Cellular and molecular life sciences, Feb 29, 2024
Advances in cancer immunotherapy over the last decade have led to the development of several agen... more Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies has been associated with adverse inflammatory responses similar to autoimmune diseases. The current review discussed the role of the NF-κB pathway as a tumor promoter, and how it can govern inflammatory responses and affect various immune checkpoints. More precise knowledge about the communication between immune checkpoints and NF-κB pathways could increase the effectiveness of immunotherapy and reduce the adverse effects of checkpoint inhibitor therapy.
Current Pharmacogenomics and Personalized Medicine
Background: Several genetic alterations in cell growth regulatory genes, such as BRAF, are associ... more Background: Several genetic alterations in cell growth regulatory genes, such as BRAF, are associated with colorectal cancer. Due to the introduction of biological agents designed to treat cancer, diagnostic tests using nucleic acids extracted from formalin-fixed and paraffin-embedded tissues are becoming more common. Objective: This study aimed to determine the incidence of BRAF mutations in colorectal cancer patients. Materials and Methods: 50 paraffin-embedded cancer specimens were obtained from Imam Reza Hospital of Birjand in Iran. PCR was used to amplify and sequence the BRAF gene exon 15, which was extracted from paraffin-embedded tissue using an improved technique. Results: 2/43 (4%) of patients with colorectal cancer exhibited the BEAF V600E mutation. Most of the mutations occurred in patients over 50 years of age. Conclusion: To understand how genetics and environment interact to influence the low incidence of BRAF mutations in the east of Iran, further research is needed ...
Drug resistance is one of the most critical challenges facing researchers in treating breast canc... more Drug resistance is one of the most critical challenges facing researchers in treating breast cancer. Despite numerous treatments for breast cancer, including conventional chemical drugs, monoclonal antibodies, and immunotherapeutic drugs known as immune checkpoint inhibitors (ICI), many patients resist various approaches. In recent years, the relationship between gene expression profiles and drug resistance phenotypes has attracted much attention. Non-coding RNAs (ncRNAs) are regulatory molecules that have been shown to regulate gene expression and cell transcriptome. Two categories, microRNAs and long non-coding RNAs have been more considered and studied among these ncRNAs. Studying the role of different ncRNAs in chemical drug resistance and ICI resistance together can be beneficial in selecting more effective treatments for breast cancer. Changing the expression and action mechanism of these regulatory molecules on drug resistance phenotypes is the main topic of this review article.
Thymic stromal lymphopoietin (TSLP) is an IL-7-like type 1 inflammatory cytokine that is mainly p... more Thymic stromal lymphopoietin (TSLP) is an IL-7-like type 1 inflammatory cytokine that is mainly produced by epithelial cells in the skin, lungs, thymus, and gastrointestinal tract. This cytokine is a master regulator involved in T helper 2 cell-type inflammation immune responses. Various cell types, including T, B, mast, dendritic, and cancer or cancer-associated cells, are activated via TSLP. TSLP expression is also associated with various human cancers and produced by Helicobacter pylori-infected human gastric epithelial cells. TSLP is a multi-functional protein that can act as both an oncogene and a tumor suppressor. The aim of this study was to examine the role of TSLP in the progression of gastric cancer (GC) and its correlation with clinicopathological features in GC patients. Because of the relationship between H. pylori infection and GC, we also examined gastric tissue specimens for H. pylori DNA. In this study, fresh tumoral tissues and distant tumor-free samples from 50 GC patients were assessed for TSLP mRNA expression by quantitative real-time PCR. The GC samples were also assessed for H. pylori DNA using primers specific for H. pylori 16S rRNA and the UreC genes by PCR. TSLP mRNA was overexpressed in 20 of the 50 (40 %) GC samples relative to their corresponding normal tissues. TSLP overexpression was significantly correlated with tumor cell metastasis to lymph nodes. Of the 20 patients with TSLP overexpression, 17 (85.0 %) had metastasis to lymph nodes (p = 0.023). In addition, the presence of H. pylori was confirmed by PCR in 22 of the 50 (44 %) cases and 10 (50 %) of the 20 TSLP overexpressors. We show that human GC cells produce TSLP and a significant correlation was seen between TSLP overexpression and GC metastasis to lymph nodes. This is the first report to indicate that TSLP may play a role in lymph node involvement in GC patients.
Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characte... more Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), thiol (p < 0.001), NO (p < 0.01), and PAB (p < 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (p < 0.001) and PAB (p < 0.001) when compared to healthy subjects. Elevated levels of MDA (p < 0.001) and PAB (p < 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979; p = 0.033), and MDA (OR: 0.996; p = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished. Conclusion: Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.
Gastric cancer is a malignancy with a high mortality rate worldwide. Cancer stem cells (CSCs) are... more Gastric cancer is a malignancy with a high mortality rate worldwide. Cancer stem cells (CSCs) are a small subpopulation of tumor cells that possess the tumor-initiating ability, self-renewal capacity, and high resistance to conventional therapies. Due to the diversity and complexity of human tumors, new cell lines are urgently needed to supply clinically and physiologically relevant cancer models. Here, we report establishing a novel cell line (BAG 50 ) with stemness properties. Chemotherapy-enriched sphere-forming cells with CSC properties isolated from a patient with GC were cultured in a serum-containing medium and passaged for up to 51 passages. The colony-forming ability and tumor-forming capacity of BAG 50 cells were evaluated in vitro and in vivo. mRNA upregulation of stemness-related transcriptional factors using real-time PCR as well as expression of CSC markers using ow cytometry was investigated. Finally, STR pro ling and chromosome studies were performed. BAG 50 cells formed oating spheroid colonies in a serum-free medium. Subcutaneous injection of these cells generated xenograft tumors in nude mice. Pluripotency markers (SOX-2, OCT4, and Cripto-1) in them were upregulated compared with normal gastric cells. The majority of them expressed CSC markers of CD44, CD54, and EpCAM, and stemness marker of oct-4. STR pro ling showed a unique DNA ngerprint. Karyotype also demonstrated multiple aneuploidies and chromosomal translocations. We suggested that the highly tumorigenic BAG 50 cell line with stem cell-like phenotypes may provide a valuable in vitro tool to support new diagnostic, prognostic, and predictive biomarkers as well as the development of more effective treatment strategies.
Background Resistant cells are a critical problem that reduce treatment efficacy of breast cancer... more Background Resistant cells are a critical problem that reduce treatment efficacy of breast cancer. Nowadays, CIP2A and PD-L1 are considered as theraputical challenges in breast cancer, because of responsible for drug resistance and immune evasion respectively. Hence, identifying agents to suppress these factors is great of interest. Specifically, epigenetic drugs can be an effective approach to alter the behavior of genes. Objective The objective of this study is to evaluate the drug effects and molecular mechanisms of valproic acid (VPA) as a HDAC inhibitor, particularly its effect on CIP2A and PD-L1 in breast cancer MCF-7 cell line. Materials and Methods In this study, MCF-7 cells were treated with various concentration of VPA for 24 h, 48 h, and 72 h. The rate of cell viability was measured by MTT assay. Finally, gene expressions of CIP2A, c-MYC, PI3K, Akt, mTOR and PD-L1 were analyzed by real time PCR and ΔCT method. Result VPA showed a growth inhibitory effect in MCF-7 cell lin...
Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characte... more Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), th...
ijbms.mums.ac.ir Expression analysis of CD44 isoforms S and V3, in patients with esophageal squam... more ijbms.mums.ac.ir Expression analysis of CD44 isoforms S and V3, in patients with esophageal squamous cell carcinoma
Drug resistance is one of the most critical challenges facing researchers in treating breast canc... more Drug resistance is one of the most critical challenges facing researchers in treating breast cancer. Despite numerous treatments for breast cancer, including conventional chemical drugs, monoclonal antibodies, and immunotherapeutic drugs known as immune checkpoint inhibitors (ICI), many patients resist various approaches. In recent years, the relationship between gene expression profiles and drug resistance phenotypes has attracted much attention. Non-coding RNAs (ncRNAs) are regulatory molecules that have been shown to regulate gene expression and cell transcriptome. Two categories, microRNAs and long non-coding RNAs have been more considered and studied among these ncRNAs. Studying the role of different ncRNAs in chemical drug resistance and ICI resistance together can be beneficial in selecting more effective treatments for breast cancer. Changing the expression and action mechanism of these regulatory molecules on drug resistance phenotypes is the main topic of this review article.
The results of this study showed that administration with either lead acetate or mercury chloride... more The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSperspecific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.
Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including ... more Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including breast, brain, lung, prostates, testis, ovary, esophagus, colon, and liver. Their origin is yet to be discovered, though a series of hypotheses have been proposed in this regard. CSCs play a role in not only the creation of cancer, but also in its evolution, metastasis, and recurrence. CSCs have an important role in cancer therapy and the resistance towards chemotherapeutic agents. This article reviews the characteristics of cancer stem cells in terms of origin, resistance towards chemotherapy, methods of isolation, and cancer therapy.
Background The most typical malignancy among women worldwide is breast cancer. Estrogen receptor ... more Background The most typical malignancy among women worldwide is breast cancer. Estrogen receptor play a vital role in this cancer. One of the most known mechanisms that affect the activity of this receptor is its phosphorylation by protein kinase pathways. Studies have shown that hesperetin has an effect on intracellular kinase pathways. Purpose The aim of this study was to investigate the effect of hesperetin on the level of expression, phosphorylation and activity of estrogen receptor . Study design and methods: MCF-7 cells were cultured in RPMI 1640 phenol red free medium containing charcoal stripped FBS and treated with hesperetin. MTT method was used to evaluate cell survival. The level of ERα protein and its phosphorylated form (Ser118) was determined by western blot technique. Luciferase reporter vector was used to evaluate ERE activity. Results The results of this study indicated that hesperetin reduced the survival of MCF-7 cells in a dose dependent manner. The level of exp...
Background. In-stent restenosis (ISR) is an important clinical complication that occurs following... more Background. In-stent restenosis (ISR) is an important clinical complication that occurs following stent implantation. The application of drug-eluting stents (DES) and even consumption of drugs such as antiplatelet agents and statins are not completely effective in reducing ISR risk. Since the number of these patients continues to rise, it is pivotal to detect patients who are at a higher risk of ISR. In addition, identification of biochemical markers of ISR could give the right perspective on choosing the proper strategy to treat these patients. Several pathophysiological pathways including oxidative stress (OS) are implicated in the progression of ISR. Hence, this study aimed to evaluate the association between oxidative/anti-oxidative markers and ISR. Methods. This was a case-control study which comprised 21 ISR, 26 NISR (non-ISR), and 20 healthy subjects. The serum levels of OS markers including malondialdehyde (MDA), thiol groups (GSH), total antioxidant capacity (TAC), and the ...
IntroductionThis study aimed to evaluate the TRE-induced changes in the serum expression levels o... more IntroductionThis study aimed to evaluate the TRE-induced changes in the serum expression levels of miRNAs associated with lipids metabolism and autophagy process in MI patients to assess the potential protective effects of TRE in these patients.Material and methodsThis post hoc investigation was performed on serum samples obtained from a pilot randomized, double blind, placebo-controlled clinical trial that recruited 14 men (aged 18-80) who had MI and systemic inflammation. The patients were randomized in a 2:1 ratio to either TRE (15 g/week, intravenous (IV) ad-ministration) (N=10) or placebo groups (equal volume of saline 0.9 %) (N=4) for a period of 12 weeks. To measure the relative serum expression levels of miRNA-155, miRNA-221, and miRNA-33, the SYBR Green qPCR method was used.ResultsmiRNA-155 showed significantly higher serum expression levels in the TRE group (2.772±0.73; P=0.009) when compared to the placebo group. Also, significant reductions in miRNA-155 (0.171±0.03; P=0....
