<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. &l...<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. <strong>Methods:</strong> 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. <strong>Results:</strong> There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). <strong>Conclusion:</strong> The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.展开更多
Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free DNA(cfDNA)in peripheral blood of patients with triple-negative breast cancer.Method:41 patients with breast...Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free DNA(cfDNA)in peripheral blood of patients with triple-negative breast cancer.Method:41 patients with breast cancer admitted to the First Central Hospital of Baoding from January 2020 to December 2021 were selected and recruited into the experimental group,42 patients with benign breast cancer admitted during the same period were recruited into the conditional control group,and 41 healthy patients admitted during the same period were recruited into the blank control group.The positive rate of peripheral blood CTCs,the level of cfDNA,and the diagnostic efficacy of peripheral blood CTCs,cfDNA alone and the combination thereof for breast cancer were analyzed.Result:The positive rates of peripheral blood CTCs in the experimental group,the conditional control group,and the blank control group were 43.90%,11.90%,and 9.74%,respectively,and there was significant difference among the groups.The levels of cfDNA in peripheral blood of the experimental group,the conditional control group,and the blank control group were 0.26±0.08 bp,0.17±0.03 bp,and 0.15±0.04 bp,respectively,which were statistically significant.The detection levels of 100 bp hTERT/ng mT1 and 241 bp hTERT/ng-mT1 in the experimental group were significantly higher than those in the conditional control group and the blank control group.The accuracy of peripheral blood CTCs detection in the three groups was 66.21%,the accuracy of cfDA241 bp/100 hp hTERT detection was 80.41%,and the accuracy of combined detection of peripheral blood CTCs and cfDNA was 94.03%.Conclusion:The clinical application of peripheral blood CTCs combined with cfDNA level detection can increase detection accuracy,provide data support for clinicians,and improve the clinical diagnostic effect of triple-negative breast cancer.展开更多
Objective:To explore the correlation between peripheral circulating tumor cells and hypercoagulability in patients with lung cancer after surgery.Methods:From January 2017 to December 2021,89 patients with lung cancer...Objective:To explore the correlation between peripheral circulating tumor cells and hypercoagulability in patients with lung cancer after surgery.Methods:From January 2017 to December 2021,89 patients with lung cancer who were treated in the Affiliated Hospital of Hebei University were selected as the research subjects,and a retrospective analysis was conducted to analyze and observe the D-dimer(DD),fibrinogen(FIB),and platelet(PLT)levels in peripheral blood,as well as detect peripheral CTC.Results:There were statistical differences in TMN staging,tumor metastasis,and lymph node metastasis in the clinical data,but there were no statistical differences in gender,smoking history,and pathological classification.After retrospective analysis and comparison of the patients,the DD(mg/ml),FIB(g/L),and PLT(×10^(9)/L)levels of the CTC positive group were 3.41±0.58,3.98±0.87,and 367.26±34.98,respectively;the CTC negative group’s DD(mg/ml),FIB(g/L),and PLT(×10^(9)/L)levels were 0.89±0.49,1.06±0.45,and 234.69±35.69,respectively,and the differences were statistically significant.The factors affecting the prognosis of patients included TMN staging and CTC;the number of CTC positives in the death group was significantly higher than that in the survival group,and there was a statistical difference between the groups.Gender,age,smoking history,pathological type,and surgical resection had no effect on the prognosis of patients.Among the enrolled patients,the survival rate was 71.91%.Conclusion:CTC-positive patients have a higher probability of hypercoagulability after surgery and are prone to tumor metastasis;thus,CTC can be used as a judgment index for the prognosis of patients.展开更多
