Clinical characteristics and differences of 802 acral tumours, categorized by anatomical sites.

BACKGROUND: Acral skin tumours are common, but information in the literature regarding their incidence is scarce. AIM: To investigate the clinical characteristics and differences in incidence of benign and malignant acral tumours by anatomical site. METHODS: A retrospective review was conducted of 802 patients with acral skin tumours confirmed by skin biopsy between January 2010 and December 2019. Age, sex, duration, symptoms and sites were obtained from medical records and photographs. RESULTS: The mean age of onset was 43.8 years, the male/female ratio was 1 : 1.41, and the mean duration was 68.8 months. Most tumours were asymptomatic (66.7%). In total, 802 acral tumours were identified: 512 (63.8%) were benign and 290 (36.2%) were malignant. The most common benign tumours were benign melanocytic lesions (n = 239), and the most common malignant tumours were melanoma (n = 234). The most common site was the sole (n = 408). Benign melanocytic lesions, melanoma and epidermal cysts were more frequent on the foot, whereas pyogenic granuloma, glomus tumours, haemangiomas and mucous cysts were more frequent on the hand. Glomus tumours, fibromas, mucous cysts and osteomas were more frequent on the nail portion, and benign melanocytic lesions and epidermal cysts were more frequent on the non-nail portion. CONCLUSION: This study reports the incidence of various benign and malignant acral tumours according to site, and we believe the results will be helpful in making a clinical diagnosis.

Transrectal ultrasound-guided targeted biopsy of transition zone prostate cancer under cognitive registration with prebiopsy MRI and sonographic findings.

AIM: To evaluate retrospectively the diagnostic usefulness of transrectal ultrasound (TRUS)-guided targeted biopsy (TB) for transition zone (TZ) prostate cancer (PCa) in patients with prebiopsy magnetic resonance imaging (MRI). MATERIALS AND METHODS: A consecutive series of 38 patients who underwent TRUS-guided TB of TZ lesions were evaluated. TB (mean core number, 2.4±0.6; range, 2-4) was performed by a single experienced radiologist under cognitive registration between prebiopsy MRI and TRUS. Tumour echogenicity on TRUS and Prostate Imaging-Reporting and Data System version 2 (PI-RADSv2) scoring on MRI for targeted TZ lesions were assessed. The interrupted midline sign was defined as a focal lesion traversing the midline of the TZ leading to discontinuity of the midline on both MRI and TRUS. TZ PCa with a Gleason score of 7 or greater was defined as clinically significant PCa (csPCa). RESULTS: The cancer detection rate of TRUS-guided TB for TZ lesions was 78.9% (30/38) for any PCa and 42.1% (16/38) for csPCa. Echogenicity of TZ PCa on TRUS was various and half did not show low echogenicity (low, 50%; intermediate, 26.7%; and high, 23.3%). The interrupted midline sign was identified in 50% (19/38) of patients, which was highly predictive of TZ PCa (94.7%, 18/19). CONCLUSION: TRUS-guided TB under cognitive registration based on prebiopsy MRI findings is useful to detect TZ PCa. Knowledge of the sonographic features of TZ PCa may help to target TZ PCa accurately under cognitive registration.

Risk factors to predict the development of chronic kidney disease in patients with lupus nephritis.

