Mesh migration into esophagogastric junction after laparoscopic hiatal hernia repair; how to prevent it? A case report.

Although the use of mesh reinforcement during large hiatal hernia repair may reduce the rate of recurrence, various mesh-related complications have been reported. A 65-year-old woman presented with dysphagia. The patient was diagnosed with a large hiatal hernia and treated with laparoscopic fundoplication and Collis gastroplasty with mesh repair. Six months after surgery, the patient presented with dysphagia and vomiting. Esophagogastroduodenoscopy showed migration of mesh material into the esophagogastric junction. We performed a proximal gastrectomy with mesh removal. The patient was discharged without any postoperative complications. Herein, we encountered a rare case requiring surgical treatment to resolve mesh-induced esophagogastric perforation after hiatal hernia repair. Mesh-associated complications, such as erosion or migration, should be considered as they may be more common than previously reported. Additionally, these complications are currently underscored in clinical practice. Regarding mesh applications, symptoms of mesh-related complications, such as dysphagia, should be carefully monitored for early detection.

Nodular Fasciitis of the Breast Mimicking Phyllodes Tumors: A Case Report and Literature Review.

Nodular fasciitis is a benign proliferative lesion of the fibroblasts and/or myofibroblasts, generally detected in the soft tissue of the upper extremities. It has also been reported in the lower extremities, head, and neck, and rarely in the breast. Its rarity and nonspecific clinical and radiological features resemble those of malignant tumors of the breast and make the differential diagnosis and management difficult. Herein, we present a rare case of nodular fasciitis of the breast, which was initially suspected to be a phyllodes tumor.

Imaging characteristics of slow-growing soft tissue chondroma of the tongue: A case report.

INTRODUCTION: Extraskeletal soft tissue chondroma (STC) is a rare benign tumor. Soft-tissue chondromas rarely occur in the oral cavity. In this study, we aimed to confirm a slow-growing tongue mass using magnetic resonance imaging. PATIENT CONCERNS: A 60-year-old woman presented with a painful, slow-growing tongue mass that had persisted for 17 years. Intraoral examination revealed a pedunculated mass covered with mucosa on the right side of her tongue. DIAGNOSIS: CT and MRI revealed a lobulated heterogeneously enhancing mass without calcification. Compared with previous images obtained 17 years prior, the mass presented slow growth, more prominent enhancement, and lobulated contour. Histopathological examination confirmed the presence of STC. INTERVENTIONS: Excision of the mass surrounding normal tissue was performed under general anesthesia. OUTCOMES: During 1-year follow-up period, no recurrence was observed. CONCLUSIONS: In this study, STC lesions were slow-growing, and changed from weakly homogeneous enhancement and clean margins to markedly heterogeneous enhancement and lobulated margins over time.

A rare case of eosinophilic cystitis involving the inside and outside of the urinary bladder associated with an infected urachal cyst.

BACKGROUND: Eosinophilic cystitis is a rare inflammatory disease of the bladder characterized by eosinophilic infiltration of the bladder wall. Most Eosinophilic cystitis cases present with mucosal lesions of the urinary bladder. We present a very rare case of large mass-forming eosinophilic cystitis, involving the inside and outside of the bladder associated with an infected urachal cyst. CASE PRESENTATION: A 59-year-old man presented with gross hematuria, fever, dysuria, and suprapubic pain. Computed tomography showed a heterogeneously enhancing mass that measured 7.6 cm × 4 cm located on the anterosuperior portion of the bladder with an internal fluid collection. Cystoscopy revealed a raspberry-like mass lesion on the bladder dome. Transurethral resection of the bladder was initially performed. The mass lesion protruding from inside the bladder was removed, and pus-like fluid was drained. The pathologic diagnosis was eosinophilic cystitis. Follow-up computed tomography showed a remnant mass outside the bladder and urachal cyst. To eliminate the remnant lesion, robot-assisted partial cystectomy was performed. The patient showed no evidence of recurrent disease on follow-up cystoscopy and computed tomography for up to 2 years. CONCLUSIONS: Clinicians should consider the possibility of eosinophilic cystitis in patients who present with hematuria, fever, and suprapubic pain and have both intravesical and extravesical masses.

