Ovarian cancer is one of the most prevalent malignancies in women. Screening of the disease is do... more Ovarian cancer is one of the most prevalent malignancies in women. Screening of the disease is done using variety of biomarkers. Diagnostic performance of current biomarkers of the disease such as human epididymis protein (HE4) and CA125 shows contradiction in previous studies. The goal of this study was to evaluate serum levels of CA125 and HE4 in Iranian patients with ovarian cancer and compare specificity and sensitivity of HE4, CA125 and HE4 ? CA125 in patients with different stages and diverse histology. To evaluate CA125 and HE4, 32 patients and 34 healthy women were selected. Origin of ovarian cancer was verified by expert gynecological oncologist. Significance and diagnostic performance were determined by ANOVA and receiver operator characteristic (ROC) and areas under the curve (AUC), respectively. Serum levels of CA125 and HE4 were significantly increased in patients in comparison with control group, especially for tumor cells originated from epithelium (p \ 0.001). ROC–AUC for HE4, CA125 and HE4 ? CA125 were 0.91, 0.86 and 0.91, respectively. Specificity of HE4 was more than CA125 (85 vs. 80 %). Conversely, sensitivity of CA125 was higher in comparison with HE4 (90 vs. 80 %). It is being noticed that cutoff point of HE4 and CA125 was 150 pmol/L and 38 U/mL, respectively. HE4 is slightly more specific for diagnosis of early stages of the disease, but the difference is not remarkable. CA125 and HE4 ? CA125 have some diagnostic performance for prediction of advanced stages. Generally, the data of present study suggest that combining of HE4 and CA125 is a better screening tool for diagnosis of ovarian cancer. Keywords Ovarian cancer Á HE4 Á CA125 Á Tumor marker Á Risk of ovarian malignancy
Introduction: Elastic bands offer variable elastic resistance (ER) throughout a range of motion a... more Introduction: Elastic bands offer variable elastic resistance (ER) throughout a range of motion and their incorporation with exercise movements has been used for variable strength training and rehabilitation purposes. Objective: Investigate the effect of acute bout of progressive elastic-band exercise on muscle damage and inflammatory response in Taekwondo athletes (TKD) compared with untrained ones. Methods: Fourteen (TKD, n = 7 and untrained, n = 7) men performed 3 sets of progressive resistance elastic exercise. Blood samples were taken pre-exercise and also immediately and 24h post exercise. Delayed onset muscle soreness (DOMS), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, total leukocyte counts, interleukin-6 and C-reactive protein (CRP) were analyzed. Results: Only DOMS increased in untrained group, but elevation of DOMS was observed in both groups (TKD and untrained) at 24h after exercise (p<0.05). CK and LDH activity increased in both groups significantly. Also TKD group only showed CK increasing 24h post exercise (p<0.05). Total circulating leukocyte counts increased immediately in post exercise experiments and decreased in 24h ones in both groups (p<0.05). Serum IL-6 immediately increased in both groups and 24h post exercises but there was no significant difference between immediate and 24h post exercise experiments in TKD group. Furthermore, CRP just increased 24h after exercise in both groups (p<0.05). Conclusion: Progressive resistance elastic exercise induced muscle damage and inflammation in TKD athletes, but also had smaller changes in comparison with untrained group and other forms of exercise.
Human leukocyte antigen-G (HLA-G) plays an important role in tumor cell escape from immune survei... more Human leukocyte antigen-G (HLA-G) plays an important role in tumor cell escape from immune surveillance and HLA-G polymorphisms might service as a potential risk factor for clinical outcomes in GAC (gastric adenocarcinoma). We investigated the association between HLA-G polymorphisms as well as soluble HLA-G level and accordance of GAC. This case-control study included 100 GAC patients and 102 unrelated Iranian individual's samples as control. The clinical stages ranged from I to IV. PCR-RFLP method was carried out in order to specify the genotypes of the HLA-G gene. Concentrations of sHLA-G in serum were determined with the sHLA-G-specific enzyme linked immunosorbent assay (ELISA) kit. The G*01:04:01 and G*01:01:02:01 alleles were the predominant alleles in GAC patients and healthy controls. The G*01:01:03:01 and G*01:01:08 allele distributions are significantly higher among controls comparing to cases and seem to have protective effect (P value = 0.026 and 0.007 respectively). There is a substantial differences in G*01:01:02:01/G*01:04:01 genotype frequencies between cases and controls (OR = 2.8, P value < 0.001). The G*01:01:03:01/G*01:04:01 and G*01:01:02:01/G*01:01:08 genotypes frequency are higher among controls in comparison to patients (P value = 0.028 and 0.007 respectively). The polymorphisms in HLA-G could affect GAC induction and its outcome. Also, increased sHLA-G levels in serum might be a useful biomarker for diagnosis.
