<strong>Introduction:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This study evaluated ...<strong>Introduction:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This study evaluated the difference in operative and clinica</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">l outc</span><span style="font-family:Verdana;">omes for patients with advanced ovarian cancer after primary debulking</span><span style="font-family:Verdana;"> surgery (PDS) versus neoadjuvant chemotherapy (NACT) followed by interval debul</span><span><span style="font-family:Verdana;">king surgery (IDS) in Bangladesh. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Sixty patients with a</span></span><span style="font-family:Verdana;">dvanced epit</span><span style="font-family:Verdana;">helial ovarian cancer presenting to the department of Gynaecologi</span><span style="font-family:Verdana;">cal Oncology at the National Institute of Cancer Research and Hospital were prospectively enrolled. Thirty patients underwent primary debulking surgery and thirty patients received NACT followed by IDS. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> In the PDS and IDS groups respectively, 56.7% and 50% of patients presented with stage IIIC and 67.7% and 56.7% respectively had ser</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">i</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ous papillary type histopathology. Duration of surgery, amount of blood loss and total hospital stay were significantly lower (p < 0.001) in IDS group than </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">in </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">the PDS group. There was a statistically significant difference in postoperative tumor residuals between IDS and PDS patients. Complete tumor resection (R0) was obtained in 24 (80%) of IDS patients versus 13 (43.3%) PDS patients. In fifteen months of follow-up, 21 (70%) in the PDS group and 5 (16.7%) in the IDS group recurred (</span><span style="font-family:Verdana;">p</span><span style="font-family:Verdana;"> = 0.021). Median progression free survival in PDS patients was twelve months while that of the IDS group was seventeen months. There was one death at 45 days in the PDS group. No other deaths were documented at fifteen months of follow-up. </span><b><span style="font-family:Verdana;">Conclusion</span></b></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Interval debulking surgery has a more favorable outcome than primary debulking surgery on progression free survival in advanced ovarian cancer patients </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">permits a less aggressive surgery to be performed in Bangladesh.</span></span></span>展开更多
Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve bette...Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.展开更多
BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics...BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.展开更多
The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the ...The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.展开更多
Small cell lung cancer(SCLC), which accounts for about one-sixth of all lung cancer cases, is the most aggressive subtype, with a high propensity for brain involvement[1]. The role of prophylactic cranial irradiation(...Small cell lung cancer(SCLC), which accounts for about one-sixth of all lung cancer cases, is the most aggressive subtype, with a high propensity for brain involvement[1]. The role of prophylactic cranial irradiation(PCI) in reducing intracranial relapse and improving survival has been a subject of intense debate for decades.展开更多
Objectives:Although standardized residency trainees are at high risk for depression,anxiety,and suicidal ideation,the psychological pathways connecting depression and anxiety to suicidal ideation,especially the modera...Objectives:Although standardized residency trainees are at high risk for depression,anxiety,and suicidal ideation,the psychological pathways connecting depression and anxiety to suicidal ideation,especially the moderating role of resilience,remain elusive.This study aimed to examine the associations between depression,anxiety,and suicidal ideation among physicians undergoing standardized residency training,and to investigate the moderating roles of different dimensions of individual resilience,namely tenacity,strength,and optimism.Methods:A convenience sampling method was adopted to recruit 133 resident physicians.Validated instruments assessing individual resilience,depressive symptoms,anxiety levels,and suicidal ideation were administered.Spearman correlation analysis was used to evaluate the relationships among the variables.Hierarchical regression analysis was conducted to assess the moderating roles of tenacity,strength,and optimism in the associations between depression,anxiety,and suicidal ideation.Results:Depressive symptoms and anxiety levels were both positively associated with suicidal ideation(p<0.001).All three resilience dimensions were negatively correlated with suicidal ideation(tenacity:r=−0.504,strength:r=−0.477,optimism:r=−0.440,all p<0.001).Tenacity,strength,and optimism significantly moderated the associations between depression and suicidal ideation(all p<0.05).When resilience levels in these dimensions were high,the associations between depression and suicidal ideation were weaker.Strength and optimism also moderated the associations between anxiety and suicidal ideation(strength:p=0.028,optimism:p=0.028).When the resiliences(strength and optimism)were high,the associations between anxiety and suicidal ideation were weaker.Conclusion:Individual resilience,particularly in the dimensions of tenacity,strength,and optimism,may serve as protective correlates for physicians in training,being associated with weaker relationships between depression,anxiety,and suicidal ideation.These findings highlight the potential value of resilience-enhancing strategies in clinical training settings,although causal inferences cannot be drawn due to the cross-sectional design.展开更多
Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh...Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.展开更多
Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significant...Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.展开更多
Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres e...Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer ceils express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the selfrenewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.展开更多
AIM:To investigate the role of the overexpression of B7-H3 in apoptosis in colorectal cancer cell lines and the underlying molecular mechanisms.METHODS:SW620 cells that highly overexpressed B7-H3(SW620-B7-H3-EGFP)and ...AIM:To investigate the role of the overexpression of B7-H3 in apoptosis in colorectal cancer cell lines and the underlying molecular mechanisms.METHODS:SW620 cells that highly overexpressed B7-H3(SW620-B7-H3-EGFP)and HCT8 cells stably transfected with B7-H3 sh RNA(HCT8-sh B7-H3)were previously constructed in our laboratory.Cells transfected with p IRES2-EGFP were used as negative controls(SW620-NC and HCT8-NC).Real-time PCR and western blotting analysis were used to detect the m RNA and protein expressions of the apoptosis regulator proteins Bcl-2,Bcl-xl and Bax.A cell proliferation assay was used to evaluate the survival rate and drug sensitivity of the cells.The effect of drug resistance was detected by a cell cycle assay.Active caspase-3western blotting was used to reflect the anti-apoptotic ability of cells.Western blotting was also performed to determine the expression of proteins associated with the Jak2-STAT3 signaling pathway and the apoptosis regulator proteins after the treatment with AG490,a Jak2 specific inhibitor,in B7-H3 overexpressing cells.The data were analyzed by Graph Pad Prism 6 using a non-paired t-test.RESULTS:Whether by overexpression in SW620cells or downregulation in HCT8,B7-H3 significantly affected the expression of anti-and pro-apoptotic proteins,at both the transcriptional and translational levels,compared with the negative control(P<0.05).A cell proliferation assay revealed that B7-H3overexpression increased the drug resistance of cells and resulted in a higher survival rate(P<0.05).In addition,the results of cell cycle and active caspase-3western blotting proved that B7-H3 overexpression inhibited apoptosis in colorectal cancer cell lines(P<0.05).B7-H3 overexpression improved Jak2 and STAT3phosphorylation and,in turn,increased the expression of the downstream anti-apoptotic proteins B-cell CLL/lymphoma 2(Bcl-2)and Bcl-xl,based on western blotting(P<0.05).After treating B7-H3 overexpressing cells with the Jak2-specific inhibitor AG490,the phosphorylation of Jak2 and STAT3,and the expression of Bcl-2 and Bcl-xl,decreased accordingly(P<0.05).This finding suggested that the Jak2-STAT3 pathway is involved in the mechanism mediating the anti-apoptotic ability of B7-H3.CONCLUSION:The overexpression of B7-H3 induces resistance to apoptosis in colorectal cancer cell lines by upregulating the Jak2-STAT3 signaling pathway,potentially providing new approaches to the treatment of colorectal cancer.展开更多
AIM： To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on esophageal cancer susceptibility in Southeast Chinese males.METHODS： Two hundred and twenty-one...AIM： To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on esophageal cancer susceptibility in Southeast Chinese males.METHODS： Two hundred and twenty-one esophageal cancer patients and 292 healthy controls from Taixing city in Jiangsu Province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase chain reaction and denaturing high-performance liquid chromatography. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （CI）.RESULTS： The ADH G allele carriers were more susceptible to esophageal cancer, but no association was found between ADH2 genotypes and risk of esophageal cancer when disregarding alcohol drinking status. Regardless of ADH2 genotype, ALDH2G/A or A/A carriers had significantly increased risk of developing esophageal cancer, with homozygous individuals showing higher esophageal cancer risk than those who were heterozygous. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk; the OR was 3.05 （95% CI： 2.49-6.25）. Compared with non-drinkers carrying both ALDH2 G/G and ADH2 A/A, drinkers carrying both ALDH2 A allele and ADH2 G allele showed a significantly higher risk of developing esophageal cancer （OR = 8.36, 95% CI： 2.98-23.46）.CONCLUSION： Both ADH2 G allele and ALDH2 A allele significantly increase the risk of esophageal cancer development in Southeast Chinese males. ALDH2 A allele significantly increases the risk of esophageal cancer development especially in alcohol drinkers. Alcohol drinkers carrying both ADH2 G allele and ALDH2 A allele have a higher risk of developing esophageal cancer.展开更多
Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, ...Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective(cell survival), cytotoxic(cell death), cytostatic(growth arrest), and nonprotective(no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental.That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.展开更多
One of the strongest risk factors for prostate cancer is a family history of the disease. Germline mutations in the breast cancer predisposition gene 2 （BRCA2） are the genetic events known to date that confer the hi...One of the strongest risk factors for prostate cancer is a family history of the disease. Germline mutations in the breast cancer predisposition gene 2 （BRCA2） are the genetic events known to date that confer the highest risk of prostate cancer （8.6-fold in men ≤ 65 years）. Although the role of BRCA2 and BRCA1 in prostate tumorigenesis remains unrevealed, deleterious mutations in both genes have been associated with more aggressive disease and poor clinical outcomes. The increasing incidence of prostate cancer worldwide supports the need for new methods to predict outcome and identify patients with potentially lethal forms of the disease. As we present here, BRCA germline mutations, mainly in the BRCA2gene, are one of those predictive factors. We will also discuss the implications of these mutations in the management of prostate cancer and hypothesize on the potential for the development of strategies for sooradic cases with similar characteristics.展开更多
