Publications by authors named "Malihe Hasanzadeh"

52 Publications

Association of a genetic variant in Interleukin-10 gene with increased risk and inflammation associated with cervical cancer.

Gene 2021 Aug 28:145933. Epub 2021 Aug 28.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Cervical-cancer is among the most commonly diagnosed cancers in women, and infection with human papillomavirus (HPV) is associated with an increased risk of cervical cancer and altered serum concentrations of inflammatory cytokines. We have explored the association between a genetic variation in the Interleukin-10 (IL-10) gene (rs1800896) and cervical cancer risk and its relationship with tissue Interferon gamma (IFN-γ), Transforming growth factor beta (TGF-β), Tumor necrosis factor alpha (TNF-α) concentrations in women with cervical cancer.

Methods: A total of 315 women with, or without cervical cancer, were recruited into the study. DNA was extracted from cervical cells, and genotyping was undertaken using Taq-man real-time PCR. The genotype frequency and allele distribution were analyzed together with their association with pathological data. The association of the rs1800896 gene variation with tissue levels of the inflammatory cytokines was also investigated.

Results: Our data showed a significant association between the A allele of the rs1800896 gene variant and the presence of cervical cancer. In particular, patients with AG/AA genotypes had an increased risk of cervical cancer with an odds ratio of 1.929 (95% confidence interval [CI]: 0.879-4.23, P<0.001) in a recessive model, compared with the GG genotype. Also, the tissue concentrations of IFN-γ, TGF-β, and TNF-α in cervical tissues were significantly higher in women with cervical cancer (P<0.001) and were associated with the AA genotype.

Conclusion: We have found an association between the polymorphism rs1800896 in the IL-10 gene and an increased risk of cervical cancer as well as a higher level of tissue inflammatory cytokines. Further investigations are necessary on the value of emerging biomarkers for the risk stratification for the management of cervical cancer patients.
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http://dx.doi.org/10.1016/j.gene.2021.145933DOI Listing
August 2021

Small Cell Neuroendocrine Cervical Carcinoma: A Case Report.

J Family Reprod Health 2020 Dec;14(4):273-275

Department of Obstetrics and Gynecology, Women's Health Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Small cell neuroendocrine cervical carcinoma is a neuroendocrine tumor with the great aggravation that comprises 0.5 to 3 percent of cervical tumors and progresses rapidly with early lymphogenous and hematogenous metastases. We reported a 40 years old woman with cervical cancer in stage IB2 that had radical hysterectomy with mistaken diagnosis of squamous cervical cancer. The disease has progressed after 50 days of surgery with a 6 cm tumor in vaginal cuff; review of pathology demonstrated small cell neuroendocrine cervical carcinoma. Recognition of this separate histopathological entity with IHC analysis is important. Chemoradiotherapy and multimodality therapeutic approaches could improve the survival rates.
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http://dx.doi.org/10.18502/jfrh.v14i4.5212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144480PMC
December 2020

Clinical significance of circulating tumor cell related markers in patients with epithelial ovarian cancer before and after adjuvant chemotherapy.

Sci Rep 2021 May 18;11(1):10524. Epub 2021 May 18.

Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Circulating tumor cells (CTCs) have recently been considered as new prognostic and diagnostic markers for various human cancers; however, their significance in epithelial ovarian cancer (EOC) remains to be elucidated. In this study, using quantitative real-time PCR, we evaluated the expression of EPCAM, MUC1, CEA, HE4 and CA125 mRNAs, as putative markers of CTCs, in the blood of 51 EOC patients before and/or after adjuvant chemotherapy. Our results demonstrated that, before chemotherapy, the expression of EPCAM, MUC1, CEA and HE4 mRNAs were correlated to each other. CEA expression was correlated with tumor stage (r = 0.594, p = 0.000) before chemotherapy, whereas its expression after chemotherapy was correlated with serum levels of CA125 antigen (r = 0.658, p = 0.000). HE4 mRNA showed the highest sensitivity both before and after chemotherapy (82.98% and 85.19%, respectively) and the persistence of this marker after chemotherapy was associated with advanced disease stage. The expression of CA125 mRNA had negative correlation with the other markers and with tumor stage and therapy response (evaluated by the measurement of serum CA125 antigen). Collectively, our results indicated a better clinical significance of tumor-specific markers (CEA and HE4 mRNAs) compared to epithelial-specific markers (EPCAM and MUC1 mRNAs).
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http://dx.doi.org/10.1038/s41598-021-88780-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131620PMC
May 2021

A comprehensive systematic review of the therapeutic effects and mechanisms of action of quercetin in sepsis.

Phytomedicine 2021 Jun 14;86:153567. Epub 2021 Apr 14.

