• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2433-2437
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• 2013

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in the development and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634 G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently available results are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms and breast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680 female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the three VEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46, 95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) had a protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikely to be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumor aggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47, 95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regional or distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed that the VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Han patients.

• 한국임상약학회지
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• 제21권2호
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• pp.122-130
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• 2011

Objective: Although recombinant human erythropoietin (rhEPO) has revolutionized the treatment of anemia in chronic kidney disease (CKD) receiving hemodialysis (HD) with no need of blood transfusion, some patients have a blunted or appear to be resistant to rhEPO. There is a controversy in the causes of rhEPO resistance in maintenance HD patients with anemia. This study is to examine current anemia treatment outcomes and the factors influencing the rhEPO responsiveness in HD patient with CKD. Methods: The clinical parameters or factors relating to erythrompoietin treatment outcomes and erythropoietin responsiveness were collected from the HD patients in two large dialysis centers for three months. The collected paramenters included serum iron, total iron biding capacity (TIBC), transferrin saturation rate, ferritin, albumin, intact PTH, C-reactive protein (CRP), nPCR and medications such as an angiotensin converting enzyme inhbitor, an angiotension II receptor blocker and an HMG-CoA reductase inhibitor (HMG-CoA RI). The data were analyzed to examine the degree of acheiveing the anemia treatment goal and factors relating to ERI. Results: Among total 111 patients, 42 (42.3%) and 47 (37.8%) patients achieved the target Hct and Hb based on the Health Insurance Review and Assessment Services (HIRA) reimbursement criteria. In the higher ERI group (upper quartile), the patients had higher CRP levels (0.5 mg/dl) (p=0.0096), and lower TIBC score (<$240{\mu}g/dl$) (p=0.0027), and less patients were taking HMG-CoA RI (p=0.0019). Male patients (p=0.0204), patients with high TIBC score ($R^2$=0.084, p=0.0021) and patients taking HMG-CoA RI (p=0.0052) required to administer less dose of rhEPO meaning higher erythropoietin responsiveness. Conclusion: Less than 50% of CKD patients were achieving the goals of anemia by erythropoietin administration in large hospitals in Korea even though the goals were lower than those of NKF-K/DOQI practice guideline. The factors influencing ERI were sex, TIBC and HMG-CoA RI administration status, and neither an ACEI nor an ARB did not influence ERI.

• 대한약침학회지
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• 제16권3호
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• pp.11-22
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• 2013

Objectives: The present investigation aimed at examining if post-cancer treatment with a potentized homeopathic drug, Condurango 30C, which is generally used to treat oesophageal cancer, could also show an ameliorating effect through apoptosis induction on lung cancer induced by benzo[a]pyrene (BaP) in white rats (Rattus norvegicus). Methods: Lung cancer was induced after four months by chronic feeding of BaP to rats through gavage at a dose of 50 mg/kg body weight for one month. After four months, the lung-cancer-bearing rats were treated with Condurango 30C for the next one ($5^{th}$), two ($5^{th}-6^{th}$) and three ($5^{th}-7^{th}$) months, respectively, and were sacrificed at the corresponding time-points. The ameliorating effect, if any, after Condurango 30C treatment for the various periods was evaluated by using protocols such as histology, scanning electron microscopy (SEM), annexinV-FITC/PI assay, flow cytometry of the apoptosis marker, DNA fragmentation, reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and western blot analyses of lung tissue samples. Results: Striking recovery of lung tissue to a near normal status was noticed after post-cancerous drug treatment, as evidenced by SEM and histology, especially after one and two months of drug treatment. Data from the annexinV-FITC/PI and DNA fragmentation assays revealed that Condurango 30C could induce apoptosis in cancer cells after post-cancer treatment. A critical analysis of signalling cascade, evidenced through a RT-PCR study, demonstrated up-regulation and down-regulation of different pro- and anti-apoptotic genes, respectively, related to a caspase-3-mediated apoptotic pathway, which was especially discernible after one-month and two-month drug treatments. Correspondingly, Western blot and immunohistochemistry studies confirmed the ameliorative potential of Condurango 30C by its ability to down-regulate the elevated epidermal growth factor receptor (EGFR) expression, a hallmark of lung cancer. Conclusion: The overall result validated a positive effect of Condurango 30C in ameliorating lung cancer through caspase-3-mediated apoptosis induction and EGFR down-regulation.

