ABSTRACT
Mesenchymal to epithelial transition factor (MET) gene alterations involve in the proliferation, invasion, and metastasis of non-small cell lung cancer. MET-tyrosine kinase inhibitors (TKIs) have been approved to treat non-small cell lung cancer with MET alterations, and resistance to these TKIs is inevitable. Molecular mechanisms of resistance to MET-TKIs are completely unclear. The review focused on potential mechanisms of MET-TKIs resistance and therapeutics strategies to delay and prevent resistance. .
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/pathology , ErbB Receptors/genetics , Drug Resistance, Neoplasm/genetics , Protein Kinase Inhibitors/therapeutic use , Epithelial-Mesenchymal Transition , MutationABSTRACT
The composition of serum is extremely complex,which complicates the discovery of new pharmaco-dynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich low-abundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and devel-oped a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56％using PC-based proteomic analysis,which was twice the number of proteins iden-tified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment.
ABSTRACT
Objective:To systematically evaluate the relationship between sedentary behavior (SB) and the risk of developing gestational diabetes mellitus (GDM).Methods:PubMed, Medline, EMBASE, CINAHL, the Cochrane Library, the Rehabilitation & Sports Medicine Source, the Sedentary Behavior Research Database (SBRD), Wanfang Database, the China Journal full-text database, and the China Biomedical Literature Database were searched for cohort studies, case-control studies, and cross-sectional studies concerning the risk of SB and GDM from the establishment of the database to January 2021. Two researchers screened the literature, extracted data, evaluated the quality of the data according to the inclusion and exclusion criteria, and, finally, produced a descriptive analysis of the results.Results:A total of 11 studies were included, including eight cohort studies, two cross-sectional studies, and one case-control study. The overall quality of the studies was moderate. The prevalence of GDM was 5.04%-26.81%, and the prevalence of SB before and during pregnancy was 39.47%-40.21% and 28.86%-93.50%, respectively. In terms of the prevalence of SB before pregnancy, four moderate-quality studies reported no association with GDM risk. In terms of SB during pregnancy, four moderate-quality studies reported no association with GDM risks, and four studies (one of high quality and three of moderate quality) reported an association with GDM risks, two of which focused on the second trimester. There was considerable heterogeneity between studies on the diagnosis of GDM and SB.Conclusion:SB before pregnancy is not associated with the risk of GDM, while the relationship between SB and the risk of GDM is unclear, but the level of SB in the second trimester of pregnancy may be positively associated with the risk of GDM.
ABSTRACT
Purpose@#Titanium implants are widely used in the treatment of dentition defects; however, due to problems such as osseointegration failure, peri-implant bone resorption, and periimplant inflammation, their application is subject to certain restrictions. The surface modification of titanium implants can improve the implant success rate and meet the needs of clinical applications. The goal of this study was to evaluate the effect of the use of porous titanium with a chitosan/hydroxyapatite coating on osseointegration. @*Methods@#Titanium implants with a dense core and a porous outer structure were prepared using a computer-aided design model and selective laser sintering technology, with a fabricated chitosan/hydroxyapatite composite coating on their surfaces. in vivo and in vitro experiments were used to assess osteogenesis. @*Results@#The quasi-elastic gradient and compressive strength of porous titanium implants were observed to decrease as the porosity increased. The in vitro experiments demonstrated that, the porous titanium implants had no biological toxicity; additionally, the porous structure was shown to be superior to dense titanium with regard to facilitating the adhesion and proliferation of osteoblast-like MC3T3-E1 cells. The in vivo experimental results also showed that the porous structure was beneficial, as bone tissue could grow into the pores, thereby exhibiting good osseointegration. @*Conclusions@#Porous titanium with a chitosan/hydroxyapatite coating promoted MC3T3-E1 cell proliferation and differentiation, and also improved osseointegration in vitro. This study has meaningful implications for research into ways of improving the surface structures of implants and promoting implant osseointegration.
