• Asian Pacific Journal of Cancer Prevention
• /
• 제13권2호
• /
• pp.451-457
• /
• 2012

One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of estrogen receptor (ER) gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-$2^+$ overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-$2^+$ tumors and in postmenopausal patients with $ER^-$, $PgR^-$, or $ER^-/PgR^-$ tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre- and postmenopausal patients. Findings revealed that aberrant hypermethylation of the ER-alpha gene frequently occurs in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.

• Asian Pacific Journal of Cancer Prevention
• /
• 제16권14호
• /
• pp.6055-6059
• /
• 2015

Background: Medication policy development in Thailand is continually promoting rational drug use. Letrozole, an endocrine therapy drug, is usually prescribed for post-menopausal status early and advanced stage breast cancer. After Ministry of Public Health announced Letrozole as compulsory licensed drug in 2009, more breast cancer patients can access to this drug at low cost especially those within universal coverage schemes. To ensure that Letrozole is rationally prescribed, the drug utilization study was conducted. Objectives: The aim of this study was to describe the appropriate use of Letrozole in breast cancer and the relationship between appropriate use and health benefit schemes. Materials and Methods: A retrospective study to evaluate use of Letrozole in breast cancer patients was performed for six months between January - June 2010 in seven regional cancer hospitals, Thailand. All prescriptions of Letrozole were identified from pharmacy dispensing databases and prescription papers. A medical record review was also performed to evaluate appropriate use referring to the drug use evaluation criteria. The approved criterion of this study was referred from the guideline of Thai National Formulary version 2010. Results: There were 681 prescriptions of Letrozole for 254 breast cancer patients with an average age of $58.6{\pm}10.0years$. The patients in universal coverage scheme (UCS), civil servant medication benefit scheme (CSMBS) and social security scheme (SSS) were 77.7%, 18.5% and 8.7% respectively. 10.6% were prescribed Letrozole for the first time. Letrozole were prescribed by oncologists (82.8%). The average number of tablets per prescription was $58{\pm}10$. Calcium supplements were prescribed concomitant with Letrozole for 19.4%. To assess drug use evaluation criteria, 45 prescriptions were excluded because of uncompleted clinical data, 636 prescriptions were evaluated. The study showed 86 prescriptions (13.5%) with inappropriate use including 6 (0.9%) not prescribed for estrogen receptor (ER) and/or progesterone receptor (PR) positive, 31 (4.9%) not prescribed for post-menopausal and 49 (7.7%) not prescribed for an appropriate duration. Appropriate use percentages in different health benefit schemes were similar, 85.7% of CSMBS, 86.4% of SSS and 86.7% of UCS. The relationship between health benefit scheme and appropriate use of Letrozole was not significantly different, ${\chi}^2$ (2, N = 636) = 0.081, p > 0.05. Conclusions: The study showed inappropriate use in breast cancer patients because of non-compliance with duration, menopausal status and hormone receptor requirements. To prescribe appropriate indication did not referred to the appropriate practice along the treatment. Drug use evaluation proved very useful for detecting the sign of inappropriate use and allows immediate feedback to the stakeholder for developing medication policy in the future. Importantly, there was no significantly difference in appropriate use of Letrozole across health benefit schemes.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권14호
• /
• pp.5709-5714
• /
• 2014

Background: An association between alcohol/tobacco use and risk of metastasis in breast cancer has been clearly shown. Materials and Methods: The present study explored, in 48 samples of tissue from mammary ductal carcinoma (taken from Mexican women with an average age of $58.2{\pm}10.9$ years), the association of risk of metastasis with the status of hormonal receptors and the c-erbB2 protein (by immunohistochemistry) as well as clinical, histopathological and sociodemographic factors. Results: Of 48 patients, 41.6% (20/48) presented with metastasis, 43.8% were positive for the estrogen receptor (RE+), 31.3% for the progesterone receptor (RP+) and 47.7% for c-erbB2 (c-erbB2+). The following combinations were found: RE+/RP+/c-erbB2+ 8.3%, RE+/RP+ 22.9%, RE+/RP- 20.8%, RE-/RP+ 8.3%, RE-/RP-/c-erbB2- 22.9% and RE-/RP- 47.8%. There were 12 patients who used alcohol/tobacco, of which 91.6% did not present metastasis and 81.9% were RE-/RP-. Compared to the RE-/RP-/c-erbB2+, the RE+/RP+/c-erbB2+ group had a 15-fold greater risk for metastasis (95%CI, 0.9-228.8, p=0.05). The carriers of the double negative hormonal receptors had a 4.7 fold greater probability of being (or having been) smokers or drinkers (95%CI, 1.0-20.4, p = 0.03). Conclusions: There was a clear protective effect of using alcohol and/or tobacco, in the cases included in the present study of mammary ductal carcinoma, associated with double negative hormonal receptors. However, this association could be due to a protective factor not measured (Neyman bias) or to a bias inherent in the rate of hospitalization (Berkson fallacy). This question should be explored in a broad prospective longitudinal study.