Fulminant Disseminating Fatal Granulomatous Amebic Encephalitis: The First Case Report in an Immunocompetent Patient in South Korea.

Central nervous system infections caused by free-living amoeba are very rare, but often fatal. The typical image findings of amebic meningoencephalitis are non-specific, showing ring-like enhancement. We report the first case of fulminant disseminating fatal granulomatous amebic encephalitis caused by Balamuthia mandrillaris in an immunocompetent patient in South Korea. Our case exhibited two interesting features: one was the unusual clinical course and the other was additional image findings. Magnetic resonance imaging revealed a rim-enhancing lesion with intralesional blooming dark signal intensity on susceptibility weighted imaging and low signal intensity on diffusion weighted images and on apparent diffusion coefficient maps. Differential diagnosis was started from a tumor or non-tumorous lesion, and diagnosis was difficult due to the rarity of the disease. Following the clinical and diagnostic courses of our case, we recommend inspecting image findings of granulomatous amebic encephalitis for early diagnosis.

Quisqualis indica extract ameliorates low urinary tract symptoms in testosterone propionate-induced benign prostatic hyperplasia rats.

Benign prostate hyperplasia (BPH) is a common disease in old-age males, accounting for approximately 77% of morbidity within the age range of 40 to 70 years. It has been shown that morbidity increases with social graying. Quisqualis indica linn (QI) has been used to treat inflammation, stomach pain, and digestion problems. In this study, we evaluated the symptom-regulating effects of QI extract on a testosterone-induced BPH rat model. After inducing BPH in rats using testosterone propionate (TP) injection, we assessed basal intraurethral pressure (IUP) and increments of IUP elicited by electrical field stimulation (5 V, 5, 10, or 20 Hz) or phenylephrine (Phe) (0.01, 0.03, 0.1 mg/kg IV). To induce BPH, 8-week-old rats were subjected to a daily subcutaneous TP (3 mg/kg) injection for 4 weeks. Finasteride (Fina) (10 mg/kg PO) was administered to the rats in the first treatment, while QI (150 mg/kg PO) was administered to those in the second group. Blood pressure was measured together with IUP, after which low urinary tract (LUT), ventral prostate (VP), testicle, and corpus spongiosum were isolated and weighed. Basal IUPs for the Fina- and QI-treated groups were 87.6 and 86.8%, respectively. LUT and VP organ weights in the QI group were lower than those in the Fina group. However, the QI group showed significantly reduced electrical stimulated or Phe-induced IUP increment compared to the Fina and BPH groups. These results proved that QI can be beneficial for BPH symptoms by inhibiting 5α-reductase and consequently decreasing prostate and releasing urinary pressure.

1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol (PLAG) Mitigates Monosodium Urate (MSU)-Induced Acute Gouty Inflammation in BALB/c Mice.

Acute gouty arthritis is an auto-inflammatory disease caused by the deposition of monosodium urate (MSU) crystals in joints or tissues. Excessive neutrophil recruitment into gouty lesions is a general clinical sign and induces a pain phenotype. Attenuation of successive periods of neutrophil infiltration might be a beneficial approach to achieve therapeutic efficacy. In this study, the activity of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) in attenuation of excess neutrophil infiltration was assessed in gout-induced lesions of BALB/c mice. Neutrophil infiltration in MSU-induced gouty lesions was analyzed using immunohistochemical staining. ELISA and RT-PCR were used to measure attenuation of expression of the major neutrophil chemoattractant, CXC motif chemokine ligand 8 (CXCL8), in a PLAG-treated animal model and in cells in vitro. The animal model revealed massive increased neutrophil infiltration in the MSU-induced gouty lesions, but the PLAG-treated mice had significantly reduced neutrophil numbers in these lesions. The results also indicated that the MSU crystals stimulated a damage-associated molecular pattern that was recognized by the P2Y6 purinergic receptor. This MSU-stimulated P2Y6 receptor was destined to intracellular trafficking. During intracellular endosomal trafficking of the receptor, endosome-dependent signaling provided expression of CXCL8 chemokines for neutrophil recruitment. PLAG accelerated initiation of the intracellular trafficking of the P2Y6 receptor and returning the receptor to the membrane. This process shortened the intracellular retention time of the receptor anchoring endosome and subsequently attenuated endosome-dependent signaling for CXCL8 expression. These study results suggested that PLAG could be used for resolution of acute inflammation induced in gout lesions.

