Polymorphisms of interleukin-1 and interleukin-2 genes in patients with gastric cancer in Korea

Background and Aim: Interleukin (IL)‐1 gene polymorphism has been reported to be associated with the increment of gastric cancer (GC) and the decrement of duodenal ulcers (DU). In addition, IL‐2 is known to induce Helicobacter pylori (H. pylori)‐associated gastric atrophy, but it is not known whether IL‐2 gene polymorphism increases the risk of GC (GC) or peptic ulcer diseases. Therefore, we compared the genotypes of IL‐1B, IL‐1RN, and IL‐2 gene polymorphisms with risk of gastric ulcers (GU), GC, and DU in Korean patients. Methods: In total, 116 GU, 122 GC, and 104 DU patients were included consecutively and compared with 100 healthy controls. Polymorphisms of the IL‐1B‐511/‐31 gene, the penta‐allelic variable number of tandem repeats of the IL‐1RN gene, and the IL‐2‐330 gene were analyzed by polymerase chain reaction with restriction fragment length polymorphism or confronting two‐pair primers methods. Results: The age–sex‐adjusted odds ratios (OR) for the IL‐1B‐511 T genotype relative to the C/C genotype (OR = 0.82, 95% confidence interval [CI] 0.41–1.65), IL‐1RN*2 genotype relative to the L/L genotype (OR = 0.85, 95% CI 0.41–1.78), and IL‐2‐330 T genotype relative to the G/G genotype (OR = 1.94, 95% CI 0.76–4.96) were not increased in GC. There was also no significant difference in the genotypes of these cytokine polymorphisms between the study group (GU or DU) and control group. In addition, genotypic frequency was not associated with H. pylori positivity and histological type of GC. Conclusion: IL‐1B‐511, IL‐1RN, and IL‐2 genetic polymorphisms were not important contributors to the pathogenesis of GU, GC, and DU in Korean patients.     

Radiation-associated urinary bladder cancer

A few data sets have been used for assessing the risk of radiation-associated bladder cancer. The most important are the Japanese atomic bomb survivors and patients exposed to ionizing radiation for medical purposes. According to a report from the United Nations Commission on the Effect of Ionizing Radiation, there is convincing evidence of a relationship between exposure to ionizing radiation and bladder cancer. In contrast to many other malignancies it is not clear how age at exposure and gender affect the risk of bladder cancer. Furthermore, the potential interaction between smoking and radiation exposure needs to be studied in greater detail.     

E-cad和EphA2在膀胱癌患者癌组织中的表达及临床意义

目的 探讨E-cad和EphA2在膀胱癌中的表达及意义.方法 通过免疫组织化学法检测E-cad和EphA2在膀胱癌和正常膀胱组织中的表达.结果 E-cad在膀胱癌组织中的阳性表达率为32.39%,正常膀胱组织表达的阳性率为100%.EphA2在膀胱癌组织中表达的阳性率为77.46%,正常膀胱组织表达的异常率为20%.E-cad和EphA2在膀胱癌组织表达呈负相关r=-0.274 94.结论 E-cad和EphA2在膀胱癌组织的表达.可以作为膀胱癌的诊断、转移以及治疗的基础理论依据.     

Epidemiology and biology of human urinary bladder cancer

The bladder constitutes the most frequent localization of malignant tumors in the urinary tract. Further prognostic factors are molecular and cytogenetic alterations, which have been identified as key mechanisms in the carcinogenetic pathway of bladder cancer. Structural or numerical chromosomal alterations lead to the activation of a variety of cancer-inducing oncogenes as well as to the inactivation of various distinct antiproliferative tumor-suppressor genes. With regard to the biological heterogeneity in transitional cell carcinoma, which is also reflected in epidemiological data, the differing clinical course and the limited value of established prognosticators, the analysis of new molecular parameters has become of interest in predicting the prognosis of bladder cancer patients. In addition, the definition of high-risk patient groups that are at at risk of progression and recurrence is a further objective of urological research in this field.     