Nutrition Research Center, Department of Clinical Nutrition, School of Nutrition & Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background: Sepsis is a life-threatening condition caused by a dysregulated host response to infection. Several studies have indicated that flavonoids exhibit a wide variety of biological actions including free radical scavenging and antioxidant activities. Quercetin, one of the most extensively distributed flavonoids in the vegetables and fruits, presents various biological activities including modulation of oxidative stress, anti-infectious, anti-inflammatory, and neuroprotective activities.

Methods: The present systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements. We searched Web of Sciences, Google Scholar, PubMed, Scopus, and Embase databases up to February 2021 by using the relevant keywords.

Results: Out of 672 records screened, 35 articles met the study criteria. The evidence reviewed here indicates that quercetin supplementation may exert beneficial effects on sepsis by attenuating inflammation and oxidative stress, downregulating the mRNA expression of toll-like receptors (TLRs), modulating the immune response, and alleviating sepsis-related organ dysfunctions.

Conclusion: Due to the promising therapeutic effects of quercetin on sepsis complications and the lack of clinical trials in this regard, future human randomized clinical trials are warranted.
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http://dx.doi.org/10.1016/j.phymed.2021.153567DOI Listing
June 2021

Molar Changes With a Normal Viable Fetus: A Case Report.

J Family Reprod Health 2020 Sep;14(3):205-208

Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

The presence of a normal fetus with normal karyotype accompanied by molar changes in the placenta is a rare condition, which carries a significant risk to the mother and fetus. There is a controversy regarding the proper management of this condition. Here, we present the case of a singleton pregnancy that showed molar changes in the pathological study of the placenta, but ended up with a normal viable neonate. A 23-year-old primigravida woman, with a 3-year history of infertility, presented with vaginal bleeding and spotting. Her ß-human chorionic gonadotropin (HCG) at 13 week was 36500 mIU/ml. Serial sonography assessments were suggestive for molar changes and a normal fetus with growth retardation but normal Doppler assessment. The patient underwent elective Cesarean section at 37 weeks gestation and a healthy female neonate with an Apgar score of 9-10, weighing 2270 g was born. Pathological assessment of the placenta confirmed the diagnosis of incomplete hydatidiform mole. After two months, the mother had no complications, her ß-HCG level was untraceable, and the infant was in good condition. Despite being a rare condition, partial moles can be accompanied by delivery of a normal fetus. The management of this condition still remains challenging and should be done under close monitoring with extreme caution.
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http://dx.doi.org/10.18502/jfrh.v14i3.4675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868656PMC
September 2020

Association of a variant in the tumor necrosis factor alpha gene with risk of cervical cancer.

Mol Biol Rep 2021 Feb 8;48(2):1433-1437. Epub 2021 Feb 8.

Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine involved in the regulation of the immune system and potentially the progression of cervical neoplastic lesions. In this study, we aimed to explore the possible relationship between polymorphisms of the TNF-α gene and susceptibility to cervical cancer. The relationship between a single nucleotide polymorphism (SNP) in the TNF-α gene (rs1800629) and the risk of cervical cancer was evaluated in a total of 445 subjects with (n = 153), or without (n = 292) cancer. Genotyping was performed using a Taq-Man based real time PCR method. Logistic regression analysis showed that individuals with AG/AA genotypes had an increased risk of cervical cancer compared to those with a GG genotype (OR 3.79, 95% CI 2.4-5.7, < 0.001). Our findings demonstrated that a genetic variant in the TNF-α gene (rs1800629) was associated with increased level and risk of developing cervical cancer, suggesting its potential use as a genetic risk factor for cervical neoplasia.
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http://dx.doi.org/10.1007/s11033-021-06185-4DOI Listing
February 2021

Covid-19: What is the best approach in gynecological oncology patient management during the coronavirus pandemic?

Asia Pac J Clin Oncol 2021 Aug 20;17(4):312-320. Epub 2020 Oct 20.

Fellowship of Gynecology Oncology, Isfahan, Medical Science School, Isfahan, Iran.

