Studies on the Chemotherapy of the Human Malarias. Vi. The Physiological Disposition, Antimalarial Activity, and Toxicity of Several Derivatives of 4-Aminoquinoline 12

Berliner, Robert W.; Earle, David P.; Taggart, John V.; Zubrod, C. Gordon; Welch, William J.; Conan, Neal J.; Bauman, Eli; Scudder, Sidney T.; Shannon, James A.

doi:10.1172/jci101980

Cited by 169 publications

(54 citation statements)

References 6 publications

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“…Based on the ophthalmologic safety guidelines for longterm use of chloroquine in humans (40), chloroquine can be administered with the low dose of 3.5 mg/kg of body weight daily for several years. Furthermore, chloroquine shows two interesting pharmacologic characteristics, extensive tissue accumulation and prolonged retention in the tissues after drug administration has ceased (41). Chloroquine has been shown to be retained in the body for several weeks after a single i.v.…”

Section: Discussionmentioning

confidence: 99%

Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis

Loehberg

Thompson²,

Kastan³

et al. 2007

Cancer Research

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The use of agents to prevent the onset of and/or the progression to breast cancer has the potential to lower breast cancer risk. We have previously shown that the tumor-suppressor gene p53 is a potential mediator of hormone (estrogen/progesterone)-induced protection against chemical carcinogen-induced mammary carcinogenesis in animal models. Here, we show for the first time a breast cancer-protective effect of chloroquine in an animal model. Chloroquine significantly reduced the incidence of N-methyl-N-nitrosourea-induced mammary tumors in our animal model similar to estrogen/progesterone treatment. No protection was seen in our BALB/c p53-null mammary epithelium model, indicating a p53 dependency for the chloroquine effect. Using a human nontumorigenic mammary gland epithelial cell line, MCF10A, we confirm that in the absence of detectable DNA damage, chloroquine activates the tumor-suppressor p53 and the p53 downstream target gene p21, resulting in G 1 cell cycle arrest. p53 activation occurs at a posttranslational level via chloroquine-dependent phosphorylation of the checkpoint protein kinase, ataxia telangiectasia-mutated (ATM), leading to ATM-dependent phosphorylation of p53. In primary mammary gland epithelial cells isolated from p53-null mice, chloroquine does not induce G 1 cell cycle arrest compared with cells isolated from wildtype mice, also indicating a p53 dependency. Our results indicate that a short prior exposure to chloroquine may have a preventative application for mammary carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis

Loehberg

Thompson²,

Kastan³

et al. 2007

Cancer Research

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“…In 1948, the chloroquine concentration required to cure patients with P. vivax malaria was the equivalent of a mean, whole blood, total chloroquine concentration of 100 ng/mL over 4 days. 28 This level was achieved with chloroquine doses of 275-650 mg (ϳ4-10 mg/kg for a 70kg adult). In Sweden in 1987, standard dose chloroquine (25 mg/kg) cured all 15 adults with non P. falciparum malaria (P. vivax, P. ovale, and P. malariae).…”

Section: Discussionmentioning

confidence: 99%

Assessing drug sensitivity of Plasmodium vivax to halofantrine or choroquine in southern, central Vietnam using an extended 28-day in vivo test and polymerase chain reaction genotyping.

Taylor¹,

Doan²,

Nguyen³

et al. 2000

The American Journal of Tropical Medicine and Hygiene

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Abstract. Chloroquine-resistant Plasmodium vivax malaria is emerging in Oceania, Asia, and Latin America. We assessed the drug sensitivity of P. vivax to chloroquine or halofantrine in two villages in southern, central Vietnam. This area has chloroquine-resistant Plasmodium falciparum but no documented chloroquine-resistant P. vivax. Standard dose chloroquine (25 mg/kg, over 48 hours) or halofantrine (8 mg/kg, 3 doses) was administered to 29 and 25 patients, respectively. End points were parasite sensitivity or resistance determined at 28 days. Of the evaluable patients, 23/23 100% (95% confidence interval [CI] 85.1-100) chloroquine and 21/24 (87.5%) (95% CI 67.6-97.3) halofantrine-treated patients were sensitive. Three halofantrine recipients had initial clearance but subsequent recurrence of their parasitemias. Genotyping of the recurrent and Day 0 parasitemias differed, suggesting either new infections or relapses of liver hypnozoites from antecedent infections. Among these Vietnamese patients, P. vivax was sensitive to chloroquine and halofantrine. Genotyping was useful for differentiating the recurrent vivax parasitemias.

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“…Normal blood may also be used for this purpose. In this case, the dilution to be used is selected as the one which, in the (4). The concentrations were done merely to confirm the presence of parasites in the circulating blood and no attempt was made to detect parasites at the earliest possible date.…”

Section: Methodsmentioning

confidence: 99%

A Technique for the Detection of Minimal Numbers of Malaria Parasites; Its Application in the Detectin of Suppressed Vivax Malaria 123

Berliner¹,

Kennedy²,

Bigelow³

1948

J. Clin. Invest.

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It has been demonstrated, by the subinoculation of large volumes of blood, that malaria parasites are present in the peripheral circulation of individuals who have been bitten by infected mosquitoes but whose disease is suppressed with adequate treatment (1). Since each examination by this procedure requires the use of an additional volunteer subject, a substitute method which yields the same information without necessitating a corresponding utilization of recipients should be highly desirable.Whereas not less than 10 malaria parasites per mm.8 or 10,000 per cm.3 of blood are required to be uniformly detectable by the usual thick smear examination, the method of Ferrebee and Geiman (2) for the preparation of concentrates of parasitized red blood cells is applicable, with slight modification, to the demonstration of Plasmodium vivax at parasite densities far below those required for detection by the routine laboratory method. The modified concentration technique permits the demonstration of parasites when they are present in concentrations of less than 100 per cm.8 of blood.

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Studies on the Chemotherapy of the Human Malarias. Vi. The Physiological Disposition, Antimalarial Activity, and Toxicity of Several Derivatives of 4-Aminoquinoline 12

Cited by 169 publications

References 6 publications

Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis

Ataxia Telangiectasia-Mutated and p53 Are Potential Mediators of Chloroquine-Induced Resistance to Mammary Carcinogenesis

Assessing drug sensitivity of Plasmodium vivax to halofantrine or choroquine in southern, central Vietnam using an extended 28-day in vivo test and polymerase chain reaction genotyping.

A Technique for the Detection of Minimal Numbers of Malaria Parasites; Its Application in the Detectin of Suppressed Vivax Malaria 123

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