Endobronchial metastasis from urinary bladder cancer

A rare case, a case of endobronchial metastasis from urinary bladder carcinoma is reported. A 70 years-old man was admitted with hematuria. He has a mass in urinary bladder and a mass in lung. He has no pulmonologic symptom. He is a smoker with 75 pack-years. Thorax computerized tomography revealed a mass in left lung upper lobe. Bronchoscopy demonstrated an endobronchial tumor in left upper lobe, apikoposterior segment. Histopathologically diagnosis was endobronchial metastasis from urinary bladder carcinoma. He received five courses of chemotherapy (cisplatin + gemcitabine). The mass was regressed after three months. Our patient lived for one year from diagnosis.     

Polymorphisms of micro RNA target genes IL12B,INSR, CCND1 and IL10 in gastric cancer

AIM To evaluate associations between mi RNA target genes IL12B,INSR,CCND1 and IL10 polymorphisms and gastric cancer(GC)in European population.METHODS Gene polymorphisms were analyzed in 508 controls and474 GC patients from 3 tertiary centers in Germany,Lithuania and Latvia.Controls were patients from the out-patient departments,who were referred for upper endoscopy because of dyspeptic symptoms and had no history of previous malignancy.Gastric cancer(GC)patients had histopathological verification of gastric adenocarcinoma.Genomic DNA was extracted using salting out method from peripheral blood mononuclear cells.IL12B TG(rs1368439),INSR TC(rs1051690),CCND1 AC(rs7177)and IL10 TC(rs3024498)SNPs were genotyped by the real-time polymerase chain reaction.Associations between gene polymorphism and GC were evaluated using multiple logistic regression analysis with adjustment for sex,age and country of birth.RESULTS We observed similar distribution of genotypes and allelic frequencies of all polymorphisms between GC patients and controls except of INSR rs1051690.The frequency of the T allele of INSR gene was significantly higher in GC patients than in controls(23.26%and 19.19%respectively,P=0.028).CT genotype was also more prevalent in patients compared to control group(38.48%and 30.12%respectively,P0.021).Logistic regression analysis revealed that only one polymorphism(rs1051690 in INSR gene)was associated with increased risk of GC.Carriers of CT genotype had higher odds of GC when compared to CC genotype(OR=1.45,95%PI:1.08-1.95,P=0.01).Similar association was observed in a dominant model for INSR gene,where comparison of TT+CT vs CC genotypes showed an increased risk of GC(OR=1.44,95%PI:1.08-1.90,P=0.01).Other analyzed SNPs were not associated with the presence of GC.CONCLUSION INSR rs1051690 SNP is associated with increased risk of GC,while polymorphisms in IL12B,CCND1 and IL10genes are not linked with the presence of GC.     

Matrix metalloproteinases and their clinical relevance in urinary bladder cancer

Matrix metalloproteinases (MMPs) have important roles in several cancer-supporting cellular processes, such as extracellular matrix (ECM) remodeling, angiogenesis, apoptosis, epithelial-to-mesenchymal transition and cell proliferation. This broad range of activity has led to considerable interest in the use of MMPs in the clinical setting as diagnostic or prognostic biomarkers and as therapeutic targets. Levels of the different MMPs can be measured in several sample types, including paraffin-embedded or fresh frozen tissue, serum, plasma and urine, and by various analytical methodologies, such as immunohistochemistry, real-time PCR, western and northern blot analyses, enzyme-linked immunosorbent assay and zymography. Several MMPs have been identified as having potential diagnostic or prognostic utility, whether alone or in combination with currently available diagnostic tests or imaging modalities. Although the early broad-spectrum anti-MMP agents showed a lack of efficacy, our continually improving understanding of the complex physiologic and pathologic roles of MMPs might enable the development of new MMP-specific and tumor-specific therapies. Accordingly, MMPs will continue to be the subjects of intensive research in bladder cancer.     

Laparoscopic multivisceral resection with bladder sparing in female patients with locally advanced sigmoid cancer infiltrating the urinary bladder and reproductive organs

Techniques in Coloproctology -     

Outcome of urinary bladder recurrence after partial cystectomy for en bloc urinary bladder adherent colorectal cancer resection

Purpose

Around 10 % of colorectal cancers are locally advanced at diagnosis. There are higher incidences for sigmoid and rectal cancer adhered to urinary bladder (UB) rather than other segments of colon cancer. Surgeons often performed partial cystectomy as possible for preservation of patient’s life quality. This study investigates prognostic factors in patients who underwent bladder preservation en bloc resection for UB adherent colorectal cancer.