• Journal of Breast Cancer
• /
• 제21권4호
• /
• pp.382-390
• /
• 2018

Purpose: PIK3CA mutation is considered to be a possible cause for resistance to neoadjuvant chemotherapy (NAC) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the association between PIK3CA mutations and the outcome of NAC in HER2-positive breast cancers. Methods: A total of 100 HER2-positive breast cancer patients who had undergone NAC and surgery between 2004 and 2016 were examined. Mutation status was sequentially assessed in pre-NAC, post-NAC, and recurrent specimens taken from these patients. Results: PIK3CA mutations were identified in the sequential specimens of 17 patients (17.0%). These 17 patients experienced shorter disease-free survival (DFS) than the rest of the patients (58.3 months vs. 119.3 months, p=0.020); however, there was no significant difference in pathologic complete response (pCR) and overall survival (OS) (pCR, 17.6% vs. 33.7%, p=0.191; OS, 84.5 months vs. 118.0 months, p=0.984). While there was no difference in pCR between the wild-type and mutant PIK3CA groups in pre-NAC specimens (25.0% vs. 31.8%, p=0.199), PIK3CA mutations correlated with lower pCR in postNAC specimens (0.0% vs. 24.3%, p<0.001). Multivariate analysis revealed significantly worse DFS in the mutant PIK3CA group than in the wild-type group (hazard ratio, 3.540; 95% confidence interval, 1.001-12.589; p=0.050). Moreover, the DFS curves of the change of PIK3CA mutation status in sequential specimens were significantly different (p=0.016). Conclusion: PIK3CA mutation in HER2-positive breast cancer was correlated with a lower pCR rate and shorter DFS. These results suggest that PIK3CA mutation is a prognostic marker for NAC in HER2-positive breast cancer, especially in post-NAC specimens.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제47권6호
• /
• pp.445-453
• /
• 2021

Objectives: Periodontitis is the most common chronic disease that causes tooth loss and is related to systemic diseases such as cardiovascular disease and diabetes. An objective indicator of the current activity of periodontitis is necessary. Soluble forms of the receptor for advanced glycation end products (sRAGE) are markers that reflect the status of inflammatory diseases. In this study, the relationship between sRAGE and periodontitis was analyzed to determine whether it can be used to diagnose the current state of periodontitis. Patients and Methods: Eighty-four patients without any systemic diseases were diagnosed with periodontitis using three classifications of periodontitis. Demographics and oral examination data such as plaque index (PI), bleeding on probing (BOP) index, and probing pocket depth (PPD) were analyzed according to each classification. In addition, correlation and partial correlation between sRAGE and the values indicating periodontitis were analyzed. Results: In each classification, the level of sRAGE tended to decrease if periodontitis was present or severe, but this change was not statistically significant. sRAGE and periodontitis-related variables exhibited a weak correlation, among which the BOP index showed a relatively strong negative correlation (ρ=-0.20). Based on this, on analyzing the correlation between the BOP index and sRAGE in the group with more severe periodontitis (PPD≥5 mm group, severe group of AAP/CDC [American Academy of Periodontology/Centers for Disease Control and Prevention], periodontitis group of López), the correlation further increased (ρ=-0.23, -0.40, -0.50). Partial correlation analysis of the sRAGE and BOP index showed a stronger negative correlation (ρ=-0.36, -0.55, -0.45). Conclusion: sRAGE demonstrated a tendency to decrease upon increased severity of periodontitis according to the classifications used. Above all, the correlation with the BOP index, which reflects the current state of periodontitis, was higher in the group with severe periodontitis. This indicates that the current status of periodontitis can be diagnosed through sRAGE.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권4호
• /
• pp.2401-2406
• /
• 2013

