Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth.Rapid release of extracellular vesicles(EVs)during exercise suggests their potential role as mediators of exercise-induced sy...Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth.Rapid release of extracellular vesicles(EVs)during exercise suggests their potential role as mediators of exercise-induced systemic effects and physiological adaptation.This study investigated the impact of exercise-induced plasma EVs on tumor growth and immune tumor microenvironment in murine models of triple-negative breast cancer(TNBC):EO771(a C57BL/6-derived TNBC cell line)and 4T1(a BALB/c-derived TNBC cell line).Methods Size exclusion chromatography was used to isolate exercise-induced EVs from plasma of healthy female mice(BALB/c and C56BL/6,n=30 per strain)that underwent ten 30-min moderate-intensity treadmill running sessions over 2 weeks.Nanoparticle tracking analysis,Western blot,and electron microscopy confirmed the presence of EVs in the samples.Tumor-bearing mice(n=72 per strain)were administered with exercise-induced EVs before or/and after tumor implantation.Local and systemic immune responses were assessed using flow cytometry,enzyme-linked immunosorbent assay(ELISA),and quantitative polymerase chain reaction(qPCR).Results Administration of exercise-induced EVs,particularly before tumor implantation,significantly suppressed tumor growth and reduced tumor burden in both TNBC models.In EO771,endpoint tumor volumes were 278–330 mm^(3)in treated groups compared to 799 mm^(3)in untreated(p<0.0001),while in 4T1,treated groups showed volumes of 287–564 mm^(3)vs.696 mm^(3)in untreated(p=0.0002).Notable differences in tumor-infiltrating lymphoid and myeloid cell subpopulations indicated immunomodulatory effects of exercise-induced EVs,particularly in the 4T1 model,where their continuous administration significantly increased intratumoral cluster of differentiation 8(CD8)T lymphocyte proportion(5.77%vs.0.90%in untreated,p<0.0001).Similarly,in the EO771 model,exercise-induced EVs administered before tumor implantation led to a marked rise in intratumoral CD8 T lymphocytes(2.24%vs.1.08%in untreated,p=0.0181).Conclusion Our findings indicate that exercise-induced EV treatment elicits a pro-inflammatory antitumor immune response,suggesting a shift of immunologically cold TNBC tumors towards a more inflamed phenotype associated with better outcomes.Our study supports the further investigation of EVs as modulators of antitumor immunity and their potential utility in enhancing the efficacy of immunotherapy.展开更多
Cellular senescence is a steady state of cell cycle arrest necessary to maintain homeostasis in organisms.However,senescent cells may cause senescence in neighboring healthy cells,inducing the onset of several disease...Cellular senescence is a steady state of cell cycle arrest necessary to maintain homeostasis in organisms.However,senescent cells may cause senescence in neighboring healthy cells,inducing the onset of several diseases,such as inflammation,neurological disorders,and atherosclerosis.Therefore,early detection of cellular senescence is extremely important.β-Galactosidase(β-gal),as a critical marker of cellular senescence,can be monitored to facilitate early diagnosis of aging-related diseases.Furthermore,β-gal is mainly found in lysosomes,which have a pH value of about 4.5-5.5.Here,we developed a near-infrared fluorescent probe(QMOH-Gal)for tracking cell senescence in vitro and in vivo via the detection ofβ-gal.In addition,the probe displayed high sensitivity and specificity forβ-gal with good fluorescence signal in the acidity range.Subsequently,this QMOH-Gal probe was successfully employed to differentiate between normal cells and senescent cells by monitoringβ-gal.Furthermore,the probe not only realized the monitoring ofβ-gal in zebrafish but also the tracking ofβ-gal in palbociclib-induced breast tumor senescence.Overall,the probe shows great promise as an effective tool for imagingβ-gal in vivo for studying the biology of aging in organisms.展开更多
The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experim...The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.展开更多
BACKGROUND Transanal total mesorectal excision(taTME)is a new technique with many potential technical advantages.Laparoscopy-assisted taTME is a combination of transabdominal taTME and transluminal endoscopic surgery ...BACKGROUND Transanal total mesorectal excision(taTME)is a new technique with many potential technical advantages.Laparoscopy-assisted taTME is a combination of transabdominal taTME and transluminal endoscopic surgery taTME.Laparoscopy-assisted taTME is a combination of techniques such as minimally invasive surgery,intersphincter-assisted resection,natural orifice extraction,ta minimally invasive surgery,and ultralow-level preservation of the anus.AIM To verify the feasibility and safety of an innovative technique of taTME for treatment of cancer located in the lower rectum.METHODS From January 2016 to March 2018,we attempted to perform laparoscopy-assisted taTME surgery in 24 patients with lower rectal cancer.RESULTS The new technique of laparoscopy-assisted taTME was successfully performed in all 24 patients.Mean operating time was 310.0 min and mean intraoperative blood loss was 69.1 mL.The mean time to passing of first flatus was 3.1 d,and mean postoperative hospital stay was 9.2 d.Two patients were given postoperative analgesics due to anal pain.Twenty-three patients were able to walk in first 2 d,and five patients had postoperative complications.CONCLUSION Laparoscopy-assisted taTME is suitable for selected patients with lower rectal cancer,and this technique is worthy of further recommendation.展开更多
