We aimed to evaluate the differences in the rates and predictive factors for ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) between ductal carcinoma in situ (DCIS) and invasive breast cancer. And, we evaluated the impact of IBTR on overall survival and distant metastasis.
We retrospectively reviewed 322 consecutive patients with DCIS or invasive breast cancer who underwent BCS between 2004 and 2010. We evaluated the rates of IBTR of DCIS and invasive breast cancer. Univariate and multivariate analyses were performed to determine the predictive factors for IBTR, and survival rates were analyzed with Kaplan-Meier estimates.
With a median follow-up period of 57 months, 5 (10 %) out of 50 DCIS patients and 14 (5.1 %) out of 272 invasive cancer patients had developed IBTR. Factors associated with IBTR on univariate and multivariate analyses were positive resection margin status in DCIS and omission of radiotherapy in invasive cancer, respectively. The hormone receptor negativity was strong independent predictive factors for IBTR in both DCIS and invasive breast cancer. Although the differences of survival curve did not reach statistical significance, the 5-year overall survival and distant metastasis-free survival of invasive cancer patients who suffered IBTR were inferior to those without (84 vs. 98 % and 63.3 vs. 96.5 %, respectively). Advanced initial stage, lymph node metastasis and experience of IBTR were associated with poor overall survival and distant metastasis on univariate and multivariate analyses.
The hormone receptor negativity was revealed as independent predictive factor for IBTR after BCS in both DCIS and invasive cancer. Experience of IBTR was independent prognostic factor for poor overall outcome in patients with invasive breast cancer. Aggressive local control and adjuvant therapy should be made in hormone receptor-negative patients who receive treatment with BCS.
Ipsilateral breast tumor recurrence (IBTR); Breast-conserving surgery (BCS); Ductal carcinoma in situ (DCIS); Breast carcinoma; Margin; Radiotherapy; Survival
Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy.
Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event.
This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy.
ClinicalTrials.gov Identifier NCT00912548. Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005. Registered October 26 2009.
Ovarian function suppression; Goserelin; Tamoxifen; Adjuvant endocrine therapy; Premenopause; Breast cancer
The purpose of the study is to reveal the association of cytogenetic compltyexi and peritumoral edema volume (PTEV) and its prognostic significance in high-grade astrocytoma patients by culturing patient tumor cells.
Twenty-seven high-grade astrocytoma patients were divided into three groups according to karyotype complexity: normal, non-complex karyotype (NCK), and complex karyotype (CK). Endothelial growth factor receptor (EGFR) amplification was detected by FISH, and its association with chromosome 7 abnormalities was analyzed. Mean PTEV of each group was compared by ANOVA to evaluate the relationship between PTEV and cytogenetic complexity.
The PTEV of patients in normal (n=6), NCK (n=8), and CK (n=13) groups were 24.52±17.73, 34.26±35.04, and 86.31±48.7 cm3, respectively (P=0.005). Ten out of 11 patients with EGFR amplification showed abnormalities in chromosome 7. The mean PTEV of EGFR-amplified and non-amplified groups were 80.4±53.7 and 41.3±37.9 cm3, respectively (P=0.035). The average survival of patients with PTEV less than 90 cm3 was 30.52±26.11 months, while in patients with PTEVs over or equal to 90 cm3, it was 10.83±5.53 months (P=0.007).
The results show an association of complex karyotype with the PTEV of high-grade astrocytoma. EGFR amplification plays a significant role in the formation of peritumoral edema, causing PTEV to increase, which is related with survival. This implies that cytogenetic karyotype can be applied as a prognostic factor.