AIM: To investigate whether the stimulation of peripheral blood mononuclear cells (PBMNC) with the cell debris and cell extraction of different probiotic strains is similar or species specific. METHODS: Three stra...AIM: To investigate whether the stimulation of peripheral blood mononuclear cells (PBMNC) with the cell debris and cell extraction of different probiotic strains is similar or species specific. METHODS: Three strains of bifidobacteria, 4 strains of lactobacilli, and E. coli nissle were sonicated and centrifuged in order to divide them into cell extract and cell debris. PBMNC were separated by density gradient and incubated for 36 h with either the cell debris or the cell extract of single strains of probiotic bacteria in doses from 10^2 to 10^8 CFU/mL. Cell supernatants were taken and interleukin (IL)-10, IL-1β, and tumor necosis factor (TNF)-α were determined by ELISA. RESULTS: Depending on the species super-family, the strains had different stimulation patterns. Except for both L. casei strains, the cell extract of bitTdobacteria and/actobacilli had less stimulating capacity than cell debris, whereas the cell extract of E. coli nissle had similar stimulating properties to that of the cell debris of the strain and significantly more stimulating capacity than that of bifidobacteria and lactobacilli. The cell debris of bifidobacteria stimulated more cytokine release than the cell debris of lactobacilli. The cell debris of lactobacilli did not have a stimulating capacity when lower concentrations were used. Neither cell extraction nor cell debris had an inhibitory effect on the production of the tested cytokines by stimulated PBMNC. CONCLUSION: The incubation of probiotic strains, which have been used in clinical trials for inflammatory diseases, with immunocompetent cells leads to different species specific reactions. High IL-10 response to cell debris of bifidobacteria and E. coli nissle can be found. This corresponds to positive effects of bihdobacteria and E. coli nissle in clinical trials for inflammatory bowel disease compared to negative outcomes obtained with lactobacilli.展开更多
Recent cancer research has demonstrated the existence of circulating tumor cells(CTCs)in cancer patient’s blood.Once identified,CTC biomarkers will be invaluable tools for clinical diagnosis,prognosis and treatment.I...Recent cancer research has demonstrated the existence of circulating tumor cells(CTCs)in cancer patient’s blood.Once identified,CTC biomarkers will be invaluable tools for clinical diagnosis,prognosis and treatment.In this review,we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample,to derive enough CTCs for accurate and reproducible characterization of the biophysical,biochemical,gene expressional and behavioral properties of the harvested cells.Because of tumor cell heterogeneity,it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis.By analyzing critical steps and technical issues in ex vivo CTC culture,we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells,relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells.展开更多
The relationship between tumour necrosis lactose (TNF-α) gene polymorphism and inhibitory effects of triptolide on TNF-α production from peripheral blood mononuclear cells (PBMC) of healthy humans was investigat...The relationship between tumour necrosis lactose (TNF-α) gene polymorphism and inhibitory effects of triptolide on TNF-α production from peripheral blood mononuclear cells (PBMC) of healthy humans was investigated. Genomic DNA from 41 healthy people was typed for TNF-α- 308 polymorphism by allele-specific polymorphism chain reaction (AS-PCR). The TNF-α concentration in the supernatant was measured by ELISA. The results showed that the production of TNF-α from TNF-α -308 non-G/G genotype PBMC was higher than that from TNF-α-308 G/G genotype PBMC after stimulated by LPS. Triptolide could lower the production of TNF-α from G/ G genotype PBMC, but had no effect on the level of TNF-α from non-G/G genotype PBMC. It was concluded that TNF-α gene polymorphism was related to the TNF-α production from triptolide-inhibited PBMC culture in healthy humans.展开更多
AIM To investigate whether circulating cytokeratin-positive(CK^+) cells in the mesenteric blood of resected colorectal specimens are prognostic and correlate with tumor budding.METHODS Fifty-six colorectal specimens w...AIM To investigate whether circulating cytokeratin-positive(CK^+) cells in the mesenteric blood of resected colorectal specimens are prognostic and correlate with tumor budding.METHODS Fifty-six colorectal specimens were collected between 9/2007 and 7/2008.Blood from the mesenteric vein was drawn immediately after receiving the fresh and unfixed specimens in the pathology department.After separation of the mononuclear cells by Ficoll-Hypaquedensity-gradient centrifugation,cytological smears were immunocytochemically stained for CK18.Tumor budding was evaluated on slides stained for pan-cytokeratin.The identification of ≥ 30 buds/1.3 mm2 was defined as high grade budding.RESULTS CK^+ cells and clusters were identified in 29(48%) and 14(25%) of the samples,respectively.Two cells were identified in one of three non-malignant cases.Clusters were found exclusively in malignant cases.The occurrence of CK^+ cells or clusters was not associated with any of the evaluated clinicopathological factors,including surgical technique and tumor budding.Moreover,the occurrence of CK^+ cells or clusters had no influence on the cancerspecific survival [75 mo(CI:61;88) vs 83 mo(CI:72;95) and 80 mo(CI:63;98) vs 79 mo(CI:69;89),respectively].CONCLUSION CK^+ cells and showed neither prognostic significance nor an association with tumor budding.It is very likely that CK18-staining is not specific enough to identify the relevant cells.展开更多