In cancer biology,mesenchymal stem cells(MSCs)display aspects that can appear contradictory.On one hand,these cells possess several features which give them the ability to specifically target and then sustain cancer c...In cancer biology,mesenchymal stem cells(MSCs)display aspects that can appear contradictory.On one hand,these cells possess several features which give them the ability to specifically target and then sustain cancer cells in their ability to survive the multifaceted host response against cancer.On the other hand,due to this excellent aptitude to home-in on tumor tissues,regardless their location in the host’s body,MSCs are considered to be extremely selective vehicles to reach cancer cells specifically.Recently,MSC sustainment of cancer cell growth is a hot research topic.Indeed,these cells are known to sustain tumor angiogenesis and metastasis formation,to create a microenvironment favorable for cancer cell growth and to down-modulate the immune system capabilities in the host organism.On the other hand,since scientists became able to take advantage of their extremely selective capability to target cancer cells,MSCs are now also thought of in a different light.Indeed,MSCs are now considered a promising vehicle for local expression or delivery of even particularly toxic anticancer agents,ranging from Herpes Simplex Virus to locally-acting antineoplastic drugs.On this basis,investigation is now focused on how to impair the pro-neoplastic features of MSCs on one hand whilst taking advantage of their specific tropism toward cancer cells,on the other.As with the two faces of Janus,this review will concisely explore the research activity in these two apparently conflicting fields.展开更多
Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and i...Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.展开更多
Objective： To find an effective treatment for advanced cancer patients with esophageal fistula. Methods： From 1998 to 2006, we studied 42 patients with advanced esophageal cancer and 5 lung cancer patients with carc...Objective： To find an effective treatment for advanced cancer patients with esophageal fistula. Methods： From 1998 to 2006, we studied 42 patients with advanced esophageal cancer and 5 lung cancer patients with carcinomatous esophageal fistula （3 females, 44 males, aged 29-92 years）. Ten patients with both esophageal cancer stricture and fistula were first dilated under endoscope, then a memory stent with a membrane was placed in the esophageal lumen. Others were treated only with a memory stent with a membrane, three of them with a large fistula （diameter 〉1.5 cm） were treated with bio-protein glue after placement of an esophageal metal stent. Results： The fistulas were covered by a stent and the patients could eat and drink immediately. Their quality of life was improved and their survival was prolonged, 44 out of 47 patients survived for 〉3 mo. Conclusion： Placement of esophageal stent with membrane or in combination with bio-protein glue through endoscope is an effective method for treating the bronchoesophageal fistula.展开更多
Objective: To explore the death-related factors of stageⅠrectal cancer patients. Methods: 89 cases of stage I rectal cancer patients between 1985 and 2000 were retrospectively studied for prognostic factors. Factors ...Objective: To explore the death-related factors of stageⅠrectal cancer patients. Methods: 89 cases of stage I rectal cancer patients between 1985 and 2000 were retrospectively studied for prognostic factors. Factors including age, gender, tumor size, circumferential occupation, gross type, pathological type, depth of tumor invasion, surgical procedure, adjuvant chemotherapy and postoperative complication were chosen for cox multivariate analysis (forward procedure) using Spss software (10.0 version). Results: multivariate analysis demonstrated that muscular invasion was an independent negative prognostic factor for stageⅠrectal cancer patients (P=0.003). Conclusion: Muscular invasion is a negative prognostic factor for stage I rectal cancer patients.展开更多
Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in th...Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in this field using the bibliometric analysis.Publications in the PubMed and Web of Science databases were retrieved.Overall,there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer.Researchers from USA,Germany,Italy,China and England have greater studies than others.Top three publication institutions are University of California System,UDICE-French Research Universities and University of Texas System.Current research hotspots include oxidative stress,breast cancer,melatonin,cell cycle,calorie restriction,prostate cancer and NF-κB.In conclusion,results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer.These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.展开更多
The epidemioiogical features of lung cancer in Beijing during 1977 ?1986 were analysed. The data collected showed that lung cancer ncidence and mortality rates ranks first among all other malignant tumor and had been ...The epidemioiogical features of lung cancer in Beijing during 1977 ?1986 were analysed. The data collected showed that lung cancer ncidence and mortality rates ranks first among all other malignant tumor and had been on the increase from year to year. The mortality rate in urban area was higher than that in its suburbs. While the male incidence was higher than that of the female. The sex ratio of the male to female incidence rates was 1.56. The incidence rate rises with age. The lung cancer is one of the lesser prevised cancer and the five-year relative survival rate is 6.5% for both sexes in 19S2 ?1983. The lung cancer mortality rate in Beijing urban area is compared in this report with other countries in the world, and it is found that the female mortality rate of lung cancer in Beijing is among the highest.展开更多
BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine recept...BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.展开更多