ABSTRACT
Purpose@#Titanium implants are widely used in the treatment of dentition defects; however, due to problems such as osseointegration failure, peri-implant bone resorption, and periimplant inflammation, their application is subject to certain restrictions. The surface modification of titanium implants can improve the implant success rate and meet the needs of clinical applications. The goal of this study was to evaluate the effect of the use of porous titanium with a chitosan/hydroxyapatite coating on osseointegration. @*Methods@#Titanium implants with a dense core and a porous outer structure were prepared using a computer-aided design model and selective laser sintering technology, with a fabricated chitosan/hydroxyapatite composite coating on their surfaces. in vivo and in vitro experiments were used to assess osteogenesis. @*Results@#The quasi-elastic gradient and compressive strength of porous titanium implants were observed to decrease as the porosity increased. The in vitro experiments demonstrated that, the porous titanium implants had no biological toxicity; additionally, the porous structure was shown to be superior to dense titanium with regard to facilitating the adhesion and proliferation of osteoblast-like MC3T3-E1 cells. The in vivo experimental results also showed that the porous structure was beneficial, as bone tissue could grow into the pores, thereby exhibiting good osseointegration. @*Conclusions@#Porous titanium with a chitosan/hydroxyapatite coating promoted MC3T3-E1 cell proliferation and differentiation, and also improved osseointegration in vitro. This study has meaningful implications for research into ways of improving the surface structures of implants and promoting implant osseointegration.
ABSTRACT
Recently, studies showed that neutrophils extracellular traps (NETs) are the fiber network structures formed by the materials released by neutrophils under various appropriate stimulation. NETs have been indicated to trap and kill microorganisms, playing a critical role in immune responses. It was pointed out that NETs can not only be involved in inflammation and thrombosis, but also is intimately related to tumor metastasis. Therefore, the study of NETs in tumor metastasis is of great significance for tumor therapy and the progress of NETs in tumor metastasis and the relevant mechanisms is summarized. .
ABSTRACT
Objective To evaluate the relationship between concurrent myocardial bridge at anterior descending branch and the formation of coronary atherosclerosis plaques by using transluminal attenuation gradient (TAG). Methods A total of 198 patients underwent coronary CTA in Renji Hospital of Shanghai Jiaotong University School of Medcine from June 2017 to March 2018 and the results showed the anterior descending myocardial bridge. The data were retrospectively analyzed. All patients completed the coronary CTA with 320?row detector CT. According to the manifestations of myocardial bridge on CTA,the patients were divided into deep and superficial myocardial bridge groups. According to whether the patients were complicated with coronary atherosclerotic plaques, they were divided into isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group. The thickness and length of myocardial bridge, the volume of coronary atherosclerotic plaques at the site of myocardial bridge, the pre?bridge and post?bridge TAG values, and the K ratio were recorded. Independent sample t test (normal distribution) or Mann?Whitney U test (skewed distribution) was used to compare the difference of measurement data among different groups. χ2 test was used to compare the difference of enumeration data among different groups. Pearson correlation test was used to analyze the correlation among pre?bridge and post?bridge TAG values,K ratio,thickness and length of myocardial bridge and plaque volume. The influence of above indexes on plaque occurrence was analyzed by binary logistic regression analysis. The relationship between main influence indexes and plaque formation was analyzed by receiver operating characteristic curve (ROC). Results Ninety nine patients had isolated myocardial bridge,99 with myocardial bridge and coronary atherosclerotic plaques,27 with superficial myocardial bridge and 171 with deep myocardial bridge. All atherosclerotic plaques occurred in pre?bridge and the mean volume of plaques was (91.6±83.0)mm3. The differences in sex, age, height, body weight and body mass index werenot statistically significant between isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group (all P>0.05). The difference in pre?bridge TAG value was statistically significant between the isolated myocardial bridge group and myocardial bridge with coronary atherosclerotic plaque group (all P<0.05), but not statistically significant in post?bridge TAG value and K ratio (all P>0.05). The difference in pre?bridge and post?bridge TAG values and K value was not statistically significant between the superficial group and the deep group (all P>0.05). There was a weak negative correlation (r=-0.205,-0.316,-0.339,respectively,P<0.05) between the plaque volume and pre?bridge&post?bridge TAG values and K ratio. The pre?bridge TAG value significantly affected the plaque formation (P=0.014) and the odds ratio was 0.884 (95% CI 0.801 to 0.976). While other factors had no significant effects on plaque formation (all P>0.05). The area under curveof plaque formation promoted by pre?bridge TAG value was 0.582. When the diagnostic critical value was －37.26 HU/mm, the sensitivity and specificity of pre?bridge TAG value in plaque formation were 31.31% and 81.82%, respectively. Conclusion The TAG value of anterior descending bridge is an independent risk factor for plaque occurrence. The abnormal TAG value of anterior descending myocardial bridge can be detected early by CTA.
