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

Seven cases of post-transfusion hepatitis type B [PTH(B)] were investigated. PTH(B) developed in 4 patients more than 65 years old and in 4 patients after treatment of a malignant disease (2 cases of gastric cancer and one each of ovarian cancer and chronic myelogenous leukemia, respectively). The mean incubation period was 78 days (70-90) in patients with non-malignant diseases and 147 days (105-200) in patients with malignant diseases. The symptoms of acute hepatic failure developed in 6 patients and 5 of them expired. One fatal case revealed 4 units of blood and an investigation of 4 donors revealed that one of them was an HBsAg carrier with negative serum HBsAg by the reverse passive hemagglutination (RPHA) method. From these results, it was concluded that compromised hosts such as aged patients or patients with malignant diseases are apt to contract severe PTH(B) with a long incubation period when the transfused blood contains small amounts of HBV.
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PMID:Post-transfusion hepatitis type B: long incubation period and poor prognosis in compromised hosts. 274 36

Marrow transplantation is effective treatment for a number of hematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is successful in the treatment of aplastic anemia with 70-85% long-term survival. It offers 10-30% apparent cures for patients with acute leukemia who have relapsed at least once, and for those with chronic myelocytic leukemia in blast crisis. Although still somewhat controversial, it appears to be the treatment of choice for patients with acute nonlymphoblastic leukemia in first chemotherapy induced remission, and for those with chronic myelogenous leukemia in the chronic phase since approximately 50-60% of these patients experience long-term, disease-free survival. Patients with acute lymphoblastic leukemia grafted in second or subsequent remission may expect a 30% "cure" of their disease. Marrow grafting is the only effective treatment for many patients with inherited immunologic deficiencies and certain genetic storage diseases. Cures of congenital Fanconi's anemia, Blackfan-Diamond anemia, osteopetrosis, paroxysmal nocturnal hemoglobinuria and thalassemia major have been achieved. Marrow transplantation is being explored for the therapy of patients with lymphoma, Hodgkin's disease, preleukemia, multiple myeloma, hairy cell leukemia, small cell lung cancer, testicular cancer, ovarian cancer and neuroblastoma. Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. More recently, marrow transplants from HLA-nonidentical family members and even from unrelated donors have been successfully explored.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marrow transplantation: the Seattle experience. 391 47

A 59-year-old woman was treated with surgery followed by monthly injections of the alkylating agent thiotepa for a granulosa cell tumor of the left ovary. Chemotherapy was continued for 22 years. At the age of 84, chronic myelogenous leukemia (CML) developed. Cytogenetic studies revealed incomplete trisomy of the long arm of chromosome No. 1 as the only karyotypic abnormality. No Philadelphia chromosome was detected. The significance of trisomy 1q as an isolated cytogenetic abnormality in CML and the occurrence of CML following treatment of ovarian cancer are discussed.
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PMID:Philadelphia-chromosome-negative chronic myelogenous leukemia with incomplete trisomy 1q following chemotherapy for ovarian carcinoma. 393 61

A prospective study of 1572 women treated with radiotherapy for cervical (1478 women) and ovarian cancer (94 women) was done. Patients had been followed clinically and especially by blood tests between 1961 and 1981, comprising 8990 woman-years (WY). Following radiotherapy, 5 patients developed non-lymphocytic leukemia [2 acute myeloblastic leukemia (AML), 1 acute monocytic leukemia (AMoL), and 2 chronic myeloid leukemia (CML)]. Based on rates for the general population, 0.45 case would be expected and, therefore, the relative risk was 11.2. The average mean marrow dose for all our subjects was calculated to be 1177 rad, the risk of radiation-induced leukemia was 0.43 excess case per year per one million women exposed to 1 rad of radiation to the bone marrow. Four patients with cervical cancer who developed leukemia were in a high-dose-rate group treated with both a linear accelerator (Linac) and remote afterloading system (RALS), and 1 patient with ovarian cancer who developed leukemia was treated with a Linac alone. This is the first report of a statistically significant increased risk of leukemia for patients treated with large doses of radiation for malignant neoplasms in the pelvic region.
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PMID:Leukemia in patients following radiotherapy for malignant neoplasms in the pelvic region. 406 51

Belonging to the vast family of cytokines, interferons (IFN) have recently been widely investigated concerning their possible clinical applications, both in virology and oncology. In this field results have been quite mixed but definitely encouraging. The best achievements have been obtained in hematology, and particularly in the treatment of hairy cell leukemia and chronic myelogenous leukemia, but new perspectives have also opened in the therapy of solid tumors, especially in the local treatment of superficial bladder cancer and ovarian cancer, AIDS-related Kaposi's sarcoma and malignant melanoma. IFN have in certain cases showed an efficacy comparable to that of classic treatments but with lower toxicity, and in some tumors they have even improved the results obtained so far, especially in combined therapy. We have here gathered the most recent results concerning the use of IFN in the therapy of solid tumors in order to highlight the new therapeutic opportunities available to clinical oncology.
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PMID:[Interferons in the therapy of solid tumors]. 853 32