Isolating rare circulating tumor cells(CTCs)from blood is critical for the downstream analysis that is important in cancer-related research,diagnosis,and medicine,and efforts are ongoing to increase the efficiency and...Isolating rare circulating tumor cells(CTCs)from blood is critical for the downstream analysis that is important in cancer-related research,diagnosis,and medicine,and efforts are ongoing to increase the efficiency and purity of CTC isolation in microfluidics.Reported in this paper is a two-stage integrated microfluidic chip for coarse-to-fine CTC isolation from whole blood.First,blood cells are removed by filtration using a micropore-array membrane,then CTCs and other cells that are trapped in the micropores are peeled off the membrane by a novel release method based on air–liquid interfacial tension,which significantly increases the recovery rate of CTCs.The second stage is CTC capture based on an on-chip dense immuno-magnetic-bead clump,which offers high capture efficiency and purity.Both the micropore filtration and immuno-magnetic-bead capture are validated and optimized experimentally.Overall,the integrated microfluidic chip can realize a recovery rate of 85.5%and a purity of 37.8%for rare cancer cells spiked in whole blood.展开更多
Objective:To investigate the effects of Shenqi Fuzheng Injection combined with chemotherapy on peripheral blood cell level, tumor markers and immune function in patients with gastric cancer.Methods: Eighty patients wi...Objective:To investigate the effects of Shenqi Fuzheng Injection combined with chemotherapy on peripheral blood cell level, tumor markers and immune function in patients with gastric cancer.Methods: Eighty patients with gastric cancer admitted to our hospital from May 2016 to October 2017 were selected as the research object and randomly divided into observation group and control group, 40 cases in each group. Control group was treated by DCF chemotherapy, while the observation group by Shenqi Fuzheng Injection based on the DCF chemotherapy. The levels of peripheral blood cells, tumor markers and immune function indexes in both groups were detected and compared before and after treatment.Results: There were no significant differences in serum RBC, WBC, PLT, Hb, NSE, CYFRA21-1, CA199, CEA, CD3+, CD4+, CD8+ and CD4+/CD8+ levels before treatment in both groups. Compared with the pretreatment group, the levels of RBC, WBC, PLT and Hb in both groups decreased to some extent after treatment, and the levels in the observation group were significantly higher than those in the control group;Compared with the same group before treatment, the levels of NSE, CYFRA21-1, CA199 and CEA in the two groups were significantly decreased, and the observation group was significantly lower than the control group;CD3+, CD4+, CD4+/CD8+ levels in control group and observation group increased to some extent after treatment, and the levels in observation group were significantly higher than those in control group. The levels of CD8+ in both groups after treatment were significantly lower than those before treatment, and the observation group was significantly lower than the control group after treatment. The above data for statistical analysis had significant differences.Conclusions: Shenqi Fuzheng injection combined with chemotherapy helps to clear and kill cancer cells, enhance immunity and reduce hematological toxicity after chemotherapy, which can be used as an adjuvant chemotherapy for gastric cancer.展开更多
INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity ...INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly展开更多
Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated wit...Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.展开更多
Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast cancers.However,approaches to obtain cancer-reactive TCR-T cells have been unsucc...Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast cancers.However,approaches to obtain cancer-reactive TCR-T cells have been unsuccessful.Methods:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints.Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized mice.The human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and cytokines.To fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 days.Then,human T cells were processed for TCRβ-chain(TRB)sequencing analysis.After the repertoires had been constructed,features such as the fraction,diversity,and immune signature were investigated.Results:The results demonstrated an increase in diversity and clonality of T cells after treatment.The preferential usage and features of TRBV,TRBJ,and the V–J combination were also changed.The stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 expansion.Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice.Conclusions:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools.Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.It therefore has the potential to greatly benefit cancer treatment.展开更多