High-grade astrocytoma; Chromosome; EGFR amplification; Peritumoral edema
Although several studies reported genetic polymorphisms in protein kinase AMP‐activated alpha 1 catalytic subunit (PRKAA1) and their associations with gastric cancer risk, few have evaluated associations between Helicobacter pylori infection and PRKAA1 gene‐environment interactions. Here, we evaluated the effects of interactions between H. pylori infection and PRKAA1 polymorphisms on gastric cancer risk in Koreans. In this hospital‐based case–control study, PRKAA1 genotypes were analyzed and H. pylori infection and CagA status were examined using a serologic method in 846 pairs of gastric cancer patients and controls matched for age and sex. H. pylori seropositivity was associated with a 1.43‐fold [95% confidence interval: 1.12–1.81] increase in the risk of gastric cancer, and CagA low‐positive titers during H. pylori infection increased the risk by 1.85‐fold (95% confidence interval, 1.38–2.48). Significant positive interaction between the PRKAA1 rs13361707 genotype and H. pylori infection was verified on an additive scale [relative excess risk due to interaction, 0.55; 95% confidence interval, 0.05–1.04; P = 0.030], and the gene‐environment interaction between PRKAA1 rs13361707 and CagA status was also statistically significant (relative excess risk due to interaction, 0.50; 95% confidence interval, 0.30–0.70; P < 0.001). Our results indicated that H. pylori infection, CagA status, and PRKAA1 polymorphisms were risk factors for gastric cancer in Koreans, and that the combination of two of these factors rather than their independent effects synergistically increased the risk.
AMP‐activated protein kinase; gastric cancer; gene‐environment interaction; Helicobacter pylori
The spinal dural arteriovenous fistula (SDAVF) is rare, presenting with progressive, insidious symptoms, and inducing spinal cord ischemia and myelopathy, resulting in severe neurological deficits. If physicians have accurate and enough information about vascular anatomy and hemodynamics, they achieve the good results though the surgery or endovascular embolization. However, when selective spinal angiography is unsuccessful due to neurological deficits, surgery and endovascular embolization might be failed because of inadequate information. We describe a patient with a history of vasospasm during spinal angiography, who was successfully treated by spinal stereotactic radiosurgery using Novalis system.
Spinal vascular disease; Dural arteriovenous fistula; Stereotactic radiosurgery
A 69-year-old man was referred with left exophthalmos. Computed tomographic (CT) findings detected a well-circumscribed mass in the left side of the intraorbital cavity. At that time, he refused the further evaluation and treatment. About three years later, the size of the mass had enlarged, and the patient's symptoms were getting worse. The mass was completely removed with frontotemporal craniotomy and superolateral orbitotomy. In operative findings, the mass had originated in the lacrimal gland and was well-encapsulated without invasion to the surrounding tissue. In the pathologic findings, the tumor consisted of pleomorphic adenoma with osteosarcomatous change of stromal components. Postoperatively, the adjuvant radiotherapy was done four weeks later. The patient's symptoms were improved. The pleomorphic adenoma with osteosarcomatous change is extremely rare and appropriate treatment is not clearly established. We would like to report this rare case with a review of the literature.
Sarcoma; Pleomorphic adenoma; Lacrimal gland; Malignant mixed tumor
The aim of this study was to evaluate the association between insulin-like growth factor 1 receptor (IGF-1R) expression in breast cancer tissue and mammographic density and the clinical significance of IGF-1R overexpression. A total of 167 patients with primary invasive breast cancer were analyzed. Mammographic breast density and IGF-1R overexpression were correlated with clinicopathological parameters and analyzed by overall survival (OS) and disease-free survival (DFS). Increased breast tissue density was significantly associated with age, body mass index, menopausal status, histological grade and IGF-1R overexpression in the univariate analysis and with age (P=0.001), histological grade (P=0.045) and IGF-1R overexpression (P=0.021) in the multivariate analysis. IGF-1R overexpression was significantly associated with dense breast tissue in patients aged >40 years (P=0.002). IGF-1R overexpression in breast cancer in premenopausal women was associated with human epidermal growth factor receptor 2 (HER-2) positivity (P=0.016) and worse DFS (P=0.0414). There was no significant difference in OS and DFS between dense and non-dense breast tissue. IGF-1R expression in breast cancer tissue was significantly associated with mammographic breast tissue density in patients aged >40 years. It appears that IGF-1R expression in breast cancer tissue plays an important role in breast cancer in patients with dense breast tissue. In premenopausal women, IGF-1R overexpression in breast cancer tissue was significantly associated with HER-2 positivity and poor DFS.
mammography; density; insulin-like growth factor 1 receptor; breast neoplasm; immunohistochemistry
AIM: To evaluate the association between genetic polymorphisms of the gene encoding AMP-activated protein kinase (PRKAA1) and the risk of gastric cancer.