Non-small cell lung cancer(NSCLC)accounts for about 85%of all lung cancer cases.The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs,such as long non-coding RNAs(lnc...Non-small cell lung cancer(NSCLC)accounts for about 85%of all lung cancer cases.The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs,such as long non-coding RNAs(lnc RNAs).The role of lnc RNAs in NSCLC is gaining an increasing interest as their function is being explored in various human cancers.Recently,a new oncogenic lnc RNA,LINC00152(cytoskeleton regulator RNA(CYTOR)),has been identified in different tumor types.In NSCLC,the high expression of LINC00152 in tumor tissue and peripheral blood samples has been shown to be associated with worse prognoses of NSCLC patients.Overexpression of LINC00152 has been confirmed to promote the proliferation,invasion,and migration of NSCLC cells in vitro,as well as increase tumor growth in vivo.This review discusses the role of LINC00152 in NSCLC.展开更多
AIM To investigate the expression and clinical significance of B7 homolog 3(B7-H3) and β-1,3-galactosyltransferase-4(B3 GALT4) in colorectal cancer(CRC) patients.METHODS Using tissue microarray, we identified the exp...AIM To investigate the expression and clinical significance of B7 homolog 3(B7-H3) and β-1,3-galactosyltransferase-4(B3 GALT4) in colorectal cancer(CRC) patients.METHODS Using tissue microarray, we identified the expression of B7-H3 and B3 GALT4 in 223 CRC patient samples by immunohistochemistry and evaluated the possible correlation between B7-H3 and B3 GALT4 and clinicaloutcomes. Further, the m RNA and protein expression were identified to establish the regulatory relationship of B7-H3 with B3 GALT4 in vitro.RESULTS A significant positive correlation between B7-H3 and B3 GALT4 was observed in CRC specimens(r = 0.219, P = 0.001). High expression of B7-H3 was identified as a significant independent predictor of poor overall survival(OS) [hazard ratio(HR) = 1.781; 95%CI: 1.027-3.089; P = 0.040]. Moreover, high expression of B3 GALT4 was also recognized as an independent predictor of inferior OS(HR = 1.597; 95%CI: 1.007-2.533; P = 0.047). Additionally, CRC patients expressing both high B7-H3 and high B3 GALT4 contributed to a significant decrease in OS(HR = 2.283; 95%CI: 1.289-4.042; P = 0.005). In CRC cell lines with stable expression of high B7-H3, the m RNA and protein expressions of B3 GALT4 were significantly upregulated. Similarly, the expression of B3 GALT4 was significantly reduced when expression of B7-H3 was knocked down.CONCLUSION The expression of B3 GALT4 in CRC is positively correlated with B7-H3 expression in vitro. B7-H3/B3 GLAT4 may be used as dual prognostic biomarkers for CRC.展开更多
RNA interference(RNAi)has become a gold standard for validating gene function in basic life science research and provides a promising therapeutic modality for cancer and other diseases.This minireview focuses on the p...RNA interference(RNAi)has become a gold standard for validating gene function in basic life science research and provides a promising therapeutic modality for cancer and other diseases.This minireview focuses on the potential of small interfering RNAs(siRNAs)in anticancer treatment,including the establishment and screening of cancer-associated siRNA libraries and their applications in anticancer drug target discovery and cancer therapy.This article also describes the current delivery approaches of siRNAs using lipids,polymers,and,in particular,gold nanoparticles to induce significant gene silencing and tumor growth regression.展开更多
BACKGROUND Recent evidence showed that combining endoscopic submucosal dissection(ESD)and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer(EMGC)pa...BACKGROUND Recent evidence showed that combining endoscopic submucosal dissection(ESD)and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer(EMGC)patients with risks of positive lymph node metastasis(pLNM).AIM To explore the predictive factors for pLNM in EMGC,and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC.METHODS Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016.Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors,providing odds ratio(OR)with 95%confidence interval.And the association between the number of predictors and the pLNM rate was also investigated.RESULTS Depth of invasion(OR=7.342,1.127-33.256,P=0.039),tumor diameter(OR=9.158,1.348-29.133,P=0.044),and lymphatic vessel involvement(OR=27.749,1.821-33.143,P=0.019)turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis.For patients with 1,2,and 3 risk factors,the pLNM rates were 9.1%,33.3%,and 75.0%,respectively.pLNM was not detected in seven patients without any of these risk factors.CONCLUSION ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size≤2 cm,and when lymphatic vessel involvement is absent by postoperative histological examination.Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.展开更多
While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We co...While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index（BMI）, lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics（FIGO） grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age,BMI, triglyceride（TG）, and high density lipoproteins（HDL） differed significantly among different stages of epithelial ovarian cancer（P〈0.05）. In the logistic regression model, elevated TG（OR： 1.883; 95% CI= 1.207-2.937）, and low HDL（OR： 0.497; 95% CI = 0.298-0.829） levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.展开更多
Objective In recent years, the rising incidence of cancer has increased patients’ living and economic burdens. This study analyzed the incidence and death due to malignant tumors in tumor registries in Heilongjiang p...Objective In recent years, the rising incidence of cancer has increased patients’ living and economic burdens. This study analyzed the incidence and death due to malignant tumors in tumor registries in Heilongjiang province (China) in 2015 to provide a scientific basis for the prevention and treatment of malignant tumors in this province. Methods Data on tumor incidence and patient deaths were collected from seven tumor registries in Heilongjiang province (China) in 2015. According to the stratification of urban and rural areas and patient sex, the crude, standard, and accumulative rates (0–74 years of age) were calculated. The 2000 China Population Census data and Segi’s standard population were used to calculate the age-standardized rates. Results In 2015, the incidence rate of malignant tumors in Heilongjiang cancer registries was 259.90/100 000. The age-standardized incidence rates in the Chinese and world standard populations