Search

Nivolumab, an immune checkpoint inhibitor is the first-line therapy for platinum-resistant recurrent/metastatic head and neck cancer, and highly effective for some patients. However, no factors have been identified that could predict response or prognosis after nivolumab administration. We retrospectively investigated the association between tumor infiltrating lymphocytes (TILs) of initial pathology and prognosis in patients treated with nivolumab. Twenty-eight patients with human papilloma virus and Epstein–Barr virus unrelated head and neck squamous cell carcinoma were enrolled. CD8+cells, FoxP3+cells and FoxP3−CD4+cells in the tumoral and peritumoral stromal area and PD-L1 were measured. In result, FoxP3−CD4+TIL, FoxP3+TIL, and CD8+TIL were not correlated with survival in either intratumoral and stromal area. In univariate analysis, objective response was significant prognostic factor both in progression-free survival and overall survival (p = 0.01, 0.006, respectively). PD-L1 was also significant prognostic factor both in progression-free survival and overall survival (p = 0.01, 0.01, respectively). ECOG Performance status was a significant prognostic factor in overall survival (p = 0.0009). In the combined analysis of stromal CD8+TIL and PD-L1, PD-L1 positive with high stromal CD8+TIL subgroups had a better prognosis than PD-L1 negative with low stromal CD8+TIL subgroups in progression-free survival (p = 0.006). Although these results require a further investigation, PD-L1 and ECOG Performance status and the combination of stromal CD8+TIL and PD-L1 positivity have potential as useful prognostic markers in patients of virus unrelated head and neck squamous cell carcinoma treated with nivolumab. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma shows a higher rate of radiation resistance than HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). Radioresistant HPV-negative OPSCC is associated with unfavourable outcomes, but validated prognostic biomarkers remain lacking. This study investigated biomarkers for radioresistant HPV-negative OPSCC. The Cancer Genome Atlas included miRNA sequence and mRNA sequence data from 528 HNSCC tumours. Of these, we used gene expression data for HPV-negative head and neck squamous cell carcinoma for which data were available on the effects of radiation, and compared miRNA sequence and mRNA sequence data between radioresistant and radiosensitive groups. We subsequently estimated downstream miRNA from the results. Finally, we validated miRNAs related to the outcomes of radiotherapy in our clinical cases. Investigation of miRNA sequence revealed expression of miR-130b as the greatest difference between radiosensitive and radioresistant groups. We subsequently evaluated miR-130b expression in our clinical OPSCC cases. Values of miR-130b >5.372 (low expression), determined from receiver operating characteristic curve analyses, were associated with significantly longer progression-free survival and overall survival (p =.006, p =.04, respectively). Our results suggest that miR-130b has potential as a biomarker for the radiosensitivity of HPV-negative OPSCC. [ABSTRACT FROM AUTHOR]

In addition, in the Ethical approval section, "The study protocol complied with the Declaration of Helsinki and was approved by the institutional review board of Saitama Medical University International Medical Center (approval no. 17-044). All patients provided written informed consent prior to enrollment." now reads: "The study protocol complied with the Declaration of Helsinki and was approved by the institutional review board of the Saitama Medical University International Medical Center (approval no. 17-044, 17-262). [Extracted from the article]

Highlights • Silica nanoparticle growth in geothermal brine is examined during the polymerization of silicic acid by observation with dynamic light scattering at the Sumikawa geothermal station. • Three types of geothermal brines, raw (pH 6.6), pH adjusted (pH 8), and diluted brines were examined. • The monosilicic acid concentration rapidly decreased over time in the raw brine but was almost constant in the samples with lower silicic acid concentrations. • The polysilicic acid particle diameters in the raw brine increased from 1 to 6 nm within 5 min and then was almost constant at 7 nm for the subsequent 30 min. Abstract Silica nanoparticle growth in geothermal brine was examined during the polymerization of silicic acid by observation with dynamic light scattering (DLS) at the Sumikawa geothermal station, examining raw (pH 6.6), pH adjusted (pH 8), and diluted brines (100 to 60%). The monosilicic acid concentration rapidly decreased over time in the raw brine but was almost constant in the samples with lower silicic acid concentrations. The average polysilicic acid particle diameter in the raw brine rapidly increased, from 1 to 6 nm, within 5 min (stage I) and then was almost constant at 7 nm for the subsequent 30 min (stage II). [ABSTRACT FROM AUTHOR]

Discusses the relationship between the noise characteristics and magnetic properties of longitudinal barium-ferrite rigid disks with different switching field distributions. Measurement of the electromotive force dependencies of reverse direct current-erase noise; Analysis of the interparticle interactions in barium-ferrite disks; Role of particle stacking in the interactions between barium ferrite particles.

Background: This study was undertaken to investigate if the prostate-specific antigen (PSA) level measured 3 months after radical prostatectomy (RP) is a predictor of biochemical recurrence (BCR)-free survival. Methods: We retrospectively reviewed the clinicopathologic data of 174 patients with a follow-up of at least 3 years after RP for clinically localized prostate cancer. None of the patients received neoadjuvant/adjuvant therapy. Subjects were categorized according to PSA level 3 months after RP (3M-PSA): <0.010 ng/mL (group 1; n = 119) or 0.010-0.100 ng/mL (group 2; n = 55). BCR was defined as two consecutive rises in PSA level ≥0.2 ng/mL. Results: At a median follow-up of 69.5 months (range 36-113 months), 32 (18.4 %) patients experienced BCR. The median time to BCR was 16 months (range 4-98 months) after RP. The 5-year BCR-free survival rate was 92.6 and 57.4 % in groups 1 and 2, respectively. Patients in group 1 had a significantly higher BCR-free survival rate than those in group 2 (log-rank P < 0.001). According to the Cox proportional hazards model, patients with a 3M-PSA level of <0.010 ng/mL were at lower risk for BCR ( P < 0.001), along with pathologic Gleason sum 6 ( P = 0.028). PSA nadir level after RP was also a risk factor for BCR (log-rank P < 0.001). Area under the receiver operating characteristic curve for 3M-PSA to predict BCR was almost equivalent to that for the PSA nadir level (0.855 vs. 0.849). Conclusions: 3M-PSA is an independent predictor of BCR-free survival. Our findings might be used for a risk-adjusted follow-up protocol. [ABSTRACT FROM AUTHOR]

