ABSTRACT
OBJECTIVES: Autoimmune and allergic diseases are outcomes of the dysregulation of the immune system. Our study aimed to elucidate differences or shared components in genetic backgrounds between autoimmune and allergic diseases. METHODS: We estimated genetic correlation and performed multi-trait and cross-population genome-wide association study (GWAS) meta-analysis of six immune-related diseases: rheumatoid arthritis, Graves' disease, type 1 diabetes for autoimmune diseases and asthma, atopic dermatitis and pollinosis for allergic diseases. By integrating large-scale biobank resources (Biobank Japan and UK biobank), our study included 105 721 cases and 433 663 controls. Newly identified variants were evaluated in 21 778 cases and 712 767 controls for two additional autoimmune diseases: psoriasis and systemic lupus erythematosus. We performed enrichment analyses of cell types and biological pathways to highlight shared and distinct perspectives. RESULTS: Autoimmune and allergic diseases were not only mutually classified based on genetic backgrounds but also they had multiple positive genetic correlations beyond the classifications. Multi-trait GWAS meta-analysis newly identified six allergic disease-associated loci. We identified four loci shared between the six autoimmune and allergic diseases (rs10803431 at PRDM2, OR=1.07, p=2.3×10-8, rs2053062 at G3BP1, OR=0.90, p=2.9×10-8, rs2210366 at HBS1L, OR=1.07, p=2.5×10-8 in Japanese and rs4529910 at POU2AF1, OR=0.96, p=1.9×10-10 across ancestries). Associations of rs10803431 and rs4529910 were confirmed at the two additional autoimmune diseases. Enrichment analysis demonstrated link to T cells, natural killer cells and various cytokine signals, including innate immune pathways. CONCLUSION: Our multi-trait and cross-population study should elucidate complex pathogenesis shared components across autoimmune and allergic diseases.
ABSTRACT
We describe the case of a patient with hyperammonemia owing to urinary tract infections. The patient, a 66-year-old-woman, was previously diagnosed with bilateral hydronephrosis. She was admitted to the emergency room with macrohematuria and bilateral lumbar pain, which persisted for 2 days. She was hospitalized with the diagnosis of pyelonephritis. Despite antibiotic treatment, she developed sudden disturbance in consciousness on the 2nd day of illness. To improve the hyperammonemia and metabolic acidosis, we initiated continuous hemodiafiltration (CHDF) and urinary drainage by bilateral nephrostomy, after which her consciousness improved, and she was discharged on day 19. For patients with urinary tract infections and who are unaware of disturbance in consciousness, it is important to consider that obstructive urinary tract infections can cause hyperammonemia.
Subject(s)
Consciousness Disorders , Hyperammonemia , Pyelonephritis , Urinary Tract Infections , Aged , Consciousness , Consciousness Disorders/etiology , Female , Humans , Hyperammonemia/complications , Hyperammonemia/etiology , Renal DialysisABSTRACT
Our recent determination of a microRNA (miRNA) expression signature in prostate cancer (PCa) revealed that miR-205-5p was significantly reduced in PCa tissues and that it acted as an antitumor miRNA. The aim of this study was to identify oncogenic genes and pathways in PCa cells that were regulated by antitumor miR-205-5p. Genome-wide gene expression analyses and in silico miRNA database searches showed that 37 genes were putative targets of miR-205-5p regulation. Among those genes, elevated expression levels of seven in particular (HMGB3, SPARC, MKI67, CENPF, CDK1, RHOU, and POLR2D) were associated with a shorter disease-free survival in a large number of patients in the The Cancer Genome Atlas (TCGA) database. We focused on high-mobility group box 3 (HMGB3) because it was the most downregulated by ectopic expression of miR-205-5p in PC3 cells and its expression was involved in PCa pathogenesis. Luciferase reporter assays showed that HMGB3 was directly regulated by miR-205-5p in PCa cells. Knockdown studies using si-HMGB3 showed that expression of HMGB3 enhanced PCa cell aggressiveness. Overexpression of HMGB3/HMGB3 was confirmed in naive PCa and castration-resistant PCa (CRPC) clinical specimens. Novel approaches to analysis of antitumor miRNA-regulated RNA networks in PCa cells may provide new insights into the pathogenic mechanisms of the disease.
