Publications by authors named "Bijan Khademi"

102 Publications

Elective Submandibular Gland Resection in Patients with Squamous Cell Carcinomas of the Tongue.

Iran J Otorhinolaryngol 2021 Jan;33(114):23-29

Otolaryngology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Introduction: Submandibular gland resection is a controversial issue in patients with oral tongue squamous cell carcinomas (SCC). This study aimed to determine the frequency of submandibular gland involvement in patients who had undergone elective submandibular gland resection following oral tongue SCC.

Materials And Methods: This cross-sectional retrospective study was performed between 2001 and 2017 on patients with oral tongue SCC who had undergone glossectomy in a referral center for otorhinolaryngology surgery, Shiraz, Iran.

Results: In this study, 131 patients were included. Their mean age was 59.84 years (range: 19-86). The mean tumor size was 2.83 cm (range 0.3-7). The vast majority (92%) of the patients were at stage III-IVa and had well (55%) to moderate (31%) differentiated tumor. The mean diameter of the submandibular gland was 3.87 cm (range: 1.5-6 cm). There was only one (0.76%) patient with submandibular involvement. She was an 80-year-old woman with a T2 well differentiated tumor without cervical lymph node involvement in the neck node dissection.

Conclusion: In patients with oral tongue SCC, submandibular gland involvement is rare and its elective resection in not recommended.
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http://dx.doi.org/10.22038/ijorl.2020.44283.2463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897437PMC
January 2021

EZB-ICR Cell Line: A New Established and Characterized Oral Squamous Cell Carcinoma Cell Line From Tongue.

Asian Pac J Cancer Prev 2021 Jan 1;22(1):99-103. Epub 2021 Jan 1.

Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Tongue cancer is one of the most aggressive forms of oral squamous cell carcinoma which needs more investigations. Herein, we aimed to establish and characterize a tongue cancer cell line.

Methods: Tumor tissue was obtained from a 70-year-old woman with tongue cancer. The established cell line named as EZB-ICR and characterized for doubling time, expression of specific markers, HPV corporation and migration status using flow cytometry, immunofluorescence staining, multiplex PCR, and migration assay.

Results: EZB-ICR was negative for expression of mesenchymal specific markers, cytokeratin19, pan-cytokeratin, vimentin and EPCAM, but was positive for S100 and Nestin. No appearance of human papilloma virus DNA was seen. The doubling time of EZB-ICR was 31 hours and migration assay confirmed its metastatic nature.

Conclusion: To the best of our knowledge, EZB-ICR is the first tongue human cancer cell line established in Iran, and its features make it appropriate for cancer-based in vitro studies and contribute to more studies on tongue cancer.
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http://dx.doi.org/10.31557/APJCP.2021.22.1.99DOI Listing
January 2021

Orbital mucormycosis in immunocompetent children; review of risk factors, diagnosis, and treatment approach.

BMC Infect Dis 2020 Oct 19;20(1):770. Epub 2020 Oct 19.

Shiraz University of Medical Sciences, Namazi Hospital, 7193711351, Zand Ave, Shiraz, Iran.

Background: Orbital mucormycosis is a rare but potentially severe and troublesome invasive fungal infection that could be occurred even in healthy individuals. The initial clinical presentation is similar to bacterial pre-septal or septal cellulitis, especially in early stages.

Case Presentation: Herein, we describe the successful management of a series of five cases presenting with orbital mucormycosis in previously healthy children.

Conclusions: Orbital mucormycosis is extremely rare in healthy children and maybe life-threatening when diagnosis delayed given a similar clinical presentation with bacterial septal cellulitis. Intravenous antifungal therapy with amphotericin B and timely surgical drainage is live-saving.
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http://dx.doi.org/10.1186/s12879-020-05460-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574198PMC
October 2020

Therapeutic effect of adipose-derived mesenchymal stem cells (ASCs) on radiation-induced skin damage in rats.

Stem Cell Investig 2020 15;7:12. Epub 2020 Jul 15.

Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Radiation-induced skin injury remains a serious concern, which may limit the duration and dose of radiation treatment. The concept that stem cell injection may reduce tissue injury or assist its recovery after radiation has been recently argued. Herein, we examined the effect of adipose-derived mesenchymal stem cells (ASCs) on radiation-induced skin damage in rats.

Methods: This study is an experimental case control study. ASCs were isolated from peri uterine fat tissue of the rats. Then the rats received a 30 Gy single dose radiation to their buttocks skin using gamma radiation. Next day stem cells were transplanted subcutaneously in 16 rats as the case group. A group of 16 rats was considered as control group with radiation but no transplantation of stem cells. Then rats were examined and observed by macroscopic analysis and phenotypic scores during 4 weeks of follow up.

Results: The wound size in control group was significantly higher than case group in the second, third and fourth weeks of evaluation (P<0.05). There was no significant difference in skin lesion severity, pathological factors, and the onset of recovery signs between two groups (P>0.05).

Conclusions: It seems that using ASCs alone has not profound effects on reducing radiation-induced cutaneous complications, while combination of these cells with growth factors may produce more promising results.
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http://dx.doi.org/10.21037/sci-2019-045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416167PMC
July 2020

The rs217727 Polymorphism Is Associated with Oral Squamous Cell Carcinoma Susceptibility in Iranian Population.

Biomed Res Int 2020 31;2020:1634252. Epub 2020 Mar 31.