Circulating tumor cells(CTCs),as important liquid biopsy target,can provide valuable information for cancer progress monitoring and individualized treatment.However,current isolation platforms incapable of balancing c...Circulating tumor cells(CTCs),as important liquid biopsy target,can provide valuable information for cancer progress monitoring and individualized treatment.However,current isolation platforms incapable of balancing capture efficiency,specificity,cell viability,and gentle release have restricted the clinical applications of CTCs.Herein,inspired by the structure and functional merits of natural membrane interfaces,we established an antibody-engineered red blood cell(RBC-Ab)affinity interface on microfluidic chip for high-performance isolation and release of CTCs.The lateral fluidity,pliability,and anti-adhesion property of the RBC microfluidic interface enabled efficient CTCs capture(96.5%),high CTCs viability(96.1%),and high CTCs purity(average 4.2-log depletion of leukocytes).More importantly,selective lysis of RBCs by simply changing the salt concentration was utilized to destroy the affinity interface for efficient and gentle release of CTCs without nucleic acid contamination.Using this chip,CTCs were successfully detected in colon cancer samples with 90%sensitivity and 100%specificity(20 patients and 10 healthy individuals).After the release process,KRAS gene mutations of CTCs were identified from all the 5 cancer samples,which was consistent with the results of tissue biopsy.We expect this RBC interface strategy will inspire further biomimetic interface construction for rare cell analysis.展开更多
目的联合检测肺腺癌患者外周血中细胞角蛋白(cytokeratin,CK,肺腺癌循环肿瘤细胞阳性)和CD133基因(肺癌干细胞标志物)的表达,探讨二者在评估肺腺癌预后的临床价值。方法选取2014年6月至2016年6月昆明总医院心胸外科和宣威市第一人民医...目的联合检测肺腺癌患者外周血中细胞角蛋白(cytokeratin,CK,肺腺癌循环肿瘤细胞阳性)和CD133基因(肺癌干细胞标志物)的表达,探讨二者在评估肺腺癌预后的临床价值。方法选取2014年6月至2016年6月昆明总医院心胸外科和宣威市第一人民医院心胸外科的178例未化疗的肺腺癌手术患者,中位年龄59岁,其中男性78例,女性100例。收集患者术前外周血标本10 m L,细胞块法和CK(免疫细胞化学法)用于检测CTC,PCR法用于检测CD133表达。免疫组化法检测肺腺癌组织中CK、Vimentin(Vim)、TTF-1、Ki-67、CD133的表达,并分析与外周血CK和CD133表达的关系。根据外周血CK和CD133的检测结果,将病例分为CK/CD133双阳性组和非双阳性组,统计学分析两组间临床病理因素的差异。结果 178例肺腺癌患者外周血CTC(CK阳性)的检出率为48.3%(86/178),与癌组织中Ki-67、Vim表达显著正相关(P<0.05);外周血的CD133阳性表达率为66.9%(119/178),与癌组织Vim、CD133表达显著正相关(P<0.05);外周血CK/CD133双阳组53例(29.8%),双阳组淋巴结转移率显著增高,肺腺癌组织学分化级别显著降低,临床分期显著提高,转移率显著增高(P<0.05)。结论肺腺癌患者外周血中CK与CD133双阳性表达提示外周血存在干性特征的循环肿瘤细胞,表明预后不良,联合检测CK与CD133可用于肺腺癌患者预后监测和指导治疗。展开更多
At present,cancer is still an important factor threatening human health.Colorectal cancer(CRC)is one of the top three most common cancers worldwide and one of the deadliest malignancies in humans.The latest data showe...At present,cancer is still an important factor threatening human health.Colorectal cancer(CRC)is one of the top three most common cancers worldwide and one of the deadliest malignancies in humans.The latest data showed that CRC incidence and mortality rank third and second,respectively,among global malignancies.Early and accurate diagnosis is crucial to reduce the morbidity,mortality and improve survival of patients with CRC,but the current early diagnostic methods have limitations.The effectiveness and compliance of diagnostic methods have a certain impact on whether people choose screening.In this editorial,we explore strategies for the early diagnosis of CRC,including stool-based,blood-based,direct visualization,and imaging examinations.展开更多
文摘<strong>Objective:</strong> To investigate the value of the number of circulating tumor cells (CTC) in peripheral blood in the prognosis and coagulation-related indicators of patients with renal cancer. <strong>Methods:</strong> 65 patients with renal cell carcinoma (RCC) confirmed pathologically were divided into CTC positive group and CTC negative group according to the CTC count (5 pcs/3.5 ml). Compare the age, gender, tumor location, TNM (clinical stage), pathological grade, tissue type, lymph node metastasis, distant metastasis, prognosis and prothrombin time (PT), fibrinogen (FIB), partial coagulation of the two groups of patients The correlation between the results of zymogen time (APTT) and D-dimer (DD) and the number of CTC. <strong>Results:</strong> There were significant differences in TNM, lymph node metastasis, and distant metastasis between the two groups (P < 0.05). The number of CTC in patients was correlated with FIB and D-D levels (P < 0.05). <strong>Conclusion:</strong> The number of CTC in patients with renal cell carcinoma is correlated with some clinical phenotypes (TNM, lymph node metastasis, distant metastasis) and some coagulation indexes (FIB, D-D), and can jointly predict the prognosis of renal cancer.
基金This present study was financially supported by Baoding City Science and Technology Plan project(2041ZF084)Key Laboratory of Molecular Pathology and Early Diagnosis of Tumor in Hebei Province.
