TFE3/PI3K/Akt/mTOR Axis in Renal Cell Carcinoma Affects Tumor Microenvironment.

The role of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been investigated thoroughly. Transcription factor E3 (TFE3) expression is related to a poorer prognosis and tumor microenvironment in patients with RCC. This study aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 down-regulation was achieved by transient transfection of siRNA and shRNA in UOK146 cells. TFE3 overexpression was induced by transient transfection with pcDNA3.1 encoding the constitutively active form of TFE3. The cells were treated with mammalian target of rapamycin (mTOR) and PI3K inhibitors. Western blot was performed to detect TFE3, programmed death-ligand 1, phospho-Akt, and Akt. Phospho-Akt expression increased significantly upon TFE3 down-regulation, and decreased significantly upon up-regulation. When RCC cells were treated with a PI3K inhibitor (LY294002), TFE3 expression increased and phospho-Akt expression decreased. Data from this study indicate that TFE3 plays a role in the PI3K/Akt pathway in RCC. The results of this study suggest that PI3K/Akt inhibitors may aid in the treatment of patients with RCC by affecting the tumor microenvironment.

Clinicopathological factors predicting pathological complete response to neoadjuvant anti-HER2 therapy in HER2-positive breast cancer.

Introduction Human epidermal growth factor receptor 2 (HER2)-targeted therapies have shown effectiveness against HER2-positive breast cancer. This makes neoadjuvant chemotherapy (NAC) a valuable option for treating both early and advanced stages of the disease. The tumor's response to HER2-targeted NAC provides crucial prognostic information. Additionally, it allows for tailoring adjuvant treatment strategies for HER2+ breast cancer based on pathological responses. This study aimed to investigate the clinicopathological factors that influence tumor response. Methods We retrospectively analyzed 122 patients diagnosed with HER2+ breast cancer. These patients received NAC and HER2-directed therapy between January 2018 and December 2022 at the Pusan National University Yangsan Hospital. Following surgery, tumor response was evaluated, categorizing patients into two groups: pathological complete response (pCR) and non-pCR groups. We analyzed data on various factors, including age, NAC regimen, type of breast and axillary surgery, clinical stage (cTNM), historical grade, and pre-operative levels of carcinoembryonic antigen, cancer antigen 15-3 (CA 15-3), estrogen receptor (ER), progesterone receptor (PR), HER2, p53, and KI-67. Results Out of the 122 patients, 75 achieved pCR, while 47 did not. Most clinicopathological factors showed no significant difference between the pCR and non-pCR groups. However, several factors were associated with a higher pCR rate: normal preoperative CA 15-3 levels (odds ratio [OR]: 3.74, confidence interval [CI]: 1.19-11.72, P = 0.02), preoperative-ER positivity (OR: 2.65, CI: 1.25-5.59, P = 0.01), PR negativity (OR: 3.92, CI: 1.82-8.45, P <0.05), and strong preoperative HER2 immunohistochemistry (IHC) 3+ staining. Multivariate analysis confirmed that PR negativity (OR: 2.8, CI: 1.23-6.42, P = 0.01) and strong preoperative-HER2 IHC 3+ staining (OR: 0.18, CI: 0.03-0.84, P = 0.04) were independent predictors of a higher pCR rate. Conclusions A pCR after NAC impacts patient prognosis and influences the choice of adjuvant treatment for HER2+ breast cancer. Clinicopathological factors can help predict responses to HER2-targeted NAC. In our study, pre-ER/PR negativity, high pre-HER2 levels, and normal CA 15-3 levels were found to be potential predictors of pCR. These findings may contribute to developing more effective treatment strategies for HER2+ breast cancer.

Impact of Neoadjuvant Chemotherapy (NAC) on Biomarker Expression in Breast Cancer.