ABSTRACT
Objective:Previous studies have shown an association between programmed death-ligand 1 expression(PD-L1)in non-small cell lung cancer(NSCLC)and clinical factors and that PD-L1 is positively correlated with TNM staging.This study aimed to explore the prognostic significance of PD-L1 and its correlation with the maximum standardized uptake value(SUVmax).Methods:Clinicopath-ological data and the follow-up information of the 122 de novo primary NSCLC patients were analyzed.PD-L1 expression was detected by immunohistochemistry in this 122 surgically resected non-small cell lung carcinoma tissues.Survival outcomes were analyzed using the Kaplan-Meier method and multivariate Cox proportional hazards model.Correlation between SUVmax and PD-L1 expression was analyzed using Spearman's rank correlation analysis.Results:Multivariate analysis revealed that PD-L1 expression(HR=4.518,95% CI:1.176-17.352,P=0.028)and tumor size(HR=1.404,95%CI:1.020-1.933,P=0.037)were independent risk factors for overall survival(OS) in early NSCLC patients.Sex,age,pathological type,CEA level,and SUVmax group had no obvious effect on OS(P 0.05)in early NSCLC patients.In univariate analyses,sex,pathological type,tumor size,and SUVmax group affected OS in stageⅢ-ⅣNSCLC patients.How-ever,age,CEA level,and PD-L1 expression had no effect on OS.PD-L1 expression was not an independent risk factor for OS in stageⅢ-ⅣNSCLC patients.The SUVmax group had no association with PD-L1 in all patients.Conclusions:PD-L1 expression is an independent risk factor for OS in early NSCLC patients but not in stageⅢ-Ⅳpatients.
ABSTRACT
PURPOSE: The treatment of triple-negative breast cancer (TNBC) remains challenging, due to the absence of estrogen, progesterone, and human epidermal growth factor receptors. This study was designed to evaluate the efficiency and safety of cytokine-induced killer (CIK) cell immunotherapy, following regular chemotherapy, for patients with TNBC. METHODS: A total of 340 patients with postmastectomy TNBC, from January 1, 2010 to June 30, 2014, were included in this retrospective study. Seventy-seven patients received CIK cell immunotherapy, following regular chemotherapy (arm 1), and 263 patients received regular chemotherapy alone (arm 2). The primary aim was overall survival (OS) and disease-free survival (DFS), and the treatment responses and adverse events were also evaluated. RESULTS: The 5-year DFS and OS rates in arm 1 were 77.9% and 94.3%, compared with 69.8% and 85.6% in arm 2, respectively (p=0.159 and p=0.035, respectively). This clearly shows that there was no statistical difference in the 5-year DFS between the two groups. Multivariate analyses of arm 1 indicated that a Karnofsky performance score (KPS) ≥90 and stage I/IIA disease were significantly associated with a prolonged DFS period (hazard ratio [HR], 0.25; 95% confidence interval [CI], 0.09–0.74; p=0.012; and HR 0.21; 95% CI, 0.06–0.82; p=0.024, respectively), but a KPS ≥90 and stage I/IIA disease were not independent prognostic factors for OS. Toxicity was mild in patients who received the CIK therapy. CONCLUSION: The data suggested that CIK cell immunotherapy improved the efficiency of regular chemotherapy in patients with TNBC, and the side effects of CIK cell immunotherapy were mild.
