Microscopic Polyangiitis Following mRNA COVID-19 Vaccination: A Case Report.

Coronavirus disease 2019 (COVID-19) is one of the most widespread viral infections in human history. As a breakthrough against infection, vaccines have been developed to achieve herd immunity. Here, we report the first case of microscopic polyangiitis (MPA) following BNT162b2 vaccination in Korea. A 42-year-old man presented to the emergency room with general weakness, dyspnea, and edema after the second BNT162b2 vaccination. He had no medical history other than being treated for tuberculosis last year. Although his renal function was normal at last year, acute kidney injury was confirmed at the time of admission to the emergency room. His serum creatinine was 3.05 mg/dL. Routine urinalysis revealed proteinuria (3+) and hematuria. When additional tests were performed for suspected glomerulonephritis, the elevation of myeloperoxidase (MPO) antibody (38.6 IU/mL) was confirmed. Renal biopsy confirmed pauci-immune anti-neutrophil cytoplasmic antibody (ANCA)-related glomerulonephritis and MPA was diagnosed finally. As an induction therapy, a combination of glucocorticoid and rituximab was administered, and plasmapheresis was performed twice. He was discharged after the induction therapy and admitted to the outpatient clinic 34 days after induction therapy. During outpatient examination, his renal function had improved with serum creatinine 1.51 mg/dL. We suggest that MPA needs to be considered if patients have acute kidney injury, proteinuria, and hematuria after vaccination.

miRNAs as potential biomarkers for the progression of gastric cancer inhibit CREBZF and regulate migration of gastric adenocarcinoma cells.

In our previous study, we identified three miRNAs (hsa-miR-421, hsa-miR-29b-1-5p, and hsa-miR-27b-5p) with two mRNAs (FBXO11 and CREBZF) that might play an important role in the development of gastric adenocarcinoma (GAC) from premalignant adenomas. However, the expression and function of these miRNAs have not been not well characterized. We investigated the roles of CREBZF and miRNAs as potential biomarkers for the progression of gastric cancer (GC) in low-/high-grade dysplasia and early gastric cancer patients using immunohistochemical staining and miRNA in situ hybridization. Considering that targets can modulate in GC, we analyzed the CREBZF expression in gastric cancer cell lines by RT-PCR and western blot analysis. We observed lower expression of CREBZF with increasing miRNAs in the MKN-74 gastric cancer cells compared to that in SNU-NCC-19. Next, the role of CREBZF in MKN-74 gastric cancer cells was investigated via cell viability and migration assays by miRNA/anti-miRNA modulation. Furthermore, we found that hsa-miR-421/hsa-miR-29b-1-5p target CREBZF and might play an important role in the migration of MKN-74 cells. This study suggests that increased CREBZF by hsa-miR-421/hsa-miR-29b-1-5p inhibition may be important to prevent the progression of gastric cancer in its early stage.

Late Onset Nephrogenic Systemic Fibrosis in a Patient with Stage 3 Chronic Kidney Disease: a Case Report.

Nephrogenic systemic fibrosis (NSF) is a progressive systemic fibrosing disease that may occur after gadolinium contrast exposure. It can lead to severe complications and even death. NSF is highly prevalent among patients with advanced chronic kidney disease (CKD). In this report, however, we describe the case of a patient with NSF that occurred during early CKD. A 65-year-old man with stage 3a CKD was transferred to our hospital because of lower extremity edema. The medical history revealed that he was exposed to gadolinium 185 days earlier, and the result of his tibial skin biopsy was consistent with NSF. The patient underwent a combined therapy with ultraviolet-A1 phototherapy and methotrexate and steroid therapy for 6 months. The combined therapy stopped the systemic progression of NSF.

Implications of NOVA1 suppression within the microenvironment of gastric cancer: association with immune cell dysregulation.

