The impact of income and education level on the clinical and pathologic characteristics, implementation of clinical breast examination (CBE), and treatment patterns of a small population of Chinese female breast cancer patients was studeied in order to provide a theoretical basis and statistical reference for further nationwide research. We included 484 pathologically confirmed female primary breast cancer inpatients of the First Affiliated Hospital of Medical College of Xi'an Jiaotong University from February 2003 to January 2004. All cases were reviewed and relevant information was collected using a designed case report form (CRF). Chisquare tests, rank-sum tests, and Fisher's exact tests were used in the analysis. Our analysis showed that: (1) women in different occupation groups had significant differences in tumor size, pre-operative mammography, surgical options, post-operative estrogen receptor (ER), progestin receptor (PR) and human epidermal growth factor receptor 2 (Her2) status, and post-operative radiotherapy and chemotherapy (P < 0.05); and (2) women with different education levels had statistically significant differences in tumor size, post-operative ER, PR and Her2 status, and post-operative chemotherapy, radiotherapy, and endocrine therapy (P < 0.05). In Xi'an, China, women in low-income occupations or with low education levels are more likely to have advanced tumor stages at presentation, lower implementation rate of clinical breast examination, and less treatment.
Recent studies have shown that environmental, biochemical, nutritional or genetic factors affect bone mineral density (BMD). The purpose of the present study was to investigate the effect of vitamin D receptor (VDR) gentotype and nutritional status on BMD of elderly women living in a rural area. Three hundred thirty five elderly women over 65 years in Asan participated the study. Data for demographic and nutrient intakes were obtained by survey with a two day 24 hr recall method. BMD was measured by broadband ultrasound attenuation (BUA) using quantitative ultrasound (QUS). VDR genotypes of the subjects analyzed with Bsm I restriction enzyme were bb (92%), Bb (7%) and BB (1%). No differences were found between genotypes bb and Bb/BB in age, menopausal age, body mass index and body fat. BUA of bb genotype was higher (62.5 $\pm$ 15.6 dB/MHz) than Bb/BB genotype (56.1 $\pm$ 17.6 dB/MHz) by Student's t-tests. Correlation analyses showed strong negative correlation of BMD and age, but positive correlation with BMI, energy and calcium intake. When subgroup analyses were conducted after stratification by the median calcium intake level (412.9 mg/d), the above median calcium intake group showed significant difference in BUA by VDR genotype while the lower median calcium intake group did not show significant difference. The current study confirmed interaction of calcium intake and VDR genotype in association with BMD. Further nutritional intervention will be needed to improve calcium status of the elderly women living in rural areas.
The adrenergic receptor beta 2 (ADRB2) plays a role in various physiological responses of the muscle to exercise, such as contraction and relaxation. Given its important role in muscle function, we investigated the structure of the horse ADRB2 gene and its expression pattern after exercise to determine if it can serve as a putative biomarker for recovery. Evolutionary analyses using synonymous and non-synonymous mutation ratios, were compared with other species (human, chimpanzee, mouse, rat, cow, pig, chicken, dog, and cat), and revealed the occurrence of positive selection in the horse ADRB2 gene. In addition, expression analyses by quantitative polymerase chain reaction exhibited ubiquitous distribution of horse ADRB2 in various tissues including lung, skeletal muscle, kidney, thyroid, appendix, colon, spinal cord and heart, with the highest expression observed in the lung. The expression of ADRB2 in skeletal muscle was significantly up-regulated about four folds 30 minutes post-exercise compared to pre-exercise. The expression level of ADRB2 in leukocytes, which could be collected with convenience compared with other tissues in horse, increased until 60 min after exercise but decreased afterward until 120 min, suggesting the ADRB2 expression levels in leukocytes could be a useful biomarker to check the early recovery status of horse after exercise. In conclusion, we identified horse ADRB2 gene and analyzed expression profiles in various tissues. Additionally, analysis of ADBR2 gene expression in leukocytes could be a useful biomarker useful for evaluation of early recovery status after exercise in racing horses.
