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Heated debates have been on-going about tea consumption and the incidence of cancer, especially in head and neck cancer types. This study aimed to review the association between tea consumption habits and nasopharyngeal cancer (NPC). Methods: This review was carried out in accordance with the PRISMA-P protocol. Literature search for journal articles that published studies on the relationship between tea consumption and NPC was performed via databases, such as Elsevier, PubMed, Science Direct, Springer Link, Google, and Google Scholar, for 10 years from 2008 to 2018. Relevant studies were obtained by applying the pre-determined keywords, such as nasopharyngeal cancer, tea consumption and NPC, risk factors of NPC and benefits of tea consumption. Results: A total of 126 articles was retrieved. These articles were subjected to eligibility assessment. Six articles remained after applying the inclusion criteria. Results suggest that habitual tea consumption reduces NPC. Tea consumption significantly reduces NPC with all the studies having a p-value ≤0.05. Meta-analysis showed statistical association between tea consumption and NPC risk with OR=0.865 at 95% CI (0.806-0.929). Conclusion: This study suggests that habitual tea consumption could be associated with prevention of NPC development. Additional studies are needed to further understand the molecular role of bioactive compound and potential health benefit of tea consumption in NPC prevention.
Background: Recently has been suggested that LINC01296 has an important role in tumor-promoting in different malignancies. We performed first meta-analysis to assess the association between the LINC01296 expression and clinicopathological criteria and the survival of patients with cancers. Methods: Relevant articles Identified by PubMed, EMBASE, Web of Science, and Scopus searching between December 2000 and 28 December 2018. Binomial data were evaluated by the odds ratio (OR) as the rapid statistic. The association between overall survival (OS) and the LINC01296 expression was evaluated using pooling the hazard ratio (HR) with its corresponding 95% confidence interval (CI). Results: Finally, 9 studies with 720 patients with cancer were included. The expression of LINC01296 showed a significant positive association with TNM stage (OR = 2.67, 95% CI = 1.83-3.88), tumor stage (OR= 2.22, 95% CI= 1.34-3.66) and lymph node metastasis (OR = 3.07, 95% CI = 2.23-4.21). A shorter OS was significantly associated with the expression of LINC01296 (HR = 3.95, 95% CI = 2.65-5.25) and lymph node metastasis (HR = 2.39, 95% CI =1.16-3.63). The OS did not show significant association with gender (HR = 0.83, 95% CI = -0.63-2.30) and tumor stage (HR= 2.66, 95% CI= -0.22-5.54). Conclusion: In conclusion, the results of this meta-analysis suggest that the expression of LINC01296 might be considered as a potential biomarker in patients with cancer.
In the following commentary, we provided discussions regarding an article bublished by Albasher et al. (2020) concerning the effects of long-term use of finasteride on women. They reported some adverse effects, including abnormal levels in the steroid hormones, irregular menstrual cycles, and heavy menstrual bleeding. Some concerns exist in the study mainly concerning the sample, particularly its size and composition. The authors recruited Saudi women. Thus, the findings cannot be generalized. Their study can be seen as a starting point in this regard. Even though the concerns can restrict the study, their study is still credible addressing critical issues that need to be taken seriously by other researchers and stakeholders.
Background: Breast cancer (BC) is a leading female cancer worldwide and cause of cancer-related death, especially in developing countries. Genetic predispositions to BC development in African population is poorly studied, and meanwhile the SNP rs17506395 in TP63 gene locus has been associated with the development of breast cancer in Asian women, no investigation has been undertaken within African population. We investigated the impact of this polymorphism in a representative African population. Methods: We undertook a case-control study including 335 women, of which 111 were breast cancer patients and 224 controls. Using blood-derived germline DNA, PCR-RFLP was used to investigate the polymorphism of TP63 gene at rs17506395 locus. Unconditional logistic regression was used to study the association between the TP63 gene polymorphism and risk of BC development. After stratification into different age and ethno-linguistic groups as well as menopausal status, the Cochran-Mantel-Haenszel test was used to measure significance of the associations. Results: Comparing cases with controls, no significant associations between genotype and disease development was observed. Similarly, when cases were stratified according to menopausal status and ethno-linguistic groups, no significant association was observed between genotype and disease development. However, in women of 40 years and below, TT and TG genotypes were associated with breast cancer development. The minor G allele seems to protective against early breast cancer onset OR of 0.5 (95%CI = 0.26-0.94, p = 0.03). Conclusion: Our data revealed an association between rs15706395 and the risk of early breast cancer onset. The GG genotype seems to reduce the risk of early breast cancer. Larger studies are needed to confirm the potential of this SNP as biomarker for breast cancer prognostic.
Background: Cervical cancer is a major reason for morbidity and mortality in Low and Middle income countries. The National Programme for Prevention and Control of Cancers, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS) sets out broad national guideline to implement Cervical cancer screening. However, an implementation strategy for cervical cancer screening is not in place for districts. Although opportunistic screening takes place, implementation is hindered by psychological and physical barriers for women, as well as insufficient capacity on the part of implementers. This qualitative study aims to identify the specific barriers that prevent the uptake of cervical cancer screening. Methods: Women who could benefit from cervical cancer program were interviewed to explore the factors that influenced their uptake of the cervical screening offered. Key informant interviews were conducted with implementers of the NPCDCS and with public health staff of three States (Himachal Pradesh, Meghalaya and Karnataka), to understand their perception of determinants of the utilization of screening services. Results: The general health concern among the participants was low, and routine check-ups were considered unimportant. Poor knowledge about cervical cancer, benefits of screening service availability, as well as a general sense of well-being, embarrassment or anxiety related to the screening procedure, fear of being judged for lack of modesty, and stigma were common barriers to screening uptake. In addition to a general unawareness of cervical cancer geographical inaccessibility of screening as a barrier to participate in cervical cancer screening, in certain regions. Conclusion: It is essential to increase the knowledge on cervical cancer and on the benefits of screening among Indian women. Providing information and cues to action by health workers and professionals can facilitate the decision to participate. Implementers need to be involved to ensure context specific implementation of the National programme to overcome these barriers.