Objectives We analyzed the clinical follow-up results of 88 lupus nephritis patients to find prognostic factors for the development of chronic kidney disease in ethnically homogeneous Korean patients with biopsy-proven lupus nephritis. Methods Sociodemographic, clinical, laboratory, and treatment-related data at the time of kidney biopsy and during follow-up were obtained. Renal biopsy specimens were reclassified according to the International Society of Pathology/Renal Pathology Society classification, separately, by two renal pathologists blinded to the previous classification. Univariate and multivariate analyses were performed using the Cox proportional hazard regression model to identify independent risk factors for chronic kidney disease in lupus nephritis patients. Results Eighteen of 88 patients (20.5%) developed chronic kidney disease during a mean follow-up of 47.6 months (range: 12-96 months). Patients who developed chronic kidney disease were older at onset of lupus nephritis, had less education, and were more likely to have hypertension; they had lower serum albumin levels, lower platelet levels, higher serum creatinine levels, lower estimated glomerular filtration rate, higher chronicity index, and lower frequency of anti-ribosomal P antibodies, and they were less likely to be in complete remission in the first year. In stepwise multivariable analyses, hypertension, lower glomerular filtration rate, and failure to achieve complete remission in the first year of treatment were significant predictors of the development of chronic kidney disease in lupus nephritis patients. Conclusions These findings suggest that patients with hypertension and decreased kidney function at the onset of lupus nephritis and showing a poor response to immunosuppressive drugs in the first year should be monitored carefully and managed aggressively to avoid deterioration of kidney function.

Expression of soluble adenylyl cyclase in acral melanomas.

Soluble adenylyl cyclase (sAC) regulates melanocytic cells, and is a diagnostic marker for pigmented skin lesions. Because only a few studies on sAC expression in acral melanomas have been performed, we investigated the histopathological significance of sAC expression in 33 cases of acral melanoma, and assessed its diagnostic value in distinguishing melanoma in situ (MIS, n = 17) from acral invasive melanomas (n = 16) and melanocytic naevi (n = 11). Acral melanomas exhibited more marked nuclear immunopositivity compared with acral melanocytic naevi. sAC expression significantly correlated with the nuclear morphology of melanocytes and melanoma cells, namely, hyperchromatic nuclei and prominent nucleoli within vesicular nuclei. sAC expression was predominantly observed in the hyperchromatic nuclei of MIS and the prominent nucleoli invasive melanomas, respectively. In vitro culture models of melanocytes and melanoma cell lines exhibited sAC staining patterns similar to those of acral melanomas. Differentiation induction showed that nuclear and nucleolar expression varied depending on cell morphology. sAC immunostaining may be useful for the differential diagnosis of acral melanocytic lesions, and sAC expressed in the nucleus and nucleolus might be related to cytological and nuclear changes associated with invasion and progression of acral melanomas.

Replication of results of genome-wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population.

Two recent genome-wide association studies have identified that the rs2274223 single-nucleotide polymorphism inphospholipase C epsilon 1 and the single-nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high-resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR]=1.86, 95% confidence interval [CI]=1.08-3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR=0.71, 95% CI=0.52-0.97) and no significant association in the older group (OR=1.19, 95% CI=0.87-1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case-control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.

Two cases of clear cell sarcoma with different clinical and genetic features: cutaneous type with BRAF mutation and subcutaneous type with KIT mutation.

Clear cell sarcoma (CCS), also known as malignant melanoma of soft parts, is a rare malignancy constituting approximately 1% of all soft-tissue sarcomas. It occurs predominantly in the lower extremities of young adults, manifesting as a deep, painless, slow-growing mass. CCS is sometimes confused with other types of melanoma because of its melanocytic differentiation. Although BRAF and KIT mutations are well-known melanocytic tumour-promoting mutations frequently found in cutaneous melanoma, they are rare or absent in CCS. We present two cases of CCS with different clinical and genetic features. Both female patients, aged 25 and 20 years, presented with a palpable nodule on a lower extremity. Biopsies of both tumours revealed features diagnostic of CCS. Each tumour cell was positive for S100 protein and HMB-45. However, one patient's tumour was localized to the dermis, with many multinucleated giant cells, whereas the other was located in the deep subcutaneous fat layer near bone. Fluorescence in situ hybridization demonstrated the presence of a characteristic Ewing sarcoma RNA-binding protein (EWSR)1 gene rearrangement in both cases. Reverse-transcription polymerase chain reaction (PCR) and sequencing of the PCR product revealed an EWSR1-activating transcription factor 1 type 1 fusion transcript in both cases. In addition, we detected BRAF mutation in the dermal type and KIT mutation in the subcutaneous type. It is of interest that the BRAF and KIT mutations are known to be very rare in CCS. On the basis of our observations, we suggest that mutation inhibitors may be useful in selected patients with mutated CCS lineages.