BACKGROUND: The neuronal splicing factor neuro-oncological ventral antigen 1 (NOVA1) is enriched in normal fibroblasts. Stromal spindle cells such as fibroblasts are major components of tissue inflammation and tertiary lymphoid structures within the microenvironment that contribute to the survival and growth of cancer cells. In the present study, we investigated changes of NOVA1 expression in tertiary lymphoid structures in early and advanced gastric cancer microenvironments in terms of tumor progression and immune regulation. METHODS: Using immunohistochemistry, we analyzed NOVA1 expression in tumor cells, T cells, and stromal spindle cells as well as infiltrating densities of CD3+ T cells, forkhead box P3 positive (FOXP3+) regulatory T cells, CD68+ macrophages, CD163+ M2 macrophages, and myeloperoxidase-positive neutrophils in 396 surgically resected gastric cancer tissues. RESULTS: Suppressed NOVA1 expression in tumor cells, T cells, and stromal spindle cells was closely related to decreased infiltration of FOXP3+ regulatory T cells, increased infiltration of CD68+ macrophages and CD163+ M2 macrophages, more advanced tumor stage, and inferior overall survival rate. In addition, low infiltration of CD3+ T cells and FOXP3+ regulatory T cells and high infiltration of CD68+ macrophages were associated with inferior overall survival. Specifically, weak NOVA1 expression in tumor cells was independently related to more advanced tumor stage and inferior overall survival. CONCLUSIONS: NOVA1 suppression was frequently noted in the gastric cancer microenvironment, and attenuated NOVA1 expression in tumor cells was associated with tumor progression and poor prognosis. This finding seems to be related to immune dysfunction through changes in the immune cell composition of T cells and macrophages.

Resveratrol Ameliorates Contrast Induced Nephropathy Through the Activation of SIRT1-PGC-1α-Foxo1 Signaling in Mice.

BACKGROUND/AIMS: SIRT1 activation promotes the resistance of renal tubular cells to oxidative stress, and resveratrol is known as a SIRT1 activator. METHODS: Resveratrol was injected intraperitoneally with iohexol for 24 hours. NRK-52E cells were pretreated with resveratrol for 24 hours and then exposed to iohexol for 3 hours. Renal function was measured by serum creatinine and cell survival was assessed by MTT assay. We investigated whether resveratrol attenuates oxidative stress and apoptosis in contrast-induced nephropathy (CIN). RESULTS: Serum creatinine and tubular injury increased significantly after iohexol treatment, and resveratrol co-treatment attenuated the renal injury. Cell survival decreased after iohexol exposure and resveratrol reduced cell death induced by iohexol. Resveratrol was accompanied with the activation of SIRT1 and PGC-1α and dephosphorylation of FoxO1 in mice with CIN. SIRT1 and PGC-1α expression were decreased by iohexol, and increased significantly in resveratrol-pretreated cells. These processes resulted in reduction of oxidative stress and apoptosis both in vivo and in vitro experiments. Resveratrol decreased inflammatory cell infiltration induced by iohexol in mice with CIN. SIRT1 inhibition using siRNA in tubular cells accentuated the decrease of cell viability by iohexol. CONCLUSION: Resveratrol attenuated CIN by modulating renal oxidative stress and apoptosis through activation of SIRT1-PGC-1α-FoxO1 signaling.

Mucosa-associated lymphoid tissue (MALT) lymphoma as an unusual cause of malignant hilar biliary stricture: a case report with literature review.