Artemisinin is a sesquitrepenelactone with an endoperoxide bridge. It is a naturally occurring su... more Artemisinin is a sesquitrepenelactone with an endoperoxide bridge. It is a naturally occurring substance from Artemisia species plants. Artemisia species have been used in oriental medicine for centuries to treat malaria, gastrointestinal helminthosia, diarrhea, and as an antipyretic and sedative agent. Antileishmanial activity of the plants has been announced a few years ago. Dogs are the most important reservoir of leishmaniasis in some parts of the world. To use it as an antileishmanial drug in dogs, its side effects on different organs, among them the kidney as the organ of elimination have to be elucidated. Artemisinin with different concentrations (0.15, 0.3, 0.6 and 1.2 μg/ml) was added to the culture of MDCK (Madin darby canine kidney) cells with and without iron (86 μg/dl). All the changes were controlled and photographed every 12 hours using an invert microscope. After 60 hours, supernatants and cell extracts were examined for LDH (lactate dehydrogenase) concentration and total protein. Also TBARS (thiobarbituric acid reactive substances) test was performed on cell extracts. Some microscopic slides were prepared from the cells and stained with hematoxylin-eosin for microscopic exams. Biochemical parameters showed cellular reaction and injury in a concentration dependent manner. Cell injury was more severe in the iron-added groups. Microscopic exams showed cell and nuclear swelling, granular degeneration, vacuole and vesicle formation, cellular detachment, piknosis, karyorrhexis, cellular necrosis and inhibition of new mitosis. On using the drug for leishmaniasis treatment in the dog, it should be done with caution and supervision.
Background: Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member t... more Background: Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member that efficiently suppresses tumor growth in several types of cancer. Photodynamic therapy (PDT) is commonly used for treatment of different types of cancer and antitumor efficacy of PDT increased upon Wnt signaling inhibition. The objective of this study is to evaluate the effects of Dkk-3 and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer cell line. Material and methods: 4T1 breast cell line were treated with either Dkk-3 (20, 40 and 80 ng/ml) 24 h followed by 5-ALA-PDT (1, 3 and 6 J/cm2). Also, 5-ALA was used at dose 1 mM. The apoptosis and post apoptotic necrosis were evaluated by FITC-Annexin-PI apoptosis detection kit. Results: Obtained findings showed that both Dkk-3 and ALA-PDT have cytotoxic effects on cancer cells in a dose-dependent manner. The subtracted mean of death cell percentage in 20, 40 and 80 ng/ml of Dkk-3 were 6.8 ± 0.7%, 10.4 ± 0.84% and 16.1 ± 1.55% respectively. The subtracted mean of cell death induction in 5-ALA mediated PDT was 5.3 ± 0.77% at 6 J/cm2. Dkk-3 with ALA-PDT significantly increased cell death compared to either Dkk-3 or 5-ALA mediated PDT in cancer 4T1 cancer cell line (P < 0.001). Conclusion: In this study, observed results revealed that Dkk-3 induced the apoptosis in 4T1 breast cancer cells and apoptotic effects of Dkk-3 intensified following photodynamic therapy. This study provided a novel insight into the development of therapeutic strategies for treatment of breast cancer using Dkk-3 combined with PDT.
Background: Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by... more Background: Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photo-dynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Material and methods: Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1 mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2 cm to achieve a total light dose of 5 Joules (J)/cm 2. Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Results: Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells (P < 0.05). Growth of cancer cells remarkably decreased after treatment with MSCs conditioned media and PDT in time-dependent manner (P < 0.01).