Coronavirus (COVID-19) infection is a new major concern and a global emergency in almost all countries worldwide; due to the higher sensibility of cancer patients, they are more susceptible to severe and fatal infections, being nearly 10 times more likely than in healthy individuals infected with this virus. Although the aggressive nature of a cancer is a matter of concern, our exact role as oncologists in this time of restricted resources is not fully clarified. Regarding some consensus recommendation for postponing surgery, there is still an essential need for a single approved protocol regarding each type of malignancy. Iran, as one of the first involved countries in this crisis in Asia, which also has a high prevalence of gynecological malignancies, will certainly require an individualized decision-making schedule based on the most accepted global consensus opinion. Considering our restricted health system resources, herein we tried to introduce a logical gynecologic cancer management protocol based on the stage and survival expectancy of each tumor, along with reviewing all recent recommendations. The limited statistics published in this short period of time have obliged us to mainly focus on expert opinions, and the individualized clinical judgments should be agreed upon by multidisciplinary tumor board consensus. In conclusion, the COVID-19 pandemic overshadows all aspects of medicine, and decision making in gynecological oncology patients requires precise and appropriate judgment based on the available local resources.
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http://dx.doi.org/10.1111/ajco.13476DOI Listing
August 2021

Distribution of the most common types of HPV in Iranian women with and without cervical cancer.

Women Health 2021 01 21;61(1):73-82. Epub 2020 Sep 21.

Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University , Tehran, Iran.

Cervical cancer is an important cause of death in women worldwide. About 99.7% of all cervical cancers have been related to human papillomavirus, especially types 16 and 18. Types 6 and 11 cause genital warts. We aimed to determine the prevalence of common HPV genotypes among women in the general population and women with cervical cancer. A total of 571 healthy women cytology specimens and 113 tissue samples of cervical cancer were investigated using HPV type-specific primers. HPV DNA was detected in 24% of healthy women: 3.3% were positive for high-risk HPV and 11.6% for low-risk HPV. HPV6 (9.3%) had the highest prevalence followed by HPV11 (2.3%), HPV16 (1.8%), HPV18 (1.2%), and 9.1% of samples were positive for unknown types. Among cervical cancer samples, HPV DNA was found in 78.8% including 43.4% HPV16, 8% HPV18, and 27.4% an unknown HPV type. HPV6 and HPV11 were not detected in any cervical cancer cases and 21.2% were negative for HPV. We found no association between HPV-16/18 and age in cervical cancer. The prevalence of HPV infection is relatively high in Iran without vaccination backgrounds. HPV DNA screening and vaccination programs can prevent cervical cancer and health problems caused by genital warts.
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http://dx.doi.org/10.1080/03630242.2020.1822490DOI Listing
January 2021

Immature teratoma of the ovary diagnosed after normal delivery: a case report.

J Obstet Gynaecol 2021 Jul 21;41(5):831-832. Epub 2020 Aug 21.

Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

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http://dx.doi.org/10.1080/01443615.2020.1755832DOI Listing
July 2021

Association of a genetic variant in the angiopoietin-like protein 4 gene with cervical cancer.

Pathol Res Pract 2020 Jul 15;216(7):153011. Epub 2020 May 15.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. Electronic address:

Background: Cervical cancer is among the most aggressive gynecological tumors and is a consequence of interactions between genetic and epigenetic factors. Several genetic polymorphisms related to cervical cancer have been reported in previous clinical studies. In this study, we aimed to explore the possible relationship between polymorphisms of the ANGPTL4 gene locus and susceptibility to cervical cancer.

Methods: We investigated the relationship between a single nucleotide polymorphism (SNP) in the ANPGTL4 gene (rs116843064) and risk of cervical cancer in a total of 378 individuals with (n = 151), or without (n = 227) cancer. DNA was extracted, and genotyped using a Taq-Man based real time PCR.

Results: The ANPGTL4 polymorphism was found to be associated with an increased risk of developing cervical neoplasia using dominant model (OR = 12.48, CI = 4.9-31.82, p < 0.0001) and additive model (OR = 30.54, CI = 7.35-126.89, p < 0.0001).

Conclusion: Our results indicate that there is a strong association between ANPGTL4 and the susceptibility for cervical cancer suggesting that it is a potential risk factor for cervical neoplasia.
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http://dx.doi.org/10.1016/j.prp.2020.153011DOI Listing
July 2020

Current insights into the metastasis of epithelial ovarian cancer - hopes and hurdles.

Cell Oncol (Dordr) 2020 Aug 16;43(4):515-538. Epub 2020 May 16.

Department of Medical Genetics and Molecular Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Background: Ovarian cancer is the most lethal gynecologic cancer and the fifth leading cause of cancer-related mortality in women worldwide. Despite various attempts to improve the diagnosis and therapy of ovarian cancer patients, the survival rate for these patients is still dismal, mainly because most of them are diagnosed at a late stage. Up to 90% of ovarian cancers arise from neoplastic transformation of ovarian surface epithelial cells, and are usually referred to as epithelial ovarian cancer (EOC). Unlike most human cancers, which are disseminated through blood-borne metastatic routes, EOC has traditionally been thought to be disseminated through direct migration of ovarian tumor cells to the peritoneal cavity and omentum via peritoneal fluid. It has recently been shown, however, that EOC can also be disseminated through blood-borne metastatic routes, challenging previous thoughts about ovarian cancer metastasis.