METHODS: The study subjects consisted of 477 age- and sex-matched case-control pairs. Genotyping was performed for 5 tag single nucleotide polymorphisms (SNPs): rs13361707, rs154268, rs3805486, rs6882903, and rs10074991. Associations between gastric cancer and putative risk factors (including the SNPs) were analyzed with multivariate conditional logistic regression models, after adjusting for potential confounding factors. Multiple testing corrections were implemented following methodology for controlling the false discovery rate. Gene-based association tests were performed by using the versatile gene-based association study (VEGAS) method.
RESULTS: In the dominant model, SNPs rs13361707 [odds ratio (OR) = 1.51, 95%CI: 1.07-2.11)], rs154268 (OR = 1.65, 95%CI: 1.22-2.22), rs6882903 (OR = 1.48, 95%CI: 1.09-2.00), and rs10074991 (OR = 1.53, 95%CI: 1.09-2.16) were significantly associated with an increased risk of gastric cancer. In the recessive model, SNPs rs154268 (OR = 1.66, 95%CI: 1.22-2.26), rs3805486 (OR = 0.63, 95%CI: 0.46-0.85), and rs10074991 (OR = 1.47, 95%CI: 1.15-1.88) were significant risk or protective factors for gastric cancer. In the codominant model, the ORs of each of the 5 SNPs were statistically significant. All SNPs in the model showed a dose-response relationship between the minor allele frequency and the risk of gastric cancer. Most notably, subjects with a homozygous minor allele in SNP rs10074991 showed 2.15 times the risk of gastric cancer as subjects without a minor allele. The PRKAA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.
CONCLUSION: All 5 tested tag SNPs of the PRKAA1 gene (rs13361707, rs154268, rs3805486, rs6882903, and rs10074991) were significantly associated with gastric cancer.
AMP-activated protein kinase; Gastric cancer; PRKAA1; Single nucleotide polymorphism; Case-control study
Neurocutaneous melanosis (NCM) is a rare congenital syndrome consisting of benign or malignant melanotic tumors of the central nervous system with large or numerous cutaneous melanocytic nevi. The Dandy-Walker complex (DWC) is characterized by an enlarged posterior fossa with high insertion of the tentorium, hypoplasia or aplasia of the cerebellar vermis, and cystic dilatation of the fourth ventricle. These each two conditions are rare, but NCM associated with DWC is even more rare. Most patients of NCM with DWC present neurological symptoms early in life such as intracranial hemorrhage, hydrocephalus, and malignant transformation of the melanocytes. We report a 14-year-old male patient who was finally diagnosed as NCM in association with DWC with extensive intracerebral and spinal cord involvement.
Melanoma; Neurocutaneous syndrome; Dandy-Walker syndrome
AIM: To evaluate the association between the genetic polymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.
METHODS: The study subjects were 477 age- and sex-matched case-control pairs. Genotyping was performed for 15 single nucleotide polymorphisms (SNPs) in ITGA1. The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models. Multiple testing corrections were carried out following methodology for controlling the false discovery rate. Gene-based association tests were performed using the versatile gene-based association study (VEGAS) method.
RESULTS: In the codominant model, the ORs for SNPs rs2432143 (1.517; 95%CI: 1.144-2.011) and rs2447867 (1.258; 95%CI: 1.051-1.505) were statistically significant. In the dominant model, polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors, with ORs of 1.337 (95%CI: 1.029-1.737) and 1.412 (95%CI: 1.061-1.881), respectively. In the recessive model, only the rs2432143 polymorphism was significant (OR = 1.559, 95%CI: 1.150-2.114). The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model (OR = 0.602, 95%CI: 0.212-0.709, P = 0.021) and the dominant model (OR = 0.653, 95%CI: 0.483-0.884). The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test. In the dominant model, the A-T type of ITGA1 haplotype block 2 was a significant risk factor (OR = 1.341, 95%CI: 1.034-1.741). SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and, thus, to the risk of developing gastric cancer.