were 158.89/100 000 and 155.06/100 000, respectively, with a cumulative incidence rate (0–74 years) of 17.68%. The incidence of malignant tumors in urban areas was 273.55/100 000, while that in rural areas was 220.32/100 000. The incidence of malignant tumors in men was 270.89/100 000, higher than that in women (249.04/100 000). Lung cancer had the highest incidence, followed by breast cancer, liver cancer, colorectal cancer, and thyroid cancer. The mortality rate of malignant tumors in Heilongjiang cancer registries was 164.69/100 000. The age-standardized mortality rates in Chinese and in world standard populations were 95.29/100 000 and 94.35/100 000, respectively, with a cumulative mortality rate (0–74 years) of 10.44%. The mortality rate of malignant tumors in urban areas was 169.51/100 000, while that in rural areas was 150.72/100 000. The mortality rate of malignant tumors in men was 201.64/100 000, higher than that in women (128.21/100 000). Lung cancer had the highest mortality, followed by liver cancer, stomach cancer, colorectal cancer, and breast cancer. Conclusion Lung, liver, breast, and colorectal cancers were the most common cancers in Heilongjiang province, China, and should be considered the key cancer types for prevention and treatment. Moreover, the incidence of thyroid cancer is increasing, and thus early preventative measures should be implemented.展开更多
As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of ...As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.展开更多
文摘<strong>Introduction:</strong><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> This study evaluated the difference in operative and clinica</span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">l outc</span><span style="font-family:Verdana;">omes for patients with advanced ovarian cancer after primary debulking</span><span style="font-family:Verdana;"> surgery (PDS) versus neoadjuvant chemotherapy (NACT) followed by interval debul</span><span><span style="font-family:Verdana;">king surgery (IDS) in Bangladesh. </span><b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> Sixty patients with a</span></span><span style="font-family:Verdana;">dvanced epit</span><span style="font-family:Verdana;">helial ovarian cancer presenting to the department of Gynaecologi</span><span style="font-family:Verdana;">cal Oncology at the National Institute of Cancer Research and Hospital were prospectively enrolled. Thirty patients underwent primary debulking surgery and thirty patients received NACT followed by IDS. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> In the PDS and IDS groups respectively, 56.7% and 50% of patients presented with stage IIIC and 67.7% and 56.7% respectively had ser</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">i</span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">ous papillary type histopathology. Duration of surgery, amount of blood loss and total hospital stay were significantly lower (p < 0.001) in IDS group than </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">in </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">the PDS group. There was a statistically significant difference in postoperative tumor residuals between IDS and PDS patients. Complete tumor resection (R0) was obtained in 24 (80%) of IDS patients versus 13 (43.3%) PDS patients. In fifteen months of follow-up, 21 (70%) in the PDS group and 5 (16.7%) in the IDS group recurred (</span><span style="font-family:Verdana;">p</span><span style="font-family:Verdana;"> = 0.021). Median progression free survival in PDS patients was twelve months while that of the IDS group was seventeen months. There was one death at 45 days in the PDS group. No other deaths were documented at fifteen months of follow-up. </span><b><span style="font-family:Verdana;">Conclusion</span></b></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><b><span style="font-family:Verdana;">:</span></b></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">Interval debulking surgery has a more favorable outcome than primary debulking surgery on progression free survival in advanced ovarian cancer patients </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">and </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">permits a less aggressive surgery to be performed in Bangladesh.</span></span></span>
基金funded by the National Natural Science Foundation of China(grant no.82273162)the National Natural Science Foundation of China(grant no.82203272)the Science and Technology Development Foundation of Nanjing Medical University(grant NMUB20240119)。
文摘Objective:To determine whether immunotherapy can bring new hope for patients with limited-stage small-cell lung cancer(LS-SCLC).We conducted this retrospective study to evaluate whether immunotherapy can achieve better efficacy in LS-SCLC patients.Methods:We evaluated 122 LS-SCLC patients who received concurrent chemoradiotherapy(CCRT)or sequential chemoradiotherapy(SCRT)(Group A)and immunotherapy combined with CCRT/SCRT followed by immunotherapy(Group B),to assess the objective response rate(ORR),disease control rate(DCR),and progression-free survival(PFS).Factors affecting prognosis were also explored using Cox analysis.The prognosis of patients with type 2 diabetes and patients with different TNM stages was compared to guide the selection of clinical regimens.Results:The overall ORR was 55.93%.The overall DCR was 98.31%.The DCR was 100%in Group A and 96.61%in Group B.There was no statistical difference in ORR and DCR.The overall median PFS was 9.86 months(95%CI,8.62-11.10),and the difference in median PFS between the two groups was statistically significant(8.94 vs.11.89 months,p=0.03).The Cox regression analysis showed type 2 diabetes was associated with the survival prognosis.Patients with type 2 diabetes tended to choose immunotherapy combined with CCRT/SCRT.Patients in TNM stage IIIB had a significantly worse prognosis than those in stage I+II+IIIA.Conclusion:We suggest that LS-SCLC patients who receive immunotherapy combined with CCRT/SCRT can achieve longer PFS than those with CCRT/SCRT.Type 2 diabetes and TNM stage affect the survival prognosis.Patients with type 2 diabetes may benefit from immunotherapy combination treatments.
基金National Natural Science Foundation of China,No.82003223and China Postdoctoral Science Foundation,No.2020M671398.
