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Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole (ABZ) kills nematode larvae in the brain. However, dead larvae can trigger a severe inflammatory response, resulting in brain damage. Accumulating evidence suggests that calycosin represents a potential anti-inflammatory therapeutic candidate. In this study, we investigated the combined effects of ABZ and calycosin in angiostrongyliasis caused by A. cantonensis in BALB/c mice. Inflammatory mediators (such as phospho-nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinase-9, tumour necrosis factor-α and interleukin-1β) are associated with the development of meningitis and immune inflammatory reactions. We found that A. cantonensis significantly induces inflammatory mediator production and increases the blood–brain barrier (BBB) permeability. However, co-administration of both ABZ and calycosin markedly suppressed meningitis and inflammatory mediator production and decreased the BBB permeability compared to treatment with a single drug. Furthermore, calycosin and ABZ plus calycosin treatment facilitated production of the antioxidant haem oxygenase-1 (HO-1). Moreover, co-therapy with ABZ and calycosin failed to mitigate angiostrongyliasis in the presence of tin-protoporphyrin IX, an HO-1-specific inhibitor. This finding suggests that the beneficial effects of ABZ plus calycosin treatment on the regulation of inflammation are mediated by the modulation of HO-1 activation. The present results provide new insights into the treatment of human angiostrongyliasis using co-therapy with ABZ and calycosin.

Calreticulin (CRT) is located in the endoplasmic reticulum (ER), it helps proteins fold correctly inside the ER, and acts as a modulator of Ca

Lung cancer is the major cause of cancer associated mortality. Mutations in EGFR have been implicated in lung cancer pathogenesis. Gefitinib (GF) is a RTKI (receptor tyrosine kinase inhibitor) first-choice drug for EGFR mutated advanced lung cancer. However, drug toxicity and cancer cell resistance lead to treatment failure. Consequently, new therapeutic strategies are urgently required. Therefore, this study was aimed at identifying tumor suppressive compounds that can synergistically improve Gefitinib chemosensitivity in the lung cancer treatment. Medicinal plants offer a vast platform for the development of novel anticancer agents. Daidzein (DZ) is an isoflavone compound extracted from soy plants and has been shown to possess many medicinal benefits. The anticancer potential of GF and DZ combination treatment was investigated using MTT, western blot, fluorescent microscopy imaging, flow cytometry and nude mice tumor xenograft techniques. Our results demonstrate that DZ synergistically induces c-Jun nuclear translocation through ROS/ASK1/JNK and downregulates EGFR-STAT/AKT/ERK pathways to activate apoptosis and a G0/G1 phase cell cycle blockade. In in-vivo, the combination treatment significantly suppressed A549 lung cancer cells tumor xenograft growth without noticeable toxicity. Daidzein supplements with current chemotherapeutic agents may well be an alternative strategy to improve the treatment efficacy of lung adenocarcinoma.

This study reports the effect of cardiac-specific insulin-like growth factor-II receptor α (IGF-IIRα) overexpression on the development of liver dysfunction in transgenic rats via STZ-induced diabetic hepatocyte damage. The cardio-hepatic syndrome comprises a number of heart and liver illnesses in which an acute or chronic disease in one organ can lead to acute or chronic disease in the other. However, the molecular mechanism involved in such a set of conditions is unclear. In this study, we developed a transgenic rat model with cardiac-specific overexpression of IGF-IIRα, which is a supplementary splicing variant of insulin-like growth factor-II receptor (IGF-IIR), expressed in pathological hearts, to investigate the relationship between late fetal gene expression in diabetic hearts and their influence on diabetic hepatopathy. STZ (55 mg/kg) was intraperitoneally delivered into IGF-IIR overexpressed transgenic (TG) and non-transgenic (NTG) animal models developed in Sprague-Dawley (SD) rats after an overnight fast. The relationship among IGF-IIRα overexpression and hepatocyte damages have been determined based on the complexity of damage in the liver. Our findings revealed that overexpression of the cardiac-specific IGF-IIRα enhances diabetes-induced morphological alterations and hepatic inflammation in the livers. The diabetic transgenic rats demonstrated the development of pathological conditions such as thick collagen fiber deposition, bridging fibrosis, and elevation of α-SMA and MMP1 related liver fibrosis mechanisms. Our data suggest that IGF-IIRα overexpression in the heart during a pathological state may worsen diabetic hepatopathy in rats.

