The relationship between free cancer cells and the pathological characteristics of gastric cancer were studied. Of 100 cases of gastric cancer, free cancer cells in the peritoneal cavity were detected in 32 cases (32%...The relationship between free cancer cells and the pathological characteristics of gastric cancer were studied. Of 100 cases of gastric cancer, free cancer cells in the peritoneal cavity were detected in 32 cases (32%). Free cancer cells were most often found in tendonoid (62.2%) and colour diffused (60.0%) serosal types. When the area of serosal invasion was over 20 cm, the positive free cancer cell rate was 56.6% and only 2.5% if below 20 cm. Free cancer cells were related to the depth of cancer infiltration, often found in the S2 and S3 invasion layers, as well as to the pathological characteristics of gastric cancer. Free cancer cells were often seen in infiltrated type cancer, histologically poorly differentiated or undifferentiated adenocarcinoma. and nest or diffused growth types. In patients without peritoneal metastasis (P0), the positive rate was 26.1%. This study proved that Chen's serosal classification is correct and useful in assessing whether the cancer cells have penetrated through the serosa or not during surgery. Different treatments should be used in the cases with different serosal types. In addition to surgery, destruction of free cancer cells should be considered in tendonoid and colour diffused serosal types, so as to prevent peritoneal metastasis.展开更多
Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducin...Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.展开更多
In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by n...In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy.We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H2O2 to release GEM.Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM.For the lung cancer cell lines that are resistant to the epidermal growth factor receptor(EGFR)-targeting inhibitor osimertinib,GEM-ZZQ showed less growth inhibition than GEM;however,GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups.In summary,we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.展开更多
Objective:To explore the intraperitoneal free cancer cell(IFCC)detection value of negative enrichment and immune fluorescence in situ hybridization(NEimFISH)on chromosomes(CEN)8/17.Methods:To verify the reliability of...Objective:To explore the intraperitoneal free cancer cell(IFCC)detection value of negative enrichment and immune fluorescence in situ hybridization(NEimFISH)on chromosomes(CEN)8/17.Methods:To verify the reliability of NEimFISH,29 gastric cancer tumors,their adjacent tissues and greater omental tissues were tested.Our study then included 105 gastric cancer patients for IFCC.We defined patients as IFCC-positive if a signal was detected,regardless of the detailed cancer cell numbers.A comparison of clinicopathological features was conducted among IFCC groups.We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods.The comparison of IFCC number was also conducted among different groups.Results:A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97%of malignant tissue samples in our study.Compared to intestinal gastric cancer,patients with diffuse gastric cancer tended to have more IFCCs(6 vs.4,P=0.002).The IFCC counts were often higher in the lymphovascular invasion positive group than negative group(3 vs.1,P=0.022).All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH.When compared to conventional cytology and paraffin pathology,NEimFISH had a higher IFCC positive rate(68.9%)and higher one-year peritoneal recurrence predictive value with area under the curve(AUC)of 0.922.Conclusions:Gastric cancer could be effectively diagnosed by NEimFISH.The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer.NEimFISH is a reliable detection modality with a higher positive detection rate,higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.展开更多
Objective:To compare laparoscopic gastrectomy and conventional surgery on the dissemina- tion and seeding of tumor cells.Methods:Intraoperative peritoneal lavage cytologic examination was per- formed in 65 patients wi...Objective:To compare laparoscopic gastrectomy and conventional surgery on the dissemina- tion and seeding of tumor cells.Methods:Intraoperative peritoneal lavage cytologic examination was per- formed in 65 patients with gastric cancer,during laparoscopic gastrectomy(n=34)and conventional surgery(n=31).Cytology was examined twice,immediately after opening the peritoneal cavity and just before closing the abdomen.Saline was poured into the peritoneal cavity,and 100 ml fluid was retrieved after irrigation.Laparoscopic instruments were lavaged after surgery with 100 ml saline.Carbon dioxide (CO_2)was derived through the trocar side orifice after pneumoperitoneum during laparoscopic gastrectomy and filtered through 100 ml saline.Cytologic examination of the filtrate was performed after the filtration process.Results:The incidence of positive cytology during laparoscopic surgery was 32.26% in the preop- erative Iavage and 22.58% in the postoperative lavage.The incidence of positive cytology during conven- tional surgery was 41.18%0 before lavage and 26.47% after lavage.Only one positive cytology was detect- ed in the CO_2 filtrate gas.The incidence of positive cytology in the lavage of the instruments during laparo- scopic surgery was 6.45%.Conclusion:During gastric laparoscopic surgery,CO_2 pneumoperitoneum does not affect tumor cell dissemination and seeding.In this study,laparoscopic techniques used in gastric can- cer surgery were not associated with a higher risk for intraperitoneal dissemination of cancer cells than the conventional surgery.展开更多
Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicin...Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicine in the management of cancer,associated with a lower risk of recur-rence and increased survival.Several avenues of research demonstrate reduction in growth,proliferation,and increased apoptosis of cancer cells,including breast,prostate,colorectal,and lung cancer,when cultured by serum collected after exercise in vitro(i.e.,the cultivation of cancer cell lines in an experimental setting,which simplifies the biological system and provides mechanistic insight into cell responses).The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors,such as skeletal muscle-induced cytokines(i.e.,myokines)and hormones.However,exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated,constraining more precise application of exercise medicine within clinical oncology.To date,it remains unclear what role different training modes(i.e.,resistance and aerobic training)as well as volume and intensity have on exercise-condi-tioned serum and its effects on cancer cells.Nevertheless,the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects,while for chronic training interventions,exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode.Insights for future research investigating training modes,volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.展开更多
Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and...Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.展开更多
BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To inves...BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.展开更多
BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained...BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.展开更多
Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapaglif...Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.展开更多
Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser captu...Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.展开更多
Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects...Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.展开更多
Objective:To construct CAR-NK-92 cells targeting carcinoembryonic antigen(CEA)and study their killing effect on gastric cancer cells.Methods:CAR-NK-92 cells targeting CEA were constructed.After co-culturing CAR-NK-92 ...Objective:To construct CAR-NK-92 cells targeting carcinoembryonic antigen(CEA)and study their killing effect on gastric cancer cells.Methods:CAR-NK-92 cells targeting CEA were constructed.After co-culturing CAR-NK-92 cells with MKN-45 gastric cancer cells,the killing effect of CAR-NK-92 cells was detected by a lactate dehydrogenase release assay.The secretion levels of gamma interferon and granulocyte-macrophage colony-stimulating factor were measured using an ELISA assay.Results:The lactate dehydrogenase release assay showed that CAR-NK-92 cells had a significant killing effect on MKN-45 cells compared to CON-NK-92 cells,and the difference was statistically significant(P<0.001).ELISA results indicated that the levels of gamma interferon and granulocyte-macrophage colony-stimulating factor secreted by CAR-NK-92 cells and MKN-45 target cells were significantly increased after co-culture(P<0.001).Conclusion:CAR-NK-92 cells targeting CEA exhibit a significant killing effect on CEA-positive gastric cancer cells.展开更多
Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on...Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data.The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity,sensitivity and clinical usability of the technique.Moreover,it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity.Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations:Variation in gene copy number or the methylation rate of the tumor tissue.Recently,circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease.Due to high-throughput technologies,liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients.展开更多
Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab ...Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.展开更多
Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and g...Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1(IGF-1)stimulation.Methods:MTT assay was performed to determine the proliferation of cancer cells.Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis.Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A.montana leaves hexane extract.Results:A.montana leaves hexane(subfraction V)blocked the constitutive stimulation of the PI3K/mTOR signaling pathways.This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNNEL)staining,activation of caspase-3,and cleavage of PPAR.It also limited the expression of various downstream genes that regulate proliferation,survival,metastasis,and angiogenesis(i.e.,cyclin D1,survivin,COX-2,and VEGF).It increased the expression of p53 and p21.Interestingly,we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.Conclusion:Our study indicates that A.montana leaves(sub-fraction V)extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.展开更多
Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers ...Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.展开更多
The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by...The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by trypsin to prepare a single-cell suspension,and mixed homogeneously into 1.2% alginate gel.Single-cell alginate gel was cultured with serum-free DMEM/F12 medium.Epirubicin(0.8μg/mL)was added to the medium to enrich CSCs.After cultured conventionally for 7 to 10 days,most of cells suspended in ...展开更多
Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells(IFCC) presence is not routinely in...Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells(IFCC) presence is not routinely investigated and their prognostic meaning is still unclear. When peritoneal washing results are positive for the presence of IFCC a worse outcome is usually expected in these colorectal cancer operated patients, but it what is not clear is whether it is associated with an increased risk of local recurrence. It is authors' belief that one of the main reasons why IFCC are not researched as integral part of the routine staging system for colon cancer is that there still isn't a diagnostic or detection method with enough sensibility and specificity. However, the potential clinical implications of a routine research for the presence IFCC in colon neoplasias are enormous: not only to obtain a more accurate clinical staging but also to offer different therapy protocols, based on the presence of IFCC. Based on this, adjuvant chemotherapy could be offered to those patients found to be positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy could be applied. Although presence of IFCC appears to have a valid prognostic significance, further studies are needed to standardize detection and examination procedures, to determine if there are and which are the stages more likely to benefit from routine search for IFCC.展开更多
Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemothe...Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.展开更多
文摘The relationship between free cancer cells and the pathological characteristics of gastric cancer were studied. Of 100 cases of gastric cancer, free cancer cells in the peritoneal cavity were detected in 32 cases (32%). Free cancer cells were most often found in tendonoid (62.2%) and colour diffused (60.0%) serosal types. When the area of serosal invasion was over 20 cm, the positive free cancer cell rate was 56.6% and only 2.5% if below 20 cm. Free cancer cells were related to the depth of cancer infiltration, often found in the S2 and S3 invasion layers, as well as to the pathological characteristics of gastric cancer. Free cancer cells were often seen in infiltrated type cancer, histologically poorly differentiated or undifferentiated adenocarcinoma. and nest or diffused growth types. In patients without peritoneal metastasis (P0), the positive rate was 26.1%. This study proved that Chen's serosal classification is correct and useful in assessing whether the cancer cells have penetrated through the serosa or not during surgery. Different treatments should be used in the cases with different serosal types. In addition to surgery, destruction of free cancer cells should be considered in tendonoid and colour diffused serosal types, so as to prevent peritoneal metastasis.
基金the support from the Guangdong Basic and Applied Basic Research Foundation (2020A1515011376)the National Natural Science Foundation of China (31601397)+2 种基金the Innovative Leading Talents Project of Guangzhou Development ZoneGuangzhou Innovation Leading Talent Projectthe 111 Project (B17018)。
文摘Polyphenol-rich foods have been shown to be good for cancer prevention as powerful antioxidants. In this study, the mechanisms of wild pink bayberry free phenolic extract(WPBFE)inhibiting the proliferation and inducing apoptotic of MDA-MB-231 breast cancer cells was examined. The main phenolic acids and flavonols in WPBFE were gallic acid((18.83 ± 0.44)μg/g FW)and myricetin((1.52 ± 0.05)μg/g FW), respectively. The maximum inhibition rate of WPBFE at non-cytotoxicity dose(below 80 mg/mL)was 81%. Western blotting analysis showed that WPBFE could cause the arrest of cell cycle in G0/G1 phase by down-regulating expression levels of PCNA, CDK4, cyclin D1 and up-regulating the expression level of p21. Meanwhile, WPBFE induced apoptosis through initiating the mitochondrial death pathway by up-regulating cleaved caspase-3 and enhancing the ratio of Bax/Bcl-2, with the maximum expression levels of 1.29 and 2.03 folds that of control group, respectively. Further study of the upstream protein, we found that WPBFE down-regulated TRAF2, while upregulated p-ASK1, p-p38 and p-p53. Furthermore, WPBFE could down-regulate the expression of p-PI3K and p-Akt. These observations indicated that WPBFE might play an anticancer role through regulating the p38 MAPK together with PI3K/Akt pathway.
