Prediction of Renal Function 1 Year After Transplantation Using Machine Learning Methods Based on Ultrasound Radiomics Combined With Clinical and Imaging Features.

Kidney transplantation is the most effective treatment for advanced chronic kidney disease (CKD). If the prognosis of transplantation can be predicted early after transplantation, it might improve the long-term survival of patients with transplanted kidneys. Currently, studies on the assessment and prediction of renal function by radiomics are limited. Therefore, the present study aimed to explore the value of ultrasound (US)-based imaging and radiomics features, combined with clinical features to develop and validate the models for predicting transplanted kidney function after 1 year (TKF-1Y) using different machine learning algorithms. A total of 189 patients were included and classified into the abnormal TKF-1Y group, and the normal TKF-1Y group based on their estimated glomerular filtration rate (eGFR) levels 1 year after transplantation. The radiomics features were derived from the US images of each case. Three machine learning methods were employed to establish different models for predicting TKF-1Y using selected clinical and US imaging as well as radiomics features from the training set. Two US imaging, four clinical, and six radiomics features were selected. Then, the clinical (including clinical and US image features), radiomics, and combined models were developed. The area under the curves (AUCs) of the models was 0.62 to 0.82 within the test set. Combined models showed statistically higher AUCs than the radiomics models (all p-values <.05). The prediction performance of different models was not significantly affected by the different machine learning algorithms (all p-values >.05). In conclusion, US imaging features combined with clinical features could predict TKF-1Y and yield an incremental value over radiomics features. A model integrating all available features may further improve the predictive efficacy. Different machine learning algorithms may not have a significant impact on the predictive performance of the model.

Expression and clinical significance of ECHS1 in gastric cancer.

Background: Gastric cancer (GC), as one of the most common malignant tumors and the 3rd primary cause of death by cancer globally, poses a great threat to public health. Despite many advancements have been achieved in current treatment avenues for GC, the 5-year survival rates of GC patients remain substandard. Short-chain enoyl-CoA hydratase (ECHS1) exerts pro- or anti-cancer activities in different cancer backgrounds. However, its clinical significance and biological role in GC remain vague and need further investigation. Methods: The expression of ECHS1 in GC tumors and adjacent normal tissues was examined using the GEPIA platform and clinical samples. The effects of ECHS1 on GC cell proliferation and migration were evaluated using colony formation and transwell migration assays. Results: ECHS1 was upregulated in GC tumor tissues in both mRNA and protein levels and increased ECHS1 was markedly linked with tumor location, depth of tumor invasion, lymph node metastasis (LNM), and tumor-node-metastasis (TNM) stage of GC patients. High ECHS1 expression was also linked with a shorter overal survival (OS), first progression (FP) and post progression survival (PPS). Further subgroup analysis showed that OS was significantly shorter in GC patients with high ECHS1 expression compared to those with low ECHS1 expression belonging to tumors with T3 stage, N2 stage or in instestinal Lauren subgroup. In addition, cytological experiments showed that there was higher ECHS1 expression in GC cell lines compared to the normal gastric epithelium (GES-1) cells, and ECHS1 can promote GC cell proliferation and migration in vitro. Conclusion: ECHS1 plays an oncogenic role in GC and might be a promising therapeutic target for GC.

The Effect of Post-Activation Potentiation Enhancement Alone or in Combination with Caffeine on Anaerobic Performance in Boxers: A Double-Blind, Randomized Crossover Study.