文摘BACKGROUND Gastric cancer(GC)is one of the most common malignant tumors of the digestive system worldwide,the prognosis of patients with advanced GC remains poor.AIM To evaluate the combined expression characteristics of cancer stem cell markers CD24 and CD133 in GC pathological tissues,and to explore their association with patients’clinicopathological parameters and postoperative survival outcomes.METHODS A total of 304 GC patients who underwent surgical treatment in our hospital from January 2018 to January 2020 were retrospectively included.Immunohistochemistry was used to detect the protein expression of CD24 and CD133 in tumor tissues,adjacent tissues,and normal gastric mucosa tissues.Based on staining intensity and the proportion of positive cells,expression levels were classified into low and high expression,while clinicopathological parameters were recorded.χ2 test was used to evaluate the correlation between expression and categorical variables,Spearman rank correlation analysis was performed to assess the correlation between the expression intensities of the two markers,and multivariate regression models were applied to identify independent risk factors influencing co-expression.Kaplan-Meier survival curves and Log-rank test were used to compare survival differences among groups with different expression patterns.RESULTS Among the 304 patients,155 cases(50.99%)were CD24 positive,including 91 low-expression and 64 highexpression;133 cases(43.75%)were CD133 positive,including 81 low-expression and 52 high-expression.There were 74 cases(24.34%)with double positivity and 81 cases(26.64%)with double negativity.Compared with tumor tissues,the positive rates of CD24 and CD133 in normal gastric tissues and adjacent tissues were significantly lower(P<0.05).Univariate analysis showed that co-expression of CD24 and CD133 in GC tissues was significantly correlated with tumor size,Lauren classification,T stage,N stage,and vascular invasion(P<0.05),but not with patient age,gender,tumor site,World Health Organization histological classification,or M stage(P>0.05).Further multivariate regression analysis suggested that tumor size,T stage,N stage,and vascular invasion were independent risk factors promoting CD24 and CD133 double positivity.Spearman rank correlation analysis indicated a moderate positive correlation between their expression intensities(r=0.420,P<0.001).During follow-up,29 of 304 patients were lost(loss rate 9.54%);146 deaths occurred.According to expression combination,there were 89 cases of CD24 single positivity(39 deaths),68 cases of CD133 single positivity(31 deaths),81 cases of double negativity(25 deaths),and 66 cases of double positivity(51 deaths).Log-rank test showed significant differences in overall survival among the four groups(χ2=20.89,P<0.001),with CD24+/CD133+group showing the worst prognosis.CONCLUSION CD24 and CD133 exhibit high positive detection rates in GC tissues,and their co-positivity is closely associated with tumor stage progression and significantly indicates unfavorable survival outcomes.The co-expression of CD24/CD133 may reflect higher aggressiveness and metastatic potential of GC,serving as a potential prognostic marker and a direction for targeted therapeutic strategies.However,as this is a single-center retrospective study with limitations such as patient loss to follow-up and sample size,further prospective,multicenter,and mechanistic studies are required to validate its clinical applicability and biological role.
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(Grant No.QL201802)the Science and Technology Development Fund of Jiangsu Cancer Hospital(Grant No.ZL202105).
文摘The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.
文摘Small cell lung cancer(SCLC), which accounts for about one-sixth of all lung cancer cases, is the most aggressive subtype, with a high propensity for brain involvement[1]. The role of prophylactic cranial irradiation(PCI) in reducing intracranial relapse and improving survival has been a subject of intense debate for decades.
基金supported by Jiangsu Cancer Hospital Science and Technology Development Fund Project(NO.XHMS202404)Nanjing Medical Science and Technology Development Fund Project(GBX22289).
文摘Objectives:Although standardized residency trainees are at high risk for depression,anxiety,and suicidal ideation,the psychological pathways connecting depression and anxiety to suicidal ideation,especially the moderating role of resilience,remain elusive.This study aimed to examine the associations between depression,anxiety,and suicidal ideation among physicians undergoing standardized residency training,and to investigate the moderating roles of different dimensions of individual resilience,namely tenacity,strength,and optimism.Methods:A convenience sampling method was adopted to recruit 133 resident physicians.Validated instruments assessing individual resilience,depressive symptoms,anxiety levels,and suicidal ideation were administered.Spearman correlation analysis was used to evaluate the relationships among the variables.Hierarchical regression analysis was conducted to assess the moderating roles of tenacity,strength,and optimism in the associations between depression,anxiety,and suicidal ideation.Results:Depressive symptoms and anxiety levels were both positively associated with suicidal ideation(p<0.001).All three resilience dimensions were negatively correlated with suicidal ideation(tenacity:r=−0.504,strength:r=−0.477,optimism:r=−0.440,all p<0.001).Tenacity,strength,and optimism significantly moderated the associations between depression and suicidal ideation(all p<0.05).When resilience levels in these dimensions were high,the associations between depression and suicidal ideation were weaker.Strength and optimism also moderated the associations between anxiety and suicidal ideation(strength:p=0.028,optimism:p=0.028).When the resiliences(strength and optimism)were high,the associations between anxiety and suicidal ideation were weaker.Conclusion:Individual resilience,particularly in the dimensions of tenacity,strength,and optimism,may serve as protective correlates for physicians in training,being associated with weaker relationships between depression,anxiety,and suicidal ideation.These findings highlight the potential value of resilience-enhancing strategies in clinical training settings,although causal inferences cannot be drawn due to the cross-sectional design.
基金supported by research grants from the Ministry of Science and Technology(MOST 108-2314-B-400-026 and 109-2013-B-400-036)National Science and Technology Council(NSTC 112-2320-B-214-010 and 113-2320-B-214-002)+1 种基金I-Shou University(ISU-112-01-12A,ISU112-S-02 and ISU114-S-04)National Health Research Institutes,Taiwan(CA-111-PP-19).
文摘Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.
文摘Alterations in the mesenchymal-epithelial transition factor(MET)gene are critical drivers of non-small cell lung cancer(NSCLC).In recent years advances in precision therapies targeting MET alterations have significantly expanded treatment options for NSCLC patients.These alterations include MET exon 14 skipping mutations(MET exon 14 skipping),MET gene amplifications,MET point mutations(primarily kinase domain mutations),and MET protein overexpression.Accurate identification of these alterations and appropriate selection of patient populations and targeted therapies are essential for improving clinical outcomes.The East China Lung Cancer Group,Youth Committee(ECLUNG YOUNG,Yangtze River Delta Lung Cancer Cooperation Group)has synthesized insights from China’s innovative drug development landscape and clinical practice to formulate an expert consensus on the diagnosis and treatment of NSCLC patients with MET alterations.This consensus addresses key areas,such as optimal testing timing,testing methods,testing strategies,quality control measures,and treatment approaches.By offering standardized recommendations,this guidance aims to streamline diagnostic and therapeutic processes and enhance clinical decision-making for NSCLC with MET alterations.