文摘Objective:To determine the clinical value of combined detection of circulating tumor cells(CTCs)and cell-free DNA(cfDNA)in peripheral blood of patients with triple-negative breast cancer.Method:41 patients with breast cancer admitted to the First Central Hospital of Baoding from January 2020 to December 2021 were selected and recruited into the experimental group,42 patients with benign breast cancer admitted during the same period were recruited into the conditional control group,and 41 healthy patients admitted during the same period were recruited into the blank control group.The positive rate of peripheral blood CTCs,the level of cfDNA,and the diagnostic efficacy of peripheral blood CTCs,cfDNA alone and the combination thereof for breast cancer were analyzed.Result:The positive rates of peripheral blood CTCs in the experimental group,the conditional control group,and the blank control group were 43.90%,11.90%,and 9.74%,respectively,and there was significant difference among the groups.The levels of cfDNA in peripheral blood of the experimental group,the conditional control group,and the blank control group were 0.26±0.08 bp,0.17±0.03 bp,and 0.15±0.04 bp,respectively,which were statistically significant.The detection levels of 100 bp hTERT/ng mT1 and 241 bp hTERT/ng-mT1 in the experimental group were significantly higher than those in the conditional control group and the blank control group.The accuracy of peripheral blood CTCs detection in the three groups was 66.21%,the accuracy of cfDA241 bp/100 hp hTERT detection was 80.41%,and the accuracy of combined detection of peripheral blood CTCs and cfDNA was 94.03%.Conclusion:The clinical application of peripheral blood CTCs combined with cfDNA level detection can increase detection accuracy,provide data support for clinicians,and improve the clinical diagnostic effect of triple-negative breast cancer.
基金Baoding Science and Technology Project(Project Number:18ZF134)Youth Fund of Affiliated Hospital of Hebei University(Project Number:2017Q018)。
文摘Objective:To explore the correlation between peripheral circulating tumor cells and hypercoagulability in patients with lung cancer after surgery.Methods:From January 2017 to December 2021,89 patients with lung cancer who were treated in the Affiliated Hospital of Hebei University were selected as the research subjects,and a retrospective analysis was conducted to analyze and observe the D-dimer(DD),fibrinogen(FIB),and platelet(PLT)levels in peripheral blood,as well as detect peripheral CTC.Results:There were statistical differences in TMN staging,tumor metastasis,and lymph node metastasis in the clinical data,but there were no statistical differences in gender,smoking history,and pathological classification.After retrospective analysis and comparison of the patients,the DD(mg/ml),FIB(g/L),and PLT(×10^(9)/L)levels of the CTC positive group were 3.41±0.58,3.98±0.87,and 367.26±34.98,respectively;the CTC negative group’s DD(mg/ml),FIB(g/L),and PLT(×10^(9)/L)levels were 0.89±0.49,1.06±0.45,and 234.69±35.69,respectively,and the differences were statistically significant.The factors affecting the prognosis of patients included TMN staging and CTC;the number of CTC positives in the death group was significantly higher than that in the survival group,and there was a statistical difference between the groups.Gender,age,smoking history,pathological type,and surgical resection had no effect on the prognosis of patients.Among the enrolled patients,the survival rate was 71.91%.Conclusion:CTC-positive patients have a higher probability of hypercoagulability after surgery and are prone to tumor metastasis;thus,CTC can be used as a judgment index for the prognosis of patients.
基金Supported by a grant from "Trainig and Mobility of Researchers" program, RX-CT98-0240
文摘AIM: To investigate whether the stimulation of peripheral blood mononuclear cells (PBMNC) with the cell debris and cell extraction of different probiotic strains is similar or species specific. METHODS: Three strains of bifidobacteria, 4 strains of lactobacilli, and E. coli nissle were sonicated and centrifuged in order to divide them into cell extract and cell debris. PBMNC were separated by density gradient and incubated for 36 h with either the cell debris or the cell extract of single strains of probiotic bacteria in doses from 10^2 to 10^8 CFU/mL. Cell supernatants were taken and interleukin (IL)-10, IL-1β, and tumor necosis factor (TNF)-α were determined by ELISA. RESULTS: Depending on the species super-family, the strains had different stimulation patterns. Except for both L. casei strains, the cell extract of bitTdobacteria and/actobacilli had less stimulating capacity than cell debris, whereas the cell extract of E. coli nissle had similar stimulating properties to that of the cell debris of the strain and significantly more stimulating capacity than that of bifidobacteria and lactobacilli. The cell debris of bifidobacteria stimulated more cytokine release than the cell debris of lactobacilli. The cell debris of lactobacilli did not have a stimulating capacity when lower concentrations were used. Neither cell extraction nor cell debris had an inhibitory effect on the production of the tested cytokines by stimulated PBMNC. CONCLUSION: The incubation of probiotic strains, which have been used in clinical trials for inflammatory diseases, with immunocompetent cells leads to different species specific reactions. High IL-10 response to cell debris of bifidobacteria and E. coli nissle can be found. This corresponds to positive effects of bihdobacteria and E. coli nissle in clinical trials for inflammatory bowel disease compared to negative outcomes obtained with lactobacilli.
