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کاربرد نوع شرط:
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Combination therapy,Metformin,Synergistic effects,Phenformin
- چکیده:
- چکیده انگلیسی: Objective(s): Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed.
Materials and Methods: Cytotoxicity of the drugs individually and in combination against T47D and MDA-MB-231 breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after 48 hr drug exposure were determined using qRT-PCR.
Results: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC50 values against MDA-MB-231 cells than against T47D cells.
Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDA-MB-231cells than in T47D cells (P<0.001).
Conclusion: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.
It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.
- انتشار مقاله: 18-12-1396
- نویسندگان: Davoud Jafari-Gharabaghlou,Younes Pilehvar-Soltanahmadi,Mehdi Dadashpour,Ali Mota,Soheila Vafajouy-Jamshidi,Leila Faramarzi,Sara Rasouli,Nosratollah Zarghami
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Combination therapy,Metformin,Synergistic effects,Phenformin
- چکیده:
- چکیده انگلیسی: Objective(s): Breast cancer remains a global challenge, and further chemopreventive therapies are still immediately required. Emerging evidence has revealed the potent anti-cancer effects of biguanides, Metformin (MET) and phenformin (PHE). Thus, to explore an efficient chemopreventive strategy for breast cancer, the antiproliferative effects of the combination of MET and PHE against breast cancer cells were assessed.
Materials and Methods: Cytotoxicity of the drugs individually and in combination against T47D and MDA-MB-231 breast cancer cells were assessed using MTT assay and the median-effect method was used to analyze the precise nature of the interaction between MET and PHE. Besides, the expression levels of hTERT after 48 hr drug exposure were determined using qRT-PCR.
Results: Based on the cytotoxicity assay, both MET and PHE further inhibited the growth of MDA-MB-231 cells compared with T47D cells. It was found that MET+PHE reduced the IC50s of MET and PHE in both cells drastically more than the single treatments in a synergistic manner. Importantly, MET+PHE showed higher antiproliferative effect with smaller IC50 values against MDA-MB-231 cells than against T47D cells.
Real-time PCR results revealed that hTERT expression was significantly reduced in both breast cancer cell lines treated with MET+PHE than the single treatments. In comparison between two types of breast cancer cells, it was detected that MET+PHE could further decline hTERT expression in MDA-MB-231cells than in T47D cells (P<0.001).
Conclusion: It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.
It is speculated that the combination of MET and PHE may be a promising and convenient approach to improve the efficiency of breast cancer treatment.
- انتشار مقاله: 18-12-1396
- نویسندگان: Davoud Jafari-Gharabaghlou,Younes Pilehvar-Soltanahmadi,Mehdi Dadashpour,Ali Mota,Soheila Vafajouy-Jamshidi,Leila Faramarzi,Sara Rasouli,Nosratollah Zarghami
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Basic Medical Sciences
- نوع مقاله: Journal Article
- کلمات کلیدی: fertility,MicroRNA,Has-mir-100,Has-let-7b
- چکیده:
- چکیده انگلیسی: Objective(s): Estrogen receptor-alpha (ERα) mediates estrogen action in regulation of different levels of the hypothalamic-pituitary-testis axis. It has a key role in spermatogenesis. Estrogen receptor alpha knock-out (ER koα) male mice were infertile and severe impairment in spermatogenesis and seminiferous tubules was observed. Recently, it has been reported that microRNA (miRNA) mir-100 and let-7b were predicted to target ERα gene. MiRNA are small, endogenous, single stranded RNA molecules that regulate gene expression and have been implicated in various disease states. It has been proved that some miRNAs expression is tissue- and disease-specific, giving potential for identifying miRNAs as a diagnostic tool.
Materials and Methods: In this study, the change in the expression levels of mir-100, let-7b and ERα expression levels were evaluated in oligospermic infertile patients (n=43) compared to control fertile subjects (n=43). After washing and separating sperms, total RNA was isolated and then cDNA was synthesized. The expression levels of mir-100 and let-7b and ERα were evaluated by real time PCR.
Results: Mir-100, let-7b levels were significantly higher than those in control group (P=0.008 and P=0.009, respectively). We have found that, ERα level was significantly decreased in comparison with normal group (P< 0.0001).