文摘Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer ceils express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the selfrenewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.
基金Supported by Project of Natural Science Foundation of Jiangsu Province,No.BK2012542the Project of Hospital Management Center of Wuxi City,No.YGZ1108
文摘AIM:To investigate the role of the overexpression of B7-H3 in apoptosis in colorectal cancer cell lines and the underlying molecular mechanisms.METHODS:SW620 cells that highly overexpressed B7-H3(SW620-B7-H3-EGFP)and HCT8 cells stably transfected with B7-H3 sh RNA(HCT8-sh B7-H3)were previously constructed in our laboratory.Cells transfected with p IRES2-EGFP were used as negative controls(SW620-NC and HCT8-NC).Real-time PCR and western blotting analysis were used to detect the m RNA and protein expressions of the apoptosis regulator proteins Bcl-2,Bcl-xl and Bax.A cell proliferation assay was used to evaluate the survival rate and drug sensitivity of the cells.The effect of drug resistance was detected by a cell cycle assay.Active caspase-3western blotting was used to reflect the anti-apoptotic ability of cells.Western blotting was also performed to determine the expression of proteins associated with the Jak2-STAT3 signaling pathway and the apoptosis regulator proteins after the treatment with AG490,a Jak2 specific inhibitor,in B7-H3 overexpressing cells.The data were analyzed by Graph Pad Prism 6 using a non-paired t-test.RESULTS:Whether by overexpression in SW620cells or downregulation in HCT8,B7-H3 significantly affected the expression of anti-and pro-apoptotic proteins,at both the transcriptional and translational levels,compared with the negative control(P<0.05).A cell proliferation assay revealed that B7-H3overexpression increased the drug resistance of cells and resulted in a higher survival rate(P<0.05).In addition,the results of cell cycle and active caspase-3western blotting proved that B7-H3 overexpression inhibited apoptosis in colorectal cancer cell lines(P<0.05).B7-H3 overexpression improved Jak2 and STAT3phosphorylation and,in turn,increased the expression of the downstream anti-apoptotic proteins B-cell CLL/lymphoma 2(Bcl-2)and Bcl-xl,based on western blotting(P<0.05).After treating B7-H3 overexpressing cells with the Jak2-specific inhibitor AG490,the phosphorylation of Jak2 and STAT3,and the expression of Bcl-2 and Bcl-xl,decreased accordingly(P<0.05).This finding suggested that the Jak2-STAT3 pathway is involved in the mechanism mediating the anti-apoptotic ability of B7-H3.CONCLUSION:The overexpression of B7-H3 induces resistance to apoptosis in colorectal cancer cell lines by upregulating the Jak2-STAT3 signaling pathway,potentially providing new approaches to the treatment of colorectal cancer.
基金Supported by Grant from Department of Health,No.H200526,Jiangsu Province,China
文摘AIM： To evaluate the impact of alcohol dehydrogenase-2 （ADH2） and aldehyde dehydrogenase-2 （ALDH2） polymorphisms on esophageal cancer susceptibility in Southeast Chinese males.METHODS： Two hundred and twenty-one esophageal cancer patients and 292 healthy controls from Taixing city in Jiangsu Province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by polymerase chain reaction and denaturing high-performance liquid chromatography. Unconditional logistic regression was used to calculate the odds ratios （OR） and 95% confidence interval （CI）.RESULTS： The ADH G allele carriers were more susceptible to esophageal cancer, but no association was found between ADH2 genotypes and risk of esophageal cancer when disregarding alcohol drinking status. Regardless of ADH2 genotype, ALDH2G/A or A/A carriers had significantly increased risk of developing esophageal cancer, with homozygous individuals showing higher esophageal cancer risk than those who were heterozygous. A significant interaction between ALDH2 and drinking was detected regarding esophageal cancer risk; the OR was 3.05 （95% CI： 2.49-6.25）. Compared with non-drinkers carrying both ALDH2 G/G and ADH2 A/A, drinkers carrying both ALDH2 A allele and ADH2 G allele showed a significantly higher risk of developing esophageal cancer （OR = 8.36, 95% CI： 2.98-23.46）.CONCLUSION： Both ADH2 G allele and ALDH2 A allele significantly increase the risk of esophageal cancer development in Southeast Chinese males. ALDH2 A allele significantly increases the risk of esophageal cancer development especially in alcohol drinkers. Alcohol drinkers carrying both ADH2 G allele and ALDH2 A allele have a higher risk of developing esophageal cancer.
基金supported by the National Natural Science Foundation of China(No.81903642)the China Postdoctoral Science Foundation(No.2020M681528)+3 种基金the Postdoctoral Science Foundation of Jiangsu Province(No.2021K369C)the Jiangsu Cancer Hospital Postdoctoral Science Foundation(No.SZL202015)the Basic Scientific Research Business Expense Project of China Pharmaceutical University(No.2632021ZD07)the Project Funded by the Priority Academic Program Development(PADP)of Jiangsu Higher Education Institutions,China。
文摘Cancer is the leading cause of death worldwide. Drugs play a pivotal role in cancer treatment, but the complex biological processes of cancer cells seriously limit the efficacy of various anticancer drugs. Autophagy, a self-degradative system that maintains cellular homeostasis, universally operates under normal and stress conditions in cancer cells. The roles of autophagy in cancer treatment are still controversial because both stimulation and inhibition of autophagy have been reported to enhance the effects of anticancer drugs. Thus, the important question arises as to whether we should try to strengthen or suppress autophagy during cancer therapy. Currently, autophagy can be divided into four main forms according to its different functions during cancer treatment: cytoprotective(cell survival), cytotoxic(cell death), cytostatic(growth arrest), and nonprotective(no contribution to cell death or survival). In addition, various cell death modes, such as apoptosis, necrosis, ferroptosis, senescence, and mitotic catastrophe, all contribute to the anticancer effects of drugs. The interaction between autophagy and these cell death modes is complex and can lead to anticancer drugs having different or even completely opposite effects on treatment. Therefore, it is important to understand the underlying contexts in which autophagy inhibition or activation will be beneficial or detrimental.That is, appropriate therapeutic strategies should be adopted in light of the different functions of autophagy. This review provides an overview of recent insights into the evolving relationship between autophagy and cancer treatment.