Conclusions: Here, we review our current understanding of the most updated cellular and molecular mechanisms underlying EOC metastasis and discuss in more detail two main metastatic routes of EOC, i.e., transcoelomic metastasis and hematogenous metastasis. The emerging concept of blood-borne EOC metastasis has led to exploration of the significance of circulating tumor cells (CTCs) as novel and non-invasive prognostic markers in this daunting cancer. We also evaluate the role of tumor stroma, including cancer associated fibroblasts (CAFs), tumor associated macrophages (TAMs), endothelial cells, adipocytes, dendritic cells and extracellular matrix (ECM) components in EOC growth and metastasis. Lastly, we discuss therapeutic approaches for targeting EOC. Unraveling the mechanisms underlying EOC metastasis will open up avenues to the design of new therapeutic options. For instance, understanding the molecular mechanisms involved in the hematogenous metastasis of EOC, the biology of CTCs, and the detailed mechanisms through which EOC cells take advantage of stromal cells may help to find new opportunities for targeting EOC metastasis.
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http://dx.doi.org/10.1007/s13402-020-00513-9DOI Listing
August 2020

Circulating and Tissue microRNAs as Biomarkers for Ovarian Cancer Prognosis.

Curr Drug Targets 2019 ;20(14):1447-1460

Metabolic syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.

Ovarian cancer (OC) is one of the most common cancers globally with a high rate of cancer- associated mortality. OC may be classified into epithelial cell neoplasms, germ cell neoplasms and stromal cell neoplasms. The five-year survival in the early and advanced stages of disease is approximately 90% and 15%, respectively. microRNAs are short, single-stranded, non-coding ribonucleic acid (RNA). miRNAs play critical roles in post transcriptionally regulations of gene expression. miRNAs are found in different tissues and body fluids. In carcinogenesis the expression of miRNAs are altered. Recent studies have revealed that there is a relationship between alteration of miRNAs expression and the prognosis of patients with OC. The aim of this review was to summarize the findings of recent studies that have investigated the expression of circulating and tissue miRNAs as novel biomarkers in the prognosis of OC.
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http://dx.doi.org/10.2174/1389450120666190708100308DOI Listing
August 2020

Unusual vaginal bleeding due to a leech bite in a girl from a tropical area: A case report.

Rev Soc Bras Med Trop 2019 Apr 11;52:e20180425. Epub 2019 Apr 11.

Department of Parasitology and Mycology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

This study describes the isolation of a leech following the presentation of unusual vaginal bleeding. Vaginal bleeding in children due to a leech bite is very rare. This is the first report of severe bleeding in a virgin 14-year-old girl from Mashhad, Iran due to the presence of a leech in the vagina.
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http://dx.doi.org/10.1590/0037-8682-0425-2018DOI Listing
April 2019

Primary Clear Cell Carcinoma with no Diethylstilbestrol Exposure; Case Series.

Iran J Med Sci 2019 Mar;44(2):163-167

Department of Obstetrics and Gynecology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

One of the rare neoplasms of cervix uteri and vagina is clear cell carcinoma; mostly in patients with a positive past medical history of intrauterine diethylstilbestrol (DES) exposure which reveals the importance of other unknown risk factors of gynecologic neoplasms. 2 Asian women referred to the gynecology-oncology department. The first one came with a complaint of prolonged vaginal discharge and the second one with irregular bleeding. Neither did report a history of DES-exposure. On vaginal examination, it was found that both cases had mass which biopsied for histologic study. They were diagnosed with primary Clear Cell Carcinoma of Vagina in the first case and Cervix uteri in the other one. Both patients underwent cytoreductive surgery soon after diagnosis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6423437PMC
March 2019

The interaction of high and low-risk human papillomavirus genotypes increases the risk of developing genital warts: A population-based cohort study.

J Cell Biochem 2019 08 13;120(8):12870-12874. Epub 2019 Mar 13.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Cervical cancer is among the most common type of cancers in women and is associated with human papillomavirus (HPV) infection. Genital warts are also reported to be linked with HPV infection types 11 and 6. In turn, clinical characteristics and morphological features of warts may be useful in the prediction of prognosis and in making treatment decisions. Thus, we have investigated the association of high and low-risk HPVs genotype with genital wart risk, as well as pathological and cytological information in cases recruited from a population-based cohort study of 1380 patients. Patients infected with HPV genotype 6 or 11 had an increased risk of having warts, with OR of 2.34 (95% CI: 0.955-5.737, P = 0.06). Also, this association was enhanced in the presence of high plus low-risk HPV for having genital wart (OR: 2.814; 95%: 1.208-6.55, P = 0.017) and cases having high-risk HPV (OR: 2.329; 95% CI: 1.029-5.269, P = 0.042). Moreover, we observed patients with genital warts having CIN2/3, indicating the importance of informing the physician to the patient to prevent more severe lesions. Our data demonstrated that patients with both low/high-risk HPV types had an increased risk of developing genital warts and persistent infection with HPV was a necessary precursor for the increase in cervical lesions.
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http://dx.doi.org/10.1002/jcb.28557DOI Listing
August 2019

Therapeutic potential of toll-like receptors in treatment of gynecological cancers.