Subject(s)
Genes, Tumor Suppressor , HMGB3 Protein/biosynthesis , MicroRNAs/biosynthesis , Neoplasm Proteins/biosynthesis , Prostatic Neoplasms, Castration-Resistant , RNA, Neoplasm/biosynthesis , Cell Line, Tumor , HMGB3 Protein/genetics , Humans , Male , MicroRNAs/genetics , Neoplasm Proteins/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/metabolism , Prostatic Neoplasms, Castration-Resistant/pathology , RNA, Neoplasm/geneticsABSTRACT
Our recent studies of microRNA (miRNA) expression signatures of prostate cancer (PCa) showed that six miRNAs (specifically, miR-26a, miR-26b, miR-29a, miR-29b, miR-29c and miR-218) were markedly reduced in cancer tissues. Moreover, ectopic expression of these miRNAs suppressed PCa cell aggressiveness, indicating that these miRNAs acted in concert to regulate genes that promoted metastasis. Genome-wide gene expression analysis and in silico database analysis identified a total of 35 candidate genes that promoted metastasis and were targeted by these 6 miRNAs. Using luciferase reporter assays, we showed that the lysyl oxidase-like 2 (LOXL2) gene was directly controlled by these tumor-suppressive miRNAs in PCa cells. Overexpression of LOXL2 was confirmed in PCa tissues and knockdown of the LOXL2 gene markedly inhibited the migration and invasion of PCa cells. Aberrant expression of LOXL2 enhanced migration and invasion of PCa cells. Downregulation of antitumor miRNAs might disrupt the tightly controlled RNA networks found in normal cells. New insights into the novel molecular mechanisms of PCa pathogenesis was revealed by antitumor miRNA-regulated RNA networks.
Subject(s)
Amino Acid Oxidoreductases/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Prostatic Neoplasms/genetics , 3' Untranslated Regions/genetics , Amino Acid Oxidoreductases/metabolism , Amino Acid Sequence , Blotting, Western , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Gene Expression Profiling/methods , Genes, Tumor Suppressor , Humans , Immunohistochemistry , Male , Neoplasm Invasiveness , Neoplasm Metastasis , Prostatic Neoplasms/metabolism , Prostatic Neoplasms/pathology , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic AcidABSTRACT
Analysis of microRNA (miRNA) expression signatures in prostate cancer (PCa) and castration-resistant PCa has revealed that miRNA-223 is significantly downregulated in cancer tissues, suggesting that miR-223 acts as a tumor-suppressive miRNA by targeting oncogenes. The aim of this study was to investigate the functional roles of miR-223 and identify downstream oncogenic targets regulated by miR-223 in PCa cells. Functional studies of miR-223 were carried out to investigate cell proliferation, migration, and invasion using PC3 and PC3M PCa cell lines. Restoration of miR-223 significantly inhibited cancer cell migration and invasion in PCa cells. In silico database and genome-wide gene expression analyses revealed that ITGA3 and ITGB1 were direct targets of miR-223 regulation. Knockdown of ITGA3 and ITGB1 significantly inhibited cancer cell migration and invasion in PCa cells by regulating downstream signaling. Moreover, overexpression of ITGA3 and ITGB1 was observed in PCa clinical specimens. Thus, our data indicated that downregulation of miR-223 enhanced ITGA3/ITGB1 signaling and contributed to cancer cell migration and invasion in PCa cells. Elucidation of the molecular pathways modulated by tumor-suppressive miRNAs provides insights into the mechanisms of PCa progression and metastasis.