Objective(s): CD44 is a member of the cell adhesion molecules family. Naturally, CD44S, along wit... more Objective(s): CD44 is a member of the cell adhesion molecules family. Naturally, CD44S, along with CD44V3 influence the cell motility, migration, and adhesion, while in tumor cells they lead to tumor invasion, progression, and metastasis. The purpose of this research is to evaluate the CD44S and CD44V3 expression in Esophageal Squamous Cell Carcinoma (ESCC) and to reveal their correlations with clinicopathological features of patients. Materials and Methods: Fresh tumoral and distant tumor-free esophageal tissues were obtained from 50 patients with ESCC. Using quantitative real-time PCR, the expression levels of CD44S and CD44V3 were quantified and compared in both groups of cells. The patients had not received any therapeutic interference, such as chemotherapy or radiation, prior to sampling. Results: Significant overexpression of CD44S and CD44V3 mRNA was observed in 13 (26.0%, P=0.03) and 11 (22.0%, P=0.007) tumor specimens, respectively. The expression of the genes were signific...
Cellular and molecular life sciences, Feb 29, 2024
Advances in cancer immunotherapy over the last decade have led to the development of several agen... more Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T-lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies has been associated with adverse inflammatory responses similar to autoimmune diseases. The current review discussed the role of the NF-κB pathway as a tumor promoter, and how it can govern inflammatory responses and affect various immune checkpoints. More precise knowledge about the communication between immune checkpoints and NF-κB pathways could increase the effectiveness of immunotherapy and reduce the adverse effects of checkpoint inhibitor therapy.
Current Pharmacogenomics and Personalized Medicine
Background: Several genetic alterations in cell growth regulatory genes, such as BRAF, are associ... more Background: Several genetic alterations in cell growth regulatory genes, such as BRAF, are associated with colorectal cancer. Due to the introduction of biological agents designed to treat cancer, diagnostic tests using nucleic acids extracted from formalin-fixed and paraffin-embedded tissues are becoming more common. Objective: This study aimed to determine the incidence of BRAF mutations in colorectal cancer patients. Materials and Methods: 50 paraffin-embedded cancer specimens were obtained from Imam Reza Hospital of Birjand in Iran. PCR was used to amplify and sequence the BRAF gene exon 15, which was extracted from paraffin-embedded tissue using an improved technique. Results: 2/43 (4%) of patients with colorectal cancer exhibited the BEAF V600E mutation. Most of the mutations occurred in patients over 50 years of age. Conclusion: To understand how genetics and environment interact to influence the low incidence of BRAF mutations in the east of Iran, further research is needed ...
Drug resistance is one of the most critical challenges facing researchers in treating breast canc... more Drug resistance is one of the most critical challenges facing researchers in treating breast cancer. Despite numerous treatments for breast cancer, including conventional chemical drugs, monoclonal antibodies, and immunotherapeutic drugs known as immune checkpoint inhibitors (ICI), many patients resist various approaches. In recent years, the relationship between gene expression profiles and drug resistance phenotypes has attracted much attention. Non-coding RNAs (ncRNAs) are regulatory molecules that have been shown to regulate gene expression and cell transcriptome. Two categories, microRNAs and long non-coding RNAs have been more considered and studied among these ncRNAs. Studying the role of different ncRNAs in chemical drug resistance and ICI resistance together can be beneficial in selecting more effective treatments for breast cancer. Changing the expression and action mechanism of these regulatory molecules on drug resistance phenotypes is the main topic of this review article.
