The Protective Effects of Silymarin on the Reproductive Toxicity: A Comprehensive Review.

The reproductive system is extremely vulnerable to chemotherapy drugs, ionizing radiation, toxic heavy metals, chemicals, and so on. These harmful stimuli are able to induce oxidative damage, apoptosis, inflammation, and other mechanisms in the reproductive organs, leading to different adverse reproductive effects. It was shown that using medicinal plants (medicinal herbs) can be an effective medication for the prevention and treatment of multiple health conditions. Silymarin is a medicinal herb extract, obtained from the seeds of Silybum marianum. This herbal agent is a nontoxic agent even at relatively high physiological dose values, which suggests that it is safe for use in the treatment of different diseases. The hepato-, neuro-, cardio- and nephro-protective effects of silymarin have been assessed previously. The protective activities of silymarin can point to anti-oxidant, anti-apoptotic, anti-inflammatory, anti-fibrotic, immunomodulatory, and membrane-stabilizing properties. In this review, we aim to summarize current studies on the protective potentials of silymarin against reproductive toxicity. The molecular mechanisms of silymarin protection against cellular toxicity are also studied. Moreover, the findings obtained from improved formulations and delivery systems of silymarin have been addressed.

Imperatorin Attenuates the Proliferation of MCF-7 Cells in Combination with Radiotherapy or Hyperthermia.

BACKGROUND: Breast cancer is one of the most common types of malignancies in the world. Cancer resistance is an unavoidable consequence of therapy with radiation or other modalities. Ongoing research aims to improve cancer response to therapy. AIM: The aim of this study was to evaluate the possible sensitization effect of imperatorin (IMP) in combination with external radiotherapy (ERT) or HT. METHODS: After treatment of MCF-7 breast cancer cells with IMP, cells were exposed to 4 Gy X-rays or HT (42 °C for 1 hour). The viability of MCF-7 cells was measured using an MTT assay. Furthermore, the expression of pro-apoptotic genes, including Bax, Bcl-2, caspase-3, caspase-8, and caspase- 9, was investigated using real-time PCR. The sensitizing effect of IMP in combination with ERT or HT was calculated and compared to ERT or HT alone. RESULTS: Results showed an increase in the expression of pro-apoptotic genes and downregulation of anti-apoptotic Bcl-2 following ERT and HT. Furthermore, cell viability was reduced following these treatments. IMP was able to augment these effects of ERT and HT. CONCLUSION: IMP could increase the efficiency of HT and ERT. This effect of IMP may suggest it as an adjuvant for increasing the therapeutic efficiency of ERT.

Synergic effects of nanoparticles-mediated hyperthermia in radiotherapy/chemotherapy of cancer.

The conventional cancer treatment modalities such as radiotherapy and chemotherapy suffer from several limitations; hence, their efficiency needs to be improved with other complementary modalities. Hyperthermia, as an adjuvant therapeutic modality for cancer, can result in a synergistic effect on radiotherapy (radiosensitizer) and chemotherapy (chemosensitizer). Conventional hyperthermia methods affect both tumoral and healthy tissues and have low specificity. In addition, a temperature gradient generates in the tissues situated along the path of the heat source, which is a more serious for deep-seated tumors. Nanoparticles (NPs)-induced hyperthermia can resolve these drawbacks through localization around/within tumoral tissue and generating local hyperthermia. Although there are several review articles dealing with NPs-induced hyperthermia, lack of a paper discussing the combination of NPs-induced hyperthermia with the conventional chemotherapy or radiotherapy is tangible. Accordingly, the main focus of the current paper is to summarize the principles of NPs-induced hyperthermia and more importantly its synergic effects on the conventional chemotherapy or radiotherapy. The heat-producing nanostructures such as gold NPs, iron oxide NPs, and carbon NPs, as well as the non-heat-producing nanostructures, such as lipid-based, polymeric, and silica-based NPs, as the carrier for heat-producing NPs, are discussed and their pros and cons highlighted.

Resveratrol Induces Apoptosis and Attenuates Proliferation of MCF-7 Cells in Combination with Radiation and Hyperthermia.