Seminal Vesicle Involvement by Carcinoma In Situ of the Bladder: Clonal Analysis Using Next-Generation Sequencing to Elucidate the Mechanism of Tumor Spread.

We present a rare case of urothelial carcinoma in situ (CIS), which invades the prostate and seminal vesicle (SV). A 70-year-old man underwent transurethral resection of bladder (TURB), and the pathologic examination revealed multiple CIS. Although the patient received intravesical bacillus Calmette-Guerin (BCG) therapy following TURB, recurrence of CIS was confirmed in the bladder and left distal ureter at 3 months following BCG. Radical cystectomy was performed due to BCG-refractory CIS. Microscopically, CIS was found throughout the mucosa of the bladder, left ureter, prostatic duct, and both SVs. Next-generation sequencing revealed significant differences in tumor clonality between bladder and SV CIS cells. Among 101 (bladder CIS) and 95 (SV CIS) somatic mutations, only two were shared, and only one gene (ARHGAP23) was common exon coding region gene. In conclusion, multicentric genetic changes, in line with the field-cancerization effect, may result in SV involvement by CIS of the bladder.

1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol (PLAG) Rapidly Resolves LPS-Induced Acute Lung Injury Through the Effective Control of Neutrophil Recruitment.

Acute lung injury (ALI) is an acute respiratory failure that is associated with excessive neutrophil recruitment and high mortality. To assess the efficacy of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) as a therapeutic agent for ALI, this compound was administered orally to mice challenged with an intranasal dose of lipopolysaccharide (LPS). Using this model, we found that PLAG promotes resolution of ALI through effective control of LPS-induced neutrophil infiltration, endothelial permeability, and inflammatory chemokine production. In addition, the Toll like Receptor 4 (TLR4) endocytosis/exocytosis cycle was significantly accelerated in Raw 264.7 cells co-treated with PLAG/LPS, as compared to cells treated only with LPS. During this cycle, a PLAG-induced exotoxin clearance pathway was observed to occur through the prompt assembly of nicotinamide adenine dinucleotide phosphate (NADPH) units and production of reactive oxygen species (ROS), which ultimately lead to earlier LPS clearance. We further detected reduced expression, as well as faster return to homeostatic levels, of macrophage inflammatory protein (MIP)-2, in PLAG/LPS- vs. LPS-treated cells. MIP-2 is a main inducer of neutrophil migration that is mainly controlled by interferon regulatory factor 3 (IRF3) activation and is involved in the TLR4 endosomal-signaling pathway. PLAG induced TLR4-mediated TRIF-related adaptor molecules/Toll-interleukin receptor (TIR) domain-containing adaptor protein including interferon (IFN)-ß/IRF3 endosomal signaling, leading to rapid association of TRAM/TRIF and TLR4 and earlier IRF3 phosphorylation in PLAG/LPS-treated vs. LPS-treated cells. PLAG specificity was further verified with PLAG analogs and metabolites known to control excessive neutrophil infiltration, suggesting that this acetylated diacylglycerol has a unique biological role in neutrophil motility. Thus, our data indicate that PLAG may represent a potential therapeutic agent for resolution of LPS-induced lung inflammation through effective MIP-2 modulation.

Metastatic Lymph Node Ratio (mLNR) is a Useful Parameter in the Prognosis of Colorectal Cancer; A Meta-Analysis for the Prognostic Role of mLNR.

