Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors.

Our understanding of human hepatocellular carcinoma (HCC) development and progression has been hampered by the lack of in vivo models. We performed a genetic screen of 10 oncogenes and genetic mutations in Fah-ablated immunodeficient mice in which primary human hepatocytes (PHHs) are used to reconstitute a functional human liver. We identified that MYC, TP53R249S , and KRASG12D are highly expressed in induced HCC (iHCC) samples. The overexpression of MYC and TP53R249S transform PHHs into iHCC in situ, though the addition of KRASG12D significantly increases the tumorigenic efficiency. iHCC, which recapitulate the histological architecture and gene expression characteristics of clinical HCC samples, reconstituted HCC after serial transplantations. Transcriptomic analysis of iHCC and PHHs showed that MUC1 and FAP are expressed in iHCC but not in normal livers. Chimeric antigen receptor (CAR) T cells against these two surface markers efficiently lyse iHCC cells. The properties of iHCC model provide a biological basis for several clinical hallmarks of HCC, and iHCC may serve as a model to study HCC initiation and to identify diagnostic biomarkers and targets for cellular immunotherapy.

NIR-responsive CN-Pt-GEM hydrogel induces necroptosis and immunotherapeutic responses prevent postoperative recurrence and wound infection in lung carcinoma.

BACKGROUND: Cancer recurrence following surgical resection is a major cause of treatment failure. Finding effective methods to prevent postoperative recurrence and wound infection is an important component of successful surgery. With the development of new nanotechnology, more treatment options have been provided for postoperative adjuvant therapy. This study presents an innovative hydrogel system that stimulates tumoricidal immunity after surgical resection of non-small cell lung cancer (NSCLC) and prevents cancer relapse. RESULTS: The hydrogel system is based on the excellent photothermal conversion performance of single-atom platinum (CN-Pt) along with the delivery and release of the chemotherapy drug, gemcitabine (GEM). The system is coated onto the wound surface after tumor removal with subsequent near-infrared (NIR) photothermal therapy, which efficiently induces necroptosis of residual cancer cells, amplifies the levels of damage-associated molecular patterns (DAMPs), and increases the number of M1 macrophages. The significantly higher levels of phagocytic macrophages enhance tumor immunogenicity and sensitize cancer cells to CD8 + T-cell immunity to control postoperative recurrence, which has been verified using an animal model of postoperative lung cancer recurrence. The CN-Pt-GEM-hydrogel with NIR can also inhibit postoperative wound infection. CONCLUSIONS: These findings introduce an alternative strategy for supplementing antitumor immunity in patients undergoing resection of NSCLC tumors. The CN-Pt-GEM-hydrogel with the NIR system also exhibits good biosafety and may be adaptable for clinical application in relation to tumor resection surgery, wound tissue filling, infection prevention, and recurrence prevention.

HSP70 promotes tumor progression by stabilizing Skp2 expression in gastric cancer cells.

Gastric cancer (GC) has one of the highest tumor incidences worldwide. Heat shock protein 70 (HSP70) is highly expressed and plays a critical role in the occurrence, progression, metastasis, poor prognosis, and drug resistance of GC. However, the underlying mechanisms of HSP70 are not clear. To explore the regulatory role of HSP70 in GC, we performed cell counting kit-8 (CCK-8) and EdU staining assays to assess cell proliferation; immunohistochemistry and western blot analyses to assess protein expression; coimmunoprecipitation (Co-IP) assays to assess interactions between two proteins; and immunofluorescence to assess protein expression and localization. HSP70 was highly expressed in clinical samples from patients with GC and indicated a poor prognosis. HSP70 inhibition enhanced the sensitivity of GC cells to thermochemotherapy. Furthermore, we found that S phase kinase-associated protein 2 (Skp2) was highly expressed in GC and correlated with HSP70 in array data from The Cancer Genome Atlas (TCGA). Importantly, HSP70 inhibition promoted Skp2 degradation. Skp2 overexpression abrogated HSP70 inhibition-induced cell cycle arrest, suggesting that the role of HSP70 in GC depends on Skp2 expression. Our results illustrate a possible regulatory mechanism of HSP70 and may provide a therapeutic strategy for overcoming resistance to thermochemotherapy.