Colorectal cancer is one of the most prevalent cancers in the world. Chemoresistance has always been a problem encountered in its treatment. It is known that SUMOylation may regulate protein stability and decomposition, and even affect the protein translocation and posttranslational modification in cells. Sentrin-specific protease 1 (SENP1) is involved in the maturation of SUMO protein, and on the other hand, plays a role in deSUMOylation, which dissociates the target protein from SUMO and prevents further degradation of the target protein. In this study, we established an Irinotecan (CPT-11) resistant human colon cancer LoVo strain (LoVoR-CPT-11 ) to investigate the role of SENP1 in the development of drug resistance in colorectal cancer. The abundant accumulation of SENP1 and HIF-1α proteins and the increase of SUMO pathway enzymes were observed in LoVoR-CPT-11 cells while the protein markers of proliferation, angiogenesis, and glycolysis were upregulated. Knockdown of SENP1 reduced the migration ability and trigged re-sensitivity of LoVoR-CPT-11 cells to CPT-11 treatment. The analysis of SENP1 and HIF-1α gene expressions from TCGA/GTEx datasets using the GEPIA web server showed a positive correlation between SENP1 and HIF-1α in colorectal cancer patients and the high expression of these two genes might predict a poor outcome clinically. In conclusion, SENP1 might play an important role in CPT-11 resistance in colorectal cancer. Targeting SENP1 to reduce the resistant property could be considered in prospective clinical studies.

Calmodulin (CaM), a Ca2+ binding protein, plays a critical role in cancer initiation and progression through binding and activating numerous target proteins, including Ca2+ /calmodulin-dependent protein kinase (CaMK) family proteins. However, the mechanisms underlying the effects of CaM/CaMKs on the survival capability of liver cancer cells is unclear, and this study investigates this mechanism in apicidin-persistent HA22T cells. CaM level was upregulated, especially in the cytosol, in apicidin-persistent HA22T cells than in parental HA22T cells and was positively associated with cell proliferation and migration capacity of apicidin-persistent HA22T cells. Further, the expression of CaM-activated CaMKs-dependent signaling cascades, including CaMKK2, CaMKIV, CaMKII-γ, and p-CaMKII was observed in apicidin-persistent HA22T cells, which were transiently activated by mitogen-activated protein kinase oncogenic signaling, such as CREB, ERK1/2, and c-fos. Furthermore, a specific CaM inhibitor trifluoperazine reduced the levels of p-CREB, p-ERK1/2, and c-fos in apicidin-persistent HA22T cells than in parental HA22T cells. Additionally, inhibition of CaM also suppressed CaM-induced Bcl-XL (an antiapoptotic protein) expression in apicidin-persistent HA22T cells. Our finding emphasizes an essential role of CaM/CaMKs in augmentation of the survival capability of apicidin-persistent liver cancer cells and suggests that CaM inhibition significantly attenuates CaM-induced tumor growth and abrogates antiapoptotic function and also offers a promising therapeutic target for cancer treatment.

Background/aim This study aimed to evaluate the association of sarcopenia and Clinical Outcomes with esophageal cancer under neoadjuvant chemoradiotherapy (CRT). Patients and methods A retrospective study assessing patients with esophageal cancer who underwent CRT between 2001 and 2014 was conducted in the medical center. Hospital patients' records on sarcopenia and treatment outcomes were statistically analyzed. Results The sarcopenia group had significantly lower body mass index than the non-sarcopenia group. CRT-related severe adverse events with mucositis, fever, and neutropenic fever were greater in the sarcopenia group. Overall survival and disease-free survival were significantly better in the non-sarcopenia group. Sarcopenic patients who received nutritional support with enteral access had less severe mucositis. There was no difference in mortality of sarcopenia patients with nutritional support via enteral access or without. Moreover, sarcopenia and advanced tumor stage were independent factors for mortality outcome. Conclusion Sarcopenia before CRT may be associated with increased toxicities and worse overall survival/ disease-free survival in esophageal cancer patients.

