Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical trial of the oral form of VP 16-213 (NSC-141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9-day rest periods. Subsequently, 65 patients were given 300-400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, thrombocytopenia, alopecia, and pruritus. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Parital remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)--2 PR, 3 IMP; adenocarcinoma, lung (4 patients)--1 PR; alveolar cell carcinoma, lung (1 patient)--1 IMP; mesothelioma (4 patients)--1 IMP; ovarian cancer (12 patients)--3 PR, 3 IMP; breast cancer (20 patients)--4 IMP; colon cancer (8 patients)--2 IMP; bladder cancer (4 patients)--2 IMP; histiocytic lymphoma (7 patients)--2 PR, 3 IMP; chronic myeloid leukemia (1 patient)--1 IMP.
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PMID:A clinical trial of the oral form of 4'-demethyl-epipodophyllotoxin-beta-D ethylidene glucoside (NSC 141540) VP 16-213. 16 75

The effect of chronic administration of 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) was studied in randombred guinea pigs. DHPN, dissolved in olive oil, was injected sc into 40 animals at a dose of 250 mg/kg body weight/week for 30 weeks, and the animals were observed until their death or termination of the experiment at the end of 40 weeks. Of the 32 guinea pigs that survived more than 20 weeks of DHPN treatment, 23 developed angiosarcoma of the liver between 22 and 40 weeks. Metastases to lungs, spleen, and peripancreatic lymph nodes were observed in 8 animals. Other tumors included hepatocellular carcinoma (1 animal), cholangiocarcinoma (1 animal), chronic myeloid leukemia (1 animal), acinar cell adenoma of pancreas (1 animal), and acinar cell carcinoma of pancreas (1 animal). In addition, megalocytic change of hepatic cells with intranuclear inclusions, pelliosis hepatis, and cholangiomatous lesions were also encountered frequently in the livers.
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PMID:Induction of malignant vascular tumors of the liver in guinea pigs treated with 2,2'-dihydroxy-di-n-propylnitrosamine. 18 51

Serum vitamin B12 and vitamin B12 binding proteins (transcobalamins, TCS) were determined in patients with malaria, amoebic liver abscess, carcinoma of the liver, infectious hepatitis, cirrhosis and chronic myelocytic leukemia (CML) as well as in 60 blood donor subjects. Serum vitamin B12 in patients with infectious hepatitis, cirrhosis and CML were higher than that of the normal subjects. The values of unsaturated vitamin B12 binding capacity (UBBC) in patients with carcinoma of the liver, infectious hepatitis, cirrhosis were lower while that of patients with CML were higher than that of the normal subjects. A markedly increased TCI and decreased TCII was observed in patients with CML while these changes was much less in patients with other liver diseases. The difference was possibly due to a flooding of vitamin B12 from damaged liver cells into the circulation and the decreased synthesis of transcobalamins in patients with liver diseases while the increased granulocytes, the source of TCI, was much increased in patients with CML.
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PMID:Vitamin B12 and vitamin B12 binding proteins in liver diseases. 60 23

Chronic myeloid leukaemia and carcinoma of the breast co-existed in three women. This combination is exceedingly rare. Although the cancerogenic properties of ionizing radiation and cytostatic drugs could be held responsible for the occurrence of two malignant tumours, no definitive conclusions can be drawn in the individual case. Co-existence of leukaemia and carcinoma does not occur more frequently than could be predicted statistically from the incidence of each.
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PMID:[Co-existence of chronic myeloid leukaemia and carcinoma of the breast (author's transl)]. 105 37

During the period between 1948-1963 a total of 3,200 tumor patients were treated in the First and Second Medical Clinics of Tg.-Mures. In these tumor patients as well as the skin cancer patients who were treated with radiotherapy the authors found in 1.5% of the patients a leukocytosis of more than 20,000. In the last ten years (1964-1974), however, in the Second Medical Clinic only, 5% of 516 tumor patients showed a leukocytosis exceeding 20,000. In the first group of patients (3,200 cases) 0.03% showed more than 50,000 leukocytes, in the other group of 516 patients 0.2% showed more than 50,000 leukocytes. These values point towards a leukemoid reaction. A shift to the left to the myelocytes or beyond in the blood picture was found in the Second Medical Clinic in 10% of patients with carcinoma during the year of 1974. In 6% of the cases erythroblasts in the peripheral blood were seen, too. This deviation occurred often independent of the total number of leukocytes and was of a temporary nature. During the same time (1949-1974) 128 patients with chronic myeloid leukemia were treated in both departments as in-patients. 6 cases (i.e., 4.6%) had a chronic myelosis simultaneous with carcinoma, in one case together with an osteosarcoma. The diagnosis was confirmed in all cases by autopsy.
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PMID:[Association of chronic myelosis and cancer]. 106 57

A case of epithelial thymoma occurring synchronously with Philadelphia chromosome-positive chronic myelogenous leukemia and urinary bladder carcinoma in a 76-year-old man is described. Thymomas have been associated with numberous hematologic, collagen-vascular and autoimmune disease states, as well as with an increased incidence of nonthymic malignancy. Human thymoma-associated leukemia is, however, extremely unusual, despite the well-documented role of the thymus in leukemogenesis in experimental animals. No previous literature reports of thymoma associated with chronic myelogeneous leukemia were found. A review of long-term followup data of surviving thymoma patients is necessary to determine if an increased propensity to develop leukemia is present in present in patients with thymoma.
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PMID:Thymoma and chronic myelogenous leukemia: a case report. 106 82