Methods

From 2000 to 2011, 123 patients with clinically UB involvement colorectal cancer underwent primary colorectal cancer with urinary bladder resection. Seventeen patients were excluded because of the concurrent distant metastasis at diagnosis and another 22 patients were excluded because of total cystectomy with uretero-ileal urinary diversion. Finally, 84 patients with clinical stage IIIC (T4bN0M0, according to AJCC 7th edition) that underwent en bloc colorectal cancer resection with partial cystectomy were enrolled into this study for further analysis.

Results

Preoperative colovesical fistula and positive CT result were significantly more in the urinary bladder invasion group (p?=?0.043 and 0.010, respectively). Pathological UB invasion is an independent predictor of intravesical recurrence (p?=?0.04; HR, 10.71; 95 % CI?=?1.12～102.94) and distant metastasis (p?=?0.016; HR, 4.85; 95 % CI?=?1.34?～?17.53) in multivariate analysis.

Conclusions

For bladder preservation en bloc resection of urinary bladder adherent colorectal cancer, the pathological urinary bladder invasion is significantly associated with more urinary bladder recurrence and distant metastasis. This result helps surgeons make decisions at surgical planning and establish follow-up protocol.     

Human leukocyte interferon in therapy of patients with urinary bladder papillomatosis,breast cancer,and melanoma

Summary The authors report the results of local and parenteral applications of human leukocyte crude interferon in the therapy of eight patients with urinary bladder papillomatosis, four patients with breast cancer, and two patients with melanoma. The doses and effects of treatment are presented in tables. Clinical application of human leukocyte interferon (HLI) to these three types of malignant tumors has yielded encouraging results. The authors believe that investigations on HLI applications to some malignant tumors should continue because the results obtained indicate that interferon possesses not only an antiviral but also an antitumor activity.     

Polymorphisms of the HLA-B and HLA-DRB1 genes in Thai malaria patients

The high degree of polymorphism of human leukocyte antigen (HLA) genes has been suggested to result from natural selection against susceptibility to a variety of infectious pathogens, including malaria. HLA molecules are considered to play a crucial role in the defense of the host against malarial infection, and different HLA class I and class II alleles have been reported to be associated with reduced susceptibility to malaria or the severity of malaria in different populations. To test for associations between HLA alleles and the severity of malaria in a Thai population, polymorphisms of HLA-B and HLA-DRB1 genes were investigated in 472 adult patients in northwest Thailand with Plasmodium falciparum malaria. In this study, malaria patients were classified into three groups: mild malaria, non-cerebral severe malaria, and cerebral malaria. Our results revealed that the allele frequencies of HLA-B46, -B56, and -DRB1*1001 were statistically different between non-cerebral severe malaria and cerebral malaria (P = 0.005), between mild malaria and cerebral malaria (P = 0.032), and between mild malaria and non-cerebral malaria (P = 0.007). However, our results may be showing false positives due to multiple testing. Thus, further study with a larger sample size must be conducted to obtain conclusive evidence of the association of these HLA-B and DRB1 alleles with the severity of malaria in Thailand.     

Polymorphisms of folate metabolism genes in patients with cirrhosis and hepatocellular carcinoma