This work demonstrated that the targeting of a polytopic membrane protein to the inner envelope membrane of chloroplasts in vivo involves multiple transmembrane segments including the indispensable transmembrane segment.The inner envelope membrane (IEM) of the chloroplast plays crucial roles in forming an osmotic barrier and controlling metabolite exchange between the organelle and the cytosol. The IEM therefore harbours a number of membrane proteins and requires the import and integration of these nuclear-encoded proteins for its biogenesis. Recent studies have demonstrated that the transmembrane segment of single-spanning IEM proteins plays key roles in determining their IEM localization. However, few studies have focused on the molecular mechanisms by which polytopic membrane proteins are targeted to the IEM. In this study, we investigated the targeting mechanism of polytopic IEM proteins using the protein Cor413im1 as a model substrate. Cor413im1 does not utilize a soluble intermediate for its targeting to the IEM. Furthermore, we show that the putative fifth transmembrane segment of Cor413im1 is necessary for its targeting to the IEM. The C-terminal portion containing this transmembrane segment is also able to deliver Cor413im1 protein to the IEM. However, the fifth transmembrane segment of Cor413im1 itself is insufficient to target a fusion protein to the IEM. These data suggest that the targeting of polytopic membrane proteins to the chloroplast IEM in vivo involves multiple transmembrane segments and that chloroplasts have evolved a unique mechanism for the integration of polytopic proteins to the IEM. [ABSTRACT FROM PUBLISHER]

Abstract: The superfluid to the Mott insulator transition is studied in the Bose–Hubbard model with contact interactions U at the density ρ=1, and at the half-filling ρ=1/2 added the next nearest interactions V which is responsible for the charge density wave (CDW). The Berezinski–Kosterlitz–Thouless transition is analyzed from the points of the dual Sine–Gordon model and the boson-spin equivalence by the conformal field theory. Eventually the prescription for the boson system is developed and the Mott insulator transition point and the superfluid to CDW transition point are estimated. [Copyright &y& Elsevier]

Chloroplast heat shock protein 90 (Hsp90C) represents a highly conserved subfamily of the Hsp90 family of molecular chaperones whose function has not been defined. We identified Hsp90C as a component that interacts with import intermediates of nuclear-encoded preproteins during posttranslational import into isolated chloroplasts. Hsp90C was specifically coprecipitated with a complex of protein import components, including Tic110, Tic40, Toc75, Tic22, and the stromal chaperones, Hsp93 and Hsp70. Radicicol, an inhibitor of Hsp90 ATPase activity, reversibly inhibited the import of a variety of preproteins during translocation across the inner envelope membrane, indicating that Hsp90C functions in membrane translocation into the organelle. Hsp90C is encoded by a single gene in Arabidopsis thaliana, and insertion mutations in the Hsp90C gene are embryo lethal, indicating an essential function for the chaperone in plant viability. On the basis of these results, we propose that Hsp90C functions within a chaperone complex in the chloroplast stroma to facilitate membrane translocation during protein import into the organelle. [ABSTRACT FROM AUTHOR]

The article presents an in vitro fluorescent analysis on the lipoprotein import of chloroplasts. It states that a green fluorescent protein (GFP)-fused precursor and a fluorescent dye-labeled one were used to observe protein localization in living cells. It further claims that while GFP and other fluorescent proteins are valuable probes, the application of fluorescent proteins to the in vitro protein transport system does not take any benefits of their fluorescence.

The translocons at the outer envelope membrane of chloroplasts (TOCs) initiate the import of thousands of nucleus-encoded proteins into the organelle. The identification of structurally and functionally distinct TOC complexes has led to the hypothesis that the translocons constitute different import pathways that are required to coordinate the import of sets of proteins whose expression varies in response to organelle biogenesis and physiological adaptation. To test this hypothesis, we examined the molecular basis for distinct TOC pathways by analyzing the functional diversification among the Toc159 family of TOC receptors. We demonstrate that the N-terminal A-domains of the Toc159 receptors regulate their selectivity for preprotein binding. Furthermore, the in vivo function of the two major Toc159 family members (atToc159 and atToc132) can be largely switched by swapping their A-domains in transgenic Arabidopsis thaliana. On the basis of these results, we propose that the A-domains of the Toc159 receptors are major determinants of distinct pathways for protein import into chloroplasts. [ABSTRACT FROM AUTHOR]

The article reports on the alternative processing of Arabidopsis HSp70 precursors during protein import into chloroplasts. An in vitro protein import assay was employed to determine the localization of three Arabidopsis homolog of Hsp70-IAP. The author notes that organelle-free processing assays revealed that the larger processes forms of both AtHsp70-6 and AtHsp70-7 were cleaved by stromal processing peptidase.

Abstract: During protein import into chloroplasts, precursor proteins are docked to these organelles under stringent energy conditions to form early translocation intermediates. Depending on the temperature and the requirement for ATP, different types of early-intermediates are present, for which the extent of precursor protein translocation differs [H. Inoue, M. Akita, J. Biol. Chem. 283 (2008) 7491–7502]. However, it has not been determined whether the environment surrounding the precursor differs for each intermediate. We therefore employed a site-specific photo-crosslinking strategy in our current study to capture any components in close proximity to the targeting signal of the precursors within the early-intermediates. Various crosslinked products, one of which contains Toc75, were identified. The appearance of these products was found to be dependent on the position of the precursor upon modification by the crosslinker and also the intermediate state. This indicated that the transition of early translocation intermediates is accompanied with the movement of the targeting signal within the early-intermediates. [Copyright &y& Elsevier]

Abstract: The in vitro protein import experiment is one of the most important techniques for determining protein localization. For chloroplastic proteins, proteins of interest are incubated with isolated chloroplasts in the presence of energy sources. Radio-labeled proteins synthesized either in vitro or in vivo have been widely used as substrate proteins. Here we report our development of the protein import assay system in which non-radio-labeled proteins, overexpressed in Escherichia coli, were applied. In this system, substrate proteins were designed to carry epitope-tags, thus allowing analysis of imported proteins by SDS-PAGE, followed by immunoblotting to detect these tags. Furthermore, the imported proteins were found to be incorporated into their native form. These observations indicated that recombinant proteins were imported into chloroplasts and folded correctly. Therefore, this assay system could represent another valuable tool for determining protein localization. [Copyright &y& Elsevier]