Subject(s)
Humans , Arm , Cytokine-Induced Killer Cells , Disease-Free Survival , Drug Therapy , Estrogens , Immunotherapy , Multivariate Analysis , Progesterone , Prognosis , ErbB Receptors , Retrospective Studies , Triple Negative Breast NeoplasmsABSTRACT
Objective To construct a ciaR gene-knockout (ΔciaR) mutant of Streptococcus pneu-moniae ( S. pneumoniae) and to investigate the effects of CiaR in CiaH/CiaR, a streptococcal two-component signal-transducing system, on the expression of genes encoding penicillin-binding proteins ( pbps genes) and cia-dependent small RNAs (csRNAs). Methods Electrophoretic mobility shift assay (ESMA) was per-formed to detect the recombinant CiaR (rCiaR)-binding pbps genes. A suicide plasmid pEVP3ciaR for ciaR gene knockout was constructed and then aΔciaR mutant was obtained through homologous recombination and insertion inactivation of the suicide plasmid, and screening with chloromycin. The mutant was identified using PCR and sequencing analysis. E-test was used to detect the minimal inhibitory concentrations ( MIC) of penicillin ( PCN) and cefotaxime ( CTX) against S. pneumoniae strains. Changes and differences in the expression of pbps genes and csRNAs in theΔciaR mutant and its wild-type strain before and after treatment with 1/4 MIC of PCN or CTX were detected using real-time quantitative RT-PCR. Results The rCiaR could bind to the promoter regions in pbp1a, pbp1b and pbp2b genes of S. pneumoniae. The ciaR gene in ΔciaR mutant was inactivated by insertion according to the results of PCR and sequencing analysis. After treatment with 1/4 MIC of PCN or CTX, the expression of pbps genes at mRNA level ( pbps-mRNAs) in theΔciaR mu-tant was significantly increased (P<0. 05), but the levels of csRNAs were significantly decreased (P<0. 05);whereas a significantly decreased pbps-mRNAs (P<0. 05) and increased csRNAs (P<0. 05) were observed in its wild-type strain. The result of E-test showed that the MICs of PCN and CTX against ΔciaR mutant were increased by 250-fold as compared with those against its wild-type strain. Conclusion The CiaR can enhance the drug resistance of S. pneumoniae to PCN and CTX through down-regulating the expres-sion of PBP1a, PBP1b and PBP2b and up-regulating the expression of csRNAs to inhibit the expression of PBPs.
ABSTRACT
Objective To study the influence of diet and behavior related factors on the peripheral blood triglyceride levels in adults,through a cross-sectional survey.Methods The current study included 13 434 subjects without histories of major chronic diseases from a population-based cross-sectional survey:the 2010 Metabolic Syndrome Survey in Zhejiang Province.A generalized linear model was used to investigate the influence of diet/behavior-related factors on the peripheral blood triglyceride levels.Results Mean TG of the sample population appeared as (1.36± 1.18) mmol/L.The proportions of elevated TG and marginally elevated TG were 10.3％ and 11.0％ respectively,with statistically significant difference seen between males and females (x2=44.135,P＜0.001).In this sampled population,the daily intake of cooking oil was exceeding the recommendation levels by over 50％ while the intake of fruit,milk,nuts and physical exercise were much below the recommendation.There were statistically significant differences between smoking,alcohol-intake,meat,fruit and water intake in male population from this study.However,in females,the intake of aquatic product and physical exercise showed statistically significant differences.After controlling for other variables,factors as age,drinking,staple food and aquatic products showed positive influence on TG,while milk presented negative influence on TG.Through interaction analysis,fruit and meat intake in males and staple food in females showed positive influence on TG,when compared to the reference group.Conclusion Hyperglyceridemia appeared as one of the major metabolic abnormities in Zhejiang province.Programs on monitoring the alcohol,staple food and meat intake should be priority on intervention,in the communities.
ABSTRACT
Objective To study the influence of diet and behavior related factors on the peripheral blood triglyceride levels in adults,through a cross-sectional survey.Methods The current study included 13 434 subjects without histories of major chronic diseases from a population-based cross-sectional survey:the 2010 Metabolic Syndrome Survey in Zhejiang Province.A generalized linear model was used to investigate the influence of diet/behavior-related factors on the peripheral blood triglyceride levels.Results Mean TG of the sample population appeared as (1.36± 1.18) mmol/L.The proportions of elevated TG and marginally elevated TG were 10.3％ and 11.0％ respectively,with statistically significant difference seen between males and females (x2=44.135,P＜0.001).In this sampled population,the daily intake of cooking oil was exceeding the recommendation levels by over 50％ while the intake of fruit,milk,nuts and physical exercise were much below the recommendation.There were statistically significant differences between smoking,alcohol-intake,meat,fruit and water intake in male population from this study.However,in females,the intake of aquatic product and physical exercise showed statistically significant differences.After controlling for other variables,factors as age,drinking,staple food and aquatic products showed positive influence on TG,while milk presented negative influence on TG.Through interaction analysis,fruit and meat intake in males and staple food in females showed positive influence on TG,when compared to the reference group.Conclusion Hyperglyceridemia appeared as one of the major metabolic abnormities in Zhejiang province.Programs on monitoring the alcohol,staple food and meat intake should be priority on intervention,in the communities.