Post-activation performance enhancement (PAPE) is a physiological phenomenon that refers to an acute excitation of the neuromuscular system following intense exercise that ends in enhanced physical performance in a subsequent bout of exercise. The scientific literature has primarily examined the effectiveness of PAPE alone or combined with caffeine (CAF) intake in all-out tests lasting ≤10 s, as the effect of PAPE is transitory. The aim of the present study was to determine the effect of a protocol to induce PAPE alone or in combination with caffeine intake on the 30 s Wingate Anaerobic Test in highly trained boxers. Twenty-five male and highly trained boxers (mean age: 20 ± 1 years) participated in a double-blind, randomized crossover study consisting of three different experimental conditions: (i) control (CON), with no substance intake and no PAPE protocol before the Wingate Anaerobic Test; (ii) PAPE + PLA, involving the intake of a placebo 60 min before and a PAPE protocol comprising a 10 s cycling sprint overloaded with 8.5% of the participants' body weight 10 min before the Wingate Anaerobic Test; and (iii) PAPE + CAF, involving the intake of 3 mg/kg of caffeine 60 min before and the same PAPE protocol used in the (ii) protocol before the Wingate Anaerobic Test. In all conditions, the participants performed the 30 s version of the Wingate Anaerobic Test with a load equivalent to 7.5% of their body weight, while the cycle ergometer setting was replicated. Immediately following the Wingate test, heart rate (HR), the rating of perceived exertion (RPE), and blood lactate concentration (Bla) were measured. In comparison to CON, PAPE + PLA enhanced mean power (p = 0.024; Effect size [ES] = 0.37) and total work (p = 0.022; ES = 0.38) during the Wingate test, accompanied by an increase in post-test blood lactate concentration (p < 0.01; ES = 0.83). In comparison to CON, PAPE + CAF enhanced mean power (p = 0.001; ES = 0.57), peak power (p = 0.013; ES = 0.57), total work (p = 0.001; ES = 0.53), post-test blood lactate concentration (p < 0.001; ES = 1.43) and participants' subjective perception of power (p = 0.041). There were no differences in any variable between PAPE + PLA and PAPE + CAF. In summary, a PAPE protocol that involves a 10 s all-out sprint 10 min before the Wingate Anaerobic Test was effective in enhancing Wingate mean power in highly trained boxers. The addition of 3 mg/kg of caffeine to the PAPE protocol produced an effect on mean power of a higher magnitude than PAPE alone, and it enhanced peak power along with participants' subjective perception of power. From a practical point of view, PAPE before exercise seems to be an effective approach for increasing Wingate performance in highly trained boxers, while the addition of caffeine can increase some benefits, especially peak power.

Tumor necrosis factor-α attenuates starvation-induced apoptosis through upregulation of ferritin heavy chain in hepatocellular carcinoma cells.

BACKGROUND: Tumor microenviroment is characteristic of inflammation, ischemia and starvation of nutrient. TNF-α, which is an extraordinarily pleiotropic cytokine, could be an endogenous tumor promoter in some tumor types. The basic objective of this study was to investigate the effects of TNF-α on the cell viability and apoptosis of hepatocellular carcinoma cells under serum starvation, and to identify the molecular mechanisms involved. METHODS: For this purpose, five different concentrations of TNF-α and two different serum settings (serum-cultured and serum-deprived) were used to investigate the effects of TNF-α on the cell viability and apoptosis of Hep3B and SMMC-7721 cells. RESULTS: TNF-α (10 ng/ml) attenuated serum starvation-induced apoptosis of hepatocellular carcinoma cells, and autophagy conferred this process. BAY11-7082, a specific inhibitor of NF-κB, reversed the suppression of serum starvation-induced apoptosis by TNF-α. Moreover, TNF-α-induced NF-κB transactivation was suppressed by autophagy inhibitor 3-MA. In addition, TNF-α up-regulated Ferritin heavy chain (FHC) transiently by NF-κB activation and FHC levels were correlated with the TNF-α-induced protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells. Furthermore, FHC-mediated inhibition of apoptosis depended on suppressing ROS accumulation. CONCLUSIONS: Our findings suggested that autophagy conferred the TNF-α protection against serum starvation-mediated apoptosis of hepatocellular carcinoma cells, the mechanism involved with the activation of the TNF-α/ NF-κB /FHC signaling pathway.

Machine Learning-Based Ultrasound Radiomics for Evaluating the Function of Transplanted Kidneys.

The aim of the study described here was to investigate the value of different machine learning models based on the clinical and radiomic features of 2-D ultrasound images to evaluate post-transplant renal function (pTRF). We included 233 patients who underwent ultrasound examination after renal transplantation and divided them into the normal pTRF group (group 1) and the abnormal pTRF group (group 2) based on their estimated glomerular filtration rates. The patients with abnormal pTRF were further subdivided into the non-severe renal function impairment group (group 2A) and the severe impairment group (group 2B). The radiomic features were extracted from the 2-D ultrasound images of each case. The clinical and ultrasound image features as well as radiomic features from the training set were selected, and then five machine learning algorithms were used to construct models for evaluating pTRF. Receiver operating characteristic curves were used to evaluate the discriminatory ability of each model. A total of 19 radiomic features and one clinical feature (age) were retained for discriminating group 1 from group 2. The area under the receiver operating characteristic curve (AUC) values of the models ranged from 0.788 to 0.839 in the test set, and no significant differences were found between the models (all p values >0.05). A total of 17 radiomic features and 1 ultrasound image feature (thickness) were retained for discriminating group 2A from group 2B. The AUC values of the models ranged from 0.689 to 0.772, and no significant differences were found between the models (all p values >0.05). Machine learning models based on clinical and ultrasound image features, as well as radiomics features, from 2-D ultrasound images can be used to evaluate pTRF.

