Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the characteristics in antitumor effects of 2-trimethylsilylethylthioethylamine(KAS-010) and its conjugate with 5-FU (KAS-011), the antitumor and immunomodulating activities of these silicon compounds were examined with various systems. Both KAS-010 and KAS-011 administered orally was found to be effective to B 16 melanoma, Meth A sarcoma and MM 46 mammary carcinoma in vivo. On the other hand, KAS-011 administered orally exhibited a marked antitumor activity against L 1210 leukemia bearing mice. Furthermore, these silicon compounds inhibited significantly metastases to the lymph nodes and lung of Lewis lung carcinoma implanted id into the right ear of BDF1 mice. Especially, KAS-011 in combination with tumor amputation resulted in a remarkable prolongation of the survival time (% ILS: 93.8%) in this antimetastatic model. The cell killing effect was mainly dependent on the exposure time of these silicon compounds in cultured KB and human lung cancer (OAT) cells. Moreover, a significant increase of delayed type hypersensitivity reaction (DTHR) to sheep red blood cell (SRBC) induced by KAS-010 was seen in old aged mice. The DTHR in B 16 melanoma and Ehrlich carcinoma bearing mice treated with KAS-010 was significantly higher than those of non-treated tumor bearing mice, indicating an enhanced cellular immunity to KAS-010 possibly resulting in a remarked antitumor effect. We also found that tumor free mice treated these silicon compounds were acquired specific tumor immunity to Meth A sarcoma and MM 46 mammary carcinoma.
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PMID:[Characteristics in antitumor effects of organic silicon related compounds]. 254 47

We observed adult T-cell leukemia (ATL) associated with cancer in four of 46 patients with ATL, including gastric cancer in two, lung cancer in one, and esophageal and gingival cancer in one. The associated cancer was recognized in three of these patients prior to the diagnosis of ATL and, in one, at autopsy. One patient suffered from a skin type of ATL, two a smoldering type and one a chronic type. No information was obtained from our patients presented here as to whether HTLV-1 influenced the appearance of other cancers, or whether the treatment for cancers influenced the appearance of ATL. Further investigations are necessary to clarify the relationship between ATL and associated cancers.
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PMID:[Adult T-cell leukemia associated with cancer]. 254 56

The Cancer and Leukemia Group B (CALGB) conducted a prospective randomized trial to evaluate the role of warfarin and alternating chemotherapy in extensive small-cell lung cancer (SCCL). After stratification for sex and performance status, patients were randomly assigned to receive chemotherapy with methotrexate, doxorubicin (Adriamycin; Adria Laboratories, Columbus, OH), cyclophosphamide, and lomustine (CCNU) (MACC), or MACC plus warfarin (MACC + W), or mitomycin, etoposide, cisplatin, and hexamethylmelamine alternating with MACC (MEPH/MACC). Warfarin was given continuously to maintain a prothrombin time of one and one half to twice the control values. A total of 328 patients were enrolled, and 294 were evaluable. There was a statistically significant advantage in objective response rates (complete [CR] and partial responses [PR], respectively) for MACC + W (17% and 50%) as compared with MACC alone (8% and 43%) or MEPH/MACC (10% and 38%) (P = .012). Both failure-free survival (P = .054 Wilcoxon test) and overall survival (P = .098 Wilcoxon test) were higher on MACC + W (median, 6.6 months and 9.3 months, respectively), as compared with MACC (5.0 months and 7.9 months) and MEPH/MACC (5.0 months and 7.9 months). Toxicity was comparable among the three arms, except for increased hemorrhagic events on MACC + W, which were life-threatening in four patients (4%), and lethal in two others (2%). These data support the role of warfarin in the treatment of SCCL, but do not establish its mechanism of action. Warfarin deserves further studies in SCCL, particularly in patients with limited disease.
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PMID:A randomized trial of anticoagulation with warfarin and of alternating chemotherapy in extensive small-cell lung cancer by the Cancer and Leukemia Group B. 215 91