Differentiation of small (≤ 3 cm) hepatocellular carcinomas from benign nodules in cirrhotic liver: the added additive value of MRI-based radiomics analysis to LI-RADS version 2018 algorithm.

BACKGROUND: Accurate characterization of small nodules in a cirrhotic liver is challenging. We aimed to determine the additive value of MRI-based radiomics analysis to Liver Imaging Reporting and Data System version 2018 (LI-RADS v 2018) algorithm in differentiating small (≤ 3 cm) hepatocellular carcinomas (HCCs) from benign nodules in cirrhotic liver. METHODS: In this retrospective study, 150 cirrhosis patients with histopathologically confirmed small liver nodules (HCC, 112; benign nodules, 44) were evaluated from January 2013 to October 2018. Based on the LI-RADS algorithm, a LI-RADS category was assigned for each lesion. A radiomics signature was generated based on texture features extracted from T1-weighted, T2W, and apparent diffusion coefficient (ADC) images by using the least absolute shrinkage and selection operator regression model. A nomogram model was developed for the combined diagnosis. Diagnostic performance was assessed using receiver operating characteristic curve (ROC) analysis. RESULTS: A radiomics signature consisting of eight features was significantly associated with the differentiation of HCCs from benign nodules. Both LI-RADS algorithm (area under ROC [Az] = 0.898) and the MRI-Based radiomics signature (Az = 0.917) demonstrated good discrimination, and the nomogram model showed a superior classification performance (Az = 0.975). Compared with LI-RADS alone, the combined approach significantly improved the specificity (97.7% vs 81.8%, p = 0.030) and positive predictive value (99.1% vs 92.9%, p = 0.031) and afforded comparable sensitivity (97.3% vs 93.8%, p = 0.215) and negative predictive value (93.5% vs 83.7%, p = 0.188). CONCLUSIONS: MRI-based radiomics analysis showed additive value to the LI-RADS v 2018 algorithm for differentiating small HCCs from benign nodules in the cirrhotic liver.

Targeting USP1-dependent KDM4A protein stability as a potential prostate cancer therapy.

The histone demethylase lysine-specific demethylase 4A (KDM4A) is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. However, the biological role and mechanism of KDM4A in prostate cancer (PC) remain unclear. Herein, we reported KDM4A expression was upregulation in phosphatase and tensin homolog knockout mouse prostate tissue. Depletion of KDM4A in PC cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of the USP1-KDM4A/androgen receptor axis in driving PC cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression was observed in most prostate tumors and inhibition of USP1 promotes PC cells response to therapeutic agent enzalutamide. Our studies propose USP1 could be an anticancer therapeutic target in PC.

Correction to: The old CEACAMs find their new role in tumor immunotherapy.

Correction is needed to the original version of this article.

The old CEACAMs find their new role in tumor immunotherapy.

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) contain 12 family members(CEACAM1、CEACAM3、CEACAM4、CEACAM5、CEACAM6、CEACAM7、CEACAM8、CEACAM16、CEACAM18、CEACAM19、CEACAM20 and CEACAM21)and are expressed diversely in different normal and tumor tissues. CEA (CEACAM5) has been used as a tumor biomarker since 1965. Here we review the latest research and development of the structures, expression, and function of CEACAMs in normal and tumor tissues, and their application in the tumor diagnosis, prognosis, and treatment. We focus on recent clinical studies of CEA targeted cancer immunotherapies, including bispecific antibody (BsAb) for radio-immuno-therapy and imaging, bispecific T cell engager (BiTE) and chimeric antigen receptor T cells (CAR-T). We summarize the promising clinical relevance and challenges of these approaches and give perspective view for future research. This review has important implications in understanding the diversified biology of CEACAMs in normal and tumor tissues, and their new role in tumor immunotherapy.