The intricate relationship between cancer,circadian rhythms,and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression.Aging is a well-est...The intricate relationship between cancer,circadian rhythms,and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression.Aging is a well-established primary risk factor for cancer,while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors.Moreover,aging itself disrupts circadian rhythms,leading to physiological changes that may accelerate cancer development.Despite these connections,the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature.In this review,we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development.We discuss how core circadian genes impact tumor risk and prognosis,highlighting the shared hallmarks of cancer and aging such as genomic instability,cellular senescence,and chronic inflammation.Furthermore,we examine the interplay between circadian rhythms and aging,focusing on how this crosstalk contributes to tumorigenesis,tumor proliferation,and apoptosis,as well as the impact on cellular metabolism and genomic stability.By elucidating the common pathways linking aging,circadian rhythms,and cancer,this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies.We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments,including chronotherapy and antiaging interventions,which may offer important benefits in the clinical management of cancer.展开更多
AIM： To determine whether any changes have occurred on the patterns of colorectal cancer in China. METHODS： Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorecta...AIM： To determine whether any changes have occurred on the patterns of colorectal cancer in China. METHODS： Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorectal cancer according to the patients＇age at diagnosis, sex, the site of the tumor, stage, and the pathology. RESULTS： From 1980s to 1990s, the mean age of the colorectal cancer patients has increased. The percentage of the female patients rose. The distribution of colorectal carcinoma shows a predominance of rectal cancer. However, the proportion of proximal colon cancer （induding transverse and ascending colon） increased significantly accompanied by a decline in the percentage of rectal cancer. Similarity in the percentage of distal colon cancer between two decades was revealed. In the 1990s, statistically more Stage B patients were found than those in 1980s. In addition, databases show a significant decrease in the Stage D cases. The proportion of adenocarcinoma increased, but the mucinous adenocarcinoma decreased during two decades. CONCLUSION： These findings indicate that the pattern of colorectal cancer in China has been changing. Especially, a proximal shift due to the increasing proportion of ascending and transverse colon cancer has occurred in China.展开更多
Epidermal growth fac tor receptor (EGFR) is one of the most commonly altered genes in human cancer by way of over-expression, amplification, and mutation. Targeted inhibition of EGFR activity suppresses signal transdu...Epidermal growth fac tor receptor (EGFR) is one of the most commonly altered genes in human cancer by way of over-expression, amplification, and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation, and resistance to apoptosis. Small molecule tyrosine kinase inhibitors and monoclonal antibodies are among the most common EGFR-targeting agents and have been used clinically for treating various malignancies. This review discusses the successes and challenges of targeting EGFR in human cancer. The genetic alterations of EGFR tend to occur more often in some solid tumors than others, as do the mechanisms of resistance to targeted inhibition. The clinical and basic science experiences with these agents thus far have important implications for the future of therapeutic targeting of EGFR.展开更多
About 75% of all breast cancers are estrogen receptor(ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. ...About 75% of all breast cancers are estrogen receptor(ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens(such as tamoxifen and fulvestrant) and aromatase inhibitors(such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy(acquired resistance) and a proportion of patients may fail to respond to initial therapy(de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectivelyovercome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.展开更多
Prostate cancer （PCa） preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is curren...Prostate cancer （PCa） preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is currently unknown, although considerable progress has been made in determining the key players in this process. In this review, we present the current understanding of the molecular processes driving PCa metastasis to the bone.展开更多
Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis...Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis are limited by lack of appropriate models for the development and pathogenesis of the disease based on human tissues. Primary culture of patient samples can help but is difficult to grow for a number of tissues. A potential opportunity to overcome these barriers is based on the landmark study by Yamanaka which demonstrated the ability of four factors;Oct4, Sox2, Klf4, and c-Myc to reprogram human somatic cells in to pluripotency. These cells were termed induced pluripotent stem cells(i PSCs) and display characteristic properties of embryonic stem cells. This technique has a wide range of potential uses including disease modelling, drug testing and transplantation studies. Interestingly i PSCs also share a number of characteristics with cancer cells including self-renewal and proliferation, expression of stem cell markers and altered metabolism. Recently, i PSCs have been generated from a number of human cancer cell lines and primary tumour samples from a range of cancers in an attempt to recapitulate the development of cancer and interrogate the underlying mechanisms involved. This review will outline the similarities between the reprogramming process and carcinogenesis, and how these similarities have been exploited to generate i PSC models for a number of cancers.展开更多
