The association between mRNA expression of resistin, TNF- α, IL-6, IL-8, and ER-α in peripheral blood mononuclear cells and breast cancer.

BACKGROUND: Adipocytokines, adipose tissue-derived proteins, were demonstrated to be involved in the pathogenesis of breast cancer. We assessed the mRNA expression of resistin, tumor necrosis factor-alpha (TNF-α), interleukins 6 and 8 (IL-6, and IL-8), and estrogen receptor alpha (ER-α) in peripheral blood mononuclear cells (PBMCs) of women with and without breast cancer. METHODS: The PBMCs were isolated from the whole blood of 32 women with breast cancer and 18 women without breast cancer using density gradient centrifugation. The mRNA expression of the target genes was measured by reverse-transcription polymerase chain reaction (RT-PCR). Body mass index was calculated, additionally, clinicopathological characteristics of the breast cancer patients were determined by histopathological examination. RESULTS: The mRNA expression of resistin (3.5-fold) and IL-6 (15-fold) in PBMCs of breast cancer patients significantly increased in comparison to healthy controls. Resistin expression was significantly associated with inflammatory markers including TNF-α, IL-6, IL-8, but not with anthropometric indices. Logistic regression analysis revealed the studied adipokines were not associated with breast cancer. Based on the ROC curve analysis the diagnostic performance of IL-6 was significant (0.825, 95% CI: 0.549-0.94, p = 0.030), thus, it might be considered as a breast cancer biomarker that reflecting an early and inflammatory stage of the disease. DISCUSSION: Breast cancer is not associated with increased expression of inflammatory cytokines in PBMCs. Our results suggested that a PBMC-based gene expression test may be developed to detect breast cancer early.

Prognostic role and therapeutic susceptibility of cathepsin in various types of solid tumor and leukemia: A systematic review.

Cathepsins (CTSs) are multifunctional proteins that can play prominent roles in cancer progression and metastasis. In this systematic review, we compared the prognosis of CTS subtypes overexpression in leukemia and solid tumors, and investigated the effect of different factors on CTS prognosis. We systematically searched published articles indexed in PubMed, Scopus, Cochrane library, ISI Web of Science, and EmBase databases from February 2000 until January 2020. Among the selected leukemia and solid tumors studies, overexpression of CTS subtypes in newly diagnosed and treated patients were with poor prognosis in 43 studies (79.6%) and with good prognosis in 9 studies (16.6%). However, there were 2 studies (3.8%) with either good or poor prognosis, depending on conditions and caner stage and host cell. The relation between CTS and human leukocyte antigen (HLA) in leukemia and solid tumors was mentioned in 7 studies (13%). Overexpression of CTS subtypes in all new case patients had contributed to the induction of poor prognosis. It seems that CTS subtypes, based on the type of cancer and its stage, the type of host cells, and the probable relation with HLA, breed good or poor prognosis in patients with cancer. Therefore, monitoring the overexpression of CTS subtypes and determining the effect of each of these factors on CTS prognosis could be helpful in predicting cancer prognosis both in newly diagnosed or under treatment patients. They could also be useful in finding ways for improving the efficiency of contemporary therapeutic strategies in various types of leukemia and solid tumors.

Evaluation of CCAAT/Enhancer Binding Protein (C/EBP) Alpha (CEBPA) and Runt-Related Transcription Factor 1 (RUNX1) Expression in Patients with De Novo Acute Myeloid Leukemia.