AIM: In the current in vitro study, we tried to examine the possible role of resveratrol as a sensitizer in combination with radiotherapy or hyperthermia. BACKGROUND: Breast cancer is the most common malignancy for women and one of the most common worldwide. It has been suggested that using non-invasive radiotherapy alone cannot eliminate cancer cells. Hyperthermia, which is an adjuvant modality, induces cancer cell death mainly through apoptosis and necrosis. However, cancer cells can also develop resistance to this modality. OBJECTIVE: The objective of this study was to determine possible potentiation of apoptosis when MCF-7 cells treated with resveratrol before hyperthermia or radiotherapy. METHODS: MCF-7 cancer cells were treated with different doses of resveratrol to achieve IC50%. Afterwards, cells treated with the achieved concentration of resveratrol were exposed to radiation or hyperthermia. Proliferation, apoptosis and the expression of pro-apoptotic genes were evaluated using flow cytometry, MTT assay and real-time PCR. Results for each combination therapy were compared to radiotherapy or hyperthermia without resveratrol. RESULTS: Both irradiation or hyperthermia could reduce the viability of MCF-7 cells. Furthermore, the regulation of Bax and caspase genes increased, while Bcl-2 gene expression reduced. Resveratrol potentiated the effects of radiation and hyperthermia on MCF-7 cells. CONCLUSION: Results of this study suggest that resveratrol is able to induce the regulation of pro-apoptotic genes and attenuate the viability of MCF-7 cells. This may indicate the sensitizing effect of resveratrol in combination with both radiotherapy and hyperthermia.

Suberosin Attenuates the Proliferation of MCF-7 Breast Cancer Cells in Combination with Radiotherapy or Hyperthermia.

AIM: The aim of this study was to determine the proliferation of MCF-7 following irradiation or hyperthermia as alone or pre-treatment with suberosin. BACKGROUND: Radiotherapy is a major therapeutic modality for the control of breast cancer. However, hyperthermia can be prescribed for relief of pain or enhancing cancer cell death. Some studies have attempted its use as an adjuvant to improve therapeutic efficiency. Suberosin is a cumarin- derived natural agent that has shown anti-inflammatory properties. OBJECTIVE: In this in vitro study, possible sensitization effect of suberosin in combination with radiation or hyperthermia was evaluated. METHODS: MCF-7 breast cancer cells were irradiated or received hyperthermia with or without treatment with suberosin. The incidence of apoptosis as well as viability of MCF-7 cells were observed. Furthermore, the expressions of pro-apoptotic genes such as Bax, Bcl-2, and some caspases were evaluated using real-time PCR. RESULTS: Both radiotherapy or hyperthermia reduced the proliferation of MCF-7 cells. Suberosin amplified the effects of radiotherapy or hyperthermia for induction of pro-apoptotic genes and reducing cell viability. CONCLUSION: Suberosin has a potent anti-cancer effect when combined with radiotherapy or hyperthermia. It could be a potential candidate for killing breast cancer cells as well as increasing the therapeutic efficiency of radiotherapy or hyperthermia.

The role of curcumin/curcuminoids during gastric cancer chemotherapy: A systematic review of non-clinical study.

AIMS: Chemotherapy is an effective therapeutic modality which is commonly used for battling various cancers. However, several side effects induced by chemotherapeutic drugs would limit their clinical use. The present systematic review aims to evaluate the role of curcumin/curcuminoids co-administration during gastric cancer chemotherapy. METHODS: This systematic review was done according to PRISMA guidelines and a full systematic search in the electronic databases up to May 2020 using search terms in the titles and abstracts for the identification of relevant literature. 279 articles were found in electronic databases and 175 articles screened by title and abstract. Finally, 13 articles were included in this systematic review according to our inclusion and exclusion criteria. KEY FINDINGS: The findings indicated that gastric cancer chemotherapy induces cytotoxicity effects in various ways including a decrease of cell viability, colony formation, metastasis, tumor growth, and weight, as well as elevation of apoptosis pathway, oxidative stress pathway compared to the control group. Co-administration of curcumin/curcuminoids with chemotherapy synergistically increased the effects of anti-cancer chemotherapy compared to the group solo treated with chemotherapeutic agents. Also, in chemoresistance gastric cancer cells, co-administration of curcumin reduced chemoresistance mainly through the reduction of NF-κB activation and elevation of apoptosis. SIGNIFICANCE: According to the findings, the use of curcumin/curcuminoids during gastric cancer chemotherapy has chemosensitizing effects, and also it can reduce chemoresistance in gastric cancer.