BACKGROUND: Biliary strictures at the hilum of the liver arise from heterogeneous etiologies. The majority is malignant entities, but some may have benign etiologies. It is difficult to distinguish between malignant and benign biliary strictures preoperatively. It has been reported that 5~15 % of preoperative diagnoses of hilar cholangiocarcinoma turn out to be benign lesions or even other types of malignancies. Primary non-Hodgkin's lymphoma of the extrahepatic bile duct is very rare, with only a few cases reported as mucosa-associated lymphoid tissue (MALT) lymphoma arising from the hepatic duct bifurcation. We herein report a case of a female patient presenting with perihilar bile ducts obstructed by primary MALT lymphoma resembling hilar cholangiocarcinoma, along with a review of the literature. CASE PRESENTATION: An 86-year-old female was referred to our hospital manifesting obstructive jaundice and abdominal pain. The reported imaging studies revealed distended intrahepatic bile duct with the stricture of common hepatic duct including bifurcation, which was suspicious of cholangiocarcinoma of the bile duct. The initial laboratory-confirmed cholestasis with a total bilirubin of 8.6 mg/dL, aspartate amino transferase (AST) 178 U/L, alanine transferase (ALT) 105 U/L, and the tumor marker CA 19-9 was elevated with a value of 167 U/mL. Viral markers for hepatitis B and C viruses were negative. She underwent extrahepatic bile duct resection and hepaticojejunostomy. Histological examination of the resected specimen revealed MALT lymphoma. Postoperative follow-up of 1 year has been completely uneventful, without any symptoms or disease recurrence. CONCLUSIONS: In exceptional cases, in which radiologic and clinical features point to cholangiocarcinoma, the actual reason for obstructive jaundice and abdominal pain can be a non-Hodgkin's lymphoma. In the case of a MALT lymphoma, it can be cured with complete resection.

Efficacy and Safety of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells in Anterior Cruciate Ligament Reconstruction of a Rabbit Model: New Strategy to Enhance Tendon Graft Healing.

PURPOSE: To investigate whether non-autologous transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) could be integrated safely at the bone-tendon junction without immune rejection and could enhance bone-tendon healing effectively during anterior cruciate ligament (ACL) reconstruction in an animal model. METHODS: ACL reconstructions using hamstring tendons were performed in 30 adult rabbits. The bone tunnels were treated with hUCB-MSCs or were untreated. The specimens were harvested at 4, 8, and 12 weeks. We performed a gross examination of the knee joint; a histologic assessment using H&E staining, as well as immunohistochemical staining, for type II collagen; and an evaluation of bone tunnel widening using micro-computed tomography. RESULTS: No evidence of immune rejection was detected. Tendon-bone healing through Sharpey-like fibers was noticed around tendon grafts at 12 weeks in the control group. A smooth transition from bone to tendon through broad fibrocartilage formation was identified in the treatment group, and the interface zone showed abundant type II collagen production on immunohistochemical staining. Histologic scores for bone-tendon healing were significantly higher in the treatment group at all time points (P < .001). Micro-computed tomography at 12 weeks showed a significantly smaller tibial (P = .029) and femoral (P = .033) bone tunnel enlargement in the treated group than in the control group. CONCLUSIONS: Non-autologous transplantation of hUCB-MSCs was applied in ACL reconstruction without early immune rejection. There was enhanced tendon-bone healing through broad fibrocartilage formation with higher histologic scores and decreased femoral and tibial tunnel widening compared with the control group (79.2% and 80%, respectively, of the control group tunnel area at 12 weeks). CLINICAL RELEVANCE: Non-autologous transplantation of hUCB-MSCs has therapeutic potential in promoting tendon-to-bone healing after ACL reconstruction. Further study in the human model is warranted.

Expression of Peroxisome Proliferator Activated Receptor gamma in Prostatic Adenocarcinoma.

Peroxisome proliferator-activated receptor gamma (PPAR-γ), a ligand-activated transcription factor has been investigated as the target for cancer treatment as well as metabolic disorders. Recent studies have demonstrated that PPAR-γ ligands are anti-tumorigenic in prostate cancer due to anti-proliferative and pro-differentiation effects. The aim of this study was to validate PPAR-γ expression in malignant and benign prostate tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (PCR). A total of 730 prostatic adenocarcinomas (PCAs) including 63 whole sections from radical prostatectomy specimens and tissue microarrays containing 667 PCAs were subject to immunostaining for two PPAR-γ antibodies. Twenty-five benign prostate tissues and PCAs were selected for investigating mRNA expression by quantitative real-time PCR. 10.7% of PCAs (78/730) showed cytoplasmic immunoreactivity of PPAR-γ and no nuclear immunoreactivity was noted in PCAs. Most benign prostatic glands showed negative immunoreactivity of PPAR-γ except for variable weak cytoplasmic staining in some glands. Nuclear immunoreactivity of PPAR-γ was noted some central zone and verumontanum mucosal epithelium. The constitutive PPAR-γ mRNA showed significantly lower level in PCAs compared to that in the benign tissues. There was no difference of PPAR-γ mRNA expression between low (≤7) and high (>7) Gleason score groups. There was no association of PPAR-γ mRNA level or cytoplasmic immunostaining with Gleason grade or pathologic stage. Our study supported the evidence of extra-nuclear localization and nongenomic actions of PPAR-γ. Further studies are needed to assess the functional role of PPAR-γ and to validate its therapeutic implication in prostate cancer.

