Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expr...Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including CRC.Abnormal expression of lncRNAs is associated with the emergence of chemoresistance.Moreover,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance.Two recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,respectively.In this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.展开更多
Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as...Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.展开更多
Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We pr...Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.展开更多
Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immuno...Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.展开更多
Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association betwee...Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.展开更多
Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） pat...Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） patients. Methods： We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. Results： Of all the EGC patients, 7.5% （17/226） were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. Conclusions： The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.展开更多
Cancers are a worldwide concern;oral,esophageal and gastrointestinal cancers represent important causes of cancer-related mortality and contribute to a signif icant burden of human health.The DNA repair systems are th...Cancers are a worldwide concern;oral,esophageal and gastrointestinal cancers represent important causes of cancer-related mortality and contribute to a signif icant burden of human health.The DNA repair systems are the genome caretakers,playing a critical role in the initiation and progression of cancers.However,the association between the genomic variations of DNA repair genes and cancer susceptibility is not well understood.This review focuses on the polymorphic genotypes of the non-homologous end-joining DNA repair system,highlighting the role of two genes of this pathway,XRCC5 and XRCC6,in the susceptibility to digestive system cancers and discussing their potential contributions to personalized medicine.展开更多
AIM: To investigate the association of Caveolin-1 (Cav-1) polymorphisms with colorectal cancer (CRC) risk in a central Taiwan Residents population. METHODS: Three hundred and sixty-two patients with colorectal cancer ...AIM: To investigate the association of Caveolin-1 (Cav-1) polymorphisms with colorectal cancer (CRC) risk in a central Taiwan Residents population. METHODS: Three hundred and sixty-two patients with colorectal cancer and the same number of recruited age-and gender-matched healthy controls were genotyped. And only those matches with all single nucleotide poly-morphisms data (case/control = 362/362) were selected for final analyzing. RESULTS: There were significant differences between CRC and control groups in the distributions of their genotypes (P = 1.6 × 10 -12 and 3.0 × 10 -4 ) and allelic frequencies (P = 2.3 × 10 -13 and 4.0 × 10 -5 ) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) poly-morphisms respectively. As for the haplotype analysis,those who had GG/AT or GG/AA at Cav-1 G14713A/ T29107A showed a 0.68-fold (95% CI: 0.48-0.98) de- creased risk of CRC compared to those with GG/TT,while those of any other combinations were of increased risk. There were joint effects of Cav-1 G14713A and T29107A genotype with smoking status on individual CRC susceptibility. CONCLUSION: This is the first report providing evidence of Cav-1 being involved in CRC and it may be novel useful genomic markers for early detection of CRC.展开更多
Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy.However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear.Methods: Clinical data and ...Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy.However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear.Methods: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas(TCGA) cohort.Results: A total of 2,392 patients across 20 cancer types were included in this study. Our results showed that patients harboring PTPRD/PTPRT mutation, especially co-mutations, had a significantly elevated response rate to immunotherapy in multiple cancers. Patients with PTPRD/PTPRT mutation had a higher objective response rate(ORR)(P=0.002), longer overall survival(OS)(P=0.005) and progression-free survival(PFS)(P=0.038).Importantly, the above findings were further verified in validation cohorts. In addition, we found that the PTPRD/PTPRT co-mutations(co-mut) subgroup exhibited an immune-activated phenotype, the wild-type subgroup tended to have an immune-desert phenotype, and the uni-mutation(uni-mut) subgroup might have an immune-mixed phenotype. Our further analyses suggested that combining programmed cell death ligand 1(PDL1) expression and PTPRD/PTPRT mutation can be used to screen patients who may benefit from immunotherapy.Conclusions: PTPRD/PTPRT mutation could serve as a potential predictive biomarker for cancer immunotherapy.展开更多
Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used micr...Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.展开更多
OBJECTIVE To explore the relationship of high S-phase kinase associated protein 2 （Skp2） expression with the characteristics of breast cancer. METHODS Using a immunohistochemical method, Skp2 expression was detected...OBJECTIVE To explore the relationship of high S-phase kinase associated protein 2 （Skp2） expression with the characteristics of breast cancer. METHODS Using a immunohistochemical method, Skp2 expression was detected and evaluated in 30 normal tissues, 30 atypical ductal hyperplasias （ADH）, 30 ductal carcinomas in situ （DCIS） and 56 invasive carcinomas （including invasive specific carcinoma and invasive nonspecific carcinoma）. The relationship between Skp2 expression and the characteristics of breast cancer was analyzed.RESULTS Skp2 expression varied among normal tissue, ADH, DCIS and invasive carcinomas （X^2=54.02, P〈0.005）. The positive level of Skp2 expression in DCIS was higher than that of normal tissue （X^2=21.82, P〈 0.005） and there was a significant difference in Skp2 between DCIS and ADH （X^2=5.08, P〈0.025） as well as between invasive carcinomas and DCIS （X^2=6.52, P〈0.01）. The positive expression level of Skp2 in invasive carcinomas with positive lymph nodes was remarkably higher compared to those with negative lymph nodes. A significant difference in Skp2 expression was found between combined histological Grades Ⅰ and Ⅱ versus Grade Ⅲ of invasive carcinomas （X^2=6.66, P〈0.01）. CONCLUSION High Skp2 expression may play an important role in carcinogenesis and biological behavior of breast cancer.展开更多
