Contribution of MicroRNAs in Chemoresistance to Cisplatin in the Top Five Deadliest Cancer: An Updated Review.

Cisplatin (DDP) is a well-known anticancer drug used for the treatment of numerous human cancers in solid organs, including bladder, breast, cervical, head and neck squamous cell, ovarian, among others. Its most important mode of action is the DNA-platinum adducts formation, inducing DNA damage response, silencing or activating several genes to induce apoptosis; these mechanisms result in genetics and epigenetics modifications. The ability of DDP to induce tumor cell death is often challenged by the presence of anti-apoptotic regulators, leading to chemoresistance, wherein many patients who have or will develop DDP-resistance. Cancer cells resist the apoptotic effect of chemotherapy, being a problem that severely restricts the successful results of treatment for many human cancers. In the last 30 years, researchers have discovered there are several types of RNAs, and among the most important are non-coding RNAs (ncRNAs), a class of RNAs that are not involved in protein production, but they are implicated in gene expression regulation, and representing the 98% of the human genome non-translated. Some ncRNAs of great interest are long ncRNAs, circular RNAs, and microRNAs (miRs). Accumulating studies reveal that aberrant miRs expression can affect the development of chemotherapy drug resistance, by modulating the expression of relevant target proteins. Thus, identifying molecular mechanisms underlying chemoresistance development is fundamental for setting strategies to improve the prognosis of patients with different types of cancer. Therefore, this review aimed to identify and summarize miRs that modulate chemoresistance in DDP-resistant in the top five deadliest cancer, both in vitro and in vivo human models.

Assessment of Renal Function in Head and Neck Cancer Patients Treated with Cisplatin: Different Biomarkers and Acute Kidney Injury Classifications.

Cisplatin is associated with dose-limiting nephrotoxicity, and the timely detection of acute kidney injury (AKI) can affect morbimortality. Therefore, this study aimed to investigate the tools for monitoring renal function in AKI. This was a retrospective, cohort study. Cisplatin-treated patients with head and neck cancer were included. Nephrotoxicity was assessed using serum creatinine, estimated creatinine clearance, serum electrolytic alterations, and plasma kidney injury molecule-1 (KIM-1). The toxicity severity was classified according to Common Terminology Criteria for Adverse Events (CTCAE), and AKI was classified by Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN). A total of 81 participants were included, of whom only 32 did not have AKI. Almost 90% of participants had a decreased estimated glomerular filtration rate five (D5) days after chemotherapy. The AKI estimate differs between AKIN and RIFLE; more participants were diagnosed by the RIFLE at D5, 19.5% versus 2.4% by AKIN, and fifteen had a discordance between these classifications. All laboratory markers showed significant changes on D5. KIM-1 appeared a possible biomarker when considering CTCAE or AKIN classifications (p < 0.05 on D5), but not when RIFLE classification was used (p = 0.0780). Further studies may seek to understand the profiles of different biomarkers together.

Dysregulated MicroRNAs as Biomarkers or Therapeutic Targets in Cisplatin-Induced Nephrotoxicity: A Systematic Review.

The purpose of this systematic review was to map out and summarize scientific evidence on dysregulated microRNAs (miRNAs) that can be possible biomarkers or therapeutic targets for cisplatin nephrotoxicity and have already been tested in humans, animals, or cells. In addition, an in silico analysis of the two miRNAs found to be dysregulated in the majority of studies was performed. A literature search was performed using eight databases for studies published up to 4 July 2021. Two independent reviewers selected the studies and extracted the data; disagreements were resolved by a third and fourth reviewers. A total of 1002 records were identified, of which 30 met the eligibility criteria. All studies were published in English and reported between 2010 and 2021. The main findings were as follows: (a) miR-34a and miR-21 were the main miRNAs identified by the studies as possible biomarkers and therapeutic targets of cisplatin nephrotoxicity; (b) the in silico analysis revealed 124 and 131 different strongly validated targets for miR-34a and miR-21, respectively; and (c) studies in humans remain scarce.

Outcomes in hepatocellular carcinoma patients undergoing sorafenib treatment: toxicities, cellular oxidative stress, treatment adherence, and quality of life.

The study of toxicities induced by sorafenib, as well as the identification of possible mechanisms and biomarkers of these toxicities, is important to improve the treatment and quality of life of hepatocellular carcinoma (HCC) patients. This study focused on toxicities, cellular oxidative stress, adherence, and quality of life of 11 patients with HCC treated with sorafenib. Dermatotoxicity, myelotoxicity, gastro toxicity, nephrotoxicity, pain, and fatigue were investigated. For oxidative stress analysis, the peripheral blood mononuclear cells were isolated and mitochondrial superoxide anion production was measured using MitoSOX Red test. Medication adherence was evaluated based on Morisky-Green and MedTake tests. Quality of life assessment was performed using EORTC QLQ C-30 and QLQ HCC18 questionnaires. The results showed that hand-foot syndrome (45.5%), thrombocytopenia (45.5%), diarrhea (54.5%), pain (54.5%), and fatigue (36.4%) were the most prevalent toxicities. A non-statistically significant change in the levels of superoxide anion was observed after the sorafenib treatment (Wilcoxon test, P = 0.4131). Moreover, 81.8% of patients had high adherence, 100% knew the correct indication of sorafenib, 81.8% knew the correct intake and drug regimen, and 36.4% knew the correct dose of antineoplastic. There was a significant worsening in the emotional and pain domains of quality of life after the sorafenib (Wilcoxon test, P = 0.0313 and P = 0.0313, respectively). A production of superoxide anion was not correlated with toxicities (Spearman's correlation and Mann-Whitney U tests, P > 0.05). This study suggests that oxidative stress might not be the mechanism of sorafenib toxicities.