CONCLUSION: ITGA1 gene SNPs rs1862610, rs24321
43, and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.
Integrin; ITGA1; Gastric cancer; Polymorphism; Haplotype
Although removal of the anterior clinoid process (ACP) is essential surgical technique, studies about quantitative measurements of the space broadening by the anterior clinoidectomy are rare. The purposes of this study are to investigate the dimension of the ACP, to quantify the improved exposure of the parasellar space after extradural anterior clinoidectomy and to measure the correlation of each structure around the paraclinoidal area.
Eleven formalin-fixed Korean adult cadaveric heads were used and frontotemporal craniotomies were done bilaterally. The length of C6 segment of the internal carotid artery on its lateral and medial side and optic nerve length were checked before and after anterior clinoidectomy. The basal width and height of the ACP were measured. The relationships among the paraclinoidal structures were assessed. The origin and projection of the ophthalmic artery (OA) were investigated.
The mean values of intradural basal width and height of the ACP were 10.82 mm and 7.61 mm respectively. The mean length of the C6 lateral and medial side increased 49%. The mean length of optic nerve increased 97%. At the parasellar area, the lengths from the optic strut to the falciform liament, distal dural ring, origin of OA were 6.69 mm, 9.36 mm and 5.99 mm, respectively. The distance between CN III and IV was 11.06 mm.
With the removal of ACP, exposure of the C6 segments and optic nerve can expand 49% and 97%, respectively. This technique should be among a surgeon's essential skills for treating lesions around the parasellar area.
Anterior clinoid process; Extradural anterior clinoidectomy; Optic strut; Ophthalmic segment
AIM: To evaluate the relationship among Helicobacter pylori (H. pylori) infection, CagA status, and dietary factors with RUNX3 promoter hypermethylation.
METHODS: Gastric cancer tissue samples were collected from 184 South Korean patients. All patients were interviewed following a semi-quantitative food frequency questionnaire. The average frequencies of intake and portion sizes of 89 common food items were documented, and total intakes of calories, nutrients, vitamins, and minerals were calculated for each subject. DNA was extracted from gastric cancer tissue samples, and amplification of the HSP60 gene was performed to detect H. pylori infection. Nested polymerase chain reaction (PCR) was used to detect the presence of the CagA gene. RUNX3 gene expression was measured by reverse transcription-PCR, and RUNX3 methylation status was evaluated by methylation-specific PCR. The odds ratios (ORs) and 95%CI associated with RUNX3 promoter hypermethylation status were estimated for each of the food groups, lifestyle factors, and the interaction between dietary and lifestyle factors with CagA status of H. pylori infection.
RESULTS: Overall, 164 patients (89.1%) were positive for H. pylori DNA, with the CagA gene detected in 59 (36%) of these H. pylori-positive samples. In all, 106 (57.6%) patients with gastric cancer demonstrated CpG island hypermethylation at the RUNX3 promoter. RUNX3 expression was undetectable in 52 (43.7%) of the 119 gastric cancer tissues sampled. A high consumption of eggs may increase the risk of RUNX3 methylation in gastric cancer patients, having a mean OR of 2.15 (range, 1.14-4.08). A significantly increased OR of 4.28 (range, 1.19-15.49) was observed with a high consumption of nuts in patients with CagA-positive H. pylori infection. High intakes of carbohydrate, vitamin B1, and vitamin E may decrease the risk of RUNX3 methylation in gastric cancer tissue, particularly in CagA- or H. pylori-negative infection, with OR of 0.41 (0.19-0.90), 0.42 (0.20-0.89), and 0.29 (0.13-0.62), respectively. A high consumption of fruits may protect against RUNX3 methylation.