Objective: The aim was to examine the association between heterocyclic amines 2-amino-1-methyl-6-phenylimidazo pyridine (PhIP) and the risk of colorectal cancer (CRC) in Viet Nam. Methods: We performed a case-control study for 512 colorectal cancer patients with the histopathological confirmation and 1,096 hospital controls. We collected information on lifestyle, diet, and cooking methods from participants by trained interviewers using the validated questionnaires. We used data of PhIP concentration in cooked beef analyzed by the LC/MS/MS and cooking questionnaire to estimate the daily intake of PhIP. We divided the estimated amount of PhIP (ng/person/day) into three levels of non-intake (the reference), medium, and high to estimate the Odds ratio and 95% confidence interval (OR, 95%CI). Results: The median intake of PhIP (ng/person/day) was 18ng and 102.8ng for medium and high PhIP intake, respectively. There was a significant association between PhIP intake and the risk of colorectal cancer. The adjusted OR (95%C), high intake vs. non-intake, were 4.89 (3.03, 7.89), p_trend
Objective: This study was designed in order to identify the prognostic relevance of CD200 expression and soluble Cytotoxic T-lymphocyte antigen-4 (CTLA-4) levels in myelodysplastic syndrome (MDS) patients. Methods: The study included 57 MDS (37 intermediate and 20 high risk) patients and 10 controls. For all of included patients; CD200 expression was identified by flowcytometry on CD33 positive cells and soluble CTLA-4 (CD152) concentration was determined by ELISA. Results: CD200 positive expression was detected in 32/57 (56.1%) of MDS cases, the mean serum CTLA-4 concentrations were significantly higher in MDS patients as compared to controls (P<0.01). Significant association between high CD200 positive expression; high CTLA-4 concentration levels and MDS risk stages being higher in high risk MDS group as compared to intermediate risk one (P < 0.01). After 36-month follow-up; the subgroup of MDS patients with high expression of CD200; and high serum CTLA-4 concentrations showed high death rate and high frequency of acute myeloid leukemia transformation. Conclusions: CD200 positive expression could be considered as a new prognostic marker for risk stratification of MDS patients. CD200 expression may exert its effect through upregulation of CTLA-4.
Introduction: Colorectal cancers (CRC) continues to increase worldwide and is associated with significant morbidity and mortality. CRC can be prevented through early detection using several modalities. However, like any screening program participation remains suboptimal. This study assessed the factors associated with participation in a stool based CRC screening that was carried out as part of an Integrated Health Screening Survey for civil servants. Materials and Methods: Civil servants who participated in a health survey (N=10,756, mean age 48.08 ± 5.26 years old) were studied. Demographic factors (gender, age groups, marital status, employment status, body mass index [BMI] categories, smoking status, personal and family history of cancers) were analyzed to assess for features associated with willingness to participate in this fecal immunohistochemistry test (FIT) screening for CRC. Comorbid conditions studied were cardiac disease, diabetes mellitus, dyslipidemia, hypertension and stroke. Multivariate analysis was performed to evaluate variables associated with participation in CRC screening programme. Results: Of the invited 10,756 participants, 7,360 returned a stool specimen giving a participation rate of 68.4%. Those who participated were significantly older (60 years [77.8%], p0.05). Multivariate analyses showed that older age (45-49, 50-54, 55-59 and >60) and employment status (professional) remained significant factors associated with participation in a stool based CRC screening. Conclusions: Our study showed that older age and professional employment status were significantly associated with willingness to participate in a stool based CRC screening.
Objective: The etiology of multiple myeloma (MM) is not known. Enzymes such as xanthine oxidase (XO) and NADPH oxidase 1 (NOX1) as relevant sources of reactive oxygen species (ROS) production may play a crucial role in the incidence and progress of MM. Uric acid generated by XO has a controversial dual role in both the prevention and promotion of cancer. We conducted a case-control study and selected patients with stage I MM to investigate the status of XO, NOX1, and uric acid in the patients and controls. Methods: We used a sample of 33 patients with stage I MM and 30 healthy controls. The enzyme-linked immunosorbent assay (ELISA) measured the enzyme concentration of XO and NOX1, and the colorimetric method measured the serum level of uric acid. Results: Mean serum levels for XO in patients and controls were 6.17±0.83 ng/ml and 4.12±0.57 ng/ml (P<0.001). serum levels of NOX1 were 4.35±1.03 ng/ml in patients and 3.54±0.91 ng/ml in controls (P<0.001). Evaluating the levels of XO and NOX1 in male and female populations showed a significant difference in the male population (NOX1 P=0.002; XO P<0.001) and female population (NOX1 P=0.002; XO P<0.001). Also, a significant correlation was observed between the two enzymes only in the female population (Pearson correlation=0.5; P=0.006). A significant inverse correlation found between albumin and XO (Pearson correlation=-0.7, P<0.001) and NOX1 (Pearson correlation=-0.5, P<0.001). XO was correlated with B2-m (Pearson correlation=0.37, P=0.003). There was no significant difference in uric acid between patients (6.2±1.2 mg/dl) and controls (5.7±1 mg/dl) (P=0.2), and no correlation was found with XO. Conclusion: The present study indicates the possible role of XO and NOX 1 in the etiology of MM. Although we found no correlation between uric acid and XO, further studies will help clarify the function of uric acid in the pathogenesis of MM.
Background: Telomerase activity is up regulated in most breast cancer subtypes but not in the adjacent normal tissues. Thus, it is a promising target for anticancer therapy. The present work investigated the effects of telomerase inhibition by siRNA on breast cancer cell lines and studied the feasibility of whether the combined effect of doxorubicin with siRNA treatment on breast cancer cells potentiates a rapid cellular response to the cytotoxic effect of chemotherapy. Methods: This study was performed on Luminal A (MCF-7), triple negative (MDA-MB-468), and HER-2/neu (SKBR-3) human breast cancer cell lines, wherein telomerase activity inhibition by hTERT siRNA and doxorubicin was detected by measuring telomerase activity using Telomeric Repeat Amplification Protocol (TRAP assay), assessing cell viability through MTT assay, and evaluating apoptosis through scanning electron microscopy (SEM) and through estimating caspase-3 and -8 activities using enzyme-linked immunosorbent assay (ELISA). Results: In the present study, hTERT siRNA effectively reduced telomerase activity and cell viability to more than 90% and 60%, respectively, in most breast cancer cell lines within 72 hours after transfection. The combination of hTERT siRNA and doxorubicin showed a cumulative effect compared with either treatment alone (P < 0.05). Meanwhile, SEM demonstrated apoptotic morphologic cell changes. Conclusion: Telomerase inhibition is a promising strategy for the effective treatment of breast cancer. When used in combination with doxorubicin, it could potentiate the cytotoxic effect of the drug on breast cancer cells.
Objective: Glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) are the key detoxification enzymes of xenobiotics, including chemotherapeutic drugs. The deletion polymorphisms of GSTM1 and GSTT1 genes are associated with reduced enzyme activity that influenced clinical outcomes of chemotherapeutic agents in breast cancer. However, there is limited information among Thai patients. This research aims to explore the frequency and role of GSTM1 and GSTT1 polymorphisms on survival among Thai patients with breast cancer. Methods: The retrospective cohort study was performed. Demographic data and clinicopathology characteristics were collected from hospital base registry data and medical records. A multiplex qualitative real-time PCR method was used to detect the presence or absence of the GSTM1 and GSTT1 gene in the genomic DNA samples of the participants. Results: The frequencies of the GSTM1 and GSTT1 null genotypes in 198 breast cancer patients were 65.70% and 33.30%, respectively. The overall survival at 1, 3 and 5 years were 95.00%, 83.00%, 71.00% respectively. The log rank test and Cox proportional hazards revealed a significant different in the 5-years overall survival according to lymph node metastasis and tumor stage (P = 0.014 and P < 0.001). No associations between overall survival and GSTM1 or GSTT1 genotype were found in single or combined genotypes analyses (P = 0.76 and P= 0.15). Conclusion: The results of our study provided the epidemiological information for prognostic of survival in breast cancer patients treated with chemotherapy.