Thiols play vital roles in cellular metabolism knowledge of which may be important in the design of future anticancer drugs. Previous work on the composition of the thiols present in human cancer cell lines has shown ...Thiols play vital roles in cellular metabolism knowledge of which may be important in the design of future anticancer drugs. Previous work on the composition of the thiols present in human cancer cell lines has shown the presence of an unknown low molecular weight species, deemed to be a “Conthiol”, which could be important in this respect. This was prepared and isolated from a human prostate cancer cell line (LNCaP) in the form of an adduct of 2-mercuri-4-nitrophenol;it accounts for 56.5% of the total cellular thiols present in this cell line. Initial LC-MS analysis of this adduct had indicated that the possible molecular weight of the thiol was in the region of 467 daltons. In further analytical studies to identify the thiol, attempts were made to release it from the adduct by passage through a Thiopropyl Sepharose6B column. LC-MS analysis of the column eluate revealed two components yielding negative ion fragments of 427 m/z and 449 m/z. Only the former component contained thiol, indicating that a breakdown and/or possible rearrangement of the Conthiol had occurred. Further investigations of the column thiol eluate using ICP-MS analysis showed that the sulfur content agreed with the spectrophotometric analysis result (Ellman assay) and that the molecule did not contain phosphate. Amino acid analyses of the eluate were negative. In an attempt to prevent the breakdown of the thiol released by the Thiopropyl Sepharose 6B column, the adduct was treated with 5% v/v bromine water prior to applying to the column. In this instance the thiol containing eluate obtained from the column was treated with an equimolar quantity of mercuric chloride forming a fresh adduct, RS-Hg-SR. LC-MS analysis of this mercurial adduct detected a negative ion fragment of 782 m/z which on further ionization gave a ladder like pattern showing loss of mass units of 58 in each rung. This would seem to suggest the presence of a repeat polymer like structure containing 5 monomers, which, plus the thiol atom, gives a possible formula weight of 322;probably revealing only a part of the unknown Conthiol molecule whose properties and formula weight do not correlate with any known cellular thiol. Further analysis of the thiol released from the adduct on the Thiopropyl Sepharose 6B column by Infra-red (FTIR) provided little information except to confirm the presence of the thiol group and C=O stretch bands together with the possibility of a lactam ring at 1651 and 1634 cm·s<sup>-</sup><sup>1</sup>.展开更多
The main purpose of the study was to enhance the stability and therapeutic effects of Curcumin(Cur)through nanoformulation with gum Arabic(GA)as a coating agent through an efficient synthetic approach.The antioxidant ...The main purpose of the study was to enhance the stability and therapeutic effects of Curcumin(Cur)through nanoformulation with gum Arabic(GA)as a coating agent through an efficient synthetic approach.The antioxidant properties of the developed nanoparticles(Cur/GANPs)were assessed through several in vitro assays,such asβ-carotene bleaching activity,DPPH,and nitric oxide scavenging activities in addition to evaluating its inhibitory activity on angiotensinconverting enzyme(ACE).The cytotoxicity of Cur/GANPs was evaluated in vitro using different types of human cancer cells including breast cancer(MCF7,MDA-MB231),liver cancer(HepG2),and colon cancer(HT29)cells.The prepared particles displayed an elliptical shape with a size ranging between 20–260 nm and a potential difference of–15 mV.The Cur/GANPs exhibited significant antioxidant activity compared to free curcumin when using concentrations between 31.5 and 500μg/mL.The Cur/GANPs also had inhibited the growth of all cancer cell lines in a proportional trend with concentrations used.Hence,the encapsulation with gum Arabic has augmented the antioxidant and anti-neoplastic effects of Curcumin.Therefore,Cur/GANPs may have effective therapeutic properties in diseases attributed to oxidative stress like cancer and hypertension.展开更多
Monoclonal antibodies against colon and pancreatic cancer, CL-2, CL-3, PS-9, PS-10, were used to detect the associated antigens in feces of patients with gastrointestinal carcinoma and non-cancer diseases. Binding inh...Monoclonal antibodies against colon and pancreatic cancer, CL-2, CL-3, PS-9, PS-10, were used to detect the associated antigens in feces of patients with gastrointestinal carcinoma and non-cancer diseases. Binding inhibition test by SABC-ELISA method were performed for the measurement of the antigen level. Results showed that the associated antigen detected in feces of patients with colon cancer were significantly higher than that of non-cancer disease or normal subjects. The positive rates were 61.1% as detected with CL-2; 53.4% with CL-3; 55.0%, PS-9; and 53.3% PS-10 in cancer patients while that in normal subjects were 7%; 9%; 8%; and 8% respectively. When 'cocktail' of CL-2, PS-9 and PS-10 were used, the positive rates were 92.5% in colon cancer and 14% in normal subjects. In seven out of the sixty patients with colon cancer studied who were graded as Dukes A, the results were all positive. The results seem superior to the serologic detection and may provide a promising new approach in the early diagnosis of colon cancer.展开更多
INTRODUCTIONHelicobacter pylori is recognized as a cause of chronicactive gastritis,gastric and duodenal ulcers,and gastriccancer,though the mechanisms of pathogenesis for H.pylori-associated diseases are not yet well...INTRODUCTIONHelicobacter pylori is recognized as a cause of chronicactive gastritis,gastric and duodenal ulcers,and gastriccancer,though the mechanisms of pathogenesis for H.pylori-associated diseases are not yet well understood.The ecological niche to which H.pylori is well-adapted展开更多
AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fix...AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.展开更多
This experiment is the first report on N, N'-dini-trosopiperazine (DNF)-induced neoplastic transformation of human embryonic nasopharyngeal (HENPE) cells. The transformed cells showed a prolonged life span, anchor...This experiment is the first report on N, N'-dini-trosopiperazine (DNF)-induced neoplastic transformation of human embryonic nasopharyngeal (HENPE) cells. The transformed cells showed a prolonged life span, anchorage independent growth, chromosome aberration, tumorigenicity and an altered cell morphological appearance. The results demonstrated that DNP was able to induce not only nasopharyngeal carcinoma (NPC) of rats in vivo, but also neoplastic transformation of HENPE cells in vitro.展开更多
Gelatins extracted from two edible insects Aspongubus viduatus （melon bug） and Agonoscelis pubescens （sorghum bug） were studied. The two insects showed 27.0 and 28.2% crude protein, respectively. Extraction of gel...Gelatins extracted from two edible insects Aspongubus viduatus （melon bug） and Agonoscelis pubescens （sorghum bug） were studied. The two insects showed 27.0 and 28.2% crude protein, respectively. Extraction of gelatin using hot water gave high yield followed by mild acid and distilled water extraction, respectively. SDS-PAGE pattern showed low molecular weight chains, and the two gelatins contained protein with molecular weight of 40 kDa as main component. The differential scanning calorimetry thermograms results confirm no difference between extraction methods concerning the extracted gelatin quality. FTIR spectra of melon and sorghum bug gelatins were similar and the absorption bands were situated in more than 6 bands in melon bug gelatin and only 6 bands in sorghum bug gelatin. Amide II bands of gelatins from both melon and sorghum bug appeared at around 1554 cm^-1, while Amide I bands （1734-1632 cmt） appeared only in melon bug method 2 （MB2） and melon bug method3 （MB3）. Microstructures of the insect gelatin examined with the scanning electron microscope showed that melon bug exhibited the finest gelatin network with very small voids. Melon bug gelatin showed finer structure with smaller protein strands and voids than sorghum bug gelatin.展开更多
The thiol components of the nonhistone proteins prepared from isolated nuclei from rat liver, regenerating liver and hepatoma 223 cells have been investigated after reaction with radio labelled N-ethylmaleimide and 5-...The thiol components of the nonhistone proteins prepared from isolated nuclei from rat liver, regenerating liver and hepatoma 223 cells have been investigated after reaction with radio labelled N-ethylmaleimide and 5-5’-dithiobis-(2-nitrobenzoic acid) (DTNB). The labelled adducts formed were examined by isoelectric focusing analysis in polyacrylamide gel and the distribution of the radiolabels within sliced portions of the gels determined. In the case of the 14C labelled NEM adduct the label was found to be spread amongst numerous protein components within the gel however, in the case of the 35S labelled DTNB adducts, only a small proportion of the label was found in the protein material which was retained in the acidic isoelectric point (pI) region of the gel. The bulk of the 35S labelled adduct (56% - 60%) was found to have migrated into the anode solution (10 mM phosphoric acid). This could be adsorbed onto a hydrophobic resin (XAD2) resin and eluted with methanol. Gel filtration chromatographic analysis of this adduct material on BioGel P2, (exclusion limit 1500 daltons) showed low molecular weight components to be present. Slightly different patterns were obtained for these nuclei, each containing several 35S components with molecular weights greater than the Ellman reagent itself. These 35S labelled thiol components did not contain any protein, peptide or amino acid components indicating strongly that a novel species of thiols could be present in these nuclei bound within the non-histone protein matrices.展开更多
Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune response.Numerous therapeutic strategies in...Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune response.Numerous therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response.However,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response.Here,we outline the current state of using nanomedicines for boosting ICD of cancer cells.Moreover,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed.We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses.Endoplasmic reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative approaches.Various challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.展开更多
基金Supported by the National Natural Science Foundation of China,No.81472782National Clinical Key Specialty Department(Oncology)of China,No.YWC-ZKJS-2023-01Research Fund of Yili Institute of Clinical Medicine,No.yl2021ms02.
文摘Long non-coding RNAs(lncRNAs),with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity,have been found to impact colorectal cancer(CRC)through various biological processes.LncRNA expression can regulate autophagy,which plays dual roles in the initiation and progression of cancers,including CRC.Abnormal expression of lncRNAs is associated with the emergence of chemoresistance.Moreover,it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance.Two recent studies titled“Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506”and“Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription”revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC,respectively.In this editorial,we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.
基金supported by the National Natural Science Foundation of China(Grant nos.82473157,82460510,82203565,82103388,31960145 and 82560591)the Natural Science Foundation of Beijing(Grant no.L248059)+1 种基金Yunnan Province applied research funds(Grant nos.202201AY070001-011,202201AY070001-043,and 202301AS070018)the Science and Technology Innovation Team of tumor metabolism research at Kunming Medical University(Grant no.CXTD202102).