ABSTRACT
microRNAs is a group of small non-coding RNAs that play a negative regulation role in expression of target genes at post-transcriptional level by inhibition or degradation of target mRNAs after combination of the seed sequence (SS) in microRNAs with the SS-binding sequences usually located at 5'ends of target mRNAs.microRNAs was firstly found in Caenorhabditis elegans.Subsequently,many different microRNAs in eukaryocytes were revealed.In eukaryocytes,microRNA precursors are transcribed at first and then become functional microRNAs with 21-23 nt in size after splice.Most of eukaryocytic microRNAs combime with the sequences at 3'end of target mRNAs that cause the translation inhibition or degradation of the mRNAs.In the recent years,many different prokaryocytes,such as bacteria,have been confirmed to possess microRNAs.However,the microRNAs in prokaryotes such as bacteria are 50-400 nt in size and have the biological activity without splice.Moreover,the characteristics,action sites and mechanisms of the prokaryotic microRNAs have some certain diversity compared to the eukaryotic microRNAs.Our review briefly introduce the major regulation mechanisms of gene expression as well as the general characteristics of microRNAs and their regulation mechanisms of gene expression in prokaryocytes and eukaryocytes,which will provide a basis for further and profound study on the gene expression regulation and pathogenic mechanisms of prokaryotic microbial pathogens.
ABSTRACT
Objective To investigate the correlation between Streptococcus pneumoniae (S.pneumoniae) StkP kinase and drug resistance and to analyze the binding ability of StkP extracellular region (EC-StkP) to β-lactam antibiotics.Methods A stkP gene knockout (ΔstkP) mutant was constructed from S.pneumoniae strain ATCC6306 by insertional inactivation method.E-test was performed to detect the minimum inhibitory concentrations (MIC) of penicillin (PCN) and cefotaxime (CTX) against ΔstkP mutant and its wild-type strain.Bioinformatic softwares were used to predict the EC-StkP of S.pneumonia strain ATCC6306,to generate the three-dimensional structure model of EC-StkP and to analyze the correlation between the structure and functions of EC-StkP.PCR was performed to amplify the extracellular segment of stkP (EC-stkP) gene and the product of it was sequenced after T-A cloning.A prokaryotic expression system of EC-stkP gene was constructed.SDS-PAGE in combination with a gel image analysis system was used to detect the expression of the recombinant EC-StkP (EC-rStkP).The expressed EC-rStkP was extracted by Ni-NTA affinity chromatography.The binding abilities of EC-rStkP to PCN and CTX were detected by isothermal titration calorimetry (VT-ITC) and surface plasmon resonance (Biacore).Results S.pneumonia strain ATCC6306 was sensitive to PCN (MIC=0.06 μg/ml) and CTX (MIC=0.12 μg/ml),but its ΔstkP mutant was resistant to the two antibiotics (PCN MIC=16 μg/ml,CTX MIC=32 μg/ml).The 295 aa segment was predicted as the extracellular region at C-end of StkP of S.pneumoniae strain ATCC6306,containing four penicillin-binding proteins and Ser/Thr kinase-associated (PASTA) domains.The cloned EC-stkP segment and the EC-stkP segment in GenBank shared 99.6% similarity in nucleotide sequence and 100% in amino acid sequence.The constructed prokaryotic expression system for EC-stkP gene expressed EC-rStkP in soluble form.Both PCN and CTX could bind to EC-rStkP and CTX was better than PCN in term of binding ability.Conclusion The stkP gene of S.pneumonia is closely related to drug resistance and the encoded protein,Ser/Thr kinase StkP,can recognize and bind to β-lactam antibiotics.