Background/purpose: Granulocyte colony-stimulating factor (G-CSF) is widely used for prophylaxis and treatment of neutropenia in cancer patients and also for peripheral blood stem cells (PBSC) mobilization. The aim of this study is to evaluate the possible changes of platelet surface antigens after G-CSF injection in PBSC donors compared with healthy control. Methods: Between January 1st and December 31st, 2014, 48 healthy voluntary PBSC donors were eligible for this study. Donors received G-CSF (Filgrastim) subcutaneously for five days, and then their whole blood was collected for complete blood count. Analysis of platelet antigens was performed by flow cytometry. Sixteen healthy controls were also included for comparison. Results: Lower platelet counts were found in PBSC donors after G-CSF use and in comparison with health controls. The platelet size evaluated by forward scattering (FSC) showed smaller platelets in PBSC donors after G-CSF use compared with healthy controls (39.3 vs 46.7 mean fluorescence intensity, P = 0.015). CD31 were higher in PBSC donor (203.2 vs. 120.7, P

Purpose: miR-100-5p has been found upregulated in Oxaliplatin-resistant LoVo colorectal cell lines, but its function still need further study. Here, we investigated its function in cell regulation chemoresistance in chemoresistant colorectal cancer cell lines.Methods: Microarray, quantitative polymerase chain reaction (qRT-PCR) and westernblot were used to analysis the level of miR-100-5p. The downstream candidate gen target of miR-100-5p, CTDSPL in Oxaliplatin resistant (OXR)-LoVo colorectal cell lines were screened using the different types of bioinformatics based miRNA target prediction data are TargetScan (http://www.targetscan.org/), miRanda (http://www.microrna.org/ and mirTar (http://mirtar.mbc.nctu.edu.tw/human/). CTDSPL, a phosphatase-like tumor suppressor level was detected by westernblot as well with cell cycle progression chemoresistance associated colorectal cancer cell CTDSPL/p-RB/E2F1. Immunofluorescence assay and westernblot showed the cell properties were altered between parental and Oxaliplatin resistant LoVo cell lines. Bioinformatic prediction, (http://alggen.1si.upc.es/cgi-bin/promo_v3) was used to extend the investigation of miR-100-5p upstream regulation through checking dissimilarity index with margin less or equal than 15%, FOXP3, trancription factor forkhead box as upstream target. Interaction between miR-100-5p and CTDSPL regulation was confirmed using mimic miR-100-5p overexpression and knockdown upstream target sh-RNA approach.Results: hsa-miR-100-5p level was found significantly upregulated in LoVo-OXR than parental LoVo cell line, resulted in downregulation CTDSPL as a major target of miR-100-5p. The downregulated of CTDSPL/p-RB/E2F1 promotes cell proliferation and cell cycle progression in LoVo OXR compared with LoVo parental cell lines. Moreover, among various upstream targets FOXP3 is an upstream regulator of miR-100-5p. In addition, mimic miR-100-5p overexpression downregulated CTDSPL/p-RB/E2F1 signaling pathway was reverted upon miR-100-5p inhibition in CRC cell lines.Conclusion: Collectively, miR-100-5p is chemoresistance inducer through modulation of CTDSPL/p-RB/E2F1 signaling pathway in CRC cell. This phenomenon might offer a therapeutic platform for overcoming chemoresistance in cancer treatment.

Oxidative stress-induced brain cell damage is a crucial factor in the pathogenesis of reactive oxygen species (ROS)-associated neurological diseases. Further, studies show that astrocytes are an important immunocompetent cell in the brain and play a potentially significant role in various neurological diseases. Therefore, elimination of ROS overproduction might be a potential strategy for preventing and treating neurological diseases. Accumulating evidence indicates that calycosin, a main active ingredient in the Chinese herbal medicine Huangqi (Radix Astragali Mongolici), is a potential therapeutic candidate with anti-inflammation and/or anticancer effects. Here, we investigated the protective effect of calycosin in brain astrocytes by mimicking in vitro oxidative stress using H

Urothelial bladder cancer is rapidly spreading across Western countries, and therapy has shown little-to-moderate effects on bladder cancer. Thus, focusing on curbing cancer incidence has become crucial. In this study, we examined the effects of tannic acid, a polyphenol with anti-fungal and anti-cancer effects, on UMUC3 bladder cancer cells. UMUC3 cells were exposed to tannic acid for 24 hours, following which we observed significant inhibition of cell proliferation. Additionally, flow cytometry and TUNEL assay revealed that tannic acid induces apoptosis in UMUC3 cells in a dose-dependent manner. Furthermore, tannic acid treatment upregulated the expression of cleaved caspase-3 which further confirmed induction of apoptosis in UMUC3 cells by treatment with tannic acid. TA treatment decreased stem cell markers expression such as SOX2, OCT4, and NANOG. Together, these results showed that tannic acid can promote apoptosis; therefore, it may have potential as treatment for bladder cancer.