Dkk3 is a member of Dkk family proteins, regulating Wnt signaling. Dkk3 plays different roles in ... more Dkk3 is a member of Dkk family proteins, regulating Wnt signaling. Dkk3 plays different roles in human and mouse tumors. Dkk3 predominantly act as a tumor suppressor, however several reports revealed that Dkk3 could accelerate cancer cell proliferation. Herein, we aimed at launching an in silico study to determine Dkk3 structure and its interactions with Kremen and LRP as Wnt signaling receptors as well as EGF receptor. Using various softwares a model was built for Dkk3 molecule. Different protein modeling approaches along with model refinement processes were employed to arrive at the final model. To achieve the final complex of Dkk3 with Kremen, LRP and EGFR molecules protein–protein docking ser-vers were employed. Model assessment softwares indicated the high quality of the finally refined Dkk3 3D structure, indicating the accuracy of modeling and refinement process. Our results revealed that Dkk3 is capable of interacting with Kremen, LRP and EGFR with comparable binding energies. Dkk3 efficiently interacts with LRP, Kremen and EGF receptor and may be a promising protein in cancer therapy by blocking Wnt and EGFR downstream signaling.
Objective: Hematopoietic stem cells (HSCs) transplantation using umbilical cord blood (UCB) has i... more Objective: Hematopoietic stem cells (HSCs) transplantation using umbilical cord blood (UCB) has improved during the last decade. Because of cell limitations, several studies fo-cused on the ex vivo expansion of HSCs. Numerous investigations were performed to introduce the best cytokine cocktails for HSC expansion The majority used the Fms-related tyrosine kinase 3 ligand (FLT3-L) as a critical component. According to FLT3-L biology, in this study we have investigated the hypothesis that FLT3-L only effectively induces HSCs expansion in the presence of a mesenchymal stem cell (MSC) feeder. Materials and Methods: In this experimental study, HSCs and MSCs were isolated from UCB and placenta, respectively. HSCs were cultured in different culture conditions in the presence and absence of MSC feeder and cytokines. After ten days of culture, total nu-cleated cell count (TNC), cluster of differentiation 34 + (CD34 +) cell count, colony forming unit assay (CFU), long-term culture initiating cell (LTC-IC), homeobox protein B4 (HoxB4) mRNA and surface CD49d expression were evaluated. The fold increase for some culture conditions was compared by the t test. Results: HSCs expanded in the presence of cytokines and MSCs feeder. The rate of expansion in the co-culture condition was twofold more than culture with cytokines (P<0.05). FLT3-L could expand HSCs in the co-culture condition at a level of 20-fold equal to the presence of stem cell factor (SCF), thrombopoietin (TPO) and FLT3-L without feeder cells. The number of extracted colonies from LTC-IC and CD49d expression compared with a cytokine cocktail condition meaningfully increased (P<0.05). Conclusion: FLT3-L co-culture with MSCs can induce high yield expansion of HSCs and be a substitute for the universal cocktail of SCF, TPO and FLT3-L in feeder-free culture.
Multiple sclerosis (MS) is an autoimmune disorder associated with neurological signs and chronic ... more Multiple sclerosis (MS) is an autoimmune disorder associated with neurological signs and chronic inflammatory demyelination of the central nervous system (CNS). MS has been thought as Th1 (T helper) and Th17 cells mediated disease, but cells of the innate immune system play an important role both in the initiation and progression of MS. The invariant Natural Killer T (iNKT) cells are the unique innate lymphocytes subtype involved in inflammation and autoimmune disorders and secretes cytokines such as interferon gamma (IFN-g), Interleukin (IL)-10, IL-4 and IL-13. A reduction in number or defect in function of iNKT cells has been associated with an increased prevalence of autoimmune disorders indicating that iNKT cells have an immune-regulatory role in autoimmune disorders. Also, the protective role of iNKT cells has been extensively studied in EAE and the results of these studies show that iNKT cells might be a target for therapeutic purposes, but needs more extensive studies of their biology. In this review, we will attempt to show the protective role of iNKT cells in the pathogenesis of EAE and human disease.