ABSTRACT
<p><b>OBJECTIVE</b>To explore the learning curve of transanal total mesorectal excision (taTME) for rectal cancer.</p><p><b>METHODS</b>Clinical data of 60 rectal cancer patients undergoing taTME from July 2014 to April 2016 were retrospectively analyzed. According to the sequence of operation date, 60 patients were divided into four groups (A, B, C, D) with 15 cases in each group. General information and perioperative, especially the operative indexes were compared among four groups.</p><p><b>RESULTS</b>There were no significant differences in age, sex, preoperative staging, BMI, tumor size among four groups (all P>0.05). The distance from tumor to anal verge in A group was(6.7±2.5) cm, which was significantly different with B group (4.6±1.2) cm, C group (4.5±1.0) cm and D group (4.0±1.0) cm (P=0.000, P=0.000, P=0.001). Ratio of receiving neoadjuvant therapy was 0, 60.0%(9 cases), 26.7%(4 cases) and 26.7%(4 cases) in A, B, C, D groups respectively with significant difference (P=0.004). Ratio of receiving complete taTME was 73.3%(11/15) in A group, 26.7%(4/15) in B group, 13.3%(2/15) in C group and 26.7%(4/15) in D group, while other patients underwent laparoscopy-assisted procedures. This ratio of A group was significantly higher as compared to B, C, D groups (P=0.003). The operation time was significantly different among four groups [A group (223.0±105.2) minutes, B group (299.0±131.0) minutes, C group(278.0±44.8) minutes, D group (246.0±34.0) min, P=0.035]. Fluctuation of operation time was more common in A and B groups, which became stable in C and D groups. Though intra-operative blood loss was not significantly different among four groups [A group (249.0±559.6) ml, B group (288.0±568.1) ml, C group (87.0±43.3) ml, D group (69.0±64.5) ml, P=0.225], but it presented a decline trend in C and D groups. Number of harvested lymph node from postoperative pathological specimen was 10.9±5.9 in A group, 9.6±2.7 in B group, 15.8±4.8 in C group, and 14.2±5.1 in D group, with significant difference among groups (P=0.008; A group vs. C group, P=0.010; B group vs. C group, P=0.002; B group vs. D group, P=0.021). There were no significant differences in specimen length, postoperative complication rate, distal margin distance and hospital stay.</p><p><b>CONCLUSION</b>A well-skilled laparoscopic colorectal surgeon, by following the standard surgical procedures, are likely to overcome the learning curve smoothly after performing approximately 30 cases of taTME for rectal cancer.</p>
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Abdomen , Anal Canal , Blood Loss, Surgical , Digestive System Surgical Procedures , Methods , Laparoscopy , Learning Curve , Length of Stay , Lymph Nodes , Neoadjuvant Therapy , Operative Time , Postoperative Complications , Rectal Neoplasms , General Surgery , Retrospective StudiesABSTRACT
Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma (DLBCL) is a rare and distinct variant of DLBCL. It is classified as a unique subtype of DLBCL in the 2008 WHO classification of lymphomas. No standard and effective therapeutic regi-men is available for ALK+DLBCL because it shows a more aggressive clinical course and frequent relapse. Therefore, a standardized and individualized treatment is needed to benefit more patients diagnosed with ALK+DLBCL through a multiple disciplinary team. This arti-cle presents a case of an ALK+DLBCL patient who relapsed after transplantation and was successfully treated with the ALK kinase inhibi-tor Crizotinib.
ABSTRACT
Objective:The implementation of a multidisciplinary team (MDT) approach for palliative treatment of patients with multi-ple primary carcinomas (MPCs) was evaluated in Tianjin Medical University Cancer Institute and Hospital. Methods:A total of 40 pa-tients with MPCs who attended the consultation by MDT in our hospital from January 1, 2014 to April 21, 2016 were analyzed retro-spectively. Clinical data of the 40 cancer patients were reviewed. The essential characteristics and results of MDT treatment decisions were summarized and expected outcomes were evaluated. Results:A total of 40 cases with MPCs were included in MDT assessment, accounting for 6.4%of the 629 patients who were handled by the MDT. A total of 39 MDT decisions were followed up successfully. Among these MDT decisions, 26 (65%) were fully implemented, 7 (17.5%) were partially implemented, and 6 (15.0%) were unimple-mented. Expected outcomes were achieved in 25 (96.2%) patients of the fully implemented concordant group, 4 (57.1%) patients of the partially concordant group, and 1 (16.7%) patient from the unimplemented group. Conclusion:MDT specializing on palliative treat-ment can provide recommendations for standardized individualized comprehensive treatment of patients with MPCs. MDT modality should be further improved and widely used for palliative treatment.