基金This work is supported by US NIH/NCI research grant(2PO1CA098912)edars-Sinai Medical Center Board of Governors Cancer Research Chair(LWKC),and US NIH/NCI(UO1CA198900)(HRT/EMP).
文摘Recent cancer research has demonstrated the existence of circulating tumor cells(CTCs)in cancer patient’s blood.Once identified,CTC biomarkers will be invaluable tools for clinical diagnosis,prognosis and treatment.In this review,we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample,to derive enough CTCs for accurate and reproducible characterization of the biophysical,biochemical,gene expressional and behavioral properties of the harvested cells.Because of tumor cell heterogeneity,it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis.By analyzing critical steps and technical issues in ex vivo CTC culture,we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells,relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells.
文摘The relationship between tumour necrosis lactose (TNF-α) gene polymorphism and inhibitory effects of triptolide on TNF-α production from peripheral blood mononuclear cells (PBMC) of healthy humans was investigated. Genomic DNA from 41 healthy people was typed for TNF-α- 308 polymorphism by allele-specific polymorphism chain reaction (AS-PCR). The TNF-α concentration in the supernatant was measured by ELISA. The results showed that the production of TNF-α from TNF-α -308 non-G/G genotype PBMC was higher than that from TNF-α-308 G/G genotype PBMC after stimulated by LPS. Triptolide could lower the production of TNF-α from G/ G genotype PBMC, but had no effect on the level of TNF-α from non-G/G genotype PBMC. It was concluded that TNF-α gene polymorphism was related to the TNF-α production from triptolide-inhibited PBMC culture in healthy humans.
文摘AIM To investigate whether circulating cytokeratin-positive(CK^+) cells in the mesenteric blood of resected colorectal specimens are prognostic and correlate with tumor budding.METHODS Fifty-six colorectal specimens were collected between 9/2007 and 7/2008.Blood from the mesenteric vein was drawn immediately after receiving the fresh and unfixed specimens in the pathology department.After separation of the mononuclear cells by Ficoll-Hypaquedensity-gradient centrifugation,cytological smears were immunocytochemically stained for CK18.Tumor budding was evaluated on slides stained for pan-cytokeratin.The identification of ≥ 30 buds/1.3 mm2 was defined as high grade budding.RESULTS CK^+ cells and clusters were identified in 29(48%) and 14(25%) of the samples,respectively.Two cells were identified in one of three non-malignant cases.Clusters were found exclusively in malignant cases.The occurrence of CK^+ cells or clusters was not associated with any of the evaluated clinicopathological factors,including surgical technique and tumor budding.Moreover,the occurrence of CK^+ cells or clusters had no influence on the cancerspecific survival [75 mo(CI:61;88) vs 83 mo(CI:72;95) and 80 mo(CI:63;98) vs 79 mo(CI:69;89),respectively].CONCLUSION CK^+ cells and showed neither prognostic significance nor an association with tumor budding.It is very likely that CK18-staining is not specific enough to identify the relevant cells.
基金This work was funded by the National Natural Science Foundation of China(Grant Nos.61774095 and 21727813)the Beijing Research Institute of Mechanical Equipment.
文摘Isolating rare circulating tumor cells(CTCs)from blood is critical for the downstream analysis that is important in cancer-related research,diagnosis,and medicine,and efforts are ongoing to increase the efficiency and purity of CTC isolation in microfluidics.Reported in this paper is a two-stage integrated microfluidic chip for coarse-to-fine CTC isolation from whole blood.First,blood cells are removed by filtration using a micropore-array membrane,then CTCs and other cells that are trapped in the micropores are peeled off the membrane by a novel release method based on air–liquid interfacial tension,which significantly increases the recovery rate of CTCs.The second stage is CTC capture based on an on-chip dense immuno-magnetic-bead clump,which offers high capture efficiency and purity.Both the micropore filtration and immuno-magnetic-bead capture are validated and optimized experimentally.Overall,the integrated microfluidic chip can realize a recovery rate of 85.5%and a purity of 37.8%for rare cancer cells spiked in whole blood.