Foxp3(+) regulatory T cells are increased in the early stages of halo nevi: clinicopathological features of 30 halo nevi.

BACKGROUND: There have been few clinical studies of the role of regulatory T cells (Tregs) in halo formation of halo nevus. OBJECTIVE: To evaluate the clinicopathologic features and the presence of Tregs in halo nevi. METHODS: We analyzed 30 halo nevi and performed immunohistochemical analysis using antibodies against CD4, CD8, CD25 and Foxp3. We also performed double immunohistochemical staining for Foxp3 and CD25. RESULTS: We found significant increases in Foxp3(+) Tregs, and the shorter the halo nevus duration, the more Foxp3(+) Tregs were detected. Also, the ratio of Foxp3 to CD8 T cells was increased in early stages of halo nevi. Double immunohistochemical staining suggested that the Tregs in the halo nevi were CD25(+)Foxp3(+) T cells. CONCLUSIONS: Foxp3(+) Tregs were greatly increased in the halo nevi. The shorter the halo nevi duration, the more Foxp3(+) Tregs were involved in the earlier developmental stages of halo nevi.

Alveolar soft part sarcoma of the uterine cervix in a woman presenting with postmenopausal bleeding: a case report and literature review.

INTRODUCTION: Alveolar soft part sarcoma (ASPS) of the uterine cervix is a rare mesenchymal malignancy that occurs in adolescents and young adults. CASE REPORT: A 52-year-old postmenopausal woman presented with profuse vaginal bleeding of one month's duration with severe anemia. The pelvic examination revealed a 3 cm mass on the posterior lip of the uterine cervix. On magnetic resonance imaging, the tumor had high signal intensity on T1- and T2-weighted images. A modified radical hysterectomy and bilateral salpingo-oophorectomy were performed. Immunohistochemical staining for TFE3 and electron microscopic examination revealed an ASPS of the uterine cervix. DISCUSSION: The better prognosis of cervical ASPS, compared to the soft counterparts, may be related to early clinical detection, small size, resectability, and demarcation of the tumor.

Incidence of venous gas embolism during robotic-assisted laparoscopic radical prostatectomy is lower than that during radical retropubic prostatectomy.

BACKGROUND: Robotic-assisted laparoscopic radical prostatectomy (RALRP) is gaining popularity as a less traumatic and minimally invasive alternative to open radical retropubic prostatectomy (RRP). The aim of this study was to evaluate the incidence and grade of venous gas embolism (VGE) during RALRP compared with those during RRP using transoesophageal echocardiography (TOE). METHODS: Fifty-two patients undergoing RRP (n=26) or RALRP (n=26) were consecutively enrolled. TOE was continuously applied during surgery and VGE was graded by an independent researcher. RESULTS: The total incidence of VGE (proportion, 95% CI) in the RRP group was higher than that in the RALRP group [20/25 (0.80, 0.60-0.92) and 10/26 (0.38, 0.22-0.58), respectively]. Most VGE in the RALRP group occurred during the transection of the deep dorsal venous complex. There was no difference in the incidence of severe VGE between the two groups. No patients with cardiorespiratory instabilities even with severe VGE were observed in this study. CONCLUSIONS: In contrast to general belief, VGE occurred less frequently during RALRP. Although the VGE in this study did not cause any cardiorespiratory instability, close monitoring for possibly fatal VGE must be considered during both types of radical prostatectomy because those who undergo radical prostatectomy frequently have cardiopulmonary co-morbidities.

Monoclonal antibody characterization of the C proteins of heterogeneous nuclear ribonucleoprotein complexes in vertebrate cells.