CONCLUSION: These results suggest that the CagA status of H. pylori infection may be a modifier of dietary effects on RUNX3 methylation in gastric cancer tissue.
Gastric cancer; RUNX3; Helicobacter pylori; CagA; Dietary factors
There are conflicting results surrounding the prognostic significance of epidermal growth factor receptor (EGFR) status in glioblastoma (GBM) patients. Accordingly, we attempted to assess the influence of EGFR expression on the survival of GBM patients receiving postoperative radiotherapy.
Materials and Methods
Thirty three GBM patients who had received surgery and postoperative radiotherapy at our institute, between March 1997 and February 2006, were included. The evaluation of EGFR expression with immunohistochemistry was available for 30 patients. Kaplan-Meier survival analysis and Cox regression were used for statistical analysis.
EGFR was expressed in 23 patients (76.7%), and not expressed in seven (23.3%). Survival in EGFR expressing GBM patients was significantly less than that in non-expressing patients (median survival: 12.5 versus 17.5 months, p=0.013). Patients who received more than 60 Gy showed improved survival over those who received up to 60 Gy (median survival: 17.0 versus 9.0 months, p=0.000). Negative EGFR expression and a higher radiation dose were significantly correlated with improved survival on multivariate analysis. Survival rates showed no differences according to age, sex, and surgical extent.
The expression of EGFR demonstrated a significantly deleterious effect on the survival of GBM patients. Therefore, approaches targeting EGFR should be considered in potential treatment methods for GBM patients, in addition to current management strategies.
Epidermal growth factor receptor; glioblastoma; radiotherapy; survival
Synchronous bilateral breast cancer is extremely rare in men and has not, up to date, been reported in Korea. A 54-year-old man presented with a palpable mass in the right breast. The right nipple was retracted and bilateral axillary accessory breasts and nipples were present. On physical examination, a 2 cm-sized mass was palpated directly under the right nipple, and, with squeezing, bloody discharge developed in a single duct of the left nipple. There was no palpable mass in the left breast, and axillary lymph nodes were not palpable. Physical examination of external genitalia revealed a unilateral undescended testis on the left side. Synchronous bilateral breast cancer was diagnosed using mammography, ultrasonography, and core-needle biopsy. Histopathological examination revealed invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast. Bilateral total mastectomy, sentinel lymph node biopsy, and excision of accessory breasts in the axilla were performed.
Breast; Male; Synchronous neoplasms
A 20-month-old boy presented with a intraparenchymal mass in the right frontoparietal area manifesting as complex partial seizure, secondary generalization and left hemiparesis. Magnetic resonance images (MRI) of the brain showed inhomogeneously enhancing mass in the right frontoparietal area which has irregular margin and perilesional edema. Based on the radiological findings, a preoperative diagnosis was an intraaxial tumor, such as pilocytic astrocytoma or dysembryoplastic neuroepithelial tumor. The patient underwent a surgery including frontal craniotomy. The tumor had a partially extreme adherence to the surrounding brain tissue but it showed no dural attachment. Gross-total resection of the tumor was achieved. Postoperative follow-up computed tomography scans showed no residual tumor. The pathological findings confirmed the tumor as a WHO grade I meningioma, transitional type. Nine months after the surgery, follow-up brain MRI showed no recurrence of the tumor, porencephaly in site where the tumor was resected; the patient's symptoms had fully recovered. We report the case of a meningioma in a 20-month-old boy.
Microglandular adenosis (MGA) of the breast is a very rare and benign proliferative lesion. Most patients complain of a palpable breast mass that may arouse a clinical suspicion of breast cancer. Histopathologically, it is hard to distinguish MGA from breast cancer because of the lack of a myoepithelial layer and infiltrative proliferation. Several studies have reported a strong relationship between MGA and carcinoma arising in MGA, so the mass should be excised completely in cases of MGA determined from a core needle biopsy rather than observation. A 72-years-old woman presented with a palpable breast mass. On physical examination, a mass was palpable in the right upper outer quadrant area and somewhat fixed to the surrounding tissues and pectoralis major muscle. We could not detect any mass or dense lesion on mammography because of a grade 4 dense breast. Ultrasonographic findings revealed a low echoic lesion with indistinct margins. The result of a core needle biopsy was MGA, which was confirmed by excision. We report one case of MGA, which was believed to breast cancer clinically.