文摘Neutrophil extracellular traps (NETs) are web-like structures of DNA and proteins that are released by activated neutrophils. While originally identified as antimicrobial defense mechanisms, NETs are now recognized as key modulators of tumor progression. NETs interact with the tumor microenvironment and metabolic pathways in renal cell carcinoma (RCC), which promotes immune evasion and metastasis. This review explores the interplay between NET formation and metabolic reprogramming in RCC, highlighting the implications for immunotherapy resistance and therapeutic targeting. NET-associated signaling, immunometabolism disruption, and current strategies to inhibit NETs in preclinical and clinical settings are discussed. Targeting NETs may represent a promising adjunct in RCC therapy, particularly when integrated with immune checkpoint blockade.
文摘Nasopharyngeal cancer(NPC) is endemic in Southern China,with Guandong province and Hong Kong reporting some of the highest incidences in the world.The journal Science has called it a "Cantonese cancer".We propose that in fact NPC is a cancer that originated in the Bai-Yue("proto-Tai-Kadai" or "proto-Austronesian" or "proto-Zhuang") peoples and was transmitted to the Han Chinese in southern China through intermarriage.However,the work by John Ho raised the profile of NPC,and because of the high incidence of NPC in Hong Kong and Guangzhou,NPC became known as a Cantonese cancer.We searched historical articles,articles cited in PubMed,Google,monographs,books and Internet articles relating to genetics of the peoples with high populations of NPC.The migration history of these various peoples was extensively researched,and where possible,their genetic fingerprint identified to corroborate with historical accounts.Genetic and anthropological evidence suggest there are a lot of similarities between the Bai-Yue and the aboriginal peoples of Borneo and Northeast India;between Inuit of Greenland,Austronesian Mayalo-Polynesians of Southeast Asia and Polynesians of Oceania,suggesting some common ancestry.Genetic studies also suggest the present Cantonese,Minnans and Hakkas are probably an admixture of northern Han and southern Bai-Yue.All these populations have a high incidence of NPC.Very early contact between southern Chinese and peoples of East Africa and Arabia can also account for the intermediate incidence of NPC in these regions.
文摘Objective： To investigate Leucine-rich repeat-containing G protein-coupled receptor 5 （LGR5） expressions in gastric cancer and to evaluate its clinical significance. Methods： LGR5 expression was assessed by immunohistochemistry in 257 gastric cancer patients after surgery. The relationships between LGR5 expression and clinicopathological features and patients prognosis were statistically analyzed. Results： The expression of LGR5 was significantly higher in gastric cancers as a cancer stem cell marker than in adjacent normal tissues （P〈0.001）, and more frequently in patients with intestinal type, well-moderate differentiation and stage I and II （P〈0.05）. Although we found gastric cancer patients with LGR5 positive expression had a poorer prognosis, it didn＇t meet statistical significance （P〉0.05）. LGR5 negative expression was significantly related to the favorable overall survival in stage I and II gastric cancer patients （P〈0.05）. Furthermore, patients with high LGR5 expression tended to be more likely to get progression and have poorer progress-free survival （P〈0.05）. Multivariate Cox regression analysis revealed that LGR5 expression was an independent factor of overall survival for the patients with stage I and II gastric cancer （P〈0.05）. Conclusions： Our results show that LGR5 may play an important role in tumorigenesis and progression and would be a powerful marker to predict the prognosis of patients with stage I and II gastric cancer.
文摘Objective：The programmed cell death-1 receptor/programmed cell death-1 ligand （PD-1/PD-L1） pathway plays a crucial role in tumor evasion from host immunity.This study was designed to evaluate the association between circulating PD-L1 expression and prognosis in patients with advanced gastric cancer.Methods：Totally 80 advanced gastric cancer patients and 40 health controls from Beijing Cancer Hospital were enrolled in the present study.Circulating PD-L1 expression was tested by enzymelinked immunosorbent assay （ELISA）.The associations between the expression level of PD-L1 and clinicopathological features and prognosis were analyzed statistically.Results：Expression of PD-L1 in advanced gastric cancer patients was significandy up-regulated compared with health people （P=0.006）.The expression of PD-L1 was significantly correlated with differentiation and lymph node metastasis （P=0.026 and P=0.041,respectively）.Although we didn＇t find significant difference in all advanced gastric cancer patients with different PD-L1 expression,the adenocarcinoma patients with higher up-regulated PD-L1 expression had much better prognosis than low expression patients （65.6％ vs.44.7％,P=0.028）.Conclusions：PD-L1 was elevated in advance gastric cancer patients and may play an important role in tumor immune evasion and patients prognosis.