During the early stage of protein import into chloroplasts, precursor proteins synthesized in the cytosol irreversibly bind to chloroplasts to form the early translocation intermediate under stringent energy conditions. Many efforts have been made to identify the components involved in protein import by analyzing the early intermediate. However, the state of the precursor within the intermediate has not been well investigated so far. In this study, an attempt was made to evaluate the extent of translocation of the precursor by determining the state of the precursor in the early intermediate under various conditions and analyzing the fragments generated by limited proteolysis of the precursors docked to chloroplasts. Our results indicate that three different sets of early intermediate are formed based on temperature and the hydrolysis of GTP/ATP. These have been identified based on the size of proteolytic fragments of the precursor as "energy-dependent association," "insertion," and "penetration" states. These findings suggest two individual ATP-hydrolyzing steps during the early stage of protein import, one of which is temperature-sensitive. Our results also demonstrate that translocation through the outer envelope membrane is mainly dependent on internal ATP. [ABSTRACT FROM AUTHOR]

Background. Renal cell carcinoma (RCC) frequently occurs in patients with long-term dialysis. Long-term dialysis causes distinctive pathological changes in the kidney, which is known as acquired cystic disease of the kidney (ACDK). It is of great interest to know whether RCCs occurring in the dialytic kidneys harbour the same or similar mutations of the von Hippel–Lindau (VHL) gene as conventional dialysis-unrelated clear cell RCCs so often do. [ABSTRACT FROM PUBLISHER]

Abstract: The present study was undertaken to test the effects of prostate cancer cell lines (LNCaP, DU145, PC3, and MDA PCa 2b) on osteoclastogenesis. Crude conditioned medium (CM) from all four prostate cancer cell lines enhanced expression of the mRNA for receptor activator of NF-κB ligand (RANKL) in a mouse osteoblast cell line, MC3T3-E1; however, CM had no effect on expression of osteoprotegerin (OPG) mRNA. Coculture of MC3T3-E1 with prostate cancer cells yielded similar results. The number of mature osteoclasts induced by soluble RANKL increased significantly when osteoclast precursor cells were cultured with CM from LNCaP and DU145 cells. CM from LNCaP and DU145 cells also induced maturation from precursor in the absence of soluble RANKL, and this effect was not blocked by OPG. Addition of CM from DU145 cells increased expression of MMP-9 mRNA by osteoclast precursors. Our findings indicate that prostate cancer mediates osteoclastogenesis through induction of RANKL expression by osteoblasts and through direct actions on osteoclast precursors mediated by some factors other than RANKL. [Copyright &y& Elsevier]

Temperature dependence on synthesis of carbon nanotube by thermal catalytic decomposition of hydrocarbon was investigated. Benzene, thiophene, and iron(III)phthalocyanine are used for synthesis. As a result, the thickness of 20 nm, 5 to 10 layers solid structured carbon nanotube was obtained. [ABSTRACT FROM PUBLISHER]

Temperature dependence on synthesis of carbon nanotube by thermal catalytic decomposition of hydrocarbon was investigated. Benzene, thiophene, and iron(III)phthalocyanine are used for synthesis. As a result, the thickness of 20 nm, 5 to 10 layers solid structured carbon nanotube was obtained. [ABSTRACT FROM AUTHOR]

Background: There have been few reports of a totally extraperitoneal approach for laparoscopic lateral lymph node dissection (LLND) for patients with metachronous lateral pelvic lymph node metastases following surgery for rectal cancer. Therefore, this study reports the short-term outcomes of LLND via an extraperitoneal approach. Methods: A total of 10 patients underwent LLND through a laparoscopic extraperitoneal approach in our hospital since October 2018. Patients with suspected resectable lateral lymph node recurrence after surgery for rectal cancer on computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography CT (PET-CT) were selected for this procedure. Results: Nine of the 10 cases were completed using this procedure, but one case was converted to an intraperitoneal approach. The median operative time was 231 min, and the median estimated blood loss was 10 ml. There was one case of wound infection, but no other postoperative complications were seen. In one patient, no metastases were found in the retrieved lymph nodes. Conclusion: The short-term outcomes of LLND through a laparoscopic extraperitoneal approach were acceptable. Because this procedure can be performed without violating the peritoneum, it is less invasive than the conventional intraperitoneal approach and is useful for metachronous lateral pelvic lymph node metastases. [ABSTRACT FROM AUTHOR]

Background: In metastatic clear cell renal cell carcinoma (ccRCC), recent studies have shown promising efficacy of immune checkpoint inhibitor (ICI) combination therapy. However, there are insufficient evidences about clinical efficacy and safety of ICI combination therapy in metastatic non-ccRCC (nccRCC). Methods: We retrospectively investigated 44 patients treated with nivolumab plus ipilimumab (ICI + ICI group) or anti-PD-1/PD-L1 inhibitor plus tyrosine kinase inhibitors (TKI) (ICI + TKI group), and assessed clinical efficacy in both groups. Results: Of all patients, overall response rate and disease control rate for ICI combination treatments were 36.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 8.8 and 23.9 months, respectively. Multivariate analysis revealed that the presence of liver metastasis significantly affected worse PFS and OS (p = 0.035 and p = 0.049). Importantly, PFS and OS seemed similar in ICI + ICI group and ICI + TKI group (p = 0.778 and p = 0.559). Although the discontinuation rate of the combination therapy due to adverse effects in patients aged ≥ 75 years was significantly higher compared to that in patients aged < 75 years (45% versus 12%, p = 0.017), there were no significant differences in PFS and OS between two groups (p = 0.290 and p = 0.257, respectively). Conclusion: This study confirms clinical benefit of ICI combination therapy for metastatic nccRCC patients in real-world settings. Furthermore, the effectiveness of combination therapy was comparable between patients aged < 75 and those ≥75 years with respect to clinical prognosis. [ABSTRACT FROM AUTHOR]

