OBJECTIVETo investigate the significance of apolipoprotein (Apo)-A1 in urine as a biomarker for early diagnosis and classification of bladder urothelial carcinoma (BUC).

METHODSUrine samples were divided into four groups: normal control group, benign bladder disease group, low-grade malignant BUC group, and high-grade malignant BUC group. Apo-A1, which showed significantly different expression among the four groups, was selected according to the two-dimensional electrophoresis (2-DE) images of the four groups, and enzyme-linked immunosorbent assay (ELISA) was used to quantify Apo-A1 in the four groups. A receiver operating characteristic (ROC) curve was generated, and the optimal operating points on the ROC curve were found to determine the critical concentrations of Apo-A1 for early diagnosis of BUC and differentiation of low-grade and high-grade malignant BUC. The results were verified clinically, and the specificity and sensitivity were calculated.

RESULTSThe 2-DE images showed that that the level of Apo-A1 increased from the normal control grouP to high-grade malignant BUC group. The ELISA showed that there was no significant difference in Apo-A1 level between the normal control grouP and benign bladder disease group, but the Apo-A1 level was significantly higher in the BUC groups than in the normal control grouP and benign bladder disease grouP (P < 0.01); the high-grade BUC grouP had a significantly higher Apo-A1 level than the low-grade BUC grouP (P < 0.01). The BUC patients and those without BUC could be differentiated with an Apo-A1 concentration of 18.22 ng/ml, while the low-grade and high-grade malignant BUC could be differentiated with an Apo-A1 concentration of 29.86 ng/ml. When used as a biomarker, Apo-A1 had a sensitivity of 91.6% (98/107) and a specificity of 85.7% (42/49) for diagnosis of BUC and had a sensitivity of 83.7% (41/49) and a specificity of 89.7% (52/58) for BUC classification.

CONCLUSIONApo-A1 may be a biomarker for early diagnosis and classification of BUC and shows promise for clinical application.

Aged ; Apolipoprotein A-I ; urine ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Urinary Bladder Neoplasms ; diagnosis ; urine

OBJECTIVETo investigate the difference in urinary proteome between patients with bladder urothelial carcinoma (BUC) and healthy volunteers and to provide a basis for the early diagnosis of BUC.

METHODSThe urine samples from BUC patients and healthy volunteers (controls) were treated by 25% ethanol precipitation and two-dimensional gel electrophoresis (2-DE), and the obtained urinary proteins were subjected to Coomassie brilliant blue staining and analysis by PDQuest 8.0 (2-DE image analysis software); the differentially expressed proteins were sequenced by matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry and identified using the Swiss-Prot database; the differential expression of these proteins was verified by western blot.

RESULTSHigh-resolution and high-reproducibility 2-DE images were obtained from the urine samples of BUC patients and controls, with 789 ± 18 and 762 ± 14 protein spots, respectively. Compared with the control group, the BUC grouP had significantly decreased expression of 6 protein spots and significantly increased expression of 11 protein spots. The mass spectrometry revealed five proteins with increased expression in the BUC group, including fibrinogen, lactate dehydrogenase B, apolipoprotein A1, clusterin, and haptoglobin, and the results were confirmed by western blot.

CONCLUSIONThere is significant difference in urinary proteome between BUC patients and healthy volunteers; the identification of differentially expressed proteins in urine lays the foundation for identifying potential molecular markers in early diagnosis of BUC.

Aged ; Case-Control Studies ; Early Detection of Cancer ; Female ; Humans ; Male ; Middle Aged ; Proteomics ; methods ; Urinary Bladder Neoplasms ; diagnosis ; urine