AIM： To evaluate endoscopic mucosal resection （EMR） in patients with high-grade dysplasia （HGD） and/or intramucosal cancer （IMC） in Barrett＇s esophagus （BE）. METHODS： Between June 2000 and December 2003, 39...AIM： To evaluate endoscopic mucosal resection （EMR） in patients with high-grade dysplasia （HGD） and/or intramucosal cancer （IMC） in Barrett＇s esophagus （BE）. METHODS： Between June 2000 and December 2003, 39 consecutive patients with HGD （35） and/or IMC （4） underwent EMR. BE 〉30 mm was present in 27 patients. In three patients with short segment BE （25.0%）, HGD was detected in a normal appearing BE. Lesions had a mean diameter of 14.8＋10.3 ram. Mucosal resection was carried out using the cap method. RESULTS： The average size of resections was 19.7± 9.4×14.6＋8.2 mm. Histopathologic assessment postresection revealed 5 low-grade dysplasia （LGD） （12.8%）, 27 HGD （69.2%）, 2 IMC （5.1%）, and 5 SMC （-12.8%）. EMR changed the pre-treatment diagnosis in 10 patients （25.6%）. Three patients with SMC underwent surgery. Histology of the surgical specimen revealed 1 TON0 and 2 TIN0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy, occurred in four patients （10.3%）. After a median follow-up of 34.9 mo, all patients remained in remission. CONCLUSION： In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.展开更多
Objective To explore the clinical significance of serum level of pro gastrin releasing peptide 31 98 (ProGRP31 98) for small cell lung cancer (SCLC), in comparison with neuron specific enolase (NSE). Methods S...Objective To explore the clinical significance of serum level of pro gastrin releasing peptide 31 98 (ProGRP31 98) for small cell lung cancer (SCLC), in comparison with neuron specific enolase (NSE). Methods Serum level of ProGRP31 98 and NSE was measured by ELISA respectively in 30 patients with SCLC, 30 with non small cell lung cancer (NSCLC), 15 with benign lung diseases and 15 normal subjects, additionally, 10 SCLC patients after having treatment with chemotherapy were included. The receiver operating characteristic (ROC) curve was used to set the cut off value and evaluate the diagnostic accuracy. Results The serum level of ProGRP31 98 was higher in patients with SCLC than that in other groups. The SCLC patients with extensive disease had a higher value than the patients with limited disease. In SCLC patients with distant metastases, it was also higher than in those without. Increase in serum ProGRP31 98 and NSE was both seen in SCLC patients, but for the former one, the increase was of much greater compared to the normal controls. Given the cut off value for ProGRP31 98 was 40ng·L -1 and for NSE 8μg·L -1 , their sensitivity of diagnosis in SCLC was 73% and 60%, respectively. The area under ROC curve of ProGRP31 98 was significantly larger than that of NSE. All patients responded to chemotherapy showed marked decrease in ProGRP31 98. Conclusion ProGRP31 98 is a more specific and sensitive marker than NSE in the diagnosis of SCLC.展开更多
基金funded by the Europe Economic Area(EEA)and Norway Grants 2014-2021,Grant No.EEA-RESEARCH-164 for AM,ALl,and ALi.
文摘Background Preclinical studies demonstrate that exercise reduces tumor incidence and growth.Rapid release of extracellular vesicles(EVs)during exercise suggests their potential role as mediators of exercise-induced systemic effects and physiological adaptation.This study investigated the impact of exercise-induced plasma EVs on tumor growth and immune tumor microenvironment in murine models of triple-negative breast cancer(TNBC):EO771(a C57BL/6-derived TNBC cell line)and 4T1(a BALB/c-derived TNBC cell line).Methods Size exclusion chromatography was used to isolate exercise-induced EVs from plasma of healthy female mice(BALB/c and C56BL/6,n=30 per strain)that underwent ten 30-min moderate-intensity treadmill running sessions over 2 weeks.Nanoparticle tracking analysis,Western blot,and electron microscopy confirmed the presence of EVs in the samples.Tumor-bearing mice(n=72 per strain)were administered with exercise-induced EVs before or/and after tumor implantation.Local and systemic immune responses were assessed using flow cytometry,enzyme-linked immunosorbent assay(ELISA),and quantitative polymerase chain reaction(qPCR).Results Administration of exercise-induced EVs,particularly before tumor implantation,significantly suppressed tumor growth and reduced tumor burden in both TNBC models.In EO771,endpoint tumor volumes were 278–330 mm^(3)in treated groups compared to 799 mm^(3)in untreated(p<0.0001),while in 4T1,treated groups showed volumes of 287–564 mm^(3)vs.696 mm^(3)in untreated(p=0.0002).Notable differences in tumor-infiltrating lymphoid and myeloid cell subpopulations indicated immunomodulatory effects of exercise-induced EVs,particularly in the 4T1 model,where their continuous administration significantly increased intratumoral cluster of differentiation 8(CD8)T lymphocyte proportion(5.77%vs.0.90%in untreated,p<0.0001).Similarly,in the EO771 model,exercise-induced EVs administered before tumor implantation led to a marked rise in intratumoral CD8 T lymphocytes(2.24%vs.1.08%in untreated,p=0.0181).Conclusion Our findings indicate that exercise-induced EV treatment elicits a pro-inflammatory antitumor immune response,suggesting a shift of immunologically cold TNBC tumors towards a more inflamed phenotype associated with better outcomes.Our study supports the further investigation of EVs as modulators of antitumor immunity and their potential utility in enhancing the efficacy of immunotherapy.
基金supported by the National Natural Science Foundation of China(No.22264013)Hainan Province Clinical Medical Center(No.2021)Hainan Province Science and Technology Special Fund(No.ZDYF2024SHFZ104).Thanks to the support and assistance in terms of instruments and facilities provided by Public Research Center of Hainan Medical University.