Purpose: Flipped learning has been applied in various fields, including medical professional education. E-learning is compatible with flipped learning; however, it is considered to be unsuitable for providing training on surgical techniques. In this study, we retrospectively examined the ligation performance of online students who underwent training with flipped learning incorporated into e-learning. Methods: We conducted a retrospective study of the ligation practices of online students at the Department of General Surgery from March 2020 to June 2021. The subjects included 134 fourth- and fifth-year medical students from Gunma University School of Medicine. We conducted mid-term checks on the 8th day of practice and an examination on the 19th day. Two instructors independently evaluated and calculated scores using the original Global Rating Scale of Gunma University. We also conducted a questionnaire survey on the ligation practice of online students. Results: The total average score of the three tasks was 12.4 for Instructor 1 and 12.0 for Instructor 2. All students had a passing score. The questionnaire survey showed that 70% of the students were trained in ligation at the time of the first evaluation. Conclusions: Our online training materials and training methods enabled the acquisition of ligation skills by students who had not previously received ligation training. [ABSTRACT FROM AUTHOR]

We present the case of a patient with renal cell carcinoma treated preoperatively with sorafenib. Complete resection of the left renal mass measuring 7.2 × 6.6 cm seemed to be difficult at diagnosis because of large renal hilar lymph nodes. With a short period of sorafenib administration, marked shrinkage of the renal mass and lymphadenopathy was observed after the patient experienced fulminant hepatic failure and a severe hand–foot skin reaction. Two-dimensional computed tomography revealed 60%, 78% and 84% reduction in the primary renal tumor, lung metastatic nodules and lymph nodes, respectively. Tumor shrinkage allowed for complete resection of the left kidney and the lymphadenopathy. Pathological findings revealed that over 90% of the renal tumor was substituted by necrotic fibrotic tissue and that the residual neoplastic component was diagnosed as clear cell carcinoma. The lymph nodes that were resected were negative for malignancy. At 6 months after radical nephrectomy, a new computed tomography scan revealed no evidence of disease with the disappearance of lung nodules. [ABSTRACT FROM AUTHOR]

Some types of antimicrobial agents such as fosfomycin, clarithromycin, and erythromycin have been known to affect the host's immunological response. We investigated whether itraconazole (ITCZ) can modulate the serum cytokine levels (tumor necrosis factor (TNF-α, interleukin (IL)-10, IL-12p40) in both patients and healthy subjects. Serum samples were collected and TNF-α, IL-10 and IL-12p40 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA). We showed increased levels of IL-12p40 in patients treated with ITCZ. In healthy subjects, moreover, ITCZ treatment significantly increased the production of IL-12p40, but not TNF-α or IL-10. These findings suggest that the effectiveness of ITCZ in the treatment of fungal infection may be due not only to its direct antifungal effect, but also to induction of an immunomodulative effect on the host defense systems by regulation of cytokine production. [ABSTRACT FROM AUTHOR]

AbstractBackgroundMaterial and methodsResultsConclusionTo evaluate the efficacy of a catheter system using a 3-Fr sheath with a steerable microcatheter through right upper limb artery access for superselective intra-arterial cisplatin infusion and concomitant radiotherapy (RADPLAT) to treat right maxillary sinus squamous cell carcinoma (MS-SCC).We retrospectively studied 46 sessions in eight patients treated between November 2020 and February 2023 using the catheter system briefly described below. A 3-Fr sheath was inserted into the distal radial, conventional radial, or brachial arteries. A coaxial catheter system with a 2.9-Fr steerable microcatheter and a 1.9-Fr microcatheter was advanced into the brachiocephalic artery. The right common carotid artery was selected by bending the tip of the steerable microcatheter. Coil embolization and intra-arterial cisplatin infusion after selecting each external carotid artery branch were achieved using this catheter system.Cisplatin infusion and coil embolization were successful in all sessions. Arterial occlusion at the sheath insertion sites was found in 29.4% (5/17) of the distal radial arteries and 33.3% (3/9) of the conventional radial arteries. No other major complications were observed during the procedure.Using a 3-Fr catheter system with a steerable microcatheter through right upper limb artery access is a feasible method for RADPLAT in treating right MS-SCC. [ABSTRACT FROM AUTHOR]

Purpose: An organ/space surgical site infection reportedly develops in 20% of patients who undergo pancreaticoduodenectomy (PD). The present study aimed to identify the predictors for developing severe infectious complications after PD. Methods: We retrospectively reviewed the records of 115 consecutive patients who underwent PD at Ehime University Hospital between January 2013 and January 2020. Severe infectious complications were defined as Clavien–Dindo classification grade ≥ III postoperative complications related to bacterial or fungal infections, including clinically relevant postoperative pancreatic fistula (CR-POPF). The patient characteristics, blood chemistry data, body composition data and operative data were evaluated as potential predictors of severe infectious complications. We also evaluated the erythrocyte indices, such as the mean corpuscular hemoglobin, the mean corpuscular hemoglobin concentration, and the mean corpuscular volume (MCV). Results: Among 115 patients, 25 (21.7%) developed severe infectious complications, which included 20 (17.4%) cases of CR-POPF. According to multivariate analyses, MCV > 97.4fL, C-reactive protein (CRP) > 1.2 mg/dL and diameter of main pancreatic duct < 5 mm were independent predictors of severe infectious complications (odds ratio, 13.891, 7.356 and 4.676, respectively, 95% confidence interval, 3.457–55.815, 1.868–28.964 and 1.391–15.716, respectively). Conclusion: Preoperative high MCV/CRP values and a small main pancreatic duct are predictive factors associated with severe infectious complications after PD. [ABSTRACT FROM AUTHOR]

Background: Follicular adenomas with papillary architecture are rare tumors of thyroid origin and are composed of completely encapsulated follicular cells with a papillary architecture lacking the nuclear characteristics of papillary carcinoma. Herein, we present a case of follicular adenoma with papillary architecture originating from an ectopic thyroid gland, diagnosed from a mass in the submandibular region. Case Presentation: A 70-year-old woman was referred to our hospital with the chief complaint of a painless left submandibular mass that had been present for one year. The patient underwent left submandibular dissection for therapy and diagnosis. Microscopically, papillary lesions with fibrovascular cores were observed in the interior, and the epithelial cells were cylindrical in shape with eosinophilic cytoplasm, round or oval nuclei, with no pathological features, leading to a diagnosis of papillary carcinoma or follicular carcinoma. The mass was diagnosed as a follicular thyroid adenoma with papillary architecture. This is the first report of a follicular adenoma with a papillary architecture originating from an ectopic thyroid gland. Conclusion: This experience suggests that follicular adenoma should be included in the differential diagnosis of ectopic thyroid tumors. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented on postoperative prostate-specific antigen monitoring interval for low recurrence risk patients who underwent radical prostatectomy.

