The Paper analyzed of investigation datas on thedeath causes of digestive tract cancer in high-incidencearea between 70s and 80s. The results showed that thecancer-adjusted mortalities were 224.14/100000 and226.66/100...The Paper analyzed of investigation datas on thedeath causes of digestive tract cancer in high-incidencearea between 70s and 80s. The results showed that thecancer-adjusted mortalities were 224.14/100000 and226.66/100000: it was 7 times as high as low-incidence(31.19/100000 and 29.82/100000). In 70s, the cancer deathof esophagus, stomach and liver (87.41/100000,73.93/100000 and 8.59/100000) were 28 times, 10 timesand 4 times as high as low-incidence area (3.70/100000,10.57/100000 and 1.94/100000), respectively (P<0.001). In80s, the cancer death of esophagus, stomach and liver(68.26/100000, 109.39/100000 and 23.89/100000) were 17times, 10 times and 4 times as high as low-incidence area(4.54/100000, 10.84/100000 and 6.35/100000), respectively(P<0.001). In high-incidence area, the cancer death ofesophagus was lower, of stomach and liver were higherin 80s than 70s, respectively (P<0.01)- The result alsoshowed that the nitrate content of drinking water andvegetables were 21.45mg/1 and 1185.27mg/kg in high-incidence area; it were significant higher than that in low-incidence area (2.14mg/1 and 41.6omg/kg), the nitritecontent (0.01mg/l) of drinking water in high-incidencearea was significant higher than that in low-incidencearea (0.004mg/l), but the nitrite content among vegetableswas no significant difference between the two regions(N0.05). Our results suggest that the nitrate and nitritecontents increase in drinking water and vegetables maybe an important risk factor of upper alimentary cancer inhigh-incidence area.展开更多
<strong>Objective: </strong>This study aimed to clarify the death characteristics of esophageal cancer in Inner Mongolia and the population distribution with various education levels. <strong>Methods...<strong>Objective: </strong>This study aimed to clarify the death characteristics of esophageal cancer in Inner Mongolia and the population distribution with various education levels. <strong>Methods:</strong> The mortality rate of esophageal cancer was calculated using the monitoring point of Death Registry System in Inner Mongolia from 2009 to 2015. The gender, age, region, ethnicity at two education levels of percentage were calculated and the <em>χ</em><sup>2</sup> test was executed. <strong>Result:</strong> The mortality rate of esophageal cancer was 10.10/105, China Adjustment Mortality was 10.97/10<sup>5</sup>, World Adjustment Mortality was 9.08/10<sup>5</sup> in Inner Mongolia. The death of esophageal cancer showed statistical significance at two educational levels (P < 0.05). High school and below accounted for 93.9% at the education level, and above high school accounted for 3.5%. In addition, there were significant differences in the percentage of death by gender, age and region at two educational levels (P < 0.05). <strong>Conclusion:</strong> Education level has a certain relation with the death of esophageal cancer. To improve the health level, health education plans can be formulated according to esophageal cancer prevention relevant policy with different education levels.展开更多
If more Americans quit smoking,lost a little weight and started eating bet-ter,at least 60,000 cancer deaths could be avoided each year,according tO a re-port issued Monday by a government advisory panel. 假如有更多...If more Americans quit smoking,lost a little weight and started eating bet-ter,at least 60,000 cancer deaths could be avoided each year,according tO a re-port issued Monday by a government advisory panel. 假如有更多的美国人戒烟,适当减肥,并开始吃得更健康些,至少每年可以减少60 000死于癌症的病例。政府顾问团周一发表的一则报告如是说。展开更多
Objective: To evaluate the population attributable risks(PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai.Methods: In total, 61,480 men ag...Objective: To evaluate the population attributable risks(PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai.Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks(RRs) and 95% confidence intervals(95% CIs) of deaths associated with cigarette smoking. PARs and 95% CIs for deaths were estimated from smoking exposure rates and the estimated RRs.Results: Cigarette smoking was responsible for 23.9%(95% CI: 19.4-28.3%) and 2.4%(95% CI: 1.6-3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5%(95% CI: 21.5-51.6%)], followed by cancer [31.3%(95% CI: 24.6-37.7%)] and cardiovascular disease(CVD) [24.1%(95% CI: 16.7-31.2%)]. While the top three PARs were 12.7%(95% CI: 6.1-19.3%), 4.0%(95% CI: 2.4-5.6%), and 1.1%(95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4%(95% CI: 58.2-76.5%) in men.Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden.展开更多
Objective To evaluate the correlation between programmed death-ligand 1(PD-L1)expression in primary lung cancer cells,tumor associated macrophages(TAM)and patients’clinicopathological characteristics.Methods From 200...Objective To evaluate the correlation between programmed death-ligand 1(PD-L1)expression in primary lung cancer cells,tumor associated macrophages(TAM)and patients’clinicopathological characteristics.Methods From 2008 to 2010,208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital,Fudan University.Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM.The relationship between PD-L1 expression and the clinical pathology was evaluated usingχ2test.Spearman’s rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages.Results Positive PD-L1 expression in primary cancer cells was found in 136(65.3%)patients,which were negatively correlated with lymph node metastasis(P=0.009)and smoking history(P=0.036).Besides,TAM with PD-L1 expression(found in 116 patients)was positively associated with smoking history(P=0.034),well-differentiation(P=0.029)and negative lymph node metastasis(P=0.0096).A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found(r=0.228,P=0.021).Conclusion PD-L1,secreted from TAM,might induce cancer cells apoptosis,and decrease lymph node metastasis.展开更多