Background and objectives: The presenting study aimed to elucidate the prognostic role of the metastatic lymph node ratio (mLNR) in patients with colorectal cancer (CRC), using a meta-analysis. Materials and Methods: Using data from 90,274 patients from 14 eligible studies, we performed a meta-analysis for the correlation between mLNR and survival rate. Besides, subgroup analyses were performed, based on tumor stage, tumor location, and mLNR. Results: A high mLNR showed significant correlation with worse overall survival and disease-free survival rates in CRC patients (hazard ratio (HR), 1.617, 95% confidence interval (CI) 1.393-1.877, and HR 2.345, 95% CI 1.879-2.926, respectively). In patients with stage III, who had regional LN metastasis, the HRs were 1.730 (95% CI 1.266-2.362) and 2.451 (95% CI 1.719-3.494) for overall and disease-free survival, respectively. According to tumor location, rectal cancer showed a worse survival rate when compared to colon cancer. In the analysis for overall survival, when mLNR was 0.2, HR was the highest across the different subgroups (HR 5.040, 95% CI 1.780-14.270). However, in the analysis for disease-free survival, the subgroup with an mLNR < 0.2 had a higher HR than the other subgroups (HR 2.878, 95% CI 1.401-5.912). Conclusions: The mLNR may be a useful prognostic factor for patients with CRC, regardless of the tumor stage or tumor location. Further studies are necessary for the detailed criteria of mLNR before its application in daily practice.

1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol Attenuates Streptozotocin-Induced Pancreatic Beta Cell Damage by Promoting Glucose Transporter 2 Endocytosis.

Streptozotocin (STZ) is widely used to induce diabetic rodent models. It is specifically toxic to pancreatic beta cells and causes severe destruction and dysfunction. We investigated the effect of 1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) on an STZ-induced diabetic mouse model. PLAG attenuated the glucose increase and maintained serum insulin at levels similar to those seen with control mice. In pancreatic beta cell line INS-1, STZ-induced cell apoptosis and intracellular reactive oxygen species (ROS) generation were significantly reduced to nearly normal levels after PLAG treatment. Glucose transporter 2 (GLUT2) localization analyses and glucose uptake assays showed that PLAG accelerated GLUT2 internalization, which ameliorated excessive entry of glucose, as well as STZ. STZ-induced cytotoxic effects were significantly reduced in PLAG-treated groups. The biological activity of PLAG was further confirmed in GLUT2-silenced cells, and the specificity of PLAG was verified using its derivative 1-palmitoyl-2-linoleoyl-3-hydroxyl-rac-glycerol (PLH). Our results suggest that PLAG may be a useful agent for protecting beta cells in the setting of excessive glucose influx.

Nrf2-Heme Oxygenase-1 Attenuates High-Glucose-Induced Epithelial-to-Mesenchymal Transition of Renal Tubule Cells by Inhibiting ROS-Mediated PI3K/Akt/GSK-3ß Signaling.

BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is thought to play a significant role in the advancement to chronic kidney disease and contributes to the deposition of extracellular matrix proteins and renal fibrosis relating to diabetic nephropathy. METHOD: We studied the effect of Nrf2-HO-1 signaling on high-glucose- (HG-) induced EMT in normal human tubular epithelial cells, that is, HK2 cells. In short, we treated HK2 cells with HG and sulforaphane (SFN) as an Nrf2 activator. EMT was evaluated by the expression activity of the epithelial marker E-cadherin and mesenchymal markers such as vimentin and fibronectin. RESULTS: Exposure of HK2 cells to HG (60 mM) activated the expression of vimentin and fibronectin but decreased E-cadherin. Treatment of HK2 cells with SFN caused HG-induced attenuation in EMT markers with activated Nrf2-HO-1. We found that SFN decreased HG-induced production of reactive oxygen species (ROS), phosphorylation of PI3K/Akt at serine 473, and inhibitory phosphorylation of serine/threonine kinase glycogen synthase kinase-3ß (GSK-3ß) at serine 9. Subsequently, these signaling led to the downregulation of the Snail-1 transcriptional factor and the recovery of E-cadherin. CONCLUSION: The present study suggests that Nrf2-HO-1 signaling has an inhibitory role in the regulation of EMT through the modulation of ROS-mediated PI3K/Akt/GSK-3ß activity, highlighting Nrf2-HO-1 and GSK-3ß as potential therapeutic targets in diabetic nephropathy.

