Disruption of the redox balance with either oxidative or anti-oxidative overloading as a promising target for cancer therapy

Abstract Oxidative stress acts as a double edged sword by being both a promoter and a suppressor of cancer. Moderate oxidative stress is beneficial for cancer cell proliferative and invasiveness features, while overexposure of the cells to oxidative insults could induce cancer cell apoptosis and reduce hypoxia along with modulating the immune system for regression of tumor. Cancer cells and cancer stem cells have highly efficient redox systems that make them resistant to oxidative insults. The redox disruptive approach is an area of current research and key for oxidative targeted cancer therapies. This disruption is applicable by using either oxidative or anti oxidative overloading strategies, specifically on cancer cells without influencing normal cells or tissues around tumor. The activity of tumor suppressor cells within tumor microenvironment is needed to be maintained in patients receiving such approaches. KEYWORDS: cancer, oxidative stress, reactive oxygen species (ROS), redo

A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer

Background: Prostate cancer is the second most common malignancy in men in the world, and radiotherapy is used as a standard treatment modality for this cancer. Although this treatment modality effectively kills prostate cancerous cells, it unavoidably irradiates the organs/tissues that are away from the treatment site. In this regard, radiation-induced testicular toxicities following prostate radiotherapy can affect sexual function, reproduction, and quality of life in cancer survivors. This review summarizes the available data on testicular exposure to radiation during prostate radiotherapy and the consequences on testicular function. Methods: To illuminate the radiation-induced testicular toxicities following prostate radiotherapy, a systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline in PubMed, Web of Science, Scopus, Embase, and clinical trials electronic databases up to September 2018. According to a set of prespecified inclusion and exclusion criteria, 31 eligible articles providing data on testicular function following radiotherapy in patients with prostate cancer were included in the study. Results: According to the different radiotherapeutic techniques used for prostate cancer treatment, the total tumor dose and scattered testicular dose values were ranging from 36.25 to 78.00 Gy and 0.06 to 6.48 Gy, respectively. Luteinizing hormone and follicle-stimulating hormone levels after prostate radiotherapy were signi�cantly higher in comparison with the pretreatment levels. Around 60 of the studies showed that testosterone levels after prostate radiotherapy were signi�cantly lower than the pretreatment levels. Furthermore, erectile dysfunction (ED), as an adverse side effect resulting from prostate radiotherapy, was reported and this complication is signi�cantly correlated with lower satisfaction with sexual life. Testicular atrophy following prostate radiotherapy has also been observed and its frequency in patients with prior prostate radiotherapy is 2.5 times more than that in the patients without prior radiotherapy. Conclusion: The data revealed that the scattered dose to testicular tissues during prostate radiotherapy can lead to testicular atrophy, variation of the male sex hormones, and quality of sexual life. © 2019 Wiley Periodicals, Inc

Melatonin as an adjuvant in radiotherapy for radioprotection and radiosensitization

It is estimated that more than half of cancer patients undergo radiotherapy during the course of their treatment. Despite its beneficial therapeutic effects on tumor cells, exposure to high doses of ionizing radiation (IR) is associated with several side effects. Although improvements in radiotherapy techniques and instruments could reduce these side effects, there are still important concerns for cancer patients. For several years, scientists have been trying to modulate tumor and normal tissue responses to IR, leading to an increase in therapeutic ratio. So far, several types of radioprotectors and radiosensitizers have been investigated in experimental studies. However, high toxicity of chemical sensitizers or possible tumor protection by radioprotectors creates a doubt for their clinical applications. On the other hand, the protective effects of these radioprotectors or sensitizer effects of radiosensitizers may limit some type of cancers. Hence, the development of some radioprotectors without any protective effect on tumor cells or low toxic radiosensitizers can help improve therapeutic ratio with less side effects. Melatonin as a natural body hormone is a potent antioxidant and anti-inflammatory agent that shows some anti-cancer properties. It is able to neutralize different types of free radicals produced by IR or pro-oxidant enzymes which are activated following exposure to IR and plays a key role in the protection of normal tissues. In addition, melatonin has shown the ability to inhibit long-term changes in inflammatory responses at different levels, thereby ameliorating late side effects of radiotherapy. Fortunately, in contrast to classic antioxidants, some in vitro studies have revealed that melatonin has a potent anti-tumor activity when used alongside irradiation. However, the mechanisms of its radiosensitive effect remain to be elucidated. Studies suggested that the activation of pro-apoptosis gene, such as p53, changes in the metabolism of tumor cells, suppression of DNA repair responses as well as changes in biosynthesis of estrogen in breast cancer cells are involved in this process. In this review, we describe the molecular mechanisms for radioprotection and radiosensitizer effects of melatonin. Furthermore, some other proposed mechanisms that may be involved are presented. © 2018, Federación de Sociedades Españolas de Oncología (FESEO)

A systematic review of radiation-induced testicular toxicities following radiotherapy for prostate cancer