Objective To investigate the expression of programmed cell death 5(PDCD5) in tissues of normal human prostate(NP),benign prostatic hyperplasia(BPH),and prostate cancer(PCa) in order to assess the clinical role of PDCD...Objective To investigate the expression of programmed cell death 5(PDCD5) in tissues of normal human prostate(NP),benign prostatic hyperplasia(BPH),and prostate cancer(PCa) in order to assess the clinical role of PDCD5 in PCa.Methods PDCD5 expression was determined by EnVision immunohistochemical staining in formalin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP,22 with BPH,and 22 with PCa.In addition,PCa cases were classified as low/middle-risk(Gleason sum≤7) and high-risk(Gleason sum>7) on the basis of Gleason grade.Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique.Expression of PDCD5 was compared among different prostatic tissues.Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH(P<0.01).However,there was no significant difference in PDCD5 expression between tissues of NP and BPH.In addition,the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa.Conclusions By downregulating apoptosis,low PDCD5 expression may play an important role in the occurrence and development of PCa.PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.展开更多
Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and ...Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends(+2.63% per year; P < 0.05 and +1.9% per year; P < 0.05). This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.展开更多
Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the...Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of MPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs.展开更多
AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability w...AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay.Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Western blotting and immuno-precipitation were used to examine protein expression and recruitment,respectively.Nuclear factorκB(NFκB) binding activities were investigated using electrophoretic mobility shift assay.Nude mice were used to investigate tumor growth. RESULTS:Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibi-tion and cell apoptosis in vitro,and increased tumor growth inhibition and cell death in the tumor mass in vivo.In MKN45 and AGS cells,oxaliplatin treatment promoted both protein kinase B(Akt) and NFκB activation,while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NFκB binding.LY294002 promoted oxaliplatin-induced Fas ligand(FasL) expression,Fas-associated death domain protein recruitment,caspase-8,Bid,and caspase-3 activation,and the short form of cellular caspase-8/FLICEinhibitory protein(c-FLIPS) inhibition.In vivo,LY294002 inhibited oxaliplatin-induced activation of Akt and NFκB,and increased oxaliplatin-induced expression of FasL,inhibition of c-FLIPS,and activation of caspase-8,Bid,and caspase-3. CONCLUSION:Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer treatment.The enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway.展开更多
Autophagy is a conserved and tightly regulated cellular catabolic process that involves the lysosomal degradation pathway. Intracellular recycling of macromolecules and organelles provided by autophagy is an integral ...Autophagy is a conserved and tightly regulated cellular catabolic process that involves the lysosomal degradation pathway. Intracellular recycling of macromolecules and organelles provided by autophagy is an integral part of normal cellular function and permits cells survival under starvation conditions, maintaining cell growth and the homeostasis of organisms. In addition to its normal role in cell physiology, auto- phagy is closely linked to both tumorigenesis and cancer cell response to treatments. In fact, anticancer drugs can induce autophagy but it remains contro- versial whether this process leads to cancer cell death or protects cancer cells from cellular stress. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. However, recent evidences demonstrate a tight interconnection of autophagy with several cell death pathways and reveal an active contribution of auto- phagy to cell death. When autophagy is directly in- volved in the death process, the cell death process is designated “autophagic cell death” (ACD). In this review, we will give a comprehensive overview of the autophagic signaling pathway, its role and regulation in cancer cells;moreover, we will try to define the molecular mechanisms at the basis of the autophagic cell death showing that PPAR-γ activation plays a role in the induction of autophagy in cancer cells.展开更多
OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mech...OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy.展开更多
Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroes...Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.展开更多
BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and...BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.展开更多
