Targeting STAT3 with SH-4-54 suppresses stemness and chemoresistance in cancer stem-like cells derived from colorectal cancer

BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC patients.Although therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer recurrence.This resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor metastasis.AIM To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment outcomes.METHODS CSCs were enriched by culturing CRC cells in serum-free medium.Hallmarks of stemness and IL-6/JAK2/STAT3 signaling were detected by Western blotting.Indicators of CSC malignancy,including proliferation,invasion,and tumor formation,were measured.RESULTS In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal CSCs.As expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC cells.The addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and Nanog.SH-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo cells.Moreover,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in vivo.Notably,SH-4-54 treatment significantly increased chemosensitivity to oxaplatin.CONCLUSION Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.

Multiparameter magnetic resonance imaging-based radiomics model for the prediction of rectal cancer metachronous liver metastasis

BACKGROUND The liver,as the main target organ for hematogenous metastasis of colorectal cancer,early and accurate prediction of liver metastasis is crucial for the diagnosis and treatment of patients.Herein,this study aims to investigate the application value of a combined machine learning(ML)based model based on the multiparameter magnetic resonance imaging for prediction of rectal metachronous liver metastasis(MLM).AIM To investigate the efficacy of radiomics based on multiparametric magnetic resonance imaging images of preoperative first diagnosed rectal cancer in predicting MLM from rectal cancer.METHODS We retrospectively analyzed 301 patients with rectal cancer confirmed by surgical pathology at Jingzhou Central Hospital from January 2017 to December 2023.All participants were randomly assigned to the training or validation queue in a 7:3 ratio.We first apply generalized linear regression model(GLRM)and random forest model(RFM)algorithm to construct an MLM prediction model in the training queue,and evaluate the discriminative power of the MLM prediction model using area under curve(AUC)and decision curve analysis(DCA).Then,the robustness and generalizability of the MLM prediction model were evaluated based on the internal validation set between the validation queue groups.RESULTS Among the 301 patients included in the study,16.28%were ultimately diagnosed with MLM through pathological examination.Multivariate analysis showed that carcinoembryonic antigen,and magnetic resonance imaging radiomics were independent predictors of MLM.Then,the GLRM prediction model was developed with a comprehensive nomogram to achieve satisfactory differentiation.The prediction performance of GLRM in the training and validation queue was 0.765[95%confidence interval(CI):0.710-0.820]and 0.767(95%CI:0.712-0.822),respectively.Compared with GLRM,RFM achieved superior performance with AUC of 0.919(95%CI:0.868-0.970)and 0.901(95%CI:0.850-0.952)in the training and validation queue,respectively.The DCA indicated that the predictive ability and net profit of clinical RFM were improved.CONCLUSION By combining multiparameter magnetic resonance imaging with the effectiveness and robustness of ML-based predictive models,the proposed clinical RFM can serve as an insight tool for preoperative assessment of MLM risk stratification and provide important information for individual diagnosis and treatment of rectal cancer patients.

Unraveling the therapeutic potential of Calculus Bovis in liver cancer:A novel step for targeted cancer treatment

Hepatocellular carcinoma is one of the leading causes of cancer-related deaths globally,and effective treatments are urgently needed.The present study aimed to investigate the inhibitory effect of Calculus Bovis(CB)on liver cancer and the underlying mechanisms.CB inhibited M2 tumor-associated macrophage polarization and modulated the Wnt/β-catenin signaling pathway,thereby suppressing the proliferation of liver cancer cells.The inhibitory effect on liver cancer growth was confirmed by both in vivo and in vitro experiments(detailed by Huang et al).The present study provides a theoretical basis for the application of CB for the treatment of liver cancer,providing new avenues for liver cancer treatment.