Background: Breast cancer is a heterogeneous disease that represents a major public health problem. The immunohistochemical determination of breast cancer subtypes with regard to estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2) status can contribute to improved selection of therapy and patientcare. The purpose of this study was to determine the prevalence of the molecular breast cancer subtypes and to assess their associations with classical clinicopathologic parameters for better therapeutic decisions in women with breast cancer in the Ivory Coast. Materials and Methods: Formalin-fixed and paraffin-embedded blocks of patients diagnosed with primary breast carcinoma were subjected to immunohistochemical assay for the assessment of ER/RP and HER2 expression. The one-way analysis of variance evaluated the difference between breast cancer subtypes and mean age of patients. The Chi-square Test was used to compare standard clinicopathologic prognostic parameters with tumor subtypes. Results. Among 302 patients, 57% were premenopausal and 43% were postmenopausal. The invasive ductal carcinoma not otherwise specified (IDC NOS) (82.8%) was the most frequent histological type, and the tumor grade 2 (56%) was predominant followed by grade 3 (20.9%). The proportion of positivity of ER, PR, and HER2 was 56%, 49%, and 15.6%, respectively. Half of patients of this study (51.6%) had luminal A breast tumor type followed by TN (32.1%). Other subtypes were luminal B (10.1% ) and non-luminal HER2+ (6.3%). Conclusions. The findings of the present study are in line with the literature and should assist in management of breast cancer in our country.
Overexpression of DNA methyltransferase 1 (DNMT1) has been detected in many cancers. Tobacco exposure is known to induce genetic and epigenetic changes in the pathogenesis of malignancy. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is an important carcinogen present in tobacco smoke; however the detailed molecular mechanism of how NNK induces esophageal carcinogenesis is still unclear. We found that DNMT1 was overexpressed in ESCC tissues compared with paired non-cancerous tissues, the overexpression being correlated with smoking status and low expression of $RAR{\beta}$. The latter could be upregulated by NNK treatment in Het-1A cells, and the increased DNMT1 expression level reflected promoter hypermethylation and downregulation of retinoic acid receptor ${\beta}$($RAR{\beta}$). RNA interference mediated knockdown of DNMT1 resulted in promoter demethylation and upregulation of $RAR{\beta}$ in KYSE30 and TE-1 cells. 3-(4,5-Dimethyl-thiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometric analysis demonstrated that NNK treatment in Het-1A cells could enhance cell proliferation and inhibit cell apoptosis in a dose-dependent manner. In conclusion, DNMT1 overexpression is correlated with smoking status and low expression of $RAR{\beta}$ in esophageal SCC patients. NNK could induce $RAR{\beta}$ promoter hypermethylation through upregulation of DNMT1 in esophageal squamous epithelial cells, finally leading to enhancement of cell proliferation and inhibition of apoptosis.
Objective: To investigate differences in mutations of epidermal growth factor receptor (EGFR) gene and relationships with clinicopathological features in patients with non-small cell lung cancer (NSCLC) between Uygur and Han ethnic groups. Methods: The Scorpions amplification refractory mutation system (Scorpions ARMS) was used to measure mutations in exons 18, 19, 20 and 21 of the EGFR gene in paraffin-embedded tumor tissue from NSCLC cases, and statistical analysis was performed to investigate links with clinicopathological features in different histological types of NSCLC. Results: Results from ARMS testing showed EGFR mutations in tumor tissues from six (6) of 50 NSCLC patients of Uygur ethnic group, with a positive rate of 12.0%; four of them (4) had exon 19 deletion in EGFR, and two (2) had L858R point mutation in exon 21 of EGFR. Statistically significant difference was noted in EGFR genetic mutation between adenocarcinoma and non-adenocarcinoma (P < 0.05), but no differences with gender, age group, smoking status, or stage (P > 0.05). EGFR mutations were detected in tumor tissues from 27 of 49 NSCLC patients of Han ethnic group, with a positive rate of 55.1%; 19 of them had exon 19 deletions, seven (7) had L858R point mutations in exon 21 of EGFR and one (1) had mutations in both exon 18 G719X and exon 20 T790M of EGFR. Statistically significant differences were noted in EGFR genetic mutations between genders and between adenocarcinoma and non-adenocarcinoma (P<0.05), but not with age group, smoking status, or stage (P > 0.05). Conclusion: Statistically significant differences were noted in the positive rates of EGFR genetic mutations in NSCLC patients between Uygur and Han ethnic groups, with lower positive rates for the Uygur cases.