Expression of ROR1, pAkt, and pCREB in gastric adenocarcinoma.

The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a transmembrane protein of receptor tyrosine kinase family. High expression of ROR1 is reported in many types of malignancies and is thought to be involved in tumor growth, apoptosis, and epithelial-mesenchymal transition. In this study, we examined the expression of ROR1, pAkt, and pCREB in gastric adenocarcinoma and analyzed with clinicopathologic factors and tumor proliferation. Tissue microarray blocks containing 424 gastric adenocarcinomas were used for immunohistochemical staining. Ki-67 labeling index was used for tumor proliferation activity. High expression of ROR1 (63%), pAkt (36%), and pCREB (20%) was observed in gastric adenocarcinomas, and expression of these proteins was well intercorrelated. ROR1 and pCREB expression was associated with Ki-67 labeling index (P < .001). Expression of pAkt and pCREB group showed longer survival in univariate analysis (P = .007 and P < .001, respectively). This is the first study that analyzed ROR1 expression in gastric adenocarcinoma tissue samples. We revealed that gastric adenocarcinomas highly express ROR1 and related proteins and its prognostic significance. ROR1 in gastric adenocarcinoma could be possible candidate of therapeutic target, and more comprehensive study is required.

Lysyl-tRNA synthetase (KRS) expression in gastric carcinoma and tumor-associated inflammation.

BACKGROUND: Lysyl-tRNA synthetase (KRS) is an aminoacyl-tRNA synthetase (ARS) that is essential for protein synthesis during ligation of specific amino acids to their cognate tRNAs. Aberrant expression of ARSs is associated with various human cancers. METHODS: Using immunohistochemical detection, the present study analyzed the clinical relevance of KRS expression in tumor cells and tumor-associated inflammatory cells (TAI) in 457 patients who underwent curative radical surgery and standard adjuvant therapy and who were observed on long-term follow-up. RESULTS: High expression of KRS in tumor cells (tumor-KRS(+)) was noted in 43.3 % (198 of 457) of cases. High expression of KRS in tumor-associated inflammatory cells (TAI-KRS(+)) including macrophages/monocytes, CD4-positive T cells, and/or neutrophils was observed in 37.2 % (170 of 457) of cases. Status of KRS in the tumor and TAI revealed an association with the known clinicopathological parameters for prognosis of gastric cancer. Tumor-KRS(+) status correlated to shorter overall survival, especially in stage III to IV cancers (P = 0.003), while TAI-KRS(+) status correlated significantly to longer overall survival in gastric cancer (P = 0.049). Cases with tumor-KRS(+) and TAI-KRS(-) status showed significantly reduced survival rates compared to those of other cases (P = 0.010), and status of tumor-KRS(+) and TAI-KRS(-) was revealed as an independently poor prognostic factor of overall survival (P = 0.001). CONCLUSIONS: KRS-related inflammation can be identified in a subset of gastric cancer. This may be a possible mechanism of immune surveillance against tumor progression. In addition, expression status of KRS in tumor and TAI may be an independent prognostic marker for gastric cancer patients.

Expression of moesin and CD44 is associated with poor prognosis in gastric adenocarcinoma.