Mesenchymal stem cells are progenitor cells that have capabilities to differentiate different cel... more Mesenchymal stem cells are progenitor cells that have capabilities to differentiate different cell types. Also, MSCs possess immune suppressive effects on DC differentiation and T cell activation through a wide range of soluble factors and receptors. The properties of MSCs change through activation of cytokines particularly IFN-γ and TNF-α. The DC phenotypes and functions including the expression of co-stimulatory and co-inhibitory molecules and capabilities of DCs to induce allogeneic activation of CFSE-labeled splenocytes as well as cytokine production when they were differentiated in the presence of MSCs, TNF-α activated MSCs, IFN-γ activated MSCs and IFN-γ & TNF-α activated MSCs were analyzed. Treg population and T cell polarization were investigated using flowcytometry and real-time PCR respectively. Here, we showed that IFN-γ slightly enhances immunosuppres-sive effects of MSCs on immune system through induction tolerogenic DCs with elevated expression of IDO and increasing Treg population. Conversely, TNF-α decreases immunomodulation properties of MSCs on immune cells through the enhancement of co-stimulatory molecules such as ICOSL and HLA-DR, reduction of PDL-1 and PDL-2 expression and decrease of TGF-β and IL-10 in DCs as well as inhibition of T cell polarization into T H 2 and Treg. Taken together, these data showed crucial effects of microenvironments on MSC behaviors indicating that functions of MSCs differentially altered in the presence of different cytokines.
Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment i... more Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy. Cancer is currently the second leading cause of death following heart disease and it is expected to be the first leading cause of death in the near future. Furthermore, Breast cancer is the third cause of death following lung and bronchus cancer in women 1. Current treatment of breast cancer is based on combination therapy using radi-otherapy, chemotherapy and cytotoxic molecules and antibodies targeting cancer cells 2. Radiotherapy as a crucial component in the management of breast cancer, implies high-energy to induce cell death in local tumors. There are a lot of evidences which indicate that the survival of patients is improved by radi-otherapy through the reduction of local recurrence 3. Radiotherapy is used either for treatment in a primary tumor or after surgery 4. Radiotherapy also used as a component in combination therapy alongside with gene therapy 5. On the other hands, it has been shown that radiotherapy modulates the tumor microenvironment by enhancing the recruitment of multipotent stromal cells (MSCs) 6. Multipotent stromal cells also known as mesenchymal stem cells are non-hematopoietic stem cells derived from diverse tissues such as bone marrow, umbilical cord and adipose tissue 7. MSCs are considered for tumor therapy as a vehicle because they can preferentially migrate towards tumor site and incorporate in tumor stroma and this capability can be improved by radiotherapy 8. In addition MSCs do not induce immune reaction in unrelated donor transplantation 9. Previous studies demonstrated that MSCs or gene modified MSCs could inhibit tumor growth 10. More recently, some reports showed that antitumor effects of MSCs were improved upon activation with either TNF-α
Ovarian cancer is one of the most prevalent malignancies in women. Screening of the disease is do... more Ovarian cancer is one of the most prevalent malignancies in women. Screening of the disease is done using variety of biomarkers. Diagnostic performance of current biomarkers of the disease such as human epididymis protein (HE4) and CA125 shows contradiction in previous studies. The goal of this study was to evaluate serum levels of CA125 and HE4 in Iranian patients with ovarian cancer and compare specificity and sensitivity of HE4, CA125 and HE4 ? CA125 in patients with different stages and diverse histology. To evaluate CA125 and HE4, 32 patients and 34 healthy women were selected. Origin of ovarian cancer was verified by expert gynecological oncologist. Significance and diagnostic performance were determined by ANOVA and receiver operator