文摘Cellular senescence is a steady state of cell cycle arrest necessary to maintain homeostasis in organisms.However,senescent cells may cause senescence in neighboring healthy cells,inducing the onset of several diseases,such as inflammation,neurological disorders,and atherosclerosis.Therefore,early detection of cellular senescence is extremely important.β-Galactosidase(β-gal),as a critical marker of cellular senescence,can be monitored to facilitate early diagnosis of aging-related diseases.Furthermore,β-gal is mainly found in lysosomes,which have a pH value of about 4.5-5.5.Here,we developed a near-infrared fluorescent probe(QMOH-Gal)for tracking cell senescence in vitro and in vivo via the detection ofβ-gal.In addition,the probe displayed high sensitivity and specificity forβ-gal with good fluorescence signal in the acidity range.Subsequently,this QMOH-Gal probe was successfully employed to differentiate between normal cells and senescent cells by monitoringβ-gal.Furthermore,the probe not only realized the monitoring ofβ-gal in zebrafish but also the tracking ofβ-gal in palbociclib-induced breast tumor senescence.Overall,the probe shows great promise as an effective tool for imagingβ-gal in vivo for studying the biology of aging in organisms.
文摘The mutagenicity and carcinogenicity of fish sauce (FS) sample from Changle County, a high gastric cancer mortality (113.20/105) area, were investigated with the biologic short-term tests and laboratory animal experiment. The results showed that the extract of FS was markedly direct mutagenic toward S. typhimurium TA100, induced high sister chromatid exchanges (SCE) and micronucleus (MN) in V79 cells after nitrosation with sodium nitrite. But the non-nitrosated FS did not. The nitrosated fish sauce (NFS) also induced SOS in E. coli PQ37 and alkylation of calfthymus DNA. The potency of NFS to induce unscheduled DNA synthesis (UDS) in human normal gastric mucosal cells was increased about fivefold compared with FS. When the NFS extract was given to newborn rats by gavage, dys-plasia and adenocaroinoma were induced in the glandular stomach in the 4th and 16th experimental week, respectively. N-nitrosamides were also found in NFS, which may account for the mutagenicity and carcinogenicity of NFS. It is indicated that FS, a traditional daily eaten seasoning, may contribute to the causes of the high gastric cancer mortality for the local residents.
基金Supported by the National Natural Sciences Foundation of China,No.81773214。
文摘BACKGROUND Transanal total mesorectal excision(taTME)is a new technique with many potential technical advantages.Laparoscopy-assisted taTME is a combination of transabdominal taTME and transluminal endoscopic surgery taTME.Laparoscopy-assisted taTME is a combination of techniques such as minimally invasive surgery,intersphincter-assisted resection,natural orifice extraction,ta minimally invasive surgery,and ultralow-level preservation of the anus.AIM To verify the feasibility and safety of an innovative technique of taTME for treatment of cancer located in the lower rectum.METHODS From January 2016 to March 2018,we attempted to perform laparoscopy-assisted taTME surgery in 24 patients with lower rectal cancer.RESULTS The new technique of laparoscopy-assisted taTME was successfully performed in all 24 patients.Mean operating time was 310.0 min and mean intraoperative blood loss was 69.1 mL.The mean time to passing of first flatus was 3.1 d,and mean postoperative hospital stay was 9.2 d.Two patients were given postoperative analgesics due to anal pain.Twenty-three patients were able to walk in first 2 d,and five patients had postoperative complications.CONCLUSION Laparoscopy-assisted taTME is suitable for selected patients with lower rectal cancer,and this technique is worthy of further recommendation.
基金Supported by Grants from Associazione Italiana Ricerca sul Cancro(AIRC) to Paggi MGMinistero della Salute grants to Paggi MGfrom Sbarro Health Research Organization funds to Galderisi U and Giordano A
文摘In cancer biology,mesenchymal stem cells(MSCs)display aspects that can appear contradictory.On one hand,these cells possess several features which give them the ability to specifically target and then sustain cancer cells in their ability to survive the multifaceted host response against cancer.On the other hand,due to this excellent aptitude to home-in on tumor tissues,regardless their location in the host’s body,MSCs are considered to be extremely selective vehicles to reach cancer cells specifically.Recently,MSC sustainment of cancer cell growth is a hot research topic.Indeed,these cells are known to sustain tumor angiogenesis and metastasis formation,to create a microenvironment favorable for cancer cell growth and to down-modulate the immune system capabilities in the host organism.On the other hand,since scientists became able to take advantage of their extremely selective capability to target cancer cells,MSCs are now also thought of in a different light.Indeed,MSCs are now considered a promising vehicle for local expression or delivery of even particularly toxic anticancer agents,ranging from Herpes Simplex Virus to locally-acting antineoplastic drugs.On this basis,investigation is now focused on how to impair the pro-neoplastic features of MSCs on one hand whilst taking advantage of their specific tropism toward cancer cells,on the other.As with the two faces of Janus,this review will concisely explore the research activity in these two apparently conflicting fields.
