• Journal of Pharmacopuncture
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• v.22 no.2
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• pp.95-101
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• 2019

Objectives: Angiotensin II (AngII), a major product of renin-angiotensin system (RAS) has important role in induction of hypertension and antihypertensive effect of several medicinal plant was mediated by effect on this agent. Therefore, this study examined the possible effect of hydroalcoholic extract of Crocus sativus (C. sativus) on hypertension induced by AngII. Methods: Six groups (n = 6) of rats were used as follow: 1) Control, 2) AngII (300 ng/kg), 3) Losartan (Los, 10 mg/kg) + AngII and 4-6) C. sativus extract (10, 20 & 40 mg/kg,) + AngII. The femoral artery and vein were cannulated for recording cardiovascular parameters and drugs administration, respectively. All drugs were injected intravenously (i.v). Los and all doses of C. sativus injected 10 min before AngII. Systolic blood pressure (SBP), mean arterial blood pressure (MAP) and heart rate (HR) were recorded throughout the experiment and those peak changes (${\Delta}$) were calculated and compared to control and AngII. Results: AngII significantly increased ${\Delta}MAP$, ${\Delta}SBP$ and ${\Delta}HR$ than control (P < 0. 01 to P < 0.001) and these increments were significantly attenuated by Los. All doses of C. sativus significantly reduced peak ${\Delta}MAP$, ${\Delta}SBP$, and ${\Delta}HR$ than AngII group (P < 0. 05 to P < 0.001). In addition, peak ${\Delta}MAP$, ${\Delta}SBP$ in doses 10 and 20 were significant than Los + AngII group (P<0.05 to P< 0.01) but in dose 40 only MAP was significant (P<0.05). Peak ${\Delta}HR$ in all doses of C sativus was not significant than Los+ AngII. Conclusion: Regarding the improving effect of the C. sativus extract on AngII induced hypertension, it seems that this ameliorating effect partly mediated through inhibition of RAS.

• Genomics & Informatics
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• v.20 no.3
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• pp.27.1-27.13
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• 2022

Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck malignancy, with frequent cervical lymph-node metastasis, leading to a poor prognosis in OSCC patients. The present study aimed to identify potential markers, including microRNAs (miRNAs) and genes, significantly involved in the etiology of early-stage OSCC. Additionally, the main OSCC's dysregulated Gene Ontology annotations and significant signaling pathways were identified. The dataset GSE45238 underwent multivariate statistical analysis in order to distinguish primary OSCC tissues from healthy oral epithelium. Differentially expressed miRNAs (DEMs) with the criteria of p-value < 0.001 and |Log2 fold change| > 1.585 were identified in the two groups, and subsequently, validated targets of DEMs were identified. A protein interaction map was constructed, hub genes were identified, significant modules within the network were illustrated, and significant pathways and biological processes associated with the clusters were demonstrated. Using the GEPI2 database, the hub genes' predictive function was assessed. Compared to the healthy controls, main OSCC had a total of 23 DEMs. In patients with head and neck squamous cell carcinoma (HNSCC), upregulation of CALM1, CYCS, THBS1, MYC, GATA6, and SPRED3 was strongly associated with a poor prognosis. In HNSCC patients, overexpression of PIK3R3, GIGYF1, and BCL2L11 was substantially correlated with a good prognosis. Besides, "proteoglycans in cancer" was the most significant pathway enriched in the primary OSCC. The present study results revealed more possible mechanisms mediating primary OSCC and may be useful in the prognosis of the patients with early-stage OSCC.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.11
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• pp.5469-5475
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• 2012

Background and Objectives: Acute lymphoblastic leukemia (ALL) is a complex genetic disease involving many fusion oncogenes (FO) having prognostic significance. The frequency of various FO can vary in different ethnic groups, with important implications for prognosis, drug selection and treatment outcome. Method: We studied fusion oncogenes in 101 pediatric ALL patients using interphase FISH and RT-PCR, and their associations with clinical features and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL t (22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 89/101 (88.1%) patients. Frequency of BCR-ABL was 44.5% (45/101). BCR-ABL positive patients had a significantly lower survival ($43.7{\pm}4.24$ weeks) and higher white cell count as compared to others, except patients with MLL-AF4. The highest relapse-free survival was documented with ETV6-RUNX1 (14.2 months) followed closely by those cases in which no gene was detected (13.100). RFS with BCR-ABL, MLL-AF4, TCF3-PBX1 and SIL-TAL1 was less than 10 months (8.0, 3.6, 5.5 and 8.1 months, respectively). Conclusions: This is the first study from Pakistan correlating molecular markers with disease biology and treatment outcome in pediatric ALL. It revealed the highest reported frequency of BCR-ABL FO in pediatric ALL, associated with poor overall survival. Our data indicate an immediate need for incorporation of tyrosine kinase inhibitors in the treatment of BCR-ABL+ pediatric ALL in this population and the development of facilities for stem cell transplantation.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.585-589
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• 2015