characteristic (ROC) and areas under the curve (AUC), respectively. Serum levels of CA125 and HE4 were significantly increased in patients in comparison with control group, especially for tumor cells originated from epithelium (p \ 0.001). ROC–AUC for HE4, CA125 and HE4 ? CA125 were 0.91, 0.86 and 0.91, respectively. Specificity of HE4 was more than CA125 (85 vs. 80 %). Conversely, sensitivity of CA125 was higher in comparison with HE4 (90 vs. 80 %). It is being noticed that cutoff point of HE4 and CA125 was 150 pmol/L and 38 U/mL, respectively. HE4 is slightly more specific for diagnosis of early stages of the disease, but the difference is not remarkable. CA125 and HE4 ? CA125 have some diagnostic performance for prediction of advanced stages. Generally, the data of present study suggest that combining of HE4 and CA125 is a better screening tool for diagnosis of ovarian cancer. Keywords Ovarian cancer Á HE4 Á CA125 Á Tumor marker Á Risk of ovarian malignancy
Introduction: Elastic bands offer variable elastic resistance (ER) throughout a range of motion a... more Introduction: Elastic bands offer variable elastic resistance (ER) throughout a range of motion and their incorporation with exercise movements has been used for variable strength training and rehabilitation purposes. Objective: Investigate the effect of acute bout of progressive elastic-band exercise on muscle damage and inflammatory response in Taekwondo athletes (TKD) compared with untrained ones. Methods: Fourteen (TKD, n = 7 and untrained, n = 7) men performed 3 sets of progressive resistance elastic exercise. Blood samples were taken pre-exercise and also immediately and 24h post exercise. Delayed onset muscle soreness (DOMS), creatine kinase (CK) and lactate dehydrogenase (LDH) activity, total leukocyte counts, interleukin-6 and C-reactive protein (CRP) were analyzed. Results: Only DOMS increased in untrained group, but elevation of DOMS was observed in both groups (TKD and untrained) at 24h after exercise (p<0.05). CK and LDH activity increased in both groups significantly. Also TKD group only showed CK increasing 24h post exercise (p<0.05). Total circulating leukocyte counts increased immediately in post exercise experiments and decreased in 24h ones in both groups (p<0.05). Serum IL-6 immediately increased in both groups and 24h post exercises but there was no significant difference between immediate and 24h post exercise experiments in TKD group. Furthermore, CRP just increased 24h after exercise in both groups (p<0.05). Conclusion: Progressive resistance elastic exercise induced muscle damage and inflammation in TKD athletes, but also had smaller changes in comparison with untrained group and other forms of exercise.
Human leukocyte antigen-G (HLA-G) plays an important role in tumor cell escape from immune survei... more Human leukocyte antigen-G (HLA-G) plays an important role in tumor cell escape from immune surveillance and HLA-G polymorphisms might service as a potential risk factor for clinical outcomes in GAC (gastric adenocarcinoma). We investigated the association between HLA-G polymorphisms as well as soluble HLA-G level and accordance of GAC. This case-control study included 100 GAC patients and 102 unrelated Iranian individual's samples as control. The clinical stages ranged from I to IV. PCR-RFLP method was carried out in order to specify the genotypes of the HLA-G gene. Concentrations of sHLA-G in serum were determined with the sHLA-G-specific enzyme linked immunosorbent assay (ELISA) kit. The G*01:04:01 and G*01:01:02:01 alleles were the predominant alleles in GAC patients and healthy controls. The G*01:01:03:01 and G*01:01:08 allele distributions are significantly higher among controls comparing to cases and seem to have protective effect (P value = 0.026 and 0.007 respectively). There is a substantial differences in G*01:01:02:01/G*01:04:01 genotype frequencies between cases and controls (OR = 2.8, P value < 0.001). The G*01:01:03:01/G*01:04:01 and G*01:01:02:01/G*01:01:08 genotypes frequency are higher among controls in comparison to patients (P value = 0.028 and 0.007 respectively). The polymorphisms in HLA-G could affect GAC induction and its outcome. Also, increased sHLA-G levels in serum might be a useful biomarker for diagnosis.
