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The role of cholesterol metabolism in leukemia.

Leukemia is a common hematological malignancy with overall poor prognosis. Novel therapies are needed to improve the outcome of leukemia patients. Cholesterol metabolism reprogramming is a featured alteration in leukemia. Many metabolic-related genes and metabolites are essential to the progress and drug resistance of leukemia. Exploring potential therapeutical targets related to cholesterol homeostasis is a promising area. This review summarized the functions of cholesterol and its derived intermediate metabolites, and also discussed potential agents targeting this metabolic vulnerability in

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… Lipids 2017 ; 52 (6) : 523 – 534 . 28488049 10.1007/s11745-017-4256-z PMC5486594 [9] Advani AS McDonough S Copelan E SWOG0919: a Phase 2 study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia . … Leuk Lymphoma 2001 ; 40 (5–6) : 659 – 662 . 11426537 10.3109/10428190109097663 [55] Kornblau SM Banker DE Stirewalt D Blockade of adaptive defensive changes in cholesterol uptake and synthesis in AML by the addition of pravastatin to idarubicin + high-dose Ara-C: a phase 1 study . …

Reduction of endoplasmic reticulum stress--a novel mechanism of action of statins in the protection against atherosclerosis.

Fatty-acid-induced endoplasmic reticulum stress has been recently described as a novel mechanism involved in the genesis of atherosclerosis. Here we show that statins, a class of drug widely employed in the clinical management of hypercholesterolemia, reduces lipid-induced macrophage endoplasmic reticulum stress in an isolated cell system and in LDL receptor knockout mice. Given the importance of endoplasmic reticulum stress as an inducer of inflammation, we suspect that the novel mechanism of action herein described for statins may play a major role on its beneficial effects in the prevention

Statins for children with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia is one of the most common inherited metabolic diseases and is an autosomal dominant disorder meani … may slightly improve flow-mediated dilatation of the brachial artery (low-quality evidence), and on pravastatin for two years may have induced a regression in carotid intima media thickness (low-quality evidence). No studies reported rhabdomyolysis (degeneration of skeletal muscle tissue) or death due to rhabdomyolysis, quality of life or compliance to study …

Lowering Targeted Atherogenic Lipoprotein Cholesterol Goals for Patients at "Extreme" ASCVD Risk.

PURPOSE OF REVIEW: To review randomized interventional clinical and imaging trials that support lower targeted atherogenic lipoprotein chole … opulations in the Heart Protection Study (HPS), the acute coronary syndrome (ACS) population in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trial (PROVE-IT), and the secondary prevention population in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) intravascular ultrasound …

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

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… Lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin are available in most parts of the world. Lovastatin, simvastatin, and pravastatin are all fungal derivatives, whereas fluvastatin and atorvastatin are synthetic. … Patients were then randomly assigned to control ( n = 42) and pravastatin ( n = 41) groups at a daily dose of 40 mg. Median survival was 18 months in the pravastatin group vs. 9 months in controls ( p = 0.006). …

[Statins in patients with kidney failure: efficacy, tolerance, and prescription guidelines in patients with chronic kidney disease and renal transplant].

BACKGROUND: Chronic kidney disease (CKD) is extremely common in adults, although often undiagnosed and thus untreated. Cardiovascular disease is the leading cause of death among patients with CKD and reducing its risk in this population is an important priority. Dyslipidemia is almost always present when proteinuria is above 3 gr/24 hours. Roughly two thirds of all patients with end-stage renal failure and kidney transplants suffer from dyslipidemia and should receive lipid-lowering therapy, as suggested by recent Afssaps (French drug agency) and NKF-K/DOQI (National Kidney Foundation-Kidney D

Early bilirubinemia after allogeneic stem cell transplantation-an endothelial complication.

Hyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0-28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, inter

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… Left panel: no statin-based endothelial protection (SEP) with pravastatin and UDA, right panel: patients with SEP. … EB and endothelial prophylaxis with statins and UDCA In the training cohort, the incidence of EB (VOD excluded) was not different in patients with SEP (with pravastatin and UDA, n = 492) compared to patients without SEP ( n = 381) (12.2% vs. 13.9%). …

[OATP 1B1 T521C/A388G is an important polymorphism gene related to neonatal hyperbilirubinemia].