Urothelial bladder cancer is rapidly spreading across Western countries, and therapy has shown little-to-moderate effects on bladder cancer. Thus, focusing on curbing cancer incidence has become crucial. The aim of the present study was to investigate the anticancer effects of Tannic acid (TA) in human bladder cancer. UMUC3 bladder cancer cells were treated with different concentrations of TA (0-100 µM) and tested for cell viability, colony formation, and apoptosis. The involvement of the phosphoinositide-3 kinase (PI3K)/Akt pathway in the action of TA was examined. TA treatment significantly inhibited the viability and increased percentage of apoptotic cells, thereby decreasing antiapoptotic proteins (BCL2, MCL-1, and BCL-XL) expression, resulting in the Caspase-3 activation. TA treatment decreased stem cell markers expression such as SOX2, OCT4, and NANOG. Additionally, TA treatment significantly reduced the phosphorylation levels of Akt in bladder cancer cells. Our study demonstrates the growth inhibitory effects of TA in bladder cancer cells, and highlights its potential as an anticancer agent for bladder cancer.

Hepatic veno-occlusive disease (VOD) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). We conducted this study to investigate the incidence and risk factors of hepatic VOD for patients receiving HSCT in Taiwan. We retrospectively analyzed the data from a nationwide registry for patients receiving HSCT, which was collected by the Taiwan Society of Blood and Marrow Transplantation. The data collection period was from 2009 to 2014. A total 2345 patients were reviewed and 39 patients among them were diagnosed as having hepatic VOD. The cumulative incidence of hepatic VOD in the whole cohort of 2345 patients was 1.66%. In multivariate analysis, disease diagnosis of myelodysplastic syndrome, chronic HCV infection, condition regimens of bulsulfan intravenously administered, and antithymocyte immunoglobulin were independent factors to predict higher risk of hepatic VOD. The overall mortality rate for patients with hepatic VOD was 79%. Patients with hepatic VOD had significant worse survival outcomes when compared with those without hepatic VOD (P = 0.00063). In conclusion, although the incidence is low, hepatic VOD remains a serious complication after HSCT in Taiwan. The findings of this study could be the basis for developing prophylactic or early treatment strategies for hepatic VOD.

Hepatocellular carcinoma is a common type of liver cancer. Resistance to chemotherapeutic agents is a major problem in cancer therapy. MicroRNAs have been reported in cancer development and tumor growth; however, the relationship between chemoresistance and hepatocellular carcinoma needs to be fully investigated. Here, we treated hepatocellular carcinoma cell line (HA22T) with a histone deacetylase inhibitor to establish hepatocellular carcinoma-resistant cells (HDACi-R) and investigated the molecular mechanisms of chemoresistance in HCC cells. Although histone deacetylase inhibitor could not enhance cell death in HDACi-R but upregulation of miR-107 decreased cell viability both in parental cells and resistance cells, decreased the expression of cofilin-1, enhanced ROS-induced cell apoptosis, and dose-dependently sensitized HDACi-R to HDACi. Further, miR-107 upregulation resulted in tumor cell disorganization in both HA22T and HDACi-R in a mice xenograft model. Our findings demonstrated that miR-107 downregulation leads to hepatocellular carcinoma cell resistance in HDACi via a cofilin-1-dependent molecular mechanism and ROS accumulation.

Background Hematopoiesis occurs in the bone marrow, producing a complete spectrum of blood cells to maintain homeostasis. In addition to light microscopy, chromosome analysis, and polymerase chain reaction, flow cytometry is a feasible and fast method for quantitatively analyzing hematological diseases. However, because sufficient specific cell markers are scarce, dyserythropoietic diseases are challenging to identify through flow cytometry. Methods Bone marrow samples from C57BL/B6 mice and one healthy donor were analyzed using traditional two-marker (CD71 and glycophorin A) flow cytometry analysis. After cell sorting, the gene expressions of membrane proteins in early and late erythropoiesis precursors and in nonerythroid cells were characterized using microarray analysis. Results Among characterized gene candidates, aquaporin 0 (AQP0) expressed as a surface protein in early- and late-stage erythropoiesis precursors and was not expressed on nonerythroid cells. With the help of AQP0 staining, we could define up to five stages of erythropoiesis in both mouse and human bone marrow using flow cytometry. In addition, because patients with dyserythropoiesis generally exhibited a reduced population of APQ0high cells relative to healthy participants, the analysis results also suggested that the levels of APQ0high cells in early erythropoiesis serve as a novel biomarker that distinguishes normal from dysregulated erythropoiesis. Conclusions AQP0 was successfully demonstrated to be a marker of erythroid differentiation. The expression levels of AQP0 are downregulated in patients with dyserythropoiesis, indicating a critical role of AQP0 in erythropoiesis. Accordingly, the level of AQP0high in early erythroid precursor cells may serve as a reference parameter for diagnosing diseases associated with dyserythropoiesis.