From January 1, 2008 to March 31, 2010, 101 patients with stage II-III breast cancer were enrolled in this study and subjected to an anthracycline-based neoadjuvant chemotherapy regimen with or without docetaxel. Surgery was performed after 2-6 cycles of chemotherapy, and the clinical response was determined by pathological and histochemical assessments. The clinical response rate, as indicated by complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), were 6.9, 52.5, 36.6, and 4.0%, respectively. A multivariable correlation analysis indicated that the overall clinical response rate correlated with the number of metastatic lymph nodes, number of chemotherapy cycles, and vessel invasion status. Importantly, the CR rate was only associated with the number of chemotherapy cycles. Nonparametric tests failed to detect a correlation between HER2 or Topo $II{\alpha}$ status and clinical response to neoadjuvant chemotherapy in these patients. When they were stratified by HER2 or HR status, for HER2-positive patients the CR rate was associated with vessel invasion and Topo $II{\alpha}$ status. Based on our findings, we propose that HR, HER-2 and Topo $II{\alpha}$ are not putative predictive biomarkers of chemotherapy outcome for breast cancer patients. Topo $II{\alpha}$ expression level was only inversely correlated with CR rate among HR-positive patients. Importantly, the achievement of CR was largely related to the number of chemotherapy cycles.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권7호
• /
• pp.4279-4282
• /
• 2013

Background: The activation and inactivation of receptor tyrosine kinases are tightly regulated to ensure faithful replication of cells. After having transduced extracellular growth activating signals, activated EGFR is subjected to downregulation either by clathrin mediated endocytosis or c-Cbl mediated proteasome degradation depending on the ligand concentration. c-Cbl is an ubiquitin ligase which requires a phosphorylated tyrosine residue at position 1045 in the cytoplasmic domain of EGFR to interact and add ubiquitin molecules. While activating mutations in exons 19 and 21 have been associated with the development of several cancers, the status of mutations at tyrosine 1045 coding exon 27 of EGFR remain to be investigated. Consistently, defective phosphorylation at 1045 has been associated with sustained phosphorylation of EGFR in non-small lung carcinomas. Hence in the present study we investigated the genetic status of the tyrosine 1045 coding site within exon 27 of EGFR gene to explore for possible occurrence of mutations in this region, especially since no studies have addressed this issue so far. Materials and Methods: Tumor chromosomal DNA isolated from thirty five surgically excised oral squamous cell carcinoma tissues was subjected to PCR amplification with intronic primers flanking the tyrosine 1045 coding exon 27 of EGFR gene. The PCR amplicons were subsequently subjected to direct sequencing to elucidate the mutation status. Results: Sequence analysis identified no mutations in the tyrosine 1045 codon of EGFR in any of the thirty five samples that were analyzed. Conclusions: The lack of identification of mutation in the tyrosine 1045 codon of EGFR suggests that mutations in this region may be relatively rare in oral squamous cell carcinomas. To the best of our knowledge, this study is the first to have explored the genetic status of exon 27 of EGFR in oral squamous cell carcinoma tissue samples.