文摘Objective:To investigate the effects of Shenqi Fuzheng Injection combined with chemotherapy on peripheral blood cell level, tumor markers and immune function in patients with gastric cancer.Methods: Eighty patients with gastric cancer admitted to our hospital from May 2016 to October 2017 were selected as the research object and randomly divided into observation group and control group, 40 cases in each group. Control group was treated by DCF chemotherapy, while the observation group by Shenqi Fuzheng Injection based on the DCF chemotherapy. The levels of peripheral blood cells, tumor markers and immune function indexes in both groups were detected and compared before and after treatment.Results: There were no significant differences in serum RBC, WBC, PLT, Hb, NSE, CYFRA21-1, CA199, CEA, CD3+, CD4+, CD8+ and CD4+/CD8+ levels before treatment in both groups. Compared with the pretreatment group, the levels of RBC, WBC, PLT and Hb in both groups decreased to some extent after treatment, and the levels in the observation group were significantly higher than those in the control group;Compared with the same group before treatment, the levels of NSE, CYFRA21-1, CA199 and CEA in the two groups were significantly decreased, and the observation group was significantly lower than the control group;CD3+, CD4+, CD4+/CD8+ levels in control group and observation group increased to some extent after treatment, and the levels in observation group were significantly higher than those in control group. The levels of CD8+ in both groups after treatment were significantly lower than those before treatment, and the observation group was significantly lower than the control group after treatment. The above data for statistical analysis had significant differences.Conclusions: Shenqi Fuzheng injection combined with chemotherapy helps to clear and kill cancer cells, enhance immunity and reduce hematological toxicity after chemotherapy, which can be used as an adjuvant chemotherapy for gastric cancer.
基金Natural Science Foundation of the Higher Education Office of Guangdong Province,No.19952901
文摘INTRODUCTIONDendritic cells (DCs) play a key regulatory role inantitumor immunity,especially in its immuneaccessory role via MHC-Ⅰ molecules.We haverecently reported that DCs were able to enhance thekilling activity of Lymphokine and PHA activatedkiller (LPAK) cells in vitro.In the presentstudy,we evaluated the effects of GM-CSF andTNF upon antitumor activities of freshly
基金Supported by Hamburger Stiftung zur Forderung der KrebsbekampfungNo.188 to Grobe A and Riethdorf SERC Advanced Investigator Grant "DISSECT"(Pantel K),No.269081.
文摘Due to a lack of substantial improvement in the outcome of patients suffering from oral squamous cell carcinoma(OSCC) during the past decades, current staging methods need to be revised. This disease is associated with poor survival rates despite considerable advances in diagnosis and treatment. The early detection of metastases is an important indicator of survival, prognosis and relapse. Therefore, a better understanding of the mechanisms underlying metastasis is crucial. Exploring alternative measures apart from common procedures is needed to identify new prognostic markers. Similar to previous findings predominantly for other solid tumours, recently published studies demonstrate that circulating tumour cells(CTCs) and disseminated tumour cells(DTCs) might serve as prognostic markers and could supplement routine staging in OSCC. Thus, the detection of CTCs/DTCs is a promising tool todetermine the individual need for therapeutic intervention. Encouraging results and new approaches point to the future use of targeted therapies for OSCC, an exceedingly heterogeneous subgroup of head and neck cancer. This review focuses on summarising technologies currently used to detect CTCs/DTCs. The translational relevance for OSCC is highlighted. The inherent challenges in detecting CTCs/DTCs will be emphasised.
基金National Natural Science Foundation of China,Grant/Award Numbers:82130003,81970158,82000180Zhejiang Provincial Key R&D Projects of Department of Science and Technology,Grant/Award Number:2021C03010Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004。
文摘Background:Cancer-targeted T-cell receptor T(TCR-T)cells hold promise in treating cancers such as hematological malignancies and breast cancers.However,approaches to obtain cancer-reactive TCR-T cells have been unsuccessful.Methods:Here,we developed a novel strategy to screen for cancer-targeted TCR-T cells using a special humanized mouse model with person-specific immune fingerprints.Rare steady-state circulating hematopoietic stem and progenitor cells were expanded via three-dimensional culture of steady-state peripheral blood mononuclear cells,and then the expanded cells were applied to establish humanized mice.The human immune system was evaluated according to the kinetics of dendritic cells,monocytes,T-cell subsets,and cytokines.To fully stimulate the immune response and to obtain B-cell precursor NAML-6-and triple-negative breast cancer MDA-MB-231-targeted TCR-T cells,we used the inactivated cells above to treat humanized mice twice a day every 7 days.Then,human T cells were processed for TCRβ-chain(TRB)sequencing analysis.After the repertoires had been constructed,features such as the fraction,diversity,and immune signature were investigated.Results:The results demonstrated an increase in diversity and clonality of T cells after treatment.The preferential usage and features of TRBV,TRBJ,and the V–J combination were also changed.The stress also induced highly clonal Science and Technology,Grant/Award Number:2021C03010;Zhejiang Provincial Natural Science Foundation of China,Grant/Award Numbers:LTGY24H080003,LY21H080004 expansion.Tumor burden and survival analysis demonstrated that stress induction could significantly inhibit the growth of subsequently transfused live tumor cells and prolong the survival of the humanized mice.Conclusions:We constructed a personalized humanized mouse model to screen cancer-targeted TCR-T pools.Our platform provides an effective source of cancer-targeted TCR-T cells and allows for the design of patient-specific engineered T cells.It therefore has the potential to greatly benefit cancer treatment.