Background Chemoresistance remains the main obstacle in hepatocellular carcinoma (HCC) therapy. Despite significant advances in HCC therapy, HCC still has a poor prognosis. Thus, there is an urgent need to identify a treatment target to reverse HCC chemotherapy resistance. Platycodon grandiflorus (PG) is a perennial herb that has been used as food and traditional Chinese medicine for thousands of years in Northeast Asia. Platycodin D (PD), a main active triterpenoid saponin found in the root of PG, has been reported to possess anticancer properties in several cancer cell lines, including HCC; however, the reversal effect of this molecule on HCC chemoresistance remains largely unknown. Purpose This study aimed to investigate the role and the mechanism of PD-mediated reversal of the histone deacetylase inhibitor (HDACi) resistance in HCC cells. Methods Human HCC cells (HA22T) and HDACi-resistant (HDACi-R) cells were used. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Combination index was used to calculate the synergism potential. Expression of ERK1/2 (total/phospho), cofilin-1 (total/phospho) and apoptosis-related protein was determined using western blotting. Mitochondrial membrane potential was assessed using the JC-1 (5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide) probe. Apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Mitochondrial reactive oxygen species generation was measured using the MitoSOX Red fluorescent probe. Results We found that PD treatment inhibited cell viability both in HA22T HCC and HDACi-R cells. Inhibition of ERK1/2 by PD98059 could reverse drug resistance in HDACi-R cells treated with PD98059 and PD. Nevertheless, pre-treatment with U46619, an ERK1/2 activator, rescued PD-induced apoptosis by decreasing levels of apoptosis-related proteins in HCC cells. The combined treatment of PD with apicidin a powerful HDACi, dramatically enhanced the apoptotic effect in HDACi-R cells. Conclusion For the first time, we showed that PD reversed HDACi resistance in HCC by repressing ERK1/2-mediated cofilin-1 phosphorylation. Thus, PD can potentially be a treatment target to reverse HCC chemotherapy resistance in future therapeutic trials.

Although various advancements in radical surgery and neoadjuvant chemotherapy have been developed in treating osteosarcoma (OS), their clinical prognosis remains poor. A synthetic chemical compound, 3-hydroxylflavone, that is reported to regulate ROS production is known to inhibit human bone osteosarcoma cells. However, its role and mechanism in human OS cells remains unclear. In this study, we have determined the potential of 3-Hydroxy-2-phenylchromone (3-HF) against OS using human osteosarcoma (HOS) cells. Our previous studies showed that Zipper sterile-alpha-motif kinase (ZAK), a kinase member of the MAP3K family, was involved in various cellular events such as cell proliferation and cell apoptosis, and encoded two transcriptional variants, ZAK&alpha, and &beta, In this study, we show that 3-HF induces the expression of ZAK and thereby enhances cellular apoptosis. Using gain of function and loss of function studies, we have demonstrated that ZAK activation by 3-HF in OS cells is confined to a ZAK&beta, form that presumably plays a leading role in triggering ZAK&alpha, expression, resulting in an aggravated cancer apoptosis. Our results also validate ZAK&beta, as the predominant form of ZAK to drive the anticancer mechanism in HOS cells.