Digestive and breast cancer patients managed during the first wave of COVID-19 pandemic:Short and middle term outcomes

BACKGROUND The first wave of coronavirus disease 2019(COVID-19)pandemic in Spain lasted from middle March to the end of June 2020.Spanish population was subjected to lockdown periods and scheduled surgeries were discontinued or reduced during variable periods.In our centre,we managed patients previously and newly diagnosed with cancer.We established a strategy based on limiting perioperative social contacts,preoperative screening(symptoms and reverse transcriptionpolymerase chain reaction)and creating separated in-hospital COVID-19-free pathways for non-infected patients.We also adopted some practice modifications(surgery in different facilities,changes in staff and guidelines,using continuously changing personal protective equipment…),that supposed new inconveniences.AIM To analyse cancer patients with a decision for surgery managed during the first wave,focalizing on outcomes and pandemic-related modifications.METHODS We prospectively included adults with a confirmed diagnosis of colorectal,oesophago-gastric,liver-pancreatic or breast cancer with a decision for surgery,regardless of whether they ultimately underwent surgery.We analysed short-term outcomes[30-d postoperative morbimortality and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection]and outcomes after 3 years(adjuvant therapies,oncological events,death,SARS-CoV-2 infection and vaccination).We also investigated modifications to usual practice.RESULTS From 96 included patients,seven didn’t receive treatment that period and four never(3 due to COVID-19).Operated patients:28 colon and 21 rectal cancers;laparoscopy 53.6%/90.0%,mortality 3.57%/0%,major complications 7.04%/25.00%,anastomotic leaks 0%/5.00%,3-years disease-free survival(DFS)82.14%/52.4%and overall survival(OS)78.57%/76.2%.Six liver metastases and six pancreatic cancers:no mortality,one major complication,three grade A/B liver failures,one bile leak;3-year DFS 0%/33.3%and OS 50.0%/33.3%(liver metastases/pancreatic carcinoma).5 gastric and 2 oesophageal tumours:mortality 0%/50%,major complications 0%/100%,anastomotic leaks 0%/100%,3-year DFS and OS 66.67%(gastric carcinoma)and 0%(oesophagus).Twenty breast cancer without deaths/major complications;3-year OS 100%and DFS 85%.Nobody contracted SARS-CoV-2 postoperatively.COVID-19 pandemic–related changes:78.2%treated in alternative buildings,43.8%waited more than 4 weeks,two additional colostomies and fewer laparoscopies.CONCLUSION Some patients lost curative-intent surgery due to COVID-19 pandemic.Despite practice modifications and 43.8%delays higher than 4 weeks,surgery was resumed with minimal changes without impacting outcomes.Clean pathways are essential to continue surgery safely.

Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis

BACKGROUND Gastric cancer(GC)is the fifth most common type of cancer and has the fourth highest death rate among all cancers.There is a lack of studies examining the impact of liver metastases on the effectiveness of immunotherapy in individuals diagnosed with GC.AIM To investigate the influence of liver metastases on the effectiveness and safety of immunotherapy in patients with advanced GC.METHODS This retrospective investigation collected clinical data of patients with advanced stomach cancer who had immunotherapy at our hospital from February 2021 to January 2023.The baseline attributes were compared using either the Chi-square test or the Fisher exact probability method.The chi-square test and Kaplan-Meier survival analysis were employed to assess the therapeutic efficacy and survival duration in GC patients with and without liver metastases.RESULTS The analysis comprised 48 patients diagnosed with advanced GC,who were categorized into two groups:A liver metastasis cohort(n=20)and a non-liver metastatic cohort(n=28).Patients with liver metastasis exhibited a more deteriorated physical condition compared to those without liver metastasis.The objective response rates in the cohort with metastasis and the cohort without metastasis were 15.0%and 35.7%(P>0.05),respectively.Similarly,the disease control rates in these two cohorts were 65.0%and 82.1%(P>0.05),respectively.The median progression-free survival was 5.0 months in one group and 11.2 months in the other group,with a hazard ratio of 0.40 and a significance level(P)less than 0.05.The median overall survival was 12.0 months in one group and 19.0 months in the other group,with a significance level(P)greater than 0.05.CONCLUSION Immunotherapy is less effective in GC patients with liver metastases compared to those without liver metastasis.