Chloroplast protein import is directed by the interaction of the targeting signal (transit peptide) of nucleus-encoded preproteins with translocons at the outer (TOC) and inner (TIC) chloroplast envelope membranes. Studies of the energetics and determinants of transit peptide binding have led to the hypothesis that import occurs through sequential recognition of transit peptides by components of TOC and TIC during protein import. To test this hypothesis, we employed a site-specific cross-linking approach to map transit peptide topology in relation to TOC-TIC components at specific stages of import in Arabidopsis thaliana and pea (Pisum sativum). We demonstrate that the transit peptide is in contact with Tic20 at the inner envelope in addition to TOC complex components at the earliest stages of chloroplast binding. Low levels of ATP hydrolysis catalyze the commitment of the preprotein to import by promoting further penetration across the envelope membranes and stabilizing the association of the preprotein with TOC-TIC. GTP hydrolysis at the TOC receptors serves as a checkpoint to regulate the ATP-dependent commitment of the preprotein to import and is not essential to drive preprotein import. Our results demonstrate the close cooperativity of the TOC and TIC machinery at each stage of transit peptide recognition and membrane translocation during protein import. [ABSTRACT FROM AUTHOR]

HEMERA (HMR) is a nuclear and plastidial dual-targeted protein. While it functions in the nucleus as a transcriptional coactivator in phytochrome signaling to regulate a distinct set of light-responsive, growth-relevant genes, in plastids it is known as pTAC12, which associates with the plastid-encoded RNA polymerase, and is essential for inducing the plastomic photosynthetic genes and initiating chloroplast biogenesis. However, the mechanism of targeting HMR to the nucleus and plastids is still poorly understood. Here, we show that HMR can be directly imported into chloroplasts through a transit peptide residing in the N-terminal 50 amino acids. Upon cleavage of the transit peptide and additional proteolytic processing, mature HMR, which begins from Lys-58, retains its biochemical properties in phytochrome signaling. Unexpectedly, expression of mature HMR failed to rescue not only the plastidial but also the nuclear defects of the hmr mutant. This is because the predicted nuclear localization signals of HMR are nonfunctional, and therefore mature HMR is unable to accumulate in either plastids or the nucleus. Surprisingly, fusing the transit peptide of the small subunit of Rubisco with mature HMR rescues both its plastidial and nuclear localization and functions. These results, combined with the observation that the nuclear form of HMR has the same reduced molecular mass as plastidial HMR, support a retrograde protein translocation mechanism in which HMR is targeted first to plastids, processed to the mature form, and then relocated to the nucleus. [ABSTRACT FROM AUTHOR]

Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated b-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. [ABSTRACT FROM AUTHOR]

This study investigated the precipitation behavior of silicic acid (Si) and iron (Fe) when acidic and weakly alkaline geothermal waters were mixed at various mixing ratios (R) (the proportion of the acidic geothermal water, which ranged from 1 to 9) at 85 ˚C under an oxidizing atmosphere at the Hatchobaru Geothermal Power Plant in Japan. The pH and total Fe concentration of the acidic and weakly alkaline geothermal waters were 2.8 and 8.7 at 25 ˚C and 6.5 and 0.5 ppm, respectively. The pH of the mixed geothermal waters at 85 ˚C ranged from 8.11 to 3.30. Although Si precipitated after they were mixed at R of 1 to 4, Fe precipitated immediately after mixing, independent of R. The amount of Fe precipitated also increased with increasing R (thus increasing the Fe initial concentration). The precipitates were divided into two groups based on their chemical composition: those with a high Si/Fe atomic ratio in the range of 100 to 150, found at R of 1 to 4, and those with a Si/Fe atomic ratio lower than 10, found at R of 5 to 9. Silicic acid polymerized after they were mixed at R between 1 and 3 and the polymerization was not observed at R above 4. Fe was present as colloidal hydrous ferric oxide (HFO) and hydrolyzed species of Fe3+ in the acidic geothermal water. From these results, it may be concluded that the precipitates with a high Si/Fe atomic ratio were formed due to the aggregation of polysilicic acid particles with Fe at R from 1 to 3, whereas the precipitates with low Si/Fe atomic ratios were formed owing to the aggregation of HFO bonding monosilicic acid because of the sudden increase in pH at all R. There was a large amount of precipitate (the sum of Fe and Si mmol) at R from 1 to 4, indicating that delaying the polymerization of the silicic acid is key in preventing large precipitation of Si and Fe. Judging from the saturation indices for minerals commonly found in geothermal fields, the amorphous precipitates with high and low Si/Fe atomic ratios may be precursors of silica polymorph and nontronite as a Fe(III) silicate because they can be formed at R from 1 to 9. [ABSTRACT FROM AUTHOR]

Objective: The Harmonic Scalpel (HS) (Johnson & Johnson K.K.) is a surgical tool that allows cutting and coagulation using ultrasonic mechanical vibrations. Its use in the field of otolaryngology has recently been attracting interest. In this study we applied the HS on the inferior nasal concha using a sword shaped blade (‘KATANA’). Methods: Subjects were 20 patients with intractable, perennial allergies that resisted conservative therapy. Subjective symptoms were evaluated as one of five stages, ‘symptoms disappeared’ ‘markedly improved’, ‘improved’, ‘unchanged’, and ‘aggravated’. Results: At the 12th week, 18 patients (90%) with nasal congestion, 16 (80%) with nasal discharge, and 15 (75%) with sneezing had shown at least ‘markedly improved’. Conclusion: Based on the improvement in subjective symptoms, local and histopathological findings, the HS is an effective surgical modality for these cases. We believe the HS is a safe and useful tool for nasal surgery. [Copyright &y& Elsevier]