Thymic stromal lymphopoietin (TSLP) is an IL-7-like type 1 inflammatory cytokine that is mainly p... more Thymic stromal lymphopoietin (TSLP) is an IL-7-like type 1 inflammatory cytokine that is mainly produced by epithelial cells in the skin, lungs, thymus, and gastrointestinal tract. This cytokine is a master regulator involved in T helper 2 cell-type inflammation immune responses. Various cell types, including T, B, mast, dendritic, and cancer or cancer-associated cells, are activated via TSLP. TSLP expression is also associated with various human cancers and produced by Helicobacter pylori-infected human gastric epithelial cells. TSLP is a multi-functional protein that can act as both an oncogene and a tumor suppressor. The aim of this study was to examine the role of TSLP in the progression of gastric cancer (GC) and its correlation with clinicopathological features in GC patients. Because of the relationship between H. pylori infection and GC, we also examined gastric tissue specimens for H. pylori DNA. In this study, fresh tumoral tissues and distant tumor-free samples from 50 GC patients were assessed for TSLP mRNA expression by quantitative real-time PCR. The GC samples were also assessed for H. pylori DNA using primers specific for H. pylori 16S rRNA and the UreC genes by PCR. TSLP mRNA was overexpressed in 20 of the 50 (40 %) GC samples relative to their corresponding normal tissues. TSLP overexpression was significantly correlated with tumor cell metastasis to lymph nodes. Of the 20 patients with TSLP overexpression, 17 (85.0 %) had metastasis to lymph nodes (p = 0.023). In addition, the presence of H. pylori was confirmed by PCR in 22 of the 50 (44 %) cases and 10 (50 %) of the 20 TSLP overexpressors. We show that human GC cells produce TSLP and a significant correlation was seen between TSLP overexpression and GC metastasis to lymph nodes. This is the first report to indicate that TSLP may play a role in lymph node involvement in GC patients.
Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characte... more Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), thiol (p < 0.001), NO (p < 0.01), and PAB (p < 0.001) were notably higher in HoFH group in comparison with healthy subjects. HeFH group also showed significantly higher levels of thiol (p < 0.001) and PAB (p < 0.001) when compared to healthy subjects. Elevated levels of MDA (p < 0.001) and PAB (p < 0.001) were also observed in HoFH relative to HeFH. No significant differences were found between the studied groups in the case of antioxidant enzyme activities. The results of binary logistic regression showed that PAB (OR: 0.979; p = 0.033), and MDA (OR: 0.996; p = 0.018) levels were inversely associated with HoFH, although, after adjustment for age and LDL-C levels, these associations were diminished. Conclusion: Several oxidant/antioxidant differences were found between FH patients and healthy individuals as well as between HoFH and HeFH patients. These differences might be strongly dependent on plasma LDL-C levels.
Gastric cancer is a malignancy with a high mortality rate worldwide. Cancer stem cells (CSCs) are... more Gastric cancer is a malignancy with a high mortality rate worldwide. Cancer stem cells (CSCs) are a small subpopulation of tumor cells that possess the tumor-initiating ability, self-renewal capacity, and high resistance to conventional therapies. Due to the diversity and complexity of human tumors, new cell lines are urgently needed to supply clinically and physiologically relevant cancer models. Here, we report establishing a novel cell line (BAG 50 ) with stemness properties. Chemotherapy-enriched sphere-forming cells with CSC properties isolated from a patient with GC were cultured in a serum-containing medium and passaged for up to 51 passages. The colony-forming ability and tumor-forming capacity of BAG 50 cells were evaluated in vitro and in vivo. mRNA upregulation of stemness-related transcriptional factors using real-time PCR as well as expression of CSC markers using ow cytometry was investigated. Finally, STR pro ling and chromosome studies were performed. BAG 50 cells formed oating spheroid colonies in a serum-free medium. Subcutaneous injection of these cells generated xenograft tumors in nude mice. Pluripotency markers (SOX-2, OCT4, and Cripto-1) in them were upregulated compared with normal gastric cells. The majority of them expressed CSC markers of CD44, CD54, and EpCAM, and stemness marker of oct-4. STR pro ling showed a unique DNA ngerprint. Karyotype also demonstrated multiple aneuploidies and chromosomal translocations. We suggested that the highly tumorigenic BAG 50 cell line with stem cell-like phenotypes may provide a valuable in vitro tool to support new diagnostic, prognostic, and predictive biomarkers as well as the development of more effective treatment strategies.