Squalene Epoxidase Correlates E-Cadherin Expression and Overall Survival in Colorectal Cancer Patients: The Impact on Prognosis and Correlation to Clinicopathologic Features

Squalene epoxidase (SE), coded by SQLE, is an important rate-limiting enzyme in the cholesterol biosynthetic pathway. Recently, the aberrant expression of SQLE, which is responsible for epithelial to mesenchymal transition (EMT), has been reported in various types of cancer. This study was undertaken to clarify the clinicopathologic implications of SE in patients with stage I to IV colorectal cancer (CRC). We also analyzed the expression patterns of SE in association with E-cadherin in a series of CRCs. We detected the cytoplasmic expression of SE in 59.4% of carcinoma samples by immunohistochemistry (IHC). There was a significant correlation between a high level of SE expression and lymphovascular (LV) invasion (p < 0.001), tumor budding (p < 0.001), invasion depth (p = 0.002), regional lymph node metastasis (p < 0.001), and pathologic TNM stage (p < 0.001). SE is more abundantly expressed at the invasive front, and reversely correlated with E-cadherin expression. Patients with SE-positive CRC had shorter recurrence-free survival (RFS) and poor overall survival (OS) than those with SE-negative CRC in multivariate analysis (p < 0.001 and p < 0.001, respectively). These data suggest that SE can serve as a valuable biomarker for unfavorable prognosis, and as a possible therapeutic target in CRCs.

Nrf2-Heme oxygenase-1 modulates autophagy and inhibits apoptosis triggered by elevated glucose levels in renal tubule cells.

BACKGROUND: Autophagy is a highly balanced process in which lysosomes remove aged and damaged organelles and cellular proteins. Autophagy is essential to maintain homeostasis in the kidneys. METHODS: Using human renal tubule cells HK-2, we assessed the impact of high glucose (HG) on autophagy. We also evaluated the capability of sulforaphane (SFN) to protect the HK-2 cells from HG-induced apoptosis by modulating autophagy. RESULTS: SFN modulated autophagy and decreased apoptosis in the HK-2 cells that were cultured in 250 mM glucose medium for two days. The reactive oxygen species (ROS) levels increased, as expected, in the cells cultured in the 250 mM glucose medium. However, the SFN decreased the ROS levels in the HK-2 cells. The overexpression of heme oxygenase-1 (HO-1) by SFN decreased the expression of LC3 and beclin-1. LC3 and beclin-1 were involved in the downregulation of caspase-3 that was observed in the HG-induced cells. CONCLUSION: The activation of nuclear factor E2-related factor 2 (Nrf2)-HO-1 inhibited ROS expression and subsequently attenuated autophagy and cell apoptosis after HG injury was decreased. HG injury led to the activation of autophagy and HO-1 in order to combat oxidative stress and protect against cell apoptosis. Therefore, HO-1 activation can prevent ROS development and oxidative stress during HG injury, which considerably decreases autophagy and apoptosis.

Gland Attenuation, a Novel Morphological Feature of Colorectal Cancer: Evidence for an Epithelial-Mesenchymal Transition.