Background and Objectives: This study aimed to explore biomarker change after NAC (neoadjuvant chemotherapy) and to investigate biomarker expression as a prognostic factor in patients with residual disease (RD) after NAC. Materials and Methods: We retrospectively evaluated 104 patients with invasive breast cancer, who underwent NAC and surgery at Pusan National University Hospital from 2015 to July 2022. The expression of the biomarker was assessed, and the overall survival (OS) and disease-free survival (DFS) were investigated. Results: After NAC, 24 patients (23.1%) out of 104 total patients had a pathological complete response (pCR). We found that changes in at least one biomarker were observed in 41 patients (51.2%), among 80 patients with RD. In patients with RD after NAC (n = 80), a subtype change was identified in 20 patients (25.0%). Any kind of change in the HER2 status was present 19 (23.7%) patients. The hormone receptor (HR)+/HER2+ subtype was significantly associated with better disease-free survival (DFS) (HR, 0.13; 95% CI, 0.02-0.99; p = 0.049). No change in p53 was associated with better DFS, and negative-to-positive change in p53 expression after NAC was correlated with worse DFS (p < 0.001). Negative-to-positive change in p53 was an independent, worse DFS factor in the multivariate analysis (HR,18.44; 95% CI, 1.86-182.97; p = 0.013). Conclusions: Biomarker change and subtype change after NAC were not infrequent, which can affect the further treatment strategy after surgery. The expression change of p53 might have a prognostic role. Overall, we suggest that the re-evaluation of biomarkers after NAC can provide a prognostic role and is needed for the best decision to be made on further treatment.

Histological subtypes of hepatocellular carcinoma: Their clinical and prognostic significance.

Assigning a hepatocellular carcinoma (HCC) to an appropriate subtype is important because this guarantees the diagnosis and treatment and allows decisions regarding the prognosis of the patient. HCC subtyping is usually based on the World Health Organization (WHO) classification and the 2019 fifth edition is the latest version. However, the WHO classification system is still in evolution and has limited clinical relevance. We aimed to evaluate the clinical relevance of HCC subtyping and to reappraise some of the major subtypes of HCC. Our archived cases (n = 589) were reclassified according to the 2019 WHO system. The percentage of each subtype was mostly similar to that in the WHO classification. However, on the contrary to the 2019 WHO system, clear cell type HCC was associated with more frequent recurrence or metastasis. Meanwhile, macrotrabecular massive HCC was related to poor prognosis as demonstrated in the 2019 WHO system and should be described in the pathology report. For steatohepatitic HCC, there is a debate on whether it is a true subtype because the steatohepatitis morphology may or may not be present in the background liver. In our study, 44 % of steatohepatitic HCCs (n = 19/43) presented underlying steatohepatitis. Additionally, the background cirrhosis did not influence survival in the HCC patients, although the 2019 WHO system indicates the presence of cirrhosis as a poor prognostic factor. In conclusion, although it is not perfect yet, HCC subtyping based on the 2019 WHO system provides valuable information to manage patients with HCC.

Comparison of Fused Diffusion-Weighted Imaging Using Unenhanced MRI and Abbreviated Post-Contrast-Enhanced MRI in Patients with Breast Cancer.