Subject(s)
Cell Movement , Gene Expression Regulation, Neoplastic/genetics , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Aged , Aged, 80 and over , Blotting, Western , Cell Line, Tumor , Gene Knockdown Techniques , Humans , Immunohistochemistry , Integrin alpha3/metabolism , Integrin beta1/metabolism , Male , Middle Aged , Neoplasm Invasiveness/genetics , Real-Time Polymerase Chain Reaction , Signal Transduction/genetics , TransfectionABSTRACT
In spite of considerable advances in multimodality therapy, including surgery, radiotherapy and chemotherapy, the overall survival rate for patients with head and neck squamous cell carcinoma (HNSCC) is very poor (only 15-45%). Understanding the molecular mechanisms of metastatic pathways underlying HNSCC using currently available genomic approaches might improve therapies for and prevention of the disease. Our previous studies showed that three tumor-suppressive microRNAs (miRNAs), miR-26a/b, miR-29a/b/c and miR-218, significantly inhibited cancer cell migration and invasion. Therefore, we hypothesized that these miRNAs-regulated target genes deeply contributed to cancer metastasis. These tumor-suppressive miRNAs directly regulate LOXL2 expression in HNSCC cells by using in silico analysis and luciferase reporter assays. Overexpressed LOXL2 was confirmed in HNSCC clinical specimens, and silencing of LOXL2 inhibited cancer cell migration and invasion in HNSCC cell lines. Our present data showed that tumor-suppressive miRNAs regulation of LOXL2 will provide new insights into the novel molecular mechanisms of HNSCC metastasis.
Subject(s)
Amino Acid Oxidoreductases/genetics , Carcinoma, Squamous Cell/genetics , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms/genetics , MicroRNAs/metabolism , Amino Acid Oxidoreductases/metabolism , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Head and Neck Neoplasms/metabolism , Head and Neck Neoplasms/pathology , Humans , Squamous Cell Carcinoma of Head and NeckABSTRACT
The urine cytology test is one of the most important tools for the diagnosis of malignant urinary tract tumors. This test is also of great value for predicting malignancy. However, the sensitivity of this test is not high enough to screen for malignant cells. In our laboratory, we were able to attain a high sensitivity of urine cytology tests after changing the preparation method of urine samples. The differences in the cytodiagnosis between the two methods are discussed here. From January 2012 to June 2013, 2,031 urine samples were prepared using the conventional centrifuge method (C method) ; and from September 2013 to March 2015, 2,453 urine samples were prepared using the filtration method (F method) for the cytology test. When the samples included in category 4 or 5, were defined as cytological positive, the sensitivities of this test with samples prepared using the F method were significantly high compared with samples prepared using the C method (72% vs 28%, pï¼0.001). The number of cells on the glass slides prepared by the F method was significantly higher than that of the samples prepared by the C method (pï¼0.001). After introduction of the F method, the number of f alse negative cases was decreased in the urine cytology test because a larger number of cells was seen and easily detected as atypical or malignant epithelial cells. Therefore, this method has a higher sensitivity than the conventional C method as the sensitivity of urine cytology tests relies partially on the number of cells visualized in the prepared samples.