Gastric cancer liver metastasis will reduce the efficacy of immunotherapy

Immune checkpoint inhibitors augment the antitumor activity of T cells by inhibiting the negative regulatory pathway of T cells,leading to notable efficacy in patients with non-small cell lung cancer,melanoma,and other malignancies through immunotherapy utilization.However,secondary malignant liver tumors not only lower the liver's sensitivity to immunotherapy but also trigger systemic immune suppression,resulting in reduced overall effectiveness of immune therapy.Patients receiving immunotherapy for non-small cell lung cancer and melanoma experience reduced response rates,progression-free survival,and overall survival when secondary malignant tumors develop in the liver.Through Liu's retrospective analysis,valuable insights are provided for the future clinical management of these patients.Therefore,in patients with gastric cancer(GC),the occurrence of liver metastasis might be indicative of reduced efficacy of immuno-therapy.Overcoming liver immune tolerance mechanisms and their negative impacts allows for the potential benefits of immunotherapy in patients with GC and liver metastasis.INTRODUCTION Gastric cancer(GC)ranks among the prevalent malignancies affecting the digestive system globally.Based on the latest epidemiological data[1,2],it holds the fifth position for incidence and the fourth position for mortality among all malignant tumors.GC cases and fatalities in China make up roughly half of the worldwide figures.Earlier investigations[3]have demonstrated that the median overall survival(mOS)among advanced GC patients left untreated typically ranges from 3 to 4 months.Systemic chemotherapy recipients often experience a mOS of around one year,accompanied by a marked improvement in the quality of life among patients with advanced GC.The mainstay of treatment for advanced GC patients involves chemotherapeutic medications such as fluoropyrimidines,platinum compounds,and taxanes.However,their efficacy in tumor control is constrained by acquired resistance and primary resistance.The rise of personalized precision therapy has propelled immunotherapy into the spotlight as a crucial component of comprehensive treatment[4].By blocking the negative regulatory pathways of T cells,immune checkpoint inhibitors(ICIs)boost the anti-tumor effect of T cells.Immunotherapy has brought about significant therapeutic benefits for patients diagnosed with non-small cell lung cancer,melanoma,and related illnesses[5,6],instilling newfound hope in those with advanced GC[7].However,phase III clinical trial data[8-12]reveals that the incorporation of immunotherapy into chemotherapy regimens improves overall survival(OS)outcomes for patients with advanced GC.The liver's immune-exempt nature renders it less responsive to immunotherapy when secondary malignant tumors are present,fostering systemic immune suppression and yielding unfavorable outcomes in immune therapy[13-15].In retrospective research[16-20]pertaining to non-small cell lung cancer and melanoma,it has been observed that the presence of secondary liver malignancies may lower the response rate,progression-free survival(PFS),and OS rates in patients treated with immunotherapy,independent of factors such as tumor mutation burden and PD-L1 expression.Despite this,there is a paucity of studies examining whether the existence of secondary malignant liver tumors affects the effectiveness of immunotherapy in patients diagnosed with advanced HER-2 negative GC.

Preparation and evaluation of As_2O _3 nanoparticles for treatment of human liver cancer cells in vitro

This paper studies the preparation method of As_2O_3 nanoparticles and theirantitumor effect on human liver cancer cells. As_2O_3 nanoparticles were prepared by sol-gel method.As_2O_3 nanoparticles were characterized by transmission electron microscope ( TEM), energydispersive spectrometer ( EDS) and computer color magic image analysis system (CMIAS). A methylthiazolyl tetrazolium (MTT) assay and a flow cytometry (FCM) assay were performed to examine theantitumor effect of As_2O_3 nanoparticlesat various concentrations(1, 2, 5, 10 mumol/L). We alsocompared the antitumor effect of As_2O_3 nanoparticles with that of As_2O_3 solution. The averagediameters of two kinds of As_2O_3 nanoparticles prepared were about 80 nm and 40 nm. It wasidentified that the prepared nanoparticles were As_2O_3 and there were no other components by EDS.After 48 h of treatment with As_2O_3 nanoparticles, the survival ratio of cells was significantlylower than that of the As2O3 solution with the same concentration(P < 0. 05). Experimental resultsdemonstrate that by sol-gel method As_2O_3 can be prepared into nanoparticles. As_2O_3 nanoparticlescan produce a better cytotoxic effect on tumor cells than the As_2O_3 solution.