Breast; Cancer; Microglandular adenosis
Spinal epidural hematoma (SEH) causing acute myelopathy is rare. The usual clinical presentation of a SEH is sudden severe neck or back pain that progresses toward paraparesis or quadriparesis, depending on the level of the lesion. Recent studies have shown that early decompressive surgery is very important for patient's recovery. We experienced five patients of cervico-thoracic epidural hematomas associated with neurologic deficits that were treated successfully with surgical intervention.
Intraspinal; Epidural; Hematoma; Laminectomy
Spinal intradural extramedullary teratoma is a rare condition that develops more commonly in children than in adults and may be associated with spinal dysraphism. We report a rare case of adult-onset intradural extramedullary teratoma in the thoracolumbar spinal cord with no evidence of spinal dysraphism and without the history of prior spinal surgery. The patient was a 38-year-old male whose chief complaint was urinary incontinence. X-ray images of the thoracolumbar spine showed the widening of the interpedicular distance and posterior marginal erosion of the vertebral bodies and pedicles at the T11, T12, and L1 level. Magnetic resonance imagings of the lumbar spine showed a lobulated inhomogeneous high signal intradural mass (87×29×20 mm) between T11 and L1 and a high signal fluid collection at the T11 level. Laminectomy of the T11-L1 region was performed, and the mass was subtotally excised. The resected tumor was histopathologically diagnosed as a mature cystic teratoma. The patient's symptom of urinary incontinence was improved following the surgery.
Spinal cord neoplasm; Mature teratoma
Although tuberculosis of the central nervous system is well known, the incidence of intramedullary tuberculomas is low and a combination of intramedullary with intracranial tuberculomas is extremely rare. We report a case of disseminated tuberculoma involving brain and spine with miliary pulmonary tuberculosis in a 66-year-old woman initially presenting with fever, general weakness, back pain and motor weakness of both lower extremities. Despite medical therapy, she developed progressive motor weakness of both lower extremities with muscle strength 1/5 in both lower extremities. Urgent surgical intervention was followed and her muscle power and motor functions were improved gradually. The anti-tuberculous drugs were continued and the follow-up magnetic resonance imaging (MRI) of brain and spine showed that the lesions had become smaller or disappeared.
Tuberculoma; Spine; Brain; Magnetic resonance imaging
AIM: Hypermethylation of the promoter of the hMLH1 gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer.
METHODS: Data were obtained from a hospital-based, case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors. Hypermethylation of the hMLH1 gene promoter, polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated.
RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene. Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation, whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region. Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53 gene.
CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, GSTT1, CYP1A1, CYP2E1, ALDH2, and L-myc genes are not independent risk factors for gastric cancer with hyperme-thylation of the hMLH1 promoter. These data also suggest that there could be two or more different molecular pathways in the development of gastric cancer, perhaps involving tumor suppression mechanisms or DNA mismatch repair.
Gastric cancer; Environmental carcinogens; Genetic polymorphisms; hMTLH1; Microsatellite instability; p53; Ki-ras
AIM: This case-control study investigated the effects of kimchi, soybean paste, fresh vegetables, nonfermented alliums, nonfermented seafood, nonfermented soybean foods, and the genetic polymorphisms of some metabolic enzymes on the risk of gastric cancer in Koreans.
METHODS: We studied 421 gastric cancer patients and 632 age- and sex-matched controls. Subjects completed a structured questionnaire regarding their food intake pattern. Polymorphisms of cytochrome P450 1A1 (CYP1A1), cytochrome P450 2E1 (CYP2E1), glutathione S-transferase mu 1 (GSTM1), glutathione S-transferase theta 1 (GSTT1) and aldehyde dehydrogenase 2 (ALDH2) were investigated.