Background and Objectives: To determine the percentage of breast cancers detectable by fused diffusion-weighted imaging (DWI) using unenhanced magnetic resonance imaging (MRI) and abbreviated post-contrast-enhanced MRI. Materials and Methods: Between October 2016 and October 2017, 194 consecutive women (mean age, 54.2 years; age range, 28-82 years) with newly diagnosed unilateral breast cancer, who underwent preoperative 3.0 T breast MRI with DWI, were evaluated. Both fused DWI and abbreviated MRI were independently reviewed by two radiologists for the detection of index cancer (which showed the most suspicious findings in both breasts), location, lesion conspicuity, lesion type, and lesion size. Moreover, the relationship between cancer detection and histopathological results of surgical specimens was evaluated. Results: Index cancer detection rates were comparable between fused DWI and abbreviated MRI (radiologist 1: 174/194 [89.7%] vs. 184/194 [94.8%], respectively, p = 0.057; radiologist 2: 174/194 [89.7%] vs. 183/194 [94.3%], respectively, p = 0.092). In both radiologists, abbreviated MRI showed a significantly higher lesion conspicuity than fused DWI (radiologist 1: 9.37 ± 2.24 vs. 8.78 ± 3.03, respectively, p < 0.001; radiologist 2: 9.16 ± 2.32 vs. 8.39 ± 2.93, respectively, p < 0.001). The κ value for the interobserver agreement of index cancer detection was 0.67 on fused DWI and 0.85 on abbreviated MRI. For lesion conspicuity, the intraclass correlation coefficients were 0.72 on fused DWI and 0.82 on abbreviated MRI. Among the histopathological factors, tumor invasiveness was associated with cancer detection on both fused DWI (p = 0.011) and abbreviated MRI (p = 0.004, radiologist 1), lymphovascular invasion on abbreviated MRI (p = 0.032, radiologist 1), and necrosis on fused DWI (p = 0.031, radiologist 2). Conclusions: Index cancer detection was comparable between fused DWI and abbreviated MRI, although abbreviated MRI showed a significantly better lesion conspicuity.

mTOR Inhibition Increases Transcription Factor E3 (TFE3) Activity and Modulates Programmed Death-Ligand 1 (PD-L1) Expression in Translocation Renal Cell Carcinoma.

The efficacy of programmed death ligand (PD-L)-1/PD-1 checkpoint blockade in renal cell carcinoma (RCC) remains unknown. The effects of mTOR inhibitors are uncertain, and patients may develop resistance to them. The limited understanding of cancer cell-intrinsic mTOR-mediated pathways remains a challenge in developing effective treatments. Whether transcription factor (TF)-E3 regulates PD-L1 expression and the tumor microenvironment was investigated, and the effects of an mammalian target of rapamycin (mTOR) inhibitor on translocation RCC were explored. TFE3 was overexpressed in clear cell RCC cell lines, and PD-L1 expression was analyzed by Western blot analysis. PD-L1 activity in translocation RCC was analyzed in relation to TFE3 expression via TFE3 knockdown and treatment with an mTOR inhibitor. The results were correlated with the gene expression profile, evaluated using digital multiplex analysis. TFE3 and PD-L1 expression were positively correlated in RCC cells. TFE3 overexpression was associated with the expression of PD-L1 in RCC. Furthermore, mTOR inhibition was associated with enhanced PD-L1 expression via TFE3 activation in translocation RCC. These data support the feasibility of combination therapy based on mTOR inhibition and PD-L1 blockade as a novel strategy for the treatment of patients with translocation RCC.

Practical scale evaluation of a photocatalytic air purifier equipped with a Titania-zeolite composite bead filter for VOC removal and viral inactivation.

A practical scale photocatalytic air purifier equipped with a TiO2/H-ZSM-5 composite bead filter was demonstrated to be able to effectively remove indoor volatile organic compounds (VOCs) and viruses with sustainable performances under UVA-LED illumination. TiO2 hybridized with 5 wt% H-ZSM-5 zeolite significantly enhanced its photocatalytic activity for degrading VOCs including formaldehyde, acetaldehyde, and toluene, than bare TiO2. H-ZSM-5 provided strong adsorption sites for these compounds, thus accelerating their photocatalytic conversion into CO2 by adjacent TiO2 photocatalyst. Moreover, owing to its superior adsorption capacity, the composite bead filter completely prevented the emission of formaldehyde produced by photocatalytic oxidation of toluene. The sustainability of this composite bead filter for VOC removal was confirmed by regeneration and accelerated durability tests. In addition, the photocatalytic air purifier was effective in removing aerosolized viral particles of bacteriophage Phi-X 174. It was confirmed that the viruses on filter surfaces were completely inactivated by photocatalytic oxidation. TiO2/H-ZSM-5 composite beads also exhibited excellent efficacies for inactivation of pathogenic coronaviruses including SARS-CoV-2. The photocatalytic process degraded viral RNAs of SARS-CoV-2 by more than 99.999% in 1 h, eliminating the viral infectivity. Results of this study suggest that the air purifier equipped with the composite bead filter is ready for practical applications for home and hospital uses.