Novel transcription regulatory sequences and factors of the immune evasion protein ICP47 (US12) of herpes simplex viruses.

BACKGROUND: Herpes simplex virus (HSV) can cause encephalitis. Its infected cell polypeptide 47 (ICP47), encoded by immediate-early gene US12, promotes immune escape. ICP47 was modified in the clinically approved oncolytic HSV (oHSV) T-Vec. However, transcription regulatory sequence (TRS) and transcription regulatory factor (TRF) of HSV US12 are seldom reported. METHODS: Previously, our laboratory isolated a new HSV strain named HSV-1-LXMW from a male patient with oral herpes in Beijing, China. Firstly, the genetic tree was used to analyze its genetic relationship. The US12 TRS and TRF in HSV-1-LXMW were found by using predictive software. Secondly, the further verification by the multi-sequence comparative analysis shown that the upstream DNA sequence of HSV US12 gene contained the conserved region. Finally, the results of literature search shown that the expression of transcription factors was related to the tissue affinity of HSV-1 and HSV-2, so as to increase the new understanding of the transcriptional regulation of HSV biology and oncolytic virus (OVs) therapy. RESULTS: Here we reported the transcriptional regulation region sequence of our new HSV-1-LXMW, and its close relationship with HSV-1-CR38 and HSV-1-17. Importantly we identified eight different kinds of novel TRSs and TRFs of HSV US12 for the first time, and found they are conserved among HSV-1 (c-Rel, Elk-1, Pax-4), HSV-2 (Oct-1, CF2-II, E74A, StuAp) or both HSVs (HNF-4). The TRFs c-Rel and Oct-1 are biologically functional respectively in immune escape and viral replication during HSV infection. CONCLUSIONS: Our findings have important implication to HSV biology, infection, immunity and oHSVs.

Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: A multicenter propensity score-matched cohort study.

OBJECTIVE: Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis (PM) in gastric cancer (GC). Hyperthermic intraperitoneal chemotherapy (HIPEC) combined with complete cytoreductive surgery (CRS) has shown promising outcomes but remains controversial. The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM. METHODS: This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone (Cx group) or with HIPEC combined with chemotherapy (HIPEC-Cx group) in four Chinese high-volume gastric medical centers between 2010 and 2017. The primary outcomes were median survival time (MST) and 3-year overall survival (OS). Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias. RESULTS: Of 663 eligible patients, 498 were matched. The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months, respectively [hazard ratio (HR)=0.71, 95% confidence interval (95% CI), 0.58-0.88; P=0.002]. The 3-year OS rate was 10.1% (95% CI, 5.4%-14.8%) and 18.4% (95% CI, 12.3%-24.5%) in the Cx and HIPEC-Cx groups, respectively (P=0.017). The complication rates were comparable. The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone (4.6±2.4 dvs. 2.7±1.8 d, P<0.001; 14.2±5.8 dvs. 11.4±7.7 d, P<0.001), respectively. The median follow-up period was 33.2 months. CONCLUSIONS: Compared with standard systemic chemotherapy, HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM, without compromising patient safety.

An immunosuppressive peptide from the horsefly inhibits inflammation by repressing macrophage maturation and phagocytosis.

Ectoparasites repress host immune responses while they obtain nutrition from their hosts. Understanding the immunosuppressive mechanisms between ectoparasites and their hosts will provide new strategies to develop potential immunosuppressive drugs against immune disorder diseases. Previously, we have discovered that a small peptide, immunoregulin HA, from the horsefly (Hybomitra atriperoides) may play an immunosuppressive role in rat splenocytes. However, the targeting cells and detailed mechanisms of immunoregulin HA in immunosuppressive reactions are not well defined. Here, we show that immunoregulin HA reduces the secretion of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. Interestingly, we discover that the major cytokines repressed by immunoregulin HA are secreted by macrophages, rather than by T cells. Furthermore, immunoregulin HA inhibits macrophage maturation and phagocytosis. Mechanically, the activations of c-JUN N-terminal kinase and extracellular signal-regulated kinase upon LPS stimulation are decreased by immunoregulin HA. Consistently, immunoregulin HA treatment exhibits an anti-inflammatory activity in a mouse model of adjuvant-induced paw inflammation. Taken together, our data reveal that immunoregulin HA conducts the anti-inflammatory activity by blocking macrophage functions.