Background: Prostate cancer is the second most common malignancy in men in the world, and radiotherapy is used as a standard treatment modality for this cancer. Although this treatment modality effectively kills prostate cancerous cells, it unavoidably irradiates the organs/tissues that are away from the treatment site. In this regard, radiation-induced testicular toxicities following prostate radiotherapy can affect sexual function, reproduction, and quality of life in cancer survivors. This review summarizes the available data on testicular exposure to radiation during prostate radiotherapy and the consequences on testicular function. Methods: To illuminate the radiation-induced testicular toxicities following prostate radiotherapy, a systematic search was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline in PubMed, Web of Science, Scopus, Embase, and clinical trials electronic databases up to September 2018. According to a set of prespecified inclusion and exclusion criteria, 31 eligible articles providing data on testicular function following radiotherapy in patients with prostate cancer were included in the study. Results: According to the different radiotherapeutic techniques used for prostate cancer treatment, the total tumor dose and scattered testicular dose values were ranging from 36.25 to 78.00 Gy and 0.06 to 6.48 Gy, respectively. Luteinizing hormone and follicle-stimulating hormone levels after prostate radiotherapy were signi�cantly higher in comparison with the pretreatment levels. Around 60 of the studies showed that testosterone levels after prostate radiotherapy were signi�cantly lower than the pretreatment levels. Furthermore, erectile dysfunction (ED), as an adverse side effect resulting from prostate radiotherapy, was reported and this complication is signi�cantly correlated with lower satisfaction with sexual life. Testicular atrophy following prostate radiotherapy has also been observed and its frequency in patients with prior prostate radiotherapy is 2.5 times more than that in the patients without prior radiotherapy. Conclusion: The data revealed that the scattered dose to testicular tissues during prostate radiotherapy can lead to testicular atrophy, variation of the male sex hormones, and quality of sexual life. © 2019 Wiley Periodicals, Inc

Intercellular communications-redox interactions in radiation toxicity; potential targets for radiation mitigation

Abstract Nowadays, using ionizing radiation (IR) is necessary for clinical, agricultural, nuclear energy or industrial applications. Accidental exposure to IR after a radiation terror or disaster poses a threat to human. In contrast to the old dogma of radiation toxicity, several experiments during the last two recent decades have revealed that intercellular signaling and communications play a key role in this procedure. Elevated level of cytokines and other intercellular signals increase oxidative damage and inflammatory responses via reduction/oxidation interactions (redox system). Intercellular signals induce production of free radicals and inflammatory mediators by some intermediate enzymes such as cyclooxygenase-2 (COX-2), nitric oxide synthase (NOS), NADPH oxidase, and also via triggering mitochondrial ROS. Furthermore, these signals facilitate cell to cell contact and increasing cell toxicity via cohort effect. Nitric oxide is a free radical with ability to act as an intercellular signal that induce DNA damage and changes in some signaling pathways in irradiated as well as non-irradiated adjacent cells. Targeting of these mediators by some anti-inflammatory agents or via antioxidants such as mitochondrial ROS scavengers opens a window to mitigate radiation toxicity after an accidental exposure. Experiments which have been done so far suggests that some cytokines such as IL-1β, TNF-α, TGF-β, IL-4 and IL-13 are some interesting targets that depend on irradiated organs and may help mitigate radiation toxicity. Moreover, animal experiments in recent years indicated that targeting of toll like receptors (TLRs) may be more useful for radioprotection and mitigation. In this review, we aimed to describe the role of intercellular interactions in oxidative injury, inflammation, cell death and killing effects of IR. Moreover, we described evidence on potential mitigation of radiation injury via targeting of these mediators. Keywords Radiation Cohort effect Bystander effect Non-targeted effect Radiation toxicity Radiation disaster Radiotherapy Intracellular communication Cytokines Redox system Mitigation Carcinogenesi

Does myoinositol supplement improve sperm parameters and DNA integrity in patients with oligoasthenoteratozoospermia after the freezing�thawing process?

Sperm cryopreservation is a routine method in andrology and IVF laboratory. However, the sperm quality and its fertilizing capacity have been decreased during this process. The purpose of this experiment was to determine the role of myoinositol as a supplement in amelioration of total and progressive sperm motility, DNA fragmentation, total antioxidant capacity (TAC), reactive oxygen species (ROS), and lipid peroxidation after the freezing�thawing process on patients with oligoasthenoteratozoospermia (OAT) syndrome. Semen samples obtained from 40 patients were divided into two aliquots and freezed with simple and 2 mg/mL myoinositol (MYO) supplemented freezing media. All samples were thawed and assessed after one month. Semen parameters were analyzed in terms of the motility by CASA, the level of total ROS by fluorimetry, TAC and MDA by colorimetric assay and finally DNA fragmentation by TUNEL assay. Our results clearly showed that MYO could improve total (37.46 vs. 12.91, p < 0.001) and progressive motility (21.92 vs. 6.49, p < 0.001) in experimental group compared to control group. A higher TAC level was observed in the MYO treated group in comparison to control group (1.11 vs. 0.91, p = 0.05). While MYO supplementation could not be effective on ROS level, it reduced DNA fragmentation of sperm after freeze�thaw process (p = 0.01). Therefore, MYO could be a good supplement for sperm freezing to reduce the detrimental effects of freezing process especially on DNA integrity, which is an important factor in the success of ART, in OAT suffered patients. © 2019, Springer Nature B.V

Additional file 1: of Clinical utility of blood neutrophil-lymphocyte ratio in Japanese COPD patients

Table S1. Predictors of high NLR (NLR ≥ 2.7) by univariate logistic regression analysis. Table S2. Predictors of moderate or severe exacerbation by univariate logistic regression analysis. Table S3. Predictors of moderate or severe exacerbation by multivariate logistic regression analysis. (DOCX 19 kb