Department of Oral and Maxillofacial Surgery, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Lack of protein-coding capacity is a main characteristic of long noncoding RNAs (lncRNAs) which, as molecular biomarkers, have found a novel pharmacological application in cancer and are reported to be important regulators of gene expression. is reportedly involved in cancer progression and tumorigenesis. One of the most common types of head and neck cancers is oral squamous cell carcinoma (OSCC). The main objective of the present study was to evaluate the correlation of OSCC susceptibility with gene in an Iranian population. This research was performed on 400 subjects of both sexes referred to the Namazi Hospital affiliated with the Shiraz University of Medical Sciences (SUMS). Individuals aged 15-88 years were divided into two groups: pathologically diagnosed patients with new-onset OSCC and healthy controls. After written and informed consent was obtained from the individuals, genomic DNA was extracted. The tetra-primer ARMS-PCR technique was performed for DNA genotyping by the use of specific primer pairs. The susceptibility of OSCC and H19 gene polymorphism sites was further analyzed (rs217727 and rs2107425). The allele and genotype frequencies of rs2107425 polymorphism were similar between OSCC cases and controls. The rs217727T allele frequency was significantly higher in OSCC cases ( = 0.002), and the polymorphism of rs217727 was associated with OSCC susceptibility in the codominant (OR = 6.04, 95%CI = 1.70 - 21.42, = 0.001 for TT genotype), dominant (OR = 1.62, 95%CI = 1.08 - 2.43, = 0.01), and recessive (OR = 5.32, 95%CI = 1.51 - 18.69, = 0.003) models. This study showed that rs217727 and OSCC susceptibility were statistically correlated in the Iranian population.
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http://dx.doi.org/10.1155/2020/1634252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154967PMC
January 2021

Aneurysm of the Internal Carotid Artery Misdiagnosed as Cervical Paraganglioma; A Case Report and Literature Review.

Bull Emerg Trauma 2019 Oct;7(4):420-423

Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran.

The aneurysms of the extracranial segment of the internal carotid artery are not common and are associated with severe neurologic deficits. They could be misdiagnosed with several lesion of the cervical region. We herein report a case of internal carotid artery aneurysm misdiagnosed as paraganglioma. A 23-year-old man presented with progressive growing mass in right enlarging mass in the upper part of the neck below the angle of the mandible. The patient underwent surgery by the ear, nose, throat (ENT) surgeon through submandibular approach with impression of paraganglioma but severe pulsatile bleeding was encountered intraoperatively. Two vascular clamps were applied and the patient was transferred to the vascular ward. Computerized tomography (CT) angiogram revealed a huge aneurysm of the internal carotid artery in the extracranial segment with injured wall. After 2 days of medical therapy the patient was transferred to the operating room and the aneurysm was repaired using Dacrons. The patient had an uneventful hospital course and was asymptomatic after 1 year of follow-up. Precise preoperative assessment and evaluation with different modalities should be performed to avoid fatal complications. Surgery is a safe and effective method in experienced hands for repair of such aneurysms.
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http://dx.doi.org/10.29252/beat-070413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911723PMC
October 2019

KIR2DS4, KIR2DL2, and KIR2DS4del are linked with basaloid tumors, lymph node metastasis, advanced stage and metastatic risk in head and neck squamous cell carcinoma.

Exp Mol Pathol 2020 02 18;112:104345. Epub 2019 Nov 18.

Shiraz Institute for Cancer Research, Shiraz University of Medical Sciences, Iran; Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Iran. Electronic address:

Backgrounds: Our previous study has suggested that KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with head and neck squamous cell carcinoma (HNSCC) development. The purpose of the current study was to investigate the possible association of killer cell immunoglobulin like receptors (KIRs) gene with the clinicopathological features of patients.

Methods: We reviewed the pathological reports of 285 pathologically confirmed cases of HNSCC and analyzed the association of KIR system with pathological characteristics.

Results: A significant increase was demonstrated in the carrier frequency of KIR2DS4 in conventional than basaloid type and a higher frequency of lymph node metastasis (LNM) in carriers of KIR2DL2 and individuals possess 5 inhibitory KIRs (iKIRs). We also observed a higher proportion of patients with advanced stage of HNSCC in carriers of KIR2DL2 and deleted variant of KIR2DS4.

Conclusion: In HNSCC, KIR2DL2 is positively while KIR2DS4 is negatively associated with advanced stage. The higher proportion of LNM in carriers of KIR2DL2 and carriers of 5 iKIRs, suggested that inhibitory KIRs are associated with metastatic risk.
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http://dx.doi.org/10.1016/j.yexmp.2019.104345DOI Listing
February 2020

Atypical Memory and Regulatory B Cell Subsets in Tumor Draining Lymph Nodes of Head and Neck Squamous Cell Carcinoma Correlate with Good Prognostic Factors.

Head Neck Pathol 2020 Sep 5;14(3):645-656. Epub 2019 Nov 5.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Research on the role of B cells in the development and modulation of antitumor immunity has increased in recent years; however, knowledge about B cell phenotype and function in tumor draining lymph nodes (TDLNs) is still incomplete. This study aimed to investigate changes in the phenotypic profile of B cells in TDLNs of head and neck squamous cell carcinoma (HNSCC) during disease progression. Mononuclear cells were isolated from TDLNs and stained with antibodies for CD19 and other B cell-related markers and analyzed by flow cytometry. CD19 B cells comprised 38.6 ± 8.9% of lymphocytes in TDLNs of HNSCC. Comparison of metastatic and non-metastatic LNs disclosed no significant differences in the frequencies of B cell subsets including antigen-experienced, naïve, switched, unswitched, atypical memory, marginal zone-like B cells, and B cells with regulatory phenotypes. The percentage of atypical memory (CD27IgMIgD) B cells was significantly higher in patients with tongue SCC with no involved LNs (p = 0.033) and correlated inversely with the number of involved LNs. The frequency of CD24CD38 B cells was significantly higher in non-metastatic LNs of patients with grade I compared to grade II (p = 0.016), and the percentage of CD5 B cells decreased as tumors progressed from stage III to IV (p = 0.008). Our data show that in TDLNs of HNSCC, the frequency of B cells with atypical memory and regulatory phenotypes was significantly associated with good prognostic factors; however, their function remains to be investigated.
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http://dx.doi.org/10.1007/s12105-019-01095-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7413970PMC
September 2020

Association of OX40 gene polymorphisms (rs17568G/A and rs229811A/C) with head and neck squamous cell carcinoma.