Matrix Regeneration Ability In Situ Induced by a Silk Fibroin Small-Caliber Artificial Blood Vessel In Vivo.

The success of a small-caliber artificial vascular graft in the host in order to obtain functional tissue regeneration and remodeling remains a great challenge in clinical application. In our previous work, a silk-based, small-caliber tubular scaffold (SFTS) showed excellent mechanical properties, long-term patency and rapid endothelialization capabilities. On this basis, the aim of the present study was to evaluate the vascular reconstruction process after implantation to replace the common carotid artery in rabbits. The new tissue on both sides of the SFTSs at 1 month was clearly observed. Inside the SFTSs, the extracellular matrix (ECM) was deposited on the pore wall at 1 month and continued to increase during the follow-up period. The self-assembled collagen fibers and elastic fibers were clearly visible in a circumferential arrangement at 6 months and were similar to autologous blood vessels. The positive expression rate of Lysyl oxidase-1 (LOXL-1) was positively correlated with the formation and maturity of collagen fibers and elastic fibers. In summary, the findings of the tissue regeneration processes indicated that the bionic SFTSs induced in situ angiogenesis in defects.

Enhanced Silk Fibroin/Sericin Composite Film: Preparation, Mechanical Properties and Mineralization Activity.

The periosteum plays an important role in bone formation and reconstruction. One of the reasons for the high failure rate of bone transplantation is the absence of the periosteum. Silk fibroin (SF) and silk sericin (SS) have excellent biocompatibility and physicochemical properties, which have amazing application prospects in bone tissue engineering, but lacked mechanical properties. We developed a series of SF/SS composite films with improved mechanical properties using boiling water degumming, which caused little damage to SF molecular chains to retain larger molecules. The Fourier transform infrared spectroscopy and X-ray diffraction results showed that there were more ß-sheets in SF/SS films than in Na2CO3 degummed SF film, resulting in significantly improved breaking strength and toughness of the composite films, which were increased by approximately 1.3 and 1.7 times, respectively. The mineralization results showed that the hydroxyapatite (HAp) deposition rate on SF/SS composite films was faster than that on SF film. The SF/SS composite films effectively regulated the nucleation, growth and aggregation of HAp-like minerals, and the presence of SS accelerated the early mineralization of SF-based materials. These composite films may be promising biomaterials in the repair and regeneration of periosteum.

Effects of core resistance training on pugilism in boxers / Efeitos do treinamento de força do centro abdominal sobre o pugilismo em boxeadores / Efectos del entrenamiento de fuerza del centro abdominal sobre el pugilismo en boxeadores