BACKGROUND: Cancer rates are increasing not only in the general population but also in patients with end-stage renal disease. We investigated the changing pattern of pretransplant malignancy in kidney transplant recipients over 5 decades.METHODS: We reviewed 3,748 kidney transplant recipients between 1969 and 2016. We divided patients into three groups (1969–1998, 1999–2006, 2007–2016) based on the era of the cancer screening system used throughout the nation. We analyzed the incidence and pattern of pretransplant malignancy among the three groups. We also evaluated recurrent and de novo malignancy in these patients compared to patients without pretransplant malignancy.RESULTS: A total of 72 patients exhibited pretransplant malignancy (1.9%). There were no cases of pretransplant cancer until 1998, but the rate of pretransplant malignancy gradually increased to 1.1% during 1999–2006 and further increased to 4.3% thereafter. The most frequent types of pretransplant malignancy changed from the bladder, liver, and stomach cancers to thyroid cancer and renal cell carcinoma. There were no de novo cases, but there were three cases of recurrent cancer in patients with pretransplant malignancy; the recurrence rate among kidney transplant recipients with pretransplant malignancy was not significantly different from the incidence rate of de novo malignancy among kidney transplant recipients without pretransplant malignancy (4.2% vs. 6.9%, P = 0.48).CONCLUSION: The incidence of pretransplant malignancy in kidney transplantation candidates is gradually increasing, and recent increases were accompanied by changes in cancer types. Pretransplant malignancy may not be a hindrance to kidney transplantation because of the low incidence of posttransplant recurrence and de novo malignancy.
Carcinoma, Renal Cell ; Early Detection of Cancer ; Humans ; Incidence ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney ; Liver ; Recurrence ; Stomach Neoplasms ; Thyroid Neoplasms ; Transplant Recipients ; Urinary Bladder

PURPOSE: The aim of this study was to evaluate the usefulness of whole body positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) for cancer screening in asymptomatic subjects. MATERIALS AND METHODS: The subjects were 1,762 men and 259 women who voluntarily underwent 18F-FDG PET for cancer screening as a part of a routine health examination. Final diagnosis was decided by other diagnostic studies, pathological results or clinical follow-up for 1 year. RESULTS: Of 2,021 subjects, 40 (2.0%) were finally proved to have cancer. Abnormal focal 18F-FDG uptake suggesting malignancy was found in 102 subjects (5.0%). Among them, 21 subjects (1.0%) were proved to have cancer. Other tests in the routine health examination could not find 9 of 21 cancers (42.9%) detected by PET. The sensitivity, specificity, positive predictive value, and negative predictive value of PET for cancer screening were 52.5%, 95.9%, 20.6%, and 99.0%, respectively. Pathologies of cancers missed on PET were adenocarcinoma (n=9; 3 colon cancers, 3 prostate cancers, 2 stomach cancers, and 1 rectal cancer), differentiated thyroid carcinoma (n=6), bronchioalveolar cell carcinoma (n=2), urinary bladder cancer (n=1), and melanoma (n=1). More than half of cancers which were not detected by PET were smaller than 1 cm in diameter. CONCLUSION: 18F-FDG PET might be useful for cancer screening in asymptomatic subjects due to its high specificity and negative predictive value and play a supplementary role to the conventional health check-up, but it could not replace due to limited sensitivity for urological cancers, small-sized tumors and some hypometaboic cancers.
Adenocarcinoma ; Colonic Neoplasms ; Early Detection of Cancer ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Male ; Melanoma ; Positron-Emission Tomography ; Prostatic Neoplasms ; Sensitivity and Specificity ; Stomach Neoplasms ; Thyroid Neoplasms ; Urinary Bladder Neoplasms ; Urologic Neoplasms

OBJECTIVETo investigate the clinical methods for reducing bladder cancer recurrence after surgical treatment for renal pelvic carcinoma.

METHODSFrom October 1997 to December 2007, the data of 227 patients undergoing total nephroureterectomy for clinically localized transitional cell carcinoma of the renal pelvis with follow-up results were analyzed retrospectively, including 126 cases of male and 101 cases of female, and the age was 34 to 78 years old. There were 2 kinds of technique used in the dissection of bladder wall circumferentially around the ureteral orifice. Technique A was dissection along the ipsilateral ureter to the bladder wall. Technique B was dissection along the vas deferens to the bladder wall circumferentially around the ipsilateral ureteral orifice and division of the lateral vesical ligament to reach the seminal vesicle. Prophylactic intravesical chemotherapy included 3 method. Method 1 was intraoperative intravesical chemotherapy and then administrated once a week, 10 times in total. Method 2 was intraoperative intravesical chemotherapy and then administrated once a week from the 4(th) week after operation, 10 times in total. Method 3 was intravesical chemotherapy was given once a week from the 4(th) week after operation, 10 times in total. The time of follow-up was 1 to 10 years with regular cystoscopy. Chi-square test and Logistic regression were used to analyzed the recurrence rate of bladder cancer.