基金supported by the National Natural Science Foundation of China(Grant Nos.81972763 and 81473241).
文摘In the present study,we introduced the H2O2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine(GEM)to synthesize a new target compound named GEM-ZZQ,and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy.We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H2O2 to release GEM.Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM.For the lung cancer cell lines that are resistant to the epidermal growth factor receptor(EGFR)-targeting inhibitor osimertinib,GEM-ZZQ showed less growth inhibition than GEM;however,GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups.In summary,we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.
基金supported by the National Science Foundation for Young Scientists of China (No. 81802735)
文摘Objective:To explore the intraperitoneal free cancer cell(IFCC)detection value of negative enrichment and immune fluorescence in situ hybridization(NEimFISH)on chromosomes(CEN)8/17.Methods:To verify the reliability of NEimFISH,29 gastric cancer tumors,their adjacent tissues and greater omental tissues were tested.Our study then included 105 gastric cancer patients for IFCC.We defined patients as IFCC-positive if a signal was detected,regardless of the detailed cancer cell numbers.A comparison of clinicopathological features was conducted among IFCC groups.We also compared the diagnosis value and peritoneal recurrence predictive value among different detection methods.The comparison of IFCC number was also conducted among different groups.Results:A cutoff of 2.5 positive cells could distinguish all benign tissue samples and 97%of malignant tissue samples in our study.Compared to intestinal gastric cancer,patients with diffuse gastric cancer tended to have more IFCCs(6 vs.4,P=0.002).The IFCC counts were often higher in the lymphovascular invasion positive group than negative group(3 vs.1,P=0.022).All IFCC samples that were considered positive using conventional cytology were also found to be positive using NEimFISH.When compared to conventional cytology and paraffin pathology,NEimFISH had a higher IFCC positive rate(68.9%)and higher one-year peritoneal recurrence predictive value with area under the curve(AUC)of 0.922.Conclusions:Gastric cancer could be effectively diagnosed by NEimFISH.The IFCC number found using NEimFISH on CEN8/17 is closely associated with Lauren type and vascular invasion of cancer.NEimFISH is a reliable detection modality with a higher positive detection rate,higher one-year peritoneal recurrence predictive value and quantitative features for IFCC of gastric cancer.
文摘Objective:To compare laparoscopic gastrectomy and conventional surgery on the dissemina- tion and seeding of tumor cells.Methods:Intraoperative peritoneal lavage cytologic examination was per- formed in 65 patients with gastric cancer,during laparoscopic gastrectomy(n=34)and conventional surgery(n=31).Cytology was examined twice,immediately after opening the peritoneal cavity and just before closing the abdomen.Saline was poured into the peritoneal cavity,and 100 ml fluid was retrieved after irrigation.Laparoscopic instruments were lavaged after surgery with 100 ml saline.Carbon dioxide (CO_2)was derived through the trocar side orifice after pneumoperitoneum during laparoscopic gastrectomy and filtered through 100 ml saline.Cytologic examination of the filtrate was performed after the filtration process.Results:The incidence of positive cytology during laparoscopic surgery was 32.26% in the preop- erative Iavage and 22.58% in the postoperative lavage.The incidence of positive cytology during conven- tional surgery was 41.18%0 before lavage and 26.47% after lavage.Only one positive cytology was detect- ed in the CO_2 filtrate gas.The incidence of positive cytology in the lavage of the instruments during laparo- scopic surgery was 6.45%.Conclusion:During gastric laparoscopic surgery,CO_2 pneumoperitoneum does not affect tumor cell dissemination and seeding.In this study,laparoscopic techniques used in gastric can- cer surgery were not associated with a higher risk for intraperitoneal dissemination of cancer cells than the conventional surgery.