Jiyoung Yoon;Eun-Kyung Kim;Min Jung Kim;Hee Jung Moon;Jung Hyun Yoon;Vivian Y. Park
Korean Journal of Radiology
/
v.21
no.8
/
pp.946-954
/
2020
Objective: To investigate preoperative magnetic resonance imaging (MRI) findings associated with resection margin status in patients with invasive lobular carcinoma (ILC) who underwent breast-conserving surgery. Materials and Methods: One hundred and one patients with ILC who underwent preoperative MRI were included. MRI (tumor size, multifocality, type of enhancing lesion, distribution of non-mass enhancement [NME], and degree of background parenchymal enhancement) and clinicopathological features (age, pathologic tumor size, presence of ductal carcinoma in situ [DCIS] or lobular carcinoma in situ, presence of lymph node metastases, and estrogen receptor/progesterone receptor/human epidermal growth factor receptor type 2 status) were analyzed. A positive resection margin was defined as the presence of invasive cancer or DCIS at the inked surface. Logistic regression analysis was performed to determine pre- and postoperative variables associated with positive resection margins. Results: Among the 101 patients, 21 (20.8%) showed positive resection margins. In the univariable analysis, NME, multifocality, axillary lymph node metastasis, and pathologic tumor size were associated with positive resection margins. With respect to preoperative MRI findings, multifocality (odds ratio [OR] = 3.977, p = 0.009) and NME (OR = 2.741, p = 0.063) were associated with positive resection margins in the multivariable analysis, although NME showed borderline significance. Conclusion: In patients with ILC, multifocality and the presence of NME on preoperative breast MRI were associated with positive resection margins.
Seo, Kyung Won;Jeon, Taeyong;Kim, Sewon;Kim, Sung Soo;Kim, Kwanghee;Suh, Byoung-Jo;Hwang, Sunhwi;Choi, SeongHee;Ryu, Seungwan;Min, Jae Seok;Lee, Young-Joon;Jee, Ye Seob;Chae, Hyeondong;Yang, Doo Hyun;Lee, Sang Ho
Journal of Gastric Cancer
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v.17
no.1
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pp.52-62
/
2017
Purpose: The Trastuzumab for gastric cancer (GC) trial identified human epidermal growth factor receptor 2 (HER2) as a predictor of successful treatment with trastuzumab (HER2 receptor targeting agent) among patients with advanced/metastatic GC. To date, the prevalence of HER2 overexpression in the Korean population is unknown. The present study aimed to assess the incidence of HER2 positivity among GC and gastroesophageal (GE) junction cancer samples and the relationship between HER2 overexpression and clinicopathological characteristics in Korean patients. Materials and Methods: Tumor samples collected from 1,695 patients with histologically proven GC or GE junction enrolled at 14 different hospitals in Korea were examined. After gathering clinicopathological data of all patients, HER2 status was assessed by immunohistochemistry (IHC) at each hospital, and IHC 2+ cases were subjected to silver-enhanced in situ hybridization at 3 central laboratories. Results: A total of 182 specimens tested positive for HER2, whereas 1,505 tested negative. Therefore, the overall HER2-positive rate in this study was 10.8% (95% confidence interval=9.3%-12.3%). The HER2-positive rate was higher among intestinal-type cases (17.6%) than among other types, and was higher among patients older than 70 years and 50 years of age, compared to other age groups. Conclusions: Our evaluation of the HER2 positivity rate (10.8%) among Korean patients with GC and GE junction indicated the necessity of epidemiological data when conducting studies related to HER2 expression in GC and GE junction.
Jang, Beom-Su;Park, Seung-Hee;Shin, In Soo;Maeng, Jin-Soo;Paik, Chang H.