The C proteins (C1 and C2) are major constituents of the 40S subparticle of heterogeneous nuclear ribonucleoprotein complexes (hnRNPs) (Beyer, A.L., M.E. Christensen, B.W. Walker, and W.M. LeStourgeon, 1977, Cell, 11:127-138) and are two of the most prominent proteins that become cross-linked by ultraviolet light to heterogeneous nuclear RNA (hnRNA) in vivo. Studies are described here on the characterization of the C proteins in vertebrate cells using monoclonal and polyclonal antibodies. Monoclonal antibodies to genuine RNP proteins, including the C proteins, were obtained by immunizing mice with purified complexes of poly(A)+ hnRNA and poly(A)+ mRNA with their contacting proteins in vivo obtained by ultraviolet cross-linking the complexes in intact cells (Dreyfuss, G., Y.D. Choi, and S.A. Adam, 1984, Mol. Cell. Biol., 4:1104-1114). One of the monoclonal antibodies identified the C proteins in widely divergent species ranging from human to lizard. In all species examined, there were two C proteins in the molecular weight range of from 39,000 to 42,000 for C1, and from 40,000 to 45,000 for C2. The two C proteins were found to be highly related to each other; they were recognized by the same monoclonal antibodies and antibodies raised against purified C1 reacted also with C2. In avian, rodent, and human cells the C proteins were phosphorylated and were in contact with hnRNA in vivo. Immunofluorescence microscopy demonstrated that the C proteins are segregated to the nucleus. Within the nucleus the C proteins were not found in nucleoli and were not associated with chromatin as seen in cells in prophase. These findings demonstrate that C proteins with similar characteristics to those in humans are ubiquitous components of hnRNPs in vertebrates.

Heterogeneous nuclear ribonucleoproteins: role in RNA splicing.

Splicing in vitro of a messenger RNA (mRNA) precursor (pre-mRNA) is inhibited by a monoclonal antibody to the C proteins (anti-C) of the heterogeneous nuclear RNA (hnRNA)-ribonucleoprotein (hnRNP) particles. This antibody, 4F4, inhibits an early step of the reaction: cleavage at the 3' end of the upstream exon and the formation of the intron lariat. In contrast, boiled 4F4, or a different monoclonal antibody (designated 2B12) to the C proteins, or antibodies to other hnRNP proteins (120 and 68 kilodaltons) and nonimmune mouse antibodies have no inhibitory effect. The 4F4 antibody does not prevent the adenosine triphosphate-dependent formation of a 60S splicing complex (spliceosome). Furthermore, the 60S splicing complex contains C proteins, and it can be immunoprecipitated with 4F4. Depletion of C proteins from the splicing extract by immunoadsorption with either of the two monoclonal antibodies to the C proteins (4F4 or 2B12) results in the loss of splicing activity, whereas mock-depletion with nonimmune mouse antibodies bodies has no effect. A 60S splicing complex does not form in a C protein-depleted nuclear extract. These results indicate an essential role for proteins of the hnRNP complex in the splicing of mRNA precursors.

Synchronous pleomorphic adenoma and oncocytic carcinoma in the ipsilateral parotid gland.

Synchronous benign and malignant tumours in the ipsilateral parotid gland are rare. We present a case of pleomorphic adenoma and oncocytic carcinoma in the same parotid gland. Clinicians should be aware of the possibility of such synchronous multiple tumours, and that careful dissection and palpation during operation are important to diagnose them.

Physical change in cytoplasmic messenger ribonucleoproteins in cells treated with inhibitors of mRNA transcription.