The CCAAT/enhancer binding protein (C/EBP) alpha (CEBPA) and Runt-related transcription factor 1 (RUNX1) genes have been traditionally regarded as two essential genes involved in normal myeloid maturation. Although the link between mutations in these genes and the development of acute myeloid leukemia (AML) has been extensively documented, the ramifications of gene expression dysregulations of CEBPA and RUNX1 has drawn less attention. The present study investigated CEBPA and RUNX1 gene expression levels in 96 primary AML specimens against a normal control group by way of real-time RT-PCR. Our results reveal that CEBPA and RUNX1 gene expression levels were unexpectedly and significantly higher in patients with AML when compared to the levels detected in the normal control group (P < 0.0001). Furthermore, the correlation between CEBPA and RUNX1 was significant and positive (P-value: 0.011, r: 0.257). Our data contradicts the widely established role of CEBPA and RUNX1 in myeloid differentiation, as we saw lower levels of CEBPA and RUNX1 expression to be exhibited in patients with AML. Likely, our data demonstrates that higher levels of CEBPA and RUNX1 expression were closely correlated with reduced myeloid maturation, but this idea needs to approved. It suggests that despite the current established functions of genes involved in cell differentiation, the leukemogenesis process has the capability to transform normal hematopoietic precursors in a manner that may employ the differentiation related gene at the service of malignancy.

Wnt/ß-catenin signaling in bone marrow niche.

The bone marrow (BM) niche is a specific physiological environment for hematopoietic and non-hematopoietic stem cells (HSCs). Several signaling pathways (including Wnt/ß-catenin) regulate various aspects of stem cell growth, function and death in the BM niche. In addition, the canonical Wnt pathway is crucial for directing self-renewal and differentiation as important mechanisms in many types of stem cells. We review the role of the Wnt/ß-catenin pathway in the BM niche and its importance in stem cells. Relevant literature was identified by a PubMed search (1997-2014) of English-language literature by using the following keywords: BM niche, Wnt/ß-catenin signaling, osteoblast, osteoclast and bone disease. The Wnt/ß-catenin pathway regulates the stability of the ß-catenin proto-oncogene. The stabilized ß-catenin then translocates to the nucleus, forming a ß-catenin-TCF/LEF complex regulating the transcription of specific target genes. Stem cells require ß-catenin to mediate their response to Wnt signaling for maintenance and transition from the pluripotent state during embryogenesis. In adult stem cells, Wnt signaling functions at various hierarchical levels to contribute to the specification of the diverse tissues. Aberrant Wnt/ß-catenin signaling and its downstream transcriptional regulators are observed in several malignant stem cells and human cancers. Because Wnt signaling can maintain stem cells and cancer cells, the ability to modulate the Wnt pathway either positively or negatively may be of therapeutic relevance. The controlled activation of Wnt signaling might allow us to enhance stem and progenitor cell activity when regeneration is needed.

Mesenchymal stem cells as a double-edged sword in suppression or progression of solid tumor cells.

Tumor cells are able to attract mesenchymal stem cells (MSCs) to primary tumor site. On the other hand, MSCs secrete various factors to attract tumor cells towards BM. In this review, in addition to assessment of MSCs function at tumor sites and their impact on growth and metastasis of tumor cells, the importance of MSC in attraction of malignant cells to BM and their involvement in drug resistance of tumor cells have also been studied. Relevant literature was identified by a PubMed search (2000-2015) of English-language literature using the terms mesenchymal stem cells, cancer cell, metastasis, and tumor microenvironment. MSCs migrate towards tumor microenvironment and are involved in both pro-tumorigenic and antitumorigenic functions. The dual function of MSCs at tumor sites is dependent upon a variety of factors, including the type and origin of MSCs, the cancer cell line under study, in vivo or in vitro conditions, the factors secreted by MSCs and interactions between MSCs, host immune cells and cancer cells. Therefore, MSCs can be regarded both as friends and enemies of cancer cells. Although the role of a number of pathways, including IL-6/STAT3 pathway, has been indicated in controlling the interaction between MSCs and tumor cells, other mechanisms by which MSCs can control the tumor cells are not clear yet. A better understanding of these mechanisms through further studies can determine the exact role of MSCs in cancer progression and identify them as important therapeutic agents or targets.

Significance of oncogenes and tumor suppressor genes in AML prognosis.

Acute myeloid leukemia (AML) is a heterogeneous disorder among hematologic malignancies. Several genetic alterations occur in this disease, which cause proliferative progression, reducing differentiation and apoptosis in leukemic cells as well as increasing their survival. In the genetic study of AML, genetic translocations, gene overexpression, and mutations effective upon biology and pathogenesis of this disease have been recognized. Proto-oncogenes and tumor suppressor genes, which are important in normal development of myeloid cells, are involved in the regulation of cell cycle and apoptosis, undergo mutation in this type of leukemia, and are effective in prognosis of AML subtypes. This review deals with these genes, the assessment of which can be important in the diagnosis and prognosis of patients as well as therapeutic outcome.