Combination effects of etoposide (ET) with each of 10 antitumor drugs were examined with P 388 leukemia cells in vitro and in vivo. Median effect analysis was applied for the evaluation of in vitro effect by the growth inhibition, and the in vivo effect by comparison of the increase of life span (ILS) in a combined group with the sum of ILS's in 2 single agent groups. Among 10 drugs combined with ET, cyclophosphamide (melphalan was used for in vitro study), cisplatin and 6-mercaptopurine exhibited a strong synergism both in vitro and in vivo. The combination of ET with mitomycin C, vincristine, vindesine or cytarabine produced additive or slightly synergistic effect in the both systems. However, methotrexate + ET combination showed an antagonistic effect. Although the combination of ET with doxorubicin or fluorouracil showed a slight synergism in vitro, it was antagonistic in vivo. Thus, the in vitro and in vivo combined effects were consistent in 8 of 10 drugs. The employed methods in the present studies could distinguish high efficacy of ET + cyclophosphamide and ET + cisplatin, which are clinically approved as effective combinations against lung cancer. The methods seem to be useful to assess the drug efficacy in experimental combination.
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PMID:[Combination effects of etoposide with other antitumor drugs in vitro and in vivo]. 259 58

A mortality study was carried out on 595 workers who were compensated for silicosis in the Latium region, Italy, during the period 1946-84 who died between 1 January 1969 and 31 December 1984. Respiratory disorders, tuberculosis, lung cancer, bone cancer, and cirrhosis of the liver showed significantly increased risk ratios (4.1, 3.7, 1.5, 4.1, and 1.9 respectively); excesses of brain cancer and leukaemia did not reach statistical significance. Lung cancer mortality was further analysed by age, period of compensation, final degree of disability, and occupational activity. The possible confounding role of smoking was assessed by comparing the lifetime smoking habits of a sample of silicotic subjects with those of the general male population as estimated by a national health survey; the prevalence of ever smokers among silicotic subjects (70.7%) was similar to that estimated for the general population (68.5%). The present study indicates that silicosis is associated with lung cancer even though it does not clarify the respective roles of exposure to silica and silicosis.
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PMID:Mortality pattern of silicotic subjects in the Latium region, Italy. 261 Nov 62

The chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and pharmacodynamics of etoposide are reviewed. Etoposide, although similar in chemical structure to podophyllotoxin, has a different mechanism of cytotoxicity compared with its parent compound. Etoposide may stabilize type II topoisomerase-DNA complexes, preventing rejoining of single- and double-strand DNA breaks. Etoposide may also require cellular activation into intermediates, which then bind to DNA and disrupt cellular function. Oral etoposide has an average bioavailability of 50% (range, 17%-137%), with substantial intrapatient and interpatient variability. Etoposide is widely distributed in the body and is highly bound to plasma proteins (greater than 95%). Approximately 50% (range, 20%-81%) of an etoposide dose is recovered in the urine as parent drug or glucuronide, with the remainder of the dose being unaccounted for. The disposition of etoposide in patients with renal and hepatic dysfunction is discussed. Etoposide is effective in combination with other agents against lung cancer, and response rates of 90% in small-cell lung cancer have been observed. When etoposide is used in combination with other agents, response rates of approximately 80% have been observed in patients with testicular cancer. The activity of etoposide in treating leukemia, lymphoma, and breast and ovarian carcinomas and other tumors is discussed. The impact of etoposide on prolonging survival in lung and testicular cancer is addressed, and studies evaluating the pharmacodynamics of etoposide are described. Adverse effects associated with etoposide therapy include myelosuppression, alopecia, nausea and vomiting, mucositis, and hypotension after rapid intravenous administration. Etoposide has demonstrated considerable clinical efficacy against a broad spectrum of tumors.
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PMID:Etoposide: an update. 279 80

The hematotoxicity of benzene exposure has been well known for a century. Benzene causes leukocytopenia, thrombocytopenia, pancytopenia, etc. The clinical and hematologic picture of aplastic anemia resulting from benzene exposure is not different from classical aplastic anemia; in some cases, mild bilirubinemia, changes in osmotic fragility, increase in lactic dehydrogenase and fecal urobilinogen, and occasionally some neurological abnormalities are found. Electromicroscopic findings in some cases of aplastic anemia with benzene exposure were similar to those observed by light microscopy. Benzene hepatitis-aplastic anemia syndrome was observed in a technician with benzene exposure. Ten months after occurrence of hepatitis B, a severe aplastic anemia developed. The first epidemiologic study proving the leukemogenicity of benzene was performed between 1967 and 1973 to 1974 among shoe workers in Istanbul. The incidence of leukemia was 13.59 per 100,000, which is a significant increase over that of leukemia in the general population. Following the prohibition and discontinuation of the use of benzene in Istanbul, there was a striking decrease in the number of leukemic shoe workers in Istanbul. In 23.7% of our series, consisting of 59 leukemic patients with benzene exposure, there was a preceding pancytopenic period. Furthermore, a familial connection was found in 10.2% of them. The 89.8% of our series showed the findings of acute leukemia. The possible factors that may determine the types of leukemia in benzene toxicity are discussed. The possible role of benzene exposure is presented in the development of malignant lymphoma, multiple myeloma, and lung cancer.
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PMID:Hematotoxicity and carcinogenicity of benzene. 267 98