Artemisinin is a sesquitrepenelactone with an endoperoxide bridge. It is a naturally occurring su... more Artemisinin is a sesquitrepenelactone with an endoperoxide bridge. It is a naturally occurring substance from Artemisia species plants. Artemisia species have been used in oriental medicine for centuries to treat malaria, gastrointestinal helminthosia, diarrhea, and as an antipyretic and sedative agent. Antileishmanial activity of the plants has been announced a few years ago. Dogs are the most important reservoir of leishmaniasis in some parts of the world. To use it as an antileishmanial drug in dogs, its side effects on different organs, among them the kidney as the organ of elimination have to be elucidated. Artemisinin with different concentrations (0.15, 0.3, 0.6 and 1.2 μg/ml) was added to the culture of MDCK (Madin darby canine kidney) cells with and without iron (86 μg/dl). All the changes were controlled and photographed every 12 hours using an invert microscope. After 60 hours, supernatants and cell extracts were examined for LDH (lactate dehydrogenase) concentration and total protein. Also TBARS (thiobarbituric acid reactive substances) test was performed on cell extracts. Some microscopic slides were prepared from the cells and stained with hematoxylin-eosin for microscopic exams. Biochemical parameters showed cellular reaction and injury in a concentration dependent manner. Cell injury was more severe in the iron-added groups. Microscopic exams showed cell and nuclear swelling, granular degeneration, vacuole and vesicle formation, cellular detachment, piknosis, karyorrhexis, cellular necrosis and inhibition of new mitosis. On using the drug for leishmaniasis treatment in the dog, it should be done with caution and supervision.
Background: Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member t... more Background: Dickkopf 3 (Dkk-3), a Wnt signaling inhibitor, is a characterized DKK family member that efficiently suppresses tumor growth in several types of cancer. Photodynamic therapy (PDT) is commonly used for treatment of different types of cancer and antitumor efficacy of PDT increased upon Wnt signaling inhibition. The objective of this study is to evaluate the effects of Dkk-3 and 5-aminolevulinic acid (5-ALA) mediated photodynamic therapy in breast cancer cell line. Material and methods: 4T1 breast cell line were treated with either Dkk-3 (20, 40 and 80 ng/ml) 24 h followed by 5-ALA-PDT (1, 3 and 6 J/cm2). Also, 5-ALA was used at dose 1 mM. The apoptosis and post apoptotic necrosis were evaluated by FITC-Annexin-PI apoptosis detection kit. Results: Obtained findings showed that both Dkk-3 and ALA-PDT have cytotoxic effects on cancer cells in a dose-dependent manner. The subtracted mean of death cell percentage in 20, 40 and 80 ng/ml of Dkk-3 were 6.8 ± 0.7%, 10.4 ± 0.84% and 16.1 ± 1.55% respectively. The subtracted mean of cell death induction in 5-ALA mediated PDT was 5.3 ± 0.77% at 6 J/cm2. Dkk-3 with ALA-PDT significantly increased cell death compared to either Dkk-3 or 5-ALA mediated PDT in cancer 4T1 cancer cell line (P < 0.001). Conclusion: In this study, observed results revealed that Dkk-3 induced the apoptosis in 4T1 breast cancer cells and apoptotic effects of Dkk-3 intensified following photodynamic therapy. This study provided a novel insight into the development of therapeutic strategies for treatment of breast cancer using Dkk-3 combined with PDT.
Background: Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by... more Background: Mesenchymal stem cells are multi-potent progenitor cells that inhibit tumor growth by some ligands and releasing factors including TRAIL, DKK-1 and DKK-3. On other hands, photo-dynamic therapy is commonly used for treatment of different types of cancer. The aims of this study are to investigate of MSCs conditioned media and ALA mediated photodynamic therapy in breast cancer. Material and methods: Condition media was derived after documentation of mouse adipose derived MSCs. For photodynamic therapy (PDT), ALA was used at the final concentrations of 1 mM for 4-h followed by exposure to red light with a peak wave length of 632-nm, delivered from diode laser located at 2 cm to achieve a total light dose of 5 Joules (J)/cm 2. Apoptosis and growth of 4T1 cancer cells were analyzed in different groups including MSCs derived condition media, PDT and MSCs derived condition media plus PDT by flow cytometry. Growth of cancer cells were assessed using MTT test. Results: Our findings showed expression of TRAIL on mouse adipose-derived MSCs surfaces. Furthermore, treatment of 4T1 cancer cells with MSCs conditioned media cause to inhibit the cancer cells growth. Also, MSCs conditioned media with PDT have significantly synergic effects to induce apoptosis in breast cancer cells (P < 0.05). Growth of cancer cells remarkably decreased after treatment with MSCs conditioned media and PDT in time-dependent manner (P < 0.01).