Background: Most effective method for reducing mortality from hepatocellular carcinoma (HCC) is early diagnosis. Despite its lack of adequate sensitivity, ultrasound is considered fundamental for HCC screening. Aim: to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) as non-invasive marker for HCC diagnosis in Egyptian patients. Methods: One hundred and twenty patients were divided into three groups (40 patients each): patients with chronic viral hepatitis (HCV or HBV), cirrhotic patients and HCC patients and 40 healthy age and gender matched subjects were enrolled as control group. After clinical assessments, urinary NGAL was measured by enzyme-linked immunosorbent assay. Results: Our results revealed that median level of urinary NGAL was 290, 834, 1090 and 1925 pg/ml in control, chronic hepatitis, cirrhotic and HCC groups respectively among studied groups (p<0.001). Receiver operating characteristics (ROC) analysis showed that urinary NGAL cutoff value of 1255 ng/ml could discriminate between HCC and cirrhosis. The area under curve (AUC) was 0.95 with 90% sensitivity, 87.5% specificity (p-value <0.001). In HCC group, urine NGAL level didn`t show significant correlation with Child Pugh score, MELD score or Barcelona Clinic Liver Cancer (BCLC) stage. Conclusion: Urinary NGAL could be a simple, non-invasive test for diagnosis of HCC in chronic liver disease patients.
Background: The occurrence rate of BRCA1 mutations is found to be high in South Asian countries where early onset of breast cancer is common. In Bangladesh, noticeable percentage of patients experience breast cancer in their reproductive ages. The objective of this study was to identify any mutation in exon2 of the BRCA1 gene in adult Bengali Bangladeshi female patients with breast cancer. Methods: In this cross-sectional descriptive study, the genomic DNA was extracted from the blood of adult fifty Bengali Bangladeshi female breast cancer patients. The whole region of exon2 of the BRCA1 gene was amplified and the amplified DNA products were sequenced using Sanger sequencing. The raw chromatogram data were analyzed using Chromas software, and analyzed sequences were compared with the NCBI RefSeq database by BLAST search. The resultant amino acid change was detected by MEGA X software. Results: We found the mean age at diagnosis 44.66 years, whereas 96% of patients were married, 90% were multiparous and 86% breastfed their children. All patients had unilateral breast cancer and among them 94% had invasive ductal carcinoma. Only 24.5% of the patients had associated omorbidity. The family history of breast cancer or other BRCA-associated cancer was positive only for 4% of patients. A total of five mutations were identified all of which caused by substitutions. Among them three were nonsynonymous and two were synonymous. Only 2.5% of the patients, within the age group of 18-50 years, were found to have mutations in their blood, whereas 26.66% of the patients above 50 years found to have mutations in this study. Conclusions: Among this small sample size, we found five mutations in exon2 of the BRCA1 gene and this indicates the necessity to find out the mutation spectra of the BRCA1 gene in the Bangladeshi population.
Background: The X-chromosome has been suggested to play a role in prostate cancer (PrCa) since epidemiological studies have provided evidence for an X-linked mode of inheritance for PrCa based on the higher relative risk among men who report an affected brother(s) as compared to those reporting an affected father. The aim of this study was to examine the potential association between the forensic STR markers located at four regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28 and the risk of BPH and PrCa to confirm the impact of ChrX in the PrCa incidence. This may be helpful in the incorporation of STRs genetic variation in the early detection of men population at risk of developing PrCa. Methods: DNA samples from 92 patients and 156 healthy controls collected from two medical centers in Riyadh, Saudi Arabia were analyzed for four regions located at X-chromosome using the Investigator® Argus X-12 QS Kit. Results: The results demonstrated that microvariant alleles of (DXS7132, DXS10146, HPRTB, DXS10134, and DXS10135) are overrepresented in the BPH group (p < 0.00001). Allele 28 of DXS10135 and allele 15 of DXS7423 could have a protective effect, OR 0.229 (95%CI, 0.066-0.79); and OR 0.439 (95%CI, 0.208-0.925). On the other hand, patients carrying allele 23 of DXS10079 and allele 26 of DXS10148 presented an increased risk to PrCa OR 4.714 (95%CI, 3.604-6.166). Conclusion: The results are in concordance with the involvement of the X chromosome in PrCa and BPH development. STR allele studies may add further information from the definition of a genetic profile of PrCa resistance or susceptibility. As TBL1, AR, LDOC1, and RPL10 genes are located at regions Xp22.31, Xq11.2-12, Xq26.2, and Xq28, respectively, these genes could play an essential role in PrCa or BPH.
Background: Differences in the geographical distributions of esophageal cancer (EC) are associated with environmental influences and genetic risk factors. The inhabitants of the Republic of Uzbekistan are at high-risk for EC; however, detailed epidemiological data regarding the dynamics of EC are not available. Methods: To address this gap in our knowledge, here we reviewed trends in the incidence of EC in Uzbekistan from 2000 through 2018. We acquired the epidemiological data for 17,144 patients with EC from the national epidemiological data base of Uzbekistan. Results: The mean incidence (per 100,000 persons) during the study period was 2.8, which peaked at 3.9 in 2007 and decreased below 2.5 in 2014 and thereafter. The incidence was highest for patients aged 61 years to 70 years (37.5%). Among patients with EC, 13,331 (80.0%) and 3,333 (20.0%) were diagnosed with squamous cell carcinoma or adenocarcinoma, respectively. The incidences of patients with EC with adenocarcinoma were 0.6 from 2010–2018 and 0.4 from 2000 to 2009. The majority of patients were diagnosed with stage III EC, which was associated with a 5-year survival rate that increased from approximately 15% (2000–2009) and plateaued at approximately 25% (2012–2018). Conclusions: We conclude that preventing the progression of EC to stage III is required to improve the prognosis of patients with EC who reside in Uzbekistan.
Background: Gliomas remain one of the most common primary brain tumors. Mutations in the isocitrate dehydrogenase (IDH) gene are associated with a distinct set of clinicopathological profiles. However, the distribution and significance of these mutations have never been studied in the Indonesian population. This study aimed to elucidate the association between IDH mutations and clinicopathological as well as prognostic profiles of Indonesian patients with gliomas. Methods: In total, 106 patients with gliomas were recruited from a tertiary academic medical center in Yogyakarta, Indonesia. Formalin-fixed paraffin-embedded and fresh tissue specimens were obtained and sectioned for hematoxylin-eosin staining and immunohistochemical examinations. Genomic DNA was isolated and analyzed for the presence of IDH mutations using standard polymerase chain reaction and nucleotide sequencing methods. Clinicopathological data were collected from medical records. Results: Although no IDH2 mutation was identified, IDH1 mutations were found in 23 (21.7%) of the patients. Patients with IDH1 mutations tended to have a history of smoking and a shorter interval between onset of symptoms and initial surgical interventions. Frontal lobe involvement, oligodendroglial histology, lower Ki67 expression, WHO grades II and III gliomas, and methylated O6-methylguanine-DNA methyltransferase (MGMT) promoters were significantly associated with the presence of IDH1 mutations. Compared with patients with IDH1-wild-type, patients with IDH1 mutation were observed to have a longer overall survival. Conclusions: IDH1 mutations are associated with certain clinicopathological and prognostic profiles in Indonesian patients with gliomas. This finding demonstrates the importance of identifying IDH mutations as part of the management of patients with glioma in Indonesia.