Gastric-type gene expression and phenotype in non-terminal respiratory unit type adenocarcinoma of the lung with invasive mucinous adenocarcinoma morphology.

AIMS: We sought to determine if non-terminal respiratory unit (TRU) type adenocarcinoma of lung with invasive mucinous adenocarcinoma (IMA) morphology shows gastric differentiation. METHODS AND RESULTS: We reviewed whole-section images of 489 cases of lung adenocarcinoma from The Cancer Genome Atlas (TCGA). TCGA data were classified into 426 TRU type adenocarcinoma, 49 IMA and 14 unclassifiable. Their RNA sequencing data was analysed by DESeq2 and WGCNA R packages. Gene expression in patients' samples was measured by NanoString assay. Overexpression of genes including REG4, TFF2, MUCL3, FER1L6, B3GALT5, ANXA10 was observed by TCGA analysis in IMA compared to TRU type adenocarcinoma. Many of these genes are those expressed in normal gastric glands and selected for NanoString experiment on 14 IMA and 10 TRU type adenocarcinoma cases. The expression of genes, including ANXA10, FER1L6, HNF4a, MUC5AC, REG4, TFF1, TFF2 and VSIGI, was increased> 15-fold in IMA. Immunohistochemistry of ANXA10, TFF2 and FER1L6 performed on 31 IMA and 135 TRU type adenocarcinomas showed a predominant expression in IMA, but are not in TRU type adenocarcinoma. CONCLUSION: Our results showed the level of genes expressed in stomach mucosa was increased in IMA compared to TRU type adenocarcinoma, supporting gastric differentiation of IMA. This finding may help the understanding of the pathogenesis of IMA and discovery of therapeutic targets.

Pneumocystis pneumonia occurrence and prophylaxis duration in kidney transplant recipients according to perioperative treatment with rituximab.

BACKGROUND: Pneumocystis pneumonia (PCP) is a life-threatening fungal infection that can occur in kidney transplantation (KT) recipients. A growing number of KT recipients are receiving perioperative treatment with rituximab, which is associated with prolonged B-cell depletion and possible risk of PCP occurrence; however, the optimal prophylaxis duration according to rituximab treatment is yet unknown. We compared the occurrence of PCP and the duration of prophylaxis in KT recipients according to rituximab treatment. METHODS: We retrospectively analyzed 2110 patients who underwent KT between January 2009 and December 2016, who were divided into non-Rituximab group (n = 1588, 75.3%) and rituximab group (n = 522, 24.7%). RESULTS: In the rituximab group, the estimated number needed to treat (NNT) for prophylaxis prolongation from 6 to 12 months was 29.0 with a relative risk reduction of 90.0%. In the non-rituximab group, the estimated NNT value was 133.3 and the relative risk reduction was 66.4%. Rituximab treatment (hazard ratio (HR) = 3.09; P <  0.01) and acute rejection (HR = 2.19; P = 0.03) were significant risk factors for PCP in multivariate analysis. CONCLUSIONS: Our results suggest that maintaining PCP prophylaxis for 12 months may be beneficial in KT recipients treated with rituximab for desensitization or acute rejection treatment.

Validation of the T category for distal cholangiocarcinoma: Measuring the depth of invasion is complex but correlates with survival.