Subject(s)
Cytodiagnosis/methods , Specimen Handling/methods , Urine/cytology , Urologic Neoplasms/diagnosis , Urologic Neoplasms/urine , Adult , Aged , Aged, 80 and over , Centrifugation , False Negative Reactions , Female , Filtration , Humans , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
BACKGROUND: Our present study of the microRNA (miRNA) expression signature in castration-resistant prostate cancer (CRPC) revealed that the clustered miRNAs microRNA-221 (miR-221) and microRNA-222 (miR-222) are significantly downregulated in cancer tissues. The aim of this study was to investigate the functional roles of miR-221 and miR-222 in prostate cancer (PCa) cells. METHODS: A CRPC miRNA signature was constructed by PCR-based array methods. Functional studies of differentially expressed miRNAs were analysed using PCa cells. The association between miRNA expression and overall survival was estimated by the Kaplan-Meier method. In silico database and genome-wide gene expression analyses were performed to identify molecular targets regulated by the miR-221/222 cluster. RESULTS: miR-221 and miR-222 were significantly downregulated in PCa and CRPC specimens. Kaplan-Meier survival curves showed that low expression of miR-222 predicted a short duration of progression to CRPC. Restoration of miR-221 or miR-222 in cancer cells revealed that both miRNAs significantly inhibited cancer cell migration and invasion. Ecm29 was directly regulated by the miR-221/222 cluster in PCa cells. CONCLUSIONS: Loss of the tumour-suppressive miR-221/222 cluster enhanced migration and invasion in PCa cells. Our data describing targets regulated by the tumour-suppressive miR-221/222 cluster provide insights into the mechanisms of PCa and CRPC progression.
Subject(s)
Biomarkers, Tumor/genetics , MicroRNAs/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , Cell Line, Tumor , Cell Movement , Disease Progression , Down-Regulation , Gene Expression Regulation, Neoplastic , Humans , Male , Multigene Family , Prognosis , Prostatic Neoplasms, Castration-Resistant/mortality , Survival AnalysisABSTRACT
Lung cancer is clearly the primary cause of cancer-related deaths worldwide. Recent molecular-targeted strategy has contributed to improvement of the curative effect of adenocarcinoma of the lung. However, such current treatment has not been developed for squamous cell carcinoma (SCC) of the disease. The new genome-wide RNA analysis of lung-SCC may provide new avenues for research and the development of the disease. Our recent microRNA (miRNA) expression signatures of lung-SCC revealed that clustered miRNAs miR-1/133a were significantly reduced in cancer tissues. Here, we found that restoration of both mature miR-1 and miR-133a significantly inhibited cancer cell proliferation, migration and invasion. Coronin-1C (CORO1C) was a common target gene of the miR-1/133a cluster, as shown by the genome-wide gene expression analysis and the luciferase reporter assay. Silencing of CORO1C gene expression inhibited cancer cell proliferation, migration and invasion. Furthermore, CORO1C-regulated molecular pathways were categorized by using si-CORO1C transfectants. Further analysis of novel cancer signaling pathways modulated by the tumor-suppressive cluster miR-1/133a will provide insights into the molecular mechanisms of lung-SCC oncogenesis and metastasis.
Subject(s)
Carcinoma, Squamous Cell/genetics , Cell Movement/genetics , Lung Neoplasms/genetics , MicroRNAs/genetics , Microfilament Proteins/genetics , Aged , Aged, 80 and over , Azacitidine/pharmacology , Blotting, Western , Carcinoma, Squamous Cell/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Proliferation/genetics , Down-Regulation , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation, Neoplastic/drug effects , Humans , Hydroxamic Acids/pharmacology , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Male , Microfilament Proteins/metabolism , Middle Aged , Multigene Family , Neoplasm Invasiveness , RNA Interference , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
OBJECTIVES: To investigate the functional roles of microRNA-205 in the modulation of novel cancer pathways in prostate cancer cells. METHODS: Functional studies of microRNA-205 were carried out to investigate cell proliferation, migration and invasion in prostate cancer cell lines (PC3 and DU145) by restoration of mature microRNA. In silico database and genome-wide gene expression analyses were carried out to identify molecular targets and pathways mediated by microRNA-205. Loss-of-function studies were applied to microRNA-205 target genes. RESULTS: Restoration of microRNA-205 in cancer cell lines significantly inhibited cancer cell migration and invasion. Our data showed that the centromere protein F gene was overexpressed in prostate cancer clinical specimens and was a direct target of microRNA-205 regulation. Silencing of centromere protein F significantly inhibited cancer cell migration and invasion. Furthermore, MCM7, an oncogenic gene functioning downstream of centromere protein F, was identified by si-centromere protein F transfectants in prostate cancer cells. CONCLUSIONS: Loss of tumor-suppressive microRNA-205 seems to enhance cancer cell migration and invasion in prostate cancer through direct regulation of centromere protein F. Our data describing pathways regulated by tumor-suppressive microRNA-205 provide new insights into the potential mechanisms of prostate cancer oncogenesis and metastasis.