基金supported by Research on Strategy and Standard Project for Secondary Prevention of Gastrointestinal Tumor (No. 201202014)National Key Technology R&D Program (Beijing Municipal Science and Technology Project Z121100007512010)
文摘Objective： To clarify the relationship between clinicopathological features and lymph node metastasis and to propose the potential indications of lymph node metastasis for prognosis in early gaswic cancer （EGC） patients. Methods： We retrospectively observed 226 EGC patients with lymph node resection, and analyzed the associations between lymph node metastasis and clinicopathological parameters using the chi-square test in univariate analysis and logistic regression analysis in multivariate analysis. Overall survival analysis was determined using the Kaplan-Meier and log-rank test. We conducted multivariate prognosis analysis using the Cox proportional hazards model. Results： Of all the EGC patients, 7.5% （17/226） were histologically shown to have lymph node metastasis. The differentiation, lymphovascular invasion and depth of invasion were independent risk factors for lymph node metastasis in EGC. The 5- and 10-year survival rates were significantly lower in patients with lymph node metastasis than in those without and the patients also had shorter progress-free survival time. Lymph node metastasis and tumor size were independent prognostic factors for EGC. The status of the lymph nodes was a significant factor in predicting recurrence or metastasis after surgery. Conclusions： The undifferentiated carcinoma and lymphovascular and/or submucosal invasion were associated with a higher incidence of lymph node metastasis in EGC patients, whom need to perform subsequent D2 lymphadenectomy or laparoscopic lymph node dissection and more rigorous follow-up or additional chemotherapy/radiation after D2 gastrectomy for poor prognosis and high recurrence/metastasis rate.
文摘Cancers are a worldwide concern;oral,esophageal and gastrointestinal cancers represent important causes of cancer-related mortality and contribute to a signif icant burden of human health.The DNA repair systems are the genome caretakers,playing a critical role in the initiation and progression of cancers.However,the association between the genomic variations of DNA repair genes and cancer susceptibility is not well understood.This review focuses on the polymorphic genotypes of the non-homologous end-joining DNA repair system,highlighting the role of two genes of this pathway,XRCC5 and XRCC6,in the susceptibility to digestive system cancers and discussing their potential contributions to personalized medicine.
基金Supported by Research Grants from the China Medical Universityand Hospital (DMR-99-041 and CMU-99-NTU-10)the Terry FoxCancer Research Foundation and the National Science Council(NSC 98-2320-B-039-010-MY3)
文摘AIM: To investigate the association of Caveolin-1 (Cav-1) polymorphisms with colorectal cancer (CRC) risk in a central Taiwan Residents population. METHODS: Three hundred and sixty-two patients with colorectal cancer and the same number of recruited age-and gender-matched healthy controls were genotyped. And only those matches with all single nucleotide poly-morphisms data (case/control = 362/362) were selected for final analyzing. RESULTS: There were significant differences between CRC and control groups in the distributions of their genotypes (P = 1.6 × 10 -12 and 3.0 × 10 -4 ) and allelic frequencies (P = 2.3 × 10 -13 and 4.0 × 10 -5 ) in the Cav-1 G14713A (rs3807987) and T29107A (rs7804372) poly-morphisms respectively. As for the haplotype analysis,those who had GG/AT or GG/AA at Cav-1 G14713A/ T29107A showed a 0.68-fold (95% CI: 0.48-0.98) de- creased risk of CRC compared to those with GG/TT,while those of any other combinations were of increased risk. There were joint effects of Cav-1 G14713A and T29107A genotype with smoking status on individual CRC susceptibility. CONCLUSION: This is the first report providing evidence of Cav-1 being involved in CRC and it may be novel useful genomic markers for early detection of CRC.
基金supported by grants from the joint fund for key projects of National Natural Science Foundation of China (No. U20A20371)Beijing Municipal Administration of Hospitals Incubating Program (No. PX2019040 and No. PX2019039)Beijing Municipal Natural Science Foundation (No. 7222023)。
文摘Objective: PTPRD and PTPRT are phosphatases of the JAK-STAT pathway related to immunotherapy.However, the role and mechanism of PTPRD and PTPRT mutations in multiple cancers remains unclear.Methods: Clinical data and PTPRD/PTPRT mutation information from 12 cohorts were collected and classified as a discovery cohort and three validation cohorts. The association between PTPRD/PTPRT mutations and immunotherapeutic efficacy was analyzed. Then, the association between PTPRD/PTPRT mutation and immune profiles was analyzed using The Cancer Genome Atlas(TCGA) cohort.Results: A total of 2,392 patients across 20 cancer types were included in this study. Our results showed that patients harboring PTPRD/PTPRT mutation, especially co-mutations, had a significantly elevated response rate to immunotherapy in multiple cancers. Patients with PTPRD/PTPRT mutation had a higher objective response rate(ORR)(P=0.002), longer overall survival(OS)(P=0.005) and progression-free survival(PFS)(P=0.038).Importantly, the above findings were further verified in validation cohorts. In addition, we found that the PTPRD/PTPRT co-mutations(co-mut) subgroup exhibited an immune-activated phenotype, the wild-type subgroup tended to have an immune-desert phenotype, and the uni-mutation(uni-mut) subgroup might have an immune-mixed phenotype. Our further analyses suggested that combining programmed cell death ligand 1(PDL1) expression and PTPRD/PTPRT mutation can be used to screen patients who may benefit from immunotherapy.Conclusions: PTPRD/PTPRT mutation could serve as a potential predictive biomarker for cancer immunotherapy.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China (No. SS2014AA020603)Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support (No. ZYLX201701)+3 种基金Beijing Municipal Science and Technology Commission (No. D1311 00005313010)the National Natural Science Foundation of China (No. 31520103905)the National High Technology Research and Development Program (“863” Program) of China (No. 2015AA020108)the Zhi-Yuan chair professorship start-up grant WF220103010 from Shanghai Jiao Tong University