Exposure of intact cells to UV light brings about cross-linking of polyadenylated mRNA to a set of cytoplasmic proteins which are in direct contact with the mRNA in vivo. Substantial amounts of an additional protein of molecular weight 38,000 (38K) become cross-linked to the mRNA when cells are treated with inhibitors of mRNA synthesis (actinomycin D, camptothecin, and 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole) or after infection with vesicular stomatitis virus. Cordycepin, which inhibits polyadenylation but not mRNA synthesis, has no such effect. Inhibitors of protein synthesis and of rRNA synthesis are also without effect on 38K cross-linking to mRNA. The onset of the effect of inhibitors of mRNA synthesis on the UV cross-linkable interaction between mRNA and 38K is rapid and reaches a maximal level in less than 60 min, and it is completely and rapidly reversible. In cells treated with actinomycin D, the amount of 38K which becomes cross-linked to mRNA is proportional to the extent of inhibition of mRNA synthesis. The association of 38K with mRNA during transcriptional arrest does not require protein synthesis because simultaneous treatment with the protein synthesis inhibitor emetine does not interfere with it. The effectors which promote the interaction of 38K with mRNA do not affect the proteins which are in contact with polyadenylated heterogeneous nuclear RNA and do not markedly affect protein synthesis in the cell. The 38K protein can be isolated with the polyribosomal polyadenylated fraction from which it was purified, and monoclonal antibodies against it were prepared. Immunofluorescence microscopy shows mostly cytoplasmic and some nuclear staining. These observations demonstrate that commonly used inhibitors of transcription affect the physical state of messenger ribonucleoproteins in vivo.

Characterization of heterogeneous nuclear RNA-protein complexes in vivo with monoclonal antibodies.

Exposure of cells to UV light of sufficient intensity brings about cross-linking of RNA to proteins which are in direct contact with it in vivo. The major [35S]methionine-labeled proteins which become cross-linked to polyadenylated heterogeneous nuclear RNA in HeLa cells have molecular weights of 120,000 (120K), 68K, 53K, 43K, 41K, 38K, and 36K. Purified complexes of polyadenylated RNA with proteins obtained by UV cross-linking in intact cells were used to immunize mice and generate monoclonal antibodies to several of these proteins. Some properties of three of the proteins, 41K, 43K, and 120K, were characterized with these antibodies. The 41K and 43K polypeptides are highly related. They were recognized by the same antibody (2B12) and have identical isoelectric points (pl = 6.0 +/- 0.2) but different partial peptide maps. The 41K and 43K polypeptides were part of the 40S heterogeneous nuclear ribonucleoprotein particle and appear to correspond to the previously described C proteins (Beyer et al., Cell II:127-138, 1977). A different monoclonal antibody (3G6) defined a new major heterogeneous ribonucleoprotein of 120K. The 41K, 43K, and 120K polypeptides were associated in vivo with both polyadenylated and non-polyadenylated nuclear RNA, and all three proteins were phosphorylated. The monoclonal antibodies recognized similar proteins in human and monkey cells but not in several other vertebrates. Immunofluorescence microscopy demonstrated that these proteins are segregated to the nucleus, where they are part of a fine particulate nonnucleolar structure. In cells extracted in situ with nonionic detergent, all of the 41K and 43K polypeptides were associated with the nucleus at salt concentrations up to 0.5 M NaCl, whereas the 120K polypeptide was completely extracted at this NaCl concentration. A substantial fraction of the 41K and 43K polypeptides (up to 40%) was retained with a nuclear matrix--a structure which is resistant to digestion with DNase I and to extraction by 2 M NaCl, but the 41K and 43K polypeptides were quantitatively removed at 0.5 M NaCl after digestion with RNase.

The prognostic role of tertiary Gleason pattern 5 in a contemporary grading system for prostate cancer.