Boosting immune system against cancer by melatonin: A mechanistic viewpoint.

Cancer is a disease of high complexity. Resistance to therapy is a major challenge in cancer targeted therapies. Overcoming this resistance requires a deep knowledge of the cellular interactions within tumor. Natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) are the main anti-cancer immune cells, while T regulatory cells (Tregs) and cancer associated fibroblasts (CAFs) facilitate immune escape of cancer cells. Melatonin is a natural agent with anti-cancer functions that has also been suggested as an adjuvant in combination with cancer therapy modalities such as chemotherapy, radiotherapy, immunotherapy and tumor vaccination. One of the main effects of melatonin is regulation of immune responses against cancer cells. Melatonin has been shown to potentiate the activities of anti-cancer immune cells, as well as attenuating the activities of Tregs and CAFs. It also has a potent effect on the mitochondria, which may change immune responses against cancer. In this review, we explain the mechanisms of immune regulation by melatonin involved in its anti-cancer effects.

Evaluating the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases: A phase 2 clinical trial.

INTRODUCTION: Since the survival time of patients with bony metastases has noticeably improved in recent years, these patients are at high risk of complications associated with this metastasis. Hence, the appropriate choice of treatment modality or combination of therapeutic approaches can lead to increasing bone pain relief, improving quality of life, etc. This study is aimed to evaluate the effectiveness of combined radiotherapy and hyperthermia for the treatment response of patients with painful bony metastases. PATIENTS AND METHODS: In a single-arm clinical trial, 23 eligible patients (14 female and 9 male) with the mean age of 67 years old and suffering from bony metastases were enrolled in the study. Two hours after radiotherapy, the patients underwent hyperthermia for 1 h in the supine position. All the patients completed the brief pain inventory (BPI) assessment tool and quality of life questionnaire (QLQ-C30) from the European Organization for Research and Treatment of Cancer (EORTC) at the baseline, end of the treatment and 1, 2 and 3 months thereafter. The response to the treatment was assessed as the zero score (complete response) or two or more than two-point drop of the worst pain within the preceding 24 h (partial response) during the 3-month posttreatment. RESULTS: All the pain intensity and interference scores, except the pain interference with the enjoyment of life score, significantly decreased. A total of 18 out of 23 patients (78%) achieved complete or partial response. The number of patients using pain relief medications decreased from 74% (n=17) at the baseline to 48% (n=11) 3 months later. Moreover, except for nausea and vomiting, appetite loss, diarrhea and financial impact problems, the patients' quality of life improved significantly in all the functional scales and symptoms within 3 months. CONCLUSION: This study showed that using hyperthermia in combination with radiotherapy significantly ameliorated bone pain among the patients suffering from cancer with painful bony metastases.

Mitigation of Radiation-Induced Lung Pneumonitis and Fibrosis Using Metformin and Melatonin: A Histopathological Study.

Background and objectives: Pneumonitis and fibrosis are the most common consequences of lung exposure to a high dose of ionizing radiation during an accidental radiological or nuclear event, and may lead to death, after some months to years. So far, some anti-inflammatory and antioxidant agents have been used for mitigation of lung injury. In the present study, we aimed to detect possible mitigatory effects of melatonin and metformin on radiation-induced pneumonitis and lung fibrosis. Materials and methods: 40 male mice were divided into 4 groups (10 mice in each). For control group, mice did not receive radiation or drugs. In group 2, mice were irradiated to chest area with 18 Gy gamma rays. In groups 3 and 4, mice were first irradiated similar to group 2. After 24 h, treatment with melatonin as well as metformin began. Mice were sacrificed after 100 days for determination of mitigation of lung pneumonitis and fibrosis by melatonin or metformin. Results: Results showed that both melatonin and metformin are able to mitigate pneumonitis and fibrosis markers such as infiltration of inflammatory cells, edema, vascular and alveolar thickening, as well as collagen deposition. Conclusion: Melatonin and metformin may have some interesting properties for mitigation of radiation pneumonitis and fibrosis after an accidental radiation event.

Selenium as an adjuvant for modification of radiation response.