Background: Majority of cancer-related deaths worldwide is attributed to non-small cell lung cancer (NSCLC). G protein-coupled receptor 56 (GPR56) is overexpressed and associated in the progression of NSCLC. The aim of this study is to use immunoinformatics approach in designing a multi-epitope vaccine to target overexpressed GPR56 which can potentially activate antibody-mediated cell death mechanisms and inhibit pathways involved in the proliferation, migration and survival of NSCLC. Methods: Herein, the reported overexpression of GPR56 was further investigated by conducting a differential gene expression analysis of NSCLC samples from GEO DataSets (GSE29249). Results confirmed significant overexpression of GPR56 in NSCLC compared to adjacent normal samples. A multi-epitope vaccine (Fvax) was constructed in silico by adjoining B lymphocytes (BL) and helper T lymphocytes (HTL) epitopes from the extracellular sequence of GPR56. Population coverage (PC) of HTL epitopes was also estimated. To enhance its immunogenicity, sequences of flagellin domains were fused as adjuvant. Fvax was evaluated in silico for antigenicity, allergenicity, peptide toxicity, physicochemical properties and cross-reactivity. Its tertiary structure was predicted, refined, and validated followed by structural epitope prediction. Lastly, Fvax DNA was optimized and cloned in silico. Results: This is the first work to design a potential vaccine against GPR56-overexpressing NSCLC. Fvax has 3 BL and 7 HTL immunogenic epitopes on GPR56. In silico evaluations suggest that Fvax is antigenic, non-toxic, non-allergenic, stable, and has accessible BL epitopes with high PC worldwide for HTL epitopes. Conclusion: Overall, results showed that Fvax is a potential vaccine against NSCLC. The approach of this study efficiently minimized the number of tests, cost and time required to select the best epitopes and to design a vaccine for the treatment of NSCLC.
Purpose: To evaluate the robustness of multiple machine learning classifiers for breast cancer risk estimation in the presence of incomplete or inaccurate information. Data and methods: Open data for this study was obtained from the BCSC Data Resource (http://breastscreening.cancer.gov/). We conducted two ablation-type experiments to compare the robustness of different classifiers where we randomly switched known information to missing with a missing probability of pm in one experiment, and randomly corrupted the existing information with a probability of pc in another experiment. We considered three prominent machine-learning classifiers such as Logistic regression (LR), Random Forests (RF) and a custom Neural Network (NN) architecture and compared their degradation of discrimination performance as a function of increasing probability of missing or inaccurate data. Results: LR, RF and custom NN resulted in an Area Under Curve (AUC) of 0.645, 0.643 and 0.649, respectively, on a test set with 500,000 total observations. When we manipulated the data by varying probabilities pm and pc from 0 to 1, NN resulted in better performance in terms of AUC compared to RF and LR as long as less than half the data was missing/inaccurate (that is, for values of pm < 0.5 and pc < 0.5). However, for missing (pm) or corruption (pc) probabilities above 0.5, LR gave similar performance as the custom NN. RF resulted in overall poorer performance when the data had additional missing or incorrect entries. Conclusion: In cases where the input information is missing or inaccurate, our experiments show that the proposed custom NN provides reliable risk estimates in medical datasets like BCSC. These results are particularly important in health care applications where not every attribute of the individual participant might be available.
Background: Malnutrition is prevalent in esophageal cancer patients which affects cancer prognosis. The purpose of this study was a comprehensive assessment of nutritional status during Chemoradiation (CRT). Methods: Newly diagnosed adults with esophageal cancer were recruited for this study. Patient-Generated- Subjective Global Assessment (PG-SGA), anthropometric indices, body composition, dietary intake, laboratory tests, and nutritional-related complications were assessed before, after, and 4 to 6 weeks after CRT. Results: Seventy-one cases were enrolled. The mean age was 66.8±12 years. Patients’ mean weight loss was 2.42±2.4 kilograms during treatment. A significant reduction observed in mean MUAC (26.68±4.9 vs. 25.42±5.1 cm), fat mass percentage (24.11±11.8 vs. 22.8±12.5), fat free mass index (16.87±2.4 vs. 16.47±2.6 kg/m2) and hand grip strength (43.2±19 vs. 36.1±20 kg) during CRT (all p-values <0.0001). We had also a non-significant change in mean energy intake (19.5±11 vs. 18.3±11 kcal/kgw. day) and protein intake (0.56±0.4 vs. 0.66±0.5 g/kgw.day) during CRT. In our assessment before, immediately after and 4-6 weeks following CRT, we recorded energy intake insufficiency in 55.7%, 58.7% and 27.3% and protein intake inadequacy in 89.8%, 89.1% and 72.7% of cases, respectively. The most common complications were dysphagia (56.7%), anorexia (25%), and constipation (47.9%) at admission. Dysphagia improved in some cases (42%), but anorexia (35%), early satiety (25%), Esophagitis (25%), dysosmia (21%) and dysgeusia (17%) were increased as CRT complication. yet, 25% of patients had dysphagia and 34.4% had constipation 4-6 weeks after CRT. The twelve-months mortality was significantly associated with lower BMI after CRT, primary PG-SGA score, weight loss, BMI<18.5, MUAC, physical performance, living in rural or urban areas, addiction. Conclusion: Our study demonstrated a high prevalence of malnutrition among esophageal cancer patients which worsened during Chemoradiotherapy. Our findings warrant early screening and monitoring of nutritional status and effective nutritional interventions with symptoms management during treatment in these patients.
Objective: Squamous Cell Carcinoma is almost always preceded by potentially malignant disorders in the oral cavity before malignant transformation. Characterization of 8-OHdG from the saliva offers a relatively non-invasive, simple and efficient methodology for monitoring oxidative stress in subjects of Premalignant oral disorders (PMOD) and Oral Squamous Cell Carcinoma (OSCC). Hence the aim of the current study is to estimate the levels of salivary 8-hydroxydeoxyguanosine (8-OHdG) as a potential DNA Damage Biomarker in OSMF and OSCC patients in comparison to healthy individuals to assess disease progression from potentially malignant oral disorder to frank malignancy. Materials and Methods: The study was conducted among 90 patients [Oral Squamous cell carcinoma (n=30) and Oral Submucous Fibrosis (n=30) and healthy gender and age matched controls (n=30)]. 4ml of unstimulated saliva was collected from each of the subjects and was subjected to Sandwich ELISA for the quantification of salivary 8-OHdG. Statistical analysis was done using ANOVA, and p value was set at ≤0.05. Results: The mean age of OSCC patients were 56.8±11.8 years. Smoking was the most prevalent adverse habit among this group (66.6%) followed by Smokeless tobacco chewers (40%). The mean age of OSMF patients was 46.2± 9.8 years. Smokeless tobacco was the most predominant habit among the OSMF patients (83.33%) followed by smoking (33.33%). The mean OHdG levels among the controls was 6.59±1.47 (ng/dl) and almost doubled in patients of OSMF 13.89±1.96(ng/dL) and further raised in OSCC patients 19.96 ± 2.11 (ng/dL). These levels showed a highly significant difference (p <0.0001) in mean on comparison by using one-way ANOVA. Pearson correlation between the groups were also statistically significant (p=0.000). Conclusion: There were significant differences in the concentration of salivary 8-OHdG between healthy controls, OSMF, and OSCC patients. Hence, 8-OHdG can be used as a novel biomarker of DNA damage to assess disease progression.