文摘Cancer is a major cause of morbidity and mortality worldwide,and the incidence is increasing,highlighting the need for effective strategies to treat this disease.Exercise has emerged as fundamental therapeutic medicine in the management of cancer,associated with a lower risk of recur-rence and increased survival.Several avenues of research demonstrate reduction in growth,proliferation,and increased apoptosis of cancer cells,including breast,prostate,colorectal,and lung cancer,when cultured by serum collected after exercise in vitro(i.e.,the cultivation of cancer cell lines in an experimental setting,which simplifies the biological system and provides mechanistic insight into cell responses).The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors,such as skeletal muscle-induced cytokines(i.e.,myokines)and hormones.However,exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated,constraining more precise application of exercise medicine within clinical oncology.To date,it remains unclear what role different training modes(i.e.,resistance and aerobic training)as well as volume and intensity have on exercise-condi-tioned serum and its effects on cancer cells.Nevertheless,the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects,while for chronic training interventions,exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode.Insights for future research investigating training modes,volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.
基金support from the National Natural Science Foundation of China(Grant Nos.11974066,12174041,12104134,T2350007,and 12347178)the Fundamental and Advanced Research Program of Chongqing(Grant No.cstc2019jcyj-msxm X0477)+3 种基金the Natural Science Foundation of Chongqing(Grant No.CSTB2022NSCQMSX1260)the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202301333)the Scientific Research Fund of Chongqing University of Arts and Sciences(Grant Nos.R2023HH03 and P2022HH05)College Students’Innovation and Entrepreneurship Training Program of Chongqing Municipal(Grant No.S202310642002)。
文摘Increasing data indicate that cancer cell migration is regulated by extracellular matrixes and their surrounding biochemical microenvironment,playing a crucial role in pathological processes such as tumor invasion and metastasis.However,conventional two-dimensional cell culture and animal models have limitations in studying the influence of tumor microenvironment on cancer cell migration.Fortunately,the further development of microfluidic technology has provided solutions for the study of such questions.We utilize microfluidic chip to build a random collagen fiber microenvironment(RFM)model and an oriented collagen fiber microenvironment(OFM)model that resemble early stage and late stage breast cancer microenvironments,respectively.By combining cell culture,biochemical concentration gradient construction,and microscopic imaging techniques,we investigate the impact of different collagen fiber biochemical microenvironments on the migration of breast cancer MDA-MB-231-RFP cells.The results show that MDA-MB-231-RFP cells migrate further in the OFM model compared to the RFM model,with significant differences observed.Furthermore,we establish concentration gradients of the anticancer drug paclitaxel in both the RFM and OFM models and find that paclitaxel significantly inhibits the migration of MDA-MB-231-RFP cells in the RFM model,with stronger inhibition on the high concentration side compared to the low concentration side.However,the inhibitory effect of paclitaxel on the migration of MDA-MB-231-RFP cells in the OFM model is weak.These findings suggest that the oriented collagen fiber microenvironment resembling the late-stage tumor microenvironment is more favorable for cancer cell migration and that the effectiveness of anticancer drugs is diminished.The RFM and OFM models constructed in this study not only provide a platform for studying the mechanism of cancer development,but also serve as a tool for the initial measurement of drug screening.
文摘BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.
基金Supported by National Natural Science Foundation of China,No.82260785.
文摘BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.
基金funded by the Deanship of Scientific Research(DSR),King Abdulaziz University,Jeddah,Saudi Arabia,under Grant No.KEP-1-166-41The authors,therefore,acknowledge DSR,with thanks for their technical and financial support.
