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)

The present experiment was undertaken to study what types of human cancers are responsive to the antiproliferative effects of suramin. The human malignant cells used were as follows: cervical cancer (HeLa), mammary cancer (MCF-7), bladder cancer (EJ), hepatoma (HuH-7, PLC/PRF/5), embryonal carcinoma (PA-1), in vitro transformed fibroblasts (KMST-6, SUSM-1, VA-13), five myeloma cell lines (KMM-1, KMS-5, KMS-11, KMS-12, RPMI 8226), Burkitt's lymphoma (Raji), acute promyelocytic leukemia (HL-60), chronic myelocytic leukemia (K562), Epstein-Barr virus nuclear antigen positive lymphoblastoid cells (KMS-9). The cells were treated with 25 to 100 micrograms/ml suramin for 72h. Proliferation of HuH-7 and two human myeloma cells (KMS-11 and KMS-12) was remarkably inhibited, and that of PA-1, PLC/PRF/5, KMST-6, two other myeloma cell lines (KMM-1 and KMS-5), Raji and HL-60, was moderately inhibited. In order to confirm part of the results obtained from in vitro experiments, in vivo experiments were also undertaken. The growth of HuH-7 cells transplanted subcutaneously into nude mice was significantly suppressed by intravenous injection of suramin. We discussed the possibility that certain types of human cancers, the growth of which seemed to be more or less dependent on polypeptide growth factors, might be sensitive to the antiproliferative effects of suramin.
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PMID:Antiproliferative effects of suramin on human cancer cells in vitro and in vivo. 148 40

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

The dose-response relationship for radiation-induced leukemia was examined in a pooled analysis of three exposed populations: Japanese atomic bomb survivors, women treated for cervical cancer, and patients irradiated for ankylosing spondylitis. A total of 383 leukemias were observed among 283,139 study subjects. Considering all leukemias apart from chronic lymphocytic leukemia, the optimal relative risk model had a dose response with a purely quadratic term representing induction and an exponential term consistent with cell sterilization at high doses; the addition of a linear induction term did not improve the fit of the model. The relative risk decreased with increasing time since exposure and increasing attained age, and there were significant (P < 0.00001) differences in the parameters of the model between datasets. These differences were related in part to the significant differences (P = 0.003) between the models fitted to the three main radiogenic leukemia subtypes (acute myeloid leukemia, acute lymphocytic leukemia, chronic myeloid leukemia). When the three datasets were considered together but the analysis was repeated separately for the three leukemia subtypes, for each subtype the optimal model included quadratic and exponential terms in dose. For acute myeloid leukemia and chronic myeloid leukemia, there were reductions of relative risk with increasing time after exposure, whereas for acute lymphocytic leukemia the relative risk decreased with increasing attained age. For each leukemia subtype considered separately, there was no indication of a difference between the studies in the relative risk and its distribution as a function of dose, age and time (P > 0.10 for all three subtypes). The nonsignificant indications of differences between the three datasets when leukemia subtypes were considered separately may be explained by random variation, although a contribution from differences in exposure dose-rate regimens, inhomogeneous dose distribution within the bone marrow, inadequate adjustment forcell sterilization effects, or errors in dosimetry could have played a role.
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PMID:Risks of leukemia in Japanese atomic bomb survivors, in women treated for cervical cancer, and in patients treated for ankylosing spondylitis. 1045 89

FRAT1 positively regulates the WNT signaling pathway by stabilizing beta-catenin through the association with glycogen synthase kinase-3beta. Here, we have cloned FRAT2 cDNAs, spanning the complete coding sequence, from a human fetal lung cDNA library. FRAT2 encoded 233 amino-acid protein, which showed 77.3% total amino-acid identity with FRAT1. FRAT2 and FRAT1 were more homologous in the acidic domain (96% identity), the proline-rich domain (92% identity), and the GSK-3beta binding domain (100% identity). The FRAT2 gene was mapped to human chromosome 10q24.1. The FRAT2 mRNA of 2.4-kb in size was relatively highly expressed in MKN45 (gastric cancer), HeLa S3 (cervical cancer), and K-562 (chronic myelogenous leukemia). Xenopus axis duplication assay revealed that the wild-type FRAT2 mRNA, but not the mutant FRAT2 mRNA lacking the acidic domain and the proline-rich domain, has the capacity to induce the secondary axis. These results indicate that FRAT2, just like FRAT1, functions as a positive regulator of the WNT signaling pathway. Thus, up-regulation of FRAT2 in human cancer might be implicated in carcinogenesis through activation of the WNT signaling pathway.
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PMID:Molecular cloning and characterization of FRAT2, encoding a positive regulator of the WNT signaling pathway. 1123 32

