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 family planning program is not restricted to population control; it also aims at the wider aspect of family welfare and human health. A large number of human diseases are due to genetic abnormalities. Examples are mongolism (Down's syndrome), ovarian dysgenesis (Turner's syndrome), nonfunctional testes (Klinefelter's syndrome), chronic myeloid leukemia, anemia, thalassemia, congenital malformations, and schizophrenia. Mental defects include imbeciles and the feebleminded. Constitutional diseases include diabetes, idiopathic epilepsy, pernicious anemia, and some thyroid abnormalities. Some chronic diseases also have a significant genetic component in their etiology, such as asthma and other allergies. About half of the stillbirths and embryonic wastage are suspected of being due to genetic malformations. Consanguinity has an important bearing on malformations and developmental anomalies. In India, where consanguinity is more frequent, malformations per 1000 births were 8.6 and 3.1 in 2 centers studied. Neural tube defects, harelip, cleft palate, and malformations of the gut and of limbs were prevalent. The population that needs genetic counseling is not large. Persons suffering from hereditary dise ases having a high risk of transmission should be advised to refrain fro m having children. A correct diagnosis, complete family history, and kn owledge of the literature on inherited disease is needed by the counselo rs. Family planning programs should include genetic counseling.
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PMID:Genetic counselling in family planning. 1225 20

Valproic acid (VPA) has been used for epilepsy treatment since the 1970s. Recently, it was demonstrated that it inhibits histone deacetylases (HDAC), modulates cell cycle, induces tumor cell death and inhibits angiogenesis in various tumor models. The exact anticancer mechanisms of VPA remains unclear, but HDAC inhibition, extracellular-regulated kinase activation, protein kinase C inhibition, Wnt-signaling activation, proteasomal degradation of HDAC, possible downregulation of telomerase activity and DNA demethylation participate in its anticancer effect. Hyperacetylation of histones, as a result of HDAC inhibition, seems to be the most important mechanism of VPA's antitumor action. Preclinical data suggest that the anticancer effect of chemotherapy is augmented when VPA is used in combination with cytostatics. Besides the effects of pretreatment with HDAC inhibitors, which increases the efficiency of 5-aza-2'-deoxycytidine, VP-16, ellipticine, doxorubicin and cisplatin, pre-exposure to VPA increases the cytotoxicity of topoisomerase II inhibitors. There are two suggested cell death mechanisms caused by potentiation of anticancer drugs by HDAC inhibitors that are neither exclusive nor synergistic. The first involves apoptosis and can be both p53 dependent or independent; the second involves mechanisms other than apoptosis. In resistant chronic myeloid leukemia (CML), VPA restores sensitivity to imatinib. We have demonstrated the synergistic effects of VPA and cisplatin in neuroblastoma cells. VPA can be taken orally, crosses the blood brain barrier and can be used for extended periods. Clinical trials in patients with malignancies are being conducted. The use of VPA prior to or together with anticancer drugs may thus prove a beneficial treatment.
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PMID:Valproic acid in the complex therapy of malignant tumors. 2021 99

Imatinib mesylate, a selective tyrosine kinase inhibitor, is the frontline therapeutic agent used for the treatment of chronic myeloid leukemia (CML), and its therapeutic efficacy is associated with trough concentrations. Therefore, monitoring imatinib trough concentrations is strongly recommended for successful treatment of CML patients. It has been recently shown that some drugs altered imatinib plasma levels in adult patients. However, drug interactions with imatinib in children are still unknown. Here, we report a case of a 12-year-old child with epilepsy who was also diagnosed with CML and given imatinib in addition to an enzyme-inducing antiepileptic drug, carbamazepine. Compared to population kinetics data, the data obtained for the patient showed a significant decrease of imatinib plasma concentrations. Our findings suggest that monitoring imatinib plasma concentrations in children receiving enzyme-inducing antiepileptic drugs is needed to optimize the therapeutic efficacy of imatinib.
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PMID:Carbamazepine-imatinib interaction in a child with chronic myeloid leukemia. 2525 68

Imatinib (IM) represents a breakthrough in the treatment of chronic myeloid leukemia (CML) by inhibiting the activity of Bcr-Abl tyrosine kinase. However, many patients exhibit resistance to IM in the clinic. Recent studies have indicated that sirtuin 1 (SIRT1), a class III histone deacetylase (HDAC), plays an important role in leukemogenesis. In addition, some HDAC inhibitors are being tested to determine their anti-cancer activities in clinical trials. Divalproex sodium (DVPX), a first-line treatment for epilepsy, is also a HDAC inhibitor. However, it is unclear whether the anti-leukemic effects of IM in combination with DVPX on CML cells are related to SIRT1. The aim of this study was to investigate the effects of IM in combination with DVPX on cell viability, apoptosis, and cell cycle arrest in CML cells and to explore the underlying mechanisms. It was found that DVPX enhanced IM-induced cell growth inhibition, apoptosis and cell cycle arrest in K562-S and K562-G cells. Surprisingly, the level of p-Bcr-Abl was similar in K562-S and K562-G cells. Moreover, IM combined with DVPX had no effects on the phosphorylation of Bcr-Abl and its downstream target STAT5. Further study revealed that SIRT1 expression was higher in K562-G cells compared with K562-S cells. DVPX enhanced the inhibitory effect of IM on SIRT1 expression in K562-S and K562-G cells. Furthermore, knockdown of SIRT1 promoted apoptosis of K562-G cells treated with IM and DVPX. These results indicate that DVPX may increase the sensitivity of CML cells to IM and reverse IM resistance by regulating SIRT1 expression.
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PMID:Divalproex sodium enhances the anti-leukemic effects of imatinib in chronic myeloid leukemia cells partly through SIRT1. 2544 87