AIMS: CD44 has been reported as a negative prognostic marker in gastric cancer. It interacts with moesin in epithelial-mesenchymal transition. To date, to our knowledge, there has been no clinical study dealing with the relationship between moesin and gastric adenocarcinoma. We analysed the expression of moesin and CD44 in gastric adenocarcinoma tissue, and correlations with clinicopathological factors. METHODS AND RESULTS: A retrospective analysis was made of 430 patients who had undergone gastrectomy at the Korea University Guro Hospital between 2002 and 2005 for gastric adenocarcinoma. Using tissue microarray and immunohistochemical staining, moesin expression was observed in 192 (44.7%) cases; it was associated significantly with poorly differentiated histology, invasion depth, lymph node metastasis, lymphatic invasion and advanced pathological TNM stage. CD44 expression was not correlated with clinicopathological features or moesin expression. Moesin expression was a strong predictor of lymph node metastasis in logistic regression analysis. Both moesin expression and CD44 expression were associated significantly with poor overall survival in univariate analysis. Furthermore, in multivariate analysis, moesin and CD44 were independent markers of poor prognosis, along with pathological TNM stage and older patient age. CONCLUSION: Moesin expression and CD44 expression might be useful markers of poor prognosis in gastric adenocarcinoma.

Low gamma-butyrobetaine dioxygenase (BBOX1) expression as a prognostic biomarker in patients with clear cell renal cell carcinoma: a machine learning approach.

Gamma-butyrobetaine dioxygenase (BBOX1) is a catalyst for the conversion of gamma-butyrobetaine to l-carnitine, which is detected in normal renal tubules. The purpose of this study was to analyze the prognosis, immune response, and genetic alterations associated with low BBOX1 expression in patients with clear cell renal cell carcinoma (RCC). We analyzed the relative influence of BBOX1 on survival using machine learning and investigated drugs that can inhibit renal cancer cells with low BBOX1 expression. We analyzed clinicopathologic factors, survival rates, immune profiles, and gene sets according to BBOX1 expression in a total of 857 patients with kidney cancer from the Hanyang University Hospital cohort (247 cases) and The Cancer Genome Atlas (610 cases). We employed immunohistochemical staining, gene set enrichment analysis, in silico cytometry, pathway network analyses, in vitro drug screening, and gradient boosting machines. BBOX1 expression in RCC was decreased compared with that in normal tissues. Low BBOX1 expression was associated with poor prognosis, decreased CD8+ T cells, and increased neutrophils. In gene set enrichment analyses, low BBOX1 expression was related to gene sets with oncogenic activity and a weak immune response. In pathway network analysis, BBOX1 was linked to regulation of various T cells and programmed death-ligand 1. In vitro drug screening showed that midostaurin, BAY-61-3606, GSK690693, and linifanib inhibited the growth of RCC cells with low BBOX1 expression. Low BBOX1 expression in patients with RCC is related to short survival time and reduced CD8+ T cells; midostaurin, among other drugs, may have enhanced therapeutic effects in this context.

Somatic hypermutation and outcomes of platinum based chemotherapy in patients with high grade serous ovarian cancer.

OBJECTIVE: The standard treatment for high grade ovarian serous cancer (HG-OSC) is aggressive cytoreductive surgery followed by platinum based chemotherapy. However, approximately 30% of patients exhibit platinum resistance, and those patients show aggressive clinical courses. Currently, it is difficult to predict which HG-OSC patients will respond to platinum-based chemotherapy. METHODS: We analyzed whole exome sequences for 174 HG-SOC patients using data obtained from The Cancer Genome Atlas (TCGA) data portal regarding platinum response. Patients were categorized as having either hypermutation or hypomutation according to the number of mutations in their sample. RESULTS: HG-SOC showed multiple somatic mutations in individual patients with an average mutated gene number of 61.9. The mean mutation number per patient significantly differed between the platinum sensitive and resistant groups (P<0.001). Patients who were platinum sensitive were more likely to have somatic hypermutation in their cancer cells and multivariate logistic regression analysis revealed that somatic hypermutation was an independent factor for risk estimation of platinum sensitivity (odds ratio [OR]=3.616; P=0.002). In multivariate Cox hazard analysis, we identified that somatic hypermutation, as well as platinum response and surgical outcome, were independent prognostic factors in HG-OSC (overall survival, P=0.012; progression free survival, P=0.036). CONCLUSIONS: Somatic hypermutation was significantly associated with platinum sensitivity and was an independent prognostic factor in HG-OSC patients treated with platinum based chemotherapy.