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

Arsenic trioxide inhibits growth and promotes apoptosis in many different cancer cell lines. The National Cancer Institute is working cooperatively with research centers across the U.S. to evaluate its clinical activity in hematologic malignancies, such as acute promyelocytic leukemia, acute myeloid leukemia, acute lymphocytic leukemia, chronic myelogenous leukemia, non-Hodgkin's lymphoma, Hodgkin's disease, chronic lymphocytic leukemia, myelodysplastic syndrome, and multiple myeloma. It is also supporting research in solid tumors, such as advanced hormone-refractory prostate cancer and renal cell cancer and in cervical cancer and refractory transitional cell carcinoma of the bladder. The safety and pharmacokinetics of arsenic trioxide are also being evaluated in pediatric patients with refractory leukemia and lymphoma. The results of these ongoing studies should provide important insights into the clinical utility of arsenic trioxide in these diseases.
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PMID:Clinical trials of arsenic trioxide in hematologic and solid tumors: overview of the National Cancer Institute Cooperative Research and Development Studies. 1133 37

FRAT1 and FRAT2 are cancer-associated genes encoding GSK-3beta-binding proteins. Over-expression of FRAT1 or FRAT2 lead to carcinogenesis through activation of WNT--beta-catenin--TCF signaling pathway. We have previously cloned and characterized FRAT2. Here, we found that FRAT1 and FRAT2 genes were clustered in the human chromosome 10q24.1 region. Blast search revealed that FRAT1 and FRAT2 genes, consisting of a single exon, were located together on human genome draft sequences AC006098.1 and AL355490.7, corresponding to the human chromosome 10q24.1 region. FRAT1 and FRAT2 genes were clustered in a tail to tail manner with an interval of about 10.7 kb. The 2.7-kb FRAT1 mRNA was relatively highly expressed in fetal brain, adult spleen, pancreas, HeLa S3 (cervical cancer), and K-562 (chronic myelogenous leukemia). FRAT1 and FRAT2 were co-expressed in 7 gastric cancer cell lines and 10 cases of primary gastric cancer, and were up-regulated together in gastric cancer cell line TMK1 and 2 cases of primary gastric cancer. These results indicated that FRAT1 and FRAT2 genes were up-regulated together in several cases of human gastric cancer. Up-regulation of FRAT1 and FRAT2 in gastric cancer might lead to carcinogenesis through activation of WNT--beta-catenin--TCF signaling pathway.
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PMID:FRAT1 and FRAT2, clustered in human chromosome 10q24.1 region, are up-regulated in gastric cancer. 1144 44

Kermit is a Xenopus orthologue of human GIPC1/GIPC, which interacts with Frizzled-3 (FZD3) class of WNT receptor to modulate WNT signaling. GIPC1 interacts with TGFbeta type III receptor to enhance TGFbeta signaling. We have recently cloned and characterized a novel GIPC1-related gene, GIPC2. During isolation of GIPC2, we identified another novel GIPC1-related gene, GIPC3, by using bioinformatics. In this study, we isolated GIPC3 cDNAs from poly(A)+ RNA of human fetal lung. GIPC3 encoded a 312-amino-acid protein with a central PDZ domain, which showed 59.9% total-amino-acid identity with GIPC1, 55.3% total-amino-acid identity with GIPC2, and 57.2% total-amino-acid identity with Xenopus Kermit. GIPC3 gene on human chromosome 19p13.3 was found to consist of 6 exons, just like GIPC1 gene and GIPC2 gene. The 4.5-kb GIPC3 mRNA was almost ubiquitously expressed in normal adult tissues as well as in normal fetal tissues. Expression level of GIPC3 mRNA was relatively higher in jejunum, followed by lymph node, parietal lobe in brain, fetal spleen, and fetal thymus. GIPC3 mRNA was expressed in cervical cancer cell line HeLa S3, chronic myelogenous leukemia cell line K-562, and melanoma cell line G-361. GIPC3 mRNA was also expressed in gastric cancer cell lines TMK1 and MKN7; however, expression level of GIPC3 mRNA in TMK1 and MKN7 cells were significantly lower than that in normal stomach. This is the first report on molecular cloning of GIPC3, the third member of the GIPC gene family.
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PMID:Molecular cloning and characterization of human GIPC3, a novel gene homologous to human GIPC1 and GIPC2. 1183 71

Chemotherapy-related acute leukemias or myelodysplasias are well-recognized entities. On the other hand, little is known about the possible occurrence of secondary chronic myeloid leukemia (CML) after radiotherapy, albeit accidental irradiation represents a classical predisposing factor for this disease. We report here three cases of Philadelphia-positive CML appearing one to 25 years after breast or uterine cervix cancer radiotherapy. One patient had also received chemotherapy. Clinical and biological characteristics of these cases did not significantly differ from those of de novo CMLs. A brief review of the literature is made about this possible peculiar entity. Large registries appear warranted to assess the real risk of developing CML after anti-cancer radiotherapy.
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PMID:Chronic myeloid leukemia as a secondary neoplasm after anti-cancer radiotherapy: a report of three cases and a brief review of the literature. 1214 86

A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries waiting to be "translated" into useful therapies and diagnostics. In addition to highlighting the major research advances over the past year, this report also identifies key barriers to accelerating the pace of cancer research and outlines ASCO's recommendations for overcoming them. Despite these and other challenges, there is much good news on the front lines of cancer research. This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States.
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PMID:Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology. 1715 28


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