Hepatic metastatic niche: from normal to pre-metastatic and metastatic niche.

Liver is the organ responsible for hematopoiesis during fetal life, which is also a target organ of metastasis for several cancers. In order to recognize the hepatic metastatic changes, obtain a better grasp of cancer prevention, treatment, and inhibition mode of hepatic metastasis progression, we investigate the changes and transformation of normal hepatic niche cells to metastatic niche ones in this review. On the other hand, since metastatic diseases alter the liver function, the changes in a number of cancers that metastasize to the liver have also been reviewed. Relevant English-language literature was searched and retrieved from PubMed (1994-2014) using the following keywords: hepatic stem cell niche, hepatic metastatic niche, chemokine, and microRNAs (miRNAs). Also, over 86 published studies were investigated, and bioinformatics analysis of differentially expressed miRNAs in hepatic cancer and metastasis was performed. Metastasis is developed in several stages with specific changes and mechanisms in each stage. Recognition of these changes would lead to detection of new biomarkers and clinical targets involved in specific stages of liver metastasis. Investigation of the hepatic stem cell niche, development of metastasis in liver tissue, as well as changes in chemokines and miRNAs in metastatic hepatic niche can significantly contribute to faster detection of liver metastasis progression.

Targeting PI3K/AKT/mTOR network for treatment of leukemia.

OBJECTIVE: Increased activity of PI3K/AKT/mTOR pathway has been observed in a huge number of malignancies. This pathway can function as a prosurvival factor in leukemia stem cells and early committed leukemic precursors and its inhibition is regarded as a therapeutic approach. Accordingly, the aim of this review is to evaluate the PI3K/Akt/mTOR inhibitors used in leukemia models. DISCUSSION: Inhibition of the PI3K/AKT/mTOR pathway has been reported to have beneficial therapeutic effects in leukemias, both in vitro in leukemia cell lines and in vivo in animal models. Overall, the use of dual PI3K/mTOR inhibitor, dual Akt/RTK inhibitor, Akt inhibitor, selective inhibitor of PI3K, mTOR inhibitor and dual PI3K/PDK1 inhibitor in CML, AML, APL, CLL, B-ALL and T-ALL has a better therapeutic effect than conventional treatments. CONCLUSIONS: Targeting the PI3K/Akt/mTOR pathway may have pro-apoptotic and antiproliferative effects on hematological malignancies. Furthermore, modulation of miRNA can be used as a novel therapeutic approach to regulate the PI3K/Akt/mTOR pathway. However, both aspects require further clinical studies.

Regulatory effect of chemokines in bone marrow niche.

Chemokines secreted from different cellular components of bone marrow (BM) play an important role in the formation of the BM niche system. The hematopoietic stem cell (HSC) pool located in specialized anatomical sites within the BM is subjected to a complex network of chemokines, such that the produced chemokines affect the fate of these cells. Expression of different chemokine receptors on leukemic stem cells (LSCs) uncovers the critical role of chemokines in the maintenance, survival and fate of these cells in the leukemic niche. As a pre-metastatic niche rich in a variety of chemokines, the BM niche is turned into a locus of tumor cell development and division. The chemokine receptors expressed on the surface of metastatic cells lead to their metastasis and homing to the BM niche. Knowledge of chemokines and their receptors leads to the production of various therapeutic antagonists at chemokine receptors expressed on leukemic and tumor cells, enabling interference with chemokine function as a therapeutic tool. New findings suggest that miRNAs, with their specific inhibitory function, affect the ability of producing and expressing chemokines and chemokine receptors. This review focuses on the emerging role of chemokines and their receptors in normal and pathologic conditions of the BM niche, and also discusses the new therapeutic methods with this background.

New insights in cellular and molecular aspects of BM niche in chronic myelogenous leukemia.