Influence of adriamycin on changes in Nanog, Oct-4, Sox2, ARID1 and Wnt5b expression in liver cancer stem cells

AIM: To determine the influence of Adriamycin (ADM) on the changes in Nanog, Oct4, Sox2, as well as, in ARID1 and Wnt5b expression in liver cancer stem cells.

UBE2T mediates the stemness properties of breast cancer cells through the mTOR signaling pathway

Objectives:This study aimed to reveal the role and possible mechanism of the ubiquitin-conjugating enzyme 2T(UBE2T)in the biological activities of breast cancer stem cells(BCSCs).Methods:The specific protein and gene expression were quantified by Western blotting and quantitative real-time polymerase chain reaction,the proportion of BCSCs was examined by flow cytometry,and the self-renewal and proliferation of BCSCs were verified by serial sphere formation and soft agar.Results:Increasing expression of UBE2T was drastically found in breast cancer than that in adjacent tissues.Furthermore,UBE2T overexpression significantly increased the proportion of BCSCs in breast cancer cells and promoted their self-renewal and proliferation.Silent UBE2T exhibited the opposite functions.UBE2T increased the levels of the mammalian target of rapamycin and the phosphorylated mammalian target of rapamycin.Mammalian target of rapamycin(mTOR)inhibitor rapamycin inhibited the function of UBE2T in BCSCs.Conclusion:UBE2T plays a role in BCSCs through mTOR pathway and may suggest a novel therapeutic strategy for breast cancer.

Effect of colorectal cancer stem cells on the development and metastasis of colorectal cancer

The relevant mechanism of tumor-associated macrophages(TAMs)in the treatment of colorectal cancer patients with immune checkpoint inhibitors(ICIs)is discussed,and the application prospects of TAMs in reversing the treatment tolerance of ICIs are discussed to provide a reference for related studies.As a class of drugs widely used in clinical tumor immunotherapy,ICIs can act on regulatory molecules on cells that play an inhibitory role-immune checkpoints-and kill tumors in the form of an immune response by activating a variety of immune cells in the immune system.The sensitivity of patients with different types of colorectal cancer to ICI treatment varies greatly.The phenotype and function of TAMs in the colorectal cancer microenvironment are closely related to the efficacy of ICIs.ICIs can regulate the phenotypic function of TAMs,and TAMs can also affect the tolerance of colorectal cancer to ICI therapy.TAMs play an important role in ICI resistance,and making full use of this target as a therapeutic strategy is expected to improve the immunotherapy efficacy and prognosis of patients with colorectal cancer.

Interplay and therapeutic implications of colorectal cancer stem cells,tumor microenvironment,and gut microbiota

This article discusses the interplay between colorectal cancer(CRC)stem cells,tumor microenvironment(TME),and gut microbiota,emphasizing their dynamic roles in cancer progression and treatment resistance.It highlights the adaptability of CRC stem cells,the bidirectional influence of TME,and the multifaceted impact of gut microbiota on CRC.The manuscript proposes innovative therapeutic strategies focusing on these interactions,advocating for a shift towards personalized and ecosystem-targeted treatments in CRC.The conclusion underscores the importance of continued research in these areas for developing effective,personalized therapies.