IUBMB Life 2019 05 6;71(5):549-564. Epub 2019 Feb 6.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Toll-like receptors (TLRs) play an important role in the innate and adaptive immune system. They are expressed in various regions of the female reproductive tract, and their regulation may be involved in the pathogenesis of gynecological lesions. There is growing evidence that ligands for several TLRs are potentially anticancer agents, some of which have already been approved by the FDA, and these compounds are now undergoing clinical evaluation. There is a rationale for using these ligands as adjuvants in the treatment or prevention of gynecological cancer. Some TLR agonists that are of potential interest in the treatment of gynecological lesions include imiquimod, motolimod, cervarix, and CpG-oligodeoxynucleotides (ODNs). In this review, we outline the different functions of TLRs in gynecological cancer with particular emphasis on the value of TLR agonists as a potential therapeutic target in the treatment of gynecological cancer. © 2019 IUBMB Life, 71(5):549-564, 2019.
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http://dx.doi.org/10.1002/iub.2011DOI Listing
May 2019

The Therapeutic Potential of Angiotensin-converting Enzyme and Angiotensin Receptor Inhibitors in the Treatment of Colorectal Cancer: Rational Strategies and Recent Progress.

Curr Pharm Des 2018 ;24(39):4652-4658

Department of Gynecology Oncology, Woman Health Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. There is a document that angiotensin (AT) which is found to be involved in the progression of CRC. Furthermore, Angiotensin receptor inhibitors (ARIs) and angiotensin-converting enzyme Inhibitors (ACE-Is) demonstrate activity in CRC by their inhibition of both Insulin-like growth factor 1 (IGF-1) and Vascular endothelial growth factor (VEGF), and therefore present a potentially novel therapeutic strategy in colorectal cancer, which have summarized in the current review. Preclinical studies have illustrated the direct effect of major active mediator angiotensin II (ATII) on the promotion of angiogenesis through VEGF and other proliferative mediators. Suppression of the angiotensin II type I receptor (AT1R) via ACE-Is has shown a reduction in the development of solid tumor and metastasis, particularly CRC incidence, polyp formation, and distant metastasis. MicroRNAs (miRs) are a family of small nucleotides without coding that plays an important role after transcribing hundreds to thousands of non-coding and coding gene. Against this background, the application of anti-hypertensive medications such as losartan might have a therapeutic impact, although further preclinical and clinical studies might provide novel insight into the potentially beneficial effect of ACE-Is in the treatment of colorectal cancer patients.
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http://dx.doi.org/10.2174/1381612825666190111145140DOI Listing
November 2019

Association of TNF-308 G>A polymorphism located in tumor necrosis factor a with the risk of developing cervical cancer and results of pap smear.

J Cell Biochem 2019 04 1;120(4):5444-5448. Epub 2018 Nov 1.

Department of Gynecology Oncology, Woman Health Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

Tumor necrosis factor a (TNFa) is an inflammatory cytokine that plays a crucial role in the immune response and the progression of cervical lesions. There is a growing body of data evaluating the value of a genetic variant in the TNFa gene with the risk of developing cervical cancer. The aim of this study was to explore the association of a variant, TNF-308 G>A, residing in the TNFa gene with cervical cancer. A total of 91 women with cervical cancer and 161 women as the control group were recruited. DNA was extracted, and Taqman®-probes-based assay was used for genotyping. Our results showed that the minor allele frequency was 0.3 in total population, and the frequency of minor allele A was more in the case group compared with the control. The regression models in different genetic models also revealed that the allele A is a potential risk factor for the development of cervical cancer. In particular, in the dominant model, patients with AG and AA genotypes had a higher risk of developing cervical cancer with odds ratio (OR) of 2.75 (95% confidence interval [CI]: 1.57-4.83, <0.001) and OR of 7.27 (95%CI: 2.5-20.8, <0.001), compared with the GG genotype. Moreover, a similar outcome was obtained for smear test results. Our study demonstrated that TNF-308 G>A located on TNF-a was associated with the risk of cervical cancer, supporting further studies in a larger population and multicenter setting to show the value of emerging markers as risk stratification biomarkers in cervical cancer.
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http://dx.doi.org/10.1002/jcb.27823DOI Listing
April 2019

The potential prognostic and therapeutic application of tissue and circulating microRNAs in cervical cancer.