文摘Objective: Tumor heterogeneity renders identification of suitable biomarkers of gastric cancer(GC)challenging. Here, we aimed to identify prognostic genes of GC using computational analysis.Methods: We first used microarray technology to profile gene expression of GC and paired nontumor tissues from 198 patients. Based on these profiles and patients’ clinical information, we next identified prognostic genes using novel computational approaches. Phosphoglucose isomerase, also known as glucose-6-phosphate isomerase(GPI), which ranked first among 27 candidate genes, was further investigated by a new analytical tool namely enviro-geno-pheno-state(E-GPS) analysis. Suitability of GPI as a prognostic marker, and its relationship with physiological processes such as metabolism, epithelial-mesenchymal transition(EMT), as well as drug sensitivity were evaluated using both our own and independent public datasets.Results: We found that higher expression of GPI in GC correlated with prolonged survival of patients.Particularly, a combination of CDH2 and GPI expression effectively stratified the outcomes of patients with TNM stage Ⅱ/Ⅲ. Down-regulation of GPI in tumor tissues correlated well with depressed glucose metabolism and fatty acid synthesis, as well as enhanced fatty acid oxidation and creatine metabolism, indicating that GPI represents a suitable marker for increased probability of EMT in GC cells.Conclusions: Our findings strongly suggest that GPI acts as a novel biomarker candidate for GC prognosis,allowing greatly enhanced clinical management of GC patients. The potential metabolic rewiring correlated with GPI also provides new insights into studying the relationship between cancer metabolism and patient survival.
基金This work was supported by the NationalScientific Foundation of China (No.30471967).
文摘OBJECTIVE To explore the relationship of high S-phase kinase associated protein 2 （Skp2） expression with the characteristics of breast cancer. METHODS Using a immunohistochemical method, Skp2 expression was detected and evaluated in 30 normal tissues, 30 atypical ductal hyperplasias （ADH）, 30 ductal carcinomas in situ （DCIS） and 56 invasive carcinomas （including invasive specific carcinoma and invasive nonspecific carcinoma）. The relationship between Skp2 expression and the characteristics of breast cancer was analyzed.RESULTS Skp2 expression varied among normal tissue, ADH, DCIS and invasive carcinomas （X^2=54.02, P〈0.005）. The positive level of Skp2 expression in DCIS was higher than that of normal tissue （X^2=21.82, P〈 0.005） and there was a significant difference in Skp2 between DCIS and ADH （X^2=5.08, P〈0.025） as well as between invasive carcinomas and DCIS （X^2=6.52, P〈0.01）. The positive expression level of Skp2 in invasive carcinomas with positive lymph nodes was remarkably higher compared to those with negative lymph nodes. A significant difference in Skp2 expression was found between combined histological Grades Ⅰ and Ⅱ versus Grade Ⅲ of invasive carcinomas （X^2=6.66, P〈0.01）. CONCLUSION High Skp2 expression may play an important role in carcinogenesis and biological behavior of breast cancer.
文摘Thiols play vital roles in cellular metabolism knowledge of which may be important in the design of future anticancer drugs. Previous work on the composition of the thiols present in human cancer cell lines has shown the presence of an unknown low molecular weight species, deemed to be a “Conthiol”, which could be important in this respect. This was prepared and isolated from a human prostate cancer cell line (LNCaP) in the form of an adduct of 2-mercuri-4-nitrophenol;it accounts for 56.5% of the total cellular thiols present in this cell line. Initial LC-MS analysis of this adduct had indicated that the possible molecular weight of the thiol was in the region of 467 daltons. In further analytical studies to identify the thiol, attempts were made to release it from the adduct by passage through a Thiopropyl Sepharose6B column. LC-MS analysis of the column eluate revealed two components yielding negative ion fragments of 427 m/z and 449 m/z. Only the former component contained thiol, indicating that a breakdown and/or possible rearrangement of the Conthiol had occurred. Further investigations of the column thiol eluate using ICP-MS analysis showed that the sulfur content agreed with the spectrophotometric analysis result (Ellman assay) and that the molecule did not contain phosphate. Amino acid analyses of the eluate were negative. In an attempt to prevent the breakdown of the thiol released by the Thiopropyl Sepharose 6B column, the adduct was treated with 5% v/v bromine water prior to applying to the column. In this instance the thiol containing eluate obtained from the column was treated with an equimolar quantity of mercuric chloride forming a fresh adduct, RS-Hg-SR. LC-MS analysis of this mercurial adduct detected a negative ion fragment of 782 m/z which on further ionization gave a ladder like pattern showing loss of mass units of 58 in each rung. This would seem to suggest the presence of a repeat polymer like structure containing 5 monomers, which, plus the thiol atom, gives a possible formula weight of 322;probably revealing only a part of the unknown Conthiol molecule whose properties and formula weight do not correlate with any known cellular thiol. Further analysis of the thiol released from the adduct on the Thiopropyl Sepharose 6B column by Infra-red (FTIR) provided little information except to confirm the presence of the thiol group and C=O stretch bands together with the possibility of a lactam ring at 1651 and 1634 cm·s<sup>-</sup><sup>1</sup>.
