In vivo efficacy and toxicity of curcumin nanoparticles in breast cancer treatment : a systematic review

Breast cancer is one of the most prevalent types of malignant tumors in the world, resulting in a high incidence of death. The development of new molecules and technologies aiming to apply more effective and safer therapy strategies has been intensively explored to overcome this situation. The association of nanoparticles with known antitumor compounds (including plant-derived molecules such as curcumin) has been considered an effective approach to enhance tumor growth suppression and reduce adverse effects. Therefore, the objective of this systematic review was to summarize published data regarding evaluations about efficacy and toxicity of curcumin nanoparticles (Cur-NPs) in in vivo models of breast cancer. The search was carried out in the databases: CINAHL, Cochrane, LILACS, Embase, FSTA, MEDLINE, ProQuest, BSV regional portal, PubMed, ScienceDirect, Scopus, and Web of Science. Studies that evaluated tumor growth in in vivo models of breast cancer and showed outcomes related to Cur-NP treatment (without association with other antitumor molecules) were included. Of the 528 initially gathered studies, 26 met the inclusion criteria. These studies showed that a wide variety of NP platforms have been used to deliver curcumin (e.g., micelles, polymeric, lipid-based, metallic). Attachment of poly(ethylene glycol) chains (PEG) and active targeting moieties were also evaluated. Cur-NPs significantly reduced tumor volume/weight, inhibited cancer cell proliferation, and increased tumor apoptosis and necrosis. Decreases in cancer stem cell population and angiogenesis were also reported. All the studies that evaluated toxicity considered Cur-NP treatment to be safe regarding hematological/biochemical markers, damage to major organs, and/or weight loss. These effects were observed in different in vivo models of breast cancer (e.g., estrogen receptor-positive, triple-negative, chemically induced) showing better outcomes when compared to treatments with free curcumin or negative controls. This systematic review supports the proposal that Cur-NP is an effective and safe therapeutic approach in in vivo models of breast cancer, reinforcing the currently available evidence that it should be further analyzed in clinical trials for breast cancer treatments

TP53 p.Arg337His geographic distribution correlates with adrenocortical tumor occurrence

Abstract Background The p.Arg337His mutation of the TP53 is the most frequent germline missense variant associated with cancer described so far in this gene. It is mainly found in the South and Southeastern regions of Brazil, where it has been associated with a high incidence of pediatric adrenocortical (ACT) and choroid plexus tumors. The frequency and geographic distribution of this mutation is largely unknown, except for the Parana State, where a mean prevalence of 0.27% was reported. In the present study, we developed a high‐throughput method for p.Arg337His genotyping, what allowed us to determine the frequency and geographic distribution of this mutation in a cohort from the most populous state in Brazil. Methods Consecutive samples from 31,612 newborns from São Paulo State were screened for p.Arg337His. The allelic discrimination was done by real‐time polymerase chain reaction (PCR) and the presence of haplotype A3 in carriers was examined by using allele‐specific oligonucleotide PCR, followed by nested‐PCR to detect the SNP rs9894946. Results We found 67 (0.21%) samples positive for this mutation. The highest p.Arg337His frequencies were found in the cities close to the boundary between São Paulo and Minas Gerais State. No association could be found between p.Arg337His and gender, ethnicity, premature birth or twinning. Remarkably, a trend was found between the geographic distribution of p.Arg337His carriers and occurrence of ACT. Conclusion We presented for the first time the p.Arg337His frequency among individuals unselected for any disease from a subset of the São Paulo State, the most populous in Brazil. The allele discrimination assay we presented here has proven to be a reliable and efficient method for high‐throughput genotyping. ACT was found to be a good sentinel cancer to suppose p.Arg337His presence in our region

Disclosing azole resistance mechanisms in resistant <i>Candida glabrata</i> strains encoding wild-type or gain-of-function <i>CgPDR1</i> alleles through comparative genomics and transcriptomics

AbstractThe pathogenic yeast Candida glabrataC. glabrataCgPDR1C. glabrataCgPDR1C. glabrataCgPDR1C. glabrat

Evaluation of biocompatibility, anti-inflammatory, and antinociceptive activities of pequi oil-based nanoemulsion in in vitro and in vivo models

Pequi oil (Caryocar brasiliense) contains bioactive compounds capable of modulating the inflammatory process; however, its hydrophobic characteristic limits its therapeutic use. The encapsulation of pequi oil in nanoemulsions can improve its biodistribution and promote its immunomodulatory effects. Thus, the objective of the present study was to formulate pequi oil-based nanoemulsions (PeNE) to evaluate their biocompatibility, anti-inflammatory, and antinociceptive effects in in vitro (macrophages—J774.16) and in vivo (Rattus novergicus) models. PeNE were biocompatible, showed no cytotoxic and genotoxic effects and no changes in body weight, biochemistry, or histology of treated animals at all concentrations tested (90–360 µg/mL for 24 h, in vitro; 100–400 mg/kg p.o. 15 days, in vivo). It was possible to observe antinociceptive effects in a dose-dependent manner in the animals treated with PeNE, with a reduction of 27 and 40% in the doses of 100 and 400 mg/kg of PeNE, respectively (p < 0.05); however, the treatment with PeNE did not induce edema reduction in animals with carrageenan-induced edema. Thus, the promising results of this study point to the use of free and nanostructured pequi oil as a possible future approach to a preventive/therapeutic complementary treatment alongside existing conventional therapies for analgesia.Instituto de Ciências Biológicas (IB)Departamento de Biologia Celular (IB CEL)Faculdade UnB Ceilândia (FCE)Curso de Farmácia (FCE-FAR)Faculdade de Medicina (FM)Faculdade UnB Gama (FGA)Faculdade UnB Planaltina (FUP)Programa de Pós-Graduação em Nanociência e NanobiotecnologiaPrograma de Pós-Graduação em Ciências e Tecnologias em Saúd

Shorter Maintenance Therapy in Childhood Acute Lymphoblastic Leukemia: The Experience of the Prospective, Randomized Brazilian GBTLI ALL-93 Protocol

Maintenance therapy is an important phase of the childhood ALL treatment, requiring 2-year long therapy adherence of the patients and families. Weekly methotrexate (MTX) with daily 6-mercaptopurine (6MP) constitutes the backbone of maintenance therapy. Reduction in the maintenance therapy could overweight problems related with poverty of children with ALL living in Limited-Income countries (LIC). Objective: To compare, prospectively, the EFS rates of children with ALL treated according to two maintenance regimens: 18 vs 24 months duration. Materials and Methods: From October 1993 to September 1999, 867 consecutive untreated ALL patients 10 years and high WBC at diagnosis). Overall death in remission rate was 6.85% (56 patients). Deaths during maintenance were 13 in group 1 and 12 in group 2, all due to infection. Over 15 years of follow-up, two patients both from Group 2 presented a second malignancy (Hodgkin’s disease and thyroid carcinoma) after 8.3 and 11 years off therapy, respectively. Conclusion: Six-month reduction of maintenance therapy in ALL children treated according to the GBTLI ALL-93 protocol, provided the same overall outcome as 2-year duration regimen