Subject(s)
Cell Movement/genetics , Chromosomal Proteins, Non-Histone/genetics , Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Microfilament Proteins/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Aged , Base Sequence , Cell Line, Tumor , Cell Proliferation/genetics , Chromosomal Proteins, Non-Histone/metabolism , Gene Expression , Gene Expression Profiling , Gene Silencing , Humans , Male , MicroRNAs/metabolism , Microfilament Proteins/metabolism , Middle Aged , Molecular Sequence Data , Neoplasm Invasiveness/genetics , Prostate/metabolism , Signal Transduction/genetics , TransfectionABSTRACT
Our recent studies of the microRNA (miRNA) expression signature in prostate cancer (PCa) indicated that miRNA-218 (miR-218) was significantly downregulated in clinical specimens, suggesting that miR-218 might act as a tumor-suppressive miRNA in PCa. The aim of the present study was to investigate the functional significance of miR-218 in PCa and to identify novel miR-218-regulated cancer pathways and target genes involved in PCa oncogenesis and metastasis. Restoration of miR-218 in PCa cell lines (PC3 and DU145) revealed that this miRNA significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that LIM and SH3 protein 1 (LASP1) is a potential target of miR-218 regulation. LASP1 is a cytoskeletal scaffold protein that plays critical roles in cytoskeletal organization and cell migration. Luciferase reporter assays showed that miR-218 directly regulated expression of LASP1. Moreover, downregulating the LASP1 gene significantly inhibited cell migration and invasion in cancer cells, and the expression of LASP1 was upregulated in cancer tissues. We conclude that loss of tumor-suppressive miR-218 enhanced cancer cell migration and invasion in PCa through direct regulation of LASP1. Our data on pathways regulated by tumor-suppressive miR-218 provide new insight into the potential mechanisms of PCa oncogenesis and metastasis.
Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cytoskeletal Proteins/metabolism , Gene Expression Regulation, Neoplastic , LIM Domain Proteins/metabolism , MicroRNAs/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Adaptor Proteins, Signal Transducing/genetics , Aged , Cell Movement/genetics , Cell Proliferation , Cytoskeletal Proteins/genetics , Humans , LIM Domain Proteins/genetics , Male , Middle Aged , Molecular Sequence Data , Tumor Cells, CulturedABSTRACT
PURPOSE: We observed abnormal expression of the microRNA-23b/27b (miR-23b/27b) cluster in our previous study of miRNA expression signatures. However, the relationship between aberrant miRNA expression and clear cell renal cell carcinoma is not well established. We investigated the functional significance of the miR-23b/27b cluster in clear cell renal cell carcinoma cells and evaluated these miRNAs as biomarkers to predict the risk of clear cell renal cell carcinoma. MATERIALS AND METHODS: Expression levels of miR-23b and miR-27b were determined by quantitative real-time reverse transcriptase-polymerase chain reaction. The association between miRNA expression and overall survival was estimated by the Kaplan-Meier method. Gain of function assays were performed using mature miR-23b and miR-27b in the 786-O and A498 renal cell carcinoma cell lines. Targets regulated by these miRNAs were predicted by in silico analysis. RESULTS: Expression of the miR-23b/27b cluster was significantly decreased in clear cell renal cell carcinoma tissue specimens and associated with pathological grade and stage. Significantly shorter overall survival was observed in patients with lower expression of the miR-23b/27b cluster. Restoration of miR-23b and miR-27b significantly inhibited cancer cell proliferation, migration and invasion. CONCLUSIONS: Expression of the miR-23b/27b cluster was frequently decreased in clear cell renal cell carcinoma tissue. Reduced expression of these miRNAs increased the risk of disease progression and predicted poor survival. Thus, miR-23b and miR-27b function as tumor suppressors, targeting several oncogenic genes in clear cell renal cell carcinoma cells.