Background Resistant cells are a critical problem that reduce treatment efficacy of breast cancer... more Background Resistant cells are a critical problem that reduce treatment efficacy of breast cancer. Nowadays, CIP2A and PD-L1 are considered as theraputical challenges in breast cancer, because of responsible for drug resistance and immune evasion respectively. Hence, identifying agents to suppress these factors is great of interest. Specifically, epigenetic drugs can be an effective approach to alter the behavior of genes. Objective The objective of this study is to evaluate the drug effects and molecular mechanisms of valproic acid (VPA) as a HDAC inhibitor, particularly its effect on CIP2A and PD-L1 in breast cancer MCF-7 cell line. Materials and Methods In this study, MCF-7 cells were treated with various concentration of VPA for 24 h, 48 h, and 72 h. The rate of cell viability was measured by MTT assay. Finally, gene expressions of CIP2A, c-MYC, PI3K, Akt, mTOR and PD-L1 were analyzed by real time PCR and ΔCT method. Result VPA showed a growth inhibitory effect in MCF-7 cell lin...
Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characte... more Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder characterizied by elevated levels of circulating low-density lipoprotein cholesterol (LDL-C) which is an important source of substrates to be oxidized by different oxidative agents. Subsequently, the oxidized LDLs (oxLDLs) induce further oxidative reactions in FH patients, which contributes to the development of atherosclerosis and advanced cardiovascular events in these patients. This study aimed to investigate the association of oxidant/antioxidant markers with FH. Methods: This case-control study comprised 18 HoFH, 18 HeFH, and 20 healthy subjects. Oxidant/antioxidant markers including MDA, MPO, thiol, nitric oxide (NO), myeloperoxidase (MPO), glutathione peroxidase (GPx), SOD, and CAT were assessed by colorimetric methods. Prooxidant-antioxidant balance was also measured by pro-oxidant antioxidant balance (PAB) assay. Results: The levels of MDA (p < 0.001), MPO activity (p < 0.001), th...
ijbms.mums.ac.ir Expression analysis of CD44 isoforms S and V3, in patients with esophageal squam... more ijbms.mums.ac.ir Expression analysis of CD44 isoforms S and V3, in patients with esophageal squamous cell carcinoma
Drug resistance is one of the most critical challenges facing researchers in treating breast canc... more Drug resistance is one of the most critical challenges facing researchers in treating breast cancer. Despite numerous treatments for breast cancer, including conventional chemical drugs, monoclonal antibodies, and immunotherapeutic drugs known as immune checkpoint inhibitors (ICI), many patients resist various approaches. In recent years, the relationship between gene expression profiles and drug resistance phenotypes has attracted much attention. Non-coding RNAs (ncRNAs) are regulatory molecules that have been shown to regulate gene expression and cell transcriptome. Two categories, microRNAs and long non-coding RNAs have been more considered and studied among these ncRNAs. Studying the role of different ncRNAs in chemical drug resistance and ICI resistance together can be beneficial in selecting more effective treatments for breast cancer. Changing the expression and action mechanism of these regulatory molecules on drug resistance phenotypes is the main topic of this review article.
The results of this study showed that administration with either lead acetate or mercury chloride... more The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSperspecific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.
Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including ... more Cancer Stem Cells (CSC) have the ability to self-renew and are present in most tissues including breast, brain, lung, prostates, testis, ovary, esophagus, colon, and liver. Their origin is yet to be discovered, though a series of hypotheses have been proposed in this regard. CSCs play a role in not only the creation of cancer, but also in its evolution, metastasis, and recurrence. CSCs have an important role in cancer therapy and the resistance towards chemotherapeutic agents. This article reviews the characteristics of cancer stem cells in terms of origin, resistance towards chemotherapy, methods of isolation, and cancer therapy.