According to the current 8th edition of the American Joint Committee of Cancer (AJCC), the T category of distal cholangiocarcinomas is classified based on the depth of invasion (DOI) (T1, < 5 mm; T2, between 5 and 12 mm; T3, > 12 mm). In consideration of the discrepancies between previous studies about the prognostic significance, we aimed to validate the current AJCC T staging system of distal cholangiocarcinomas. DOI was measured using three different methods: DOI1, DOI2, and DOI3. DOI1 was defined and stratified according to the AJCC 8th edition. DOI2 was measured as the distance from an imaginary curved line approximated along the distorted mucosal surface to the deepest invasive tumor cells. DOI3 was defined as the total tumor thickness. DOI2 and DOI3 were also divided into three categories using the same cut-off points as in the AJCC 8th edition. We compared these three DOI methods to the AJCC 7th edition as well. In contrast with the AJCC 7th edition, all three groups showed a correlation with patients' overall survival. Above all, the DOI2 group demonstrated the best significance in multivariate analysis. However, when the C indices were compared between these groups, differential significance proved to be negligible (DOI1 vs DOI2, p = 0.915; DOI2 vs DOI3, p = 0.057). Therefore, the measurement of DOI does not need to be rigorously and stringently performed. In conclusion, we showed that the current T classification system better correlates with the overall survival of patients with distal cholangiocarcinomas than the previous system.

The results of HLA-incompatible kidney transplantation according to pre-transplant crossmatch tests: Donor-specific antibody as a prominent predictor of acute rejection.

BACKGROUND: Crossmatching (XM) between organ donors and recipients is correlated with clinical outcomes. This study evaluates the results of HLA-incompatible kidney transplant (HLA-i KT) according to pre-transplant XM modalities. METHODS: This study included 731 consecutive patients. HLA-i KT was defined as a transplant under conditions of complement-dependent cytotoxicity (CDC) XM positivity, flow-cytometric XM (FCXM) positivity, and/or maximal donor-specific antibody (DSA) mean fluorescence intensity (MFI) ≥5000. RESULTS: The incidence of antibody-mediated rejection (AMR) within 1 year after transplant was significantly higher in the HLA-i group than in the HLA compatible (HLA-c) group (15 vs 9 patients, 14.2% vs 1.4%; P < 0.01). Multivariate analysis indicated that a DSA MFI ≥5000 (odds ratio [OR] = 2.63; 95% confidence interval [CI], 1.00-6.98; P = 0.05) was significantly associated with acute rejection (AR), whereas CDC (OR = 2.09; 95% CI, 0.55-7.99; P = 0.28) and FCXM positivity (OR = 2.07; 95% CI, 0.73-5.87; P = 0.17) were not. Similarly, DSA MFI ≥ 5000 (OR = 4.14; P = 0.02) was the only significant factor affecting the risk of AMR. CONCLUSIONS: Of the various XM tests, DSA MFI ≥5000 was the most prominent predictor of AR in patients undergoing HLA-i KT.

Intracranial aneurysms in patients receiving kidney transplantation for autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease, leading to kidney failure. One of the most serious extrarenal complications of ADPKD is comorbid intracranial aneurysms. The aim of this study is to evaluate the prevalence, rupture rate, and treatment outcomes of intracranial aneurysms in ADPKD. METHODS: Adult patients with a documented diagnosis of ADPKD who received kidney transplantation at our center from January 1994 to December 2018 were included in the study. Medical history, physical examination, laboratory findings, imaging studies, and operation records were collected and analyzed from our database. RESULTS: Among 154 kidney transplant recipients with ADPKD, 113 (73.4%) patients were screened for intracranial aneurysms preoperatively. Twenty three patients (14.9%) had intracranial aneurysms with mean diameter size of 4.5 ± 2.7 mm. Nine patients (5.8%) experienced aneurysm rupture and the mean age at time of rupture was 34.9 ± 9.3 years. Twelve patients (52.2%) presented with multiple aneurysms. The most common aneurysm location was the bifurcation of the middle cerebral artery (34.9%). Clipping was the most common treatment in both ruptured and unruptured aneurysms. CONCLUSIONS: Intracranial aneurysms are more frequent in patients with ADPKD, and the average age of intracranial artery rupture in patients with ADPKD is earlier than in the general population. It is necessary to consider proper evaluation and management of intracranial aneurysms when counseling ADPKD patients who will undergo kidney transplantation.