Physical inactivity may an important outcome in the prognosis of breast cancer. Physical activity levels decrease significantly for breast cancer patients following the treatment and remain low after oncology treatment is completed. The aim of this study was to determine physical activity levels and to examine associations among physical activity, comorbidity, functional capacity, peripheral muscle strength, and psychosocial status in breast cancer patients. Forty breast cancer survivors were included in this study. Demographic and clinical characteristics were recorded. Physical activity was assessed with a short form of the International Physical Activity Questionnaire (IPAQ). We defined comorbid diseases according to the Charlson Comorbidity Index (CCI). Functional capacity was evaluated with a six-minute walk test (6MWT). Peripheral muscle strength was measured for quadriceps femoris muscle with a hand-held dynamometer. Psychosocial status was measured with the Hospital Anxiety Depression Scale (HADS). Forty percent of patients were inactive. The IPAQ total score was significantly related with quadriceps muscle strength (r=0.492; p<0.001) and HADS depression score (r=0.341; p<0.05). Marked correlations were also observed between IPAQ walking score and quadriceps muscle strength (r=0.449; p<0.001), HADS depression score (r=0.341; p<0.05), and CCI (r=-0.433; p<0.001). The CCI score was also markedly associated with quadriceps muscle strength (r=-0.413; p<0.001). 6MWT distance was not significantly correlated with any of the parameters. Regression analyses revealed that psychosocial status and peripheral muscle strength were significant predictors of physical activity estimated with the IPAQ short form and when combined, they explained 35% of the variance. Comorbidities, peripheral muscle strength and psychosocial status partially explain the variability of physical activity level in breast cancer survivors. These results suggest that physical inactivity contributes to worsening health in breast cancer survivors.

• Genomics & Informatics
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• v.20 no.4
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• pp.44.1-44.13
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• 2022

Brugada syndrome (BS) is an autosomal dominant inheritance cardiac arrhythmia disorder associated with sudden death in young adults. Thailand has the highest prevalence of BS worldwide, and over 60% of patients with BS still have unclear disease etiology. Here, we performed a new viral metagenome analysis pipeline called VIRIN and validated it with whole genome sequencing (WGS) data of HeLa cell lines and hepatocellular carcinoma. Then the VIRIN pipeline was applied to identify viral integration positions from unmapped WGS data of Thai males, including 100 BS patients (case) and 100 controls. Even though the sample preparation had no viral enrichment step, we can identify several virus genes from our analysis pipeline. The predominance of human endogenous retrovirus K (HERV-K) viruses was found in both cases and controls by blastn and blastx analysis. This study is the first report on the full-length HERV-K assembled genomes in the Thai population. Furthermore, the HERV-K integration breakpoint positions were validated and compared between the case and control datasets. Interestingly, Brugada cases contained HERV-K integration breakpoints at promoters five times more often than controls. Overall, the highlight of this study is the BS-specific HERV-K breakpoint positions that were found at the gene coding region "NBPF11" (n = 9), "NBPF12" (n = 8) and long non-coding RNA (lncRNA) "PCAT14" (n = 4) region. The genes and the lncRNA have been reported to be associated with congenital heart and arterial diseases. These findings provide another aspect of the BS etiology associated with viral genome integrations within the human genome.

• Parasites, Hosts and Diseases
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• v.55 no.4
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• pp.367-374
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• 2017

Despite the broad distribution of leishmaniasis among Iranians and animals across the country, little is known about the genetic characteristics of the causative agents. Applying both HSP70 PCR-RFLP and sequence analyses, this study aimed to evaluate the genetic diversity and phylogenetic relationships among Leishmania spp. isolated from Iranian endemic foci and available reference strains. A total of 36 Leishmania isolates from almost all districts across the country were genetically analyzed for the HSP70 gene using both PCR-RFLP and sequence analysis. The original HSP70 gene sequences were aligned along with homologous Leishmania sequences retrieved from NCBI, and subjected to the phylogenetic analysis. Basic parameters of genetic diversity were also estimated. The HSP70 PCR-RFLP presented 3 different electrophoretic patterns, with no further intraspecific variation, corresponding to 3 Leishmania species available in the country, L. tropica, L. major, and L. infantum. Phylogenetic analyses presented 5 major clades, corresponding to 5 species complexes. Iranian lineages, including L. major, L. tropica, and L. infantum, were distributed among 3 complexes L. major, L. tropica, and L. donovani. However, within the L. major and L. donovani species complexes, the HSP70 phylogeny was not able to distinguish clearly between the L. major and L. turanica isolates, and between the L. infantum, L. donovani, and L. chagasi isolates, respectively. Our results indicated that both HSP70 PCR-RFLP and sequence analyses are medically applicable tools for identification of Leishmania species in Iranian patients. However, the reduced genetic diversity of the target gene makes it inevitable that its phylogeny only resolves the major groups, namely, the species complexes.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.113-117
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• 2016