Hematoproliferative neoplasias like chronic myelogenous leukemia (CML) progressively affect bone marrow niche; however, there are only few specific clinical markers for prediction of disease progression. Here, we review the myeloproliferative niche and molecular changes including signaling pathways as well as microRNA (miRNA) in CML in order to better understand the therapeutic approaches. CML is a three-stage myeloproliferative disorder caused by reciprocal translocation between chromosome 9 and 22. There has been a new interest on treatment of this disorder. Therefore, in order to develop the appropriate therapy, an analysis of the molecular changes involved in malignant cells can be effective. A review of the signaling pathways, miRNA, and related targets can be helpful for better understanding of molecular pathogenesis of CML. Characterizing malignant cells and molecular changes with a focus on their targets may help researchers use molecular targets as effective therapeutic means for CML. On the other hand, interactions between leukemic stem cells and CML niche will help researchers investigate the causes of drug resistance in this disease.

Evaluation of the Total Oxidant Status to the Antioxidant Capacity Ratio as a Valuable Biomarker in Breast Cancer Patients.

Background: The oxidative balance is a state of equilibrium between oxidants and antioxidants disrupted in various disorders, including BC. This study aimed to assess this equilibrium in breast cancer (BC) patients by looking at the oxidant-to-antioxidant ratio. Methods: This case-control study comprised 40 women patients with breast cancer and 30 age-matched healthy individuals. The oxidation-reduction colorimetric technique was used to determine serum levels of total oxidant status (TOS) and total antioxidant capacity (TAC). The oxidant-to-antioxidant balance was estimated using the TOS- to- TAC ratio (TOS/TAC). Results: The mean TOS in healthy individuals was 8.40±2.06 µmol/L, while in BC patients it was 13.31±2.16 µmol/L (P< 0.001). The mean serum level of TAC was 1.43±0.21 mmol/L in healthy individuals and 1.19±0.15 mmol/L in BC patients (P< 0.001). The mean serum TOS/TAC was 6.01±0.32 in the healthy individuals and 11.42±0.41 in the BC patients (P< 0.0001). There were direct correlations between TAC and estrogen receptor (r=0.339, P=0.038). The TOS/TAC level has a sensitivity of 100% and specificity of 83.33%, distinguishing patients with BC from healthy controls (P< 0.001). A significant trend of increasing risk with rising TOS/TAC levels was also seen [OR=3.62, (95 % CI 1.79, 7.35)]. Conclusions: In breast cancer, the serum TOS to TAC ratio can better diagnose oxidative equilibrium than either component alone.

Defining the at risk patients for contrast induced nephropathy after coronary angiography; 24-h urine creatinine versus Cockcroft-Gault equation or serum creatinine level.

BACKGROUND: Definitions of chronic kidney disease (CKD) in many catheterization laboratories have relied on the serum creatinine (Scr) rather than glomerular filtration rate (GFR). Regarding that CKD is the primary predisposing factor for contrast induced nephropathy (CIN), we compared the sensitivity of calculated GFR by 24-h Urine creatinine with Cockcroft-Gault (CG) equation and Scr level to define at risk patients for CIN who were undergone coronary angiography (CAG). MATERIALS AND METHODS: Two hundred fifty four subjects who were candidate for CAG and had normal creatinine level were enrolled. Before CAG, GFR was calculated from a 24-h urine collection, CG equation and a single Scr sample regarding to previously described protocol. Contrast volume used for each case <100 ml. CIN was defined as a 0.5 mg/dL or 25% elevation in the Scr. RESULTS: CIN occurred in 10.6%. Baseline GFR, the volume of contrast agent, and diabetes were the independent risk factors for CIN. GFR was less than 60 ml/min/1.73 m2 in 28% and 23.2% of patients regarding to 24-h urine creatinine and CG equation, respectively. In CIN prediction, 24-h urine creatinine estimated GFR had 85.2%, 59.3% and CG equation GFR had 78.9%, 81.1% sensitivity and specificity, respectively. CONCLUSION: Although, GFR estimated by CG equation has less sensitivity than GFR calculated from 24-h creatinine in CIN probability, but it is better than Scr alone and because of cost-effectiveness and convenience using of this method, we suggest at least using CG equation for GFR calculation before CIN, especially in diabetic and/or older than 60 years cases.