基金supported by the Malaysian Ministry of Higher Education Fundamental Research Grant Scheme(FRGS17-005-0571)Prototype Research Grant Scheme(PRGS19-005-0049)Ministry of Science,Technology,and Innovation(MOSTI)Grant No.SMF18-001-0001.
文摘The main purpose of the study was to enhance the stability and therapeutic effects of Curcumin(Cur)through nanoformulation with gum Arabic(GA)as a coating agent through an efficient synthetic approach.The antioxidant properties of the developed nanoparticles(Cur/GANPs)were assessed through several in vitro assays,such asβ-carotene bleaching activity,DPPH,and nitric oxide scavenging activities in addition to evaluating its inhibitory activity on angiotensinconverting enzyme(ACE).The cytotoxicity of Cur/GANPs was evaluated in vitro using different types of human cancer cells including breast cancer(MCF7,MDA-MB231),liver cancer(HepG2),and colon cancer(HT29)cells.The prepared particles displayed an elliptical shape with a size ranging between 20–260 nm and a potential difference of–15 mV.The Cur/GANPs exhibited significant antioxidant activity compared to free curcumin when using concentrations between 31.5 and 500μg/mL.The Cur/GANPs also had inhibited the growth of all cancer cell lines in a proportional trend with concentrations used.Hence,the encapsulation with gum Arabic has augmented the antioxidant and anti-neoplastic effects of Curcumin.Therefore,Cur/GANPs may have effective therapeutic properties in diseases attributed to oxidative stress like cancer and hypertension.
文摘Monoclonal antibodies against colon and pancreatic cancer, CL-2, CL-3, PS-9, PS-10, were used to detect the associated antigens in feces of patients with gastrointestinal carcinoma and non-cancer diseases. Binding inhibition test by SABC-ELISA method were performed for the measurement of the antigen level. Results showed that the associated antigen detected in feces of patients with colon cancer were significantly higher than that of non-cancer disease or normal subjects. The positive rates were 61.1% as detected with CL-2; 53.4% with CL-3; 55.0%, PS-9; and 53.3% PS-10 in cancer patients while that in normal subjects were 7%; 9%; 8%; and 8% respectively. When 'cocktail' of CL-2, PS-9 and PS-10 were used, the positive rates were 92.5% in colon cancer and 14% in normal subjects. In seven out of the sixty patients with colon cancer studied who were graded as Dukes A, the results were all positive. The results seem superior to the serologic detection and may provide a promising new approach in the early diagnosis of colon cancer.
基金the Research Service of the Henry Ford Health Sciences Center and Research Foundation(JCB,RSB)National Cancer Institute Grant R01 CA69480(RSB)
文摘INTRODUCTIONHelicobacter pylori is recognized as a cause of chronicactive gastritis,gastric and duodenal ulcers,and gastriccancer,though the mechanisms of pathogenesis for H.pylori-associated diseases are not yet well understood.The ecological niche to which H.pylori is well-adapted
基金Supported by A grant from the Beijing Municipal Science and Technology Commission’s NOVA Program,No.2009BG-02Beijing Municipal Health System Special funds of High-Level Medical Personnel Construction,No.2013-3-082
文摘AIM:To investigate the differential expression of leu-cine-rich repeat-containing G protein-coupled receptor5(LGR5)in gastric cancer tissues and its significance related to tumor growth and spread.METHODS:Formalin-fixed biopsy specimens of intestinal metaplasia(n=90),dysplasia(n=53),gastric adenocarcinoma(n=180),metastases in lymph nodes and the liver(n=15),and lesion-adjacent normal gastric mucosa(controls;n=145)were obtained for analysis from the Peking University Cancer Hospital’s Department of Pathology and Gastrointestinal Surgery tissue archives(January 2003 to December 2011).The biopsied patients’demographic and clinicopathologic data were retrieved from the hospital’s medical records database.Each specimen was subjected to histopathological typing to classify the tumor node metastasis(TNM)stage and to immunohistochemistry staining to detect the expression of the cancer stem cell marker LGR5.The intergroup differences in LGR5 expression were assessed by Spearman’s rank correlation analysis,and the relationship between LGR5 expression level and the patients’clinicopathological characteristics was evaluated by theχ2test or Fisher’s exact test.RESULTS:Significantly more gastric cancer tissues showed LGR5+staining than normal control tissues(all P<0.01),with immunoreactivity detected in 72.2%(65/90)and 50.9%(27/53)of intestinal metaplasia and dysplasia specimens,respectively,52.8%(95/180)of gastric adenocarcinoma specimens,and 73.3%%(11/15)of metastasis specimens,but 26.9%(39/145)of lesion-adjacent normal gastric mucosa specimens.Comparison of the intensity of LGR5+staining showed an increasing trend that generally followed increasing dedifferentiation and tumor spread(normal tissue<dysplasia,<gastric adenocarcinoma<metastasis;all P<0.001),with the exception of expression level detected in intestinal metaplasia which was higher than that in normal gastric tissues(P<0.001).Moreover,gastric cancer-associated enhanced expression of LGR5 was found to be signifcantly associated with age,tumor differentiation,Lauren type and TNM stage(Ⅰ+ⅡvsⅢ+Ⅳ)(all P<0.05),but not with sex,tumor site,location,size,histology,lymphovascular invasion,depth of invasion,lymph node metastasis or distant metastasis.Patients with LGR5+gastric cancer specimens and without signs of metastasis from the original biopsy experienced more frequent rates of recurrence or metastasis during follow-up than patients with LGR5-specimens(P<0.05).CONCLUSION:Enhanced LGR5 is related to progressive dedifferentiation and metastasis of gastric cancer,indicating the potential of this receptor as an early diagnostic and prognostic biomarker.