Background To investigate the survival prognostic value of the radiomic features of 18F-FDG PET in patients who had EGFR (epidermal growth factor receptor) mutated lung adenocarcinoma and received targeted TKI (tyrosine kinase inhibitor) treatment. Methods Fifty-one patients with stage III-IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI were retrospectively analyzed. All patients underwent pretreatment 18F-FDG PET/CT, and we calculated the PET-derived radiomic features. Cox proportional hazard model was used to examine the association between the radiomic features and the survival outcomes, including progression-free survival (PFS) and overall survival (OS). A score model was established according to the independent prognostic predictors and we compared this model to the TNM staging system using Harrell's concordance index (c-index). Results Forty-eight patients (94.1%) experienced disease progression and 41 patients (80.4%) died. Primary tumor SUV entropy > 5.36, and presence of pleural effusion were independently associated with worse OS (both p < 0.001) and PFS (p = 0.001, and 0.003, respectively). We used these two survival predictors to devise a scoring system (score 0–2). Patients with a score of 1 or 2 had a worse survival than those with a score of 0 (HR for OS: 3.6, p = 0.006 for score 1, and HR: 21.8, p < 0.001 for score 2; HR for PFS: 2.2, p = 0.027 for score 1 and HR: 8.8, p < 0.001 for score 2). Our scoring system surpassed the TNM staging system (c-index = 0.691 versus 0.574, p = 0.013 for OS, and c-index = 0.649 versus 0.517, p = 0.004 for PFS). Conclusions In this preliminary study, combining PET radiomics with clinical risk factors may improve survival stratification in stage III-IV lung adenocarcinoma with actionable EFGR mutation. Our proposed scoring system may assist with optimization of individualized treatment strategies in these patients.

Background Enteral feeding tubes used to manage the nutritional status of esophageal cancer were evaluated regarding their effectiveness in patients receiving neoadjuvant therapy. Patients and methods A retrospective study evaluating patients with esophageal squamous cell carcinoma undergoing neoadjuvant therapy between 2001 and 2014 was conducted at a medical center. Hospital patients' records for enteral access (EA) insertion and treatment outcomes were statistically analyzed. Results Patients with EA at initial diagnosis had lower body mass index than the group without EA (p=0.012). Chemotherapy-related adverse events with grade 3-4 mucositis were significantly less frequent in the EA group (p=0.008), and grade 3-4 anemia was significantly more frequent (p=0.012). The 4-year mortality rate was 63.0% in the EA group and 67.7% in the group without EA (pnon-inferiority=0.035), which met the non-inferiority criterion with a non-inferiority margin of 10%. Conclusion Patients with esophageal squamous cell carcinoma with malnutrition status undergoing neoadjuvant therapy with EA showed an improved outcome at maintaining nutritional status, reduced severity of mucositis and improved survival rate.

Aim This study was conducted to evaluate the effect of clinical factors on the treatment outcomes of lung cancer patients with active epidermal growth factor receptor (EGFR) mutations treated by first-line tyrosine kinase inhibitors (TKIs). Methods Patients of stage IIIb or IV lung adenocarcinoma harboring mutated EGFR were enrolled between March 2010 and June 2014 and followed up until December 2015. The effects of various clinical features, such as age, sex, smoking history, EGFR mutation types, TKIs used, presence of pleural effusion, metastatic sites on progression-free survival (PFS) and overall survival (OS), were analyzed retrospectively. Results A total of 104 patients were included in this study. Patients with pleural effusion at initial diagnosis had significantly shorter PFS and OS than those without pleural effusion (median PFS: 8.2 months vs 15.3 months, P = 0.0004; median OS: 16.3 months vs 28.2 months, P = 0.0003). Univariate analysis revealed that being male or a smoker was associated with short PFS, whereas smoking history, bony metastasis and malignant pleural effusion were associated with poor OS. Stepwise multivariate Cox regression analysis showed that the presence of pleural effusion and different TKI use were independent prognostic factors for PFS [hazard ratio [HR] = 2.50 (95% confidence interval [CI], 1.53-4.10), P = 0.0003 and HR = 0.55 (95% CI, 0.31-0.97), P = 0.0396, respectively], whereas the presence of pleural effusion and liver metastasis were associated with poor OS [HR = 2.79 (95% CI: 1.46-5.30), P = 0.0018 and HR = 2.12 (95% CI, 1.02-4.40), P = 0.0440, respectively]. Conclusion The presence of pleural effusion predicts poor PFS and OS in lung adenocarcinoma patients receiving TKIs as the first-line treatment. Additional studies are warranted to elucidate the underlying mechanisms and determine novel strategies for improving the outcome of these patients.