Mol Biol Rep 2019 Jun 28;46(3):2609-2616. Epub 2019 Mar 28.

Department of Immunology and Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, P.O. Box 71345-1798, Shiraz, Iran.

Head and neck squamous cell carcinoma (HNSCC) is the sixth leading incident cancer worldwide. In this study, we aimed to investigate the possible association of OX40 gene polymorphisms, rs17568G/A and rs229811A/C, with susceptibility to HNSCC and its clinicopathological features. Two hundred and two HNSCC patients and 200 healthy age-sex matched individuals were enrolled. rs17568G/A and rs229811A/C polymorphisms in OX40 gene were genotyped using RFLP-PCR method. We observed more than 2 times increased risk for squamous cell carcinoma development in nose and paranasal sinuses among individuals who inherited GG genotype at rs17568 region (OR 2.29; CI 1.01-5.20; P = 0.035). Considering rs2298211 SNP, AA genotype was also observed with higher frequency, in comparison with other two genotypes (AC or CC), among patients with HNSCC originated from these regions (P = 0.003). Besides, we observed that patients with C allele at this locus (AC and CC genotypes) have tumors with significantly higher histological grade (P = 0.042). Our findings suggest the possible association of rs17568 GG genotype, as well as rs2298211 AA genotype with susceptibility to develop squamous cell carcinoma in the nose and sinonasal cavities.
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http://dx.doi.org/10.1007/s11033-019-04602-3DOI Listing
June 2019

Serum Levels of Zinc, Copper and Ferritin in Patients with Salivary Gland Tumors

Asian Pac J Cancer Prev 2019 Feb 26;20(2):545-548. Epub 2019 Feb 26.

Oral and Dental Disease Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Email:

Background: Variation in serum levels of trace elements including zinc, copper and ferritin has been reported in cancer patients. The aim of this study was to evaluate these trace elements in the patients’ sera with benign and malignant salivary gland tumors (SGTs) and compare them with normal individuals. Methods: In this cross-sectional study, 60 patients with SGTs including 16 pleomorphic adenoma and 44 malignant SGTs, as well as 28 healthy controls, were enrolled. Serum levels of zinc, copper and ferritin were determined by atomic absorption and ELISA methods. Data were analyzed using one way ANOVA, Chi-square, Kruskal-Wallis and Mann- Whitney tests. Results: The mean concentration of zinc, copper, ferritin was1.5± 2 ppm, 1.2± 0.5 ppm, and 96.7± 65.7 ng/ml in PA, 1.5± 1.4,1.3± 0.4, and 111.2± 112 in malignant SGTs, and1.1±0.3, 1.2± 0.23 and 124±135.8 in normal control groups. There was no statistically significant difference between the patients and control groups, and between benign and malignant SGTs (P>0.05). Conclusion: The serum levels of trace elements in SGTs were not different from normal individuals. The results might have been affected by some interventional factors. Therefore, designing cohort complementary studies might result in obtaining more accurate data.
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http://dx.doi.org/10.31557/APJCP.2019.20.2.545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6897009PMC
February 2019

PD-1 Haplotype Combinations and Susceptibility of Patients to Squamous Cell Carcinomas of Head and Neck.

Immunol Invest 2019 Jan 30;48(1):1-10. Epub 2018 Oct 30.

a Department of Immunology , School of Medicine, Shiraz University of Medical Sciences , Shiraz , Iran.

Introduction: Head and neck squamous cell carcinomas (HNSCCs) are the most common cancers of head and neck and the sixth most common malignancy worldwide. Programmed cell death 1 (PD-1) is an immune inhibitory molecule which through interaction with its ligands recruits protein phosphatase resulting in immune response inhibition. Expression of PD-1 ligands on tumor cells is considered as one of the crucial immune evasion mechanisms. This study aimed to investigate the association of PD-1 gene polymorphisms at positions PD1.3 (rs11568821), PD1.5 (rs2227981) and PD1.9 (rs2227982) with susceptibility to HNSCCs.

Subjects And Methods: 150 patients pathologically confirmed to suffer from HNSCCs and 150 age-sex matched healthy controls were recruited in this study. Genomic DNA was extracted from white blood cells of all participants. Restricted fragment length polymorphisms (RFLP)-PCR was performed using site specific primers to determine the genotypes in each position.

Results: Statistical analyses indicated no significant differences in the frequencies of genotypes, alleles as well as haplotypes between patients and controls (P > 0.05), however, haplotype combination differed significantly between two groups. GCC/GCT, GCC/GCC and GCT/GCC were higher in the HNSCC patients than the control group (P < 0.05). On the other hand, in the controls, GCT/GCT, GCT/ACC, GCT/ACT and ACC/GCT were more frequent. No significant association was found with various HNSCC clinicopathological characteristics.

Discussion: Our results suggested that although PD-1 gene polymorphisms at three investigated positions are not solely associated with susceptibility to HNSCCs, haplotype combinations emerged from these three loci may render susceptibility.
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http://dx.doi.org/10.1080/08820139.2018.1538235DOI Listing
January 2019

Assessing whether EORTC QLQ-30 and FACT-G measure the same constructs of quality of life in patients with total laryngectomy.

Health Qual Life Outcomes 2018 Sep 14;16(1):183. Epub 2018 Sep 14.

Department of Otorhinolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: The European Organization for Research and Treatment of Cancer QOL Core Questionnaire 30 (EORTC QLQ-30) and the Assessment of Cancer Therapy-General (FACT-G) are the two most widely used measures of cancer-specific health-related quality of life (HRQOL). This study aims to assess whether the two instruments measure the same constructs of HRQOL in patients with total laryngectomy.

Methods: The EORTC QLQ-30 and the FACT-G was completed by 132 patients with total laryngectomy. Convergent, discriminant, and construct validity of the EORTC QLQ-C30 and the FACT-G were assessed by Spearman's correlation and explanatory factor analysis.