Five types of troponoids including 40 molecules were prepared by means of palladium(0)-catalyzed carbonylation and successive acylation or benzoylation after immobilization of 2-methoxy-5-trifluoromethylsulfonyloxytropone on solid support. Four types of them showed mesophases. The final products have enough purity to detect their mesomorphic properties. [Copyright &y& Elsevier]

It is important to identify prognostic and predictive markers of metastatic urothelial carcinoma (mUC) treated with immunocheckpoint inhibitors. We sought to establish a prognostic marker for patients with mUC treated with pembrolizumab based on only blood test results. We included 165 patients with mUC in the discovery cohort and 103 with mUC who were treated with pembrolizumab in the validation cohort. Multivariate and Cox regression analyses were used to analyse the data. In the discovery cohort, the fibrosis-4 index (hazard ratio [HR]: 2.13, 95% confidence interval [CI] 1.20–3.76, p = 0.010), albumin–bilirubin score (HR 1.91, 95% CI 1.27–2.88, p = 0.002), and neutrophil–lymphocyte ratio (HR: 1.84, 95% CI 1.22–2.79, p = 0.004) were independent significant prognostic factors. We established a 'FAN score' that included these three aforementioned items, which were assigned one point each. We divided patients into the 0–1 point (n = 116) and 2–3 points (n = 49) groups. The FAN score was a significant prognostic marker for cancer-specific survival (CSS) (HR 1.48, 95% CI 1.19–1.83, p < 0.001) along with the Eastern Cooperative Oncology Group Performance Status. The FAN score was also a prognostic factor of progression-free survival (PFS) (HR: 1.25, 95% CI 1.01–1.54, p = 0.036) along with the presence of liver metastasis. In the validation cohort, the FAN score was a significant prognostic factor for CSS (HR: 1.48, 95% CI 1.19–1.85, p = 0.001) and PFS (HR: 1.29, 95% CI 1.02–1.62, p = 0.034). We established the FAN score as a prognostic marker for patients with mUC treated with pembrolizumab. [ABSTRACT FROM AUTHOR]

We report a case of rupture of a synchronous metastatic liver tumor secondary to a thymoma. A 56-year-old woman was referred to our hospital with acute abdomen. Computed tomography (CT) revealed a 10 cm diameter tumor in the left lateral segment of the liver, together with ascites, which was suggestive of intra-abdominal bleeding. She was in stable condition and hemostasis was confirmed by angiography. CT also revealed a mass in the anterior mediastinum. Elective laparoscopic left lateral segmentectomy was performed to make a pathological diagnosis and for radical resection. No peritoneal dissemination was observed and the liver tumor was curatively resected. The patient subsequently underwent thymectomy. The pathological diagnoses were thymoma with the liver metastasis. Currently, at 30 months post-treatment, she has had no tumor recurrence. Rupture of a metastatic liver tumor secondary to a thymoma is a rare condition; careful preoperative management and aggressive treatment might improve the patient's prognosis. [ABSTRACT FROM AUTHOR]

Background and purpose: To describe the procedure for a left-side approach to the superior mesenteric artery (SMA) during pancreaticoduodenectomy (PD) in a cadaveric study. Operative procedure: After dividing the upper jejunum, the jejunal artery (JA) is followed to its origin. At the cranial side of the JA, the mesojejunum to be dissected is detached from the ventral to the dorsal side and from the peripheral to the origin side of the SMA. The inferior pancreatoduodenal artery (IPDA), which is usually the common trunk of the IPDA and the first JA, is able to be visualized at the cranio-dorsal side of the origin of the JA. After cutting the IPDA, the mesojejunum can be detached from the SMA from the dorsal aspect to the right side. Subsequently, the pancreas head is dissected easily from the right aspect of the SMA. Conclusion: This left-side approach to the SMA may become a standard procedure. [ABSTRACT FROM AUTHOR]

Proinsulinoma is a subtype of insulinoma that is surgically curable, but localization can be difficult as these tumors are typically too small to be visualized by imaging. We report the case of a 53-year-old woman referred to our hospital with dizziness and headache. Her blood glucose level was 46 mg/dl and Whipple's triad was present. Although her immunoreactive insulin level during hypoglycemia was in the normal range (5.0 μU/ml), the proinsulin level was elevated (408 pmol/l). Imaging examinations showed no evidence of pancreatic tumor. A preoperative selective arterial calcium injection (SACI) test showed excessive insulin secretion in the splenic artery region, which localized the proinsulinoma to the body or tail of the pancreas, and laparoscopic spleen-preserving distal pancreatectomy was performed. Intraoperative SACI test performed after tumor removal did not show excessive insulin secretion. The intraoperative SACI test appears to be useful for localization and for confirming complete resection of proinsulinoma. [ABSTRACT FROM AUTHOR]

Liver cirrhosis can cause splenic artery aneurysms (SAA) that pose a threat to patients undergoing liver transplantation. However, liver transplantation with multiple visceral artery aneurysms including giant SAA caused by arterial fragility has never been reported. We describe a 36-year-old man with decompensated liver cirrhosis due to Wilson disease that was complicated by giant SAA and multiple aneurysms in the bilateral renal arteries caused by fibromuscular dysplasia (FMD). The maximal diameter of the triple snowball-shaped SAA was 11 cm. We planned a 2-stage strategy consisting of a splenectomy with distal pancreatectomy to treat the SAA and subsequent living donor liver transplantation (LDLT) to address the liver cirrhosis. This strategy was selected to prevent fatal postoperative infectious complications caused by the potential development of pancreatic fistula during simultaneous procedures and to histopathologically diagnose the arterial lesion before LDLT to promote safe hepatic artery reconstruction. However, a postoperative pancreatic fistula did not develop after a splenectomy with distal pancreatectomy, and the pathologic findings of the artery indicated FMD. The patient underwent ABO-identical LDLT with a right lobe graft donated by his brother. Other than postoperative rupture of the aneurysm in the left renal artery requiring emergency interventional radiology, the patient has remained free of any other arterial complications and continues to do well at 2 years after LDLT. • The patient underwent LDLT with giant splenic artery aneurysm caused by FMD. • A 2-stage strategy, which consisted of distal pancreatectomy and LDLT, was performed. • The patient has remained free of arterial anastomotic complications. [ABSTRACT FROM AUTHOR]