Evaluation of Nrf2, Keap1 and Apoptotic Pathway Genes Expression in Acute Myeloid Leukemia Patients.

The aim of this study was to evaluate the expression Nrf2 (Nuclear factor-erythroid 2-p45 derived factor 2) and Keap1 (Kelch-like ECH-associated protein 1) genes and Bcl-2 (B-cell lymphoma 2), Bcl-XL (B-cell lymphoma-extra large), Bax (Bcl2-associated X protein) apoptotic pathway genes in acute myeloid leukemia patients. In this case-control study, the expression of genes encoding Nrf2, Keap1, Bcl2, Bcl- XL and Bax in 40 acute myeloid leukemia (AML) patients were compared with 40 normal individuals in the Iranian population. We evaluated the mRNA expression of genes by using the real-time quantitative polymerase chain reaction. The expression of Nrf2, Bcl2 and Bcl- XL genes in new AML patients were increased (p < 0.05). The patients treated with chemotherapy had a significantly more than four times higher expression level of Nrf2 than new case patients (P < 0.05), while there was a decrease in the expression level of Bcl2 and Bcl-XL, which was not statistically significant. In other hands in relapsed patients, the expressions of Nrf2, Bcl2 and Bcl- XL were higher level than new case patients (p < 0.05) but this was less than patients treated with chemotherapy (p > 0.05). The high levels of mentioned genes may be associated with poor treatment response, chemoresistance and disease recurrence. Because of hyperactivation and overexpression of Nrf2 in leukemia, suggest that Nrf2 inhibitors could be used as a pharmacological target in combination with classical chemotherapeutic agents to increase the efficacy of anticancer therapy.

Slow-Stroke Back Massage Compared With Music Therapy for Leukemia-Related Pain and Fatigue: A Randomized Controlled Trial.

PURPOSE: Comparison of two safe complementary medicine methods to treat cancer-related pain and fatigue in adult patients with acute leukemia during active treatment with chemotherapy. METHODS: A randomized trial with three groups (light massage, music therapy, and standard care) in Ahvaz, Iran, between 2018 and 2019. A total of 104 participants of the massage and music therapy groups received 15-minute intervention sessions, thrice weekly for 4 weeks, and participants of the control group received standard care. Cancer-related pain and fatigue intensity were measured by numeric self-report rating scales. During the 4 weeks of the interventions, pain and fatigue intensity were measured weekly. All the groups were followed up for 2 weeks after the end of the intervention. RESULTS: Pain and fatigue intensity decreased significantly over time between the intervention groups compared with the standard care group. In the massage and music therapy groups, a progressive reduction of pain and fatigue intensity over time (from the baseline to the fourth week) was observed. Fatigue intensity did not differ between the two intervention groups. Pain intensity decreased more in the massage group compared with the music therapy group. The durable effects of the massage therapy were greater compared with the music therapy 2 weeks after the intervention was completed. CONCLUSION: Light massage was more effective and persisted longer than the music therapy for controlling leukemia-related pain and fatigue in adult patients with acute leukemia.