PURPOSE: Along the invasive margin, colorectal cancer may show distinctive morphologic changes characterized by an asymmetrically attenuating tumor gland with loss of polarity. The author coined the term 'gland attenuation (GA)' for these peculiar changes. The aims of this study were to compare the immunoreactivity of the epithelial-mesenchymal transition (EMT) markers E-cadherin and ß-catenin and thus determine whether EMTs occurs at tumor budding (TB) or GA sites and to assess the association of TB and/or GA levels with clinicopathological parameters and prognosis. METHODS: Expression patterns of E-cadherin and ß-catenin in the tumor centers at GA and TB sites were examined in 101 patients with well or moderately differentiated CRCs, and the prognostic significance of TB and/or GA was statistically evaluated. RESULTS: GA foci, as well as TB foci, revealed loss of membranous and cytoplasmic E-cadherin expressions and aberrant ß-catenin expression with reduced membranous expression and increased localization to the nucleus, suggesting that EMTs occur in GA as well as in TB. The high-TB and the TB-dominant groups were significantly correlated with advanced invasion depth, presence of lymph node metastasis, advanced pathologic staging and presence of lymphovascular invasion. The high-TB and the TB-dominant groups showed poor overall survival (OS) and recurrence-free survival (RFS), and high TB was an independent prognostic factor in the multivariate analyses for OS and RFS. CONCLUSION: This study showed evidence that EMTs occurs at GA sites as well as TB foci. TB is a strong and independent prognostic factor, and TB-dominance may be an indicator of adverse clinical outcome.

Activation of the complement system in an osteosarcoma cell line promotes angiogenesis through enhanced production of growth factors.

There is increasing evidence that the complement system is activated in various cancer tissues. Besides being involved in innate immunity against pathogens, the complement system also participates in inflammation and the modulation of tumor microenvironment. Recent studies suggest that complement activation promotes tumor progression in various ways. Among some cancer cell lines, we found that human bone osteosarcoma epithelial cells (U2-OS) can activate the alternative pathway of the complement system by pooled normal human serum. Interestingly, U2-OS cells showed less expression of complement regulatory proteins, compared to other cancer cell lines. Furthermore, the activated complement system enhanced the production of growth factors, which promoted angiogenesis of human endothelial cells. Our results demonstrated a direct linkage between the complement system and angiogenesis using the in vitro model, which suggest the complement system and related mechanisms might be potential targets for cancer treatment.

Clinical, prognostic, and therapeutic significance of heat shock protein 27 in bladder cancer.

Heat shock protein 27 (HSP27) is highly expressed in many cancers, and its prognostic and predictive value has been reported. HSP27 knockdown using siRNA or OGX-427 (an anti-sense oligonucleotide sequence targeting HSP27) is reported to have anti-cancer effects and to enhance chemosensitivity of cancer cells to chemotherapeutic agents. However, conflicting results have been reported regarding the clinical significance of HSP27 in bladder cancer (BC). Furthermore, long-term suppression of HSP27 has not been investigated in BC. In this study, we investigated the association between HSP27 expression and BC characteristics in 132 BC patient samples, as well as its prognostic value to determine the potential of HSP27 as a clinical biomarker. Additionally, we applied five different shRNAs targeting HSP27 in three invasive BC cell lines to analyze the long-term knockdown effects of HSP27. Our study revealed a significant association between HSP27 expression and adverse pathological characteristics such as high-stage and -grade BC. However, HSP27 expression was not associated with clinical outcomes such as tumor recurrence, progression, and patient survival. Interestingly, although our shRNAs had obvious knockdown effects on HSP27 in BC cells, we did not find consistent effects on apoptosis of BC cells or chemotherapeutic sensitivity of BC cells to cisplatin. Therefore, although HSP27 may be a predictor of adverse pathological characteristics in BC, its role as a prognostic biomarker and therapeutic target seems to be limited.

Pathophysiological and neurobehavioral characteristics of a propionic acid-mediated autism-like rat model.