SURF4 has oncogenic potential in NIH3T3 cells.

SURF4, which is located in the Surfeit gene cluster, encodes for a conserved integral membrane protein containing multiple putative transmembrane regions. However, the physiological role of SURF4 has not been determined. We found that SURF4 demonstrated aberrant amplification and increased expression in the tumor tissues of several human cancer patients. Overexpression of SURF4 led to increased cell proliferation, migration, and maintenance of anchorage-independent growth. In addition, NIH3T3 cells overexpressing SURF4 induced tumor growth in the mice. Collectively, our findings demonstrate that SURF4 has the potential for inducing cellular transformation and cell migration in vitro and has oncogenic transformation ability in vivo.

TFE3 translocation and protein expression in renal cell carcinoma are correlated with poor prognosis.

AIMS: Since Xp11.2 translocation-associated renal cell carcinoma (TRCC) was first recognised, its morphological features and the clinical significance of TFE3 expression, frequency of gene translocation and diagnostic criteria have been the subject of limited studies. The present retrospective analysis aimed to evaluate the correlation between TFE3 immunoreactivity and its gene translocation status using fluorescence in-situ hybridisation (FISH) and determine how TFE3 translocation and expression affect patient prognosis differently. METHODS AND RESULTS: We enrolled 303 consecutive renal cell carcinoma cases. Immunohistochemical staining for TFE3 was performed in 303 cases, and FISH analysis was performed for molecular testing. The TCGA data set of renal cell carcinoma was evaluated to validate TFE3 expression and survival analysis. TFE3 expression was associated significantly with the nested alveolar pattern, papillary pattern, eosinophilic cytoplasm, voluminous expansile cytoplasm, nuclear grade, tumour necrosis, sarcomatoid pattern and picket fence appearance. FISH analysis showed break-apart signals in 26 of 32 (81.25%) cases expressing strong or moderate nuclear TFE3 immunoreactivity. Thirteen of 56 samples that showed no or weak TFE3 expression with morphologically suspicious cases were translocation-positive in the FISH assay. The TFE3-translocation group (harbouring TFE3 translocation regardless of TFE3 expression) showed the poorest progression-free survival (PFS), and the TFE3-expressing group (expressing TFE3 but negative for translocation) was correlated significantly with decreased PFS. CONCLUSION: Increased TFE3 expression in RCC was associated with poor PFS regardless of the gene translocation status. Moreover, morphological analysis should help to select candidates who would benefit from TFE3 staining and FISH analysis.

Active {001} Facet Exposed TiO2 Nanotubes Photocatalyst Filter for Volatile Organic Compounds Removal: From Material Development to Commercial Indoor Air Cleaner Application.

TiO2 nanotubes (TNT) have a highly ordered open structure that promotes the diffusion of dioxygen and substrates onto active sites and exhibit high durability against deactivation during the photocatalytic air purification. Herein, we synthesized {001} facet-exposed TiO2 nanotubes (001-TNT) using a new and simple method that can be easily scaled up, and tested them for the photocatalytic removal of volatile organic compounds (VOCs) in both a laboratory reactor and a commercial air cleaner. While the surface of TNT is mainly composed of {101} facet anatase, 001-TNT's outer surface was preferentially aligned with {001} facet anatase. The photocatalytic degradation activity of toluene on 001-TNT was at least twice as high as that of TNT. While the TNT experienced a gradual deactivation during successive cycles of photocatalytic degradation of toluene, the 001-TNT did not exhibit any sign of catalyst deactivation under the same test conditions. Under visible light irradiation, the 001-TNT showed degradation activity for acetaldehyde and formaldehyde, while the TNT did not exhibit any degradation activity for them. The 001-TNT filter was successfully scaled up and installed on a commercial air cleaner. The air cleaner equipped with the 001-TNT filters achieved an average VOCs removal efficiency of 72% (in 30 min of operation) in a 8-m3 test chamber, which satisfied the air cleaner standards protocol (Korea) to be the first photocatalytic air cleaner that passed this protocol.