文摘Cancer frequently develops resistance to the majority of chemotherapy treatments.This study aimed to examine the synergistic cytotoxic and antitumor effects of SGLT2 inhibitors,specifically Canagliflozin(CAN),Dapagliflozin(DAP),Empagliflozin(EMP),and Doxorubicin(DOX),using in vitro experimentation.The precise combination of CAN+DOX has been found to greatly enhance the cytotoxic effects of doxorubicin(DOX)in MCF-7 cells.Interestingly,it was shown that cancer cells exhibit an increased demand for glucose and ATP in order to support their growth.Notably,when these medications were combined with DOX,there was a considerable inhibition of glucose consumption,as well as reductions in intracellular ATP and lactate levels.Moreover,this effect was found to be dependent on the dosages of the drugs.In addition to effectively inhibiting the cell cycle,the combination of CAN+DOX induces substantial modifications in both cell cycle and apoptotic gene expression.This work represents the initial report on the beneficial impact of SGLT2 inhibitor medications,namely CAN,DAP,and EMP,on the responsiveness to the anticancer properties of DOX.The underlying molecular mechanisms potentially involve the suppression of the function of SGLT2.
基金supported by the National Natural Science Foundation of China[Grant Number:81972803]。
文摘Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.
文摘Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.
基金Henan Provincial Health Commission's 2020 National Health Commission Science Research Fund Henan Provincial Medical Science and Technology Tackling Plan Provincial-Ministerial Joint Project and Soft Science Project"Clinical Study of CAR-NK Cells Targeting Carcinoembryonic Antigen on Gastric Cancer Cells"(Grant No.SBGJ202002093)Henan Province 2022 Science and Technology Development Plan"Study on Pyroglutamate Targeting DJ-1 to Trigger ROS-Induced Cell Death and Protective Autophagy in Pancreatic Cancer"(Grant No.222102310725)。
文摘Objective:To construct CAR-NK-92 cells targeting carcinoembryonic antigen(CEA)and study their killing effect on gastric cancer cells.Methods:CAR-NK-92 cells targeting CEA were constructed.After co-culturing CAR-NK-92 cells with MKN-45 gastric cancer cells,the killing effect of CAR-NK-92 cells was detected by a lactate dehydrogenase release assay.The secretion levels of gamma interferon and granulocyte-macrophage colony-stimulating factor were measured using an ELISA assay.Results:The lactate dehydrogenase release assay showed that CAR-NK-92 cells had a significant killing effect on MKN-45 cells compared to CON-NK-92 cells,and the difference was statistically significant(P<0.001).ELISA results indicated that the levels of gamma interferon and granulocyte-macrophage colony-stimulating factor secreted by CAR-NK-92 cells and MKN-45 target cells were significantly increased after co-culture(P<0.001).Conclusion:CAR-NK-92 cells targeting CEA exhibit a significant killing effect on CEA-positive gastric cancer cells.
文摘Metastatic castrate-resistant prostate cancer remains a disease hard to cure,and for this reason predictive tools to monitor disease progression and therapy response are an urgent need.In this respect,liquid biopsy on circulating cell-free nucleic acids represents an interesting strategy based on robust data.The low invasiveness and the possibility to target circulating cell-free tumor deoxyribonucleic acid underline the high specificity,sensitivity and clinical usability of the technique.Moreover,it has been observed that the cell-free tumor deoxyribonucleic acid of metastatic castrate-resistant prostate cancer patients can be representative of the tumor heterogeneity.Cell-free tumor deoxyribonucleic acids express the same behaviors as mutations:Variation in gene copy number or the methylation rate of the tumor tissue.Recently,circulating cell-free ribonucleic acid molecules have emerged as interesting markers to stratify the disease.Due to high-throughput technologies,liquid biopsy on circulating cell-free nucleic acids will soon be utilized in the clinical management of metastatic castrate-resistant prostate cancer patients.