ABSTRACT
Background and purpose:Inhibitor of apoptosis-stimulating protein of p53 (iASPP) is one of the ASPP family. It binds to p53 to inhibit the transcriptional activity of p53-target genes and cell apoptosis, which is asso-ciated with tumor formation. Previously, we found a new subtype of iASPP, iASPP splice variant (iASPP-SV), which is a nuclear protein containing 407 amino acid residues and can bind to p53, inhibiting p53 transcriptional activity. However, the relationship of iASPP-SV and breast cancer is still obscure. Therefore, the purpose of this research was to study the role of iASPP-SV on breast cancer tumorigenesis and progression.Methods:5’-rapid ampliifcation of cDNA ends (RACE) was used to identify the 5’-end of iASPP-SV mRNA in MCF-7 cells. HEK 293 cells were transfected with pFLAG-iASPP-SV and pFLAG-iASPP (828). Then Western blot was used to identify whether endogenous iASPP-SV was expressed in HEK 293 cells and 8 types of human tumor cell lines. This study established the stable clones of NIH 3T3 expressing FLAG-iASPP-SV and FLAG-iASPP (828). Cell proliferation assay, colony formation and soft agar colony formation assay were used to identify whether iASPP-SV and iASPP (828) can promote cell proliferation and iASPP-SV is an oncogene. Real-time lfuorescent quantitative polymerase chain reactive (RTFQ-PCR) was used to de-tect the levels of iASPP-SV and iASPP (828) mRNA in primary breast cancers. Luciferase assays were used to identify the relationships between iASPP-SV, iASPP (828), p53 and NF-κB p65.Results:The study identiifed that iASPP-SV was encoded by previously reported NF-κB p65 subunit (RelA)-associated inhibitor (RAI), and endogenously expressed in many human cancer cell lines. Analysis of cell proliferation, colony formation assay and soft agar assay for colony formation identiifed that similarly to iASPP (828), iASPP-SV promoted tumor cell proliferation and acted as an onco-gene. RTFQ-PCR result showed that the median values of iASPP-SV and iASPP (828) in breast cancers with wild-type p53 were more signiifcantly over-expressed than those of mutant p53. Luciferase assays showed that iASPP-SV and iASPP (828) could suppress NF-κB p65 transcriptional activity. Thus iASPP family may participate in the regulation of p53 and NF-κB activity, which imply that iASPP perhaps shows pro- or anti-survival activities when it interacts with different proteins.Conclusion:These ifndings indicate that iASPP-SV may be a potential target for breast cancer thera-py.
ABSTRACT
Systemic chemotherapy is the main treatment which can improve the survival time of bladder cancer patients,though its efficacy is quite limited.The applications of targeted therapeutic drugs in bladder cancer has become more needed in clinic.At present the targeted drugs for bladder cancer include bevacizumab,cetuximab,sunitinib,gefitinib,everolimus and the inhibitor of programmed cell death-1 and its ligand,they provide a new direction for the treatment of advanced bladder cancer.
ABSTRACT
BACKGROUND:Co-culture withembryonic stem cels or embryonic tissues can induce differentiation of carcinoma cels into normal epithelial cels or decreasemalignancyof carcinoma cels.Acelular embryoid bodies retain the structure and important cytokines of embryonic tissues. OBJECTIVE:To prepare acelular embryoid bodies from mouse embryonic stem cels and to investigate their effects on differentiation of mouse Lewis lung carcinoma cels at three-dimensional culturein vitro. METHODS:Mouse embryonic stem cels(D3)were dynamicaly cultured for 7 days to produce embryoid bodiesfolowedbydecelularization with 0.1% sodium dodecyl sulfate. Mouse Lewis lung carcinoma cels were co-cultured with acelular embryoid bodiesas test group or culturedinthree-dimensionalmatrigel mediumfor 7 days as control group, respectively. Cel proliferation and expression of E-cadherin were detected by immunohistochemical staining and western blot assay, respectively. In addition, mRNA expressions ofSlug and E-cadherin were observed using RT-PCR technology. RESULTSAND CONCLUSION:Uniform mouse embryoid bodieswere successfuly prepared, andwere completely decelularized with sodium dodecyl sulfate. After 7-day three-dimensionalmatrigelculture, in the control group,multicelular tumor spheroidswere formed,accompanied byahigherKi67positive rate;Lewis lung carcinoma cels in the test group were repopulated in the acelular embryoid bodies showing significantly lowerKi67positive rate. Compared with the control group, the absorbance ofPaxilin in the test group was significantly smaler, and the absorbance of E-cadherin was significantly higher (P< 0.05). Besides, mRNA expressions of Slug and E-cadherin were significantly decreased and increasedin the test group compared with the control group, respectively(P< 0.05). These findings indicate that the acelular embryoid bodies can promote differentiation of mouse Lewis lung carcinoma celsinthree-dimensional culturein vitro.