Background: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. Methods: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. Results: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline. Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Conclusion: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.
Objectives: Chemotherapy is used as an indispensable therapy for advanced gastric cancer. Different chemotherapy regimens have been used for this purpose. Toxicity due to the Chemotherapy drugs is one limiting factor. In this study we aim to compare the efficacy and toxicity of two regimens FOLFOX (leucoverin, 5-fluorouracil and oxaliplatin) and modified DCF (mDCF) (docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced gastric adenocarcinoma. Methods: In this analytical cross-sectional study, 47 patients treated with FOLFOX regimen and 57 patients treated with mDCF regimen were recruited, Patients in both groups were compared for demographic findings, response rate, mortality rate, overall survival (OS) and progression free survival (PFS). Results: In FOLFOX and mDCF group, complete response (CR) occurred in 4.3% and 5.3%, partial response (PR) in 42.6% and 29.8%, stable disease in 34% and 52.6% and disease progression in 19.1% and 12.3%, respectively (p=0.25). Overall response rate was 48.9% and 56.1%, respectively. There was no significant difference between two regimens in OS and PFS (p=0.22). mDCF compared to FOLFOX had significantly higher hematologic, gastrointestinal complications, as well as creatinine rise, stomatitis and hair loss, but peripheral neuropathy was significantly lower. Conclusion: The results of current study showed that in patients with advanced gastric adenocarcinoma, FOLFOX regimen compared to mDCF regimen have similar ORR, OS and PFS. Toxicity rate are also lower in FOLFOX group, thus it seems a better regimen for chemotherapy.
Background: To determine progression free survival (PFS) and predictor of recurrence in patients with diffuse large B-cell lymphoma (DLBCL) with negative interim 18FDG PET/CT (iPET) using standardized imaging and reporting protocols. Materials and Methods: This prospective study was conducted at PET/CT Section of a JCIA accredited healthcare facility from December 2015 till February 2020. Patients with DLBCL having complete metabolic response (CMR; Deauville score: 1-3) on iPET were selected and followed for a median period of 11 months (4-144 months). End point response on follow-up PET/CT (either end of treatment or surveillance) was categorized as sustained CMR (sCMR) and disease recurrence. Kaplan Meier survival curve was used to measure PFS and receiver operating characteristics (ROC) was plotted for age, largest lesion size, highest standardized uptake value (SUVmax), disease stage and body mass index (BMI) on baseline scan to find their impact on recurrence. Results: Total 185 patients with DLBCL who had achieved CMR on iPET with a median age 55 years (19 – 88 yr.) with male predominance (63% male) were selected. On follow-up, 123 (66%) had sCMR while recurrence was found in 34% (p <0.05). No significant difference in demographics was found between two groups. Median PFS time was 34 months (22.8 – 45.1 months). On ROC analysis, only baseline highest SUVmax was found as a significant independent predictor of disease recurrence at a cut off >22.6 (highest area under curve: 0.595; SE 0.046; p <0.05). Conclusion: We conclude that recurrence is found in 34% of DLBCL patients with a negative interim 18FDG PET/CT using standardized imaging and reporting protocols. Despite of early response, these patients need continued intensive follow-up especially those with a baseline SUVmax > 22.6.
Background: Wild edible plants are good sources for bioactive compounds, vitamins, and minerals with various applications. They can play a role in supporting the immune system and are highly beneficial as resources. Suaeda monoica Forssk is a wild edible plant that grows in Iraq and it’s biological activities have not yet reported. Methods: Saueda monoica Forssk bioactive compounds were extracted by a microwave-assisted extraction method using ethanol as a solvent, and its chemical composition was analyzed by GC-MS. The biological activities were evaluated via antioxidant, anti-liver-cancer, antibacterial, and toxicity tests in vitro. Results: The results of GC-MS analysis showed that there were about 20 bioactive compounds. The most abundant compound was N,N-Dimethylglycine methyl ester, followed by 9,12,15-Octadecatrienoic acid, n-Hexadecanoic acid, and N,N-Dimethylglycine. The antioxidant activity of the ethanol extract of the plant showed a significant IC50. The extract of S. monoica against liver cancer cells (HCAM) showed significant toxicity. Flow cytometric analysis showed a significant induced apoptosis and cell cycle arrested at G1 phase. Conclusions: The results indicated the significance of the components of Iraqi S. monoica Forssk by MAE method as a potential food supplement in nutrition systems to prevent liver cancer and enhance the liver’s defense against diseases.
Background: Colorectal cancer (CRC) is the fourth most common cancer worldwide. Both HER2 and SKP2 have a carcinogenic role in CRC making them attractive targets for tailored treatment. This work aims to correlate HER2 and SKP2 protein expression as well as HER2 gene amplification with clinicopathological parameters aiming at identifying potential candidates for targeted therapy. Methods: This Study was conducted on 127 paraffin-embedded tissue samples of different colorectal lesions [controls, chronic colitis, ulcerative colitis (UC), hyperplastic polyps (HPs), adenomas and CRCs] to investigate HER2 and SKP2 expression by immunohistochemistry (IHC), Selected CRC cases [equivocal (2+) and positive (3+) by IHC] were further evaluated by ISH (CISH and SISH ) to assess HER2 gene amplification. Results: Chronic colitis, UC, HPs and adenomas were HER2-negative. HER2 positivity (scores 2+ and 3+) was found only in15% of CRCs. Both SISH and CISH showed the same results with high concordance as 66.7% of equivocal and 100% of positive cases showed amplification of HER2 gene. SKP2 positivity was detected in 26.7% and 45% of adenomas and CRCs respectively, while other studied groups were negative. A significant correlation was noted between HER2 and SKP2 expression. Conclusion: A small percent of CRCs exhibited HER2 gene amplification, which would be potential candidates for anti HER2 therapy whereas IHC could be a primary screening test for patient selection. A potential carcinogenic role of SKP2 was suggested by the findings that SKP2 expression was undetectable in normal colonic mucosa but significantly increases from adenoma to carcinoma, hoping adenoma patients to get benefit from targeted therapy.