Development of a high-precision bladder hyperthermic intracavitary chemotherapy device for bladder cancer and pharmacokinetic study.

BACKGROUND: Bladder hyperthermic intracavitary chemotherapy (HIVEC) has good effectiveness for bladder cancer, but conventional HIVEC systems lack precision and convenient application. To test the safety of a new HIVEC device (BR-TRG-II-type) in pigs and to perform a preliminary clinical trial in patients with bladder cancer. METHODS: This device was tested on six pigs to optimize the temperature and time parameters. Then, 165 patients (HIVEC after transurethral resection (TUR), n = 128; or HIVEC, n = 37) treated between December 2006 and December 2016 were recruited. Mitomycin C (MMC) was the chemotherapeutic agent. A serum pharmacokinetic study was performed. The primary endpoints were tumor recurrence, disease-free survival (DFS), and cumulative incidence rate (CIR) during follow-up. The adverse effects were graded. RESULTS: The animal experiment showed that 45 °C for 1 h was optimal. HIVEC was successful, with the infusion tube temperature stably controlled at about 45 °C, and outlet tube temperature of about 43 °C in all patients, for three sessions. Serum MMC levels gradually increased during HIVEC and decreased thereafter. The mean DFS was 39 ± 3.21 months (ranging from 8 to 78 months), and the DFS rate was 89.1% during follow-up. No adverse events occurred. CONCLUSION: The use of the BR-TRG-II-type HIVEC device is feasible for the treatment of bladder cancer. Future clinical trials in patients with different stages of bladder cancer will further confirm the clinical usefulness of this device. TRIAL REGISTRATION: chictr.org.cn: ChiCTR1900022099 (registered on Mar. 252,019). Retrospectively registered.

Chinese version of the Cancer Support Person's Unmet Needs Survey-Sort Form: A psychometric study.

OBJECTIVE: Psychometrically rigorous and comprehensive needs assessment measures for Chinese general cancer caregivers are relatively scarce. We described the development and psychometric evaluation of the Chinese version of the Cancer Support Person's Unmet Needs Survey-Short Form (SPUNS-SFC). METHODS: A forward-backward translation method was utilised to develop the SPUNS-SFC. The construct validity, internal consistency, convergent validity and discriminant validity of the SPUNS-SFC were evaluated. RESULTS: A total of 1,026 Chinese cancer caregivers completed the SPUNS-SFC. Items 10, 11, 13, 24 and 26 were removed as more than 80% of respondents reported having no unmet needs on these items. Exploratory factor analysis revealed a five-factor structure, which accounted for 78.47% of the total variance, and consisted of the following domains: information, healthcare access and continuity, personal and emotional needs, worries about the future, and financial needs. Internal consistency of the measure was high, with Cronbach's alpha coefficients ranging from 0.87 to 0.95 for the five domains. The measure illustrated adequate evidence of convergent validity, demonstrated by significant correlations with multiple measures of psychological well-being. Known-groups validity was established, as 87.5% of the hypotheses were supported. CONCLUSION: This study indicates the SPUNS-SFC is a reliable and valid measure of the unmet needs of Chinese cancer caregivers.

BRD4 promotes gastric cancer progression through the transcriptional and epigenetic regulation of c-MYC.