Aim: The impact of donor‐specific anti‐human leukocyte antigen (HLA) antibodies (DSAs) on living donor liver transplantation (LDLT) is unclear. The aim of this study was to investigate the association between DSAs and short‐term outcomes in LDLT recipients, and to clarify the clinical impact of DSAs. Method: Anti‐HLA antibodies were screened in preoperative serum samples taken from 40 liver transplant recipients at Ehime University (Toon, Japan) between August 2001 and July 2015. Screening was carried out using the Flow‐PRA method, and DSAs were detected in anti‐HLA antibody‐positive recipients using the Luminex single‐antigen identification test. A mean fluorescence intensity of 1000 was used as the cut‐off for positivity. We retrospectively reviewed the clinical courses of patients who were DSA‐positive to elucidate early clinical manifestations in LDLT recipients. Results: Fifteen (12 female and 3 male) patients (38%) had anti‐HLA antibodies. Eight of the 15 anti‐HLA antibody‐positive patients were positive for DSAs, and all were women. The 90‐day survival rate of DSA‐positive patients (50%) was significantly lower than that of DSA‐negative patients (84.4%) (0.0112; Wilcoxon test). On univariate analysis, the DSA‐positive rate was significantly higher in the 90‐day mortality group. Postoperatively, the incidence of acute cellular rejection was higher in DSA‐positive than DSA‐negative patients. Thrombotic microangiopathy developed only in DSA‐positive patients. We found no relationship between DSA status and bile duct stricture. Conclusion: Preformed DSAs could be associated with elevated 90‐day mortality in LDLT recipients. Further large‐scale studies are required to verify the risk associated with DSAs in LDLT. [ABSTRACT FROM AUTHOR]

Congestion of the anterior section of the grafted liver might be a problem when performing living donor liver transplant using a right lobe graft without middle hepatic vein (MHV). This can be prevented by MHV tributary reconstruction. We report our procedure and results of reconstructing MHV tributaries using artificial vascular grafts (AVGs). We consider venous reconstruction when the estimated territory of each MHV tributary of the transplanted liver is more than 100 mL. For tributaries distant from the stump of the right hepatic vein of the graft, we use heparin-bonded AVGs made of expanded polytetrafluoroethylene with circular rings as the interposition graft between the MHV tributary and the inferior vena cava. During donor surgery, the suturing margin of the MHV tributary is secured before cutting, and it is anastomosed to the AVG during back-bench surgery. After restoration of portal flow in the recipient, we anastomose the AVG at a new position on the inferior vena cava. The above procedure was performed for 4 cases. The estimated drainage territory of the vein that was reconstructed using the AVG ranged from 104 to 180 mL. The AVG patency was achieved for about 2 months in all cases. In terms of morbidity, biloma and pancreatic fistula were observed in 2 cases, although removal of the AVG was not required postoperatively in any of the cases. The heparin-bonded expanded polytetrafluoroethylene AVG with circular rings is a feasible option for MHV tributary reconstruction in living donor liver transplant using right liver lobe grafts without MHVs. [ABSTRACT FROM AUTHOR]

Aim: The clinical impact of serosal invasion by hepatocellular carcinoma (HCC) remains unclear. This study aimed to clarify the significance of serosal invasion as a prognostic factor for patients who underwent hepatectomy for HCC. Methods: This retrospective study investigated patients who underwent hepatectomy for HCC between October 2003 and September 2016 in Ehime University Hospital (Toon, Japan). A total of 161 cases were enrolled after excluding cases of concomitant distant metastasis, macroscopic tumor remnant, mixed HCC, and rehepatectomy. We classified these 161 patients into groups with serosal invasion detected (S[+]) and serosal invasion undetected (S[−]). We compared patient characteristics, perioperative data, pathological findings, and prognosis between S(+) and S(−) groups. Results: Serosal invasion was observed in 19 of the 161 patients (12%). The 5‐year recurrence‐free survival rate was lower for S(+) (13.0%) than for S(−) (28.7%, P = 0.006). The 5‐year overall survival (OS) rate was lower for S(+) (24.7%) than for S(−) (63.9%, P < 0.001). Regarding OS, serosal invasion, preoperative α‐fetoprotein value, presence of invasion to hepatic veins, and liver cirrhosis were independent predictors in multivariate analyses. The 3‐year OS rate after recurrence was poorer in the S(+) group (22.9%) than in the S(−) group (49.7%, P = 0.001). Conclusions: Serosal invasion was a strong predictor of worse outcomes after hepatectomy for HCC. Patients showing serosal invasion need close postoperative follow‐up or consideration of adjuvant treatment. [ABSTRACT FROM AUTHOR]

The first in-house, 9-cell, superconducting radio-frequency cavity made of large grain Nb was fabricated at KEK. Some characteristic techniques were employed for the fabrication that were not used for fine grain (FG) Nb. Even though a penetrated hole was created during electron beam welding, it was successfully repaired and did not affect the cavity performance. The completed cavity then underwent vertical tests (VTs) via several surface treatment processes. A defect that caused quenches was found after a VT at 25 mm from the equator where the typical local grinding machine developed at KEK could not be utilized. A new local grinding machine using a 3D printer was thus developed for the first time, and it completely removed this defect. Finally, the cavity achieved a maximum Q 0 value of 3.8 × 10 10 and accelerating gradient of 38 MV/m. The obtained Q 0 value is about 1.5 times higher than that for the KEK in-house FG cavity. [ABSTRACT FROM AUTHOR]