ABSTRACT Introduction: Resistance training aims to improve the physical fitness of an athlete by improving their balance, movement, and agility skills. Boxers should have complementary attention to the strength of the core, a key area for boxing skills. Objective: Examine the effects of core strength training on pugilism in boxers. Methods: Ten volunteer professional boxers were selected. All undergo three months of core strength training under the described protocol. The athletes' sport quality index was studied using mathematical statistics. Results: After 3 months of core strength training, the physical test result was significantly higher (P<0.01). Although in 400-meter runs, sandbag training and interval running scores were higher than before training, the difference was insignificant (P>0.05). Conclusion: The core strength exercises improve the body mass of a boxing athlete and the level of their boxing. Supplementing athletes with core resistance training during regular exercise is indicated. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: O treinamento de força visa a melhorar a aptidão física de um atleta melhorando suas habilidades de equilíbrio, movimento e agilidade. Os boxeadores devem ter uma atenção complementar na força do centro abdominal, área fundamental para as habilidades pugilistas. Objetivo: Examinar os efeitos do treinamento de força do centro abdominal sobre o pugilismo em boxeadores. Métodos: Foram selecionados dez boxeadores profissionais voluntários. Todos passam por três meses de treinamento de força do centro abdominal sob protocolo descrito. O índice de qualidade esportiva dos atletas foi estudado com a utilização de estatísticas matemáticas. Resultados: Após 3 meses de treinamento de força do centro abdominal, o resultado de teste físico foi significativamente superior (P<0,01). Embora nos 400 metros de corrida, treinamento com saco de areia e pontuação de corrida em intervalos fossem mais altos do que aqueles antes do treinamento, a diferença não foi significativa (P>0,05). Conclusão: Exercícios de força do centro abdominal melhoram a massa corporal de um atleta do boxe e o nível de seu pugilismo. É indicado aos atletas um complemento com fortalecimento do centro abdominal durante o exercício regular. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El entrenamiento de fuerza tiene como objetivo mejorar la condición física de un deportista mediante la mejora de sus habilidades de equilibrio, movimiento y agilidad. Los boxeadores deben prestar una atención complementaria a la fuerza del núcleo abdominal, una zona fundamental para las habilidades pugilísticas. Objetivo: Examinar los efectos del entrenamiento de la fuerza del núcleo abdominal en el pugilismo de los boxeadores. Métodos: Se seleccionaron diez boxeadores profesionales voluntarios. Todos se someten a tres meses de entrenamiento de fuerza en el centro abdominal según el protocolo descrito. El índice de calidad deportiva de los atletas se estudió mediante estadísticas matemáticas. Resultados: Después de 3 meses de entrenamiento de fuerza en el núcleo abdominal, el resultado de la prueba física fue significativamente mayor (P<0,01). Aunque en la carrera de 400 metros, el entrenamiento con saco de arena y la puntuación de la carrera a intervalos fueron superiores a los de antes del entrenamiento, la diferencia no fue significativa (P>0,05). Conclusión: Los ejercicios de fuerza del núcleo abdominal mejoran la masa corporal de un atleta de boxeo y el nivel de su boxeo. Para los deportistas está indicado un complemento con el entrenamiento de fuerza del núcleo abdominal durante el ejercicio regular. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Measuring Endotracheal Tube Depth by Bedside Ultrasound in Adult Patients in an Intensive Care Unit: A Pilot Study.

The aim of the study described here was to evaluate the feasibility and accuracy of measuring endotracheal tube (ETT) depth with ultrasound in adult patients in an intensive care unit (ICU). The distance between the upper margin of the cuff and the upper margin of the aortic arch (Duc-ua) of 67 ICU patients was measured by ultrasound, and the time of measurement was recorded. The level of agreement between the distance between the tip of the ETT and the carina (Dtt-c) measured by ultrasound (U-Dtt-c) and Dtt-c measured by bronchoscopy (B-Dtt-c) was assessed using linear regression and a Bland-Altman plot. There was a significant correlation between B-Dtt-c and U-Dtt-c (r = 0.844, p < 0.001). Also, the Bland-Altman plot revealed strong agreement between B-Dtt-c and U-Dtt-c. The time it took to measure ETT depth by ultrasound was 33.91 ± 5.43 s. In conclusion, bedside ultrasound provides a novel and convenient method for measuring the depth of ETT in ICU patients.

LPS-induced CXCR4-dependent migratory properties and a mesenchymal-like phenotype of colorectal cancer cells.

Colorectal cancer (CRC) is the most commonly diagnosed cancer worldwide, and over 50% of patients will develop hepatic metastasis during the course of their disease. CXCR4 and its ligand, stromal cell-derived factor 1α (SDF-1α)/chemokine (C-X-C motif) ligand 12 (CXCL12) have been revealed as regulatory molecules involved in the spreading and progression of a variety of tumors. Here we have shown that lipopolysaccharides (LPS) promoted the migratory capacity of colon cancer cells in vivo and in vitro, which correlated with the activation of SDF-1α/CXCR4 axis and epithelial-mesenchymal transition (EMT) occurrence. Additionally, we found that LPS-induced CXCR4 expression and EMT through NF-κB signaling pathway activation. And inhibition of NF-κB pathway, which recovered the epithelial phenotype and attenuated CXCR4 expression, inhibited cell migratory capacity. Clinically, high levels of CXCR4 always correlated with metastasis and poor prognosis of CRC patients. In conclusion, LPS participate in the whole process of hepatic metastasis of CRC, not only causing liver damage resulting in the production of SDF-1α, but also enhancing the invasive potential of CRC cells by promoting CXCR4 expression and EMT occurrence, which would contribute to the enhancement of cell migration and invasion.

Hepatic stellate cell promoted hepatoma cell invasion via the HGF/c-Met signaling pathway regulated by p53.