Subject(s)
Carcinoma, Renal Cell/metabolism , Kidney Neoplasms/metabolism , MicroRNAs/biosynthesis , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Tumor Cells, CulturedABSTRACT
Our recent study of microRNA (miRNA) expression signature of prostate cancer (PCa) has revealed that the microRNA-143/145 (miR-143/145) cluster is significantly downregulated in cancer tissues, suggesting that these cluster miRNAs are candidate tumor suppressors. The aim of this study was to investigate the functional significance of the miR-143/145 cluster in PCa cells and to identify novel targets regulated by these cluster miRNAs in PCa. Restoration of miR-143 or miR-145 in PCa cell lines (PC3 and DU145) revealed that these miRNAs significantly inhibited cancer cell migration and invasion. Gene expression data and in silico analysis demonstrated that Golgi membrane protein 1 (GOLM1) resembling a type II golgi transmembrane protein was a potential target of miR-143/145 cluster target gene. Gene expression studies and luciferase reporter assays showed that GOLM1 was directly regulated by the miR-143/145 cluster. Silencing of GOLM1 resulted in significant inhibition of cell migration and invasion in PCa cells. Furthermore, the expression of GOLM1 was upregulated in cancer tissues by immunohistochemistry. Loss of the tumor-suppressive miR-143/145 cluster enhanced cancer cell migration and invasion in PCa through directly regulating GOLM1. Our data on target genes regulated by the tumor-suppressive miR-143/145 cluster provide new insights into the potential mechanisms of PCa oncogenesis and metastasis.
Subject(s)
Cell Movement , Gene Expression Regulation , Membrane Proteins/biosynthesis , MicroRNAs/metabolism , Multigene Family , Neoplasm Proteins/biosynthesis , Prostatic Neoplasms/metabolism , RNA, Neoplasm/metabolism , Aged , Cell Line, Tumor , Humans , Male , Membrane Proteins/genetics , MicroRNAs/genetics , Middle Aged , Neoplasm Invasiveness , Neoplasm Proteins/genetics , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , RNA, Neoplasm/geneticsABSTRACT
Pre-chemotherapeutic factors to assess the prognosis of patients with advanced urothelial carcinoma have not yet been completely established. The immune response of the host to the tumor is lymphocyte dependent. However, the effect of lymphocytes on chemotherapy prognosis is unknown. In this study, we investigated the correlation between pre-chemotherapeutic lymphocyte counts and the clinical characteristics of urothelial carcinoma and determined the effectiveness of lymphocytes as a prognostic predictor for metastatic urothelial carcinoma treated with chemotherapy. Between April 2003 and March 2011, data from 34 patients with unresectable or metastatic urothelial carcinoma were retrospectively subjected to multivariate regression analysis to determine the patient characteristics with independent prognostic significance for survival. The median patient age was 71 ; 21 patients were male and 13 female. The number of primary tumors in the pelvis, ureter, and bladder were four, six, and 24, respectively. Seventeen patients underwent prior curative resections, and visceral metastases at chemotherapy were detected in 14 patients. The median lymphocyte count at chemotherapy was 1,292/ml. Cancer-specific survival was significantly lower in patients with lymphocyte counts ï¼1,000/ml than in patients with lymphocyte counts ≥1,000/µl (pï¼0. 001). During multivariate analysis, visceral metastasis and lymphocyte counts were independent factors for predicting poor prognosis. In addition, lymphocyte counts of ï¼1, 000/ml or positive visceral metastases also affected survival. This information may be useful for identifying patients who are likely to benefit from chemotherapy.