Quantile regression is an efficient method for predicting and estimating the relationship between explanatory variables and percentile points of the response distribution, particularly for extreme percentiles of the distribution. To study the relationship between urbanization and cancer morbidity, we here applied quantile regression. This cross-sectional study was conducted for 9 cancers in 345 cities in 2007 in Iran. Data were obtained from the Ministry of Health and Medical Education and the relationship between urbanization and cancer morbidity was investigated using quantile regression and least square regression. Fitting models were compared using AIC criteria. R (3.0.1) software and the Quantreg package were used for statistical analysis. With the quantile regression model all percentiles for breast, colorectal, prostate, lung and pancreas cancers demonstrated increasing incidence rate with urbanization. The maximum increase for breast cancer was in the 90th percentile (${\beta}$=0.13, p-value<0.001), for colorectal cancer was in the 75th percentile (${\beta}$=0.048, p-value<0.001), for prostate cancer the 95th percentile (${\beta}$=0.55, p-value<0.001), for lung cancer was in 95th percentile (${\beta}$=0.52, p-value=0.006), for pancreas cancer was in 10th percentile (${\beta}$=0.011, p-value<0.001). For gastric, esophageal and skin cancers, with increasing urbanization, the incidence rate was decreased. The maximum decrease for gastric cancer was in the 90th percentile(${\beta}$=0.003, p-value<0.001), for esophageal cancer the 95th (${\beta}$=0.04, p-value=0.4) and for skin cancer also the 95th (${\beta}$=0.145, p-value=0.071). The AIC showed that for upper percentiles, the fitting of quantile regression was better than least square regression. According to the results of this study, the significant impact of urbanization on cancer morbidity requirs more effort and planning by policymakers and administrators in order to reduce risk factors such as pollution in urban areas and ensure proper nutrition recommendations are made.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.2
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• pp.141-150
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• 2008

We studied 1809 oral cancer patients who visited and were treated in 2002 at the 148 institutions certified as training facilities by the Japanese Society of Oral and Maxillofacial Surgeons, which is composed of 39 dental university hospitals, 44 medical university hospitals, 64 general hospitals, and 1 unknown institution. The patients consisted of 1071 (59.2%) males and 738 (40.8%) females (male:female ratio, 1.45:1), who had a mean age of 65.2 years old. The tongue (40.2%) was the most common site affected, followed by the gingiva (32.7%), buccal mucosa (10.1%), and oral floor (9.0%). There were 6 cases of intraoral multiple cancer. In histopathological examinations, squamous cell carcinoma (88.7%) was the most common type found, followed by adenoid cystic carcinoma (2.1%), and mucoepidermoid carcinoma (1.7%). In addition, non-epithelial tumors comprised 1.8%, among which malignant melanoma was the most common type. Cases classified as T2N0 were the most common (32.1%), followed by T1N0 (21.4%), T4N0 (8.0%), and T2N1 (7.6%). Distant metastasis occurred in 17 patients (1.0%). The sizes of the non-epithelial malignant tumors ranged from 1.0 to 7.0 cm, with a mean size of 3.7 cm.

• Anatomy and Cell Biology
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• v.56 no.3
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• pp.304-307
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• 2023

The nervus conarii provides sympathetic nerve innervation to the pineal gland, which is thought to be the primary type of stimulus to this gland. This underreported nerve has been mostly studied in animals. One function of the nervus conarii may be to activate pinealocytes to produce melatonin. Others have also found substance P and calcitonin gene-related peptide from the nervus conarii ending in the pineal gland. The following paper reviews the extant medical literature on the nervus conarii including its anatomy and potential function.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.33-38
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• 2014

Background: Meningiomas are the second most common primary intracranial tumors after gliomas. Epigenetic biomarkers such as DNA methylation, which is found in many tumors and is thus important in tumorigenesis can help diagnose meningiomas and predict response to adjuvant chemotherapy. We investigated aberrant O6-methyl guanine methyltransferase (MGMT) methylation in meningiomas. Materials and Methods: Sixty-one patients were classified according to the WHO grading, and MGMT promoter methylation status was examined via the methylation-Specific PCR(MSP) method. Results: MGMT promoter methylation was found in 22.2% of grade I, 35% of grade I with atypical features, 36% of grade II, and 42.9% of grade III tumors. Conclusions: There was an increase, albeit not statistically significant, in MGMT methylation with a rise in the tumor grade. Higher methylation levels were also observed in the male gender.