Purpose: This study aims to understand how elderly patients with advanced cancer and their families make a decision for a place of death for the patient. Methods: Semi-structured interviews were conducted with 17 pair...Purpose: This study aims to understand how elderly patients with advanced cancer and their families make a decision for a place of death for the patient. Methods: Semi-structured interviews were conducted with 17 pairs of elderly patients and members of their family. The patients had finished anticancer treatment and made some decision about the preferred place of death. A modified grounded-theory approach was used for the data analysis. Results: Making a “tentative” decision for the place of death of the elderly patients is a process with the core category [carefully choosing the final place for self-fulfillment]. The patients were “conducting a comprehensive review of the place of death” and “embracing the wishes for a way of life without difficulty”. Involving the family in making a “tentative” decision about the place of death of the elderly patients is the process with the core category [realizing the wish of patients in the terminal condition for the way for death]. The families were “examining the place of death from different aspects” and “respecting the patient’s intention as far as possible”. Conclusions: When the patients [carefully choosing the final place for self-fulfillment], it was important to reconcile their wishes with the burden on the families. When the families were trying to [realize the wish of patients in the terminal condition for the way for dying], it was important to balance the respect for the patient intentions and homecare they can provide for the patient. For the patients and their families, it is essential to mutually understand the intentions and wishes of the other party in decision making about the place of death.展开更多
OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)anal...OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)analysis and tissue microarray(TMA)analysis.ULK1agonist was designed by using in silico screening,as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities.The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis,as well as in vitro kinase assay and ADP-Glo kinase assay.The mechanisms of LYN-1604 induced cell death were investigated by fluorescence microscope,western blotting,flow cytometry analysis,immunocytochemistry,as well as si RNA and GFP-m RFP-LC3 plasmid transfections.Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model.RESULTS We found that ULK1 was remarkably downregulated in breast cancer tissue samples,especial y in triple negative breast cancer(TNBC).32 candidate smal molecules were synthesized,and we discovered a small molecule named LYN-1604 as the best candidate ULK1agonist.Additionally,we identified that three amino acid residues(LYS50,LEU53 and TYR89)were key to the activation site of LYN-1604 and ULK1.Subsequently,we demonstrated that LYN-1604 could induce autophagy-associated cell death via ULK complex(ULK1-m ATG13-FIP200-ATG101)in MDA-MB-231 cells.We also found that LYN-1604 induced cell death involved in ATF3,RAD21 and caspase 3,accompanied with autophagy and apoptosis.Moreover,we demonstrated that LYN-1604 had a good therapeutic potential on TNBC by targeting ULK1-modulated cell death in vivo.CONCLUSION We discovered a small molecule(LYN-1604)has therapeutic potential by targeting ULK1-modulated cell death associated with autophagy and apoptosis of TNBC in vitro and in vivo,which could be utilized as a new anti-TNBC drug candidate.展开更多
Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass;that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-ch...Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass;that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-chemotherapy, disease relapse and poor prognosis. Recent studies have established that the drug resistant cancers and cancer cell lines possess high stem cell like traits compared to their drug sensitive counterparts. Histone demethylases are recently been linked to drug induced reversible tolerant state in cancers. Lysine histone demethylases are enzymes those demethylate lysines in histones and can act as transcriptional repressors or activators. Apart from histones other cellular proteins like E2F1, Rb, STAT3 and p53 are also regulated by methylation and demethylation cycles. In cancer cells these enzymes regulate cell survival, migration, invasion, and proliferation. This review summarizes the current progress of research on the role of histone demethylases in supporting drug tolerant cancer stem cell state and their potential as a drug target.展开更多
<strong>Purpose:</strong> <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">To identify clinical predictors for redu...<strong>Purpose:</strong> <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">To identify clinical predictors for reduced long-term survival and </span><span><span style="font-family:Verdana;">describe the cause of death after surgical treatment for rectal cancer. </span><b><span style="font-family:Verdana;">Me</span></b></span><b><span style="font-family:Verdana;">thods:</span></b> <span style="font-family:Verdana;">A retrospective follow-up study of 442 consecutive, unselected patients</span><span style="font-family:Verdana;"> treated for rectal cancer at a tertiary centre from 1990 until 2000 and followed for 17 </span><span style="font-family:Verdana;">years or until death. Predictors for death were assessed by Cox regression</span><span style="font-family:Verdana;"> analysis. The cause of death was obtained from the Norwegian Cause of Death Registry. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">254 men and 188 women with a median age of 71 years (21 - 95 years) were resected for rectal cancer with low anterior resection (n = 266), abdominoperineal resection (n = 125), Hartmann’s procedure (n = 19) or diverting stoma only (n = 32). Median follow-up was 5 years (0 - 17 years). The relative five-year survival rates for stages I, II, III and IV was 83.9%, 65.2%, 41.1% and 9.3%, respectively. The proportion of deaths due to recurrence from colorectal cancer in stages I, II, III and IV was 23.5%, 55.8%, 72.3% and 98.0%, respectively. Heart, lung and cerebrovascular disease and other malignancies were the cause of death in the other patients. Higher age, </span><span style="font-family:Verdana;">abdominoperineal resection compared to low anterior resection, lack of</span><span style="font-family:Verdana;"> lymph node dissection compared to total mesorectal excision (TME), postoperative reoperations, TNM stages II and III compared to stage I and residual tumours after surgery were all significant independent predictors of reduced survival in the adjusted Cox regression model. </span><b><span style="font-family:Verdana;">Conclusions: </span></b><span style="font-family:Verdana;">Age, tu</span><span style="font-family:Verdana;">mour stage, type of surgery, lymph node dissection, residual tumour after</span><span style="font-family:Verdana;"> surgery and reoperations are predictors for survival after surgery for rectal cancer. In the patients who died, the cause of death was due to a condition other than colorectal cancer recurrence in 32.3% of the patients. The five-year relative survival rate was related to tumour stage.</span></span></span></span>展开更多