基金the National Natural Science Foundation of China(21775128,21974113,21735004,21974112,and 21874089)National Key R&D Program of China(2019YFA0905800)+2 种基金Program for Chang Jiang Scholars and Innovative Research Teams in University(IRT13036)Medical and Health Program of Xiamen(3502Z20189005)the National Science Fund for Fostering Talents in Basic Science(NFFTBS,J1310024)for their financial support.
文摘Circulating tumor cells(CTCs),as important liquid biopsy target,can provide valuable information for cancer progress monitoring and individualized treatment.However,current isolation platforms incapable of balancing capture efficiency,specificity,cell viability,and gentle release have restricted the clinical applications of CTCs.Herein,inspired by the structure and functional merits of natural membrane interfaces,we established an antibody-engineered red blood cell(RBC-Ab)affinity interface on microfluidic chip for high-performance isolation and release of CTCs.The lateral fluidity,pliability,and anti-adhesion property of the RBC microfluidic interface enabled efficient CTCs capture(96.5%),high CTCs viability(96.1%),and high CTCs purity(average 4.2-log depletion of leukocytes).More importantly,selective lysis of RBCs by simply changing the salt concentration was utilized to destroy the affinity interface for efficient and gentle release of CTCs without nucleic acid contamination.Using this chip,CTCs were successfully detected in colon cancer samples with 90%sensitivity and 100%specificity(20 patients and 10 healthy individuals).After the release process,KRAS gene mutations of CTCs were identified from all the 5 cancer samples,which was consistent with the results of tissue biopsy.We expect this RBC interface strategy will inspire further biomimetic interface construction for rare cell analysis.
文摘目的联合检测肺腺癌患者外周血中细胞角蛋白(cytokeratin,CK,肺腺癌循环肿瘤细胞阳性)和CD133基因(肺癌干细胞标志物)的表达,探讨二者在评估肺腺癌预后的临床价值。方法选取2014年6月至2016年6月昆明总医院心胸外科和宣威市第一人民医院心胸外科的178例未化疗的肺腺癌手术患者,中位年龄59岁,其中男性78例,女性100例。收集患者术前外周血标本10 m L,细胞块法和CK(免疫细胞化学法)用于检测CTC,PCR法用于检测CD133表达。免疫组化法检测肺腺癌组织中CK、Vimentin(Vim)、TTF-1、Ki-67、CD133的表达,并分析与外周血CK和CD133表达的关系。根据外周血CK和CD133的检测结果,将病例分为CK/CD133双阳性组和非双阳性组,统计学分析两组间临床病理因素的差异。结果 178例肺腺癌患者外周血CTC(CK阳性)的检出率为48.3%(86/178),与癌组织中Ki-67、Vim表达显著正相关(P<0.05);外周血的CD133阳性表达率为66.9%(119/178),与癌组织Vim、CD133表达显著正相关(P<0.05);外周血CK/CD133双阳组53例(29.8%),双阳组淋巴结转移率显著增高,肺腺癌组织学分化级别显著降低,临床分期显著提高,转移率显著增高(P<0.05)。结论肺腺癌患者外周血中CK与CD133双阳性表达提示外周血存在干性特征的循环肿瘤细胞,表明预后不良,联合检测CK与CD133可用于肺腺癌患者预后监测和指导治疗。
基金Supported by the Talent Scientific Research Start-up Foundation of Wannan Medical College,No.WYRCQD2023045。
文摘At present,cancer is still an important factor threatening human health.Colorectal cancer(CRC)is one of the top three most common cancers worldwide and one of the deadliest malignancies in humans.The latest data showed that CRC incidence and mortality rank third and second,respectively,among global malignancies.Early and accurate diagnosis is crucial to reduce the morbidity,mortality and improve survival of patients with CRC,but the current early diagnostic methods have limitations.The effectiveness and compliance of diagnostic methods have a certain impact on whether people choose screening.In this editorial,we explore strategies for the early diagnosis of CRC,including stool-based,blood-based,direct visualization,and imaging examinations.