Deep learning model to predict Epstein-Barr virus associated gastric cancer in histology.

The detection of Epstein-Barr virus (EBV) in gastric cancer patients is crucial for clinical decision making, as it is related with specific treatment responses and prognoses. Despite its importance, the limited medical resources preclude universal EBV testing. Herein, we propose a deep learning-based EBV prediction method from H&E-stained whole-slide images (WSI). Our model was developed using 319 H&E stained WSI (26 EBV positive; TCGA dataset) from the Cancer Genome Atlas, and 108 WSI (8 EBV positive; ISH dataset) from an independent institution. Our deep learning model, EBVNet consists of two sequential components: a tumor classifier and an EBV classifier. We visualized the learned representation by the classifiers using UMAP. We externally validated the model using 60 additional WSI (7 being EBV positive; HGH dataset). We compared the model's performance with those of four pathologists. EBVNet achieved an AUPRC of 0.65, whereas the four pathologists yielded a mean AUPRC of 0.41. Moreover, EBVNet achieved an negative predictive value, sensitivity, specificity, precision, and F1-score of 0.98, 0.86, 0.92, 0.60, and 0.71, respectively. Our proposed model is expected to contribute to prescreen patients for confirmatory testing, potentially to save test-related cost and labor.

Increased VEGF-A in solid type of lung adenocarcinoma reduces the patients' survival.

The histological classification of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival differences between the other types were not significant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.

Chronic Gastritis Is Associated with a Decreased High-Density Lipid Level: Histological Features of Gastritis Based on the Updated Sydney System.

Chronic gastritis could activate a systemic inflammatory response that could result in adverse lipid profiles. To determine the severity of chronic gastritis, Helicobacter pylori (HP), mononuclear cell (lymphocytes and plasma cells), and neutrophil scores were assessed on the basis of the updated Sydney system (USS), which is widely used for histological grading. The aim of this study was to assess the relationships between gastric histological features and lipid profile levels. This study included 15,322 males and 5929 females who underwent a health checkup and gastric biopsy at the Kangbuk Samsung Medical Center (KBSMC). We analyzed whether the HP, mononuclear cell, and neutrophil grades according to the USS were related to serum leukocyte count, unhealthy behaviors, and lipid profile levels. Gastritis with HP, neutrophils, or moderate to severe mononuclear cells was associated with an elevated serum leukocyte count. A high leukocyte count was related to increased low-density lipoproteins (LDL) and triglycerides/very-low-density lipoprotein (VLDL) and decreased high-density lipoproteins (HDL). In multivariate analyses, chronic gastritis with HP or moderate to severe mononuclear cells was significantly associated with decreased HDL in males, while mononuclear cells were significantly related to decreased HDL in females. Chronic gastritis was associated with an increased systemic inflammatory response, which was associated with unfavorable lipid profiles, especially low HDL levels.

Significantly different expression levels of microRNAs associated with vascular invasion in hepatocellular carcinoma and their prognostic significance after surgical resection.