A retrospective cohort study was performed to determine the cause of death among 5923 farmers in Iceland. Information on deaths occurring between 1977 and 1985 was obtained through the Statistical Bureau of Iceland. The vital status could be ascertained for all subjects in the study. Expected death rates were calculated, based on the national rates for males in the corresponding age groups and calendar years. The number of deaths from all causes, malignant neoplasms, lung cancer, ischaemic heart disease, respiratory diseases and accidents was less than expected in the total cohort and in nearly all subcohorts. There was no statistically significant excess risk, however: SMR for skin cancer was 2.30, SMR for Hodgkin's disease was 1.71, for leukaemia SMR was 1.60, and for brain cancer SMR was 1.23 in the total cohort. The results are in agreement with those of most previous studies of farmers, but because of the short follow-up time, the excess risk found for deaths from skin and haematological malignancies did not reach statistical significance. Further follow-up is planned in the future.
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PMID:Mortality among farmers in Iceland. 272 58

The cancer occurrence in relatives (N = 407) of 40 case probands (who had leukemia and rearrangements at the same chromosomal location as at least one of 23 recognized rare [heritable] autosomal fragile sites [Sutherland and Mattei 1987]) was compared both to cancer occurrence in relatives (N = 390) of 40 control probands (who had leukemia or other hematologic illness but no recognized chromosomal rearrangements) and to cancer incidence in the general population of the United States. Fragile-site carrier status was not determined in case or control probands. No significant excess of cancer in case relatives, compared with either control relatives or to general (SEER) population expectancies, was found. Furthermore, there was neither evidence of cancer at younger ages, when cases were compared with control relatives, nor an excess of cancer at multiple sites. Male relatives of cases did, however, show a small excess of cancer, especially in older age groups. There was a slight, but not statistically significant, excess of lung cancer in case relatives, with this deviation occurring almost exclusively in relatives of probands having rearrangements at 11q23 and having lymphoid leukemia. It is possible that heritable tendency to chromosomal rearrangement--and thus to cancer--is expressed in such a small proportion of family members that cancer excess in these families could not be detected with the numbers of relatives analyzed in this study, although there was no significant evidence for a hereditary predisposition to cancer in the families of probands with leukemia and with chromosomal rearrangements at the same apparent chromosomal location as rare fragile sites.
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PMID:Cancer in relatives of leukemic patients with chromosomal rearrangements at rare (heritable) fragile-site locations in their malignant cells. 272 77

In order to clarify the present state of terminal pulmonary infections, all autopsy cases from 1976 to 1985 reported in the annual records of autopsy cases in Kyushu University Hospital were reviewed. Of the total of 2,238 autopsy cases, pulmonary infections were present in 1,042 (46.6%) and in 595 (26.6%) pulmonary infections were fatal. Among the primary diseases associated with pulmonary infections, hematologic diseases such as leukemia and malignant lymphoma, lung cancer, esophageal cancer and cerebrovascular disease were most frequent. The pathogens of fatal pulmonary infections occurring in autopsy cases were bacteria (26.6%), Aspergillus (3.2%), Candida (1.8%), cytomegalovirus (1.7%), Pneumocystis carinii (1.1%), Mycobacterium (0.9%), Cryptococcus (0.6%) and phycomycetes (0.1%). The incidence of non-bacterial, especially fungal, pulmonary infections has increased during the recent five-year period. Among the pulmonary infections associated with lung cancer in autopsy cases, mycobacteriosis occurred more frequently than fungal infection. The incidence of fatal mycobacteriosis was more frequent in cases receiving steroids than in those not receiving steroids. Antemortem diagnosis of pulmonary infections was made in only 4.6% and 26.3% of cases of non-bacterial infection and mycobacteriosis, respectively. There was no autopsy case diagnosed before death as aspergillosis, which most frequently occurred among the fungal pulmonary infections in autopsy cases.
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PMID:[Autopsy cases of terminal pulmonary infections]. 274 58


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