Autism spectrum disorder (ASD) is induced by complex hereditary and environmental factors. However, the mechanisms of ASD development are poorly understood. The purpose of this study was to identify standard indicators of this condition by comparing clinical, pathophysiological, and neurobehavioral features in an autism-like animal model. A total of 22 male Sprague-Dawley rats were randomly divided into control and 500 mg/kg propionic acid (PPA)-treated groups. Rats were subjected to behavioral tests, gene expression analyses, and histological analyses to detect pathophysiological and neurobehavioral alterations. Exploratory activity and non-aggressive behavior were significantly reduced in PPA-treated rats, whereas enhanced aggressive behavior during adjacent interactions was observed on day 14 after PPA administration. To evaluate gene expression after PPA administration, we analyzed hippocampal tissue using reverse transcription PCR. Glial fibrillary acidic protein was augmented in the PPA-treated group on day 14 after appearance of ASD-like behaviors by PPA administration, whereas octamer-binding transcription factor 4 expression was significantly decreased in the PPA-treated group. Histological evaluation revealed significantly reduced diameter and layer thickness of granule cells in PPA-treated rats compared with control rats. We conclude that PPA administration induced abnormal neural cell organization, which may have led to autism-like neurobehaviors, including increased aggressive behavior, reduced exploratory activity, and isolative and passive behaviors.

NDRG2 contributes to cisplatin sensitivity through modulation of BAK-to-Mcl-1 ratio.

The downregulation of N-Myc downstream-regulated gene 2 (NDRG2) is known to be associated with the progression and poor prognosis of several cancers. Sensitivity to anti-cancer may be associated with a good prognosis in cancer patients, and NDRG2, which is induced by p53, sensitizes the cells to chemotherapy. However, the unique function of NDRG2 as an inducer of apoptosis under chemotreatment has not been sufficiently studied. In this study, we investigated the role of NDRG2 in chemo-sensitivity, focusing on cisplatin in U937 histiocytic lymphoma, which has the loss-of-functional mutation in p53. NDRG2 promoted the sensitivity to cisplatin through the modulation of the BAK-to-Mcl-1 ratio. The degradation of Mcl-1 and increase in BAK were mediated by JNK activation and the eIF2α/p-eIF2α pathway, respectively, which depended on PKR activation in NDRG2-overexpressed U937 (U937-NDRG2) cells. NOX5 was highly expressed in U937-NDRG2 cells and contributed to ROS production after cisplatin treatment. ROS scavenging or NOX5-knockdown successfully inhibited the sensitivity of U937-NDRG2 cells to cisplatin. Taken together, these findings indicate that NDRG2 contributed to the increased sensitivity to ciplatin through the modulation of Bak-to-Mcl-1 ratio regulated by NOX5-ROS-PKR pathway; therefore, we suggest that NDRG2 may be a molecular target for improving the efficacy of drug treatment in cancer patients.

Clinicopathological Significance of Micropapillary Pattern in Lung Adenocarcinoma.

The aim of this study was to elucidate the clinicopathological characteristics of the micropapillary (MP) subtype and its correlation with survival in lung adenocarcinoma. We investigated the clinicopathological characteristics, including the incidence, sex, smoking history, tumor size, lymph node metastasis, lymphovascular invasion, distant metastasis, genetic alteration, and prognosis in lung adenocarcinoma with the MP pattern through a meta-analysis. From 48 eligible studies, 19,502 lung adenocarcinomas were included. The incidence rate of the MP pattern was 0.101 [95% confidence interval (CI) 0.075-0.136]. There was no significant difference between stage I and III tumors. Lung adenocarcinoma with the MP pattern showed higher rates of lymphatic invasion (0.526, 95% CI 0.403-0.645). MP pattern was found in 0.150 (95% CI 0.008-0.790) of lung adenocarcinoma with distant metastasis. In lung adenocarcinoma with the MP pattern, the estimated rates of ALK, EGFR, and KRAS mutations were 0.102 (95% CI 0.027-0.322), 0.620 (95% CI 0.444-0.769), and 0.118 (95% CI 0.027-0.393), respectively. The MP pattern of lung adenocarcinoma was significantly correlated with worse overall and disease-free survival rates (hazard ratio 1.704, 95% CI 1.216-2.387, and 2.082, 95% CI 1.541-2.813, respectively). Taken together, identification of the MP pattern in lung adenocarcinoma is useful for prediction of clinicopathological characteristics and prognosis of patients.