Background: Lung cancer is a major cause of cancer death worldwide. The incidence of lung cancer in Thailand increasing, but risk factors are rarely reported. Objective: To investigate the effect of coffee consumption on lung cancer in Thai population. Methods: Between 1990 and 2001, lifestyle and demographic data were collected from 24,528 participants in the Khon Kaen Cohort Study (KKCS), who were followed through 2016, by linking to the Khon Kaen Population-based Cancer Registry. A total of 12,668 eligible participants (68.8% females, mean age 51.0 years at baseline) having complete datasets (239,488 person-years of follow up with 138 incident cases of lung cancer observed) were analyzed using a multi-variable adjusted Cox proportional hazard models. Results: Coffee consumption was associated with reduced risk for lung cancer (adj. HR = 0.54; 95% CI: 0.35-0.84) after adjusting for age and gender. Cigarette smoking (adj. HR = 2.76; 95% CI: 1.32-5.78) and family history of cancer (adj. HR = 1.65; 95% CI: 1.10-2.48) were associated with higher risk. Conclusion: This study suggests coffee consumption may be a protective factor for lung cancer in among this cohort.
Objective: The present study aimed to investigate the impact of preoperative C-reactive protein to albumin (CRP/Alb) ratio on the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC). Methods: 82 patients who underwent hepatic resection for mass-forming type of ICC were evaluated. The relationship between preoperative CRP/Alb ratio and survival outcomes was investigated. Results: The optimal cutoff value of CRP/Alb ratio for assessing overall survival (OS) was determined as 0.089. Univariate analysis for recurrence-free survival (RFS) showed that CRP/Alb ratio >0.089, carbohydrate antigen 19-9 (CA 19-9) >37 U/mL, lymph node metastasis, vascular invasion, and multiple tumors were significantly associated with postoperative recurrence. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.006), and multiple tumors (p < 0.001). Univariate analysis for OS showed that CRP/Alb ratio >0.089, CA 19-9 >37 U/mL, lymph node metastasis, vascular invasion, multiple tumors, and positive surgical margin were significantly associated with overall death. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.01), and multiple tumors (p = 0.005). Conclusion: Preoperative CRP/Alb ratio may predict poor long-term outcomes after hepatic resection in patients with ICC.
Background and objective: Ovarian, fallopian tube, or primary peritoneal cancer patients with BRCA gene mutation have enhanced sensitivity to platinum-based regimens and PARP inhibitors. However, the knowledge regarding BRCA mutation in Thai patients is limited. This study aimed at identifying the prevalence and characteristics of somatic and germline BRCA 1 and 2 mutations in Thai patients with these cancers. Materials and Methods: The paraffin blocks of tumors with histology of high grade serous, high grade endometrioid, or clear cell carcinoma obtained between June 2016 and December 2017 were analyzedto evaluate BRCA mutation using next-generation sequencing system. Blood or normal tissue paraffin blocks of positive patients were further tested for germline BRCA mutation. Results: Tissue paraffin blocks of 178 patients were collected but only 139 were analyzed. Positive BRCA mutation was identified in 24 patients (17.3%): BRCA1 in 13 cases, BRCA2 in 10 cases, and BRCA1 and 2 in the rest one. Germline mutation study in blood or normal tissue in 23 positive patients revealed BRCA mutation in 14 cases, BRCA1 in 8 cases and BRCA 2 in 6 cases. Overall, the prevalence of somatic and germline mutation was 6.5% (9 out of 138 patients) and 8.7% (14 out of 138 patients), respectively. The most common histology associated with BRCA mutation was high grade serous cancer (27.3%). No significant difference was found between patients with or without BRCA mutation in terms of stage, outcome, platinum status, and survival outcome. Conclusion: BRCA mutation was demonstrated in less than 10% of Thai ovarian cancer patients. Higher rate of mutation was found in high grade serous cancer.
Purpose: Shoulder and cervical pain, reduced mobility and disability are some of the major complications associated with surgeries of head and neck cancers affecting several domains of quality of life. In the present study we aimed to compare the effectiveness of Muscle Ener-gy Techniques (METS) and Active Range of Motion Exercises in reducing pain, improving shoulder mobility and function in patients post Modified Radical Neck Dissection (MRND). Methods: Forty eight subjects were randomly assigned to two groups. Group A received active range of motion (AROM) exercises and group B received Muscle energy techniques (METS). Both the groups were treated for a period of 10 consecutive days starting from the 3rd to 5th postoperative day. Data was collected on the 1st and 10th day of intervention. Results: Both groups showed highly significant improvements in shoulder range of motion , decrease in pain and better Global Rating Change cores(GRCS) (p=0.005). GRCS and shoul-der abduction showed significant improvement in group B when compared to group A, sug-gesting better clinical outcomes in those treated with Muscle Energy Techniques. Conclusion: This study showed that both METs and AROM exercises were effective in im-proving shoulder range of motion, function and reducing pain in patients post MRND but-Muscle Energy Techniques were more effective when compared to AROM exercises.
Objective: The purpose of our study was to determine the frequency of BRCA1 promoter hypermethylation and its association with expression changes of BRCA1 and main morphological features in sporadic breast cancer. Methods: A retrospective review of cases was performed to select those with specific morphological features suggestive of breast cancer. BRCA1 promoter hypermethylation and changes in protein expression were evaluated in 30 cancerous and 30 non-cancerous tissue samples. A tissue microarray containing samples from normal and tumor tissue was prepared and stained for BRCA1 protein expression using a commercially available monoclonal antibody against BRCA1 (Ab-1) clone MS110 (mAb). DNA was extracted using modified protocol of Qiagen minikit. DNA was modified using a Bisulfite conversion kit and BRCA1 hypermethylation was detected using a methylation specific PCR. Results: Promoter hypermethylation was negative in 30 non-cancerous samples with retained BRCA1 protein expression. Methylation was positive in 82.6% (n=19/23) of the sporadic cancer samples that had loss of BRCA1 expression and 50% (n=2/4) of the samples with equivocal protein expression. Methylation was negative in all the sporadic breast cancer samples (n=3/3) with retained protein expression. Chi-square analysis showed significant association of BRCA1 promoter methylation with decreased protein expression (P=0.016) and co-existence of loss of BRCA1 and Her2neu at chromosome 17 (P=0.026) respectively. There was no significant association of BRCA1 methylation with morphological features excluding necrosis (P=0.035). Promoter hypermethylation was found to be most common (68.75%) among Triple Negative Breast Cancer (TNBC) females less than 45 years old. Conclusion: Our study suggests that BRCA1 promoter hypermethylation has significant contribution in sporadic breast carcinogenesis. This was our preliminary study in Pakistan. Further studies aimed to determine the in-depth mechanisms of BRCA1 epigenetics in TNBC. BRCAness enriched phenotype in TNBC might be used as a biomarker for the exploitation of therapeutic and clinical implications.
