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

Individuals with Down syndrome have an increased risk of leukaemia, but reliable estimates of the age-specific risk of leukaemia are lacking and very little is known about the risk of solid tumours. We identified 2814 individuals with Down syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated on the basis of age- and sex-specific cancer rates in the general population. Sixty cases of cancer were observed, with 49.8 expected (SIR = 1.20; CI: 0.92-1.55). Leukaemia constituted 60% of the malignancies overall and 97% of the malignancies in children. The SIR for leukaemia varied considerably with age, being 56 (CI: 38-81) at age 0-4 years and 10 (CI: 4-20) at 5-29 years. No cases of leukaemia were observed after age 29. The cumulative risk of leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were observed with 47.8 expected (SIR = 0.50; CI: 0.32-0.75). No cases of breast cancer were observed, with 7.3 expected (p = 0.0007). Increased risks of testicular cancer, ovarian cancer, and retinoblastoma were observed but were not statistically significant. The occurrence of cancer in Down syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age groups. The distinctive pattern of malignancies may provide clues in the search for leukaemogenic genes and tumour suppressor genes on chromosome 21.
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PMID:[Occurrence of cancer in individuals with Down syndrome]. 1098 Dec 21

Individuals with Down syndrome have an increased risk of leukaemia, but reliable estimates of the age-specific risk of leukaemia are lacking and very little is known about the risk of solid tumours. We identified 2814 individuals with Down syndrome from the Danish Cytogenetic Register, and linked the data to the Danish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated on the basis of age- and sex-specific cancer rates in the general population. Sixty cases of cancer were observed, with 49.8 expected (SIR = 1.20; CI: 0.92-1.55). Leukaemia constituted 60% of the malignancies overall and 97% of the malignancies in children. The SIR for leukaemia varied considerably with age, being 56 (CI: 38-81) at age 0-4 years and 10 (CI: 4-20) at 5-29 years. No cases of leukaemia were observed after age 29. The cumulative risk of leukaemia by the age of 5 years was 2.1% and that by 30 years was 2.7%. Only 24 solid tumours were observed with 47.8 expected (SIR = 0.50; CI: 0.32-0.75). No cases of breast cancer were observed, with 7.3 expected (p = 0.0007). Increased risks of testicular cancer, ovarian cancer, and retinoblastoma were observed but were not statistically significant. The occurrence of cancer in Down syndrome is unique with a high risk of leukaemia in children and a decreased risk of solid tumours in all age groups. The distinctive pattern of malignancies may provide clues in the search for leukaemogenic genes and tumour suppressor genes on chromosome 21.
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PMID:[Incidence of cancer in individuals with Down syndrome]. 1114 9

A report of a 5-year survival rate of 39% for all patients with testis cancer in Kenya contrasts sharply with the 62% 5-year survival rate after tandem high-dose chemotherapy in first-line salvage of metastatic nonseminoma, and this figure provides a stark reminder of the differences in level of health care in the world. Nothing matches, however, the international significance of the success of Lance Armstrong in winning the Tour de France for the second time. It brings home the message of how complete the cure of this disease is and the need for more to be done to educate people about this success and encourage us to seek to discover the scientific basis for why this cancer is so different from all other cancers. The discovery that Lance Armstrong's brain metastases were totally necrotic at day 21 after the first treatment, taken with a report on the use of day 21 computed tomograph response to predict outcome, reinforces that message. With a second report suggesting that there are regions of the world that may have escaped the environmental damage to fertility that is now increasingly accepted as the most significant risk factor for development of this disease, we also need to remember the importance of germ cells as a weather vane of the environment. The first breakthrough in identifying a specific genetic region on the X chromosome with susceptibility to germ cell cancer of the testis by its association with development of undescended testis was one of the scientific landmarks of this past year. Clinically, with such high cure rates after salvage treatments, most of the controversy focuses now on early management of this disease. Debate continues regarding the need for orchidectomy or node dissection before chemotherapy in patients with metastases. There is also considerable debate concerning the need for any adjuvant treatment in stage 1 disease, whether surgical, chemotherapeutic, or radiotherapeutic. With reviews on late events highlighting the possibility that cisplatin dosage may be critical in synergizing with etoposide in causing leukemia and late cardiovascular events and reports suggesting that circulating cisplatin can be detected in the plasma as long as 20 years after treatment, the message of the year is clearly how to safely minimize the amount of treatment.
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PMID:Testicular cancer. 1130 64

