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)

Artesunate (ART) is a semi-synthetic derivative of artemisinin, the active principle of the Chinese herb Artemisia annua. ART reveals remarkable activity against otherwise multidrug-resistant Plasmodium falciparum and P. vivax malaria. ART has now been analyzed for its anti-cancer activity against 55 cell lines of the Developmental Therapeutics Program of the National Cancer Institute, USA. ART was most active against leukemia and colon cancer cell lines (mean GI50 values: 1.11+/-0.56 microM and 2.13+/-0.74 microM , respectively). Non-small cell lung cancer cell lines showed the highest mean GI50 value (25.62+/-14.95 microM) indicating the lowest sensitivity towards ART in this test panel. Intermediate GI50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines. Importantly, a comparison of ART's cytotoxicity with those of other standard cytostatic drugs showed that ART was active in molar ranges comparable to those of established anti-tumor drugs. Furthermore, we tested CEM leukemia sub-lines resistant to either doxorubicin, vincristine, methotrexate, or hydroxyurea which do not belong to the N.C.I. screening panel. None of these drug-resistant cell lines showed cross resistance to ART. To gain insight into the molecular mechanisms of ART's cytotoxicity, we used a panel of isogenic Saccaromyces cerevisiae strains with defined genetic mutations in DNA repair, DNA checkpoint and cell proliferation genes. A yeast strain with a defective mitosis regulating BUB3 gene showed increased ART sensitivity and another strain with a defective proliferation-regulating CLN2 gene showed increased ART resistance over the wild-type strain, wt644. None of the other DNA repair or DNA check-point deficient isogenic strains were different from the wild-type. These results and the known low toxicity of ART are clues that ART may be a promising novel candidate for cancer chemotherapy.
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PMID:The anti-malarial artesunate is also active against cancer. 1125 Nov 72

Any leukopenia of less than 1000/microliter poses an acute threat to life, and mandates an immediate search for the underlying cause. An extensive history-taking (use of drugs? visits abroad? previous illnesses?) and physical examination (splenomegaly? exanthema? signs of hemorrhage?) are mandatory. In addition to a manual differential blood count, bone marrow aspiration for cytological and histological evaluation must be requested. In this overview, the major differential diagnoses, such as allergic agranulocytosis, leukemia, pernicious illnesses (e.g. malaria), hypersplenic syndrome and a number of infectious diseases are discussed.
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PMID:[Leukocytopenia as an incidental finding. Finding the etiology]. 1126 49

One hundred and ninety plants, of which 51 are used to treat malaria in traditional medicine, were collected in five different ecosystems of Madagascar for a screening programme devoted to the search of naturally-occurring antimalarial compounds. Thirty-nine plants, of which 12 are used as herbal antimalarials, were found to display in vitro activity against Plasmodium falciparum with a median inhibitory concentration (IC50) lower than 5 microg/ml while 9 had an IC50 ranging from 5 to 7.5 microg/ml. Seventeen of them exhibited cytotoxic effects on murine P388 leukemia cells with an IC50 < 10 microg/ml. The biological activities were mostly located in the ethyl acetate fractions. Bioassay-directed fractionation is underway to isolate the active constituents.
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PMID:Screening extracts of Madagascan plants in search of antiplasmodial compounds. 1547

Aspartic proteases have emerged as targets for substrate-based inhibitor design due to their vital roles in the life cycles of the organisms that cause AIDS, malaria, leukemia, and other infectious diseases. Based on the concept of mimicking the substrate transition-state, we designed and synthesized a novel class of aspartic protease inhibitors containing the hydroxymethylcarbonyl (HMC) isostere. An unnatural amino acid, allophenylnorstatine [Apns; (2 S ,3 S )-3-amino-2-hydroxy-4-phenylbutyric acid], was incorporated at the P1 site in a series of peptidomimetic compounds that mimic the natural substrates of the HIV, HTLV-I, and malarial aspartic proteases. From extensive structure-activity relationship studies, we were able to identify a series of highly potent peptidomimetic inhibitors of HIV protease. One highly potent inhibitor of the malarial aspartic protease (plasmepsin II) was identified. Finally, a promising lead compound against the HTLV-I protease was identified.
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PMID:Design of inhibitors against HIV, HTLV-I, and Plasmodium falciparum aspartic proteases. 1557 23