Dkk3 is a member of Dkk family proteins, regulating Wnt signaling. Dkk3 plays different roles in ... more Dkk3 is a member of Dkk family proteins, regulating Wnt signaling. Dkk3 plays different roles in human and mouse tumors. Dkk3 predominantly act as a tumor suppressor, however several reports revealed that Dkk3 could accelerate cancer cell proliferation. Herein, we aimed at launching an in silico study to determine Dkk3 structure and its interactions with Kremen and LRP as Wnt signaling receptors as well as EGF receptor. Using various softwares a model was built for Dkk3 molecule. Different protein modeling approaches along with model refinement processes were employed to arrive at the final model. To achieve the final complex of Dkk3 with Kremen, LRP and EGFR molecules protein–protein docking ser-vers were employed. Model assessment softwares indicated the high quality of the finally refined Dkk3 3D structure, indicating the accuracy of modeling and refinement process. Our results revealed that Dkk3 is capable of interacting with Kremen, LRP and EGFR with comparable binding energies. Dkk3 efficiently interacts with LRP, Kremen and EGF receptor and may be a promising protein in cancer therapy by blocking Wnt and EGFR downstream signaling.
Objective: Hematopoietic stem cells (HSCs) transplantation using umbilical cord blood (UCB) has i... more Objective: Hematopoietic stem cells (HSCs) transplantation using umbilical cord blood (UCB) has improved during the last decade. Because of cell limitations, several studies fo-cused on the ex vivo expansion of HSCs. Numerous investigations were performed to introduce the best cytokine cocktails for HSC expansion The majority used the Fms-related tyrosine kinase 3 ligand (FLT3-L) as a critical component. According to FLT3-L biology, in this study we have investigated the hypothesis that FLT3-L only effectively induces HSCs expansion in the presence of a mesenchymal stem cell (MSC) feeder. Materials and Methods: In this experimental study, HSCs and MSCs were isolated from UCB and placenta, respectively. HSCs were cultured in different culture conditions in the presence and absence of MSC feeder and cytokines. After ten days of culture, total nu-cleated cell count (TNC), cluster of differentiation 34 + (CD34 +) cell count, colony forming unit assay (CFU), long-term culture initiating cell (LTC-IC), homeobox protein B4 (HoxB4) mRNA and surface CD49d expression were evaluated. The fold increase for some culture conditions was compared by the t test. Results: HSCs expanded in the presence of cytokines and MSCs feeder. The rate of expansion in the co-culture condition was twofold more than culture with cytokines (P<0.05). FLT3-L could expand HSCs in the co-culture condition at a level of 20-fold equal to the presence of stem cell factor (SCF), thrombopoietin (TPO) and FLT3-L without feeder cells. The number of extracted colonies from LTC-IC and CD49d expression compared with a cytokine cocktail condition meaningfully increased (P<0.05). Conclusion: FLT3-L co-culture with MSCs can induce high yield expansion of HSCs and be a substitute for the universal cocktail of SCF, TPO and FLT3-L in feeder-free culture.
Multiple sclerosis (MS) is an autoimmune disorder associated with neurological signs and chronic ... more Multiple sclerosis (MS) is an autoimmune disorder associated with neurological signs and chronic inflammatory demyelination of the central nervous system (CNS). MS has been thought as Th1 (T helper) and Th17 cells mediated disease, but cells of the innate immune system play an important role both in the initiation and progression of MS. The invariant Natural Killer T (iNKT) cells are the unique innate lymphocytes subtype involved in inflammation and autoimmune disorders and secretes cytokines such as interferon gamma (IFN-g), Interleukin (IL)-10, IL-4 and IL-13. A reduction in number or defect in function of iNKT cells has been associated with an increased prevalence of autoimmune disorders indicating that iNKT cells have an immune-regulatory role in autoimmune disorders. Also, the protective role of iNKT cells has been extensively studied in EAE and the results of these studies show that iNKT cells might be a target for therapeutic purposes, but needs more extensive studies of their biology. In this review, we will attempt to show the protective role of iNKT cells in the pathogenesis of EAE and human disease.