Results: The results of factor analysis showed that the EORTC QLQ-C30 and the FACT-G measure different aspects of HRQOL. Moreover, both instruments showed excellent convergent and discriminant validity, except for nausea and vomiting symptom subscale in the EORTC QLQ-C30 questionnaire. The internal consistency was close or greater than 0.7 for all domains of both instruments except for functional wellbeing in FACT-G.

Conclusions: This study revealed that neither of the two instruments can be replaced by the other in the assessment of HRQOL in Iranian patients with total laryngectomy. Accordingly, clinicians should exactly define their research questions related to patient-reported outcomes before choosing which instrument to use.
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http://dx.doi.org/10.1186/s12955-018-1012-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137753PMC
September 2018

Investigation of IL-33 serum levels in patients with benign and malignant salivary gland tumors.

Cancer Biomark 2018 ;23(1):61-65

Oral and Dental Disease Research Center, Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Interleukin-33 (IL-33) has been recently discovered as an influential factor in the process of tumor immunity, and is presented in cancer pathogenesis.

Objective: This study aimed to determine the serum levels of IL-33 in patients with benign and malignant Salivary gland tumors (SGTs).

Methods: This descriptive cross-sectional study was performed on 47 samples of malignant SGTs including 18 mucoepidermoid carcinoma (MEC), 8 adenoid cystic carcinoma (ADCC), 21 malignant mixed tumor (MMT), and 14 benign pleomorphic adenoma (PA). A control group was considered consisting of 28 healthy subjects. The serum level of IL-33 was measured by using sandwich ELISA method. The data were statistically analyzed through Kruskal-Wallis and Mann-Whitney tests.

Results: The median concentration of IL-33 was 6.91 in malignant, 5.14 in benign, and 5.01 in healthy cases, with a statistically significant difference (P= 0.001). The median serum levels of IL-33 increased significantly in ADCC (7.15), MEC (7.03), and MMT (6.91) compared with the control group (5.01) (P< 0.05). The mean rank of MEC was significantly higher than PA (P= 0.01). IL-33 concentration was positively and significantly correlated with the tumor stage (P= 0.02) and tumor size (P= 0.03).

Conclusions: IL-33 could be suggested as a novel biomarker to distinguish different types of SGTs.
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http://dx.doi.org/10.3233/CBM-181309DOI Listing
October 2018

Serum Endostatin Levels in Oral Squamous Cell Carcinoma.

Iran J Otorhinolaryngol 2018 May;30(98):125-130

Undergraduate Student, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Introduction: Endostatin is a C-terminal proteolytic fragment of collagen XVIII and, as with angiostatin and thrombospondin, is known as an antiangiogenic agent. The aim of this study was to assess the level of serum endostatin in patients with oral squamous cell carcinoma (SCC), and its association with the clinicopathological characteristics of the tumor.

Materials And Methods: Using an enzyme-linked immunosorbent assay (ELISA) kit, we investigated the circulating levels of endostatin in the blood serum of 45 patients with oral SCC and 45 healthy controls.

Results: The mean level of serum endostatin in patients was significantly lower (68.8±85 ng/ml) than in healthy controls (175.6±73 ng/ml) (P<0.001). Serum endostatin levels were significantly lower in patients with lymph node metastasis compared with patients without lymph node metastasis (P<0.001). In addition, serum endostatin level was associated with higher histological grade (P<0.001). There were no apparent correlations between serum endostatin concentration and clinicopathological features such as age, gender, and tumor stage (P>0.05).

Conclusion: Findings of the present study suggest the prognostic and anti-metastatic role of endostatin, and this may be used as a tool for monitoring tumor progression.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985613PMC
May 2018

Serum CXCL12, but not CXCR4, Is Associated with Head and Neck Squamous Cell Carcinomas

Asian Pac J Cancer Prev 2018 04 25;19(4):901-904. Epub 2018 Apr 25.

Oral and Dental Disease Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Email:

Background: Squamous cell carcinoma (SCC) is the most frequent malignancy of the head and neck (HN) region. We here evaluated associations of stromal cell derived factor-1 (SDF-1or CXCL12) and its receptor, CXCR4, with HNSCCs. Materials and Methods: Sixty newly diagnosed HNSCC patients were enrolled in the patient group, and 28 healthy individuals in the control group. Plasma levels of CXCL12 and CXCR4 were measured using ELISA kits. Results: There was a significant difference in mean CXCL12, but not CXCR4, plasma levels between the patient and control groups (P=0.0001). No significant associations were found between mean plasma levels of either CXCL12 or CXCR4 with age, gender, tumor site, tumor size, lymph-node involvement or tumor stage. Conclusion: For the first time, our findings demonstrate a significant association between serum CXCL12 but not CXCR4 levels and HNSCCs.
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http://dx.doi.org/10.22034/APJCP.2018.19.4.901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031803PMC
April 2018

Galectin-3 Serum Levels Could Help Clinicians Screen for Salivary Gland Tumor Patients

Asian Pac J Cancer Prev 2018 Mar 27;19(3):689-692. Epub 2018 Mar 27.

Oral and Dental Disease Research Center, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran. Email:

Objective: To identify serum levels of galectin-3 in salivary gland cancer and healthy populations; a prospective analysis was performed on serum specimens from 105 patients with salivary gland cancer and 56 healthy persons. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to measure levels of galectin-3 (GAL-3). Serum levels were compared between patients with salivary gland tumors and healthy control. A total of 105 patients were enrolled in the study (55 men, 50 women). Result: Mean age was 45.5 years. Thirty-nine patients with malignant and 66 cases with benign tumors were compared with 56 healthy participants with a mean age of 51.7. No statistically significant differences were observed when comparing GAL-3 serum levels between malignant and benign salivary gland tumor patients, but a statistically significant difference was found between case and control patients with p-values of 0.02. Serum levels of galectin-3 protein were elevated in patients with salivary gland cancer compared with the healthy population. Conclusion: The difference between benign and malignant tumor patients was significant, but revealed no clinic pathological characteristics in malignant tumors. To the best of the authors’ knowledge, this is the first time a study suggests that GAL-3 serum levels could help clinicians screen for salivary gland cancer.
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http://dx.doi.org/10.22034/APJCP.2018.19.3.689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980842PMC
March 2018

The Prevalence of Human Papilloma Virus in Squamous Cell Carcinoma of Oral Tongue.