Ionizing radiation plays a central role in several medical and industrial purposes. In spite of the beneficial effects of ionizing radiation, there are some concerns related to accidental exposure that could pose a threat to the lives of exposed people. This issue is also very critical for triage of injured people in a possible terror event or nuclear disaster. The most common side effects of ionizing radiation are experienced in cancer patients who had undergone radiotherapy. For complete eradication of tumors, there is a need for high doses of ionizing radiation. However, these high doses lead to severe toxicities in adjacent organs. Management of normal tissue toxicity may be achieved via modulation of radiation responses in both normal and malignant cells. It has been suggested that treatment of patients with some adjuvant agents may be useful for amelioration of radiation toxicity or sensitization of tumor cells. However, there are always some concerns for possible severe toxicities and protection of tumor cells, which in turn affect radiotherapy outcomes. Selenium is a trace element in the body that has shown potent antioxidant and radioprotective effects for many years. Selenium can potently stimulate antioxidant defense of cells, especially via upregulation of glutathione (GSH) level and glutathione peroxidase activity. Some studies in recent years have shown that selenium is able to mitigate radiation toxicity when administered after exposure. These studies suggest that selenium may be a useful radiomitigator for an accidental radiation event. Molecular and cellular studies have revealed that selenium protects different normal cells against radiation, while it may sensitize tumor cells. These differential effects of selenium have also been revealed in some clinical studies. In the present study, we aimed to review the radiomitigative and radioprotective effects of selenium on normal cells/tissues, as well as its radiosensitive effect on cancer cells.

The effect of date palm seed extract as a new potential radioprotector in gamma-irradiated mice.

OBJECTIVE: Date palm seed extract (DPSE) has various compounds revealing antioxidant features. This study aimed to evaluate the radioprotective effect of DPSE in total body gamma irradiation. MATERIALS AND METHODS: At first, chemical characteristics of DPSE were analyzed by ultraviolet, visible and Fourier transform infrared spectroscopy. Then, the toxicity of DPSE was assessed. For this purpose, 60 mice were divided into five groups, and each of the groups were injected by the doses of 100, 200, 300, 400, and 500 mg/kg, respectively. At the termination of the experiment, mortality rate and weight loss of all mice were evaluated over a period of 30 days. Finally, the radioprotective effect of DPSE was evaluated by dividing 36 mice into three groups: control, test, and placebo and then were irradiated by Cobalt-60. RESULTS: According to the findings, there was no mortality due to DPSE. Furthermore, for the maximum dose of 500 mg/kg, the number of mice surviving at the termination of the experiment with and without injection of DPSE was reported as 83% and 41%, respectively. In addition, a significant difference was obtained between radiated mice with and without DPSE injection (P = 0.035). CONCLUSION: The findings showed that DPSE injected into mice before irradiation has no toxicity and could protect mice from lethal effects of total body irradiation. The use of DPSE as a new radioprotector agent in the human needs further studies, particularly clinical trials.

Modulation of apoptosis by melatonin for improving cancer treatment efficiency: An updated review.

Radio- and chemotherapy are the most common cancer treatment modalities. They cause acute and late side effects on normal tissues, which is a burden for delivery of a high dose of radiation or drugs on tumor cells. In addition, tumor cells achieve adaptive responses to subsequent doses of radiation and chemotherapy, leading to tumor resistance and accelerated repopulation. Resistance to radiotherapy and chemotherapy can occur following adaptive responses, which itself is due to the release of large numbers of inter- and intracellular mediators by immune cells as well as other tumor microenvironment (TME) cells. Melatonin is a potent natural antioxidant and anti-inflammatory agent that protects against toxic side effects of radiation and chemotherapy. Furthermore, in some cancer cells, melatonin aids sensitizing cancer cells to therapy. Apoptosis is one of the main mechanisms of cell death following exposure to radiation and chemotherapy. Evidences have shown a direct relation between apoptosis induction in tumor cells with increased tumor delay regression and survival. Melatonin through modulation of several apoptosis mediators such as mitochondria, Bax, Bcl-2, endogenous ROS, and apoptosis receptors facilitate apoptosis. The current review aims to explain mechanisms of apoptosis induction following exposure to radiation and chemotherapy drugs. We also reviewed the modulatory effect of melatonin on apoptosis signaling pathways.