The Effect of CoQ10 Supplementation on Quality of Life in Women with Breast Cancer Undergoing Tamoxifen Therapy: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: Survival rates among breast cancer patients and the number of patients living with treatment side effects have improved, leading to increased focus on quality of life (QOL). The objective of this study was to determine the efficacy of CoQ10 on QOL scores among breast cancer patients in Iranian undergoing tamoxifen therapy. METHODS: Thirty breast cancer patients were randomized into two groups. The first group received 100 mg CoQ10, and the second group took fplacebo once a day for 8 weeks. QOL was evaluated by a standard QOL questionnaire and a specific questionnaire on QOL of breast cancer patients at baseline and the end of the study. Also, physical activity of patients was assessed with the IPAQ questionnaire and dietary intake determined by a 3-day dietary record. RESULTS: The data of 30 subjects were analyzed. According to QOL C30 data, CoQ10 led to a significant increase in physical functioning (P=0.029), emotional functioning (P=0.031), and cognitive functioning (P=0.023) compared to placebo. Symptom scales revealed a notable reduction in appetite loss in the first group (P=0.01). Global health status showed no significant changes in either study arm. On the QOL BR23, progress in functions and decline in symptoms were not statistically significant. Arm symptoms showed significant reduction (P=0.022) in patients that received placebo. CONCLUSION: This trial indicates that CoQ10 supplementation has effects in ameliorating some dimensions of QOL in breast cancer patients. To generalize the results, larger and longer intervention studies are needed. CLINICAL TRIAL REGISTRATION: IRCT2015042021874N1.

The Efficacy and Safety of Modified Docetaxel, Cisplatin, and 5-Fluorouracil Vs. Epirubicin, Oxaliplatin, and Capecitabine Regimen in the Advanced Gastric Cancer: A Randomized Controlled Clinical Trial.

INTRODUCTION: One of the major challenges of advanced gastric cancer treatment is the lack of a standard regimen for patients. However, several clinical trials have shown that modified docetaxel, cisplatin, and 5-fluorouracil (m-DCF) and epirubicin, oxaliplatin, and capecitabine (EOX) regimens are superior to other regimens. METHODS: This randomized, single-center clinical trial was performed on 40 patients with advanced gastric cancer. The first group received the m-DCF regimen as follows: docetaxel (40 mg/m2) on the first day; cisplatin (40 mg/m2) on the first and second days; and 5-fluorouracil (400 mg/m2) from the first to fourth day. The second group received the EOX regimen, including epirubicin (50 mg/m2) and oxaliplatin (130 mg/m2) i.v on the first day and capecitabine at a twice-daily dose of 625 mg/m2 p.o for 21 days. Treatment was applied every three weeks for a total of eight cycles in both groups. In each group, the overall and progression-free survival rates and toxicity were assessed. RESULTS: A total of 40 patients were enrolled in this study (21 samples in the m-DCF group and 19 samples in the EOX group), 62.5% of whom were male. The median survival rate was 14.00 (95% CI: 11.82-16.18) months in the m-DCF group and 15.00 (95% CI: 9.56-20.43) months in the EOX group; however, differences between the groups were not significant. The progression-free survival rate was higher in the EOX group, although there was no significant difference between the two groups. Also, there was no significant difference regarding the side effects (e.g., toxicity) or need for supportive care between the groups. CONCLUSION: It seems that both m-DCF and EOX regimens are similar in terms of survival and toxicity and are recommended as first-line treatment for advanced gastric cancer with respect to the patient's status.

Evaluation of growth factor independence 1 expression in patients with de novo acute myeloid leukemia.

OBJECTIVE: Growth factor independence 1 (GFI1), a transcriptional repressor, is required for hematopoietic stem cell maintenance and self-renewal in addition to controlling differentiation and proliferation of myeloid cells. As murine studies have demonstrated that this transcription factor has a notable role in the initiation and progression of acute myeloid leukemia (AML) disease, the aim of the current study was to investigate and review the influence of GFI1 in human AML cells. METHODS: GFI1 expression levels were measured by means of real-time polymerase chain reaction in 96 primary AML samples which were then compared to gene expression levels observed in 18 healthy subjects. Moreover, GFI1 expression patterns were analyzed based on specific AML subtypes including acute promyelocytic leukemia (APL). Finally, leukemic cells were stained to measure levels of myeloperoxidase (MPO) activity. RESULTS: This study reports that AML patients have significantly higher GFI1 mRNA levels in comparison to healthy subjects and that, when considering AML subtypes, patients with APL have higher GFI1 expression than non-APL patients. CONCLUSION: It is also concluded that GFI1 overexpression in patients with high MPO levels, such as those of the APL subtype, is correlated with favorable disease prognosis as supported by other studies which demonstrate that increased peroxide activity and GFI1 are independently correlated with a favorable prognosis.