文摘One of the strongest risk factors for prostate cancer is a family history of the disease. Germline mutations in the breast cancer predisposition gene 2 （BRCA2） are the genetic events known to date that confer the highest risk of prostate cancer （8.6-fold in men ≤ 65 years）. Although the role of BRCA2 and BRCA1 in prostate tumorigenesis remains unrevealed, deleterious mutations in both genes have been associated with more aggressive disease and poor clinical outcomes. The increasing incidence of prostate cancer worldwide supports the need for new methods to predict outcome and identify patients with potentially lethal forms of the disease. As we present here, BRCA germline mutations, mainly in the BRCA2gene, are one of those predictive factors. We will also discuss the implications of these mutations in the management of prostate cancer and hypothesize on the potential for the development of strategies for sooradic cases with similar characteristics.
基金Project supported by the Health Technology Innovation Project of Jilin Province(No.2017J025),China.
文摘Non-small cell lung cancer(NSCLC)accounts for about 85%of all lung cancer cases.The pathogenesis of NSCLC involves complex gene networks that include different types of non-coding RNAs,such as long non-coding RNAs(lnc RNAs).The role of lnc RNAs in NSCLC is gaining an increasing interest as their function is being explored in various human cancers.Recently,a new oncogenic lnc RNA,LINC00152(cytoskeleton regulator RNA(CYTOR)),has been identified in different tumor types.In NSCLC,the high expression of LINC00152 in tumor tissue and peripheral blood samples has been shown to be associated with worse prognoses of NSCLC patients.Overexpression of LINC00152 has been confirmed to promote the proliferation,invasion,and migration of NSCLC cells in vitro,as well as increase tumor growth in vivo.This review discusses the role of LINC00152 in NSCLC.
基金Supported by the Natural Science Foundation of Jiangsu Province,No.BK20171150the National Natural Science Foundation of China,No.81502042
文摘AIM To investigate the expression and clinical significance of B7 homolog 3(B7-H3) and β-1,3-galactosyltransferase-4(B3 GALT4) in colorectal cancer(CRC) patients.METHODS Using tissue microarray, we identified the expression of B7-H3 and B3 GALT4 in 223 CRC patient samples by immunohistochemistry and evaluated the possible correlation between B7-H3 and B3 GALT4 and clinicaloutcomes. Further, the m RNA and protein expression were identified to establish the regulatory relationship of B7-H3 with B3 GALT4 in vitro.RESULTS A significant positive correlation between B7-H3 and B3 GALT4 was observed in CRC specimens(r = 0.219, P = 0.001). High expression of B7-H3 was identified as a significant independent predictor of poor overall survival(OS) [hazard ratio(HR) = 1.781; 95%CI: 1.027-3.089; P = 0.040]. Moreover, high expression of B3 GALT4 was also recognized as an independent predictor of inferior OS(HR = 1.597; 95%CI: 1.007-2.533; P = 0.047). Additionally, CRC patients expressing both high B7-H3 and high B3 GALT4 contributed to a significant decrease in OS(HR = 2.283; 95%CI: 1.289-4.042; P = 0.005). In CRC cell lines with stable expression of high B7-H3, the m RNA and protein expressions of B3 GALT4 were significantly upregulated. Similarly, the expression of B3 GALT4 was significantly reduced when expression of B7-H3 was knocked down.CONCLUSION The expression of B3 GALT4 in CRC is positively correlated with B7-H3 expression in vitro. B7-H3/B3 GLAT4 may be used as dual prognostic biomarkers for CRC.
文摘RNA interference(RNAi)has become a gold standard for validating gene function in basic life science research and provides a promising therapeutic modality for cancer and other diseases.This minireview focuses on the potential of small interfering RNAs(siRNAs)in anticancer treatment,including the establishment and screening of cancer-associated siRNA libraries and their applications in anticancer drug target discovery and cancer therapy.This article also describes the current delivery approaches of siRNAs using lipids,polymers,and,in particular,gold nanoparticles to induce significant gene silencing and tumor growth regression.