文摘Polycomb group proteins represent a global silencing system involved in development regulation.In specific,they regulate the transition from proliferation to differentiation,contributing to stem-cell maintenance and inhibiting an inappropriate activation of differentiation programs.Enhancer of Zeste Homolog 2(EZH2) is the catalytic subunit of Polycomb repressive complex 2,which induces transcriptional inhibition through the tri-methylation of histone H3,an epigenetic change associated with gene silencing.EZH2 expression is high in precursor cells while its level decreases in differentiated cells.EZH2 is upregulated in various cancers with high levels associated with metastatic cancer and poor prognosis.Indeed,aberrant expression of EZH2 causes the inhibition of several tumor suppressors and differentiation genes,resulting in an uncontrolled proliferation and tumor formation.This editorial explores the role of Polycomb repressive complex 2 in cancer,focusing in particular on EZH2.The canonical function of EZH2 in gene silencing,the non-canonical activities as the methylation of other proteins and the role in gene transcriptional activation,were summarized.Moreover,mutations of EZH2,responsible for an increased methyltransferase activity in cancer,were recapitulated.Finally,various drugs able to inhibit EZH2 with different mechanism were described,specifically underscoring the effects in several cancers,in order to clarify the role of EZH2 and understand if EZH2 blockade could be a new strategy for developing specific therapies or a way to increase sensitivity of cancer cells to standard therapies.
文摘Objective： To find an effective treatment for advanced cancer patients with esophageal fistula. Methods： From 1998 to 2006, we studied 42 patients with advanced esophageal cancer and 5 lung cancer patients with carcinomatous esophageal fistula （3 females, 44 males, aged 29-92 years）. Ten patients with both esophageal cancer stricture and fistula were first dilated under endoscope, then a memory stent with a membrane was placed in the esophageal lumen. Others were treated only with a memory stent with a membrane, three of them with a large fistula （diameter 〉1.5 cm） were treated with bio-protein glue after placement of an esophageal metal stent. Results： The fistulas were covered by a stent and the patients could eat and drink immediately. Their quality of life was improved and their survival was prolonged, 44 out of 47 patients survived for 〉3 mo. Conclusion： Placement of esophageal stent with membrane or in combination with bio-protein glue through endoscope is an effective method for treating the bronchoesophageal fistula.
文摘Objective: To explore the death-related factors of stageⅠrectal cancer patients. Methods: 89 cases of stage I rectal cancer patients between 1985 and 2000 were retrospectively studied for prognostic factors. Factors including age, gender, tumor size, circumferential occupation, gross type, pathological type, depth of tumor invasion, surgical procedure, adjuvant chemotherapy and postoperative complication were chosen for cox multivariate analysis (forward procedure) using Spss software (10.0 version). Results: multivariate analysis demonstrated that muscular invasion was an independent negative prognostic factor for stageⅠrectal cancer patients (P=0.003). Conclusion: Muscular invasion is a negative prognostic factor for stage I rectal cancer patients.
基金supported by the Chinese Scholarship Council(No.202206240086)Zhejiang Province Public Welfare Technology Application Research Project in China(No.TGY23H160090 and No.LGF21H160029)+1 种基金Taizhou Science and Technology Project,Zhejiang Province(No.20ywb12)Program for Talents of Chongqing University Three Gorges Hospital(No.2022YJKYXM-036).
文摘Aging and circadian rhythms have been connected for decades,but their molecular interaction has remained unknown,especially for cancers.In this situation,we summarized the current research actuality and problems in this field using the bibliometric analysis.Publications in the PubMed and Web of Science databases were retrieved.Overall,there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer.Researchers from USA,Germany,Italy,China and England have greater studies than others.Top three publication institutions are University of California System,UDICE-French Research Universities and University of Texas System.Current research hotspots include oxidative stress,breast cancer,melatonin,cell cycle,calorie restriction,prostate cancer and NF-κB.In conclusion,results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer.These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.
文摘The epidemioiogical features of lung cancer in Beijing during 1977 ?1986 were analysed. The data collected showed that lung cancer ncidence and mortality rates ranks first among all other malignant tumor and had been on the increase from year to year. The mortality rate in urban area was higher than that in its suburbs. While the male incidence was higher than that of the female. The sex ratio of the male to female incidence rates was 1.56. The incidence rate rises with age. The lung cancer is one of the lesser prevised cancer and the five-year relative survival rate is 6.5% for both sexes in 19S2 ?1983. The lung cancer mortality rate in Beijing urban area is compared in this report with other countries in the world, and it is found that the female mortality rate of lung cancer in Beijing is among the highest.
基金Supported by Grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute,funded by the Ministry of Health&Welfare,Republic of Korea,No.RS-2022-KH129889.