AIM To evaluated the association of the risk factors and polymorphisms in MTHFR C677 T, MTHFR A1298 C, MTR A2756 G and MTRR A66 G genes.METHODS Patients with cirrhosis(n = 116), hepatocellular carcinoma(HCC)(n = 71) and controls(n = 356) were included. Polymerase chain reaction followed by enzymatic digestion and allelic discrimination technique real-time PCR techniques were used for analysis. MINITAB-14.0and SNPstats were utilized for statistical analysis. RESULTS Showed that age ≥ 46 years(OR = 10.31; 95%CI: 5.66-18.76; P 0.001) and smoking(OR = 0.47; 95%CI: 0.28-0.78; P = 0.003) were associated with cirrhosis. Age ≥ 46 years(OR = 16.36; 95%CI: 6.68-40.05; P 0.001) and alcohol habit(OR = 2.01; 95%CI: 1.03-3.89; P = 0.039) were associated with HCC. MTHFR A1298 C in codominant model(OR = 3.37; 95%CI: 1.52-7.50; P = 0.014), recessive model(OR = 3.04; 95%CI: 1.43-6.47; P = 0.0051) and additive model(OR = 1.71; 95%CI: 1.16-2.52; P = 0.0072) was associated with HCC, as well as MTR A2756 G in the additive model(OR = 1.68; 95%CI: 1.01-2.77; P = 0.047), and MTRR A66 G in the codominant model(OR = 3.26; 95%CI: 1.54-6.87; P 0.001), dominant model(OR = 2.55; 95%CI: 1.24-5.25; P = 0.007) and overdominant model(OR = 3.05; 95%CI: 1.66-5.62; P 0.001). MTR A2756 G in the additive model(OR = 1.54; 95%CI: 1.02-2.33; P = 0.042) and smokers who presented at least one polymorphic allele for MTRR A66G(OR = 1.71; 95%CI: 0.77-3.82; P = 0.0051) showed increased risk for cirrhosis. There was no association between clinical parameters and polymorphisms. CONCLUSION Age ≥ 46 years, alcohol habit and MTR A2756 G, MTHFR A1298 C and MTRR A66 G polymorphisms are associated with an increased risk of HCC development; age ≥ 46 years, tobacco habit and the MTR A2756 G polymorphism are associated with cirrhosis.     

下尿路梗阻与男性膀胱癌发病的相关性

目的评价下尿路梗阻暴露与男性膀胱癌发生的联系。方法采用成组病例对照研究,设计调查表,收集男性膀胱癌患者104例为病例组,同期住院男性非膀胱癌患者206例为对照组,采用SPSS 17.0软件行数据资料管理和单因素、多因素非条件Logistic回归分析。结果下尿路梗阻与膀胱癌发生有一定联系,危险性可能随梗阻时间的延长而增大。结论下尿路梗阻是膀胱癌发生的危险因素,应当重视该领域的流行病学研究,以期合理预防和选择适当的手术方式。     

Detection of bladder bacteriuria in patients with acute urinary symptoms

Quantitative culture of midstream urine fails to yield a significant microorganism in many patients with acute urinary symptoms. We cultured bladder urine, obtained by aspiration, from symptomatic adults with equivocal findings on standard testing of midstream urine for low numbers of conventional uropathogens and fastidious bacteria. We found 561 (31%) of 1817 women and 36 (12%) of 300 men to be culture positive. Five hundred eighty-one (70%) of 830 isolates were fastidious bacteria; 191 (34%) of 561 culture positive women and 0 of 36 culture-positive men had polymicrobic bacteriuria. Bacterial counts were less than 10(5) colony-forming units/mL in 67% of samples; 204 of 406 patients with single-species infections had increased leukocyte counts in urine. Patients with symptoms of urinary tract infection who are culture negative on standard testing may harbor fastidious bacteria or low numbers of conventional uropathogens in the bladder. In these patients, culture of bladder aspiration urine for low counts and fastidious species is necessary to diagnose bacteriuria.     

Toxicity of local,continuous and cyclic,high-dose bladder perfusion with recombinant and natural interleukin-2 in advanced cancer of the urinary bladder

We evaluated the toxicity of high-dose local interleukin-2 (IL-2) in 18 patients not eligible for standard treatment of advanced transitional cell bladder carcinoma. Seven received continuous high-dose local natural IL-2 via pump system in the bladder for up to 420 days. 11 received cyclic high-dose local natural IL-2 or recombinant IL-2 for up to 420 days. Treatment was well tolerated and, considering the low rate of toxicity, could be offered in an outpatient setting. Except for local contrast-media hypersensitivity, no serious side-effects were observed. This study provides a basis for the non-toxic use of local IL-2 in future studies to evaluate effectiveness of the treatment or prophylaxis of patients with superficial bladder cancer in order to prevent recurrences.Abbreviations IL-2 interleukin-2 - TUR transurethral resection - TNF tumor necrosis factor This study was supported by the Deutsche Forschungsgemeinschaft