RESULTSRecurrence rate of bladder cancer was 27.8% (63/227). The recurrence rates of bladder cancer in patients using technique A and B were 18.0% (7/39) and 12.5% (3/24), respectively (P < 0.05). The postoperative recurrence rates of bladder cancer in patients using 3 kinds of intravesical chemotherapy regimen were 17.9% (11/67), 20.8% (10/48) and 33.3% (17/51), respectively. There was significant difference between the recurrence rates of patients using method 1 and method 3 intravesical chemotherapy (P < 0.05).

CONCLUSIONComplete removal of the bladder mucosa circumferentially around the ureteral orifice, administration of the intraoperative intravesical chemotherapy instillation and instillation once a week may be a useful approach to reduce the recurrence of bladder cancer after operation for renal pelvic carcinoma.

Adult ; Aged ; Carcinoma, Renal Cell ; surgery ; Chemotherapy, Cancer, Regional Perfusion ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; surgery ; Kidney Pelvis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Care ; Retrospective Studies ; Urinary Bladder Neoplasms ; prevention & control ; secondary

OBJECTIVETo develop a novel vaccine by immobilizing interleukin-21 (IL-21) on the surface of MB49 cells and evaluate its effect in inducing specific cytotoxic T lymphocytes (CTLs) and antitumor immunity in a mouse model of subcutaneous metastatic bladder cancer.

METHODSSA-IL-21 was immobilized on the surface of 30% ethanol-fixed MB49 cells to prepare the cell vaccine. C57BL/6 mice with subcutaneous implantation of MB49 bladder cancer cells were randomized into 5 groups to receive treatments with IL-21/MB49 vaccine, soluble IL-21, GFP surface-modified MB49 cells, ethanol-fixed MB49 cells, or PBS. The tumor growth and CTL were examined to assess the antitumor efficacy of the vaccine.

RESULTSIL-21 surface-modified MB49 cell vaccine significantly inhibited the tumor growth and generated a long-lasting memory response (P<0.05). At the same effector-target (E:T) ratio, the specific CTLs induced by IL-21/MB49 vaccine showed the most potent cytotoxicity against MB49 cells (P<0.05).

CONCLUSIONWith the protein-anchor technique, IL-21 can be efficiently immobilized on the surface of MB49 cells to prepare IL-21/MB49 cells vaccine. The novel vaccine can maintain its biological activity and significantly enhance the cytotoxicity of CTLs against bladder cancer cells.

Amino Acid Motifs ; Animals ; Cancer Vaccines ; therapeutic use ; Cell Line, Tumor ; Female ; Immunotherapy ; Interleukins ; immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Neoplasm Metastasis ; Neoplasms, Experimental ; therapy ; T-Lymphocytes, Cytotoxic ; immunology ; Urinary Bladder Neoplasms ; therapy

Animals ; B7-1 Antigen ; genetics ; Cancer Vaccines ; immunology ; Combined Modality Therapy ; Female ; Genetic Therapy ; Mice ; Mice, Inbred C3H ; Sulfinic Acids ; pharmacology ; therapeutic use ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Urinary Bladder Neoplasms ; therapy ; Vaccination

Eosinophilic cystitis is a rare form of allergic cystitis. We reported a case of eosinophilic cystitis coexisting with superficial bladder cancer, which seemed to be invasive bladder cancer on imaging. We performed total cystectomy in this case. When invasive bladder cancer is diagnosed by imaging, coexistence of eosinophilic cystitis with superficial bladder cancer should be considered if biopsy does not show invasive bladder cancer.
Cancer of Bladder ; Cystitis ; Eosinophilic ; Superficial ; Diagnostic Imaging