• 생물정신의학
• /
• 제2권2호
• /
• pp.218-236
• /
• 1995

The author studied prognostic indicators of sixty Korean male alcoholics in psychological, social and biological aspects who were divided into abstinent and drinking groups. Thirty patients were assigned to each group. They were controlled in age and sex. Both groups were compared in terms of the demographic characteristics, past drinking history, treatment history, famaily history, ego strength and personality factors differences and distribution of dopamine $D_2$ receptor gene Al allele. Also the author studied relation of clinical course, alcoholic family history and dopamine $D_2$ receptor gene Al allele in both groups. The results were as follows; 1) The abstinent group had higher rate of married state, higher economic status, longer education years and maintained more stable job than the drinking group. But made no differences in occupation and religion. 2) The abstinent group showed higher rate of living with family members than the drinking group, and wives and fellows of the alcoholics anonymous were important factors for maintenance of abstinence. Family loading and parent's characters were not different. 3) The abstinent group had longer maximal length of abstinence but mean amount of alcohol consumption per day were larger than the drinking group. But there were no differences in duration of past drinking, drinking pattern, main drinking time, first drinking age and preference of the kind of alcoholic beverage in the past drinking history. 4) The abstinent group showed stronger treatment motivation, absolute abstinence in treatment goal, more voluntary adimission and maintained longer therapeutic relationship otter discharge than the drinking group. But both groups showed negative attitude toward antabuse therapy. 5) The abstinent group had higher mean score in ego strength scale than the drinking group. 6) In the personality factor questionnaire, the abstinent group showed strong laugh poise and the trait of praxernia, conservatism personality but the drinking group showed tough poise, the trait of weak ego strength(unstableness) and tough mindedness personality. 7) In comparision of dopamine $D_2$ receptor gene A1 allele, the prevalence of A1 allele was seventy percent and the frequency was 0.38 in the abstinent group. The prevalence of A1 allele was sixty percent and the frequency was 0.42 in the drinking group. Both groups were not significantly different in A1 allele prevalence and frequency. 8) In comparision of dopamine $D_2$ receptor gene A1 allele according to alcoholic family history, the prevalence of A1 allele was seventy percent and the frequency was 0.43 in the family history positive group. The prevalence of A1 allele was sixty-one percent and the frequency was 0.38 in the family history negative group. Both groups were not significantly different in A1 allele prevalence and frequency. In comparision of past drinking history according to alcoholic family history, the family history positive group showed earlier first drinking and problem drinking, but the family history negative group hod longer duration of past drinking. The mean amount of alcohol consumption per day, the longest duration of abstinence and Alcoholism Screening Test of Seoul Natoinal Mental Hospital(NAST) results were not significant. In conclusion, the results suggest that successful prognostic indicators of Korean alcoholics are married state, higher economic status, longer education years, stable job, living with family members, longer abstinence during past drinking history, strong treatment motivation, absolute abstinence in treatment goal, voluntary adimission, maintained therapeufic relationship, strong ego strength and the trait of praxernia, conservatism personality. But occupation, religion, alcoholic family history, parent's characters, duration of past drinking, drinking pattern, main drinking time, first drinking age, preference of the kind of alcoholic beverage, attitude to antabuse therapy and distribution of dopamine $D_2$ receptor A1 allele were not significantly related to the prognostic indicators of Korean alcoholics.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권2호
• /
• pp.657-662
• /
• 2014

Background: The epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors. Materials and Methods: One hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively. Results: There were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:$3.66{\pm}4.53$) in positron emission tomography-computed tomography of mutant LC was significantly lower than that ($8.26{\pm}6.11$) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148). Conclusions: Mutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

• Tuberculosis and Respiratory Diseases
• /
• 제67권1호
• /
• pp.8-13
• /
• 2009

Background: The insulin receptor substrate-1 (IRS-1) is the primary docking molecule for the insulin-like growth factor I receptor (IGF-IR), and is required for activation of the phosphatidylinositol 3'-kinase (PI3K) pathway. IRS-1 activation of the (PI3K) pathway regulates IGF-mediated survival, enhancement of cellular motility and apoptosis. Therefore, we attempted to ascertain whether IRS-1 genetic variations affect an individual's risk for non-small cell lung cancer (NSCLC). Methods: Two-hundred and eighteen subjects, either diagnosed with NSCLC or control subjects, were matched by age, gender and smoking status. Genomic DNA from each subject was amplified by PCR and analyzed according to the restriction fragment length polymorphism (RFLP) profile to detect the IRS-1 G972R polymorphism. Results: The frequencies of each polymorphic variation, in the control population, were as follows: GG=103 (94.5%) and GR=6 (5.5%); for the NSCLC subjects, the genotypic frequencies were as follows: GG=106 (97.2%) and GR=3 (2.8%). We could not demonstrate statistically significant differences in the genotypic distribution between the NSCLC and the control subjects (p=0.499, Fisher's Exact test). The relative risk of NSCLC, associated with the IRS-1 G972R polymorphic variation, was 1.028 (95% CI; 0.63~9.90). In addition, we found no differences between polymorphic variants with regard to the histological subtype of NSCLC. Conclusion: We did not observe any noteworthy differences in the frequency of the IRS-1 G972R polymorphism in NSCLC patients, compared to control subjects. These results suggest suggesting that, in our study population, the IRS-1 G972R polymorphism does may not appear to be associated with an increased risk of NSCLC.