Prostaglandin D2 regulation of autophagy affects stemness of gastric cancer stem cells

Objective:To explore the effect and mechanism of prostaglandins D2(PGD2)on the stemness of gastric cancer stem cells(GCSCs).Methods:7901-GCSCs were enriched by serum-free culture method;then the positivity rate of CD44,a stemness marker,was detected by flow cytometry in serum-free cultured 7901-GCSCs;the sphere-forming ability was detected by the sphere-forming assay after stimulation with different concentrations of PGD2(2.5,5,10)μg/mL,and the expression of stemness-related indicators(OCT4,CD44)and autophagyrelated proteins(LC3,Beclin-1)after PGD2 stimulation was detected by the western blot assay in different concentrations.The expression of stemness-related indexes(OCT4,CD44)and autophagy-related proteins(LC3,Beclin-1)were detected by Western blot assay after stimulation with different concentrations of PGD2.The expression of autophagy-related proteins after stimulation with different concentrations of CQ(2.5,5,10)μM was detected by Western blot experiment.The protein expression of autophagy-related proteins(LC3,Beclin-1)and stemness-related indexes(OCT4,CD44)was detected by Western blot experiment after PGD2 as well as PGD2+CQ treatment.Results:Flow cytometry results showed that the expression of CD44 positivity was increased in serum-free cultured 7901-GCSCs compared with gastric cancer cells SGC-7901(P<0.05),which fulfilled the needs of subsequent experiments.The results of stem cell spheroid formation assay showed that the spheroid formation ability of 7901-GCSCs in the PGD2 group was significantly weakened compared with that of the DMSO group(P<0.05).Western blot results showed that the protein expression of stemness-related indexes(OCT4,CD44)was down-regulated in the 7901-GCSCs in the PGD2 group compared with that of the DMSO group(P<0.05),and the expression of autophagy-related proteins(LC3,Beclin-1)expression increased(P<0.05).Compared with the DMSO group,the expression of autophagy-related proteins(LC3,Beclin-1)was decreased in the CQ group(P<0.05).Western blot results also showed that the expression of cellular autophagy-related proteins and stemness-related indexes in the PGD2+CQ group was not significantly changed compared with that of the DMSO group(ns:the difference was not significant),suggesting that the CQ could block the effect of PGD2 on the expression of stemness markers in 7901-GCSCs.7901-GCSCs stemness inhibition.Conclusion:PGD2 may affect the stemness of 7901-GCSCs by regulating autophagy.

Role of immunotherapy in gastric cancer with liver metastasis

Gastric cancer continues to be a significant issue for public health,marked by its widespread occurrence and high mortality rates,even as the incidence of the disease shows a declining trend.The liver is the primary site for metastatic spread,with the peritoneum,lungs,and bones also being common targets.With the advent of biologic treatments and the introduction of immunotherapy for patients with metastatic conditions,the options to treat metastatic gastric cancer have expanded.This diversified therapeutic approach is designed to enhance patient quality of life and prolong survival,showcasing the progress in treatment modalities for individuals with gastric cancer and liver metastases.

Surgical treatment of liver cancer and pancreatic cancer under the China Healthcare Security Diagnosis Related Groups payment system

BACKGROUND Data from the World Health Organization’s International Agency for Research on Cancer reported that China had the highest prevalence of cancer and cancer deaths in 2022.Liver and pancreatic cancers accounted for the highest number of new cases.Real-world data(RWD)is now widely preferred to traditional clinical trials in various fields of medicine and healthcare,as the traditional research approach often involves highly selected populations and interventions and controls that are strictly regulated.Additionally,research results from the RWD match global reality better than those from traditional clinical trials.AIM To analyze the cost disparity between surgical treatments for liver and pancreatic cancer under various factors.METHODS This study analyzed RWD 1137 cases within the HB1 group(patients who underwent pancreatectomy,hepatectomy,and/or shunt surgery)in 2023.It distinguished different expenditure categories,including medical,nursing,technical,management,drug,and consumable costs.Additionally,it assessed the contribution of each expenditure category to total hospital costs and performed cross-group comparisons using the non-parametric Kruskal–Wallis test.This study used the Steel–Dwass test for post-hoc multiple comparisons and the Spearman correlation coefficient to examine the relationships between variables.RESULTS The study found that in HB11 and HB13,the total hospitalization costs were significantly higher for pancreaticoduodenectomy than for pancreatectomy and hepatectomy.Although no significant difference was observed in the length of hospital stay between patients who underwent pancreaticoduodenectomy and pancreatectomy,both were significantly longer than those who underwent liver resection.In HB15,no significant difference was observed in the total cost of hospitalization between pancreaticoduodenectomy and pancreatectomy;however,both were significantly higher than those in hepatectomy.Additionally,the length of hospital stay was significantly longer for patients who underwent pancreaticoduodenectomy than for those who underwent pancreatectomy or liver resection.CONCLUSION China Healthcare Security Diagnosis Related Groups payment system positively impacts liver and pancreatic cancer surgeries by improving medical quality and controlling costs.Further research could refine this grouping system and ensure continuous effectiveness and sustainability.