Lung cancer survivors need to undergo continuous care by primary care physicians after acute treatment. The health problems of lung cancer survivors are associated with their treatment: for example, severe pain, respiratory difficulty, poor quality of life, or pneumonitis. They also have various comorbidities, such as stroke, myocardial infarction, arrhythmia, chronic obstructive pulmonary disease, or psychological problems. Surveillance of lung cancer survivors is based on an annual chest CT with routine physical examination. Incidence of second primary cancer in lung cancer survivors is reported to increase in the remnant lung, head and neck, kidney, bladder, thyroid, stomach, and breast. Therefore, lung cancer survivors need to undergo regular health examination for early detection of cancer. Smoking status, weight change, drinking behavior, and vaccination, especially influenza and pneumococcal vaccination, should be assessed whenever the patient meets a clinician. The primary care physician would be expected to take on the role of managing the health problems of Korean lung cancer survivors comprehensively, including physical and psychosocial problems, from screening to survivorship care.
Arrhythmias, Cardiac ; Breast ; Comorbidity ; Drinking Behavior ; Early Detection of Cancer ; Head ; Humans ; Incidence ; Influenza, Human ; Kidney ; Korea* ; Long-Term Care ; Lung Neoplasms* ; Lung* ; Mass Screening ; Myocardial Infarction ; Neck ; Neoplasms, Second Primary ; Physical Examination ; Physicians, Primary Care ; Pneumonia ; Primary Health Care ; Pulmonary Disease, Chronic Obstructive ; Quality of Life ; Smoke ; Smoking ; Stomach ; Stroke ; Survival Rate ; Survivors* ; Thyroid Gland ; Tomography, X-Ray Computed ; Urinary Bladder ; Vaccination

OBJECTIVETo prepare IL-2-anchored and tumor-derived exosomes vaccine, and investigate the antitumor efficiency of the special cytotoxic T-lymphocytes induced by Ex/GPI-IL-2.

METHODSTo construct pEGFP-N1-IL2gpi plasmid coding a fusion gene of a DNA oligo encoding GPI-anchor signal sequence attaching to human IL-2 cDNA. Then T24 cell lines stably expressing GPI-IL-2 proteins (T24/GPI-IL-2) were established. Ex/GPI-IL-2 were isolated and purified by ultrafiltration and sucrose gradient centrifugation, and the morphology and molecule markers were analyzed. The mixed lymphocyte reaction study and cytotoxic study were performed to determine the proliferative effect of T lymphocytes and the cytotoxicity induced by Ex/GPI-IL-2.

RESULTSThe pEGFP-N1-IL2gpi plasmid was successfully constructed, and cell lines stably expressing GPI-IL-2 fusion proteins were established. Ex/GPI-IL-2 were small vesicular and saucer-shaped in diameter of 30-90 nm, containing heat shock protein 70, intercellular adhesion molecule-1, MAGE-1 and GPI-IL-2. Ex/GPI-IL-2-pulsed could dendritic cells induce proliferation of T cells and cytotoxic immune response more efficiently (P<0.05).

CONCLUSIONSGPI-IL-2 gene-modified tumor cells can make the exosomes containing GPI-IL-2 with an increased anti-tumor effect. Our study provides a feasible approach for exosome-based tumor immunotherapy of bladder transitional cell tumors.

Cancer Vaccines ; immunology ; Carcinoma, Transitional Cell ; immunology ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Exosomes ; genetics ; metabolism ; Glycosylphosphatidylinositols ; metabolism ; HSP70 Heat-Shock Proteins ; metabolism ; Humans ; Intercellular Adhesion Molecule-1 ; metabolism ; Interleukin-2 ; metabolism ; Melanoma-Specific Antigens ; metabolism ; Plasmids ; Recombinant Fusion Proteins ; metabolism ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Urinary Bladder Neoplasms ; immunology ; metabolism ; pathology