Previous in vitro and in vivo studies have shown a synergism between interferon (IFN) and 5-fluorouracil (5-FU) against different tumor cell lines. In the present study we report that the combination of IFN-alpha and 5-FU has a significant effect not only on the inhibition of tumor cell growth but also on the regulation of natural killer cell-mediated cytotoxicity (NK-CMC). The addition of 5-FU to effector cell population neither affects NK cell activity nor activation of NK cells by IFN or by interleukin (IL)-2. However, pretreatment of target cells with 5-FU increased their susceptibility to NK activity and abolished the protective effect induced by IFN against NK-CMC. This dual effect of IFN-alpha and 5-FU was found to be applicable to target cells of different origins including a cervical carcinoma cell line (ME-180), a hairy cell leukemia-like cell line (Eskol), a CML cell line (K-562) and a primary culture of AIDS-related Kaposi's sarcoma cells. Similar results were found with IL-2 treatment of Eskol cells but not other cells. Combination of IL-2 with 5-FU resulted in enhancement of the sensitivity of the cells to NK activity and abolished the protection against NK-CMC. Based on these results we propose that the combination of IFN-alpha and 5-FU not only has a direct growth inhibitory effect on tumor cells but also has a regulatory role on the immunological arm of the NK-CMC. Moreover, since the combination gave the same pattern of response in different tumor cells, both NK-sensitive and NK-resistant, this combination treatment may be a candidate for clinical trials in various types of tumors.
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PMID:A dual anti-tumor effect of a combination of interferon-alpha or interleukin-2 and 5-fluorouracil on natural killer (NK) cell-mediated cytotoxicity. 137 Feb 57

The usefulness of phosphotyrosine antibodies for the detection of physiologically regulated or deregulated tyrosine kinases is discussed in this report. This rather rare enzymatic activity is shared by receptors for some polypeptide growth factors and by the products of Class 1 oncogenes. The antibodies are able to detect proteins phosphorylated on tyrosine in fibroblasts stimulated with growth factors such as EGF and PDGF. The major phosphorylated protein species are the receptors themselves, which undergo phosphorylation only after the addition of the exogenous factor and only transiently. Phosphotyrosine antibodies were able to detect the products of the retroviral Class 1 oncogenes, which are endowed with deregulated tyrosine kinase activity. In fact, in these cases a constitutive phosphorylation of the relevant proteins was observed, which occurred continuously and independently of the presence or lack of exogenous ligands. A tyrosine kinase constitutively activated in human gastric carcinoma cells was detected by P-Tyr antibodies. This molecule has been characterized at the molecular level, and the mechanisms responsible for its enzymatic activation have been investigated. The question of whether the tyrosine kinase identified is responsible for the induction and the maintenance of the transformed phenotype in gastric carcinomas remains to be answered. It is reasonable to suggest that this might be the case by analogy with other situations such as Class 1 oncogenes activated by transduction by retroviruses, abnormal expression of EGF receptors, or deregulated activity of c-abl-encoded proteins in chronic myelogenous leukemia and acute lymphoblastic leukemia. Thus, the search for deregulated kinases by means of phosphotyrosine antibodies seems to be useful for identifying new activated oncogenes in clinical oncology.
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PMID:Tyrosine kinase and control of cell proliferation. 170 Dec 90

Diagnosis- and/or prognosis-related alterations of (proto) oncogenes may be detected in neuroblastoma (N-myc), carcinoma of breast and ovary (HER2/neu), NHL (c-myc, bcl-2), CML (c-abl/bcr), and some other neoplasias. A wide variety of methods for the detection of gene alterations can be applied. The methods of detection have to be chosen according to the expected mechanisms of oncogene activation, the availability of adequately prepared tissue, and the technical standard of the laboratory. The sensitivity, specificity, and quantitation of morphological techniques (immunohistochemistry and in situ hybridization) is restricted and their results have to be interpreted most carefully. Whenever possible, at least two different techniques should be used, preferably on two different levels, i.e. RNA/DNA and protein. Furthermore, the combination of morphological and non morphological methods should be aspired.
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PMID:[Oncogenes and oncogene products--possibilities and significance of their detection]. 170 8

The usefulness of phosphotyrosine antibodies for the detection of physiologically regulated or deregulated kinases is shown in this paper. This rather rare enzymatic activity is shared by receptors for some polypeptide growth factors and by the products of class 1 oncogenes. The antibodies are able to detect proteins phosphorylated on tyrosine in fibroblasts stimulated with growth factors, such as EGF and PDGF. The major phosphorylated protein species are the receptors themselves, which undergo phosphorylation only following the addition of the exogenous factor and only transiently. Phosphotyrosine antibodies were able to detect the products of the retroviral class 1 oncogenes, which are endowed of deregulated tyrosine kinase activity. In fact, in these cases a constitutive phosphorylation of the relevant proteins was observed, which occurred continuously and independently of the presence or lack of the growth factor. A tyrosine kinase constitutively activated in human gastric carcinoma cells was detected by P-Tyr antibodies. This molecule has been characterized at molecular level and the mechanisms responsible for its enzymatic activation has been investigated. The question of whether the tyrosine kinase identified is responsible for the induction and the maintenance of the transformed phenotype in gastric carcinomas remains to be answered. It is reasonable to suggest that this might be the case by analogy with other known pathologies, such as class 1 oncogenes activated by transduction by retroviruses, abnormal expression of EGF receptors or deregulated activity of c-abl encoded proteins in CML and ALL. Thus, the search for deregulated kinases by means of phosphotyrosine antibodies seems to be useful for identifying new activated oncogenes in clinical oncology.
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PMID:Phosphotyrosine antibodies as probes for activated oncogene products endowed with tyrosine kinase activity. 172 Feb 92


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