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)

Male breast cancer represents about only 1% of all breast cancers. We have analysed a retrospective, multicentric series of 404 patients, initially non-metastatic, with mean age of 63 years. The 5 and 10-year overall survival rates were 65 and 36% respectively. Sixty-eight patients developed secondary cancer. From ten patients who already presented with cancer (2.5%) 3 cases corresponded to prostatic cancer treated by estrogen. Four had synchronous cancer (1%). Three and eight patients respectively had a synchronous and metachronous contralateral breast cancer (2.7% of bilateral cancer). Forty-three other patients (10.6%) developed metachronous cancer. The main tumor types were: prostate (9), lung (6), colon and rectum (6), esophagus (4). Four patients developed various hematologic malignancies and 14 patients, various types of solid tumors. From these 43 patients, 27 died; 19 as a result of secondary cancer. This represents 9% of all deaths among the 404 patients. While the bilateral cancer rate is similar to women, the second cancer rate appears to be higher in men. From hematological malignancies, chemotherapy and radiotherapy do not seem to contribute to this high incidence of second cancer.
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PMID:[Breast cancer in men: incidence and types of associated previous synchronous and metachronous cancers]. 146 95

The authors report two cases of malignant melanoma associated with hairy cell leukemia. Skin neoplasia preceded hematological malignancy in the first observation. Among reports concerning the association of malignant melanoma with hematological diseases, chronic lymphocytic leukemia, Hodgkin's lymphoma and non Hodgkin's lymphoma are preponderant. Epidemiological studies would be of value to predict the expected risk of malignant melanoma in hairy cell leukemia.
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PMID:Malignant melanoma and hairy cell leukemia. Two cases. 150 30

Much progress has been made in the therapeutic use of immunotoxins since the first clinical trials, especially in the prevention and treatment of AGVHD. This is also further discussed in this symposium by Champlin. Research in immunotoxin use has gone beyond cancer and into the treatment of immunologic disorders, such as rheumatoid arthritis and HIV infection. Before further advances can take place several problems must be overcome, including the rapid clearance of immunotoxin by the liver, the generation of anti-immunotoxin antibodies, and poor penetration by the immunotoxin in solid tumors. Other obstacles to the wide use of immunotoxins are the heterogeneity of tumor cells, the shedding of tumor antigens into the circulation, and the inability to identify neoplastic renewal cell specific antigens that are not cross-reactive with normal tissues. Despite these obstacles, the early success of immunotoxins, especially in hematologic malignancies, reinforces the feasibility of designing rational targeting reagents in cancer therapy.
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PMID:Therapeutic use of immunotoxins. 150 95

In a population-based case-control study in Sweden on multiple myeloma, the occurrence of different diseases in relatives, particularly hematologic malignancies and different types of cancer, was investigated. Through a questionnaire mailed to all living subjects, i.e. cases and controls, and to the next-of-kin for deceased subjects, information was obtained on malignant and certain other diseases among relatives. All malignant diseases reported among first-degree relatives were verified, if possible, through parochial authorities and the Swedish Cancer Register. In total, data from 239 cases with myeloma and 220 controls were analyzed. An increased risk was found for persons with first-degree relatives with hematologic malignancies (relative risk [RR] = 2.36, 90 percent confidence interval [CI ) = 0.90-6.15), and also with multiple myeloma specifically (RR = 5.64, CI = 1.16-27.51). An increased risk also was seen if the close relatives had experienced another tumor disease (RR = 1.21, CI = 0.86-1.71). Particularly, occurrence of prostatic cancer (RR = 3.11, CI = 1.25-7.71) or brain tumor (RR = 6.61, CI = 1.42-30.67) in relatives increased the risk for multiple myeloma.
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PMID:Familial occurrence of hematologic malignancies and other diseases in multiple myeloma: a case-control study. 153 15

III Purine antagonists Biosynthesis of guanine nucleotides has been reported to be up regulated in tumor cells. In guanine nucleotide synthesis, there are 2 rate-limiting enzymes, i.e. inosine monophosphate dehydrogenase for de novo synthesis and hypoxanthine guanine phosphoribosyltransferase for the salvage pathway. Therefore, agents acting on these 2 enzymes to inhibit guanine nucleotide synthesis could be expected to have a superior effect on tumor proliferation. The main antitumor agents belonging to this class are thiopurines [including 6-mercaptopurine (6 MP), 6-thioguanine (6 TG) and 6-thioinosine (TIR)], thiazofurin (TZF), and arabinofuranosylfluoroadenine (F-ara-A). In the activation of 6MP to its ribotide. PRPP is the rate limiting factor. After the ribotide is produced, it is metabolized to another active form by enzymes catalyzing purine nucleotide metabolism. The antitumor effect of TZF is enhanced by the combination of TZF with allopurinol, which increases the plasma hypoxanthine level and subsequently inhibits recovery of the reduced guanine nucleotide pool by TZF. F-ara-A induces DNA strand damage as well as inhibiting DNA synthesis and is expected to have a significant antitumor effect on slowly growing tumors. These agents are mainly effective for treating hematological malignancies. IV Antifolic agents Among the antifolates, methotrexate (MTX) is the most useful drug for both hematologic malignancies and solid tumors. MTX primarily inhibits one-carbon transfer through the inhibition of dihydrofolate reductase and thus blocks the biosynthesis of both purine and pyrimidine nucleotides. Formyl polyglutamate synthetase catalyzes folate to its polyglutamate, both the active and retention forms. It is also important as an activating enzyme as well as being a target of MTX. MTX directly inhibits thymidylate synthetase, which could be the main target during high-dose therapy. High-dose MTX therapy with leucovorin (LV) rescue is effective even for tumors which are resistant to conventional treatment. During clinical use, not only MTX levels but also those of its inactive metabolites [7-hydroxy-MTX and 2, 4-diamino-N10-methylpteroic acid(DAMPA)] should be monitored. High-dose MTX therapy with LV rescue requires precise monitoring and LV rescue should be continued until the MTX level falls below 5 x 10(-8) M. MTX is also known as the safest drug which can be directly administered to into the central nervous system. Many other antifolates are under development, among which trimetrexate might be the most promising. Studies on antimetabolites have developed side by side with research on nucleotide tumor cell metabolism, which has produced a number of the antitumor agents now available for cancer chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Clinical pharmacology of anticancer agents [Part 5] Antimetabolites (2)]. 154 70