J Cell Physiol 2019 02 7;234(2):1289-1294. Epub 2018 Sep 7.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Cervical cancer (CC) is a common malignancy in women and a major cause of cancer-related mortality globally. Some novel biomarkers may enable the early diagnosis and monitoring of CC. MicroRNAs (miRNAs) are small noncoding RNAs that control gene translation at a posttranscriptional level. Hence the deregulation of these molecules can cause many diseases. There appears to be an association between aberrant miRNA expression and CC, but the molecular mechanisms involved in the development of CC remain unknown. The upregulation of some circulating miRNAs, for example, miRNA-20a, miRNA-203, miRNA-21, miRNA-205, miRNA-218, and miR-485-5, as well as tissue-specific miRNAs, for example, miR-7, miR-10a, miR-17-5p, miR-135b, miR-149, and miR-203 have been found in patients with CC. There is also growing evidence for the importance of miRNAs in the development of drug resistance. This review therefore highlights recently published preclinical and clinical investigation performed on tissue specific and circulating miRNAs, as potential biomarkers for the detection of patients at early stages of CC, in the prediction of prognosis, and monitoring of their response to therapy.
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http://dx.doi.org/10.1002/jcp.27160DOI Listing
February 2019

The efficacy of vaginal suppository based on myrtle in patients with cervicovaginal human papillomavirus infection: A randomized, double-blind, placebo trial.

Phytother Res 2018 Oct 26;32(10):2002-2008. Epub 2018 Jun 26.

Department of Biostatistics, Faculty of Health, Mashhad University of Medical Sciences, Mashhad, Iran.

Human papillomavirus (HPV) can be detected in most of cervical cancers. Due to antiviral, antimutagenic, and proapoptotic activities of myrtle, this study was designed to investigate the effect of a herbal suppository based on myrtle in cervicovaginal HPV infections. This study was performed as a double-blind randomized trial at the Clinic of Traditional Medicine in Mashhad University of Medical Sciences between 2016 and 2017. Sixty women, 18 to 50 years old, with cervicovaginal HPV infection, were included and randomly allocated to two groups. Sixty placebo or herbal vaginal suppositories were prescribed for 3 months (20 suppositories at each menstrual cycle). Each herbal vaginal suppository contained 10% of myrtle aqueous extract and 0.5% of myrtle essential oil. The HPV test and colposcopic findings were evaluated after treatment. There was no difference between two groups as regards lesion site, diagnosis time of disease, and HPV type before intervention (p ≥ 0.05). At the end of the study, the HPV test was negative in 92.6% and 62.6% of the intervention and placebo groups, respectively (p = 0.036). The change in cervical lesion size was 71.4% and 30.4% in the intervention and placebo groups, respectively, based on colposcopic findings (p = 0.015). It seems that herbal suppository can speed up virus clearance and can be effective in treating HPV infection.
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http://dx.doi.org/10.1002/ptr.6131DOI Listing
October 2018

The 9p21 locus: A potential therapeutic target and prognostic marker in breast cancer.

J Cell Physiol 2018 07 23;233(7):5170-5179. Epub 2018 Jan 23.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Breast cancer is an important cause of cancer related mortality in women. Despite extensive efforts to identify valid biomarkers for risk stratification, there are relatively few with proven clinical utility. It is recognized that genetic factors play a major role in determining susceptibility to breast cancer. Recent genome-wide-association-studies and gene expression analysis have demonstrated that a locus on chromosome 9p21, which contains three genes; CDKN2B (encoding p15ink4b), CDKN2A (encoding p16ink4a and p14ARF) and the 3' end of CDKN2BAS (an antisense noncoding RNA in the INK4 locus [ANRIL]) are associated with an increased risk of this malignancy. ANRIL has a post transcriptional modulatory activity, which has been shown to perturb the expression of nearby genes and may play an important role in coordinating tissue remodeling through regulation of cell proliferation, apoptosis, aging, extra-cellular matrix remodeling, and inflammatory response. However, the role of ANRIL is not well understood in breast cancer. Hypermethylation of the p14 and p16 genes is found in some tumor types. Nevertheless, further studies are necessary to confirm the clinical utility of these putative markers in risk stratification, or assessing prognosis. In this review, we have summarized the prognostic and therapeutic potential of the p14 and p16 genes in patients with breast cancer.
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http://dx.doi.org/10.1002/jcp.26332DOI Listing
July 2018

Clinical and prognostic value of the C-Met/HGF signaling pathway in cervical cancer.

