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)

Thalidomide, an antiemetic administered in 60th of the 20th century to pregnant women, has become notorious for a range of adverse effects which led to its taking off market. In recent years, its antimyeloma effect was discovered. The aim of the work was to evaluate the incidence of adverse reactions to thalidomide. Its therapeutic effect has not been assessed because of a short period of monitoring and diversity of a sample. The assessed sample consisted of 17 patients with diagnosis of multiple myeloma (10 men and 7 women). An average age of patients was 62.9 +/- 9.4. An average time elapsed from making the diagnosis to starting the treatment with thalidomide was 51.0 +/- 23.7 months. An average length of therapy was 20.1 +/- 9.6 weeks. An average daily maximum therapeutic dose was 138.3 +/- 83.2 mg. Data were collected from outpatient physicians reports, regular laboratory tests, and direct interviews with patients. To classify severity of adverse drug effects (grades 0-4) we used WHO criteria, Cancer and Leukemia Group B criteria, and in cases where certain adverse effects were not included in the above mentioned criteria, we defined our own criteria. The most frequent adverse effects included: leucopenia or neutropenia in 12 (70.6%) patients, altered state of consciousness in 11 (64.7%) patients, obstipation in 10 (58.8%) patients, skin alterations in 9 (52.9%) patients, dizziness in 8 (47.1%) patients, peripheral neuropathy in 7 (41.2%) patients, spasms and spasmodic convulsions in 7 (41.2%) patients, and altered liver tests in 6 (35.3%) patients. From the perspective of necessity to interrupt treatment or reduce the dose the most severe disorders included: peripheral neuropathy in 2 patients (inability to control lower extremities), altered consciousness in 1 patient (protracted somnolence during a day), skin alteration in 1 patient (generalized toxoalergic reaction), leucopenia or neutropenia in 1 patient (1.0 resp < 0.5 x 10(9)/l), altered vision in 1 patient (blurred vision), hypothyroidism in 1 patient, and altered mood in 1 patient (subjective feeling of depression). This work proved thalidomide to be beneficial for the patients with multiple myeloma but it also shoved necessity to intensively monitor its adverse effects and to adjust its doses.
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PMID:[Desirable and undesirable effects of thalidomide in patients with multiple myeloma]. 1468 82

In an attempt to study the whole protein expression alterations of tumer cells after becoming multidrug-resistant, which may provide useful information on new drug target identification, an adriamycin-resistant variant of the human leukemia cell line K562 (K562/ADR) was developed in vitro by continuous exposure to adrimycin. MTT assay was used to determine IC50 of K562/ADR cells to adriamycin (ADR), cisplatin (DDP), 5-fluorouracil (5-FU) and vincristin (VCR). The total proteins of K562 and K562/ADR were separated by two-dimensional gel electrophoresis and visualized by silver staining. Proteins with significant expression alterations were selected and their peptide mass fingerprints (PMFs) were obtained by matrix-assisted laser desorption/ionization time of flying mass spectrometry (MALDI-TOF-MS). The PMFs were used to search NCBInr database by AutoMS-Fit software. The results showed that K562/ADR cell demonstrated cross-resistance to other antineoplastic drugs. The IC50 of K562/ADR cells to ADR, DDP, 5-FU, VDR were much higher than those of K562. The proteins differentially expressed in the two cell lines were identified as cell cycle-related proteins, zinc finger protein 165, etc. These proteins are involved in cell cycling and transcription regulation, whose expression alterations may contribute to the multidrug resistant phenotype of K562/ADR cells.
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PMID:[Development of a K562 multidrug-resistant cell line and study on proteins with altered expression]. 1472 45

Time changes in mortality rates can be used to suggest future trends in the prognosis of childhood cancer. Estimates provided from recent studies led to divergent previsions of future trends. In this study we used data from the population-based Childhood Cancer Registry of Piedmont (CCRP) in order to measure the decrease in mortality. The study included 1,060 deaths in the period 1971-1998. Analyses were carried out using Poisson regression models and considered separately the total tumours, acute lymphoblastic leukaemia (ALL) and tumours of the central nervous system (CNS). We observed a progressive decline in the mortality rates: for all tumours the estimated annual percentage change was -3.6% (P < 0.05), for ALL it was -5.2%, (P < 0.05) and for CNS tumours it was -3.8% (P < 0.05). The statistical test for effect modification due to age at death was not significant. For all cancer types, the Poisson model fits the data well, corresponding to an exponential decrease of mortality rates and leading to the conclusion that current therapies, despite their proven effectiveness, are not sufficient to cure all cases of childhood cancer.
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PMID:Time trends of childhood cancer mortality rates: a report from the Childhood Cancer Registry of Piedmont, Italy, 1971-1998. 1539 Feb 82