Early poliovirus vaccines, both inactivated and live attenuated, were inadvertently contaminated with simian virus 40 (SV40), a monkey virus known to be oncogenic for newborn hamsters. Although large epidemiologic studies have not identified an elevated cancer risk in persons who received SV40-contaminated vaccines, fragments of SV40 DNA have recently been identified in certain human tumours. We report the follow-up of a cohort of 1073 persons, unique because they received SV40-contaminated poliovirus vaccines as newborns in 1961-63. A previous report of the status of these subjects as of 1977-79 identified 15 deaths, none due to cancer. The present study utilized the National Death Index to identify deaths in the cohort for the years 1979-96. Expected deaths were calculated from Cleveland area sex-, age-, race- and year-specific mortality rates. Increased mortality from all causes was not found. 4 deaths from cancer were found compared to 3.16 expected (P = 0.77). However, 2 deaths from testicular cancer occurred, compared to 0.05 expected (P = 0.002), which may be a chance finding due to multiple comparisons. There were 2 deaths due to leukaemia, a non-significant finding, and no deaths due to tumours of the types putatively associated with SV40. Although these results are, for the most part, consistent with other negative epidemiologic investigations of risks from SV40-contaminated vaccines, further study of testicular cancer may be warranted, and it will be important to continue monitoring this cohort which is now reaching middle-age.
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PMID:Thirty-five year mortality following receipt of SV40- contaminated polio vaccine during the neonatal period. 1172 Apr 63

Testicular germ cell tumor comprises about 1% of all the malignancies of males in Japan, and occurs in only one over 100,000 males annually. A susceptibility gene may be located on the short arm of the chromosome 12. Among the genes in this region, the expression of the KRAS2 mRNA was increased in testicular cancer compared to the normal testicular tissue. By DNA typing, HLA-DR4 and 0405 allele in HLA-DRB1 showed high relative risk for testicular cancer. We analyzed the expression of the WT1 gene, reported to be a growth promoter for leukemia, by quantitative reverse transcription-PCR. Relative expression of the WT1 gene was significantly increased in high-stage cases than in low-stage cases, suggesting that WT1 could be useful as a tumor marker for progression of testicular cancers. Testicular germ cell tumors are usually very sensitive to chemotherapeutic agents such as cisplatin, and p53 has been reported to play an important role in chemosensitivity. Therefore, mutations of the p53 gene or other genes downstream may be responsible for their chemoresistance. The expression of the GML (GPI--anchored molecule like protein) gene was examined in testicular cancers. Its expression was not correlated with histology or stage. However, 4 refractory cases, 2 of which were recurrent cases from stage I and the others were at high stages, showed no expression of the GML mRNA. These interesting facts suggest that the expression of GML gene could be a good marker for the prognosis of testicular germ cell tumors.
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PMID:[A prospect of molecular biology in the field of urologic oncology: mechanisms of carcinogenesis or tumor development in testicular cancer]. 1177 Nov 75

This study reports on over 40 years of mortality follow-up of 40,581 Navy veterans of the Korean War with potential exposure to high-intensity radar. The cohort death rates were compared with mortality rates for White US men using standardized mortality ratios, and the death rates for men in occupations considered a priori to have high radar exposure were compared with the rates for men in low-exposure occupations using Poisson regression. Deaths from all diseases and all cancers were significantly below expectation overall and for the 20,021 sailors with high radar exposure potential. There was no evidence of increased brain cancer in the entire cohort (standardized mortality ratio (SMR) = 0.9, 95% confidence interval (CI): 0.7, 1.1) or in high-exposure occupations (SMR = 0.7, 95% CI: 0.5, 1.0). Testicular cancer deaths also occurred less frequently than expected in the entire cohort and high-exposure occupations. Death rates for several smoking-related diseases were significantly lower in the high-exposure occupations. Nonlymphocytic leukemia was significantly elevated among men in high-exposure occupations but in only one of the three high-exposure occupations, namely, electronics technicians in aviation squadrons (SMR = 2.2, 95% CI: 1.3, 3.7). Radar exposure had little effect on mortality in this cohort of US Navy veterans.
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PMID:Cancer in Korean war navy technicians: mortality survey after 40 years. 1254 30

The genetic and environmental components in 15 common cancers were estimated using the nationwide Swedish Family-Cancer Database. Tetrachoric correlations were used to describe similarity in cancer liability among family members. Structural equation modeling was used to derive estimates of the importance of genetic and environmental effects. Statistically significant estimates of proportion of cancer susceptibility, accounted for by genetic effects, were obtained for all studied cancers except for leukemia. The estimate was highest in thyroid cancer (53%), followed by tumors at endocrine glands (28%), testis (25%), breast (25%), cervix (22%), melanoma (21%), colon (13%), nervous system (12%), rectum (12%), non-Hodgkin lymphoma (10%), lung (8%), kidney (8%), urinary bladder (7%), stomach (1%) and leukemia (1%). The estimates of shared environmental effects ranged from 0% (cervix) to 15% (stomach). The childhood shared environmental effects were most important in testicular cancer (17%), stomach cancer (13%) and cervix in situ (13%). Our results indicate that environment has a principal causative role in cancer at all studied sites except for thyroid. The relatively large effect of heritability in cancer at some sites, on the other hand, indicates that even though susceptibility genes have been described at many cancer sites, they are likely to explain only part of the genetic effects.
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PMID:Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. 1197 42