Although the significance of BRD4 in the epigenetic memory and cancer genesis has been intensively investigated, little is known about its function and potential roles during the generation and progression of gastric cancer. We report here that BRD4 increases the proliferation and represses the apoptosis of gastric cancer cells through activating c-MYC via transcriptional and epigenetic regulation mechanisms. Expression analyses in both small and large cohort of sample show that BRD4 is highly expressed in gastric cancer tissues/cells when compared with the adjacent non-tumor tissues/normal cells. We also find a positive correlation between the expression of BRD4 and c-MYC in patient samples. The repression of BRD4 by siRNAs leads to the down-regulation of c-MYC in gastric cancer cells. Chromatin immunoprecipitation-qPCR and luciferase assays show that BRD4 binds to and coordinately activates c-MYC promoter, indicating that c-MYC is transcriptional target of BRD4 and BRD4 regulates its basal expression. Further evidence show that the histone acetylation inhibitor reduces the binding of BRD4 as well as the histone activation level on c-MYC promoter, and leads to the down-regulation of c-MYC, suggesting that BRD4 regulates the expression of c-MYC through epigenetic mechanism. Functionally, the suppression of BRD4 leads to growth inhibition and apoptosis in gastric cancer cells. Force expression of c-MYC alongside with BRD4 repression rescue the anti-cancer effects caused by BRD4 repression. Collectively, our data not only uncovered the mechanism of BRD4 in regulating the proliferation of gastric cancer cells but also provides a new therapeutic strategy for this type of cancer.

Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death.

LINC01133 as ceRNA inhibits gastric cancer progression by sponging miR-106a-3p to regulate APC expression and the Wnt/ß-catenin pathway.

BACKGROUND: Gastric cancer (GC) is a common malignancy and frequent cause of cancer-related death. Long non-coding RNAs (lncRNAs) have emerged as important regulators and tissue-specific biomarkers of multiple cancers, including GC. Recent evidence has indicated that the novel lncRNA LINC01133 plays an important role in cancer progression and metastasis. However, its function and molecular mechanism in GC remain largely unknown. METHODS: LINC01133 expression was detected in 200 GC and matched non-cancerous tissues by quantitative reverse transcription PCR. Gain- and loss-of-function experiments were conducted to investigate the biological functions of LINC01133 both in vitro and in vivo. Insights into the underlying mechanisms of competitive endogenous RNAs (ceRNAs) were determined by bioinformatics analysis, dual-luciferase reporter assays, quantitative PCR arrays, TOPFlash/FOPFlash reporter assay, luciferase assay, and rescue experiments. RESULTS: LINC01133 was downregulated in GC tissues and cell lines, and its low expression positively correlated with GC progression and metastasis. Functionally, LINC01133 depletion promoted cell proliferation, migration, and the epithelial-mesenchymal transition (EMT) in GC cells, whereas LINC01133 overexpression resulted in the opposite effects both in vitro and in vivo. Bioinformatics analysis and luciferase assays revealed that miR-106a-3p was a direct target of LINC01133, which functioned as a ceRNA in regulating GC metastasis. Mechanistic analysis demonstrated that miR-106a-3p specifically targeted the adenomatous polyposis coli (APC) gene, and LINC01133/miR-106a-3p suppressed the EMT and metastasis by inactivating the Wnt/ß-catenin pathway in an APC-dependent manner. CONCLUSIONS: Our findings suggest that reduced expression of LINC01133 is associated with aggressive tumor phenotypes and poor patient outcomes in GC. LINC01133 inhibits GC progression and metastasis by acting as a ceRNA for miR-106a-3p to regulate APC expression and the Wnt/ß-catenin pathway, suggesting that LINC01133 may serve as a potential prognostic biomarker and anti-metastatic therapeutic target for GC.

