Objectives The frontline drug doxorubicin has been used for treating cancer for over 30 years. While providing a cure in select cases, doxorubicin causes toxicity to most major organs, especially life-threatening cardiotoxicity, which forces the treatment to become dose-limiting.

Key findings  Doxorubicin is known to bind to DNA-associated enzymes, intercalate with DNA base pairs, and target multiple molecular targets to produce a range of cytotoxic effects. For instance, it causes the activation of various molecular signals from AMPK (AMP-activated protein kinase inducing apoptosis) to influence the Bcl-2/Bax apoptosis pathway. By altering the Bcl-2/Bax ratio, downstream activation of different caspases can occur resulting in apoptosis. Doxorubicin also induces apoptosis and necrosis in healthy tissue causing toxicity in the brain, liver, kidney and heart. Over the years, many studies have been conducted to devise a drug delivery system that would eliminate these adverse affects including liposomes, hydrogel and nanoparticulate systems, and we highlight the pros and cons of these drug delivery systems.

Summary  Overall the future for the continued use of doxorubicin clinically against cancer looks set to be prolonged, provided certain enhancements as listed above are made to its chemistry, delivery and toxicity. Increased efficacy depends on these three aims being met satisfactorily as discussed in turn in this review.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.2042-7158.2012.01567.x

Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems

The Metabolic Basis of Inherited Disease

Tier Institution Type 2009 Rate Primary/secondary school (on site access only) Private practice office or private clinic Residency program (independent from larger institution; on site access only) General reference public library, museum, or non‐profit administrative office; government library without major scientific research program (on site access only) Junior college/2‐year college, tech school Nursing school or allied health training program; seminary 1

THE JOURNAL OF BIOLOGICAL CHEMISTRY: The Biochemical Behavior of LeadL I. Influence of Calcium, Phosphorus, and Vitamin D on Lead in Blood and Bone

Acanthamoeba spp. are free-living amebae that inhabit a variety of air, soil, and water environments. However, these amebae can also act as opportunistic as well as nonopportunistic pathogens. They are the causative agents of granulomatous amebic encephalitis and amebic keratitis and have been associated with cutaneous lesions and sinusitis. Immuno compromised individuals, including AIDS patients, are particularly susceptible to infections with Acanthamoeba. The immune defense mechanisms that operate against Acanthamoeba have not been well characterized, but it has been proposed that both innate and acquired immunity play a role. The ameba's life cycle includes an active feeding trophozoite stage and a dormant cyst stage. Trophozoites feed on bacteria, yeast, and algae. However, both trophozoites and cysts can retain viable bacteria and may serve as reservoirs for bacteria with human pathogenic potential. Diagnosis of infection includes direct microscopy of wet mounts of cerebrospinal fluid or stained smears of cerebrospinal fluid sediment, light or electron microscopy of tissues, in vitro cultivation of Acanthamoeba, and histological assessment of frozen or paraffin-embedded sections of brain or cutaneous lesion biopsy material. Immunocytochemistry, chemifluorescent dye staining, PCR, and analysis of DNA sequence variation also have been employed for laboratory diagnosis. Treatment of Acanthamoeba infections has met with mixed results. However, chlorhexidine gluconate, alone or in combination with propamidene isethionate, is effective in some patients. Furthermore, effective treatment is complicated since patients may present with underlying disease and Acanthamoeba infection may not be recognized. Since an increase in the number of cases of Acanthamoeba infections has occurred worldwide, these protozoa have become increasingly important as agents of human disease.

Acanthamoeba spp. as agents of disease in humans.

https://www.internationaljournalofcardiology.com/article/S0167-5273(15)30342-9/pdf

Regulation of uric acid metabolism and excretion

Deoxycoformycin (DCF), a powerful inhibitor of adenosine deaminase1, by virtue of its immunosuppresive action2, has found clinical application for the treatment of several types of lymphatic leukemia3, 4. In fact, the prevention of the catabolism of deoxyAdo to deoxylno, results both in the accumulation of intracellular deoxyATP5, an inhibitor of ribonucleotide reductase, and in the depletion of ATP6. Indeed, it has been reported that human T lymphocyte cells are very sensitive to the cytotoxic action of deoxyAdo, and that their sensitivity to DCF is higher than B lymphocyte cells probably as a result of a reduced cytosolic 5’deoxynucletidase activity, with a concomitant preservation of the deoxyATP pool7. While many studies have been performed on the cytotoxicity of DCF on human lymphocytes and several reports describe its possible mechanism of action in this type of cells8, 9, the effect of this drug on different mammalian cells has not been thoroughly examined so far, also on account of the reported inefrkacy of DCF on the growth of cultured cells 10. Human colon carcinoma cultured cells are a model for the study of the responsiveness of this solid tumor to possible Chemotherapic agents. In view of the involvement of the purine salvage enzymes in the activation of purine analogs, the knowledge of their program in tumor cells might be of great help not only for the understanding of the analog mechanism of action, but also for the design of specific pro-drugs. In this line is the present study on the cytotoxicity of DCF in combination with deoxyAdo on both two human colon carcinoma (LOVO and HT29) and a Chinese hamster ovary (CHO K-l) cell Unes. The different sensitivity of the three cell lines to DCF is well related to their distinct purine salvage enzyme pattern, thus supporting, in a general point of view, the enzymatic approach to the choice of a suitable Chemotherapic agent.

Cytotoxicity of deoxycoformycin on human colon carcinoma cell lines.

Cytosolic 5'-nucleotidase/nucleoside phosphotransferase: a single assay for a bifunctional enzyme.

Bovine cytosolic 5'-nucleotidase IMP-GMP specific: cloning and expression of active enzyme in E. coli

Identification of the 5′‐Nucleotidase Activity Altered in Neurological Syndromes

Substrates and/or Inhibitors of IMP-GMP Specific Cytosolic 5′-Nucleotidase (cN-II)

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