Patterns of malignant non-mass enhancement on 3-T breast MRI help predict invasiveness: using the BI-RADS lexicon fifth edition.

Background Non-mass enhancements (NME) with invasive components account for 10-42% of total malignant NMEs. The factors associated with invasiveness on magnetic resonance imaging (MRI) could be useful for clinical assessment and treatment. Purpose To evaluate the clinical significances of the distributions and internal enhancement patterns (IEP) of malignant NMEs on 3-T breast MRI. Material and Methods A total of 448 consecutive women with newly diagnosed breast cancer that had undergone preoperative MRI and surgery between February 2013 and March 2016 were identified. After exclusions, 72 malignant NMEs without a mass in 72 women (mean age = 51.5 years) were included. Two readers independently assessed distributions and IEPs of NME, according to the Breast Imaging Reporting and Data System lexicon fifth edition. Collected data included the presence of invasion and histopathologic factors. Results A clustered ring IEP was significantly associated with invasive cancer (75.0%, P = 0.001, Reader1; 72.9%, P < 0.001, Reader 2), absence of necrosis (79.0%, P < 0.001; 72.1%, P < 0.001, respectively), and high Ki-67 expression (74.2%, P = 0.048; 74.2%, P = 0.003, respectively). A clumped IEP was related to ductal carcinoma in situ (33.3%, P = 0.025; 50.0%, P = 0.001, respectively), absence of lymph node metastasis (24.1%, P = 0.029; 31.5%, P = 0.030, respectively), and presence of necrosis (34.5%, P = 0.003; 44.8%, P = 0.001, respectively). Conclusion The presence of a clustered ring IEP in patients with breast cancer was found to be significantly associated with invasive breast cancer and high Ki-67 expression.

IDH1 R132C mutation is detected in clear cell hepatocellular carcinoma by pyrosequencing.

BACKGROUND: Isocitrate dehydrogenase 1 (IDH1) mutation is common in low-grade glioma (approximately 80%) and acute myeloid leukemia (approximately 10%). Other than brain tumor or hematologic malignancies, intrahepatic cholangiocarcinoma (iCC) is a well-known solid tumor with IDH1 mutation (6.8-20%). Histologically, poor differentiation and clear cell change are associated with IDH1 mutation in iCC. Since hepatocellular carcinoma (HCC) shares histologic features with iCC, some specific subtypes of HCC might show a higher IDH1 mutation rate than reported before (0.5-1.5%). METHODS: Forty-six cases of iCC and 48 cases of HCC (including 20 cases of clear cell type and 13 cases of pseudoglandular pattern) were tested for IDH1 mutation by pyrosequencing. RESULTS: Three cases in iCC (6.5%) and five cases in HCC (10.4%) had IDH1 mutation, all of which were Arg132Cys. IDH1 mutant HCCs were all clear cell type. Although the IDH1 mutation rate between iCC and HCC demonstrated no significant difference, clear cell HCC revealed statistically increased mutation rate compared to that of HCC without clear cell change (P = 0.009). Presence of IDH1 mutation was related with poor survival in clear cell HCC patients (P = 0.004). CONCLUSIONS: Clear cell HCC showed higher frequency of IDH1 mutation rate than other variants of HCC. This result consolidates the assumption that morphological features of tumors reflect molecular alterations.

Feasibility Study of Extended-Gate-Type Silicon Nanowire Field-Effect Transistors for Neural Recording.