CD36 is a multiligand receptor associated with a broad array of physiological processes and involved in markedly diverse disorders, including atherosclerosis, insulin resistance and diabetes, dyslipidemia, tumor angiogenesis, and host defense against Plasmodium falciparum. CD36 deficiency has proved to be common, particularly in ethnic groups such as African Americans and Asians. CD36 is commonly expressed on blasts in acute monocytic leukemia, megakaryoblastic leukemia, and erythroleukemia. The role of CD36 in sickle cell crises and cerebral malaria is debatable. As a receptor for thrombospondin 1, CD36 plays a role in the regulation of angiogenesis, which may be a therapeutic strategy for controlling the dissemination of malignant neoplasms. The future challenge will be to further understand the mechanisms by which CD36 affects these diverse functions and to design therapeutic strategies that can alter the course of the diseases.
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PMID:CD36: a multiligand molecule. 1579 May 50

Acute renal failure (ARF) is a significant cause of morbidity and mortality in children. It may be pre-renal, intrinsic, or post-renal (obstructive) in aetiology. ARF was investigated in children in the south-southern part of Nigeria to determine the prevalence, aetiology, management and outcome of ARF. A retrospective review of data from all children from birth to 16 years of age admitted into the Department of Paediatrics, University of Port Harcourt Teaching Hospital (UPTH), with the diagnosis of ARF over an 18 year period (January 1985 to December 2003) was performed. Information was obtained about the age, sex, clinical features, blood pressure, laboratory and radiological investigations, aetiology, and treatment received including dialysis. Information on the outcome, factors influencing outcome, and possible causes of death were reviewed. There were 211 patients, 138 (65.4%) males and 73 (34.6%) females (M:F, 1.9:1), with a hospital prevalence of 11.7 cases/year. The patients were aged 5 days to 16 years (mean 5.6+/-4.7 years). Oliguria was the most common clinical presentation in 184 (87.2%) patients. Hypertension was seen in only 39 (18.5%) patients. The causes were age-related. The neonates had ARF from severe birth asphyxia 27 (35.5%), septicaemia 17 (22.4%), with tetanus 4 (5.3%) and congenital malformations 11 (14.5%). Sixty-one (28.9%) and 29 (13.7%) patients had ARF from gastroenteritis and malaria respectively. The patients with leukaemia were all more than 10 years old and had acute lymphoblastic leukaemia. Two patients (1.9%) had Burkitts lymphoma involving the abdomen and 3 patients had HIVAN. 112 (53%) patients had anaemia with a mean haematocrit of 20.25+/-6.9%. Dialysis was indicated in 108 patients, but only 24 patients (22.2%) had peritoneal dialysis (PD), because of financial constraints and lack of dialysis equipment. Mortality rate was 40.5%. The causes of death were uraemia 60 (70.6%), overwhelming infection 5 (5.9%), and recurrent anaemia 20 (23.5%). Hypertension (X2 15.7, P<0.001) and lack of dialysis (X2 7.96, P<0.01) significantly affected outcome. Other factors associated with demise were delayed presentation (58.8%), use of herbal treatment (35%), and unaffordability of treatment (40%). ARF is a significant cause of mortality in Nigerian children. The patients are not adequately managed because of poverty and lack of facilities for dialysis. The causes of ARF in our environment are preventable, and should be expected.
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PMID:Acute renal failure in Nigerian children: Port Harcourt experience. 1594 80

Artesunate (ART) is a derivative of artemisinin, the active principle of the Chinese herb Artemisia annua L. Artesunate is approved for the treatment of multidrug-resistant malaria and has an excellent safety profile. It has been shown that Artesunate, apart from its anti-malarial activity, has cytotoxic effects on a number of human cancer cell lines, including leukemia, colon cancer and melanoma. We report on the first long-term treatment of two cancer patients with ART in combination with standard chemotherapy. These patients with metastatic uveal melanoma were treated on a compassionate-use basis, after standard chemotherapy alone was ineffective in stopping tumor growth. The therapy-regimen was well tolerated with no additional side effects other than those caused by standard chemotherapy alone. One patient experienced a temporary response after the addition of ART to Fotemustine while the disease was progressing under therapy with Fotemustine alone. The second patient first experienced a stabilization of the disease after the addition of ART to Dacarbazine, followed by objective regressions of splenic and lung metastases. This patient is still alive 47 months after first diagnosis of stage IV uveal melanoma, a situation with a median survival of 2-5 months. Despite the small number of treated patients, ART might be a promising adjuvant drug for the treatment of melanoma and possibly other tumors in combination with standard chemotherapy. Its good tolerability and lack of serious side effects will facilitate prospective randomized trials in the near future.
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PMID:Artesunate in the treatment of metastatic uveal melanoma--first experiences. 1627 63