• Asian-Australasian Journal of Animal Sciences
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• 제33권7호
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• pp.1156-1166
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• 2020

Objective: The aim of this study was to evaluate the effects of compound organic acid calcium (COAC) on growth performance, hepatic antioxidant status and intestinal barrier of male broilers under high ambient temperature (32.7℃). Methods: Nine hundred healthy one-d-old Cobb-500 male broiler chicks were randomly assigned into three groups with six replicates of 50 birds each. A basal diet supplemented with 0% (control), 0.4% and 0.8% COAC, respectively were fed to birds for 6 weeks. All treatments were under high ambient indoor temperature of 32.7℃, and had a constant calcium and available phosphorus ratio. Results: The results showed that, compared with control, the average daily gain of broilers in 0.4% and 0.8% was significantly increased and the ratio of feed to gain in in 0.4% and 0.8% was significantly decreased at 1 to 21, 22 to 42 and 1 to 42 days of age (p<0.05). Compared with control, 0.8% COAC slightly decreased (p = 0.093) the content of malondialdehyde in liver at 42 days of age while 0.4% COAC significantly decreased (p<0.05) the activity of alkaline phosphatase. Furthermore, 0.4% COAC significantly enhanced the intestinal barrier function via increasing jejunal and ileal ocln transcription, promoting jejunal mucin 2 transcription at 42 days of age (p<0.05), and decreasing jejunal toll-like receptor 2 (TLR-2) and ileal TLR-15, inducible nitric oxide synthase compared with control group (p<0.05). Whereas, no significant differences on the transcription of interleukin-1β in jejunum and ileum were observed among three treatments (p>0.05). Overall, heat stress caused by high natural environment temperature may induce the damage to hepatic antioxidation and intestinal barrier. Conclusion: Dietary inclusion of COAC can improve the tolerance of broilers to thermal environment through the modification of antioxidative parameters in liver and the mRNA expression of genes in intestinal barrier, resulting in an optimal inclusion level of 0.4%.

• Asian-Australasian Journal of Animal Sciences
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• 제25권1호
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• pp.44-51
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• 2012

Calcium ions play an important role in the establishment and maintenance of pregnancy, but molecular and cellular regulatory mechanisms of calcium ion action in the uterine endometrium are not fully understood in pigs. Previously, we have shown that calcium regulatory molecules, transient receptor potential vanilloid type 5 (TRPV6) and calbindin-D9k (S100G), are expressed in the uterine endometrium during the estrous cycle and pregnancy in a pregnancy status- and stage-specific manner, and that estrogen of conceptus origin increases endometrial TRPV6 expression. However, regulation of S100G expression in the uterine endometrium and conceptus expression of S100G has been not determined during early pregnancy. Thus, we investigated regulation of S100G expression by estrogen and interleukin-$1{\beta}$ (IL1B) in the uterine endometrium and conceptus expression of S100G during early pregnancy in pigs. We obtained uterine endometrial tissues from day (D) 12 of the estrous cycle and treated with combinations of steroid hormones, estradiol-$17{\beta}$ ($E_2$) and progesterone ($P_4$), and increasing doses of IL1B. Real-time RT-PCR analysis showed that $E_2$ and IL1B increased S100G mRNA levels in the uterine endometrium, and conceptuses expressed S100G mRNA during early pregnancy, as determined by RT-PCR analysis. To determine if endometrial expression of S100G mRNA during the implantation period was affected by the somatic cell nuclear transfer (SCNT) procedure, we compared S100G mRNA levels in the uterine endometrium from gilts with SCNT-derived conceptuses with those from gilts with conceptuses derived from natural mating on D12 of pregnancy. Real-time RT-PCR analysis showed that levels of S100G mRNA in the uterine endometrium from gilts carrying SCNT-derived conceptuses was significantly lower than those from gilts carrying conceptuses derived from natural mating. These results showed that S100G expression in the uterine endometrium was regulated by estrogen and IL1B of conceptus origin, and affected by the SCNT procedure during early pregnancy. These suggest that conceptus signals regulate S100G, an intracellular calcium transport protein, for the establishment of pregnancy in pigs.