OBJECTIVE: Multiple genetic and environmental factors contribute to the onset of many human diseases, such as neonatal hyperbilirubinemia. OATP 1B1 is an important polymorphism gene which transmembrane transports unconjugated bilirubin(UCB). Genetic polymorphisms that affect the functionality of the protein may potentially lead to altered transport characteristics. The T521C/A388G polymorphism of this gene has been reported to considerably reduce the transporting property of drugs like pravastatin, and may be involved in the membrane translocation of bilirubin. Some studies have shown that OAT…

Results of a safety initiative for patients on concomitant amiodarone and simvastatin therapy in a Veterans Affairs medical center.

BACKGROUND: The FDA revised the labels of amiodarone and simvastatin in 2002 to warn of increased risk of rhabdomyolysis, the most severe fo … ozil and nicotinic acid, that may increase the risk of myopathy). Patients were converted to either pravastatin or rosuvastatin based on baseline simvastatin dose, low-density lipoprotein cholesterol (LDL-C) level, and renal function. The conversion protocol was developed to maintain LDL-C lowering with potentially safer statins. Follow-up lipid and aminotran …

16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends.

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive ther

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… All women received treatment with LDA plus LMWH and 11/21 received additional pravastatin (20 mg/d). … Pravastatin blocks TF and PAR2 expression on neutrophils and increases vitamin D levels in animal models, 84,98 suggesting that these effects could underlie its potential efficacy in treating pregnant patients with APS. …

Lenalidomide-Associated Rhabdomyolysis Progressing to Bilateral Compartment Syndrome and Permanent Foot Drop.

Lenalidomide is widely used for the treatment and maintenance of multiple myeloma and is generally considered to have a favorable safety profile. However, severe skeletal muscle toxicity associated with lenalidomide has been rarely reported. We describe a 52-year-old man with multiple myeloma who developed acute bilateral lower-extremity pain, cramping, weakness, and paresthesia while receiving lenalidomide therapy. Laboratory evaluation revealed marked rhabdomyolysis, and imaging and clinical findings were consistent with bilateral lower-leg compartment syndrome. Despite emergent bilateral fa

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… . | 49 F | 5 mg: 3 months 10 mg: 8 days a | Fludarabine and rituximab | 1051 | 2.39 | No | Pravastatin Urata et al. | 77 M | 5 days | Dexamethasone | 16,126 | 1.49 | No | Pravastatin Rathore and Singh | 75 F | — | Dexamethasone and bortezomib | 4489 | — | No | Acute dehydration Blair et al. | 49 M | … C., Rhabdomyolysis in a Multiple Myeloma Patient Secondary to Concurrent Treatment With Lenalidomide and Pravastatin and to Lenalidomide Alone, International Journal of Hematology. (2012) 96, no. 6, 818–819, 10.1007/s12185-012-1226-3, 23188472. 12. …

Repurposing Drugs for Acute Myeloid Leukemia: A Worthy Cause or a Futile Pursuit?

Acute myeloid leukemia (AML) is a clinically and genetically heterogenous malignancy of myeloid progenitor cells that affects patients of all ages. Despite decades of research and improvement in overall outcomes, standard therapy remains ineffective for certain subtypes of AML. Current treatment is intensive and leads to a number of secondary effects with varying results by patient population. Due to the high cost of discovery and an unmet need for new targeted therapies that are well tolerated, alternative drug development strategies have become increasingly attractive. Repurposing existing d

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… Escalating doses of pravastatin were co-administered with idarubicin/high dose cytarabine to block the adaptive cholesterol response in AML cells [ 51 ]. … Of the 37 patients enrolled, 20 achieved CR/complete remission with incomplete platelet recovery (CRp) without toxicity associated with pravastatin [ 51 ]. …

Combined therapy with atorvastatin and calcineurin inhibitors: no interactions with tacrolimus.