Iran J Pathol 2017 1;12(2):144-149. Epub 2017 Apr 1.

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Background And Objective: Oral tongue Squamous Cell carcinoma (SCC) commonly involves males between the sixth to eighth decades of life. Major risk factors are tobacco usage and alcohol consumption. The increasing number of patients developing oral tongue cancer without these well-known risk factors suggests that a viral infection, such as Human Papillomavirus (HPV), may be responsible for this increase, by acting as an oncogenic agent. This study investigated the prevalence of HPV infection and its clinicopathologic significance in oral tongue SCCs.

Methods: Tissue blocks from a total of 50 cases (patients with oral tongue SCC) and 50 controls (palatine tonsillar tissues with benign diagnosis) were selected. DNA was extracted from tumoral and non-tumoral tissue blocks. Detection of common HPV DNA by nested Polymerase Chain Reaction (PCR), and high-risk genotypes, HPV 16 and HPV 18, by conventional PCR, was achieved and the results correlated with clinicopathological parameters.

Results: Of the 50 patients (18 males and 32 females with a mean age of 57.36±12.18 years, and age range of 27 to 86 years), 7 (14%) had HPV positive results. None of the control group subjects had HPV DNA positive results (P-value of 0.012). The HPV genotype 16/18 was not detected in positive cases. No statistically significant association was found between HPV status and gender, age, tumor grade, tumor stage or lymph node involvement.

Conclusion: Although there was a significantly higher prevalence of HPV in oral tongue SCC, its association with carcinogenesis in this area requires further studies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5831070PMC
April 2017

KIR2DS1, 2DS5, 3DS1 and KIR2DL5 are associated with the risk of head and neck squamous cell carcinoma in Iranians.

Hum Immunol 2018 Apr 9;79(4):218-223. Epub 2018 Feb 9.

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address:

Background: Activating and inhibitory KIR receptors (aKIR, iKIR) control the development and function of NK cells whose function alterations adjust the tumor microenvironment immunity. This research was conducted to determine the KIRs gene impact on genetic predisposition to Head and Neck Squamous Cell Carcinoma (HNSCC) in Iranians.

Methods: KIR genotyping using sequence-specific primers-polymerase chain reaction (SSP-PCR) method was performed to identify the presence of all 16 KIR genes in 285 HNSCC patients, including laryngeal, oral cavity and pharyngeal SCC and 273 controls (CNs).

Results: Comparison of KIRs gene frequency between HNSCC and CNs revealed a highly significant increase in KIR2DL5, 2DS1, 2DS5, 3DS1 and CxT4 genotype and a decrease in KIR2DS4 deleted variant and AA genotype carriers. A significant increase was noted in individuals withhigher iKIRs than aKIRs in HNSCC compared with CNs. Individuals with ≥4 iKIR and those with ≥5 aKIRs were significantly more common in HNSCC than CNs. 68distinct KIR genotypes were identified in 558 individuals.

Conclusion: Our findings determined the detrimental impact of KIR2DS1, 2DS5, 3DS1, 2DL5 and CxT4 genotype as well as the protective impact of KIR2DS4del and AA genotype on genetic predisposition to HNSCC in Iranians.
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http://dx.doi.org/10.1016/j.humimm.2018.01.012DOI Listing
April 2018

Evaluation of the Ki-67 and MCM3 Expression in Cytologic Smear of Oral Squamous Cell Carcinoma.

J Dent (Shiraz) 2017 Sep;18(3):207-211

Otolaryngology Research Center, Dept. of Otorhinolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran.

Statement Of The Problem: Squamous cell carcinoma (SCC) is the most frequent oral cancer whose 5-year survival rate is 80% for early-detected lesions and nearly 30-50% for advanced lesions. Early detection of oral cancers and precancerous lesions can improve the patient's survival and decrease the morbidity.

Purpose: This study aimed to evaluate and compare the Ki-67 and MCM3 expression in cytologic smear of oral SCC (OSCC).

Materials And Method: We examined 48 oral brush biopsies including 28 OSCC and 20 healthy non-smoking samples. Immunocytochemistry staining was performed for Ki-67 and MCM3 by using an EnVision-labeled peroxidase system, and labeling index (LI) was calculated.

Results: Out of 28 OSCC cases, 27(96.4%) cases contained MCM3 positive cells and 22(78%) cases contained Ki-67 positive cells. All normal mucosa were Ki-67 and MCM3 negative. MCM3 and Ki-67 LI were significantly higher in OSCC than normal mucosa (< 0.001). MCM3 LI was significantly higher than Ki-67 LI in OSCC group (< 0.001).

Conclusion: Immunocytologic evaluation of Ki-67 and MCM3 can be used for early detection of OSCC. Furthermore, MCM3 may be a more sensitive cytologic biomarker than Ki-67 in SCC patients.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634361PMC
September 2017

Long-lasting chondromyxoid fibroma of the zygoma: A rare case report and review of literature.

J Educ Health Promot 2017 9;6:78. Epub 2017 Aug 9.