J Cell Physiol 2018 06 24;233(6):4490-4496. Epub 2017 Nov 24.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Aberrant activation of the HGF/c-Met signalling pathway is reported to be associated with cell proliferation, progression, and metastasis features of several tumor types, including cervical cancer, suggesting that it may be of potential value as a novel therapeutic target. Furthermore, HPV-positive patients had a higher serum level of HGF or c-Met protein, compared with HPV-negative patients. c-Met or HGF overexpression in lesions of cervical cancer is reported to be related to a poorer prognosis, and hence this may be of value as a prognostic and predictive biomarker. Several approaches have been developed for targeting HGF and/or c-Met. One of these is crizotinib (a dual c-Met/ALK inhibitor). This has been approved by FDA for the treatment of lung-cancer. Further investigations are required to evaluate and optimize the use of c-Met inhibitors in cervical cancer or parallel targeting signalling pathway associated/activated via MET/HGF pathway. The main aim of current review was to give an overview of the potential of the c-Met/HGF pathway as a prognostic, or predictive biomarker in cervical cancer.
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http://dx.doi.org/10.1002/jcp.26232DOI Listing
June 2018

Genetic variation in the DNA repair pathway as a potential determinant of response to platinum-based chemotherapy in breast cancer.

J Cell Physiol 2018 04 30;233(4):2752-2758. Epub 2017 Aug 30.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Platinum-based chemotherapy is often used as a first-line treatment for patient with breast cancer. Platinum agents bind to DNA, forming adducts that contain intra and inter-strand crosslinks. It is possible that genetic variations of the DNA repair pathways may affect the activity, or efficacy of platinum, and hence resistance to platinum chemotherapy may be related to these genetic variants. We have summarized the known variants in the DNA repair pathway that have been reported to predict the response to platinum-based therapy in breast cancer.
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http://dx.doi.org/10.1002/jcp.26091DOI Listing
April 2018

Adenosine: An endogenous mediator in the pathogenesis of gynecological cancer.

J Cell Physiol 2018 04 8;233(4):2715-2722. Epub 2017 Sep 8.

Faculty of Medicine, Department of Medical Biochemistry, Mashhad University of Medical Sciences, Mashhad, Iran.

Extracellular concentration of adenosine increases in the hypoxic tumor microenvironment. Adenosine signaling regulates apoptosis, angiogenesis, metastasis, and immune suppression in cancer cells. Adenosine-induced cell responses depend upon different subtypes of adenosine receptors activation and type of cancer. Suppression of adenosine signaling via inhibition of adenosine receptors or adenosine generating enzymes including CD39 and CD73 on ovarian or cervical cancer cells is a potentially novel therapeutic approach for gynecological cancer patients. This review summarizes the role of adenosine in the pathogenesis of gynecological cancer for a better understanding and hence a better management of this disease.
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http://dx.doi.org/10.1002/jcp.26056DOI Listing
April 2018

The Therapeutic Potential of Targeting Tumor Microenvironment in Breast Cancer: Rational Strategies and Recent Progress.

J Cell Biochem 2018 01 4;119(1):111-122. Epub 2017 Jul 4.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

The tumor microenvironment (TME) is cellular environment in addition to harboring carcinoma cells, consists of different components (e.g., blood vessels, immune cells, fibroblasts, bone marrow-derived inflammatory cells, lymphocytes, signaling molecules, and the extracellular matrix) that have an essential role on drug activity and efficacy. There is growing body of evidence showing its involvement in the progression and metastasis of different cancers, including breast cancer (BC). These observations provide a proof of concept of targeting TME compartments as a novel potential therapeutic approach in treatment of this malignancy, which is the main interested for current review. J. Cell. Biochem. 119: 111-122, 2018. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcb.26183DOI Listing
January 2018

Genetic susceptibility in cervical cancer: From bench to bedside.

J Cell Physiol 2018 Mar 7;233(3):1929-1939. Epub 2017 Sep 7.

Metabolic Syndrome Research center, Mashhad University of Medical Sciences, Mashhad, Iran.

Cervical cancer (CC) is the third most common malignancy in women globally, and persistent infection with the oncogenic human papillomaviruses (HPV) is recognized as the major risk factor. The pathogenesis of CC relies on the interplay between the tumorigenic properties of the HPV and host factors. Host-related genetic factors, including the presence of susceptibility loci for cervix tumor is substantial importance. Preclinical and genome-wide association studies (GWAS) have reported the associations of genetic variations in several susceptibility loci for the development of cervical cancer. However, many of these reports are inconsistent. In this review, we discuss the findings to date of candidate gene association studies, and GWAS in cervical cancer. The associations between these genetic variations with response to chemotherapy are also discussed.
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http://dx.doi.org/10.1002/jcp.26019DOI Listing
March 2018

Angular Ectopic Pregnancy Presenting as Rupture of Lateral Wall of the Uterus: Late Presentation in Gestation Week 20.