基金funded by the National Natural Science Foundation of China(Grant Nos.81972796,82272845,81972863,and 82030082)the Key Research and Development Program of Shandong(Major Science&Technology Innovation Project Grant No.2021SFGC0501)+1 种基金the CSCO-Haosen Foundation(Grant No.Y-HS202102-0089)the CSCO-Xinda Foundation(Grant No.Y-XD202001-0008)。
文摘Maintenance immunotherapy after concurrent chemoradiotherapy remains the standard therapeutic approach in patients with unresectable locally advanced non-small cell lung cancer(LA-NSCLC).The efficacy of pembrolizumab without chemotherapy in stage IV NSCLC has incited interest in similar approaches for LA-NSCLC.Several recent investigations involving the synergistic potential of immunotherapy combined with radiotherapy(i RT)have generated encouraging results.This review discusses the existing studies and prospective directions of chemotherapy-free i RT strategies in unresectable LA-NSCLC.Although the initial findings of chemotherapy-free i RT strategies have shown promising efficacy,we must consider the methodologic limitations of current studies and the myriad of challenges that accompany the implementation of chemotherapy-free i RT.These challenges include determining the optimal dose and fractionation,precise target volume delineation,and identification of additional suitable patient cohorts.Furthermore,the feasibility of chemotherapy-free i RT as a novel treatment modality for select patients with LA-NSCLC is contingent upon validation through randomized phase III trials.
基金supported by the National Institutes of Health Grant SC1DK084343(to MAB)by Mass Spectrometry Research and Education Center must cite funding from NIH S10 OD021758-01A1.
文摘Backgorund:Fruits and seed extracts of Annona montana have significant cytotoxic potential in several cancer cells.This study evaluates the effect of A.montana leaves hexane extract on several signaling cascades and gene expression in metastatic breast cancer cells upon insulin-like growth factor-1(IGF-1)stimulation.Methods:MTT assay was performed to determine the proliferation of cancer cells.Propidium iodide staining and flow cytometry analysis of Annexin V binding was utilized to measure the progression of the cell cycle and the induction of apoptosis.Protein expression and phosphorylation were determined by western blotting analysis to examine the underlying cellular mechanism triggered upon treatment with A.montana leaves hexane extract.Results:A.montana leaves hexane(subfraction V)blocked the constitutive stimulation of the PI3K/mTOR signaling pathways.This inhibitory effect was associated with apoptosis induction as evidenced by the positivity with Annexin V and terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNNEL)staining,activation of caspase-3,and cleavage of PPAR.It also limited the expression of various downstream genes that regulate proliferation,survival,metastasis,and angiogenesis(i.e.,cyclin D1,survivin,COX-2,and VEGF).It increased the expression of p53 and p21.Interestingly,we also observed that this extract blocked the activation of AKT and ERK without affecting the phosphorylation of the IGF-1 receptor and activation of Ras upon IGF-1 stimulation.Conclusion:Our study indicates that A.montana leaves(sub-fraction V)extract exhibits a selective anti-proliferative and proapoptotic effect on the metastatic MDA-MB-231 breast cancer cells through the involvement of PI3K/AKT/mTOR/S6K1 pathways.
文摘Despite recent advances in surgical techniques and perioperative management, the prognosis of pancreatic cancer(PCa) remains extremely poor. To provide optimal treatment for each patient with Pca, superior biomarkers are urgently needed in all phases of management from early detection to staging, treatment monitoring, and prognosis. In the blood of patients with cancer, circulating tumor cells(CTCs) and cell-free nucleic acids(cf NAs), such as DNA, m RNA, and noncoding RNA have been recognized. In the recent years, their presence in the blood has encouraged researchers to investigate their potential use as novel blood biomarkers, and numerous studies have demonstrated their potential clinical utility as a biomarker for certain types of cancer. This concept, called "liquid biopsy" has been focused on as a less invasive, alternative approach to cancer tissue biopsy for obtaining genetic and epigenetic aberrations that contribute to oncogenesis and cancer progression. In this article, we review the available literature on CTCs and cfN As in patients with cancer, particularly focusing on PCa, and discuss future perspectives in this field.
