24 to 50 mg/m2/day for 5 days; 28-day cycles) given i.v. over 30 min without routine antiemetic prophylaxis or hydration. Of the 29 patients evaluable for maximum tolerated dose determination, most had a performance status of 0 or 1, and most had received prior chemotherapy. Neutropenia was dose limiting at 40 and 50 mg/m2/day. Recovery from neutropenia was generally rapid with nadir counts and recovery usually occurring by Days 15 and 22, respectively. Drug-associated thrombocytopenia was uncommon and never severe, even in patients with Grade 4 neutropenia. Anemia was common, but did not appear dose related. Drug-related nausea and vomiting and changes in renal function were relatively infrequent and mild. No clinically evident ototoxicity was reported, although changes in audiograms were noted in several patients. CI-973 concentrations were measured in plasma ultrafiltrate and urine by high-pressure liquid chromatography. The harmonic mean terminal half-life was 2.0 h. The mean CI-973 renal and nonrenal clearance values were 42.3 and 37.4 ml/min/m2, respectively. The mean recovery of CI-973 in urine was 53% of the administered dose. The mean ratio of CI-973 renal clearance to creatinine clearance was 0.92. Total clearance correlated with creatinine clearance (r2 = 0.63). A relationship between toxicity, expressed as the percentage of reduction in absolute granulocyte count, and area under the CI-973 plasma concentration-time curve was found in a subgroup of "good-risk" patients. This relationship, described well by a sigmoidal Emax pharmacodynamic model, did not hold for patients with extensive prior therapy or poor performance status. A model for toxicity prediction based on dose and creatinine clearance has been derived and will be validated in future studies. The recommended Phase II dose of CI-973 is 30 mg/m2/day for 5 days.
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PMID:Phase I and pharmacokinetic study of the novel platinum analogue CI-973 on a 5-daily dose schedule. 145 62

Two neonates with a giant hemangioma associated with thrombocytopenia (Kasabach-Marritt syndrome) have been managed at Kure National Hospital. The first case was initially difficult to distinguish from overwhelming infection or other tumors but improved after radiotherapy. The second case was resistant to radiation and steroid therapy. Magnetic resonance imaging determined a tumor extending into the surrounding soft tissues better than did enhanced computed tomography. Subtotal excision of the tumor and various drugs were effective only transiently and 51Cr-labeled platelets sequestrated into the residual hemangioma. Severe thrombocytopenia persisted for approximately 15 months requiring extra care for head and body contusions, but finally improved by treatment with platelet-active drugs such as acetylsalicylic acid, dipyridamole, and pentoxifylline.
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PMID:Kasabach-Merritt syndrome in two neonates. 146 53

58-year-old man was admitted with cervical tumor and leukocytosis. Physical examination indicated splenomegaly and cervical abscess. Laboratory data showed WBC 55,000/microliters, Hb 7.9g/dl, and PLT 4.5 x 10(4)/microliters. After cure of the abscess, WBC counts were still high with 1,500-2,000/microliters monocytes, and anemia and thrombocytopenia persisted. Bone marrow aspiration showed myeloid hyperplasia and trilineage myelodysplasia. The Ph1 chromosome could not be detected. The case was diagnosed as chronic myelomonocytic leukemia and treated with oral etoposide (25mg/day). After 2 weeks, the dose was increased to 50mg, and then modified according to the blood counts. WBC counts are presently being maintained between 7,000 and 12,000/microliters, and RBC and PLT counts have gradually become normal. Splenomegaly almost disappeared and dysplastic change in bone marrow improved somewhat. At nine months following the start of chemotherapy with etoposide, remission is maintained by treatment with 25mg of etoposide on alternate days. This case suggests that low-dose etoposide is useful for treating CMMoL.
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PMID:[Chronic myelomonocytic leukemia with good response to low-dose etoposide]. 147 4

Because etoposide is a cell-cycle phase-specific drug, its degree of cytotoxicity likely relies on duration of cell exposure to a specific concentration. We investigated the maximum tolerated duration of oral etoposide treatment at doses of 100, 75, and 50 mg/d in previously treated patients with biopsy-proven, advanced cancer. "Maximum tolerated" was defined as tumor progression or hematologic toxicity (World Health Organization [WHO] grade > or = 2). The maximum tolerated duration in 19 patients given 100 mg/d was > or = 21 days, since this was the predetermined cutoff point; 3 patients discontinued etoposide because of early tumor progression, and 6 others had developed leukopenia or thrombocytopenia (WHO grade > 2) by day 21. The maximum tolerated duration in 13 patients given 75 mg/d was a median of 11 weeks (range, 2 to 19); 6 patients developed tumor progression and 6 others leukopenia (WHO grade > or = 2) requiring discontinuation of treatment. Ten patients given 50 mg/d tolerated therapy for a median of 13 weeks (range, 3 to 26 weeks); treatment was halted in seven patients because of tumor progression, two because of leukopenia (WHO grade > or = 2), and one because of stomatitis. The data from this study and others suggest that above a certain minimal plasma level, etoposide induces concentration-dependent cumulative toxicity. What remains to be determined is the minimal plasma level per tumor type. It will also be interesting to see whether myelopoiesis, thrombocytopoiesis, and erythropoiesis have differential sensitivity to etoposide, since thrombocytopenia did not occur using daily etoposide doses of 50 and 75 mg, whereas at the same doses 10 of 23 patients required erythrocyte transfusion.
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PMID:What is the optimal dose and duration of treatment with etoposide? I. Maximum tolerated duration of daily treatment with 50, 75, and 100 mg of oral etoposide. 148 50

Six infants with acute megakaryoblastic leukemia and a translocation (1;22)(p13;q13) were studied. There were five female infants and one male infant, and the age at initial examination varied from 0.8 to 6.5 months (median, 2.3 months). All the patients had hepatosplenomegaly and anemia (6 to 8.3 g/dL), and four patients had thrombocytopenia (9,000 to 63,000/mm3). The bone marrow showed prominent fibrosis in five cases and reticulin fibrosis in one patient at presentation. Crush artifact often made the histologic sections difficult to interpret, but typical megakaryoblasts could be identified in the smears. Biopsy specimens of the liver and lymph node were suggestive of a nonhematopoietic malignant condition because of the cohesiveness of the tumor cells, stromal fibrosis, and the prominent sinusoidal and vascular pattern of infiltration. Immunophenotyping of peripheral blood mononuclear cells was helpful in identifying the blasts as belonging to the megakaryoblastic lineage. Using a panel of mononclonal antibodies, it was also possible to confirm the nature of the infiltration in paraffin sections and to differentiate it from other childhood small round cell tumors, especially neuroblastoma in paraffin sections (typical staining pattern: CD45-, CD43+, vW Factor, Ulex europeus I+, CD20-, CD45RO-, synaptophysin-, chromogranin-, cytokeratin-, desmin-). This special type of infantile acute leukemia can be recognized with confidence if one is aware of its clinical features, peculiar pathologic characteristics, the morphologic features and immunophenotype of the megakaryoblasts, and the unique cytogenetic abnormality.
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PMID:Acute megakaryoblastic leukemia in infants with t(1;22)(p13;q13) abnormality. 151 33


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