Limonin inhibits the stemness of cancer stem-like cells derived from colorectal carcinoma cells potentially via blocking STAT3 signaling

BACKGROUND Limonin is one of the most abundant active ingredients of Tetradium ruticarpum.It exerts antitumor effects on several kinds of cancer cells.However,whether limonin exerts antitumor effects on colorectal cancer(CRC)cells and cancer stem-like cells(CSCs),a subpopulation responsible for a poor prognosis,is unclear.AIM To evaluate the effects of limonin on CSCs derived from CRC cells.METHODS CSCs were collected by culturing CRC cells in serum-free medium.The cytotoxicity of limonin against CSCs and parental cells(PCs)was determined by cholecystokinin octapeptide-8 assay.The effects of limonin on stemness were detected by measuring stemness hallmarks and sphere formation ability.RESULTS As expected,limonin exerted inhibitory effects on CRC cell behaviors,including cell proliferation,migration,invasion,colony formation and tumor formation in soft agar.A relatively low concentration of limonin decreased the expression stemness hallmarks,including Nanog andβ-catenin,the proportion of aldehyde dehydrogenase 1-positive CSCs,and the sphere formation rate,indicating that limonin inhibits stemness without presenting cytotoxicity.Additionally,limonin treatment inhibited invasion and tumor formation in soft agar and in nude mice.Moreover,limonin treatment significantly inhibited the phosphorylation of STAT3 at Y705 but not S727 and did not affect total STAT3 expression.Inhibition of Nanog andβ-catenin expression and sphere formation by limonin was obviously reversed by pretreatment with 2μmol/L colievlin.CONCLUSION Taken together,these results indicate that limonin is a promising compound that targets CSCs and could be used to combat CRC recurrence and metastasis.

Exploring the Pivotal Association of AI in Cancer Stem Cells Detection and Treatment

Cancer stem cells(CSCs),or tumor-initiating cells(TICs),are cancerous cell subpopulations that remain while tumor cells propagate as a unique subset and exhibit multiple applications in several diseases.They are responsible for cancer cell initiation,development,metastasis,proliferation,and recurrence due to their self-renewal and differentiation abilities in many kinds of cells.Artificial intelligence(AI)has gained significant attention because of its vast applications in various fields including agriculture,healthcare,transportation,and robotics,particularly in detecting human diseases such as cancer.The division and metastasis of cancerous cells are not easy to identify at early stages due to their uncontrolled situations.It has provided some real-time pictures of cancer progression and relapse.The purpose of this review paper is to explore new investigations into the role of AI in cancer stem cell progression and metastasis and in regenerative medicines.It describes the association of machine learning and AI with CSCs along with its numerous applications from cancer diagnosis to therapy.This review has also provided key challenges and future directions of AI in cancer stem cell research diagnosis and therapeutic approach.