Objectives: This tissue microarray (TMA) immunohistochemical (IHC) study elucidates the role of Wilms’ tumor 1 protein (WT1) in diagnosis and prognostication of astrocytic tumors. Methods: IHC was applied to 75 astrocytic lesions (18 astrogliosis and 57 astrocytic tumors) using antibodies directed against WT1 clone 6F-H2, isocitrate dehydrogenase 1(IDH1), Bcl2 and Ki67. WT1 IHC staining was evaluated and scored blindly by 2 pathologists. Bcl2 and Ki67 scores and labelling indices were assessed and IDH1 status determined. Statistical analysis was performed using the appropriate methodology. Results: WT1 cytoplasmic expression was detected in 89.5% of astrocytic tumors but not in astrogliosis. Positive WT1 differentiated astrocytic tumors (92.6% accuracy) and grade II diffuse astrocytomas (93.5% accuracy) from astrogliosis with high sensitivity, specificity and positive predictive values (p<0.001). Increased WT1 score significantly associated higher Bcl2 and Ki67 labelling indices, increasing WHO tumor grade and tumor’s histopathologic type (p<0.05) showing staining pattern variability by tumor entity and cell type. Glioblastomas, gliosarcomas and subependymal giant cell astrocytomas were the most frequently WT1 expressing tumors with frequent +3 WT1 score. About 21.4% of pilocytic astrocytomas had +3WT1 score in association with increased Bcl2 and Ki67 indices. Low WT1 scores in grade II and III diffuse astrocytomas were linked to the high frequency of IDH1 positivity, and were associated with low Bcl2 and Ki67 labelling indices. In glioblastomas, WT1 significantly associated poor prognostic variables: older age, negative-IDH1 status, high Bcl2 and Ki67 labelling indices (p=0.04, <0.001, =0.001 and
Objective: Transcription factor activating protein 2 B (TFAP2 B) is a transcription factor that regulates many steps of embryogenesis, cell growth, apoptosis and recently oncogenesis and cancer progression. AP-1 is a transcription factor that is a downstream molecule of the MAPK signaling pathway. Juxtaposed with zinc finger gene 1 (JAZF1) is a recently detected transforming growth factor which has a role in carcinogenesis. Hence the present study aimed to assess those markers expression in tissues from patients with such cancer correlation their expression with clinic-pathological findings of the tumor and prognostic and follow-up findings of patients. Methods: We have collected tissue samples from papillary thyroid cancer patients and adjacent non-neoplastic tissues from 80 patients. We assessed the expression of TFAP2B, AP-1 and JAZF1 using immunohistochemistry. Results: Expression of TFAP2B was positively associated with lymph nodes metastases (p=0.003), distant metastases (p=0.002), recurrence of the tumor (p=0.002), unfavourable disease-free survival rate (p=0.003). AP-1 expression is positively associated with advanced stage (p=0.002), presence of extra-thyroid invasion (p=0.005), recurrence of the tumor (p=0.005), unfavorable disease-free survival rate (p=0.01). JAZF1 expression is negatively associated with huge tumor size (0.023), vascular invasion (p=0.007) and unfavorable overall survival rate (p=.030). Conclusion: High expression levels of TFAP2B and AP-1 and low expression levels of JAZF1 were associated with unfavourable pathological, prognostic parameters and dismal patient’s outcome.
Background: Breast cancer is a multifactorial disease that affects women worldwide. Its progression is likely to be executed by oxidative stress wherein elevated levels of reactive oxygen and nitrogen species drive several breast cancer pathologies. Spider venom contains various pharmacological peptides which exhibit selective activity to abnormal expression of ion channels on cancer cell surface which can confer potent anti-cancer activities against this disease. Methods: Venom was extracted from a Philippine tarantula by electrostimulation and fractionated by reverse phase-high performance liquid chromatography (RP-HPLC). Venom fractions were collected and used for in vitro analyses such as cellular toxicity, morphological assessment, and oxidative stress levels. Results: The fractionation of crude spider venom generated several peaks which were predominantly detected spectrophotometrically and colorimetrically as peptides. Treatment of MCF-7 cell line of selected spider venom peptides induced production of several endogenous radicals such as hydroxyl radicals (•OH), nitric oxide radicals (•NO), superoxide anion radicals (•O2−) and lipid peroxides via malondialdehyde (MDA) reaction, which is comparable with the scavenging effects afforded by 400 µg/mL vitamin E and L-cysteine (p<0.05). Concomitantly, the free radicals produced decrease the mitochondrial membrane potential and metabolic activity as detected by rhodamine 123 and tetrazolium dye respectively (p>0.05). This is manifested by cytotoxicity in MCF-7 cells as seen by increase in membrane blebbing, cellular detachment, caspase activity and nuclear fragmentation. Conclusion: These data suggest that the Philippine tarantula venom contains peptide constituents exhibiting pro-oxidative and nitrosative-dependent cytotoxic activities against MCF-7 cells and can indicate mechanistic insights to further explore its potential application as prooxidants in cancer therapy.
Background: H. pylori infection may play a role in the development of colorectal cancers (CRC). We aimed to examine the association between H. pylori infection and the risk of CRC by anatomical locations. Methods: We conducted a case-control study on 91 incidence cases of CRC and 224 hospital controls. CRC was determined by histopathological examinations. H. pylori IgG antibody in serum was tested. We collected data on the diet, nutrition, and lifestyle by the validated semi-quantitative food frequency and demographic lifestyle questionnaire. The odds ratio and 95% confidence interval (OR (95%CI) were estimated for CRC and its subgroups. Results: Overall 54.95% of CRC cases and 42.41% of the controls were H. pylori-seropositive, OR (95%CI): 1.56 (0.88, 2.74), p for trend=0.115. Positive dose-response association in quartiles, highest vs lowest, was observed for total CRC, OR (95%CI): 2.14 (1.00, 4.58), p for trend=0.049, for proximal colon, OR (95%CI): 1.52 (0.37, 6.25), p for trend=0.571), and for distal colon and rectum cancers combined, OR (95%CI): 2.38 (1.03, 5.50), p for trend=0.039. Conclusions: There is a positive association between H. pylori and colorectal cancers, especially distal colon and rectum cancers combined, but additional research is needed to determine the underlying mechanism of chronic H. pylori infection-induced CRC in humans.
Objective: The length of stay is an important indicator of hospital performance and efficiency. Regarding the importance of the length of stay, this study aimed to design a structural model of the inpatients’ length of stay in the educational and therapeutic health care facilities of Iran in order to identify the influencing dimensions. Methods: The present study was an analytical and applied study. The face validity of the data gathering tool was investigated by the expert judgment and the construct validity was examined by using the exploratory factor analysis. In order to verify the reliability of the tool, the internal consistency was also trialed by using the Cronbach’s alpha. For ranking the influencing dimensions and factors and also in order to examine the causal relationships between the variables in a coherent manner and presenting the final model, the structural equation modeling technique was used in AMOS software at a significant level of 0.05. Results: The mentioned structural model consists of 4 dimensions and 29 factors influencing the length of stay of hospitalized patients. The independent variables are based on priority and importance as follows: patients’ conditions, the underlying factors, the clinical staff performance, and hospitals’ service delivery, which were examined by second-order factor analysis in order to study the relationship between them and the inpatients’ length of stay. Conclusion: Considering the importance of each one of the proposed dimensions from the point of view of service providers in some therapeutic centers of the country by paying attention to the role of each one of them in preventing prolonged hospitalization can be essential in the effectiveness of the treatment and cost reduction.