BACKGROUND: Recently, a new prostate cancer (PC) grading system has been introduced, where Gleason score (GS) 7 (3+4) and GS 7 (4+3) are categorized into two separate groups. However, GS 7 with tertiary Gleason pattern 5 (TGP5) was not incorporated in the new grading system. In the present study, we validated the prognostic role of TGP5 in the new classification. METHODS: We retrospectively reviewed the records of 1396 patients with localized GS 6-8 PC (pT2-3N0M0) who underwent radical prostatectomy at our institution between 2005 and 2014. After excluding patients who received neoadjuvant or adjuvant therapy, or had incomplete pathological or follow-up data, 1229 patients were included in the final analysis. The Kaplan-Meier method was used to estimate and compare the probabilities of biochemical recurrence (BCR). Cox regression models were used to investigate associations between variables and the risk of BCR. RESULTS: Of 732 GS 7 patients, 75 (10.2%) had a TGP5. The BCR-free survival rate for men with TGP5 was significantly worse than for those without TGP5 (P<0.001). In multivariate Cox regression analyses for GS 7 PC, TGP5 was a significant predictor of BCR (hazard ratio 1.750, P=0.027). When the total cohort was stratified into four grade groups according to the new classification, group 2 with TGP5 had a BCR risk comparable to group 3, and group 3 with TGP5 behaved like group 4. CONCLUSIONS: Our study shows that TGP5 increased the BCR risk after RP in GS 7 PC. Moreover, we demonstrated that the presence of a TGP5 in GS 7 upgraded the BCR risk to one comparable with the next higher category under the new classification. These findings support incorporating TGP5 into GS 7 to aid with future risk assessment and follow-up scheduling for PC.

Anatomical Retzius-space preservation is associated with lower incidence of postoperative inguinal hernia development after robot-assisted radical prostatectomy.

BACKGROUND: Postoperative inguinal hernia (IH) is a non-negligible sequelae with a wide array of rates after robot-assisted laparoscopic radical prostatectomy (RALP). Our aim was to evaluate the incidence and risk factors of postoperative IH development in men undergoing RALP. METHODS: A retrospective analysis of 839 patients "541 of conventional-RALP (C-RALP), and 298 of Retzius sparing-RALP (RS-RALP)" received treatment of prostate cancer between 2005 and 2016 and met with our inclusion criteria was performed. Primary endpoint was incidence of IH after RALP, while secondary endpoint was to assess risk factors of IH occurrence. RESULTS: Overall incidence of postoperative IH was 6.3% (53 out of 839). Mean follow-up period and median time of IH development were 24.1 and 14.0 months, respectively. Among patients who developed IH, there was a higher incidence in C-RALP compared to RS-RALP, (79.2 vs 20.8%, respectively, P = 0.02). Multivariate analysis showed that BMI group (HR 0.471, P = 0.023) and C-RALP (HR 2.834, P = 0.002) were significant predictors of IH development. Kaplan-Meier curve showed that 3-year IH-disease progression free rate was significantly higher after RS-RALP compared to C-RALP (94.2 vs 71.6%, respectively, P < 0.001), likewise in obese versus non-obese patients (87.7 vs 76.6%, respectively, P < 0.003). CONCLUSION: Our study showed that overall incidence of IH was 6.3% after RALP. Nevertheless, RS-RALP carries a lower incidence of IH after surgery, while C-RALP and low BMI are predictors of IH development.

Expression of cyclooxygenase-2 in breast carcinogenesis and its relation to HER-2/neu and p53 protein expression in invasive ductal carcinoma.

The purpose of this study was to evaluate cyclooxygenase-2 (COX-2) expression in the successive steps of breast carcinogenesis and to determine its correlation with HER-2/neu and p53 expression in invasive ductal carcinomas of the breast. Immunohistochemical staining with anti-COX-2 antibody was performed in normal breast tissue, usual hyperplasia, ductal carcinoma in situ, and invasive ductal carcinoma. Expression of COX-2 in invasive ductal carcinoma was correlated with immunohistochemical expression of HER-2/neu and p53 protein. COX-2 expression was found to be progressively elevated along the continuum from normal breast tissue to invasive ductal carcinoma (P<0.001). COX-2 expression significantly correlated with p53 and HER-2/neu protein expression (P<0.05 and P<0.001). On multivariate analysis, only TNM stage and elevated COX-2 expression correlated with survival. Our results suggest that COX-2 may be involved in the carcinogenesis of the breast and may be an independent prognostic indicator in patients with invasive ductal carcinoma. HER-2/neu and p53 are likely to be involved in the regulation of COX-2 expression in invasive ductal carcinomas of the breast.