Background This study evaluated the effect of clinical factors on the treatment outcomes of patients with lung adenocarcinoma with active epidermal growth factor receptor (EGFR) mutations who received tyrosine kinase inhibitors (TKIs) as first-line treatment. Methods Patients with stage IIIb or IV lung adenocarcinoma with mutated EGFR were enrolled retrospectively between March 2010 and December 2017. The effects of various clinical features and hematologic markers on progression-free survival (PFS) and overall survival (OS) were analyzed. Results A total of 190 patients were enrolled in this study. In univariate analysis, the male sex, smoking history, EGFR mutation with L858R, and presentation with malignant pleural effusion at initial diagnosis were significantly associated with shorter PFS or OS. Among hematologic markers, lower lymphocyte percentage and higher platelet count were associated with significantly poor PFS and OS. Stepwise multivariate Cox regression analysis showed that smoking history, EGFR mutation with L858R, and lower lymphocyte percentage were independent poor prognostic factors for PFS and OS. Presentation with malignant pleural effusion and higher platelet count was an independent poor prognostic factor for OS only. Conclusion Patients with lung adenocarcinoma receiving TKIs as the first-line treatment and having hematologic markers with lower lymphocyte percentage, and higher platelet count had poorer prognoses compared with other patients. Additional studies are warranted to elucidate the underlying mechanisms.

Immune thrombocytopenia (ITP) is known as an immune-mediated disease and often evolves to chronic type in adult. Corticosteroids only work in around 60% of patients. This study evaluated the roles of subgroup lymphocytes from peripheral blood in ITP adults with different treatment response.Between October 2009 and March 2017, 37 adults were newly diagnosed as ITP requiring treatment. The patients were separated into two groups: 23 patients with platelet count50,000/μL with corticosteroid dependence or second-line treatment (Poor-responder Group), and 14 patients with platelet counts50,000/μL with standard steroid treatment, which stopped within three months (Good-responder Group). Subgroup lymphocyte percentages of peripheral blood were determined through flow cytometry before treatment. Data analysis with Mann-Whitney test and receiver operating characteristic curves were performed using GraphPad Prism (Version 7). A p-value of0.05 was considered significant.Lymphocyte percentage was significantly lower in Poor-responder Group than in Good-responder Group (p = 0.008). In subgroup lymphocytes, higher percentages of CD19+ B lymphocytes were found in Good-responder Group (p = 0.03). In Poor-responder Group, a higher CD2+ and CD56+ lymphocytes were observed (p = 0.02 and 0.03). By the cut-off value of percentage of CD56+ lymphocytes with 24.5% or CD2+ lymphocytes with 85.7%, the specificity showed 92.86%.This study found that newly diagnosed ITP patients with increased percentages of CD56+ or CD2+ lymphocytes in peripheral blood associated with a poorer response to steroid treatment.

Background/aim This study aimed to evaluate the clinical outcome of esophageal cancer (EC) patients with enteral access (EA) undergoing multimodality therapy. Patients and methods This retrospective study analyzed data between 1997 and 2012 in Taiwan using the National Health Insurance Research Database. Patients with newly-diagnosed EC undergoing multimodality therapy were identified and classified as either EA group or no-EA group. Results The mortality incidence of EC patients with EA was significantly higher than in no-EA patients. The Cox model revealed the EA group had a higher risk of mortality than the no-EA group. Patients with chronic obstructive pulmonary disease (COPD) were at significantly higher risk of mortality compared to patients without COPD. Conclusion EA in EC patients undergoing multimodality therapy was associated with an increased risk of mortality.

Nonmetastatic esophageal cancer can demonstrate a high local recurrence rate even under the standard treatment. We evaluated platelet counts before and after concurrent chemoradiotherapy (CCRT), neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio for predicting esophageal cancer prognosis under CCRT. Newly diagnosed patients with esophageal cancer (stages IA–IIIC) who underwent CCRT during January 2013–December 2017 were enrolled. The data were collected retrospectively. Overall survival (OS), time to progressive disease (TPD), and time to metastasis (TM) were recorded for indicating prognosis. Kaplan–Meier curves were plotted and univariate and multivariate analyses were performed. In total, 105 patients were enrolled. The stages of esophageal cancer and surgery were associated with prognosis (i.e., OS, TPD, and TM). Based on TPD and TM, women had better prognosis than men. In the univariate analysis, high pre- and post-CCRT platelet counts (>300,000/μL), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) as well as low lymphocyte percentage were significantly associated with poor prognosis. However, in the multivariate analysis, only post-CCRT high platelet count (>300,000/μL) remained significantly associated with poor prognosis (P = .041, .045, and .023 for OS, TPD, and TM, respectively). Poor prognosis was observed in patients with high platelet counts, PLR, NLR, and low lymphocyte percentage. Surgery was an independent factor predicting better prognosis. Our findings may have clinical significance with regard to therapeutic decision-making.