Conclusion: Changes in mir-100, let-7b and ERα expression levels in oligospermic patients may be associated with the susceptibility and progression of infertility. The results of this study indicate that miRNA can have a key role in spermatogenesis and might have a diagnostic and prognostic value in men infertility.- انتشار مقاله: 29-11-1392
- نویسندگان: Alireza Abhari,Nosratollah Zarghami,Vahideh Shahnazi,Abolfazl Barzegar,Laya Farzadi,Hadi Karami,Sepideh Zununi Vahed,Mohammad Nouri
- مشاهده
- جایگاه : پژوهشی
- مجله: Iranian Journal of Biotechnology
- نوع مقاله: Journal Article
- کلمات کلیدی: EGFR,Cancer target therapy,HuscFv,Immunotoxin,Pseudomonas exotoxin A
- چکیده:
- چکیده انگلیسی: Background: Epidermal growth factor receptor (EGFR) plays an important role in the progression and tumorigenesis of the various cancers. In this regards, anti-EGFR antibodies are valuable approved therapeutics for the EGFR over-expressing cancers. However, the occurrence of mutations in the EGFR and/or KRAS genes; a common phenomenon which is seen in many cancers, lead to the resistance to the EGFR-directed antibodies. EGFR based immunotoxins are capable of overcoming this limitation by directing the toxin moieties to the cancer cells resulting in cell death.
Objectives: In the present study, a novel immunotoxin consisting of the truncated Pseudomonas exotoxin A (PE-40) and anti-EGFR huscFv was developed and evaluated for the induction of cell death in EGFR positive A431tumoral cells.
Materials and Methods: PE-40 fragment of the exotoxin A was amplified by using PCR and ligated to pET22b-huscFv. The reaction was confirmed by PCR and restriction digestion. The immunotoxin was expressed in E. coli BL21 (plysS) and then was purified by Ni-NTA affinity column. Subsequently, the toxicity of the purified immunotoxin was evaluated on EGFR over-expressing epidermoid carcinoma of skin, A431 cell line.
Results: PCR and restriction digestion experiments have verified the integrity of the immunotoxin construct. Purification by affinity column resulted in a highly purified recombinant immunotoxin. MTT assay revealed the growth inhibitory effect of the huscFv-PE40 immunotoxin on EGFR-over-expressing A431 cells with an IC50 value of 250 ng.mL-1.
Conclusion: In conclusion, the results indicated that the immunotoxin developed in this study has a high toxicity on the EGFR-over-expressing tumor cells and could be considered as a promising candidate for the treatment of the EGFR positive cancers.
- انتشار مقاله: 28-09-1395
- نویسندگان: Dianoush Falahatgar,Safar Farajnia,Nosratollah Zarghami,Asghar Tanomand,Shiva Ahdi Khosroshahi,Bahman Akbari,Hadi Farajnia
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Colorectal cancer,Flux balance analysis,Omics integration,Regulome
- چکیده:
- چکیده انگلیسی: Colorectal cancer (CRC) is one of the most malignant cancers and results in a substantial rate of morbidity and mortality. Diagnosis of this malignancy in early stages increases the chance of effective treatment. High-throughput data analyses reveal omics signatures and also provide the possibility of developing computational models for early detection of this disease. Such models would be able to use as complementary tools for early detection of different types of cancers including CRC. In this study, using gene expression data, the Flux balance analysis (FBA) applied to decode metabolic fluxes in cancer and normal cells. Moreover, transcriptome and genome analyses revealed driver agents of CRC in a biological network scheme. By applying comprehensive publicly available data from TCGA, different aspect of CRC regulome including the regulatory effect of gene expression, methylation, microRNA, copy number aberration and point mutation profile over protein levels investigated and the results provide a regulatory picture underlying CRC. Compiling omics profiles indicated snapshots of changes in different omics levels and flux rate of CRC. In conclusion, considering obtained CRC signatures and their role in biological operating systems of cells, the results suggest reliable driver regulatory modules that could potentially serve as biomarkers and therapeutic targets and furthermore expand our understanding of driving mechanisms of this disease.