Prognostic impact of preoperative neutrophil-to-lymphocyte ratio after radical prostatectomy in localized prostate cancer.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) has a prognostic value in patients with metastatic castration-resistant prostate cancer receiving systemic therapy. However, the prognostic significance of NLR was never previously evaluated in patients who underwent radical prostatectomy (RP) for prostate cancer. In the present study, we investigated the influence of NLR on survival after a RP for prostate cancer. METHODS: We retrospectively reviewed clinical data of 2301 patients with prostate cancer who underwent RP at our institution between 2000 and 2010. Among these patients, we considered only patients who had a preoperative complete blood count with differential result available. Patients who received neoadjuvant or postoperative adjuvant treatment (radiation, androgen deprivation therapy or both) and those without adequate medical record were excluded. A Kaplan-Meier analysis was performed to analyze biochemical recurrence-free survival (BCRFS), overall survival (OS) and prostate cancer-specific survival (CSS). Univariate and multivariate Cox regression models were used for each end point. RESULTS: In total, 2067 patients were evaluated; median follow-up time was 78 months (interquartile range (IQR) 65-96), median age at RP was 66 years (IQR 61-70) and median preoperative NLR was 1.76 (IQR 1.35-2.40). A Kaplan-Meier analysis showed a significant association between high NLR (⩾1.76) and decreased CSS (P=0.005) and OS (P=0.003) but not with BCRFS (P=0.223). In the univariate and multivariate regression analyses, a high NLR was a significant predictor of CSS (hazard ratio (HR) 2.012, 95% confidence interval (CI) 1.222-3.310, P=0.006) and OS (HR 1.650, 95% CI 1.127-2.416, P=0.010). CONCLUSIONS: This study shows that in patients with prostate cancer preoperative NLR is an independent prognostic factor for OS and CSS after a RP and suggests that a preoperative hematologic workup should be considered in the risk assessment of these patients.

CHIP-mediated degradation of transglutaminase 2 negatively regulates tumor growth and angiogenesis in renal cancer.

The multifunctional enzyme transglutaminase 2 (TG2) primarily catalyzes cross-linking reactions of proteins via (γ-glutamyl) lysine bonds. Several recent findings indicate that altered regulation of intracellular TG2 levels affects renal cancer. Elevated TG2 expression is observed in renal cancer. However, the molecular mechanism underlying TG2 degradation is not completely understood. Carboxyl-terminus of Hsp70-interacting protein (CHIP) functions as an ubiquitin E3 ligase. Previous studies reveal that CHIP deficiency mice displayed a reduced life span with accelerated aging in kidney tissues. Here we show that CHIP promotes polyubiquitination of TG2 and its subsequent proteasomal degradation. In addition, TG2 upregulation contributes to enhanced kidney tumorigenesis. Furthermore, CHIP-mediated TG2 downregulation is critical for the suppression of kidney tumor growth and angiogenesis. Notably, our findings are further supported by decreased CHIP expression in human renal cancer tissues and renal cancer cells. The present work reveals that CHIP-mediated TG2 ubiquitination and proteasomal degradation represent a novel regulatory mechanism that controls intracellular TG2 levels. Alterations in this pathway result in TG2 hyperexpression and consequently contribute to renal cancer.

Identification of one of the major viruses infecting garlic plants, garlic virus X.

A partial cDNA clone for garlic virus X (GVX) was isolated. GVX was identified immunologically with an antibody raised against the recombinant coat protein (CP) and demonstrated to be one of the major viruses infecting garlic plants showing mosaic or streak symptoms. GVX belongs to an unassigned group of ShVX and GarV-type viruses rather than to carlaviruses or potexviruses. The recombinant CP of GVX was purified by Ni(2+)-NTA affinity chromatography. Anti-GVX CP antibody was raised against the purified recombinant CP. GVX particle is flexuous, rod-shaped, and about 750 nm long as determined by immunoelectron microscopy. The extent of infection by GVX of garlic plants was analyzed by Northern or immunoblot analyses of individual garlic plants cultivated in different regions. These results showed that almost all of the garlic plants tested from 40 different regions including America, China, Japan, and Korea are infected with GVX.