Reprofiling a Classical Anthelmintic, Pyrvinium Pamoate, as an Anti-Cancer Drug Targeting Mitochondrial Respiration.

Reprofiling a classical anthelmintic, pyrvinium pamoate, as an anti-cancer drug targeting mitochondrial respiration.

Filed under: Drug and Alcohol Rehabilitation

Front Oncol. 2012; 2: 137
Ishii I, Harada Y, Kasahara T

Pyrvinium pamoate (PP) is an FDA-approved classical anthelmintic, but is now attracting particular attention as an anti-cancer drug after recent findings of its potent cytotoxicity against various cancer cell lines only during glucose starvation, as well as its anti-tumor activity against hypovascular pancreatic cancer cells transplanted in mice. The molecular mechanisms by which PP promotes such preferential toxicity against cancer cells are currently under extensive investigation. PP suppressed the NADH-fumarate reductase system that mediates a reverse reaction of the mitochondrial electron-transport chain complex II in anaerobic organisms such as parasitic helminthes or mammalian cells under tumor microenvironment-mimicking hypoglycemic/hypoxic conditions, thereby inhibiting efficient ATP production. PP also inhibited the unfolded protein response induced by glucose starvation, thereby inhibiting the proliferation of pancreatic cancer cells. Even under normoglycemic/normoxic conditions, PP suppressed the mitochondrial electron-transport chain complex I and thereby STAT3, inhibiting the proliferation of myeloma/erythroleukemia cells. Here, we review accumulating knowledge on its working mechanisms and evaluate PP as a novel anti-cancer drug that targets mitochondrial respiration.
HubMed – drug


Plasmodium falciparum RuvB proteins: Emerging importance and expectations beyond cell cycle progression.

Filed under: Drug and Alcohol Rehabilitation

Commun Integr Biol. 2012 Jul 1; 5(4): 350-61
Ahmad M, Tuteja R

The urgent requirement of next generation antimalarials has been of recent interest due to the emergence of drug-resistant parasite. The genome-wide analysis of Plasmodium falciparum helicases revealed three RuvB proteins. Due to the presence of helicase motif I and II in PfRuvBs, there is a high probability that they contain ATPase and possibly helicase activity. The Plasmodium database has homologs of several key proteins that interact with RuvBs and are most likely involved in the cell cycle progression, chromatin remodeling, and other cellular activities. Phylogenetically PfRuvBs are closely related to Saccharomyces cerevisiae RuvB, which is essential for cell cycle progression and survival of yeast. Thus PfRuvBs can serve as potential drug target if they show an essential role in the survival of parasite.
HubMed – drug


Albuminuria-reducing effect of angiotensin II receptor blocker plus hydrochlorothiazide combination therapy in renal transplant recipients.

Filed under: Drug and Alcohol Rehabilitation

Exp Ther Med. 2012 Jul; 4(1): 105-108
Naganuma T, Takemoto Y, Uchida J, Ootoshi T, Kuwabara N, Maeda S, Nakatani T

In recent years, the combined use of angiotensin II receptor blockers (ARBs) and low-dose diuretics has become clinically possible. Moreover, the GUARD and J-CORE studies have confirmed that the addition of low-dose diuretics to renin-angiotensin system inhibitors reduces albuminuria. In this study, we investigated the clinical effects of a combination drug containing an ARB and a low-dose diuretic in renal transplant recipients. A total of 13 renal transplant recipients who were receiving the maximum dose of the ARB and presenting with microalbuminuria [urine albumin-creatinine ratio (ACR) of 30-300 mg/g-Cre] were converted to a single pill combination drug containing the same amount of the ARB and 12.5 mg of hydrochlorothiazide (HCTZ) and an intervention study of a crossover trial design was conducted. The clinical parameters were measured at baseline, 3 months after ARB/HCTZ conversion and 3 months after reverting to the ARB and the resulting data were compared. Serum creatinine (S-Cre) and uric acid (UA) levels at 3 months after conversion were significantly higher than those at baseline. The levels of the estimated glomerular filtration rate (eGFR) and ACR at 3 months were significantly lower than those at baseline. S-Cre and UA levels at 3 months after reversion were significantly lower than those at 3 months after conversion. The eGFR and levels of ACR and UA at 3 months after ARB reversion were significantly higher than those at 3 months after conversion. The results of this preliminary study suggest that the combination drug containing an ARB and low-dose diuretic was effective for reducing microalbuminuria in renal transplant recipients. In the future, larger cohort studies are needed to confirm these findings.
HubMed – drug


Retrospective analysis of 119 cases of pediatric acute promyelocytic leukemia: Comparisons of four treatment regimes.

Filed under: Drug and Alcohol Rehabilitation

Exp Ther Med. 2012 Jul; 4(1): 93-98
Li EQ, Xu L, Zhang ZQ, Xiao Y, Guo HX, Luo XQ, Hu Q, Lai DB, Tu LM, Jin RM

Clinical trials have demonstrated that pediatric acute promyelocytic leukemia (APL) is highly curable. Small-scale studies have reported on the treatment of APL using one or two treatment regimes. Here, we report a multiple center-based study of 119 cases of pediatric APL treated with four regimes based on all-trans-retinoic acid (ATRA). We retrospectively analyzed the clinical characteristics, laboratorial test results and treatment outcome of the pediatric APL patients. Regime 1 used an in-house developed protocol, regime 2 was modified from the PETHEMA LPA99 protocol, regime 3 was modified from the European-APL93 protocol, and regime 4 used a protocol suggested by the British Committee for Standards in Haematology. The overall complete remission rates for the four regimes were 88.9, 87.5, 97.1 and 87.5%, respectively, which exhibited no statistical difference. However, more favorable results were observed for regimes 2 and 3 than regimes 1 and 4, in terms of the estimated 3.5-year disease-free survivals, relapse rates, drug toxicity (including hepatotoxicity, cardiac arrhythmia, and differentiation syndrome) and sepsis. In conclusion, the overall outcomes were more favorable after treatment with regimes 2 and 3 than with regimes 1 and 4, and this may have been due to the specific compositions of regimes 2 and 3.
HubMed – drug



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