Mesenchymal stem cells are progenitor cells that have capabilities to differentiate different cel... more Mesenchymal stem cells are progenitor cells that have capabilities to differentiate different cell types. Also, MSCs possess immune suppressive effects on DC differentiation and T cell activation through a wide range of soluble factors and receptors. The properties of MSCs change through activation of cytokines particularly IFN-γ and TNF-α. The DC phenotypes and functions including the expression of co-stimulatory and co-inhibitory molecules and capabilities of DCs to induce allogeneic activation of CFSE-labeled splenocytes as well as cytokine production when they were differentiated in the presence of MSCs, TNF-α activated MSCs, IFN-γ activated MSCs and IFN-γ & TNF-α activated MSCs were analyzed. Treg population and T cell polarization were investigated using flowcytometry and real-time PCR respectively. Here, we showed that IFN-γ slightly enhances immunosuppres-sive effects of MSCs on immune system through induction tolerogenic DCs with elevated expression of IDO and increasing Treg population. Conversely, TNF-α decreases immunomodulation properties of MSCs on immune cells through the enhancement of co-stimulatory molecules such as ICOSL and HLA-DR, reduction of PDL-1 and PDL-2 expression and decrease of TGF-β and IL-10 in DCs as well as inhibition of T cell polarization into T H 2 and Treg. Taken together, these data showed crucial effects of microenvironments on MSC behaviors indicating that functions of MSCs differentially altered in the presence of different cytokines.
Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment i... more Gene modified or cytokine activated mesenchymal stem cells (MSCs) have been used as a treatment in various types of cancer. Moreover, irradiation is usually applied as either a standard primary or adjuvant therapy. Here, we showed that the expression of TNF related apoptosis-inducing ligand (TRAIL) and Dickouf-3 (Dkk-3), the promising anticancer proteins, increased in murine adipose-derived mesenchymal stromal cells (AD-MSCs) following activation with TNF-α, resulting in the induction of apoptosis in cancer cells. Also, anticancer effects of TNF-α activated AD-MSCs were intensified with irradiation. In vivo results showed that TNF-α preactivated AD-MSCs combined with irradiation decreased tumor size and increased survival rate in tumor bearing mice. On the other hands, both TNF-α preactivated AD-MSCs with or without irradiation prevented metastasis in ling and liver, and increased apoptosis in tumor mass. Finally, flowcytometry assay demonstrated that naïve AD-MSCs combined with irradiation but not TNF-α activated MSCs with irradiation increased Treg population in lymph node and spleen. Altogether, obtained results suggest that TNF-α activated MSCs combined with irradiation therapy can serve as new strategy in breast cancer therapy. Cancer is currently the second leading cause of death following heart disease and it is expected to be the first leading cause of death in the near future. Furthermore, Breast cancer is the third cause of death following lung and bronchus cancer in women 1. Current treatment of breast cancer is based on combination therapy using radi-otherapy, chemotherapy and cytotoxic molecules and antibodies targeting cancer cells 2. Radiotherapy as a crucial component in the management of breast cancer, implies high-energy to induce cell death in local tumors. There are a lot of evidences which indicate that the survival of patients is improved by radi-otherapy through the reduction of local recurrence 3. Radiotherapy is used either for treatment in a primary tumor or after surgery 4. Radiotherapy also used as a component in combination therapy alongside with gene therapy 5. On the other hands, it has been shown that radiotherapy modulates the tumor microenvironment by enhancing the recruitment of multipotent stromal cells (MSCs) 6. Multipotent stromal cells also known as mesenchymal stem cells are non-hematopoietic stem cells derived from diverse tissues such as bone marrow, umbilical cord and adipose tissue 7. MSCs are considered for tumor therapy as a vehicle because they can preferentially migrate towards tumor site and incorporate in tumor stroma and this capability can be improved by radiotherapy 8. In addition MSCs do not induce immune reaction in unrelated donor transplantation 9. Previous studies demonstrated that MSCs or gene modified MSCs could inhibit tumor growth 10. More recently, some reports showed that antitumor effects of MSCs were improved upon activation with either TNF-α
Uploads
Papers by hemn mohammadpour