BACKGROUND: Although gross vascular invasion (VI) has prognostic significance in patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between gross VI and aberrant expression of microribonucleic acids (miRNAs and miRs). Thus, the objective of this study was to identify miRNAs selectively expressed in HCC with gross VI and investigate their prognostic significance. MATERIALS AND METHODS: Eligible two datasets (accession number: GSE20594 and GSE67140) were collected from the National Center for Biotechnology Information's (NCBI) Gene Expression Omnibus (GEO) database to compare miRNAs expression between HCC with and without gross VI. Differentially expressed miRNAs were externally validated using expression data from The Cancer Genome Atlas (TCGA) database. Prognostic significance and predicted functions of selected miRNAs for HCC were also investigated. RESULTS: Thirty-five miRNAs were differentially expressed between HCC with and without gross VI in both datasets. Among them, three miRNAs were validated using TCGA database. miR-99a, miR-100, and miR-148a were downregulated to a greater extent in patients with HCC and gross VI than in those with HCC but no gross VI. Receiver operating characteristic (ROC) curve analysis showed discriminatory power of these miRNAs in predicting gross VI. Multivariate survival analysis revealed that types of surgery, advanced tumor node metastasis (TNM) stage, and low expression of miR-100-5p were independently associated with tumor recurrence. It also revealed that types of surgery, advanced TNM stage, low expression of miR-100-5p and miR-148a-3p were independent risk factors for overall survival (OS) after hepatic resection for HCC. A text mining analysis revealed that these miRNAs were linked to multifaceted hallmarks of cancer, including "invasion and metastasis." CONCLUSIONS: Low expressions of miR-100-5p and miR-148a-3p were associated with gross VI and poor survival of patients after hepatic resection for HCC.

Theragnosis by a miR-141-3p molecular beacon: simultaneous detection and sensitization of 5-fluorouracil resistant colorectal cancer cells through the activation of the TRIM13-associated apoptotic pathway.

We developed a molecular beacon targeting miR-141-3p, aberrantly increased in 5-fluorouracil-resistant colorectal cancer cells (R-CRCCs). It consists of a fluorophore-labeled oligonucleotide, antisense to miR-141-3p, and a quencher. It detected R-CRCCs and recovered the chemosensitivity of them to 5-fluorouracil by hybridization with miR-141-3p, which is applicable to cancer treatment.

Exosome-Mediated Ultra-Effective Direct Conversion of Human Fibroblasts into Neural Progenitor-like Cells.

Exosomes, naturally secreted nanoparticles, have been introduced as vehicles for horizontal transfer of genetic material. We induced autologous exosomes containing a cocktail of reprogramming factors ("reprosomes") to convert fibroblasts into neural progenitor cells (NPCs). The fibroblasts were treated with ultrasound and subsequently cultured in neural stem cell medium for 1 day to induce the release of reprosomes composed of reprogramming factors associated with chromatin remodeling and neural lineage-specific factors. After being treated with reprosomes, fibroblasts were converted into NPCs (rNPCs) with great efficiency via activation of chromatin remodeling, so quickly that only 5 days were required for the formation of 1500 spheroids showing an NPC-like phenotype. The rNPCs maintained self-renewal and proliferative properties for several weeks and successfully differentiated into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. Reprosome-mediated cellular reprogramming is simple, safe, and efficient to produce autologous stem cells for clinical application.

Increased expression of matrix metalloproteinase 9 and tubulin-alpha in pulmonary sclerosing hemangioma.

Pulmonary sclerosing hemangioma (PSH) is relatively rare and is usually considered a benign tumor because of its slow growth and solitary characteristics. However, several cases with lymph node metastasis have been reported, and its pathogenesis has not been fully elucidated. Three sets of PSH specimens from the Korea Lung Tissue Bank, obtained with IRB approval, were analyzed through the construction of an oligo-microarray that contained about 32,000 genes. The resulting data were confirmed by real-time RT-PCR. Protein expression levels were checked by performing immunohistochemistry (IHC) and immunoblot analysis. In the 3 specimens of PSH tissues, 72 of the 32,000 genes were commonly found up-regulated and 290 were commonly found down-regulated as compared to non-tumor tissues from each patient. Paraffin-embedded tissues from 11 cases were used to confirm the expression of matrix metalloproteinase 9 (MMP-9) and tubulin-alpha proteins in the non-tumor and PSH tissues via IHC. In addition, the upregulation of protein expression was confirmed by immunoblot analysis. As expected, in all cases MMP-9 and tubulin-alpha were expressed at significantly higher levels in the PSH than in the non-tumor tissues. This is the first report on a study of the whole genome of PSH. Increased expression of MMP-9 could induce the metastatic ability of PSH and tubulin-alpha might be responsible for the sclerotic character of this disease. The results of this study will be useful in helping to understand and effectively manage patients suffering from PSH.