Department of Otolaryngology, Clinical Pathology Division, Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Chondromyxoid fibroma (CMF) is a benign tumor which usually occurs in skeletal long bones. Its presence in zygoma is extremely rare. The patient was a 47-year-old female, with chief complaint of painful swelling in the left side of zygoma since 1 month ago after a long-lasting painless swelling for about 15 years. Computed tomography scan showed an osteolytic lesion, in the body of left zygomatic bone with lobulated and well-demarcated margins. During surgery, the mass was completely excised and the histological feature of the tumor was in favor of CMF. CMF is benign tumor and complete resection is the treatment of choice.
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http://dx.doi.org/10.4103/jehp.jehp_33_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561685PMC
August 2017

Chemokine and chemokine receptor patterns in patients with benign and malignant salivary gland tumors: a distinct role for CCR7.

Eur Cytokine Netw 2017 Mar;28(1):27-35

Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

To explore the molecular mechanisms involved in pathophysiology of malignant and benign salivary gland tumors (SGTs), we investigated main tumor-inducing chemokines and chemokine receptors, CXCL12/CXCR4/ACKR3 (CXCR7), CXCR3/CXCL10, CCR5/CCL5, CCL21/CCR7, CCL2, CCR4, CXCR5, CCR6, and CXCL8 in tumor tissues. Parotid tissues were obtained from 30 patients with malignant and benign SGTs. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the mRNA expression pattern of the mentioned chemokines/chemokine receptors and immunohistochemistry (IHC) was performed to verify the expression of CCR7. Expression levels of CCR7 and CCR4 transcripts were higher in the tumor tissues of malignant cases in comparison to benign ones (p = 0.03 and 0.02). Immunohistochemistry analysis confirmed that the protein level of CCR7 concurred with the mRNA expression. CCL2 gene transcripts were observed with a higher expression in patients with tumor-free lymph nodes (LN) and early stages, whereas CCR7 transcript was higher in LN and late stages of the disease. A significant inverse correlation was found between CXCL10 transcript and tumor size in benign cases. The mRNA expression of CCR7, CCR4, CXCR3, CCL21, CCL5, and CXCL12 was significantly higher in mucoepidermoid carcinoma in comparison to pleomorphic adenoma subtypes (p < 0.05). On the basis of the present study, it was determined that malignant and benign SGTs exhibit a distinct pattern of chemokines and chemokine receptors, which are probably associated with known biological and clinical behaviors of these tumors. Significant increased CCR4 and CCR7 expression in malignant SGTs might play a central role in malignant transformation that introduces them as new targets for cancer immunotherapy.
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http://dx.doi.org/10.1684/ecn.2017.0388DOI Listing
March 2017

Serum Levels of Cyfra 21 in Patients with Benign and Malignant Salivary Gland Tumors.

Iran J Otorhinolaryngol 2017 Jul;29(93):203-208

Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Introduction: Cyfra 21 is a serum-soluble fragment of cytokeratin19. Increased Cyfra 21 serum levels and their benefit as a tumor marker have been shown in some malignancies. This study aimed to evaluate the serum levels of Cyfra 21 in patients with benign and malignant salivary gland tumors.

Materials And Methods: In this cross-sectional study, the serum level of Cyfra 21 in 44 patients with malignant salivary gland tumors and 16 cases of pleomorphic adenoma were compared with 28 healthy controls using enzyme-linked immunosorbent assay (ELISA). Data were analyzed statistically using the Kruskal Wallis test, analysis of variance (ANOVA) and Spearman's correlation tests.

Results: Mean serum levels of Cyfra 21 were 0.135 ± 0.285 ng/ ml in the control group, 0.167 ± 0.142 ng/ ml in patients with pleomorphic adenoma and 1.059 ± 3.251 ng/ml in patients with malignant salivary gland tumors. There was no significant difference among groups. Cyfra 21 levels did not correlate with location of tumor, clinical stage or cigarette smoking.

Conclusion: Results of the present study showed no significant difference in Cyfra 21 serum level in salivary gland tumors compared with normal individuals. In addition, Cyfra 21 serum level was not sufficiently sensitive to function as a tumor marker in salivary gland tumors.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554811PMC
July 2017

Prevalence of Human Papilloma Virus in Sinonasal Papilloma in Southern Iranian Population.

J Dent (Shiraz) 2017 Jun;18(2):143-148

Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Statement Of The Problem: Sinonasal papilloma (SNP) is a rare benign lesion characterized by high recurrence rate and malignant transformation.

Purpose: This study aimed to investigate the prevalence of human papilloma virus (HPV) infection in these lesions in South of Iran.

Materials And Method: In this cross sectional retrospective study, a total of 41 patients, 38 SNP and 3 SNP/Squamous cell carcinoma cases, from 2007 to 2014 were studied. Human papilloma virus (HPV) DNA detection was performed by nested PCR method and positive cases were analyzed for high risk HPV-16 and HPV-18.

Results: HPV was detected in 31.7%; HPV- 16 in 4.9% and HPV 18 was not detected at all. Dysplastic epithelium was detected in 53% that was not associated with HPV. Three cases were accompanied with malignant transformation that HPV genome was detected in only one case and none of them were positive for HPV16 /18 genomic DNA.

Conclusion: Current research suggests that HPV may be involved in the development of SNP. But the high risk HPV is not important in malignant transformation. More studies are needed to elucidate the possible etiologic mechanism between HPV, inverted papilloma, and squamous cell carcinoma.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463771PMC
June 2017

Adenoid Cystic Carcinoma of the Larynx Presenting as a Thyroid Mass and Brief Literature Review.

Acta Cytol 2017 11;61(3):237-241. Epub 2017 May 11.

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Background: Adenoid cystic carcinoma (ACC) of the larynx and trachea is very rare.