Residual disease remains a major problem in the treatment of human neoplasia. To effectively monitor minimal leukemic activity after bone marrow transplantation (BMT), we used a competitive polymerase chain reaction (PCR) amplification technique to quantify expression of the characteristic bcr-abl fusion message in patients with chronic myelogenous leukemia (CML). Quantitative results were obtained between the 0.001% and 0.1% level in control experiments. This represents a significant advantage over cytogenetic and Southern blotting techniques routinely used to diagnose CML, which may not be sensitive below the 1% level. To illustrate the potential clinical usefulness of the quantitative PCR strategy, we compared results of bcr-abl messenger RNA expression with those obtained using cytogenetic and Southern blotting techniques, in a study of consecutive BM and peripheral blood (PB) samples from two CML patients at high risk for relapse after BMT. One patient received a syngeneic transplant during the chronic phase of the disease and relapse was apparent at the molecular level 4.5 months after BMT, while the patient was in complete clinical remission. The second patient was treated with an allogeneic BMT during the accelerated phase of the disease. A slow, but progressive decrease in bcr-abl expression was observed during the first 12 months after BMT, and expression was undetectable thereafter. Our results indicate that the competitive PCR technique can be used to monitor disease activity in patients at high risk of relapse, while the patients are in complete clinical remission, which should facilitate the early detection of relapse or the identification of progressive disappearance of leukemic activity. The approach used may serve as a model for the study of residual disease in an increasing number of other hematologic malignancies that express cancer-specific RNAs.
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PMID:Molecular quantification of residual disease in chronic myelogenous leukemia after bone marrow transplantation. 154 52

The Muir-Torre syndrome (MTS) is defined as the concurrent or sequential discovery of at least one sebaceous gland tumor and a minimum of one internal malignancy. A man with Hodgkin's lymphoma who subsequently developed an ocular sebaceous carcinoma in situ is described and the world literature of patients with the MTS and hematologic malignancies is reviewed.
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PMID:Muir-Torre syndrome in patients with hematologic malignancies. 156 50

The p53 gene is currently considered to function as a tumor-suppressor gene in various human malignancies. In hematologic malignancies, alterations in the p53 gene have been shown in some human leukemias and lymphomas. Although mutations in the p53 gene are infrequent in acute myelogenous leukemia (AML) patients, we show in this report that alterations in the p53 gene are frequent in myeloid leukemia cell lines. We studied alterations of the p53 gene in nine human myeloid leukemia cell lines by reverse transcriptase-polymerase chain reaction (RT-PCR), single-strand conformation polymorphism (SSCP) analysis, and direct sequencing. Expression of the p53 gene was not detected at all by RT-PCR in two of the nine cell lines. In these two cell lines, Southern blot analysis showed gross rearrangements and deletions in both of the p53 alleles. Six of the nine cell lines were found to express only mutant p53 mRNA by RT-PCR/SSCP analysis and direct sequencing, and wild-type p53 mRNA was not detected. Two of the mutant p53 mRNAs were shown to be products of abnormal splicing events induced by intronic point mutations. Taken together, eight of nine human myeloid leukemia cell lines expressed no or an undetectable amount of wild-type p53 mRNA. Three of the eight cell lines were growth factor-dependent. Our results suggest that inactivation of the p53 gene may be a common feature in myeloid leukemia cell lines and may play an important role in the establishment of these cell lines.
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PMID:Frequent mutations in the p53 gene in human myeloid leukemia cell lines. 157 49

The endocytosis and degradation of 125I-labeled anti-mu monoclonal antibody DA4-4 by a Burkitt's lymphoma cell line was investigated using biochemical, chromatographic, electrophoretic, radioautographic, and electron microscopic techniques. 125I-DA4-4 was rapidly internalized by Ramos cells and routed from endosomes to lysosomes. Proteolysis of radiolabeled antibodies began in a late endosomal compartment, but lysosomes were primarily responsible for the terminal degradation of 125I-DA4-4. Catabolism of 125I-DA4-4 could be inhibited by 74-95% by blocking its delivery to late endosomes and lysosomes by incubation at 18 degrees C, by neutralizing the pH in intracellular organelles with monensin or ammonium chloride, or by inhibiting lysosomal enzymes with leupeptin. Radiolabeled antibodies synthesized using the chloramine T or Iodo-Gen techniques were degraded three times faster than conjugates made using a nonmetabolizable 125I-tyramine cellobiose adduct. Five major intermediate metabolites (Mr 48,000, 42,000, 25,000, 15,000, and 10,000) were generated during the intracellular catabolism of 125I-DA4-4, but 125I-tyrosine was responsible for 95% of the small-molecular-weight metabolites released by cells into the culture medium. We anticipate that a full comprehension of the catabolism of radiolabeled antibodies by tumor cells will make possible the development of clinical interventions which will enhance the retention of radioimmunoconjugates by hematologic malignancies and improve the efficacy of radioimmunotherapy.
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PMID:Intracellular catabolism of radiolabeled anti-mu antibodies by malignant B-cells. 158 8

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


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