An investigation into the effect of gabapentin capsules on the reduction of nausea and vomiting after chemotherapy in cancerous patients under platinum-based treatment.

INTRODUCTION AND OBJECTIVE: Chemotherapy-induced nausea and vomiting (CINV) is a condition that occur in most patients. This study aimed to investigate the effect of gabapentin capsules on the reduction of chemotherapy-induced nausea and vomiting in patients admitted in the hematological ward for adult patients with platinum-based treatment. MATERIALS AND METHODS: The present study was a randomized clinical trial, which consisted of a control group and an experimental one. The study population consisted of 126 women and men with colonic and gastric cancer who were admitted to Ahwaz Shafa Hospital of adult hematology ward. Of these, 120 subjects were eligible to enter the study. Immediately after chemotherapy, gabapentin capsules were taken. Up to 72 hours later, nausea and vomiting were compared. Descriptive statistics was used to investigate the demographic characteristics. Paired t-test, independent t-test and ANOVA were used to compare the results. RESULTS: The results showed that most of the patients had gastric cancer in the experimental (70%) and control group (66.66%). The results also showed that chemotherapy-induced nausea and vomiting in gabapentin recipient group was different from the placebo group. Accordingly, chemotherapy induced nausea and vomiting in gabapentin group was lower than the placebo group. CONCLUSION: Post-operative nausea and vomiting is an unpleasant experience. Today, the patients find it worse than pain, and they believe it is hard to afford the cost of treatment. Gabapentin seems to be a good drug for reducing nausea and vomiting.

The Effect of Coenzyme Q10 Supplementation on Vascular Endothelial Growth Factor and Serum Levels of Interleukin 6 and 8 in Women with Breast Cancer: A Double-Blind, Placebo-Controlled, Randomized Clinical Trial.

BACKGROUND: To better evaluate the efficacy of CoQ10 on the inflammatory markers in breast cancer patients, we conducted a clinical study of patients with breast cancer undergoing tamoxifen therapy. CoQ10 serves as an antioxidant and inhibits oxidation caused by reactive oxygen species. The aim of the current study was to assess the effect of coenzyme Q10 supplementation on serum levels of interleukin 6, 8, and vascular endothelial growth factor (VEGF) in patients with breast cancer undergoing tamoxifen therapy by a double-blind, placebo-controlled, randomized clinical trial. METHODS: In the study, 30 breast cancer patients and 29 healthy subjects were randomized into four groups. Two groups of intervention received 100 mg CoQ10, and two control groups took placebo once a day for 2 months. Blood draws were obtained at baseline and at the end of the study. Serum levels of IL-6, IL-8 and VEGF were analyzed using ELISA kits. RESULTS: The data of the 59 participants were analyzed. Supplementation with CoQ10 demonstrated a significant decrease in IL-8 and IL-6 serum levels compared to placebo (P< 0.05). Although the downward trend was evident, CoQ10 supplementation did not reveal any significant effect on serum VEGF concentration. The group of patients who received supplements showed the most reduction in serum levels of cytokines among other groups. CONCLUSION: CoQ10 supplementation could be effective in ameliorating inflammatory cytokine levels, thereby reducing the consequences of inflammation caused by breast cancer. To generalize the results, larger and longer intervention studies with higher safe doses are needed and should take account of possible costs and harms as well as benefits (registration number: IRCT2015042021874N1).

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial.

Background: Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitamin D3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstrate the power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDR polymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation on the serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in the VDR gene in breast cancer women. Methods: A randomized, double-blind, placebo-controlled trial was conducted on 56 breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention. Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and after the intervention to measure the 25(OH) D3, TNF-α, TGF- ß and TAC. Genotyping was performed for FokI, BsmI, ApaI, and TaqI polymorphism. Results: After eight weeks supplementation, the intervention group showed a significant increase in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017). Changes in TNF-α, TGF- ß1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes were more responsive to supplementation. Conclusions: Supplementation with a vitamin D3 increased the TAC in breast cancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive to vitamin D supplement compared with those with the FF/ff and tt genotypes.