Case: A 45-year-old man with ACC of the larynx presenting as a thyroid mass is reported in this study. Physical examination revealed a large solid thyroid nodule in the left lobe without any lymphadenopathy. A technetium thyroid scan showed multinodular goiter with cold nodules in the left lobe, isthmus, and functioning nodules in the right lobe. A large thyroid mass originating from the left side of the larynx, mostly the left vocal cord and the infraglottic part, was seen using enhanced magnetic resonance imaging after rupture of the thyroid cartilage on the left side. Ultrasound-guided fine needle aspiration smears and cell blocks of the thyroid nodule showed highly cellular smears composed of large tissue fragments, three-dimensional clusters, and sheets of neoplastic cells with slightly enlarged round and hyperchromatic nuclei. Immunohistochemical study showed that the cell block expressed C-kit and CK 7 on the cribriform growth pattern of the tumoral cells. However, protein expression of thyroglobulin and thyroid transcription factor-1 was not detectable.

Conclusion: To approach a thyroid nodule, direct invasion or metastatic tumors of other organs must be borne in mind.
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http://dx.doi.org/10.1159/000464271DOI Listing
July 2017

Spectrum of pediatric tumors diagnosed by fine-needle aspiration cytology.

Medicine (Baltimore) 2017 Feb;96(6):e5480

Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran Shiraz Molecular Pathology Research Center, Dr Daneshbod Pathology Lab, Shiraz, Iran Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Department of Otolaryngology, Shiraz University of Medical Sciences, Shiraz, Iran Department of Immunology, Tehran University of Medical Sciences, Tehran, Iran Department of Virology, Pasteur Institute of Iran, Tehran, Iran Department of Pediatrics, Children's Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran.

Pediatric tumors differ markedly from adult tumors in their nature, distribution, and prognosis. In this 10-year retrospective study, we present our experience with fine-needle aspiration (FNA) in pediatric patients 18 years of age and younger and correlate relationship between gender with organ, diagnosis, malignancy, and age. In our study, FNA material of pediatric tumors or masses with 18 years aged and younger were analyzed retrospectively.All FNAs in pediatric patients during this time period were identified and analyzed for age, gender, cytologic diagnosis, and site of aspiration. A total 1000 FNAs were performed from January 2007 to October 2015 in 499 children. Regardless the gender, the most frequently aspirated organ was lymph node, comprising 129 of the 499 cases followed by thyroid (112), neck cyst (79), and parotid (35) cases. The majority of the cases were diagnosed as benign lesions (436 of 499 cases). Other 63 cases comprising 40 female and 23 male cases had malignant lesions. There was significant age difference between people with or without malignancy. In malignant cases, there was a significant difference between the age on males and females. In regard to gender and diagnosis, cytologic diagnosis was stratified into 9 broad diagnostic categories: lymphadenitis, benign and malignant thyroid, cyst contents, benign breast, benign and malignant salivary, and negative for malignancy.In conclusion, our study supports the use of FNA cytology (FNAC) in lesions of various anatomic sites in the children less than 18 years old. As a simple, minimally invasive, and rapid procedure, cytopathologists can reliably utilize FNAC in children. The mean age of children receiving a malignant diagnosis was significantly higher than that of benign lesions. The mean age of malignancy in boys is significantly lower than that of girls with malignancy.
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http://dx.doi.org/10.1097/MD.0000000000005480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312980PMC
February 2017

Decreased Serum Monocyte Chemoattractant Protein1 in Salivary Gland Tumor Patients.

Asian Pac J Cancer Prev 2016 ;17(7):3601-4

Department of Oral Medicine, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran Email :

Background: The monocyte chemoattractant protein1 (MCP1/CCL2) is a potent chemoattractant for natural killer cells, monocytes, and memory T lymphocytes. However, any role in the genesis of salivary gland tumors (SGT) is unknown. To assess the diagnostic relevance of chemokines in SGT, MCP1 levels in the serum of patients were investigated in association with tumor progression and clinical aggressiveness.

Materials And Methods: Using an ELISA kit, we assessed and compared the circulating levels of MCP1 in blood serum of 70 SGT patients with 44 healthy control samples.

Results: The results of this study showed that the concentration of MCP1 was significantly lower in patients with benign (463.8±158.5pg/ml, P=0.033) and malignant (454.8±190.4pg/ ml, P=0.007) SGT than in healthy subjects (645.7±338.9). No significant difference in mean serum levels of MCP1 was observed between the benign and malignant group (p=0.9). While MCP1 levels were lower in patients with an advanced clinical stage, advanced tumor size, higher tumor grade, or lymph node involvement, but the mean MCP1 level between groups showed no statistically significant difference (p>0.05).

Conclusions: MCP1 levels in the serum of patients with SGT were decreased, indicating that this might a good marker for discriminating patients with SGT from healthy people. However, no clearcut relationship was detected between MCP1 levels and clinicopathologic factors, and MCP1 is not a good marker for evaluating tumor dissemination.
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January 2017

T-helper Type 1 and 2 Cytokine Levels in Patients with Benign and Malignant Salivary Gland Tumors.

Iran J Immunol 2016 Mar;13(1):9-15

Cancer Immunology Group, Shiraz Institute for Cancer Research, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Background: Salivary gland tumors are among malignancies that have high recurrence rate. Immune responses in salivary gland tumors have not been well elucidated. T helper type 1 (Th1) and Th2 cytokines have been reported to play a role in the outcome of head and neck cancers.

Objective: To evaluate the serum levels of interferon gamma (IFN-γ), as the hallmark of Th1 cytokines, and interleukin-4 (IL-4), as the hallmark of Th2 cytokines, in patients with benign and malignant salivary gland tumors in comparison with healthy controls.

Methods: Fifty patients with benign and 14 patients with malignant salivary gland tumors, as well as 23 healthy individuals were recruited. Serum levels of IFN-γ and IL-4 were measured using ELISA method. Nonparametric tests were used for data analysis.

Results: Serum levels of IFN-γ and IL-4 were found not to be significantly different in patients compared to the control group (0.68±0.29 vs. 1.03±0.57pg/ml, p=0.58 for IFN-γ, 4.57±1.57vs. 4.41±1.31pg/ml, p=0.28 for IL-4). IFN-γ and IL-4 serum levels were also not significantly different between patients with benign and malignant salivary gland tumors (p=0.54 and p=0.86, respectively).