Organization of genomic DNA into chromatin aids in the regulation of gene expression by limiting access to transcriptional machinery. The SWI/SNF family of complexes, which are conserved from yeast to humans, are ATP-dependent chromatin-remodeling enzymes required for the transcription of a number of genes in yeast. In humans, the gene encoding the BAF47/hSNF5 subunit of the complex, located at 22q11.2, has been found to be mutated in a number of human tumors including rhabdoid, rhabdomyosarcoma, chronic myeloid leukemia, and CNS tumors such as medulloblastomas and choroid plexus carcinomas. In addition, loss of heterozygosity (LOH) has been reported for the BAF47 region in breast and liver cancer. LOH has also been reported in breast and ovarian cancer within 17q12-25, a gene-rich area including BRCA1, BAF60B, and BAF57. Interestingly, the gene encoding the BAF155/hSWI3 subunit of the complex maps to 3p21-p23, an area of chromosomal deletion seen in a number of human adenocarcinomas including breast, kidney, pancreas, and ovary. To look for abnormalities in these proteins as well as the SWI/SNF complex in general, we have determined the protein status of core human SWI/SNF components BAF170, BAF155, BAF57, BAF53a, and BAF47 in 21 breast cell lines. The complex status in other human tumor cell lines of various tissue types was also examined. We also determined the protein status of the human SWI2 homologues, hBRM/SWI2alpha and BRG1/SWI2beta as well as two other proteins found in human SWI/SNF complexes, BAF180 and BAF250. In this study, we identified the first cell line negative for the BAF57 protein as well as a pancreatic carcinoma cell line negative for both the BRG-1 and hBRM proteins.
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PMID:Characterization of SWI/SNF protein expression in human breast cancer cell lines and other malignancies. 1114 8

Tiazofurine is a nucleoside analog with oncolytic activity being developed by Ribapharm (formerly ICN Pharmaceuticals) as a potential treatment for leukemia. It is metabolized to TAD (thiazole-4-carboxamide adenine dinucleotide), an inhibitor of IMP dehydrogenase. This inhibition results in the reduction of guanylate levels and the halting of neoplastic proliferation. The compound is in phase II/III trials [215553]. It is expected that Ribapharm will file an orphan drug application for tiazofurine, as a treatment for myelogenous leukemia, following the drug's completion of phase III trials by the end of 2002. The company has reported that phase III trials will begin by the end of 2000. Preliminary studies involving 21 patients have been carried out and the results reported by the company. During these studies, seven patients with chronic myelogenous leukemia had a complete hematologic response and two patients had a partial response. Of the patients with a complete response, six had marrow and peripheral responses. Ribapharm, through a Russian subsidiary of ICN, is also planning to conduct phase II studies of tiazofurine involving patients suffering from advanced ovarian cancer or multiple myeloma which is resistant to conventional therapy. The company has reported that the multiple myeloma limited phase II study is still undergoing planning, with an intended start date in late 2000 [381453]. In March 2000, Chase Hambrecht & Quist predicted that first approval could be towards the end of 2001 [384894].
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PMID:Tiazofurine ICN Pharmaceuticals. 1124 83

L-asparaginase (EC 3.5.1.1) was purified to homogeneity from Thermus thermophilus. The apparent molecular mass of L-asparaginase was found to be 33 kDa by SDS-PAGE, whereas by Sephacryl S-300 superfine column it was found to be 200 kDa, indicating that the enzyme in the native stage acts as hexamer. It is a thermostable enzyme and keeps all of its activity at 80 degrees C for 10 min. The antiproliferative activity of the purified L-asparaginase from T. thermiphilus was tested against the following human cell lines: K-562 (chronic myelogenous leukemia), Raji (Burkitt's lymphoma), SK-N-MC (primitive neuroectodermal tumor), HeLa (cervical cancer), BT20 and MCF7 (breast cancers), HT-29 (human colon cancer), and OAW-42 (ovarian cancer). The antiproliferative activity of T. thermophilus enzyme was compared with Erwinase, the commercially available L-asparaginase from Erwinia corotovora. The potency difference between the two L-asparaginases was greater in HeLa and SK-N-MC than in other cell lines. The fact that L-asparaginase from T. thermophilus does not hydrolyse L-glutamine makes it advantageous for future clinical trials.
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PMID:Antitumor activity of L-asparaginase from Thermus thermophilus. 1126 87

Cancer testis (CT) antigens have an expression pattern that is predominantly restricted to testis in normal tissues, yet they are expressed in many different histological types of cancers. One previously described member of the CT antigen family, XAGE-1, was shown to be expressed in Ewing's sarcomas and rhabdomyosarcomas. Here we show that XAGE-1 is also expressed in breast cancer, prostate cancer, and different types of lung cancers, including lung squamous cell carcinoma, adenocarcinoma, small cell lung carcinoma, and non-small cell lung carcinoma. In addition, XAGE-1 mRNA was present in ovarian cancer, melanoma, glioblastoma, T-cell lymphoma, chronic myelogenous leukemia, and histiocytic lymphoma cell lines. We also characterized the XAGE-1 transcript by primer extension analysis and found that transcription of the XAGE-1 gene is initiated from two distinct start sites, resulting in two overlapping transcripts, XAGE-1a and XAGE-1b. XAGE-1a contains two in-frame ATG translational start codons; whereas XAGE-1b initiates downstream of the first ATG start codon. Our results suggest that XAGE-1b is the dominant transcript, and that translation begins with the second ATG start codon, producing a 9 kDa protein. Because XAGE-1 is expressed in such a diverse range of cancers, it has potential to be used as a target for many cancer immunotherapies.
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PMID:Characterization of overlapping XAGE-1 transcripts encoding a cancer testis antigen expressed in lung, breast, and other types of cancers. 1247 62


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