The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the...The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.展开更多
文摘The Paper analyzed of investigation datas on thedeath causes of digestive tract cancer in high-incidencearea between 70s and 80s. The results showed that thecancer-adjusted mortalities were 224.14/100000 and226.66/100000: it was 7 times as high as low-incidence(31.19/100000 and 29.82/100000). In 70s, the cancer deathof esophagus, stomach and liver (87.41/100000,73.93/100000 and 8.59/100000) were 28 times, 10 timesand 4 times as high as low-incidence area (3.70/100000,10.57/100000 and 1.94/100000), respectively (P<0.001). In80s, the cancer death of esophagus, stomach and liver(68.26/100000, 109.39/100000 and 23.89/100000) were 17times, 10 times and 4 times as high as low-incidence area(4.54/100000, 10.84/100000 and 6.35/100000), respectively(P<0.001). In high-incidence area, the cancer death ofesophagus was lower, of stomach and liver were higherin 80s than 70s, respectively (P<0.01)- The result alsoshowed that the nitrate content of drinking water andvegetables were 21.45mg/1 and 1185.27mg/kg in high-incidence area; it were significant higher than that in low-incidence area (2.14mg/1 and 41.6omg/kg), the nitritecontent (0.01mg/l) of drinking water in high-incidencearea was significant higher than that in low-incidencearea (0.004mg/l), but the nitrite content among vegetableswas no significant difference between the two regions(N0.05). Our results suggest that the nitrate and nitritecontents increase in drinking water and vegetables maybe an important risk factor of upper alimentary cancer inhigh-incidence area.
文摘<strong>Objective: </strong>This study aimed to clarify the death characteristics of esophageal cancer in Inner Mongolia and the population distribution with various education levels. <strong>Methods:</strong> The mortality rate of esophageal cancer was calculated using the monitoring point of Death Registry System in Inner Mongolia from 2009 to 2015. The gender, age, region, ethnicity at two education levels of percentage were calculated and the <em>χ</em><sup>2</sup> test was executed. <strong>Result:</strong> The mortality rate of esophageal cancer was 10.10/105, China Adjustment Mortality was 10.97/10<sup>5</sup>, World Adjustment Mortality was 9.08/10<sup>5</sup> in Inner Mongolia. The death of esophageal cancer showed statistical significance at two educational levels (P < 0.05). High school and below accounted for 93.9% at the education level, and above high school accounted for 3.5%. In addition, there were significant differences in the percentage of death by gender, age and region at two educational levels (P < 0.05). <strong>Conclusion:</strong> Education level has a certain relation with the death of esophageal cancer. To improve the health level, health education plans can be formulated according to esophageal cancer prevention relevant policy with different education levels.
文摘If more Americans quit smoking,lost a little weight and started eating bet-ter,at least 60,000 cancer deaths could be avoided each year,according tO a re-port issued Monday by a government advisory panel. 假如有更多的美国人戒烟,适当减肥,并开始吃得更健康些,至少每年可以减少60 000死于癌症的病例。政府顾问团周一发表的一则报告如是说。
基金supported by the funds of Key Discipline and Specialty Foundation of Shanghai Municipal Commission of Health and Family Planningthe National Key Basic Research Program "973 project" (2015CB554000)grants from US National Institutes of Health (R37 CA070867, R01 CA82729, UM1CA173640, and UM1 CA182910)
文摘Objective: To evaluate the population attributable risks(PARs) between cigarette smoking and deaths of all causes, all cancers, lung cancer and other chronic diseases in urban Shanghai.Methods: In total, 61,480 men aged 40-74 years from 2002 to 2006 and 74,941 women aged 40-70 years from 1997 to 2000 were recruited to undergo baseline surveys in urban Shanghai, with response rates of 74.0% and 92.3%, respectively. A Cox proportional hazards regression model was used to estimate relative risks(RRs) and 95% confidence intervals(95% CIs) of deaths associated with cigarette smoking. PARs and 95% CIs for deaths were estimated from smoking exposure rates and the estimated RRs.Results: Cigarette smoking was responsible for 23.9%(95% CI: 19.4-28.3%) and 2.4%(95% CI: 1.6-3.2%) of all deaths in men and women, respectively, in our study population. Respiratory disease had the highest PAR in men [37.5%(95% CI: 21.5-51.6%)], followed by cancer [31.3%(95% CI: 24.6-37.7%)] and cardiovascular disease(CVD) [24.1%(95% CI: 16.7-31.2%)]. While the top three PARs were 12.7%(95% CI: 6.1-19.3%), 4.0%(95% CI: 2.4-5.6%), and 1.1%(95% CI: 0.0-2.3%), for respiratory disease, CVD, and cancer, respectively in women. For deaths of lung cancer, the PAR of smoking was 68.4%(95% CI: 58.2-76.5%) in men.Conclusions: In urban Shanghai, 23.9% and 2.4% of all deaths in men and women could have been prevented if no people had smoked in the area. Effective control programs against cigarette smoking should be strongly advocated to reduce the increasing smoking-related death burden.