Iran J Med Sci 2017 May;42(3):314-317

Endoscopic and Minimally Invasive Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

The differential diagnosis of acute abdominal pain in pregnancy is broad and can be complicated by atypical manifestations that are due to the anatomic distortions and physiologic changes of pregnancy. Due to the lack of clinical understanding, angular pregnancy does not appear to be recognized as a clinical entity and many cases are likely to go undiagnosed. This is a case report of a 34-year-old woman who was referred to the obstetrics emergency department with sudden abdominal pain and in a state of hypovolemic shock. She had 20 weeks amenorrhea with a positive blood pregnancy test. She underwent laparatomy with internal hemorrhage diagnosis. During the emergency laparotomy, the authors were surprised to encounter the conceptus of 20 weeks angular pregnancy extruded through the left lateral angulation of uterine cavity. The placenta and amnion were removed and the uterine was repaired. Angular pregnancy is rare, but it should be fully understood since its clinical management, outcomes, and maternal mortality are different.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5429502PMC
May 2017

The Therapeutic Potential of PI3K/Akt/mTOR Inhibitors in Breast Cancer: Rational and Progress.

J Cell Biochem 2018 01 4;119(1):213-222. Epub 2017 Jul 4.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Breast cancer (BC) is the most commonly diagnosed cancer in women. The PI3K/AKT/mTOR pathway is among the most frequently dysregulated pathways in patients with BC. The activation of this pathway is associated with increased cell growth and clinical outcome, and its overexpression is associated with a poor prognosis. It has been proposed that it may be of importance as a potential therapeutic target in the treatment of BC. The aim of current review is to provide an overview of the potential utility of PI3K/Akt/mTOR inhibitors in patients with BC, with particular emphasis on recent preclinical and clinical studies. J. Cell. Biochem. 119: 213-222, 2018. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcb.26136DOI Listing
January 2018

The Potential Value of the PI3K/Akt/mTOR Signaling Pathway for Assessing Prognosis in Cervical Cancer and as a Target for Therapy.

J Cell Biochem 2017 12 22;118(12):4163-4169. Epub 2017 Jun 22.

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Cervical cancer is a common gynecological cancer and a leading cause of cancer-related death in women globally. There is a need for the identification of prognostic and predictive biomarker for risk stratification. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is often dysregulated in cervical cancer, indicating that it may be a potential therapeutic target in the treatment of this malignancy, and could perhaps be used as a novel biomarker in the assessment of risk of developing cervical cancer. We aimed to provide an overview of the potential applications of the PI3K/Akt/mTOR pathway as biomarker for risk stratification, in predicting the prognosis of cervical cancer, and for developing new therapeutic approaches in patients with cervical cancer. J. Cell. Biochem. 118: 4163-4169, 2017. © 2017 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/jcb.26118DOI Listing
December 2017

Therapeutic potential of novel formulated forms of curcumin in the treatment of breast cancer by the targeting of cellular and physiological dysregulated pathways.

J Cell Physiol 2018 Mar 23;233(3):2183-2192. Epub 2017 May 23.

Metabolic syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Breast cancer is among the most important causes of cancer related death in women. There is a need for novel agents for targeting key signaling pathways to either improve the efficacy of the current therapy, or reduce toxicity. There is some evidence that curcumin may have antitumor activity in breast cancer. Several clinical trials have investigated its activity in patients with breast cancer, including a recent trial in breast cancer patients receiving radiotherapy, in whom it was shown that curcumin reduced the severity of radiation dermatitis, although it is associated with low bioavailability. Several approaches have been developed to increase its absorption rate (e.g., nano crystals, liposomes, polymers, and micelles) and co-delivery of curcumin with adjuvants as well as different conjugation to enhance its bioavailability. In particular, micro-emulsions is an option for transdermal curcumin delivery, which has been reported to increase its absorption. Lipid-based nano-micelles is another approach to enhance curcumin absorption via gastrointestinal tract, while polymer-based nano-formulations (e.g., poly D, L-lactic-co-glycolic [PLGA]) allows the release of curcumin at a sustained level. This review summarizes the current data of the therapeutic potential of novel formulations of curcumin with particular emphasis on recent preclinical and clinical studies in the treatment of breast cancer.
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http://dx.doi.org/10.1002/jcp.25961DOI Listing
March 2018
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