Targeting the mechano-microenvironment and liver cancer stem cells:a promising therapeutic strategy for liver cancer

Over the past 2 decades,cancer stem cells(CSCs)have been identified as the root cause of cancer occurrence,progression,chemoradioresistance,recurrence,and metastasis.Targeting CSCs is a novel therapeutic strategy for cancer management and treatment.Liver cancer(LC)is a malignant disease that can endanger human health.Studies are increasingly suggesting that changes in the liver mechanical microenvironment are a primary driver triggering the occurrence and development of liver cancer.In this review,we summarize current understanding of the roles of the liver mechano-microenvironment and liver cancer stem cells(LCSCs)in liver cancer progression.We also discuss the relationship between the mechanical heterogeneity of liver cancer tissues and LCSC recruitment and metastasis.Finally,we highlight potential mechanosensitive molecules in LCSCs and mechanotherapy in liver cancer.Understanding the roles and regulatory mechanisms of the mechano-microenvironment and LCSCs may provide fundamental insights into liver cancer progression and aid in further development of novel therapeutic strategies.

Deleted in liver cancer 1 suppresses the growth of prostate cancer cells through inhibiting Rho-associated protein kinase pathway

Objective:Deleted in liver cancer 1(DLC1)is a GTPase-activating protein that is reported as a suppressor in certain human cancers.However,the detailed biological function of DLC1 is still unclear in human prostate cancer(PCa).In the present study,we aimed to explore the function of DLC1 in PCa cells.Methods:Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line(LNCaP)using RNA interference and lentiviral vector transduction.The Cell Counting Kit-8 assay was performed to determine cell proliferation.The cell cycle was examined by performing a propidium iodide staining assay.Results:Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells.Moreover,DLC1 expression was negatively correlated with Rho-associated protein kinase(ROCK)expression in LNCaP cells.Importantly,this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo.Conclusion:Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.

Design and optimization of nano-antenna for thermal ablation of liver cancer cells

One method of cancer therapy is to utilize nano-antenna for thermal ablation.In this method,the electromagnetic waves emitted from the nano-antenna are absorbed by the tissue and lead to heating of cancer cells.If temperature of cancer cells reaches a threshold,they will begin to die.For this purpose,an L-shaped frame nano-antenna(LSFNA) is designed to introduce into the biological tissue.Thus,the radiation characteristics of the LSFNA such as near and far-field intensities,directivity,and sensitivity to its gap width are studied to the optimization of the nano-antenna.The bio-heat and Maxwell equations are solved using the finite element method.To prevent damage to healthy tissues in this method,the antenna radiation must be completely controlled and performed carefully.Thus,penetration depth,special absorption rate,temperature distribution,and the fraction of tissue necrosis are analyzed in the biological tissue.That is why the design and optimization of the nano-antennas as a radiation source is important.Also,a pulsed source is used to excite the LSFNA.Furthermore,focusing and efficiency of the nano-antenna radiation on the cancer cell is tuned using an adjustable liquid crystal lens.The focus of this lens is changing under an electric field applied to its surrounding cathode.

Inhibition of lung cancer stem cells self-renewal and tumorigenicity by lentivirus-delivered Bmi1 shRNA

Objective： The aim of the study was to observe the effect of Bmil reduction on the self-renewal and tumorigenicity ability of lung cancer stem cells （LCSCs） in human lung adenocarcinoma. Methods： Human lung adenocarcinoma cells A549 were consecutively passaged in NOD/SCID mice treated with Paclitaxel weekly. The proportions of LCSCs in A549 cells and the cells from the third passage （A549-3rd） were compared. The expression of Bmil in LCSCs was silenced by intratumoral injection with lentivirus-delivered Broil small hairpin RNA （shRNA）. RT-PCR and Western blot were used to test the mRNA and protein expressions of Broil in LCSCs. The protein level of p16INK4A was analyzed by Western blotting. The self- renewal and tumorigenicity ability of LCSCs were evaluated by counting the sphere formation rate in serum-free medium and the tumor formation rate in NOD/SCID mice. Results： In vivo passaging ofA549 cells under chemotherapy pressure enriched for LCSCs. The expression of Broil in LCSCs increased. Down-regulation of Bmil by RNA interference resulted in reduced self-renewal and tumorigenicity ability of LCSCs and paralleled the increased expression of p16INK4A, a Bmil target. Conclu- sion： Broil regulates self-renewal and tumorigenicity of LCSCs by silencing some target genes, including p16INK4A.