文摘Objective To evaluate the correlation between programmed death-ligand 1(PD-L1)expression in primary lung cancer cells,tumor associated macrophages(TAM)and patients’clinicopathological characteristics.Methods From 2008 to 2010,208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital,Fudan University.Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM.The relationship between PD-L1 expression and the clinical pathology was evaluated usingχ2test.Spearman’s rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages.Results Positive PD-L1 expression in primary cancer cells was found in 136(65.3%)patients,which were negatively correlated with lymph node metastasis(P=0.009)and smoking history(P=0.036).Besides,TAM with PD-L1 expression(found in 116 patients)was positively associated with smoking history(P=0.034),well-differentiation(P=0.029)and negative lymph node metastasis(P=0.0096).A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found(r=0.228,P=0.021).Conclusion PD-L1,secreted from TAM,might induce cancer cells apoptosis,and decrease lymph node metastasis.
文摘Objective To investigate the expression of programmed cell death 5(PDCD5) in tissues of normal human prostate(NP),benign prostatic hyperplasia(BPH),and prostate cancer(PCa) in order to assess the clinical role of PDCD5 in PCa.Methods PDCD5 expression was determined by EnVision immunohistochemical staining in formalin-fixed and paraffin-embedded specimens obtained from 12 subjects with NP,22 with BPH,and 22 with PCa.In addition,PCa cases were classified as low/middle-risk(Gleason sum≤7) and high-risk(Gleason sum>7) on the basis of Gleason grade.Positive expression rates and intensity of PDCD5 protein were observed under light microscope and analyzed with computer imaging technique.Expression of PDCD5 was compared among different prostatic tissues.Results The expression of PDCD5 was significantly lower in tissue of PCa than in tissues of NP and BPH(P<0.01).However,there was no significant difference in PDCD5 expression between tissues of NP and BPH.In addition,the expression of PDCD5 was further downregulated with the increase of Gleason sum in PCa.Conclusions By downregulating apoptosis,low PDCD5 expression may play an important role in the occurrence and development of PCa.PDCD5 is supposed to have a potential clinical value to be a new predictor of progression and target of gene therapy in PCa.
基金supported by the National Natural Science foundation of China[Grant No.81673248]a grant from the Fundamental Research Funds for the Central Universites[Grant No.lzujbky-2017-k04]
文摘Population-based cancer registration data were collected to estimate the cancer incidence and mortality in Wuwei, Hexi Corridor Region, China in 2018. We used the 2011-2013 data to predict the number of new cases and deaths in 2018 and the 2003-2013 data to analyze trends in cancer incidence and mortality. The goal is to enable cancer prevention and control directions. Our results indicated that stomach cancer is the most common cancer. For all cancers combined, the incidence and mortality rates showed significantly increasing trends(+2.63% per year; P < 0.05 and +1.9% per year; P < 0.05). This study revealed a significant cancer burden among the population of this area. Cancer screening and prevention should be performed after an epidemiological study of the cause of the cancer is completed.
文摘Human tumors tend to activate the immune system regulatory checkpoints as a means of escaping immunosurveillance. For instance, interaction between program death-1(PD-1) and program death-ligand 1(PD-L1) will lead the activated T cell to a state of anergy. PD-L1 is upregulated on a wide range of cancer cells. Anti-PD-1 and anti-PD-L1 monoclonal antibodies(m Abs), called immune checkpoint inhibitors(ICIs), have consequently been designed to restore T cell activity. Accumulating data are in favor of an association between PD-L1 expression in tumors and response to treatment. A PD-L1 expression is present in 30% to 50% of digestive cancers. Multiple anti-PD-1(nivolumab, pembrolizumab) and anti-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluation in digestive cancers. Preliminary results in metastatic gastric cancer with pembrolizumab are highly promising and phase Ⅱ will start soon. In metastatic colorectal cancer(CRC), a phase Ⅲ trial of MPDL3280 A as maintenance therapy will shortly be initiated. Trials are also ongoing in metastatic CRC with high immune T cell infiltration(i.e., microsatellite instability). Major challenges are ahead in order to determine how, when and for which patients we should use these ICIs. New radiologic criteria to evaluate tumor response to ICIs are awaiting prospective validation. The optimal therapeutic sequence and association with cytotoxic chemotherapy needs to be established. Finally, biomarker identification will be crucial to selection ofpatients likely to benefit from ICIs.