Objective: Oral submucous fibrosis (OSF) is the premalignant disorder associated with fibrosis and epithelial atrophy. Areca Nut (AN) is the most significant risk factors for OSF. However, the molecular mechanism behind AN induced OSF remains unclear, and there exists no effective treatment for the malignant disorder. We aimed to investigate whether AN-extract causes epithelial-mesenchymal transition (EMT) in oral keratinocytes, and evaluated the therapeutic potential of antioxidants. Methods: The HPV16 E6/E7-transfected immortalized human oral keratinocytes (IHOK) were employed in the present study. For the preparation of AN-extract, dried AN was dissolved in distilled water overnight. The solution was centrifuged and the supernatant was collected for further use. For the determination of change in cytokine levels, ELISA was performed. To investigate EMT-related protein expression and phenotype, immunoblot and immunofluorescence were performed. Results: Among tumor-promoting cytokines (Gro-α, IL-6 and IL-8), IL-6 was remarkably increased by AN in IHOK. AN-extract induced EMT phenotypes, such as cell elongation, up-regulation of vimentin and snail. After treatment with neutralizing antibody of IL-6, AN-induced snail expression was reduced remarkably. Collectively, AN-extract induced IL-6 expression and mediated EMT. The use of antioxidants (EGCG, glutathione and NAC) significantly reduced IL-6 expression in AN-treated IHOK. Also, AN-decreased E-cadherin and increased vimentin were reversed by antioxidants, indicating that the effectiveness of antioxidants in inhibiting IL-6-induced EMT by AN. Conclusion: AN promotes EMT and antioxidants interrupt AN-induced-EMT in oral keratinocytes. Consequently, it is proposed that antioxidants could prevent AN-induced carcinogenesis and function as a prototype for developing therapeutic interventions of OSF.
The chemotherapy drug doxorubicin (DOX) is effective in treating many types of cancers. However, due to its pro-inflammatory and cardiotoxic side effects, other remedies have also been explored as alternative treatments. The plant Alangium longiflorum was reported to contain cytotoxic activity against cancer cells, but it is unclear whether this plant would also yield side effects similar to doxorubicin. Hence, this study investigated cytotoxic activity of A. longiflorum leaf extract against lung cancer cells and compared its pro-inflammatory and cardiotoxic side effects with those of DOX. Methods: Cytotoxic activity of A. longiflorum in human lung (A549) and breast (MCF-7) cancer cells was initially assessed by MTT assay and then was compared with doxorubicin. Presence of secondary metabolites in the leaf extract was examined by phytochemical screening. The ability of the plant extract to induce apoptosis was determined by measuring caspase-3/7 activity and apoptosis-related gene expression. Pro-inflammatory response was assessed by quantifying NFκB transcriptional activity and nuclear translocation with dual luciferase reporter and immunofluorescence assays, respectively. Cardiotoxicity was measured using zebrafish as a model organism. Results: A. longiflorum leaf extract displayed high cytotoxic activity against A549 versus MCF-7, which led this study to focus further on A549. Phytochemical screening showed that the extract contained terpenoids, alkaloids, phenols, cardiac glycosides, and tannins. The extract induced apoptosis through activation of caspase-3/7 and upregulation of pro-apoptotic genes without causing NFκB transcriptional activation and nuclear localization. The extract also did not significantly reduce heart function in zebrafish. Conclusion: Overall, our data suggested that extract from leaves of A. longiflorum can have the potential to serve as apoptotic agent towards lung cancer without inducing significant cardiotoxicity.
Objective: Metabolic processes in the body of people with and without esophageal cancer (EC) are significantly different. Therefore, changes in the metabolism of amino acids in the body of EC patients can lead to metabolic disorders, such as increased gluconeogenesis. The aim of this study was the comparison of the plasma levels of gluconeogenic amino acids between patients with EC and the control group. Methods: Plasma samples of 37 patients with EC who were selected before any treatment or surgery, and 37 healthy adults who did not have history of family cancer and malignant diseases were taken. Analysis of the plasma levels of amino acids including, alanine, asparagine, aspartate, glutamate, glutamine, glycine, serine, arginine, histidine, methionine, threonine, valine, tyrosine, isoleucine, phenylalanine, tryptophan was done by High Performance Liquid Chromatography (HPLC) based on reverse-phase-chromatography. Data analysis was done by SPSS-16 software. Results: In the patient group the mean age ± SD was 63±13.64 and 21 (56.8%) were male.The plasma levels of the alanine, asparagine, histidine, methionine, threonine, valine amino acids in the patients with esophageal cancer was significantly reduced and glycine was increased (p-value<0.05). Conclusion: Gluconeogenic amino acids are the main precursor of glucose synthesis in the gluconeogenesis pathway. Cancer cells need more energy to grow and multiply, and glucose is used as the main fuel for cells. Given the importance of metabolic pathways in cancer cells, more detailed studies at the molecular level can provide new insights into early detection and appropriate treatment strategies for cancer.
Objective: Many studies suggested that fucoidan has anticancer potential. The objective of the present study was to determine the cytotoxic effects and mechanism of cell death induced by fucoidan extracted from Fucus vesiculosus on HSC-3 oral squamous cell carcinoma. Methods: HSC-3 cells were treated with 0, 100, 200, and 400 μg/mL of fucoidan. Cell viability was measured using MTT assay. Apoptosis and cell cycle were measured with a flow cytometry-based assay. Chromatin condensation and nuclear fragmentation were determined using Hoechst 33342 staining. Mitochondrial membrane potential (ΔΨm) was determined using the JC-1 kit. The apoptotic, anti-apoptotic, and autophagic markers study were done by western blot analysis. Results: the viable cell number of treated HSC-3 cells was decreased. Moreover, treated cells were arrested in the G0/G1 phase. Annexin V/PI staining revealed that fucoidan could induce apoptosis in HSC-3 cells. Western blot analysis suggested the up-regulation of apoptotic markers including cleaved caspase-3, cleaved PARP, Bax, and autophagic markers including LC3-II and Beclin-1 but down-regulation of anti-apoptotic markers, Bcl-2. Fucoidan could disturb ΔΨm and induce chromatin condensation with nuclear fragmentation. Conclusion: fucoidan has potential in anticancer properties against HSC-3 cells manifested by the induction of apoptosis, cell cycle arrest, and autophagy.
Background: Today, the role of microRNAs in the pathogenesis of breast cancer has been established. Genetic mutations play a significant role in determining the risk factors of cancer. The polymorphism of these two genes can alter their expression. This study has been performed to investigate the relationship between polymorphisms of rs6715345 of miR-375 gene and rs4939827 of the SMAD7 gene and development of breast cancer in a population in southeastern Iran. Methods: This case-control study was performed on the blood sample of 205 patients with breast cancer and 200 healthy individuals for investigating the rs34917480 and rs4939827 polymorphisms using the PCR-RFLP method. The data were analyzed by t-test, χ2, and logistic regression. The SPSS v18.0 used for data analysis. Results: The findings of this study indicated that the risk of developing breast cancer does not have a significant relationship with rs6715345 polymorphism of miR-375 gene (p<0.1). However, the rs4939827 polymorphism of the SMAD7 gene was significantly linked to the risk of developing breast cancer in the southeastern population in Iran (p>0.01). Conclusion: The results suggest that the rs4939827 polymorphism of the SMAD7 gene can lead to an increased risk of incidence of breast cancer in the southeastern population in Iran.