Folic acid functionalized nanoparticles as pharmaceutical carriers in drug delivery systems.

Conventional chemotherapeutic approaches in cancer therapy such as surgery, chemotherapy, and radiotherapy have several disadvantages due to their nontargeted distributions in the whole body. On the other hand, nanoparticles (NPs) based therapies are remarkably progressing to solve several limitations of conventional drug delivery systems (DDSs) including nonspecific biodistribution and targeting, poor water solubility, weak bioavailability and biodegradability, low pharmacokinetic properties, and so forth. The enhanced permeability and retention effect escape from P-glycoprotein trap in cancer cells as a passive targeting mechanism, and active targeting strategies are also other most important advantages of NPs in cancer diagnosis and therapy. Folic acid (FA) is one of the biologic molecules which has been targeted overexpressed-folic acid receptor (FR) on the surface of cancer cells. Therefore, conjugation of FA to NPs most easily enhances the FR-mediated targeting delivery of therapeutic agents. Here, the recent works in FA which have been decorated NPs-based DDSs are discussed and cancer therapy potency of these NPs in clinical trials are presented.

Photosensitizer effects of MWCNTs-COOH particles on CT26 fibroblastic cells exposed to laser irradiation.

In the current study, photosensitizer effect of carboxylate multiwalled carbon nanotubes (MWCNTs-COOH) on CT26 fibroblastic cells following near infrared (NIR) irradiation was quantized in photo-thermal therapy (PTT). Moreover, it was tried to achieve optimal dose of MWCNTs-COOH and laser exposure time. Characterizations of MWCNTs-COOH were scrutinized using scanner electron microscope (SEM), spectrophotometer, and particle size analyzer. The seeded CT26 cells were treated with nontoxic concentrations of MWCNTs-COOH and then irradiated. Finally, viability (%) of the CT26 cells was determined using MTT assay. The findings revealed that 10, 50, and 80 µg/mL of MWCNTs-COOH have remarkable photosensitizer effects on CT26 cancerous cell lines against NIR irradiation (2.5 W/cm2). It was shown that using the 80 µg/mL concentration of MWCNTs-COOH against 60, 120, 180, 240, and 300 s of NIR irradiation and also, 10 and 50 µg/mL concentration of MWCNTs-COOH against 180, 240, and 300 s of NIR irradiation can lead to significant decrease in mean cell viability (%) by more than 50%. According to the obtained data, it seems that using the PPT with MWCNTs-COOH, as adjunct therapy in CT26 fibroblastic cells, can help to increase therapeutic ratio of main modalities of cancer treatment such as radiotherapy, chemotherapy, and surgery.

Mechanisms of apoptosis modulation by curcumin: Implications for cancer therapy.

Cancer incidences are growing and cause millions of deaths worldwide. Cancer therapy is one of the most important challenges in medicine. Improving therapeutic outcomes from cancer therapy is necessary for increasing patients' survival and quality of life. Adjuvant therapy using various types of antibodies or immunomodulatory agents has suggested modulating tumor response. Resistance to apoptosis is the main reason for radioresistance and chemoresistance of most of the cancers, and also one of the pivotal targets for improving cancer therapy is the modulation of apoptosis signaling pathways. Apoptosis can be induced by intrinsic or extrinsic pathways via stimulation of several targets, such as membrane receptors of tumor necrosis factor-α and transforming growth factor-ß, and also mitochondria. Curcumin is a naturally derived agent that induces apoptosis in a variety of different tumor cell lines. Curcumin also activates redox reactions within cells inducing reactive oxygen species (ROS) production that leads to the upregulation of apoptosis receptors on the tumor cell membrane. Curcumin can also upregulate the expression and activity of p53 that inhibits tumor cell proliferation and increases apoptosis. Furthermore, curcumin has a potent inhibitory effect on the activity of NF-κB and COX-2, which are involved in the overexpression of antiapoptosis genes such as Bcl-2. It can also attenuate the regulation of antiapoptosis PI3K signaling and increase the expression of MAPKs to induce endogenous production of ROS. In this paper, we aimed to review the molecular mechanisms of curcumin-induced apoptosis in cancer cells. This action of curcumin could be applicable for use as an adjuvant in combination with other modalities of cancer therapy including radiotherapy and chemotherapy.

Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy.

Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.

Macrophage polarity in cancer: A review.

Macrophages are the most abundant cells within the tumor stroma displaying noticeable plasticity, which allows them to perform several functions within the tumor microenvironment. Tumor-associated macrophages commonly refer to an alternative M2 phenotype, exhibiting anti-inflammatory and pro-tumoral effects. M2 cells are highly versatile and multi-tasking cells that directly influence multiple steps in tumor development, including cancer cell survival, proliferation, stemness, and invasiveness along with angiogenesis and immunosuppression. M2 cells perform these functions through critical interactions with cells related to tumor progression, including Th2 cells, cancer-associated fibroblasts, cancer cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells. M2 cells also have negative cross-talks with tumor suppressor cells, including cytotoxic T cells and natural killer cells. Programed death-1 (PD-1) is one of the key receptors expressed in M2 cells that, upon interaction with its ligand PD-L1, plays cardinal roles for induction of immune evasion in cancer cells. In addition, M2 cells can neutralize the effects of the pro-inflammatory and anti-tumor M1 phenotype. Classically activated M1 cells express high levels of major histocompatibility complex molecules, and the cells are strong killers of cancer cells. Therefore, orchestrating M2 reprogramming toward an M1 phenotype would offer a promising approach for reversing the fate of tumor and promoting cancer regression. Macrophage switching toward an anti-inflammatory M1 phenotype could be used as an adjuvant with other approaches, including radiotherapy and immune checkpoint blockades, such as anti-PD-L1/PD-1 strategies.

A systematic review of clinical applications of polymer gel dosimeters in radiotherapy.

Radiotherapy has rapidly improved because of the use of new equipment and techniques. Hence, the appeal for a feasible and accurate three-dimensional (3D) dosimetry system has increased. In this regard, gel dosimetry systems are accurate 3D dosimeters with high resolution. This systematic review evaluates the clinical applications of polymer gel dosimeters in radiotherapy. To find the clinical applications of polymer gel dosimeters in radiotherapy, a full systematic literature search was performed on the basis of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in electronic databases up to January 31, 2017, with use of search-related terms in the titles and abstracts of articles. A total of 765 articles were screened in accordance with our inclusion and exclusion criteria. Eventually, 53 articles were included in the study. The findings show that most clinical applications of polymer gel dosimeters relate to external radiotherapy. Most of the gel dosimeters studied have acceptable dose accuracy as a 3D dosimeter with high resolution. It is difficult to judge which is the best polymer gel dosimeter to use in a clinical setting, because each gel dosimeter has advantages and limitations. For example, methacrylic acid-based gel dosimeters have high dose sensitivity and low toxicity, while their dose response is beam energy dependent; in contrast, N-isopropylacrylamide gel dosimeters have low dose resolution, but their sensitivity is lower and they are relatively toxic.

Adjuvant chemotherapy with melatonin for targeting human cancers: A review.

Melatonin is a multifunctional hormone that has long been known for its antitumoral effects. An advantage of the application of melatonin in cancer therapy is its ability to differentially influence tumors from normal cells. In this review, the roles of melatonin adjuvant therapy in human cancer are discussed. Combination of melatonin with chemotherapy could provide synergistic antitumoral outcomes and resolve drug resistance in affected patients. This combination reduces the dosage for chemotherapeutic agents with the subsequent attenuation of side effects related to these drugs on normal cells around tumor and on healthy organs. The combination therapy increases the rate of survival and improves the quality of life in affected patients. Cancer cell viability is reduced after application of the combinational melatonin therapy. Melatonin does all these functions by adjusting the signals involved in cancer progression, re-establishing the dark/light circadian rhythm, and disrupting the redox system for cancer cells. To achieve effective therapeutic outcomes, melatonin concentration along with the time of incubation for this indoleamine needs to be adjusted. Importantly, a special focus is required to be made on choosing an appropriate chemotherapy agent for using in combination with melatonin. Because of different sensitivities of cancer cells for melatonin combination therapy, cancer-specific targeted therapy is also needed to be considered. For this review, the PubMed database was searched for relevant articles based on the quality of journals, the novelty of articles published by the journals, and the number of citations per year focusing only on human cancers.