• Radiation Oncology Journal
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• 제37권2호
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• pp.91-100
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• 2019

Purpose: Internal mammary lymph node (IMN) involvement is associated with poor prognosis in breast cancer. This study investigated the treatment outcomes of initial clinically IMN-positive breast cancer patients who received adjuvant radiotherapy (RT), including IMN irradiation, following primary breast surgery. Materials and Methods: We retrospectively reviewed data of 95 breast cancer patients with clinically detected IMNs at diagnosis treated with surgery and RT between June 2009 and December 2015. Patients received adjuvant RT to the whole breast/chest wall and regional lymph node (axillary, internal mammary, and supraclavicular) areas. Twelve patients received an additional boost to the IMN area. Results: The median follow-up was 43.2 months (range, 4.5 to 100.5 months). Among 77 patients who received neoadjuvant chemotherapy, 52 (67.5%) showed IMN normalization and 19 (24.6%) showed a partial response to IMN. There were 3 and 24 cases of IMN failure and any recurrence, respectively. The 5-year IMN failure-free survival, disease-free survival (DFS), and overall survival (OS) were 96%, 70%, and 84%, respectively. IMN failure-free survival was significantly affected by resection margin status (97.7% if negative, 87.5% for close or positive margins; p = 0.009). All three patients with IMN failure had initial IMN size ≥1 cm and did not receive IMN boost irradiation. The median age of the three patients was 31 years, and all had hormone receptor-negative tumors. Conclusion: RT provides excellent IMN control without the support of IMN surgery. Intensity-modulated radiotherapy, including IMN boost for breast cancer patients, is a safe and effective technique for regional lymph node irradiation.

• Asian Pacific Journal of Cancer Prevention
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• 제16권2호
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• pp.541-549
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• 2015

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with higher metastatic rate and both local and systemic recurrence compared to non-TNBC. The generation of reactive oxygen species (ROS) secondary to oxidative stress is associated with DNA damage, chromosomal degradation and alterations of both hypermethylation and hypomethylation of DNA. This study concerns differential methylation of promoter regions in specific groups of genes in TNBC and non-TNBC Saudi females in an effort to understand whether epigenetic events might be involved in breast carcinogenesis, and whether they might be used as markers for Saudi BCs. Methylation of glutathione S-transferase P1 (GSTP1), T-cadherin (CDH13), Paired box protein 5 (PAX5), death associated protein kinase (DAPK), twist-related protein (TWIST), DNA-binding protein inhibitor (ID4), High In Normal-1 (HIN-1), cyclin-dependent kinase inhibitor 2A (p16), cyclin D2 and retinoic acid receptor-${\beta}$ ($RAR{\beta}1$) genes was analyzed by methylation specific polymerase chain reaction (MSP) in 200 archival formalin-fixed paraffin embedded BC tissues divided into 3 groups; benign breast tissues (20), TNBC (80) and non-TNBC (100). The relationships between methylation status, and clinical and pathological characteristics of patients and tumors were assessed. Higher frequencies of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 hypermethylation were found in TNBC than in non-TNBC. Hypermethylation of GSTP1, CDH13, ID4, DAPK, HIN-1 and PAX5 increased with tumor grade increasing. Other statistically significant correlations were identified with studied genes. Data from this study suggest that increased hypermethylation of GSTP1, ID4, TWIST, DAPK, PAX5 and HIN-1 genes in TNBC than in non-TNBC can act as useful biomarker for BCs in the Saudi population. The higher frequency of specific hypermethylated genes paralleling tumor grade, size and lymph node involvement suggests contributions to breast cancer initiation and progression.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1471-1477
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• 2015