基金Supported by The National Natural Science Foundation of China,No.30470782
文摘AIM:To examine the effects of combined treatment of oxaliplatin and phosphatidylinositol 3'-kinase inhibitor,2-(4-morpholinyl) -8-phenyl-4H-1-benzopyran-4-one(LY294002) for gastric cancer. METHODS:Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay.Apoptotic cells were detected by flow cytometric analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay.Western blotting and immuno-precipitation were used to examine protein expression and recruitment,respectively.Nuclear factorκB(NFκB) binding activities were investigated using electrophoretic mobility shift assay.Nude mice were used to investigate tumor growth. RESULTS:Treatment with combined oxaliplatin and LY294002 resulted in increased cell growth inhibi-tion and cell apoptosis in vitro,and increased tumor growth inhibition and cell death in the tumor mass in vivo.In MKN45 and AGS cells,oxaliplatin treatment promoted both protein kinase B(Akt) and NFκB activation,while pretreatment with LY294002 significantly attenuated oxaliplatin-induced Akt activity and NFκB binding.LY294002 promoted oxaliplatin-induced Fas ligand(FasL) expression,Fas-associated death domain protein recruitment,caspase-8,Bid,and caspase-3 activation,and the short form of cellular caspase-8/FLICEinhibitory protein(c-FLIPS) inhibition.In vivo,LY294002 inhibited oxaliplatin-induced activation of Akt and NFκB,and increased oxaliplatin-induced expression of FasL,inhibition of c-FLIPS,and activation of caspase-8,Bid,and caspase-3. CONCLUSION:Combination of oxaliplatin and LY294002 was therapeutically promising for gastric cancer treatment.The enhanced sensitivity of the combined treatment was associated with the activation of the death receptor pathway.
文摘Autophagy is a conserved and tightly regulated cellular catabolic process that involves the lysosomal degradation pathway. Intracellular recycling of macromolecules and organelles provided by autophagy is an integral part of normal cellular function and permits cells survival under starvation conditions, maintaining cell growth and the homeostasis of organisms. In addition to its normal role in cell physiology, auto- phagy is closely linked to both tumorigenesis and cancer cell response to treatments. In fact, anticancer drugs can induce autophagy but it remains contro- versial whether this process leads to cancer cell death or protects cancer cells from cellular stress. The role of autophagy in cancer is complex and is likely dependent on tumor type, stage, and genetic context. However, recent evidences demonstrate a tight interconnection of autophagy with several cell death pathways and reveal an active contribution of auto- phagy to cell death. When autophagy is directly in- volved in the death process, the cell death process is designated “autophagic cell death” (ACD). In this review, we will give a comprehensive overview of the autophagic signaling pathway, its role and regulation in cancer cells;moreover, we will try to define the molecular mechanisms at the basis of the autophagic cell death showing that PPAR-γ activation plays a role in the induction of autophagy in cancer cells.
基金supported by National Natural Science Foundation of China(81473091,81673290 and U1603123)
文摘OBJECTIVE To discover a small-molecule bromodomain-containing protein 4(BRD4)inhibitor that induces AMP-activated protein kinase-modulated autophagy-associated cell death in breast cancer and exploreits potential mechanisms.METHODS BRD4 interactors were analyzed by PPI network prediction and The Cancer Genome Atlas(TCGA)analysis.The interaction between BRD4 and AMPK was confirmed by co-immunoprecipitation assay.Novel BRD4 inhibitors were designed and synthesized based upon pharmacophore analysis of BRD4(1),then screened by antiproliferative activity and Alpha Screen of BRD4(1).The selectivity of the best candidate compound 8f was validated by co-crystallization,FRET assay and co-immuno precipitation assay.The mechanisms of 8f were investigated by fluorescence microscopy,electron microscopy,Western blotting,immunocytochemistry,si RNA and GFP-m RFP-LC3 plasmid transfections,as well as immunohistochemistry and immunofluorescence.Potential mechanisms were discovered by i TRAQ-based proteomics analysis and the therapeutic effect of 8f was assessed by xenograft breast cancer mouse and zebrafish models.RESULTS We identified that BRD4 interacted with AMPK,which was remarkably downregulated in breast cancer.We next designed and synthesized 49 candidate compounds,and eventually discovered a selective small-molecule inhibitor of BRD4(8f).Subsequently,8f was discovered to induce autophagyassociated cell death(ACD)by BRD4-AMPK interaction,and thus activating AMPK-m TOR-ULK1-modulated autophagic pathway in breast cancer cells.Interestingly,the i TRAQ-based proteomics analyses revealed that 8f induced ACD pathways,involved in HMGB1,VDAC1/2 and e EF2.Moreover,8f displayed a therapeutic potential on both xenograft breast cancer mouse and zebrafish models.CONCLUSION We discovered a novel small-molecule inhibitor of BRD4 that induces BRD4-AMPK-modulated ACD in breast cancer,which may provide a candidate drug for future cancer therapy.
文摘Blockade of the programmed death ligand 1(PD-L1) and programmed cell death 1(PD-1) receptor axis represents an effective form of cancer immunotherapy. Preclinical evidence initially suggested that gastric and gastroesophageal junction(GEJ) cancers are potentially immunotherapy-sensitive tumors. Early phase clinical trials have demonstrated promising antitumor activity with PD-1/PD-L1 blockade in advanced or metastatic gastric/GEJ cancer. Microsatellite instability(MSI) and PD-L1 expression have been shown to predict higher response to PD-1 inhibitors as highlighted by the recent approvals of pembrolizumab in treatmentrefractory solid tumors with MSI status and the thirdline or greater treatment of PD-L1 positive advanced gastric/GEJ cancers. However, predictive and prognostic biomarkers remain an ongoing need. In this review, we detail the preclinical evidence and early tissue biomarker analyses illustrating potential predictive biomarkers to PD-1/PD-L1 blockade in gastric/GEJ cancer. We also review the clinical development of PD-1/PD-L1 inhibitors in gastric/GEJ cancer and highlight several areas in need of future investigation in order to optimize the efficacy of PD-1/PD-L1 blockade in gastric/GEJ cancer.