Increased systemic exposure to statins and consequent risk for complications has been reported in patients concomitantly treated with cyclosporin A (CsA). This has been ascribed to inhibition of drug catabolism by cytochrome P450 3A4 (CYP3A4) or drug transport by P-glycoprotein (PGP) and organic anion transporting polypeptide (OATP1B1). It is not known whether the combination of statins and tacrolimus (Tac) also suffers from this drawback. Therefore, a pharmacokinetic study of atorvastatin and its metabolites was performed in 13 healthy volunteers after 4 days' treatment, and after short (12 h

Statins for non-alcoholic fatty liver disease and non-alcoholic steatohepatitis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common causes of elevated liver enzymes i … sess the beneficial and harmful effects of statins (that is, lovastatin, atorvastatin, simvastatin, pravastatin, rosuvastatin, and fluvastatin) on all-cause and liver-related mortality, adverse events, and histological, biochemical, and imaging responses in patients with NAFLD or NASH. SEARCH METHODS: We performed a computerised literature search in the Coch …

Statins for the primary prevention of venous thromboembolism.

BACKGROUND: Venous thromboembolism (VTE) involves the formation of a blood clot in a vein, and includes deep venous thrombosis (DVT) or pulm … als who had never experienced VTE. The statins used in the studies were atorvastatin, rosuvastatin, pravastatin, lovastatin, fluvastatin, and simvastatin. Twenty-three studies followed up participants for over a year, with six of those extending follow-ups for over five years. Twenty-five studies were based in hospitals, and 24 studies were funded by industry …

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE.

OBJECTIVE: The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Director … sin/kexin type 9 Post CABG = Post Coronary Artery Bypass Graft trial PROSPER = Prospective Study of Pravastatin in the Elderly at Risk trial QALY = quality-adjusted life-year ROC = receiver-operator characteristic SOC = standard of care SHARP = Study of Heart and Renal Protection T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus TG = triglycerid …

Japan Atherosclerosis Society (JAS) Guidelines for Prevention of Atherosclerotic Cardiovascular Diseases 2022.

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… In a sub-analysis of the MEGA Study, which was a randomized controlled trial examining the effect of pravastatin on the primary prevention of CVD in patients aged 40-70 years with hypercholesterolemia, associations between HbA1c and CVD incidence were evaluated by multivariable Cox proportional hazards …

Polymorphisms in CXCR3 ligands predict early CXCL9 recovery and severe chronic GVHD.

Chronic graft-versus-host disease (cGVHD) is a major cause of mortality and morbidity after allogeneic stem cell transplantation (alloSCT). The individual risk of severe cGVHD remains difficult to predict and may involve CXCR3 ligands. This study investigated the role of single-nucleotide polymorphisms (SNPs) of CXCL4, CXCL9, CXCL10, and CXCL11, and their day +28 serum levels, in cGVHD pathogenesis. Eighteen CXCR3 and CXCL4, CXCL9-11 SNPs as well as peri-transplant CXCL9-11 serum levels were analyzed in 688 patients without (training cohort; n = 287) or with statin-based endothelial protection

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… SEP consists of pravastatin 20 mg/day and ursodeoxycholic acid (UDCA) 3 × 250 mg/day 28 , 29 , and was used as a standard treatment in Heidelberg University Hospital since 01/2010. … Effects of pravastatin on murine chronic graft-versus-host disease. Transplantation. 2010;90:853–860. doi: 10.1097/TP.0b013e3181f2c92b. 54. Rotta M, et al. Impact of recipient statin treatment on graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biol. …

Current Approaches in the Treatment of Relapsed and Refractory Acute Myeloid Leukemia.

The limited sensitivity of the historical treatment response criteria for acute myeloid leukemia (AML) has resulted in a different paradigm for treatment compared with most other cancers presenting with widely disseminated disease. Initial cytotoxic induction chemotherapy is often able to reduce tumor burden to a level sufficient to meet the current criteria for "complete" remission. Nevertheless, most AML patients ultimately die from their disease, most commonly as clinically evident relapsed AML. Despite a variety of available salvage therapy options, prognosis in patients with relapsed or r

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… SWOG0919: A phase 2 study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukaemia. Br. J. Haematol. 2014;167:233–237. doi: 10.1111/bjh.13035. 57. … Idarubicin, cytarabine and pravastatin as induction therapy for untreated acute myeloid leukemia and high-risk myelodysplastic syndrome. Blood. 2014;124:3732. doi: 10.1002/ajh.23981. 119. …