文摘This experiment is the first report on N, N'-dini-trosopiperazine (DNF)-induced neoplastic transformation of human embryonic nasopharyngeal (HENPE) cells. The transformed cells showed a prolonged life span, anchorage independent growth, chromosome aberration, tumorigenicity and an altered cell morphological appearance. The results demonstrated that DNP was able to induce not only nasopharyngeal carcinoma (NPC) of rats in vivo, but also neoplastic transformation of HENPE cells in vitro.
文摘Gelatins extracted from two edible insects Aspongubus viduatus （melon bug） and Agonoscelis pubescens （sorghum bug） were studied. The two insects showed 27.0 and 28.2% crude protein, respectively. Extraction of gelatin using hot water gave high yield followed by mild acid and distilled water extraction, respectively. SDS-PAGE pattern showed low molecular weight chains, and the two gelatins contained protein with molecular weight of 40 kDa as main component. The differential scanning calorimetry thermograms results confirm no difference between extraction methods concerning the extracted gelatin quality. FTIR spectra of melon and sorghum bug gelatins were similar and the absorption bands were situated in more than 6 bands in melon bug gelatin and only 6 bands in sorghum bug gelatin. Amide II bands of gelatins from both melon and sorghum bug appeared at around 1554 cm^-1, while Amide I bands （1734-1632 cmt） appeared only in melon bug method 2 （MB2） and melon bug method3 （MB3）. Microstructures of the insect gelatin examined with the scanning electron microscope showed that melon bug exhibited the finest gelatin network with very small voids. Melon bug gelatin showed finer structure with smaller protein strands and voids than sorghum bug gelatin.
文摘The thiol components of the nonhistone proteins prepared from isolated nuclei from rat liver, regenerating liver and hepatoma 223 cells have been investigated after reaction with radio labelled N-ethylmaleimide and 5-5’-dithiobis-(2-nitrobenzoic acid) (DTNB). The labelled adducts formed were examined by isoelectric focusing analysis in polyacrylamide gel and the distribution of the radiolabels within sliced portions of the gels determined. In the case of the 14C labelled NEM adduct the label was found to be spread amongst numerous protein components within the gel however, in the case of the 35S labelled DTNB adducts, only a small proportion of the label was found in the protein material which was retained in the acidic isoelectric point (pI) region of the gel. The bulk of the 35S labelled adduct (56% - 60%) was found to have migrated into the anode solution (10 mM phosphoric acid). This could be adsorbed onto a hydrophobic resin (XAD2) resin and eluted with methanol. Gel filtration chromatographic analysis of this adduct material on BioGel P2, (exclusion limit 1500 daltons) showed low molecular weight components to be present. Slightly different patterns were obtained for these nuclei, each containing several 35S components with molecular weights greater than the Ellman reagent itself. These 35S labelled thiol components did not contain any protein, peptide or amino acid components indicating strongly that a novel species of thiols could be present in these nuclei bound within the non-histone protein matrices.
文摘Resistance to cancer immunotherapy is mainly attributed to poor tumor immunogenicity as well as the immunosuppressive tumor microenvironment(TME)leading to failure of immune response.Numerous therapeutic strategies including chemotherapy,radiotherapy,photodynamic,photothermal,magnetic,chemodynamic,sonodynamic and oncolytic therapy,have been developed to induce immunogenic cell death(ICD)of cancer cells and thereby elicit immunogenicity and boost the antitumor immune response.However,many challenges hamper the clinical application of ICD inducers resulting in modest immunogenic response.Here,we outline the current state of using nanomedicines for boosting ICD of cancer cells.Moreover,synergistic approaches used in combination with ICD inducing nanomedicines for remodeling the TME via targeting immune checkpoints,phagocytosis,macrophage polarization,tumor hypoxia,autophagy and stromal modulation to enhance immunogenicity of dying cancer cells were analyzed.We further highlight the emerging trends of using nanomaterials for triggering amplified ICD-mediated antitumor immune responses.Endoplasmic reticulum localized ICD,focused ultrasound hyperthermia,cell membrane camouflaged nanomedicines,amplified reactive oxygen species(ROS)generation,metallo-immunotherapy,ion modulators and engineered bacteria are among the most innovative approaches.Various challenges,merits and demerits of ICD inducer nanomedicines were also discussed with shedding light on the future role of this technology in improving the outcomes of cancer immunotherapy.