文摘BACKGROUND Recent evidence showed that combining endoscopic submucosal dissection(ESD)and laparoscopic sentinel lymph node dissection may avoid unnecessary gastrectomy in treating early mucinous gastric cancer(EMGC)patients with risks of positive lymph node metastasis(pLNM).AIM To explore the predictive factors for pLNM in EMGC,and to optimize the clinical application of combing ESD and sentinel lymph node dissection in a proper subgroup of patients with EMGC.METHODS Thirty-one patients with EMGC who had undergone gastrectomy with lymph node dissection were consecutively enrolled from January 1988 to December 2016.Univariate and multivariate logistic regression analyses were used to estimate the association between the rates of pLNM and clinicopathological factors,providing odds ratio(OR)with 95%confidence interval.And the association between the number of predictors and the pLNM rate was also investigated.RESULTS Depth of invasion(OR=7.342,1.127-33.256,P=0.039),tumor diameter(OR=9.158,1.348-29.133,P=0.044),and lymphatic vessel involvement(OR=27.749,1.821-33.143,P=0.019)turned out to be significant and might be the independent risk factors for predicating pLNM in the multivariate analysis.For patients with 1,2,and 3 risk factors,the pLNM rates were 9.1%,33.3%,and 75.0%,respectively.pLNM was not detected in seven patients without any of these risk factors.CONCLUSION ESD might serve as a safe and sufficient treatment for intramucosal EMGC if tumor size≤2 cm,and when lymphatic vessel involvement is absent by postoperative histological examination.Combining ESD and sentinel lymph node dissection could be recommended as a safe and effective treatment for EMGC patients with a potential risk of pLNM.
基金supported by Jiangsu Cancer Hospital (ZK201606ZK201610)
文摘While obesity and fat intake have been associated with the risk and prognosis of epithelial ovarian cancer, the association between the lipid levels and epithelial ovarian cancer phenotype remains controversial. We conducted a retrospective study of 349 epithelial ovarian cancer patients who received treatment at Jiangsu Cancer Hospital, China between 2011 and 2017. We analyzed age at diagnosis, blood pressure, plasma glucose content, body mass index（BMI）, lipid levels and clinical parameters. Severity of epithelial ovarian cancer was classified according to the International Federation of Gynecology and Obstetrics（FIGO） grading system. Univariate analysis of the clinical factors according to the severity of epithelial ovarian cancer was followed by logistic regression analysis to identify clinical factors significantly associated with epithelial ovarian cancer severity. Univariate analysis indicated that age,BMI, triglyceride（TG）, and high density lipoproteins（HDL） differed significantly among different stages of epithelial ovarian cancer（P〈0.05）. In the logistic regression model, elevated TG（OR： 1.883; 95% CI= 1.207-2.937）, and low HDL（OR： 0.497; 95% CI = 0.298-0.829） levels were significantly associated with the high severity epithelial ovarian cancer. Our data indicate that high TG and low HDL levels correlate with a high severity of epithelial ovarian cancer. These data provide important insight into the potential relationship between the lipid pathway and epithelial ovarian cancer phenotype and development.
文摘Objective In recent years, the rising incidence of cancer has increased patients’ living and economic burdens. This study analyzed the incidence and death due to malignant tumors in tumor registries in Heilongjiang province (China) in 2015 to provide a scientific basis for the prevention and treatment of malignant tumors in this province. Methods Data on tumor incidence and patient deaths were collected from seven tumor registries in Heilongjiang province (China) in 2015. According to the stratification of urban and rural areas and patient sex, the crude, standard, and accumulative rates (0–74 years of age) were calculated. The 2000 China Population Census data and Segi’s standard population were used to calculate the age-standardized rates. Results In 2015, the incidence rate of malignant tumors in Heilongjiang cancer registries was 259.90/100 000. The age-standardized incidence rates in the Chinese and world standard populations were 158.89/100 000 and 155.06/100 000, respectively, with a cumulative incidence rate (0–74 years) of 17.68%. The incidence of malignant tumors in urban areas was 273.55/100 000, while that in rural areas was 220.32/100 000. The incidence of malignant tumors in men was 270.89/100 000, higher than that in women (249.04/100 000). Lung cancer had the highest incidence, followed by breast cancer, liver cancer, colorectal cancer, and thyroid cancer. The mortality rate of malignant tumors in Heilongjiang cancer registries was 164.69/100 000. The age-standardized mortality rates in Chinese and in world standard populations were 95.29/100 000 and 94.35/100 000, respectively, with a cumulative mortality rate (0–74 years) of 10.44%. The mortality rate of malignant tumors in urban areas was 169.51/100 000, while that in rural areas was 150.72/100 000. The mortality rate of malignant tumors in men was 201.64/100 000, higher than that in women (128.21/100 000). Lung cancer had the highest mortality, followed by liver cancer, stomach cancer, colorectal cancer, and breast cancer. Conclusion Lung, liver, breast, and colorectal cancers were the most common cancers in Heilongjiang province, China, and should be considered the key cancer types for prevention and treatment. Moreover, the incidence of thyroid cancer is increasing, and thus early preventative measures should be implemented.
基金the National Natural Science Foundation of China(No.82073308 and No.81773211)the High-level startup fund of Nanjing Medical University(No.KY109RC2019010).
文摘As a well-known anticancer drug,paclitaxel(PTX),a first-line chemotherapeutic agent,remains unsatisfactory for gastric cancer therapy.It is reported that triptolide(TPL)could enhance the anti-gastric cancer effect of PTX.Considering the poor solubility of both drugs,we developed a red blood cell membrane-biomimetic nanosystem,an emerging tool in drug delivery,to co-load paclitaxel and triptolide(red blood cell membrane coated PTX and TPL co-loaded poly(lactic-co-glycolic acid)[PLGA]nanoparticles,RP(P/T)).The successful preparation was confirmed in terms of particle size,morphology,and surface markers assays.This biomimetic system could prolong circulation and escape immune surveillance.And these properties were verified by stability,in vitro drug release,and cellular uptake assays.Moreover,the MTT and colony formation assays demonstrated the superior anti-proliferation effect of the RP(P/T)to free drugs.The enhanced antitumor effects of RP(P/T)on migration and invasion were also evaluated by wound-healing and transwell assays.Overall,the bionic co-delivery nanoplatform with improved efficacy in vitro is a promising therapy for gastric cancer.