The biological behaviors of hepatocellular carcinoma (HCC) are complex mainly due to heterogeneity of progressive genetic and epigenetic mutations as well as tumor environment. Hepatocyte growth factor (HGF)/c-Met signaling pathway is regarded to be a prototypical example for stromal-epithelial interactions during developmental morphogenesis, wound healing, organ regeneration and cancer progression. And p53 plays as an important regulator of Met-dependent cell motility and invasion. Present study showed that 2 HCC cell lines, Hep3B and HepG2, displayed different invasive capacity when treated with HGF which was secreted by hepatic stellate cells (HSCs). We found that HGF promoted Hep3B cells invasion and migration as well as epithelial-mesenchymal transition (EMT) occurrence because Hep3B was p53 deficient, which leaded to the c-Met over-expression. Then we found that HGF/c-Met promoted Hep3B cells invasion and migration by upregulating Snail expression. In conclusion, HGF/c-Met signaling is enhanced by loss of p53 expression, resulting in increased ability of invasion and migration by upregulating the expression of Snail.

Toll like receptor 4 facilitates invasion and migration as a cancer stem cell marker in hepatocellular carcinoma.

Cancer stem cells (CSCs) or tumor-initiating cells (TICs), a small subset of tumor cells, are involved in tumor initiation, progression, recurrence and metastasis. In human hepatocellular carcinoma (HCC), TICs are enriched with cell surface markers and play a key role in chemotherapy resistance, tumor invasion and migration. Toll like receptor 4 (TLR4), acting as a receptor for lipopolysaccharide (LPS), has been reported to be responsible for carcinogenesis, invasion, metastasis and cancer progression. In our study, two HCC cell lines and a splenic vein metastasis of the nude mouse model were used to study the invasive ability of TLR4 positive HCC cells in vitro and in vivo. Stem-like features were also detected in TLR4 positive HCC cells. A total of 88 clinical samples from HCC patients were used to evaluate the association of TLR4 and stem-cell marker expression, and the relationship between TLR4 expression and clinicopathological characteristics was analyzed. The in vitro and in vivo experiments indicated that TLR4 positive HCC cells displayed significantly enhanced invasion and migration, and stem-like properties were also detected in TLR4 positive HCC cells. Clinically, TLR4 expression levels were found to be significantly higher in HCC tissues with microvascular invasion. Additionally, high expression of TLR4 in HCC tissues was strongly associated with both early recurrence and poor survivals in patients. Our results indicated that there was a relationship between TLR4 expression and CSC's features, TLR4 may act as a CSC marker, prompting tumor invasion and migration, which contributes to the poor prognosis of HCC.

Hepatitis B virus (HBV) receptors: Deficiency in tumor results in scant HBV infection and overexpression in peritumor leads to higher recurrence risk.

Hepatitis B virus (HBV) infection is a risk factor for hepatocarcinogenesis and recurrence. Here, we sought to characterize intratumoral and peritumoral expression of HBsAg and its specific receptors in HBsAg-positive hepatocellular carcinoma (HCC) patients and further examined their correlation with the recurrence-free survival (RFS). HCC tissue and adjacent normal tissue specimens were acquired from HBsAg-positive patients. The presence of HBsAg and receptors, as well as hepatic progenitor cells (HPCs) were detected by tissue microassay and immunohistochemistry. Necroinflammatory activity was evaluated by HE staining. The mean IOD of HBsAg and HBV DNA in the intratumoral tissues was markedly lower than that in the peritumoral tissues (P < 0.001). Pearson correlation analysis further showed a significant correlation between the expression of HBsAg and NTCP (r = 0.461, P < 0.001) or ASGPR (r = 0.506, P < 0.001) in peritumoral tissues. And the peritumoral HBsAg and receptors presented a positive association with necroinflammatory activity (P < 0.05). Inflammation induced by HBV infection presented a positive association with HPCs activation (P < 0.05). Additionally, due to lack of HBV receptors, HPCs was not preferentially infected with HBV, but activated HPCs had a significant correlation with HBsAg expression in peritumoral tissues, and the peritumoral HPCs activation was associated with RFS of HCC patients, therefore, the overexpression of HBsAg and receptors in peritumor were also with higher recurrence risk (P < 0.05). In conclusion, lack of HBV receptors resulted in scant HBV infection in tumor cells, and overexpression of HBsAg and receptors in peritumor was strongly associated with higher recurrence risk in HCC patients.

Tumor-associated macrophages promote cancer stem cell-like properties via transforming growth factor-beta1-induced epithelial-mesenchymal transition in hepatocellular carcinoma.