Subject(s)
Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/drug therapy , Lymphocyte Count , Urologic Neoplasms/blood , Urologic Neoplasms/drug therapy , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Multivariate Analysis , Neoplasm Metastasis , PrognosisABSTRACT
Tertiary syphilis is recently a rare disease in Japan. In this paper, we report a rare case of syphilitic orchitis. The patient was in his early forties. The left scrotal contents were swelling and a low echoic nodule measuring about 30 mm in diameter was detected on ultrasonography. Serum alpha fetoprotein, lactate dehydrogenase, and beta subunit of human chorionic gonadotropin were within the normal range, whereas Treponema pallidum hemagglutination assay and rapid plasma reagin were strongly positive. High orchiectomy was performed for suspicion of testicular tumor. Histological findings showed the non-specific inflammatory granuloma with lympho-plasmatic infiltration. It was diagnosed as granulomatous inflammation of left testis caused by syphilis.
Subject(s)
Orchitis/etiology , Syphilis/complications , Adult , Humans , Male , Orchiectomy , Orchitis/pathology , Orchitis/surgery , Syphilis/diagnosis , Syphilis SerodiagnosisABSTRACT
A 66-year-old woman visited our hospital complaining of painful, irritative urinary symptoms and macroscopic hematuria. Cystoscopy revealed a non-papillary tumor covered with necrotic tissue on the right side of the posterior wall of the bladder. Transurethral resection was performed ; histologically, the tumor was found to be composed of carcinomatous and sarcomatous elements. The carcinomatous element consisted of urothelial and squamous cell carcinomas. The sarcomatous element was composed of osteosarcoma, chondrosarcoma and spindle cell sarcoma. Immunohistochemical examination showed that the carcinomatous component was positive for cytokeratin and the sarcomatous component was positive for S-100 protein. The patient underwent total cystectomy with ileal conduit under the diagnosis of carcinosarcoma. Pathological examination showed no residual tumor. She was followed up with no signs of recurrence or metastasis. Computed tomography (CT) at nine months following surgery showed no evidence of recurrence. However, thirteen months after the operation, she complained of lower abdominal pain, and CT demonstrated a bulky intrapelvic tumor and right hydronephrosis. Her condition worsened rapidly and she died one month later.
Subject(s)
Carcinosarcoma/surgery , Urinary Bladder Neoplasms/surgery , Aged , Carcinosarcoma/chemistry , Cystectomy , Female , Histocytochemistry , Humans , Keratins/analysis , Neoplasm Recurrence, Local , S100 Proteins/analysis , Urinary Bladder Neoplasms/chemistry , Urinary DiversionABSTRACT
No established treatment exists for urachal carcinoma,except curative resection,and its prognosis is poor. More than 80% of urachal carcinomas are adenocarcinomas. We report a case of advanced urachal carcinoma treated with S-1 and cisplatin combination (S-1/CDDP) chemotherapy. The patient,a 61-year-old woman,presented with macroscopic hematuria. A tumor was detected on the bladder dome and transurethral resection was performed. Histopathological findings indicated poorly differentiated adenocarcinoma. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels were 3.5 ng/ml and 140 U/ml respectively. Magnetic resonance images indicated an extension of this tumor to the retroperioneal space. Metastasis to her right ischium was suspected from bone scintigraphy results. The tumor was diagnosed as stage IVB (Sheldon's category) urachal carcinoma. After one cycle of S-1/CDDP chemotherapy,the size of the tumor on the bladder dome decreased,after which total cystectomy was performed. The surgical margin of the cystectomy specimen was negative for malignant cells,although poorly differentiated adenocarcinoma was still observed in this specimen. The findings of this study indicate that this therapy might be beneficial for treating advanced urachal carcinomas. This is the second report of successful treatment of advanced urachal carcinoma with S-1/CDDP chemotherapy.
Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Urachus/abnormalities , Urinary Bladder Neoplasms/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Agents/administration & dosage , Cisplatin/administration & dosage , Combined Modality Therapy , Cystectomy , Drug Combinations , Female , Humans , Middle Aged , Oxonic Acid/administration & dosage , Tegafur/administration & dosage , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/therapyABSTRACT
A 48-year-old man with a history of cerebral infarction presented with gross hematuria. The patient's limping accompanies twisting trunk on his walking. The diagnosis was right upper ureteral stone. Prior to Extracorporeal shockwave lithotripsy (ESWL) ureteral stent was inserted. After the second ESWL ureteral stent was displaced upwardly without patient's unknown. Retrograde intrarenal surgery (RIRS) was performed for both removal of ureteral stent and fragmentation of residual stone. Spontaneously, post RIRS ureteral stent was migrated upwardly to the same position. Ureteral stent migration is uncommon. Twisting walk may cause the position of ureteral stent upwardly.
ABSTRACT
Mycobacterium haemophilum is a slow-growing, non-tuberculous mycobacteria that causes cutaneous infection. We describe a case of cutaneous infection in a 68-year-old Japanese man with polymyositis. This was caused by M. haemophilum harboring one base insertion in gene sequence. At first, the causal microorganism was misidentified as M. intracellulare by COBAS® TaqMan® MAI test. However, poor growth on Ogawa media and growth enhancement on 7H11C agar around a hemin-containing disk prompted us to reinvestigate the causal microorganisms, which were revealed to be M. haemophilum. Amplified polymerase chain reaction products were sequenced, and the 16S rRNA gene, rpoB, hsp65 and internal transcribed spacer region sequences showed a 100%, 100%, 99.66% and 99.7% match, respectively, with the corresponding regions of M. haemophilum, but it harbored a novel gene sequence in hsp65. The sequences determined by gene analysis of the M. haemophilum strain were deposited into the International Nucleotide Sequence Database. Although numerous cases of M. haemophilum infection have been reported in other countries, only six cases have been reported in Japan to date. It could be possible that this novel mutation lead to misdiagnosis. As M. haemophilum prefers a lower growth temperature (30-32°C) and it requires iron in the culture medium, M. haemophilum could be misidentified or overlooked. Accordingly, a M. haemophilum infection should be considered in cases of cutaneous infection of the body sites, of which surface temperature is low.
Subject(s)
Mycobacterium avium-intracellulare Infection/diagnosis , Mycobacterium haemophilum/isolation & purification , Skin Diseases, Bacterial/microbiology , Aged , Diagnostic Errors , Humans , Male , Mutagenesis, Insertional , Mycobacterium haemophilum/genetics , Polymyositis/complications , Skin Diseases, Bacterial/diagnosisABSTRACT
Anti-tumor necrosis factor (TNF)-α therapy is used for the treatment of psoriasis, with varying outcomes. However, the specific cause of inadequate response or treatment failure remains unknown. The aim of the present study was to identify useful clinical biomarkers for predicting therapeutic responses or to serve as new drug targets for refractory psoriasis cases. We performed a genome-wide association study (GWAS) of 65 psoriasis patients who were prospectively followed after beginning anti-TNF-α therapy using Human Omni Express-8 v1.2 Beadchips. Patients were enrolled at the dermatology departments of Kobe University Hospital and six collaborative hospitals. Associations between single nucleotide polymorphisms (SNP) and changes in the Psoriasis Area and Severity Index (PASI) after 12 weeks of treatment were evaluated. After genome data collection and quality control, a total of 731 442 SNPs were identified in 65 Asian psoriasis patients who were treated with adalimumab or infliximab. Here, we present 10 SNPs, such as those in JAG2 and ADRA2A, that were associated with treatment responses to anti-TNF-α agents (strongest effect, P < 7.11E-06). This is the first GWAS to examine SNP associated with treatment responses in psoriasis patients. In addition, we identified other SNP that exhibited potential associations with anti-TNF-α treatment response, which merit further study. Of these, rs11096957 on TLR10, which is associated with increased TNF-α production, was previously reported to be associated with treatment responses to TNF-α inhibitors.