文摘The cancer stem cells(CSCs)from human osteosarcoma by serum-free three-dimensional culture combined with anticancer drugs were isolated and identified.The primary cells derived from human osteosarcoma were digested by trypsin to prepare a single-cell suspension,and mixed homogeneously into 1.2% alginate gel.Single-cell alginate gel was cultured with serum-free DMEM/F12 medium.Epirubicin(0.8μg/mL)was added to the medium to enrich CSCs.After cultured conventionally for 7 to 10 days,most of cells suspended in ...
文摘Peritoneal washing is now part of the standard clinical practice in several abdominal and pelvic neoplasias. However, in colorectal cancer surgery, intra-peritoneal free cancer cells(IFCC) presence is not routinely investigated and their prognostic meaning is still unclear. When peritoneal washing results are positive for the presence of IFCC a worse outcome is usually expected in these colorectal cancer operated patients, but it what is not clear is whether it is associated with an increased risk of local recurrence. It is authors' belief that one of the main reasons why IFCC are not researched as integral part of the routine staging system for colon cancer is that there still isn't a diagnostic or detection method with enough sensibility and specificity. However, the potential clinical implications of a routine research for the presence IFCC in colon neoplasias are enormous: not only to obtain a more accurate clinical staging but also to offer different therapy protocols, based on the presence of IFCC. Based on this, adjuvant chemotherapy could be offered to those patients found to be positive for IFCC; also, protocols of proactive intraperitoneal chemotherapy could be applied. Although presence of IFCC appears to have a valid prognostic significance, further studies are needed to standardize detection and examination procedures, to determine if there are and which are the stages more likely to benefit from routine search for IFCC.
基金supported by the National Key Research and Development Plan of China(No.2017YFC1309100)the National Science Fund for Distinguished Young Scholars(No.81925023)the National Natural Scientific Foundation of China(No.81771912,81901910,82072090,and 82001986)。
文摘Objective:To develop and validate a radiomics prognostic scoring system(RPSS)for prediction of progressionfree survival(PFS)in patients with stageⅣnon-small cell lung cancer(NSCLC)treated with platinum-based chemotherapy.Methods:In this retrospective study,four independent cohorts of stageⅣNSCLC patients treated with platinum-based chemotherapy were included for model construction and validation(Discovery:n=159;Internal validation:n=156;External validation:n=81,Mutation validation:n=64).First,a total of 1,182 three-dimensional radiomics features were extracted from pre-treatment computed tomography(CT)images of each patient.Then,a radiomics signature was constructed using the least absolute shrinkage and selection operator method(LASSO)penalized Cox regression analysis.Finally,an individualized prognostic scoring system incorporating radiomics signature and clinicopathologic risk factors was proposed for PFS prediction.Results:The established radiomics signature consisting of 16 features showed good discrimination for classifying patients with high-risk and low-risk progression to chemotherapy in all cohorts(All P<0.05).On the multivariable analysis,independent factors for PFS were radiomics signature,performance status(PS),and N stage,which were all selected into construction of RPSS.The RPSS showed significant prognostic performance for predicting PFS in discovery[C-index:0.772,95%confidence interval(95%CI):0.765-0.779],internal validation(C-index:0.738,95%CI:0.730-0.746),external validation(C-index:0.750,95%CI:0.734-0.765),and mutation validation(Cindex:0.739,95%CI:0.720-0.758).Decision curve analysis revealed that RPSS significantly outperformed the clinicopathologic-based model in terms of clinical usefulness(All P<0.05).Conclusions:This study established a radiomics prognostic scoring system as RPSS that can be conveniently used to achieve individualized prediction of PFS probability for stageⅣNSCLC patients treated with platinumbased chemotherapy,which holds promise for guiding personalized pre-therapy of stageⅣNSCLC.