Background: Adding taxanes to adjuvant antracycline and cyclophosphamide (AC) in combination may provide significant improvement in node-positive and high risk node-negative breast cancer (BC) patients. However, the optimal dose and the role of dose-dense (DD) chemotherapy have yet to be determined. The aim of this study was to compare the efficacy of a DD paclitaxel (P)-AC combination with conventional weekly P-AC or docetaxel D-AC combinations in patients with node-positive breast cancer. Materials and Methods: Newly diagnosed 280 node-positive BC patients diagnosed from 1998 to 2013 in three clinics were retrospectively analyzed. Demographic and medical data were collected from the medical charts. Patients were categorized to 3 groups according to treatment arms: arm A, ddAC-P; arm B, weekly P and AC combination; and arm C; T and AC combination. Adjuvant trastuzumab was added for HER2-positive patients. Kaplan-Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). The log-rank test was used to examine the statistical significance of the differences observed between the groups. Two-sided P values <0.05 were considered statistically significant. Results: Of the total of 280 patients, 101 were in arm A, 114 in arm B and 65 in arm C.The median ages were 49, 50 and 46, respectively (p=0.11). Median follow-up was 39 (3-193) months. Stage, lymphovascular and perineural invasion, receptor patern, and menopausal status were similar in the 3 treatment arms, but HER2 positivity was significantly lower in arm A, compared to arms B and C (25.7%, 53.1%, 41.5% in arms A, B and C, respectively; p<0.001). Also grade 3 tumors were significantly less frequent in treatment arm A compared to arm B and C (27.3%, 56.8% and 49.2%, respectively, p=0.01). Afterunivariate and multivariate analysis were performed, 3-year DFS rates were 89%, 81%, and 75%, respectively (p=0.12) and three year OS rates were 96.6%, 89%, and 75% (p=0.62). Conclusions: In this study, no significant difference was found between adjuvant dose dense and conventional taxane treatment regimens.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5257-5261
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• 2012

Background: High incidence of breast cancer and its fatal effect has reached an alarming stage across the globe, including the third world countries. Many factors have been reported to be associated with the development of breast cancer but detailed structural and functional information is missing. CA 15-3 is one of the known potential tumor marker of breast cancer; however little is known about structure and functional site of this protein. Present study aims to investigate the functional role of CA 15-3 in breast cancer, especially in development and metastasis. Material and Methods: Hundred female breast cancer patients confirmed by histopathological reports were included in the study. Their physiological characters were recorded in a performa. Enzyme linked immunosorbent assay (ELISA) technique was used to estimate serum CA 15-3 level. Immunohistochemistry was done for estrogen (ER), progesterone (PR) and Her2/neu receptors expression. Results: The study revealed the details of physiological characteristics of female breast cancer. Mean age was $37.72{\pm}5.99$ and $55.05{\pm}7.28$ years and serum CA 15-3 (MUC1) level was $60.47{\pm}8.59$ and $63.17{\pm}4.58$ U/ml in pre and post-menopause respectively, and both groups of women had sedentary life style. Their receptor status especially of progesterone, estrogen and HER-2/neu were positive in 50% of premenopausal women and 65% of postmenopausal women. Conclusion: There are multiple physiological factors promoting breast cancer. High serum CA 15-3 level and hormonal imbalance of ER, PR and Her2/neu appears to be the main cause of breast cancer. It may be possible that the functional sites of these proteins may be altered which may increase the chances of metastasis in breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.957-961
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• 2014

Purpose: With regard to the protective effect of vitamin D against colorectal cancer (CRC), we evaluated genetic variants that might influence vitamin D metabolism: vitamin D receptor (VDR), vitamin D binding protein (GC), vitamin D 25-hydroxylase (CYP2R1), and vitamin D 25-hydroxy 1-alpha hydroxylase (CYP27B1). Materials and Methods: A total of 657 subjects, including 303 cases with CRC and 354 controls were enrolled in this case-control study. All 657 were genotyped for the four gene variants using PCR-RFLP methods. Results: In this study, no significant difference was observed for VDR (rs2238136), GC (rs4588), CYP2R1 (rs12794714), and CYP27B1 (rs3782130) gene variants in either genotype or allele frequencies between the cases with CRC and the controls and this lack of difference remained even after adjustment for age, BMI, sex, smoking status, NSAID use, and family history of CRC. Furthermore, no evidence for effect modification of the variants and CRC by BMI, sex, or tumor site was observed. Conclusions: Our findings do not support a role for VDR, GC, and CYP27B1 genes in CRC risk in our Iranian population. Another interesting finding, which to our knowledge has not been reported previously, was the lack of association with the CYP2R1 gene polymorphism. Nonetheless, our findings require confirmation and possible roles of vitamin D metabolism-related genes in carcinogenesis need to be further investigated.