Toxicological Research
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v.29
no.1
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pp.21-25
/
2013
The selective targeting of an integrin ${\alpha}_v{\beta}_3$ receptor using radioligands may enable the assessment of angiogenesis and integrin ${\alpha}_v{\beta}_3$ receptor status in tumors. The aim of this research was to label a peptidomimetic integrin ${\alpha}_v{\beta}_3$ antagonist (PIA) with $^{99m}Tc(CO)_3$ and to test its receptor targeting properties in nude mice bearing receptor-positive tumors. PIA was reacted with tris-succinimidyl aminotriacetate (TSAT) (20 mM) as a PIA per TSAT. The product, PIA-aminodiacetic acid (ADA), was radiolabeled with $[^{99m}Tc(CO)_3(H_2O)_3]^{+1}$, and purified sequentially on a Sep-Pak C-18 cartridge followed by a Sep-Pak QMA anion exchange cartridge. Using gradient C-18 reverse-phase HPLC, the radiochemical purity of $^{99m}Tc(CO)_3$-ADA-PIA (retention time, 10.5 min) was confirmed to be > 95%. Biodistribution analysis was performed in nude mice (n = 5 per time point) bearing receptor-positive M21 human melanoma xenografts. The mice were administered $^{99m}Tc(CO)_3$-ADA-PIA intravenously. The animals were euthanized at 0.33, 1, and 2 hr after injection for the biodistribution study. A separate group of mice were also co-injected with 200 ${\mu}g$ of PIA and euthanized at 1 hr to quantify tumor uptake. $^{99m}Tc(CO)_3$-ADA-PIA was stable in phosphate buffer for 21 hr, but at 3 and 6 hr, 7.9 and 11.5% of the radioactivity was lost as histidine, respectively. In tumor bearing mice, $^{99m}Tc(CO)_3$-ADA-PIA accumulated rapidly in a receptor-positive tumor with a peak uptake at 20 min, and rapid clearance from blood occurring primarily through the hepatobiliary system. At 20 min, the tumor-to-blood ratio was 1.8. At 1 hr, the tumor uptake was 0.47% injected dose (ID)/g, but decreased to 0.12% ID/g when co-injected with an excess amount of PIA, indicating that accumulation was receptor mediated. These results demonstrate successful $^{99m}TC$ labeling of a peptidomimetic integrin antagonist that accumulated in a tumor via receptor-specific binding. However, tumor uptake was very low because of low blood concentrations that likely resulted from rapid uptake of the agent into the hepatobiliary system. This study suggests that for $^{99m}Tc(CO)_3$-ADA-PIA to be useful as a tumor detection agent, it will be necessary to improve receptor binding affinity and increase the hydrophilicity of the product to minimize rapid hepatobiliary uptake.
Izadi, Pantea;Noruzinia, Mehrdad;Fereidooni, Foruzandeh;Nateghi, Mohammad Reza
Asian Pacific Journal of Cancer Prevention
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v.13
no.8
/
pp.4113-4117
/
2012
Breast cancer is a prevalent heterogeneous malignant disease. Gene expression profiling by DNA microarray can classify breast tumors into five different molecular subtypes: luminal A, luminal B, HER-2, basal and normal-like which have differing prognosis. Recently it has been shown that immunohistochemistry (IHC) markers including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2), can divide tumors to main subtypes: luminal A (ER+; PR+/-; HER-2-), luminal B (ER+;PR+/-; HER-2+), basal-like (ER-;PR-;HER2-) and Her2+ (ER-; PR-; HER-2+). Some subtypes such as basal-like subtype have been characterized by poor prognosis and reduced overall survival. Due to the importance of the ER signaling pathway in mammary cell proliferation; it appears that epigenetic changes in the $ER{\alpha}$ gene as a central component of this pathway, may contribute to prognostic prediction. Thus this study aimed to clarify the correlation of different IHC-based subtypes of breast tumors with $ER{\alpha}$ methylation in Iranian breast cancer patients. For this purpose one hundred fresh breast tumors obtained by surgical resection underwent DNA extraction for assessment of their ER methylation status by methylation specific PCR (MSP). These tumors were classified into main subtypes according to IHC markers and data were collected on pathological features of the patients. $ER{\alpha}$ methylation was found in 25 of 28 (89.3%) basal tumors, 21 of 24 (87.5%) Her2+ tumors, 18 of 34 (52.9%) luminal A tumors and 7 of 14 (50%) luminal B tumors. A strong correlation was found between $ER{\alpha}$ methylation and poor prognosis tumor subtypes (basal and Her2+) in patients (P<0.001). Our findings show that $ER{\alpha}$ methylation is correlated with poor prognosis subtypes of breast tumors in Iranian patients and may play an important role in pathogenesis of the more aggressive breast tumors.
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