Despite substantial progress in the management of childhood acute myeloid leukemia (AML), only about 50% of patients are cured by intensive chemotherapy. The long-term results of clinical trials may reveal principles that can guide the development of future therapy. From 1980 to 2000, 251 patients <15 years of age with newly diagnosed AML were enrolled on one of the five consecutive St Jude AML studies. The median age of the 128 boys and 123 girls was 6.2 years; 193 were white, 45 black, and 13 of other racial groups. With the exception of one protocol (AML-83), outcomes improved in general over the two decades. The estimated 5-year event-free survival (+/-s.e.) was 30.8+/-5.6% for AML-80; 11.1+/-4.3% for AML-83; 35.9+/-7.4% for AML-87; 43.5+/-6.2% for AML-91; and 45.0+/-11.1% for AML-97. Resistant or relapsed AML caused the great majority of treatment failures. Increasing the intensity of chemotherapy (AML-87) did not improve outcome, partially because of toxicity, nor did prolonging postremission therapy by adding sequential myeloablative (AML-80) or nonmyeloablative (AML-83) chemotherapy cycles. We conclude that subtype-specific therapies are needed to replace the 'one size fits all' strategy of the past two decades.
Leukemia 2005 Dec
PMID:Successive clinical trials for childhood acute myeloid leukemia at St Jude Children's Research Hospital, from 1980 to 2000. 1628 Oct 77

In this communication, we report an acute leukemia patient who developed conversion disorder mimicking the adverse effects of high-dose cytosine arabinoside (Ara-C) treatment after the patient received high-dose Ara-C treatment. A 21-year-old woman, with acute recurrent leukemia after bone marrow transplantation, received high-dose Ara-C treatment and 10 days later was referred for psychiatric consultation because of an abrupt onset of convulsion. On neurologic examination, she showed convulsion of all the limbs without loss of consciousness. All limbs looked paretic; however, tendon reflexes in all limbs were normal and pathological reflex was not recognized. When her hand was dropped onto her own face, it fell next to her face but not on her face. Laboratory data were unremarkable. She had no history of psychiatric illness or drug or alcohol abuse. The patient explained that she knew about the recurrence of her own leukemia and the news of the death of a close friend due to leukemia at the same time, which was a shocking event for her, focusing her attention on her own fears of dying from the same disease. Conversion disorder in cancer patients is not common; however, appropriate diagnosis is very important to avoid inappropriate examinations and treatments. In leukemia patients receiving chemotherapy, various kinds of signs and symptoms may develop due to the adverse effects of chemotherapy and/or infection. Therefore, conversion disorder might be overlooked and inappropriate treatment and examinations might be performed. Clinicians should consider conversion disorder in the differential diagnosis when patients develop unexplained neurological symptoms.
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PMID:Conversion disorder with convulsion and motor deficit mimicking the adverse effects of high-dose Ara-C treatment in a posttransplant acute myeloid leukemia patient: a case report and review of the literature. 1659 37

There is much uncertainty about cancer risks at the high radiation doses used in radiotherapy (RT). It has generally been assumed that cancer induction decreases rapidly at high doses due to cell killing. However, this is not seen in all RT groups, and a model recently developed by Sachs and Brenner [2005. Solid tumor risks after high doses of ionizing radiation. Proc. Natl Acad. Sci. USA 102, 13040-13045] proposed a mechanism for repopulation of cells after radiation exposure that explained why this might happen, at least for solid tumours. In this paper, this model is generalized to allow for heterogeneity in the dose received, and various alternate patterns of repopulation are also considered. The model is fitted to the Japanese atomic bomb survivor leukaemia incidence data, and data for various therapeutically irradiated groups. Two sets of parameters from these model fits are used to assess the sensitivity of model predictions. It is shown that in general allowing for heterogeneity in dose distribution and haematopoietic stem cell migration results in lower risks than the same average dose administered uniformly and without such migration, although this does not hold in the limiting case of complete stem cell repopulation between radiation dose fractions. We also investigate the difference made by assuming a compartmental repopulation signal, and a global repopulation signal. In general we show that in the absence of stochastic extinction, compartmental repopulation always predicts a larger number of mutated cells than global repopulation. However, in certain dose regimes stochastic extinction cannot be ignored, and in these cases the numbers of mutated cells predicted with global repopulation can exceed that for compartmental repopulation. In general, mutant cell numbers are highly overdispersed, with variance much greater than the mean.
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PMID:A multi-compartment cell repopulation model allowing for inter-compartmental migration following radiation exposure, applied to leukaemia. 1709 22