文摘BACKGROUND The classification of uterine sarcomas is based on distinctive morphological and immunophenotypic characteristics,increasingly supported by molecular genetic diagnostics.Data on neurotrophic tyrosine receptor kinase(NTRK)gene fusionpositive uterine sarcoma,potentially aggressive and morphologically similar to fibrosarcoma,are limited due to its recent recognition.Pan-TRK immunohistochemistry(IHC)analysis serves as an effective screening tool with high sensitivity and specificity for NTRK-fusion malignancies.CASE SUMMARY We report a case of a malignant mesenchymal tumor originating from the uterine cervix,which was pan-TRK IHC-positive but lacked NTRK gene fusions,accompanied by a brief literature review.A 55-year-old woman presented to the emergency department with abdominal pain and distension,exhibiting significant ascites and multiple solid pelvic masses.Pelvic examination revealed a tumor encompassing the uterine cervix,extending to the vagina and uterine corpus.A punch biopsy of the cervix indicated NTRK sarcoma with positive immunochemical pan-TRK stain.However,subsequent next generation sequencing revealed no NTRK gene fusion,leading to a diagnosis of poorly differentiated,advanced-stage sarcoma.CONCLUSION The clinical significance of NTRK gene fusion lies in potential treatment with TRK inhibitors for positive sarcomas.Identifying such rare tumors is crucial due to the potential applicability of tropomyosin receptor kinase inhibitor treatment.
基金supported by the Chinese Scholarship Council(grant no.202206240086)a regional innovation cooperation project of Sichuan Province(grant no.23QYCX0136)。
文摘The intricate relationship between cancer,circadian rhythms,and aging is increasingly recognized as a critical factor in understanding the mechanisms underlying tumorigenesis and cancer progression.Aging is a well-established primary risk factor for cancer,while disruptions in circadian rhythms are intricately associated with the tumorigenesis and progression of various tumors.Moreover,aging itself disrupts circadian rhythms,leading to physiological changes that may accelerate cancer development.Despite these connections,the specific interplay between these processes and their collective impact on cancer remains inadequately explored in the literature.In this review,we systematically explore the physiological mechanisms of circadian rhythms and their influence on cancer development.We discuss how core circadian genes impact tumor risk and prognosis,highlighting the shared hallmarks of cancer and aging such as genomic instability,cellular senescence,and chronic inflammation.Furthermore,we examine the interplay between circadian rhythms and aging,focusing on how this crosstalk contributes to tumorigenesis,tumor proliferation,and apoptosis,as well as the impact on cellular metabolism and genomic stability.By elucidating the common pathways linking aging,circadian rhythms,and cancer,this review provides new insights into the pathophysiology of cancer and identifies potential therapeutic strategies.We propose that targeting the circadian regulation of cancer hallmarks could pave the way for novel treatments,including chronotherapy and antiaging interventions,which may offer important benefits in the clinical management of cancer.
文摘AIM： To determine whether any changes have occurred on the patterns of colorectal cancer in China. METHODS： Data from 21 Chinese articles published from 1980 to 1999, were used to analyze the time trend of colorectal cancer according to the patients＇age at diagnosis, sex, the site of the tumor, stage, and the pathology. RESULTS： From 1980s to 1990s, the mean age of the colorectal cancer patients has increased. The percentage of the female patients rose. The distribution of colorectal carcinoma shows a predominance of rectal cancer. However, the proportion of proximal colon cancer （induding transverse and ascending colon） increased significantly accompanied by a decline in the percentage of rectal cancer. Similarity in the percentage of distal colon cancer between two decades was revealed. In the 1990s, statistically more Stage B patients were found than those in 1980s. In addition, databases show a significant decrease in the Stage D cases. The proportion of adenocarcinoma increased, but the mucinous adenocarcinoma decreased during two decades. CONCLUSION： These findings indicate that the pattern of colorectal cancer in China has been changing. Especially, a proximal shift due to the increasing proportion of ascending and transverse colon cancer has occurred in China.
基金supported by an award from the Goldhirsh FoundationNIH Grant P01-CA95616+1 种基金NIH(NINDS)Fellowship Award F32NS066519Fellow Awardfrom the National Foundation for Cancer Research
文摘Epidermal growth fac tor receptor (EGFR) is one of the most commonly altered genes in human cancer by way of over-expression, amplification, and mutation. Targeted inhibition of EGFR activity suppresses signal transduction pathways which control tumor cell growth, proliferation, and resistance to apoptosis. Small molecule tyrosine kinase inhibitors and monoclonal antibodies are among the most common EGFR-targeting agents and have been used clinically for treating various malignancies. This review discusses the successes and challenges of targeting EGFR in human cancer. The genetic alterations of EGFR tend to occur more often in some solid tumors than others, as do the mechanisms of resistance to targeted inhibition. The clinical and basic science experiences with these agents thus far have important implications for the future of therapeutic targeting of EGFR.