Conclusion: The systemic levels of IL-4 and IFN-γ seem not to be associated with salivary gland tumor in our study. Investigation of other cytokines produced by Th1 and Th2 cells are warranted.
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http://dx.doi.org/IJIv13i1A2DOI Listing
March 2016

MTA1 Expression in Benign and Malignant Salivary gland Tumors.

Iran J Otorhinolaryngol 2016 Jan;28(84):51-9

Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, Shiraz, Iran.

Introduction: Salivary gland tumors (SGTs) are important parts of human neoplasms. The most common SGT is pleomorphic adenoma and the most common malignant SGTs are mucoepidermoid carcinoma and adenoid cystic carcinoma (ACC). Metastasis-associated genes 1 (MTA1), a member of the nucleosome remodeling and histone deacetylation complex, is one newly discovered gene which recruits histone deacetylation, causing ATP-dependent chromosome remodeling, and regulating transcription. MTA1 had been shown to be overexpressed in malignant tumors with the enhancement of invasion and metastasis.

Materials And Methods: Fifty-six samples of salivary gland tumors from the Khalili Hospital archive, including 20 cases of pleomorphic adenoma, 17 cases of mucoepidermoid carcinoma, 19 cases of ACC, and 23 cases of normal salivary gland tissues were chosen for immunohistochemical analysis of MTA1.

Results: MTA1 expression in the malignant tumors was significantly higher than that in pleomorphic adenoma (P<0.001), and higher in pleomorphic adenoma than the normal salivary glands(P< 0.001). In total, 69.6% of normal salivary gland tissues showed MTA1, but all cases of salivary gland tumors were positive for MTA1. High nuclear expression of MTA1 was detected in 83.3% (30/36) of the malignant salivary gland tumors and 45% (9/20) of pleomorphic adenoma, while low MTA1 expression was seen in all of the normal salivary gland tissues. No statistically significant correlation was found between MTA1 protein expression and any clinicopathological features (P>0.05).

Conclusion: Our findings demonstrate that MTA1 was significantly overexpressed in malignant salivary gland neoplasm in comparison to a lower level in benign pleomorphic adenoma, suggesting that MTA1 protein might be involved in carcinogenesis.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4735617PMC
January 2016

Twist Expression in Pleomorphic Adenoma, Adenoid Cystic Carcinoma and Mucoepidermoid Carcinoma of Salivary Glands.

Turk Patoloji Derg 2016 ;32(1):15-21

Department of Oral and Maxillofacial Pathology, School of Dentistry, Shiraz University of Medical Sciences, SHIRAZ, IRAN.

Objective: Twist is an important transcription factor that induces epithelial-mesenchymal transition and therefore plays an important role in tumor progression. There are a few studies on Twist expression in salivary gland carcinomas. The aim of this study was to evaluate and compare the expression of Twist in the most common benign and malignant salivary gland tumors and to determine whether its expression was correlated with any tumor characteristics.

Material And Method: In this retrospective cross-sectional study, 45 cases including 11 cases of normal salivary gland, 12 pleomorphic adenomas, 12 adenoid cystic carcinomas and 10 mucoepidermoid carcinomas were enrolled. The mean and intensity of Twist expression were evaluated immunohistochemically and were compared using statistical analysis.

Results: The expression of Twist was higher in malignant salivary gland tumors in comparison with normal glands and benign tumors (p= 0.03). It was also higher in pleomorphic adenomas in comparison with normal tissue. Adenoid cystic carcinomas and mucoepidermoid carcinomas showed no significant difference in Twist expression (p= 0.50). There was no correlation with the size, stage or grade of tumor.

Conclusion: The findings showed that Twist might play a role in the formation of salivary gland neoplasm and also may affect malignant transformation and tumoral invasion. The exact mechanism of this marker and the possibility of using it as a therapeutic target require further investigation.
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http://dx.doi.org/10.5146/tjpath.2015.01343DOI Listing
January 2017

Reduced serum levels of syndecan-1 in patients with tongue squamous cell carcinoma.

Laryngoscope 2016 05 15;126(5):E191-5. Epub 2015 Dec 15.

Department of Immunology , School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Objectives/hypothesis: To investigate soluble syndecan-1 (Sdc-1) in the sera of patients with tongue squamous cell carcinoma (SCC) and its correlation with the histopathological criteria of tumors.

Study Design: In a case-control study using a convenient method of sampling, 18 female and 25 male patients with confirmed diagnosis of tongue SCC, and 19 healthy females and 27 males were studied.

Methods: Soluble Sdc-1 was measured in the sera of 43 patients with tongue SCC and was compared with that of healthy age-/sex-matched controls using a commercial enzyme-linked immunosorbent assay. Clinical and pathological data, along with the demographic characteristics of the patients, were recorded at the time of sampling.

Results: The levels of soluble Sdc-1 were decreased in the sera of patients compared to controls (91.17 ± 88.60 vs. 158.17 ± 103.47 ng/mL, P = .002). Although patients who smoke tended to have higher grades (P = .043), there was no significant difference in the level of syndecan-1 between smokers and non-smokers. A significant difference between syndecan-1 in the sera of patients with tumors of different stages was observed (Kruskal-Wallis test P=0.039); however, scarcity of patients in stages I and III decreased the power of the comparison.

Conclusions: Sdc-1 levels in the sera of patients do not correlate with the tumor progression in the tongue SCC. This is in contrast with the reported inverse correlation between the expression level of membranous Sdc-1 and the histological grade and size of head and neck tumors. Therefore, Sdc-1 shedding may not be a major mechanism in the progressive loss of its expression regarding tongue tumor.

Level Of Evidence: NA Laryngoscope, 126:E191-E195, 2016.
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http://dx.doi.org/10.1002/lary.25812DOI Listing
May 2016