10-Decarbamoyl-mitomycin C (DMC), a mitomycin C (MC) derivative, generates an array of DNA monoadducts and interstrand cross-links stereoisomeric to those that are generated by MC. DMC was previously shown in our laboratory to exceed the cytotoxicity of MC in a human leukemia cell line that lacks a functional p53 pathway (K562). However, the molecular signal transduction pathway activated by DMCDNA adducts has not been investigated. In this study, we have compared molecular targets associated with signaling pathways activated by DMC and MC in several human cancer cell lines. In cell lines lacking wild-type p53, DMC was reproducibly more cytotoxic than MC, but it generated barely detectable signal transduction markers associated with apoptotic death. Strikingly, DMCs increased cytotoxicity was not associated with an increase in DNA double-strand breaks but was associated with early poly(ADP-ribose) polymerase (PARP) activation and Chk1 kinase depletion. Alkylating agents can induce increased PARP activity associated with programmed necrosis, and the biological activity of DMC in p53-null cell lines fits this paradigm. In cell lines with a functional p53 pathway, both MC and DMC induced apoptosis. In the presence of p53, both MC and DMC activate procaspases; however, the spectrum of procaspases involved differs for the two drugs, as does induction of p73. These studies suggest that in the absence of p53, signaling to molecular targets in cell death can shift in response to different DNA adduct structures to induce non-apoptotic cell death.
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PMID:Mitomycin-DNA adducts induce p53-dependent and p53-independent cell death pathways. 1753 Jul 33

A methodology is developed that determines age-specific transition rates between cell cycle phases during balanced growth by utilizing age-structured population balance equations. Age-distributed models are the simplest way to account for varied behavior of individual cells. However, this simplicity is offset by difficulties in making observations of age distributions, so age-distributed models are difficult to fit to experimental data. Herein, the proposed methodology is implemented to identify an age-structured model for human leukemia cells (Jurkat) based only on measurements of the total number density after the addition of bromodeoxyuridine partitions the total cell population into two subpopulations. Each of the subpopulations will temporarily undergo a period of unbalanced growth, which provides sufficient information to extract age-dependent transition rates, while the total cell population remains in balanced growth. The stipulation of initial balanced growth permits the derivation of age densities based on only age-dependent transition rates. In fitting the experimental data, a flexible transition rate representation, utilizing a series of cubic spline nodes, finds a bimodal G(0)/G(1) transition age probability distribution best fits the experimental data. This resolution may be unnecessary as convex combinations of more restricted transition rates derived from normalized Gaussian, lognormal, or skewed lognormal transition-age probability distributions corroborate the spline predictions, but require fewer parameters. The fit of data with a single log normal distribution is somewhat inferior suggesting the bimodal result as more likely. Regardless of the choice of basis functions, this methodology can identify age distributions, age-specific transition rates, and transition-age distributions during balanced growth conditions.
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PMID:Identification of age-structured models: cell cycle phase transitions. 1778 14

Excess body weight (overweight and obesity) is characterized by chronic hyperinsulinaemia and insulin resistance, and is implicated both in cancer risk and cancer mortality. The list of cancers at increased risk of development in an "obesogenic" environment include common adult cancers such as endometrium, post-menopausal breast, colon and kidney, but also less common malignancies such as leukaemia, multiple myeloma, and non-Hodgkin's lymphoma. The pathophysiological and biological mechanisms underpinning these associations are only starting to be understood. Insulin resistance is at the heart of many, but there are several other candidate systems including insulin-like growth factors, sex steroids, adipokines, obesity-related inflammatory markers, the nuclear factor kappa beta (NF-kappa B) system and oxidative stresses. With such as diversity of obesity-related cancers, it is unlikely that there is a "one system fits all" mechanism. While public health strategies to curb the spread of the obesity epidemic appear ineffective, there is a need to better understand the processes linking obesity and cancer as a pre-requisite to the development of new approaches to the prevention and treatment of obesity-related cancers.
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PMID:Obesity and cancer: pathophysiological and biological mechanisms. 1846 61

In 1982, chronic myelomonocytic leukemia (CMML) was first classified in the category of myelodysplastic syndromes (MDSs), but it always seemed somewhat out of place compared with the rest of the MDS categories. In the 1990s, many argued that there were two different forms of CMML, a proliferative type and a myelodysplastic type. Then in 2001 the World Health Organization created a new category called the mixed myelodysplastic/myeloproliferative diseases, under which CMML was included. Although we still do not understand much about CMML pathogenesis nor do we have specific therapies for this disease, at least now most agree that it is in an appropriate category such that other areas of investigation can now proceed. On the other hand, we now understand a great deal of the pathogenesis underlying the disease now called juvenile myelomonocytic leukemia (JMML). JMML also fits in the new category of mixed myelodysplastic/myeloproliferative diseases. JMML is an excellent model malignancy for investigating and understanding dysregulated and aberrant signal transduction in the Ras pathway. It has also served as a teaching tool for exploring inherited predispositions to cancer.
Leukemia 2008 Jul
PMID:Juvenile myelomonocytic leukemia and chronic myelomonocytic leukemia. 1854 91


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