- انتشار مقاله: 02-04-1399
- نویسندگان: Fatemeh Nikmanesh,Shamim Sarhadi,Mehdi Dadashpour,Yazdan Asghari,Nosratollah Zarghami
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,Biomarkers,miR-140,miR-196a,Quantitative PCR
- چکیده:
- چکیده انگلیسی: Objective: MiR-140 and miR-196a were known to be correlated with cancer diagnosis and prognosis. The current study aimed at the analysis of miR-140 and miR-196a expression patterns and their clinical significance for breast cancer (BC) patients. Methods: Differentially expressed miR-140 and miR-196a were examined via quantitative PCR in 110 cases of BC and their adjacent non-tumor (ANT) tissues. Results: The results indicated that miR-140 and miR-196a, respectively, notably decreased and increased expression in BC samples in comparison with ANT (p<0.001). Reduced miR-140 expression was also related to Lymph node metastasis (LNM, P= 0.023) and stage (P = 0.009). Additionally, Receiver Operating Characteristics (ROC) analysis illustrated that miR-140 had a significant diagnostic accuracy for stage and LNM of BC patients. We also discovered a strong negative correlation between miR-196a expression with histological grade (P = 0.038), LNM (P = 0.012) and stage (P = 0.001). Conclusion: Overall, exploring the miR-140 and miR-196a profiles not only can statistically different among BC and ANT samples, but it is also expected to become potential BC biomarkers.
- انتشار مقاله: 15-07-1398
- نویسندگان: Arman Shahabi,Behrooz Naghili,Khalil Ansarin,Vahid Montazeri,Nosratollah Zarghami
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Ovarian Cancer,Notch signaling pathway,Metalloproteinases
- چکیده:
- چکیده انگلیسی: Background: Ovarian cancer is one of the most important gynecological malignancies, causing significant mortality.
Recently, there has been extensive attention to the involvement of signaling cascades in its initiation/progression. In this
study, we focused on the possible role of Notch signal transduction in proliferation and metalloproteinase 2 and 9 function
in human ovarian cancer OVCAR-3 cells. Methods: MTT proliferation assays were used to evaluate effects of a DAPT
inhibitor on cell proliferation. For measurement of Hes-1 mRNA levels, quantitative reverse transcription polymerase
chain reaction (qRT-PCR) was applied following 48 h incubation with the inhibitor. In addition, metalloproteinase
(MMPs) activity was assessed by zymography. Results: Inhibition of Notch signaling resulted in a significant reduction
in OVCAR-3 cell proliferation. Additionally, DAPT treatment of cells significantly decreased Hes-1 mRNA levels
(p < 0.05) as well as activity of MMP-2 and -9 (p < 0.05). Conclusion: Our results suggested that suppression of Notch
signaling by a specific inhibitor can effectively decrease proliferation and the potential for metastasis of OVCAR-3 cells
via a reduction in the activity of metalloproteinases 2 and 9. Thus, pharmacological targeting of the Notch signaling
pathway could be a promising future treatment for ovarian cancer.- انتشار مقاله: 26-11-1396
- نویسندگان: Maryam Akbarzadeh,Maryam Majidinia,Sedigheh Fekri Aval,Soltanali Mahbub,Nosratollah Zarghami
- مشاهده
- جایگاه : پژوهشی
- مجله: Asian Pacific Journal of Cancer Prevention
- نوع مقاله: Journal Article
- کلمات کلیدی: Breast cancer,silibinin,Cyclin D1,hTERT,Metformin
- چکیده:
- چکیده انگلیسی: Objective: To explore the possibility of a novel chemopreventive strategy for improving breast cancer treatment,
the anticancer effects of a combination two natural compounds, Chrysin and Metformin, against T47D breast cancer
cells were investigated. Materials and Methods: After treatment of T47D cells with Metformin, Chrysin and the two
drugs in combination, toxicity to cancer cells was evaluated by MTT assay. Real time PCR was then used to determine
the expression levels of hTERT and cyclin D1 genes. Results: The MTT test findings showed that the combination of
metformin and chrysin had high synergistic effects in killing cancer cells. In addition PCR demonstrated a significant
decrease in cyclin D1 and hTERT gene expression in the T47D breast cancer cell line. Conclusion: The conmbination
of metformin and chrysin suppressing hTERT and cyclin D1 gene expression might offer an appropriate approach for
breast cancer therapy.- انتشار مقاله: 23-07-1396
- نویسندگان: Sara Rasooli,Nosratollah Zarghami
- مشاهده