文摘About 75% of all breast cancers are estrogen receptor(ER)-positive. They generally have a more favorable clinical behavior, prognosis, and pattern of recurrence, and endocrine therapy forms the backbone of treatment. Anti-estrogens(such as tamoxifen and fulvestrant) and aromatase inhibitors(such as anastrozole, letrozole, and exemestane) can effectively control the disease and induce tumor responses in a large proportion of patients. However, the majority of patients progress during endocrine therapy(acquired resistance) and a proportion of patients may fail to respond to initial therapy(de novo resistance). Endocrine resistance is therefore of clinical concern and there is great interest in strategies that delay or circumvent it. A deeper knowledge of the molecular mechanisms that drive endocrine resistance has recently led to development of new strategies that have the promise to effectivelyovercome it. Many resistance mechanisms have been described, and the crosstalk between ER and growth factor receptor signaling pathways seems to represent one of the most relevant. Compounds that are able to inhibit key elements of these pathways and restore endocrine sensitivity have been studied and more are currently under development. The aim of this review is to summarize the molecular pathophysiology of endocrine resistance in breast cancer and its impact on current clinical management.
文摘Prostate cancer （PCa） preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is currently unknown, although considerable progress has been made in determining the key players in this process. In this review, we present the current understanding of the molecular processes driving PCa metastasis to the bone.
文摘Cancer is a highly heterogeneous group of diseases that despite improved treatments remain prevalent accounting for over 14 million new cases and 8.2 million deaths per year. Studies into the process of carcinogenesis are limited by lack of appropriate models for the development and pathogenesis of the disease based on human tissues. Primary culture of patient samples can help but is difficult to grow for a number of tissues. A potential opportunity to overcome these barriers is based on the landmark study by Yamanaka which demonstrated the ability of four factors;Oct4, Sox2, Klf4, and c-Myc to reprogram human somatic cells in to pluripotency. These cells were termed induced pluripotent stem cells(i PSCs) and display characteristic properties of embryonic stem cells. This technique has a wide range of potential uses including disease modelling, drug testing and transplantation studies. Interestingly i PSCs also share a number of characteristics with cancer cells including self-renewal and proliferation, expression of stem cell markers and altered metabolism. Recently, i PSCs have been generated from a number of human cancer cell lines and primary tumour samples from a range of cancers in an attempt to recapitulate the development of cancer and interrogate the underlying mechanisms involved. This review will outline the similarities between the reprogramming process and carcinogenesis, and how these similarities have been exploited to generate i PSC models for a number of cancers.
文摘AIM： To evaluate endoscopic mucosal resection （EMR） in patients with high-grade dysplasia （HGD） and/or intramucosal cancer （IMC） in Barrett＇s esophagus （BE）. METHODS： Between June 2000 and December 2003, 39 consecutive patients with HGD （35） and/or IMC （4） underwent EMR. BE 〉30 mm was present in 27 patients. In three patients with short segment BE （25.0%）, HGD was detected in a normal appearing BE. Lesions had a mean diameter of 14.8＋10.3 ram. Mucosal resection was carried out using the cap method. RESULTS： The average size of resections was 19.7± 9.4×14.6＋8.2 mm. Histopathologic assessment postresection revealed 5 low-grade dysplasia （LGD） （12.8%）, 27 HGD （69.2%）, 2 IMC （5.1%）, and 5 SMC （-12.8%）. EMR changed the pre-treatment diagnosis in 10 patients （25.6%）. Three patients with SMC underwent surgery. Histology of the surgical specimen revealed 1 TON0 and 2 TIN0 lesions. The remaining two patients were cancer free at 32.5 and 45.6 mo, respectively. A metachronous lesion was detected after 25 mo in one patient with HGD. Intra-procedural bleeding, controlled at endoscopy, occurred in four patients （10.3%）. After a median follow-up of 34.9 mo, all patients remained in remission. CONCLUSION： In the medium term, EMR is effective and safe to treat HGD and/or IMC within BE and is a valuable staging method. It could become an alternative to surgery.
文摘Objective To explore the clinical significance of serum level of pro gastrin releasing peptide 31 98 (ProGRP31 98) for small cell lung cancer (SCLC), in comparison with neuron specific enolase (NSE). Methods Serum level of ProGRP31 98 and NSE was measured by ELISA respectively in 30 patients with SCLC, 30 with non small cell lung cancer (NSCLC), 15 with benign lung diseases and 15 normal subjects, additionally, 10 SCLC patients after having treatment with chemotherapy were included. The receiver operating characteristic (ROC) curve was used to set the cut off value and evaluate the diagnostic accuracy. Results The serum level of ProGRP31 98 was higher in patients with SCLC than that in other groups. The SCLC patients with extensive disease had a higher value than the patients with limited disease. In SCLC patients with distant metastases, it was also higher than in those without. Increase in serum ProGRP31 98 and NSE was both seen in SCLC patients, but for the former one, the increase was of much greater compared to the normal controls. Given the cut off value for ProGRP31 98 was 40ng·L -1 and for NSE 8μg·L -1 , their sensitivity of diagnosis in SCLC was 73% and 60%, respectively. The area under ROC curve of ProGRP31 98 was significantly larger than that of NSE. All patients responded to chemotherapy showed marked decrease in ProGRP31 98. Conclusion ProGRP31 98 is a more specific and sensitive marker than NSE in the diagnosis of SCLC.
