Comparison of therapeutic effects of N-Acetylcysteine with pregabalin in improving the clinical symptoms of painful diabetic neuropathy: a randomized, double-blind clinical trial.

OBJECTIVES: Painful diabetic neuropathy (PDN) is highly prevalent and annoyingly in patients with diabetes. The aim of this study was to investigate the effects of oral N-acetylcysteine (NAC) compared to pregabalin in PDN. METHODS: One hundred two eligible patients with type 2 diabetes and PDN were randomly recievied pregabalin (150 mg/day) or N-Acetylcysteine (NAC) (600 mg/ twice a day) for 8 weeks. Mean pain score, Sleep interference score (SIS), Patient Global Impression of Change (PGIC), Clinical Global Impression of Change (CGIC), and also, serum levels of total antioxidant capacity (TAC), total thiol groups (TTG), catalase activity (CAT), nitric oxide (NO), and malondialdehyde (MDA) were assessed at baseline and at the end of the study. RESULTS: NAC was well tolerated in all patients. The decrease in mean pain scores and increase in SIS was similar between two groups. More improvement in PGIC and CGIC from the baseline was reported in NAC group. NAC, significantly, decreased serum levels of MDA, and NO, but increased TAC, TTG, and CAT. Pregabalin, significantly, decreased serum levels of MDA, and NO and increased TAC. DISCUSSION: NAC is efficacious in alleviate symptoms of PDN which is probably related to its antioxidant effects. TRIAL REGISTRATION: The research protocol received approval from the Ethics Committee of Hamadan University of Medical Sciences (IR.UMSHA.REC.1397.137). The trial registry URL and number in Iranian Registry of Clinical Trials (IRCT): https://www.irct.ir/trial/33313 , IRCT20180814040795N2 (Registration date: 2019-01-21, Retrospectively registered).

A Randomized, Controlled, Parallel-Group, Trial on the Long-term Effects of Melatonin on Fatigue Associated With Breast Cancer and Its Adjuvant Treatments.

OBJECTIVE: Cancer related fatigue is a distressing condition and correlated with decrease in quality of life of patients with malignant conditions. In continuation of our previous research, we assessed long term anti-fatigue effects of melatonin in patients with the breast cancer. MATERIAL AND METHODS: In this clinical trial, 92 breast cancer patients were randomly assigned to receive either melatonin (18 mg/day) or placebo from 1 week before the adjuvant treatments until 2 years after their completion. The levels of fatigue were assessed before and after intervention using Brief Fatigue Inventory (BFI) and were compared at a significance level of P ≤ .05. RESULTS: The BFI scores were similar between the 2 groups at the baseline (placebo group: 5.56 ± 1.59 and melatonin group: 5.72 ± 1.68, P = .67). After the intervention, not only the mean fatigue score was significantly lower in melatonin group (2.93 ± 1.04 vs 1.99 ± 1.02, P < .001, P ≤ .05), but also a greater reduction in fatigue score in intervention group was evident over time (P ≤ .001). CONCLUSION: Long-term usage of melatonin even after completion of adjuvant therapies in women with breast cancer decreased the levels of fatigue associated with the malignant condition and its treatments. THE TRIAL REGISTRY NAME AND URL, AND REGISTRATION NUMBER: Iranian Registry of Clinical Trials, https://en.irct.ir/trial/62267, IRCT20180426039421N3.

The role of myeloid-derived suppressor cells in lung cancer and targeted immunotherapies.

INTRODUCTION: Lung cancer is the deadliest cancer in both sexes combined globally due to significant delays in diagnosis and poor survival. Despite advances in the treatment of lung cancer, the overall outcomes remain poor and traditional chemotherapy fails to provide long-term benefits for many patients. Therefore, new treatment strategies are needed to increase overall survival. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive cells taking part in lung cancer, as has been described in other types of tumors. MDSCs immunosuppressive activity is mediated by arginases (ARG-1 and ARG-2), nitric oxide (NO), reactive oxygen species (ROS), peroxynitrite, PD-1/PD-L1 axis, and different cytokines. MDSCs can be a target for lung cancer immunotherapy by inducing their differentiation into mature myeloid cells, elimination, attenuation of their function, and inhibition of their accumulation. AREAS COVERED: In this review, the immunosuppressive function of MDSCs, their role in lung cancer, and strategies to target them, which could result in increased efficacy of immunotherapy in patients with lung cancer, are discussed. EXPERT OPINION: Identification of important mechanisms and upstream pathways involved in MDSCs functions paves the way for further preclinical and clinical lung cancer research, which could lead to the development of novel therapeutic approaches.

Ewing's Sarcoma of Mandible: Practical Approach to a Challenging Case.

As a rare entity, sarcomas of the head and neck are challenging cases. In this paper, we represent a unique case of Ewing sarcoma of mandible, serving as an example of multidisciplinary team importance in a developing country.

Review of the recent clinical trials for PD-1/PD-L1 based lung cancer immunotherapy.

INTRODUCTION: Lung cancer is known for its high mortality rate and prevalence in the world today. For decades, chemotherapy has been used as the main treatment for this cancer, but this has changed over time. Immune checkpoint inhibitors (ICIs) such as programmed death 1 and programmed death-ligand 1 (PD-1/PD-L1) blocking agents have been assessed in numerous clinical trials as single or combination therapy and have shown overall promising results. Nevertheless, various challenges have been encountered, which cast doubts over this method. AREAS COVERED: We provide an introduction to the mechanisms underlying the PD-1/PD-L1 pathway. Then, we discuss the latest results from the most leading-edge studies evaluating PD-1/PD-L1 inhibitors in different lines of lung cancer therapy (some of which have gained FDA approval), potential biomarkers, and major challenges of ICI therapy. EXPERT OPINION: Currently, the standard of care (SoC) for lung cancer consists mostly of chemotherapeutics. With further studies and ongoing trials evaluating novel ICI therapy, FDA has been approving specific ICI therapeutics, including PD-1/PD-L1 inhibitors, for particular types of lung cancer. However, for ICIs to play a key role in SoC, we need to overcome the major challenges of ICI therapy.

The role of Hypoxia-Inducible Factor-1alpha and its signaling in melanoma.

Adaptation to the loss of O2 is regulated via the activity of hypoxia-inducible factors such as Hypoxia-Inducible Factor-1 (HIF-1). HIF-1 acts as a main transcriptional mediator in the tissue hypoxia response that regulates over 1000 genes related to low oxygen tension. The role of HIF-1α in oncogenic processes includes angiogenesis, tumor metabolism, cell proliferation, and metastasis, which has been examined in various malignancies, such as melanoma. Melanoma is accompanied by a high death rate and a cancer type whose incidence has risen over the last decades. The linkage between O2 loss and melanogenesis had extensively studied over decades. Recent studies revealed that HIF-1α contributes to melanoma progression via different signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MEK/ERK, JAK/STAT, Wnt/ß-catenin, Notch, and NF-κB. Also, various microRNAs (miRs) are known to mediate the HIF-1α role in melanoma. Therefore, HIF-1α offers a diagnostic/prognostic biomarker and a candidate for targeted therapy in melanoma.