Tumor-associated macrophages (TAMs), a crucial component of immune cells infiltrated in tumor microenvironment, have been found to be associated with progression and metastasis of hepatocellular carcinoma (HCC). In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and cancer stem cells (CSCs) in HCC. Mouse macrophage cell line RAW264.7 cells were used to investigate the effects of TAMs on mouse hepatoma cell line Hepa1-6 cells in vivo and vitro. A total of 90 clinical samples had pathology-proven HCC were used to evaluate the distribution of TAMs and CSCs and analyze their value in predicting the prognosis. In the study, we have found that the number of TAMs has a positive correlation with the density of CSCs in the marginal of human HCC. Our results show that, cocultured with TAM-conditioned medium (CM) promoted CSC-like properties in Hepa1-6 cells, which underwent EMT and gained higher invasive capability. TAMs secreted more transforming growth factor- beta1 (TGF-beta1) than other phenotypes of macrophage. Furthermore, depletion of TGF-beta1 blocked acquisition of CSC-like properties by inhibition of TGF-beta1-induced EMT. High expression of CD68 in the EpCAM positive expression HCC tissues was strongly associated with both poor cancer-free survival and overall survival in patients. Our results indicate that the TAMs promote CSC-like properties via TGF-beta1-induced EMT and they may contribute to investigate the prognosis of HCC.

Proliferative ductular reactions correlate with hepatic progenitor cell and predict recurrence in HCC patients after curative resection.

BACKGROUND: Ductular reactions (DRs) are well documented in many acute and chronic liver disease.The DRs are thought to be the transit amplifying cells deriving from activation of the stem/progenitor cell compartments of the liver. The aim of this study was to examine the presence of proliferative index of DR (PI-DR) and HPC markers' expression in HCCs after curative hepatectomy, as well as their relationship with clinicopathological features and prognosis. RESULTS: Tissue microarray with peritumoral and intratumoral tissue samples of 120 HCCs after hepatectomy was analysed for peritumoral expression of proliferating cell nuclear antigen for PI-DR. Peritumoral and intratumoral expression status of HPC markers including EpCAM, OV6, CD133 and c-kit were also examined by immunohistochemistry. TMA analysis of HCCs revealed that peritumoral PI-DR strongly correlated with the degree of inflammation and fibrosis. The peritumoral PI-DR positively correlated with peritumoral HPC markers EpCAM, OV6, CD133 and c-kit expression. Moreover, there were highly significant correlations between peritumoral PI-DR and intratumoral HPC markers EpCAM, OV6, CD133 and c-kit expression. Further, multivariate analysis showed that peritumoral PI-DR was the independent prognostic factor for overall survival (HR; 3.316, P < 0.001), and peritumoral PI-DR had a better power to predict disease-free survival (HR; 2.618, P < 0.001). CONCLUSIONS: Peritumoral PI-DR, as a valid surrogate for peritumoral and intratumoral expression of HPC markers, could be served as a potential prognostic marker for recurrence and survival in HCC after hepatectomy.

Hepatic stellate cells secreted hepatocyte growth factor contributes to the chemoresistance of hepatocellular carcinoma.

As the main source of extracellular matrix proteins in tumor stroma, hepatic stellate cells (HSCs) have a great impact on biological behaviors of hepatocellular carcinoma (HCC). In the present study, we have investigated a mechanism whereby HSCs modulate the chemoresistance of hepatoma cells. We used human HSC line lx-2 and chemotherapeutic agent cisplatin to investigate their effects on human HCC cell line Hep3B. The results showed that cisplatin resistance in Hep3B cells was enhanced with LX-2 CM (cultured medium) exposure in vitro as well as co-injection with LX-2 cells in null mice. Meanwhile, in presence of LX-2 CM, Hep3B cells underwent epithelial to mesenchymal transition (EMT) and upregulation of cancer stem cell (CSC) -like properties. Besides, LX-2 cells synthesized and secreted hepatic growth factor (HGF) into the CM. HGF receptor tyrosine kinase mesenchymal-epithelial transition factor (Met) was activated in Hep3B cells after LX-2 CM exposure. The HGF level of LX-2 CM could be effectively reduced by using HGF neutralizing antibody. Furthermore, depletion of HGF in LX-2 CM abolished its effects on activation of Met as well as promotion of the EMT, CSC-like features and cisplatin resistance in Hep3B cells. Collectively, secreting HGF into tumor milieu, HSCs may decrease hepatoma cells sensitization to chemotherapeutic agents by promoting EMT and CSC-like features via HGF/Met signaling.