Predictive Value of LINC01133 for Unfavorable Prognosis was Impacted by Alcohol in Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIMS: Considerable evidence indicates that long noncoding RNAs (lncRNAs) exert importantly regulatory functions during human cancer initiation and progression and are promising biotargets in the flight against cancer. METHODS: In this study, we evaluated the role of the lncRNA LINC01133 in esophageal squamous cell carcinoma (ESCC). LINC01133 expression in ESCC was examined by quantitative real-time PCR. The correlations between LINC01133 expression and clinicopathological variables and survival were examined by the χ2 test, Kaplan-Meier method, log-rank test, and univariate Cox regression analysis. RESULTS: LINC01133 expression levels were frequently lower in ESCC tissues and cell lines than in paired normal tissues and an immortalized esophageal epithelial cell line, respectively. The expression of LINC01133 decreased in a TNM stage- and lifestyle-independent manner. LINC01133 was an independent protective factor and had an anti-tumor effect in the early stage of ESCC development. More importantly, we discovered that drinking status in our cohort impaired the predictive accuracy of LINC01133 for patients with ESCC. Furthermore, a new risk model combining LINC01133 expression, drinking status, and TNM stage provided better survival discrimination compared with three other predictors. CONCLUSIONS: Our data indicate that a loss of LINC01133 expression is a potential poor prognostic biomarker and therapeutic target for ESCC and provide additional prognostic information to improve the outcomes of ESCC patients.

Long Non-Coding RNA XLOC_006753 Promotes the Development of Multidrug Resistance in Gastric Cancer Cells Through the PI3K/AKT/mTOR Signaling Pathway.

BACKGROUND/AIMS: The development of multidrug resistance (MDR), which results in disease recurrence and metastasis, is a crucial obstacle to successful chemotherapy for patients with gastric cancer (GC). Long non-coding RNAs (lncRNAs) have been found to play various roles in cancer. This study aimed to investigate the effect of XLOC_006753 on the development of MDR in GC cells. METHODS: The expression levels of XLOC_006753 in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell line) were assessed by qRT-PCR. Statistical analyses were conducted to determine the relationship between XLOC_006753 expression and clinical features and to assess the prognostic value of XLOC_006753 for overall survival and progression-free survival. Then, a CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry was used to detect cell cycle and cell apoptosis. A wound-healing assay and transwell assay were used to detect cell migration. The expression of markers for MDR, G1/S transition, epithelial-mesenchymal transition (EMT) and PI3K/ AKT/mTOR signaling pathway were examined by western blot. RESULTS: XLOC_006753 was highly expressed in GC patients and MDR GC cell lines (SGC-7901/5-FU and SGC-7901/DDP cell lines), and its high expression was positively associated with metastasis, TNM stage, tumor size, and poor survival in GC patients. Moreover, XLOC_006753 was an independent prognostic biomarker of overall survival and progression-free survival for gastric cancer patients. Knocking down XLOC_006753 in the two MDR GC cell lines significantly inhibited cell proliferation, cell viability, cell cycle G1/S transition, and migration. XLOC_006753 knockdown also promoted apoptosis. Furthermore, western blots showed that XLOC_006753 knockdown decreased some markers of MDR, G1/S transition, and EMT expression, while increasing caspase9 expression and inhibiting the PI3K/AKT/mTOR signaling pathway in SGC-7901/5-FU and SGC-7901/DDP cells. CONCLUSION: High expression of XLOC_006753 promoted the development of MDR, which was activated by the PI3K/AKT/mTOR pathway in GC cells.

Mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death.

Mild hyperthermia enhances anti-cancer effects of chemotherapy, but the precise biochemical mechanisms involved are not clear. This study was carried out to investigate whether mild hyperthermia sensitizes gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death. In total, 20 BABL/c mice of MKN-45 human gastric cancer tumor model were divided into hyperthermia + chemotherapy group, hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group. Reactive oxygen species production and expression of autophagy-related genes Beclin1, LC3B, and mammalian target of rapamycin were determined. The relationships between tumor growth regression, expression of autophagy-related genes, and reactive oxygen species production were evaluated. Tumor size and wet weight of hyperthermia + chemotherapy group was significantly decreased relative to values from hyperthermia group, chemotherapy group, N-acetyl-L-cysteine group, and mock group ( F = 6.92, p < 0.01 and F = 5.36, p < 0.01, respectively). Reactive oxygen species production was significantly higher in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. The expression levels of Beclin1 and LC3B were significantly higher, while those of mammalian target of rapamycin were significantly lower in hyperthermia + chemotherapy group than in hyperthermia, chemotherapy, and mock groups. Tumor growth regression was consistent with changes in reactive oxygen species production and expression of autophagy-related genes. N-acetyl-L-cysteine inhibited changes in the expression of the autophagy-related genes and also suppressed reactive oxygen species production and tumor growth. Hyperthermia + chemotherapy increase expression of autophagy-related genes Beclin1 and LC3B, decrease expression of mammalian target of rapamycin, and concomitantly increase reactive oxygen species generation. These results strongly indicate that mild hyperthermia enhances sensitivity of gastric cancer cells to chemotherapy through reactive oxygen species-induced autophagic death.