基金Supported by Heilongjiang Provincial Health and Family Planning Commission Research Project,No.2017-413
文摘BACKGROUND Oral cancer(OC)is the most common malignant tumor in the oral cavity,and is mainly seen in middle-aged and elderly men.At present,OC is mainly treated clinically by surgery or combined with radiotherapy and chemotherapy;but recently,more and more studies have shown that the stress trauma caused by surgery and the side effects of radiotherapy and chemotherapy seriously affect the prognosis of patients.AIM To determine the significance of 125I radioactive seed implantation on growth differentiation factor 11(GDF11)and programmed death receptor-1(PD-1)during treatment of OC.METHODS A total of 184 OC patients admitted to The Second Affiliated Hospital of Jiamusi University from May 2015 to May 2017 were selected as the research subjects for prospective analysis.Of these patients,89 who received 125I radioactive seed implantation therapy were regarded as the research group(RG)and 95 patients who received surgical treatment were regarded as the control group(CG).The clinical efficacy,incidence of adverse reactions and changes in GDF11 and PD-1 before treatment(T0),2 wk after treatment(T1),4 wk after treatment(T2)and 6 wk after treatment(T3)were compared between the two groups.RESULTS The efficacy and recurrence rate in the RG were better than those in the CG(P<0.05),while the incidence of adverse reactions and survival rate were not different.There was no difference in GDF11 and PD-1 between the two groups at T0 and T1,but these factors were lower in the RG than in the CG at T2 and T3(P<0.05).Using receiver operating characteristic(ROC)curve analysis,GDF11 and PD-1 had good predictive value for efficacy and recurrence(P<0.001).CONCLUSION 125I radioactive seed implantation has clinical efficacy and can reduce the recurrence rate in patients with OC.This therapy has marked potential in clinical application.The detection of GDF11 and PD-1 in patients during treatment showed good predictive value for treatment efficacy and recurrence in OC patients,and may be potential targets for future OC treatment.
文摘Purpose: This study aims to understand how elderly patients with advanced cancer and their families make a decision for a place of death for the patient. Methods: Semi-structured interviews were conducted with 17 pairs of elderly patients and members of their family. The patients had finished anticancer treatment and made some decision about the preferred place of death. A modified grounded-theory approach was used for the data analysis. Results: Making a “tentative” decision for the place of death of the elderly patients is a process with the core category [carefully choosing the final place for self-fulfillment]. The patients were “conducting a comprehensive review of the place of death” and “embracing the wishes for a way of life without difficulty”. Involving the family in making a “tentative” decision about the place of death of the elderly patients is the process with the core category [realizing the wish of patients in the terminal condition for the way for death]. The families were “examining the place of death from different aspects” and “respecting the patient’s intention as far as possible”. Conclusions: When the patients [carefully choosing the final place for self-fulfillment], it was important to reconcile their wishes with the burden on the families. When the families were trying to [realize the wish of patients in the terminal condition for the way for dying], it was important to balance the respect for the patient intentions and homecare they can provide for the patient. For the patients and their families, it is essential to mutually understand the intentions and wishes of the other party in decision making about the place of death.
基金supported by National Natural Science Foundation of China(81402496,81673455and 81602627)China Postdoctoral Special Science Foundation(2017T100704)China Postdoctoral Science Foundation(2015M580794)
文摘OBJECTIVE To discover a small molecule targeting ULK1-modulated cell death of triple negative breast cancer and exploreits potential mechanisms.METHODS ULK1 expression was analyzed by The Cancer Genome Atlas(TCGA)analysis and tissue microarray(TMA)analysis.ULK1agonist was designed by using in silico screening,as well as modified by chemical synthesis and screened by kinase and anti-proliferative activities.The amino acid residues that key to the activation site of LYN-1604 were determined by site-directed mutagenesis,as well as in vitro kinase assay and ADP-Glo kinase assay.The mechanisms of LYN-1604 induced cell death were investigated by fluorescence microscope,western blotting,flow cytometry analysis,immunocytochemistry,as well as si RNA and GFP-m RFP-LC3 plasmid transfections.Potential ULK1 interactors were discovered by performing comparative microarray analysis and the therapeutic effect of LYN-1604 was assessed by xenograft breast cancer mouse model.RESULTS We found that ULK1 was remarkably downregulated in breast cancer tissue samples,especial y in triple negative breast cancer(TNBC).32 candidate smal molecules were synthesized,and we discovered a small molecule named LYN-1604 as the best candidate ULK1agonist.Additionally,we identified that three amino acid residues(LYS50,LEU53 and TYR89)were key to the activation site of LYN-1604 and ULK1.Subsequently,we demonstrated that LYN-1604 could induce autophagy-associated cell death via ULK complex(ULK1-m ATG13-FIP200-ATG101)in MDA-MB-231 cells.We also found that LYN-1604 induced cell death involved in ATF3,RAD21 and caspase 3,accompanied with autophagy and apoptosis.Moreover,we demonstrated that LYN-1604 had a good therapeutic potential on TNBC by targeting ULK1-modulated cell death in vivo.CONCLUSION We discovered a small molecule(LYN-1604)has therapeutic potential by targeting ULK1-modulated cell death associated with autophagy and apoptosis of TNBC in vitro and in vivo,which could be utilized as a new anti-TNBC drug candidate.