Background The most typical malignancy among women worldwide is breast cancer. Estrogen receptor ... more Background The most typical malignancy among women worldwide is breast cancer. Estrogen receptor play a vital role in this cancer. One of the most known mechanisms that affect the activity of this receptor is its phosphorylation by protein kinase pathways. Studies have shown that hesperetin has an effect on intracellular kinase pathways. Purpose The aim of this study was to investigate the effect of hesperetin on the level of expression, phosphorylation and activity of estrogen receptor . Study design and methods: MCF-7 cells were cultured in RPMI 1640 phenol red free medium containing charcoal stripped FBS and treated with hesperetin. MTT method was used to evaluate cell survival. The level of ERα protein and its phosphorylated form (Ser118) was determined by western blot technique. Luciferase reporter vector was used to evaluate ERE activity. Results The results of this study indicated that hesperetin reduced the survival of MCF-7 cells in a dose dependent manner. The level of exp...
Background. In-stent restenosis (ISR) is an important clinical complication that occurs following... more Background. In-stent restenosis (ISR) is an important clinical complication that occurs following stent implantation. The application of drug-eluting stents (DES) and even consumption of drugs such as antiplatelet agents and statins are not completely effective in reducing ISR risk. Since the number of these patients continues to rise, it is pivotal to detect patients who are at a higher risk of ISR. In addition, identification of biochemical markers of ISR could give the right perspective on choosing the proper strategy to treat these patients. Several pathophysiological pathways including oxidative stress (OS) are implicated in the progression of ISR. Hence, this study aimed to evaluate the association between oxidative/anti-oxidative markers and ISR. Methods. This was a case-control study which comprised 21 ISR, 26 NISR (non-ISR), and 20 healthy subjects. The serum levels of OS markers including malondialdehyde (MDA), thiol groups (GSH), total antioxidant capacity (TAC), and the ...
IntroductionThis study aimed to evaluate the TRE-induced changes in the serum expression levels o... more IntroductionThis study aimed to evaluate the TRE-induced changes in the serum expression levels of miRNAs associated with lipids metabolism and autophagy process in MI patients to assess the potential protective effects of TRE in these patients.Material and methodsThis post hoc investigation was performed on serum samples obtained from a pilot randomized, double blind, placebo-controlled clinical trial that recruited 14 men (aged 18-80) who had MI and systemic inflammation. The patients were randomized in a 2:1 ratio to either TRE (15 g/week, intravenous (IV) ad-ministration) (N=10) or placebo groups (equal volume of saline 0.9 %) (N=4) for a period of 12 weeks. To measure the relative serum expression levels of miRNA-155, miRNA-221, and miRNA-33, the SYBR Green qPCR method was used.ResultsmiRNA-155 showed significantly higher serum expression levels in the TRE group (2.772±0.73; P=0.009) when compared to the placebo group. Also, significant reductions in miRNA-155 (0.171±0.03; P=0....
Objective(s): CD44 is a member of the cell adhesion molecules family. Naturally, CD44S, along wit... more Objective(s): CD44 is a member of the cell adhesion molecules family. Naturally, CD44S, along with CD44V3 influence the cell motility, migration, and adhesion, while in tumor cells they lead to tumor invasion, progression, and metastasis. The purpose of this research is to evaluate the CD44S and CD44V3 expression in Esophageal Squamous Cell Carcinoma (ESCC) and to reveal their correlations with clinicopathological features of patients. Materials and Methods: Fresh tumoral and distant tumor-free esophageal tissues were obtained from 50 patients with ESCC. Using quantitative real-time PCR, the expression levels of CD44S and CD44V3 were quantified and compared in both groups of cells. The patients had not received any therapeutic interference, such as chemotherapy or radiation, prior to sampling. Results: Significant overexpression of CD44S and CD44V3 mRNA was observed in 13 (26.0%, P=0.03) and 11 (22.0%, P=0.007) tumor specimens, respectively. The expression of the genes were signific...
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Papers by atena mansouri