This review considers recent studies regarding the role of environmental factors in the etiology of childhood leukemia and lymphoma. Potential environmental risk factors identified for childhood leukemia include exposure to magnetic fields of more than 0.4 micro Tessla, exposure to pesticides, solvents, benzene and other hydrocarbons, maternal alcohol consumption (but only for certain genotypes), contaminated drinking water, infections, and high birth weight. The finding of space-time clustering and seasonal variation also supports a role for infections. There is little evidence linking childhood leukemia with lifetime exposure to ionizing radiation although fetal exposures to X-rays are associated with increased risk. Breast-feeding, consumption of fresh fruit and vegetables and having allergies all appear to be protective. Burkitt lymphoma (BL) is confined to areas of the world where malaria is endemic, with the additional involvement of the Epstein-Barr virus (EBV) as a co-factor. Environmental risk factors suggested for other types of non-Hodgkin lymphoma (NHL) include exposure to ionizing radiation (both lifetime and antenatal), pesticides, and, in utero exposure to cigarette smoke, benzene and nitrogen dioxide (via the mother). Hodgkin lymphoma (HL) is especially associated with higher levels of socioeconomic deprivation, but breast-feeding seems to confer lower risk. This is consistent with an infection or immune-response mediated etiology for HL.
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PMID:Environmental factors and childhood acute leukemias and lymphomas. 1669 May 16

Child mortality has declined remarkably during the last decades. While neonatal disorders, diarrhoea, pneumonia, and malaria as well as being underweight account for most of the child deaths worldwide, children's health discussions in Europe and the USA focus on other issues such as asthma, neurodevelopmental disorders, male genital malformations, and childhood cancer. There is clear evidence of increasing rates of asthma in various countries during the last decades, although rates in some countries may now have stabilised or even decline as recent UK data indicate. Although an increase in the frequency of neurodevelopmental disorders such as autism and attention deficit disorder has frequently been discussed, the limited data in this field does not justify such a conclusion. While geographic heterogeneity regarding reproductive outcomes is apparent, global trends have not been identified. Interpretation of the available information on asthma, neurodevelopmental disorders and reproductive outcomes is hampered by inconstant diagnostic criteria over place and time and the lack of good and comprehensive population-based surveillance data, which makes it impossible to ascertain trends in actual disease frequency. Data indicate that developed countries have a gradually increasing incidence in leukaemia with a corresponding drop in the incidence of lymphoma. Increases in brain tumour frequency may be related to the development and wide application of new diagnostic capabilities, rather than a true change in the incidence of malignant disease. With a better prognosis for childhood cancer survival, secondary cancers following chemotherapy appear to be increasing. A wide range of environmental factors is thought to have an impact on children's health. These factors include nutrition (protein, vitamins, antioxidants), lifestyle and behaviour choices such as tobacco and alcohol use, parental health, socio-economic status, choice of living environment (urban versus rural, etc.), and parent-sibling behaviour. From the available data, no general conclusions on the contribution of specific chemicals can be drawn.
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PMID:Trends in childhood disease. 1685 14

Hyper reactive malarial splenomegaly (HMS) is a relatively rare chronic complication of malaria. Previous name of the disease was Tropical splenomegaly syndrome (TSS). It is seen in endemic zone of malaria. In Bangladesh it is very rare. It is more prevalent in Africa, India, Sri Lanka, Thailand etc. It is due to abnormal immune response to malaria. Recently we got a typical case of HMS in our pediatric department of Community Based Medical College Hospital (CBMCH) Mymensingh. The patient, a seven years old boy came from Haluaghat, Mymensingh, which is a hyper endemic zone of malaria. The boy had history of repeated attack of malaria with huge chronic splenomegaly for five years. Antibody to malaria was positive & titer was markedly raised. Other causes of massive splenomegaly namely chronic Kala azar, Typhoid, congenital hemolytic anemia, Leukaemia, Lymphoma etc were excluded by laboratory examination. The boy was discharged with malaria prophylaxis for a long time & advised to come to our unit every month for further follow up.
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PMID:Hyper reactive malarial splenomegaly (HMS). 1687 6


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