RESULTS: A decreased risk of gastric cancer was noted among people with high consumption of nonfermented alliums and nonfermented seafood. On the other hand, consumption of kimchi, and soybean pastes was associated with increased risk of gastric cancer. Individuals with the CYP1A1 Ile/Val or Val/Val genotype showed a significantly increased risk for gastric cancer. Increased intake of kimchi or soybean pastes was a significant risk factor for the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the GSTM1 non-null, the GSTT1 non-null, or the ALDH2 *1/*1 genotype. In addition, eating soybean pastes was associated with the increased risk of gastric cancer in individuals with the GSTM1 null type. Nonfermented alliums were significant in individuals with the CYP1A1 Ile/Ile, the CYP2E1 c1/c2 or c2/c2, the GSTT1 null, the GSTT1 non-null, or the ALDH2 *1/*2 or *2/*2 genotype, nonfermented seafood was those with the CYP1A1 Ile/Ile, the CYP2E1 c1/c1, the ALDH2 *1/*1 genotype or any type of GSTM1 or GSTT1. In homogeneity tests, the odds ratios of eating kimchi for gastric cancer according to the GSTM1 or GSTT1 genotype were not homogeneous.
CONCLUSION: Kimchi, soybean pastes, and the CYP1A1 Ile/Val or Val/Val are risk factors, and nonfermented seafood and alliums are protective factors against gastric cancer in Koreans. Salt or some chemicals contained in kimchi and soybean pastes, which are increased by fermentation, would play important roles in the carcinogenesis of stomach cancer. Polymorphisms of the CYP1A1, CYP2E1, GSTM1, GSTT1, and ALDH2 genes could modify the effects of some environmental factors on the risk of gastric cancer.
Kimchi; Soybean pastes; Gastric cancer
A new monoclonal antibody recognizing CEACAM6, which we named AP11, was generated by immunizing BALB/c mice with phytohemagglutinin-activated human peripheral blood mononuclear cells. This study aims to evaluate whether CEACAM6 can serve as a tumor marker using AP11. We examined the expression of CEACAM6 with AP11 in 11 human carcinoma cell lines by flow cytometry and 439 human tissues including 282 tumor tissues and 157 normal tissues by immunohistochemistry. CEACAM6 epitope recognized by AP11 was well preserved in formalin-fixed and paraffin-embedded tissues. Adenocarcinomas of the stomach (86 %), colorectum (95 %), pancreas (100 %), and lung (83 %), urinary bladder (100 %), and mucinous ovarian tumors (88 %) had a high rate of CEACAM6 immunoreactivity. We observed a variable expression of CEACAM6 in hepatocellular carcinomas (35 %), squamous cell carcinomas of the lung (60 %), renal cell carcinomas (14 %), urothelial carcinomas (13 %), serous carcinomas of the ovary (17 %), and breast carcinomas (11 %). Small-cell carcinomas of the lung, prostatic adenocarcinomas, papillary thyroid carcinomas, malignant melanomas, giant cell tumors, and osteosarcomas were negative for CEACAM6. All normal tissues of various organs were negative for CEACAM6. In conclusion, CEACAM6 as detected by AP11, may serve as a marker for mucin-producing adenocarcinomas of the gastrointestinal tract and ovary as well as non-small cell lung cancer. Thus, AP11 represents a valuable diagnostic tool for detecting CEACMA6-positive cancers.
CEACMA6; AP11; Monoclonal antibody; Tumor marker
Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis of small- and medium-sized arteries in multiorgan systems. PAN may affect the gastrointestinal tract in 14%-65% of patients, but rarely involves the biliary tract and liver. We describe a patient without underlying disease who was diagnosed with PAN during resection of the gallbladder and liver.
Polyarteritis nodosa; Liver; Intrahepatic bile duct; Biliary stone; Gallbladder
This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K+ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, NG-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.
Circular smooth muscle; Corpus; H2 receptors; Histamine; Human stomach; Nitric Oxide (NO); Relaxation