Six cavities of the same type (TESLA-like shape) made from six different niobium sources or types were produced at KEK using various materials and fabrication methods. Throughout these sequential in-house fabrications, comparisons of the properties of the various materials for use in superconducting radio-frequency cavities were conducted. The advantages and disadvantages of these properties, together with different fabrication methods, were examined. The cavities were fabricated primarily using existing facilities within KEK to control the fabrication quality. Vertical tests to evaluate single-cell cavity performances were conducted at the Superconducting RF Test Facility in KEK. The technical details of each fabrication method and the obtained high-gradient test results are described and discussed. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Sorafenib is a multikinase inhibitor used as a second-line treatment for metastatic renal cell carcinoma (mRCC). However, it is very difficult to estimate sorafenib dosage because it is difficult to maintain stable administration and dosage intervals due to several side-effects. We examined the correlation between relative dose intensity (RDI) and clinical outcome of sorafenib therapy in a multi-institutional study. Methods: A study population of 70 first-line therapy-refractory patients with pathologically confirmed RCC was eligible for this investigation. Clinical outcomes were evaluated according to clinicopathological features and RDI for 1month (1M-RDI). Results: There was significant difference in progression-free survival (PFS) time but not overall survival (OS) time when the 1M-RDI cut-off value was ⩾50%. In 15 patients (21.4%) with 1M-RDI of <50%, median PFS time was 4.1months (95% I collagen (95% CI): 2.0–6.2), whereas it was 10.5months (95% CI: 7.6–13.4) in the patients with 1M-RDI of ⩾50% (P =0.022). Multivariate analysis showed 1M-RDI status to be significantly associated with PFS (HR: 3.838, 95% CI: 1.658–8.883, P =0.002) but not OS (P =0.328). Conclusion: Although this study was retrospective, a 1M-RDI cut-off value of ⩾50% for sorafenib may be the first factor to predict PFS but not OS in cytokine pretreated mRCC patients. The data indicate that a dose of 400mg/day of sorafenib administered successively for the first one month was necessary to prolong disease stabilisation and could be tolerated by Japanese patients. [Copyright &y& Elsevier]

Objectives: To investigate the regulation of interferon-α (IFN-α) receptor expression in metastatic renal cell carcinoma (RCC) after IFN-α administration. Methods: Blood sampling was carried out in eight patients with metastatic RCC and six healthy volunteers. Flow-cytometric analysis using a monoclonal antibody against the active subunit of the type-I IFN-α receptor (IFNAR2) was carried out to examine the circadian rhythm of IFNAR2 expression in peripheral blood mononuclear cells (PBMC) as well as its downregulation after IFN-α administration. Results: According to its circadian rhythm IFNAR2 in PBMC had a peak expression at night. Once IFN-α is administered, IFNAR2 levels in PBMC showed downregulation within 48 h and recovered within another 48 h. Conclusions: Our findings might support the establishment of an optimal schedule for IFN-α administration. [ABSTRACT FROM AUTHOR]

Segmental infarction of the testis represents a rare entity in that there have been fewer than 40 cases documented in the literature. Like global infarction, segmental infarction of the testis can masquerade as a mass lesion or torsion of the testis. Reported herein is a very rare case of segmental testicular infarction due to atheroembolism in a 58-year-old man. The patient presented with severe left testicular pain and underwent left high orchiectomy on the clinical diagnosis of testicular torsion. The testis had a segmental hemorrhagic necrosis around which many cholesterol emboli were observed. This is the first report to describe cholesterol embolism-associated segmental testicular infarction. [ABSTRACT FROM AUTHOR]

Background: The paclitaxel, ifosfamide, and cisplatin regimen has been used to treat metastatic testicular cancer with successful results. We investigated the usefulness of a paclitaxel, ifosfamide, and nedaplatin (TIN) regimen as salvage therapy for patients with advanced testicular germ cell tumors (GCTs). Methods: Eight patients with advanced GCTs were treated with TIN. The treatment was performed as salvage therapy for cases refractory to therapies, such as bleomycin, etoposide and cisplatin, and irinotecan with nedaplatin. The TIN regimen consisted of paclitaxel (200 mg/m2) by 24-h infusion on day 1, followed by ifosfamide (1.2 g/m2) infusions over 2 h on days 2–6, and nedaplatin (100 mg/m2) given over 2 h on day 2. Results: Seven out of eight patients achieved a disease-free status after chemotherapy, followed by surgical resection of the residual tumor. Six of the seven patients have continued to show no evidence of disease after salvage therapy, with a median follow-up period of 27 months, but one patient developed a ‘growing teratoma syndrome’ in the mediastinum 31 months after TIN chemotherapy. All patients developed grade 4 leukocytopenia. However, it could be managed by using granulocyte colony-stimulating factor. Only one patient developed grade 2 sensory neuropathy and no patient developed nephrotoxicity. Conclusion: The TIN regimen was efficacious and well-tolerated as salvage chemotherapy for Japanese patients with advanced GCTs. [ABSTRACT FROM AUTHOR]

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value. TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence. Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer. The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt). [ABSTRACT FROM AUTHOR]

Objectives: In a variety of cancers, several polymorphisms of the tumor necrosis factor (TNF) genes have been reported to result in different clinical outcomes. We investigated whether a polymorphism of the TNF gene is associated with a susceptibility to bladder cancer and its disease status. Methods: Polymorphisms in the TNF-α gene promoter (−308 bp) and the NcoI site in the first intron of the TNF-β gene were analyzed in 141 Japanese patients with bladder cancer and 173 Japanese controls by polymerase chain reaction-restriction fragment length polymorphism. The correlations between the polymorphisms of the TNF genes and the clinicopathological features were analyzed. Results: The number of cases and controls with TNF-α2 was too small to be assessable. In contrast, the TNF-β1/2 genotype at the NcoI site in the first intron conferred a 1.71-fold increased risk of bladder cancer compared to the TNF-β2/2 genotype. In the bladder cancer group, patients with the TNF-β1 allele had a significantly higher risk for a high-grade tumor (grade 3) or carcinoma in situ (CIS) than those without the TNF-β1 allele. Moreover, in the superficial bladder cancers, patients with the TNF-β1 allele showed a significantly higher intravesical recurrence rate than those without the TNF-β1 allele. Conclusion: This polymorphism in the TNF-β gene appears to be associated with tumor occurrence and disease status, such as the tumor grade and the presence of CIS. Further study with an increased sample size is warranted. [ABSTRACT FROM AUTHOR]