Among the 25 bis(cyclopentadienyl)vanadium(IV) and 14 oxovanadium(IV) compounds synthesised and evaluated for anticancer activity, bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (metvan) was identified as the most promising multitargeted anticancer vanadium complex with apoptosis-inducing activity. At nanomolar and low micromolar concentrations, metvan induces apoptosis in human leukaemia cells, multiple myeloma cells and solid tumour cells derived from breast cancer, glioblastoma, ovarian, prostate and testicular cancer patients. It is highly effective against cisplatin-resistant ovarian cancer and testicular cancer cell lines. Metvan is much more effective than the standard chemotherapeutic agents dexamethasone and vincristine in inducing apoptosis in primary leukaemia cells from patients with acute lymphoblastic leukaemia, acute myeloid leukaemia or chronic acute myeloid leukaemia. Metvan-induced apoptosis is associated with a loss of mitochondrial transmembrane potential, the generation of reactive oxygen species and depletion of glutathione. Treatment of leukaemia cells from acute lymphoblastic leukaemia, acute myeloid leukaemia and chronic acute myeloid leukaemia patients with metvan inhibits the constitutive expression as well as the gelatinolytic activities of matrix metalloproteinase-9 and -2. Treatment of human malignant glioblastoma and breast cancer cells with metvan at concentrations > 1 microM is associated with a nearly complete loss of the adhesive, migratory and invasive properties of the treated cancer cell populations. Metvan shows favourable pharmacokinetics in mice and does not cause acute or subacute toxicity at the dose levels tested (12.5 - 50 mg/kg). Therapeutic plasma concentrations > or = 5 microM, which are highly cytotoxic against human cancer cells, can be rapidly achieved and maintained in mice for at least 24 h after intraperitoneal bolus injection of a single 10 mg/kg non-toxic dose of metvan. Metvan exhibits significant antitumour activity, delays tumour progression and prolongs survival time in severe combined immunodeficient mouse xenograft models of human malignant glioblastoma and breast cancer. The broad spectrum anticancer activity of metvan together with favourable pharmacodynamic features and lack of toxicity warrants further development of this oxovanadium compound as a new anticancer agent. Metvan could represent the first vanadium complex as an alternative to platinum-based chemotherapy.
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PMID:Metvan: a novel oxovanadium(IV) complex with broad spectrum anticancer activity. 1245 42

Testicular cancer is the most common solid tumour among young males aged 15-35 years. Cisplatin-based combination chemotherapy has changed the outlook of this disease. Disseminated testicular cancer, once uniformly fatal, now has a cure rate of more than 80% with combination chemotherapy. Systematic randomised trials have shown that cisplatin, etoposide and bleomycin (PEB) combination chemotherapy remains the mainstay of treatment. While there is a high cure rate with chemotherapy in patients with this disease, some long-term complications from chemotherapy have now been recognised, including secondary leukaemia, therapy-related solid tumours, nephrotoxicity, neurotoxicity, pulmonary toxicity, vascular toxicity and infertility. Etoposide, a DNA topoisomerase II inhibitor, is a significant risk factor for developing leukaemia; the risk appears to be correlated with the total dose given. Patients receiving cisplatin-based combination chemotherapy for testicular cancer also appear to have a higher relative risk for developing second non-germ cell malignancies; the greatest risks for therapy-related solid tumours were seen with a combination of radiation therapy plus chemotherapy. Long-term vascular toxicities associated with chemotherapy include Raynaud's phenomenon, acute myocardial infarction and cerebrovascular events. Bleomycin is thought to be the most important drug in the pathogenesis of Raynaud's phenomenon, while cisplatin is the most likely agent involved in myocardial infarction. Peripheral neuropathy is the most common form of neurotoxicity observed with cisplatin-based chemotherapy. Risk factors for the development of neural damage include a high cumulative dose of cisplatin, the use of vinblastine and the concomitant development of Raynaud's phenomenon. Cisplatin is also well known to cause significant nephrotoxicity. Approximately 25% of patients present with azoospermia after undergoing combination chemotherapy with a follow up of 2-5 years. Physician awareness of complications associated with chemotherapy is vital to maximise efficacy, minimise toxicity, and preserve quality of life after treatment. Sperm cryopreservation should be considered for patients who desire children. Close monitoring during therapy allows for the early diagnosis of complications, and close follow up of patients after the completion of therapy is necessary to monitor for relapse and development of long-term complications such as myelodysplastic syndrome and leukaemia. Despite these complications, given the potential for cure rates in this young group of patients, the benefits far outweigh the risks.
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PMID:Long-term complications of chemotherapy for germ cell tumours. 1288 63

Leukaemia cases among European UN soldiers in the Balkans have been related hypothetically to exposure to depleted uranium. This study was performed to investigate the risk of cancer among Swedish personnel (8750 men and 438 women) involved in UN missions in the Balkans 1989-99. The overall incidence of cancer was slightly higher than expected; 34 cancers were observed and 28.1 were expected based on national cancer rates. Among military men, there were eight cases of testicular cancer versus 4.6 expected. There was one case of chronic myeloid leukaemia, and no cases of acute leukaemia. The overall risk of cancer was increased in a subgroup of 648 men taking part in convoy operations, based on only five cancers at four different sites. The study gives no support for the hypothesis that UN service in the Balkans could lead to haematolymphatic malignancies after short latency. However, no exposure assessment was performed, and future follow up is necessary for evaluation of long term risks.
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PMID:Incidence of cancer among Swedish military and civil personnel involved in UN missions in the Balkans 1989-99. 1473 85


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