Psychometric testing of the Mandarin version of the 34-item Short-Form Supportive Care Needs Survey in patients with cancer in mainland China.

PURPOSE: Although the Supportive Care Needs Survey is one of the most comprehensive and robust cancer-specific needs assessment instruments, no version exists specifically for cancer patients in mainland China. This study tested the psychometric properties of the Mandarin version of the 34-item Short-Form Supportive Care Needs Survey (SCNS-SF34-C (Mandarin)) in mainland Chinese cancer patients. METHODS: From December 2015 to May 2016, patients were recruited from two cancer centers in Guangzhou, China, to complete the SCNS-SF34-C (Mandarin). Exploratory factor analysis (EFA) was used to test the factor structure. The internal consistency, convergent validity, and discriminant validity of the resulting factor structure were evaluated by traditional psychometric analysis. RESULTS: A total of 861 patients completed the SCNS-SF34-C (Mandarin). Item 14 was removed for its low factor loadings on every factor in the initial EFA. Using the remaining 33 items, the reiterated EFA produced a five-dimension structure that was consistent with the dimensions of the original version of the SCNS-SF34 (health system and information, psychological, patient care and support, physical and daily living, and sexuality), accounting for 69.757% of the total variance. Cronbach's alpha coefficients ranged from 0.854 to 0.942 for the five domains and 0.947 for the whole scale. Convergent validity was verified by significant correlations with all corresponding instruments. It discriminated between groups based on age, sex, marital status, and stage of disease. CONCLUSIONS: Preliminary evidence suggests that the SCNS-SF34-C (Mandarin) is a reliable and valid instrument for assessing the supportive care needs of cancer patients in mainland China.

Hyperthermic Intraperitoneal Perfusion Chemotherapy and Cytoreductive Surgery for Controlling Malignant Ascites From Ovarian Cancer.

BACKGROUND: Malignant ascites, a complication often seen in patients with ovarian cancer (OC), is difficult to treat, but hyperthermic intraperitoneal chemotherapy (HIPEC) has a good efficacy. OBJECTIVE: The aim of this study was to assess the efficacy of cytoreductive surgery (CRS) combined with HIPEC for controlling malignant ascites from OC. MATERIALS AND METHODS: From December 2009 until December 2014, 53 patients with OC and malignant ascites were treated with CRS and HIPEC. Patients in good health condition were treated with CRS followed by HIPEC (CRS + HIPEC), and patients in poor health condition were treated initially with B-mode ultrasound-guided HIPEC followed by delayed CRS upon improvement of their health condition (HIPEC + delayed CRS). Resolution of ascites, complete CRS, overall survival, and disease-free survival were analyzed. RESULTS: All patients showed ascites regression. The total objective remission rate was 100%, even for patients in the poor condition group before CRS. Complete CRS was successful in 30 (88.23%) of 34 patients in the good condition group, and 17 (89.47%) of 19 patients in the poor condition group (P > 0.05). Median disease-free survival and median overall survival were 21 and 39 months in the good condition group, and 22 and 38 months in the poor condition group, respectively (P > 0.05). CONCLUSIONS: Hyperthermic intraperitoneal chemotherapy is effective at controlling ascites in patients with OC, even for patients in poor condition before CRS, or when complete CRS is not feasible. Furthermore, the regression of ascites appears not to be dependent on complete resection.