文摘Cancer stem cells (CSCs) are tumor initiating cells within the tumor mass;that play a critical role in cancer pathogenesis. CSCs regulate cancer cell survival, metastatic potential, resistance to conventional radio-chemotherapy, disease relapse and poor prognosis. Recent studies have established that the drug resistant cancers and cancer cell lines possess high stem cell like traits compared to their drug sensitive counterparts. Histone demethylases are recently been linked to drug induced reversible tolerant state in cancers. Lysine histone demethylases are enzymes those demethylate lysines in histones and can act as transcriptional repressors or activators. Apart from histones other cellular proteins like E2F1, Rb, STAT3 and p53 are also regulated by methylation and demethylation cycles. In cancer cells these enzymes regulate cell survival, migration, invasion, and proliferation. This review summarizes the current progress of research on the role of histone demethylases in supporting drug tolerant cancer stem cell state and their potential as a drug target.
文摘<strong>Purpose:</strong> <span><span><span style="font-family:;" "=""><span style="font-family:Verdana;">To identify clinical predictors for reduced long-term survival and </span><span><span style="font-family:Verdana;">describe the cause of death after surgical treatment for rectal cancer. </span><b><span style="font-family:Verdana;">Me</span></b></span><b><span style="font-family:Verdana;">thods:</span></b> <span style="font-family:Verdana;">A retrospective follow-up study of 442 consecutive, unselected patients</span><span style="font-family:Verdana;"> treated for rectal cancer at a tertiary centre from 1990 until 2000 and followed for 17 </span><span style="font-family:Verdana;">years or until death. Predictors for death were assessed by Cox regression</span><span style="font-family:Verdana;"> analysis. The cause of death was obtained from the Norwegian Cause of Death Registry. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">254 men and 188 women with a median age of 71 years (21 - 95 years) were resected for rectal cancer with low anterior resection (n = 266), abdominoperineal resection (n = 125), Hartmann’s procedure (n = 19) or diverting stoma only (n = 32). Median follow-up was 5 years (0 - 17 years). The relative five-year survival rates for stages I, II, III and IV was 83.9%, 65.2%, 41.1% and 9.3%, respectively. The proportion of deaths due to recurrence from colorectal cancer in stages I, II, III and IV was 23.5%, 55.8%, 72.3% and 98.0%, respectively. Heart, lung and cerebrovascular disease and other malignancies were the cause of death in the other patients. Higher age, </span><span style="font-family:Verdana;">abdominoperineal resection compared to low anterior resection, lack of</span><span style="font-family:Verdana;"> lymph node dissection compared to total mesorectal excision (TME), postoperative reoperations, TNM stages II and III compared to stage I and residual tumours after surgery were all significant independent predictors of reduced survival in the adjusted Cox regression model. </span><b><span style="font-family:Verdana;">Conclusions: </span></b><span style="font-family:Verdana;">Age, tu</span><span style="font-family:Verdana;">mour stage, type of surgery, lymph node dissection, residual tumour after</span><span style="font-family:Verdana;"> surgery and reoperations are predictors for survival after surgery for rectal cancer. In the patients who died, the cause of death was due to a condition other than colorectal cancer recurrence in 32.3% of the patients. The five-year relative survival rate was related to tumour stage.</span></span></span></span>
文摘The recent discovery of immune checkpoints inhibitors, especially anti-programmed cell death protein 1(PD-1)and anti-programmed cell death protein ligand 1(PD-L1) monoclonal antibodies, has opened new scenarios in the management of non-small cell lung cancer(NSCLC) and this new class of drugs has achieved a rapid development in the treatment of this disease. However, considering the costs of these drugs and the fact that only a subset of patients experience long-term disease control, the identification of predictive biomarkers for the selection of candidates suitable for treatment has become a priority. The research focused mainly on the expression of the PD-L1 receptor on both tumor cells and/or immune infiltrates determined by immunohistochemistry(IHC). However, different checkpoint inhibitors were tested, different IHC assays were used, different targets were considered(tumor cells, immune infiltrates or both) and different expression thresholds were employed in clinical trials. In some trials the assay was used prospectively to select the patients, while in other trials it was evaluated retrospectively. Some confusion emerges, which makes it difficult to easily compare the literature data and to translate them in practice management. This mini-review shows the possibilities and pitfalls of the PD-L1 expression to predict the activity and efficacy of anti PD1/PD-L1 monoclonal antibodies in the treatment of NSCLC.