In this research, a high performance silicon nanowire field-effect transistor (transconductance as high as 34 µS and sensitivity as 84 nS/mV) is extensively studied and directly compared with planar passive microelectrode arrays for neural recording application. Electrical and electrochemical characteristics are carefully characterized in a very well-controlled manner. We especially focused on the signal amplification capability and intrinsic noise of the transistors. A neural recording system using both silicon nanowire field-effect transistor-based active-type microelectrode array and platinum black microelectrode-based passive-type microelectrode array are implemented and compared. An artificial neural spike signal is supplied as input to both arrays through a buffer solution and recorded simultaneously. Recorded signal intensity by the silicon nanowire transistor was precisely determined by an electrical characteristic of the transistor, transconductance. Signal-to-noise ratio was found to be strongly dependent upon the intrinsic 1/f noise of the silicon nanowire transistor. We found how signal strength is determined and how intrinsic noise of the transistor determines signal-to-noise ratio of the recorded neural signals. This study provides in-depth understanding of the overall neural recording mechanism using silicon nanowire transistors and solid design guideline for further improvement and development.

Preoperative chemoradiotherapy for clinically diagnosed T3N0 rectal cancer.

PURPOSE: This retrospective study compared the recurrence-free survival (RFS) and local recurrence rates of patients who received preoperative chemoradiotherapy (PCRT) for cT3N0 vs. those who did not. METHODS: We analyzed the records of 593 patients with transrectal ultrasound (TUS) or magnetic resonance image (MRI)-staged cT3N0 mid and low locally advanced rectal cancer, including 255 who received PCRT and 338 who did not. The RFS and cumulative local recurrence rates were compared in the two groups. We also investigated the rates of pathologic complete response (pCR) and mesorectal lymph node (LN) involvement in the PCRT group. RESULTS: The overall pCR rate was 13.3 %. Of the 338 non-PCRT patients, 125 (37.0 %) had pathologically positive mesorectal LNs. Sphincter-preserving surgery was performed in 431 (72.7 %) of the 593 patients, with similar rates in the two groups. However, the sphincter preservation rate in patients with low rectal cancer was higher among those who received PCRT than among those who did not (64.8 vs. 47 %, P = 0.002). The 5-year RFS (76.4 vs. 75.5 %, P = 0.92) and local recurrence (3.9 vs. 3.0 %, P = 0.97) rates were similar in the PCRT and non-PCRT groups. CONCLUSION: Although PCRT did not improve the RFS or local recurrence rates, it increased the chance of sphincter preservation in patients with low rectal cancer. The advantages of PCRT for patients with cT3N0 should be re-evaluated considering the limitation of pretreatment staging, oncologic benefits, and improved sphincter preservation.

Prognostic significance of WT1 expression in soft tissue sarcoma.

BACKGROUND: Soft tissue sarcomas (STS) are rare. We evaluated the WT1 protein expression level in various types of STS and elucidated the value of WT1 as a prognostic factor and a possible therapeutic target. METHODS: Immunohistochemical staining for WT1 was performed in 87 cases of STS using formalin-fixed, paraffin-embedded blocks. The correlation between WT1 expression and clinicopathological factors was analyzed. Survival analysis was conducted in 67 patients. We assessed the validity of WT1 immunohistochemistry as an index of WT1 protein expression using Western blot analysis. RESULTS: WT1 expression was noted in 47 cases (54.0%). Most rhabdomyosarcomas and malignant peripheral nerve sheath tumors showed WT1 expression (91.7% and 71.4%, respectively; P = 0.005). WT1 expression was related to higher FNCLCC histologic grade and AJCC tumor stage. In the group with high grade STS, strong WT1 expression was correlated with better survival (P = 0.025). The immunohistochemical results were correlated quantitatively with the staining score and the concentration of the Western blot band. CONCLUSIONS: This study demonstrates that various types of STS show positive immunostaining for WT1 and that WT1 expression has a prognostic significance. So STS should be considered candidates for WT1 peptide--based immunotherapy.