Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is...Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.展开更多
Introduction Neutrophils,a crucial component of the innate immune system,are the most abundant bone marrow-derived eukaryotic cell in human blood.The functional importance of neutrophils is often overlooked because ne...Introduction Neutrophils,a crucial component of the innate immune system,are the most abundant bone marrow-derived eukaryotic cell in human blood.The functional importance of neutrophils is often overlooked because neutrophils are short-lived,terminally differentiated,and do not proliferate.Although traditionally considered anti-bacterial cells,research has demonstrated the multifaceted roles of neutrophils in cancer.Studies have suggested that neutrophils with normal functions co-exist with pathologically activated neutrophils that support tumorprogression and metastasis in the context of cancer.展开更多
Objective:To assess the clinical outcomes and toxicities of once daily(QD)simultaneous dose reduction intensity-modulated radiotherapy(SDR-IMRT-QD;SDR-QD)versus conventional QD IMRT(C-QD)and twice daily(BID)IMRT in pa...Objective:To assess the clinical outcomes and toxicities of once daily(QD)simultaneous dose reduction intensity-modulated radiotherapy(SDR-IMRT-QD;SDR-QD)versus conventional QD IMRT(C-QD)and twice daily(BID)IMRT in patients with limited-stage small cell lung cancer(LS-SCLC).Methods:After propensity score matching(PSM),a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD,C-QD,or BID was performed from January 1,2014 to December 31,2019.The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD.The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort.The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort.Toxicities,short-term effects,and survival outcomes were recorded.A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed.Results:The median overall survival time(MST)in the 3 cohorts were 32.7 months(SDR-QD),26.3 months(C-QD),and 33.6 months(BID);the differences between groups were statistically significant.Lower toxicities and doses to organs-at-risk(OARs)occurred in the SDR-QD and BID cohorts.Further,the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival(r=-0.35,P=0.007).A Vheart40 value of 16.5%was recommended as a cut-off point,which yielded 54.7%sensitivity and 85.7%specificity for predicting negative survival outcomes.The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy,but not radiotherapy.Conclusions:SDR-QD was shown to have similar toxicities and survival compared with BID,but fewer toxicities and better survival than C-QD.In addition,cardiac dose exposure was negatively associated with survival.Thus,16.5%of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point,and a Vheart40>16.5%predicts poor survival.展开更多
Gastric cancer (GC) is a major health concern globally,ranking fifth in frequency and fourth in cancer-associated mortality1.In China,an estimated 396,500 new cases are diagnosed each year,and late-stage disease compr...Gastric cancer (GC) is a major health concern globally,ranking fifth in frequency and fourth in cancer-associated mortality1.In China,an estimated 396,500 new cases are diagnosed each year,and late-stage disease comprises more than 80%of cases2.Because of late diagnosis and heterogeneous characteristics,the prognosis of GC remains poor.For patients with advanced disease,traditional chemotherapy has been the mainstay of treatment,but its clinical outcomes are far from satisfactory,with a 5-year survival rate below 10%.展开更多
Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence h...Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.展开更多
Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according...Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according to a US report~1.展开更多
Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream...Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。展开更多
A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and wa...A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.展开更多
Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)...Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.展开更多
Biobanks bridge the gap between basic and translational research.Traditional cancer biobanks typically contain normal and tumor tissues,and matched blood.However,biospecimens in traditional biobanks are usually nonren...Biobanks bridge the gap between basic and translational research.Traditional cancer biobanks typically contain normal and tumor tissues,and matched blood.However,biospecimens in traditional biobanks are usually nonrenewable.In recent years,increased interest has focused on establishing living biobanks,including organoid biobanks,for the collection and storage of viable and functional tissues for long periods of time.The organoid model is based on a 3D in vitro cell culture system,is highly similar to primary tissues and organs in vivo,and can recapitulate the phenotypic and genetic characteristics of target organs.Publications on cancer organoids have recently increased,and many types of cancer organoids have been used for modeling cancer processes,as well as for drug discovery and screening.On the basis of the current research status,more exploration of cancer organoids through technical advancements is required to improve reproducibility and scalability.Moreover,given the natural characteristics of organoids,greater attention must be paid to ethical considerations.Here,we summarize recent advances in cancer organoid biobanking research,encompassing rectal,gastric,pancreatic,breast,and glioblastoma cancers.Living cancer biobanks that contain cancerous tissues and matched organoids with different genetic backgrounds,subtypes,and individualized characteristics will eventually contribute to the understanding of cancer and ultimately facilitate the development of innovative treatments.展开更多
Gastric cancer is one of the most common malignant tumors worldwide.China is a large country in which gastric cancer ranks among the top 3 malignant tumors in terms of incidence,and related morbidity and mortality1.In...Gastric cancer is one of the most common malignant tumors worldwide.China is a large country in which gastric cancer ranks among the top 3 malignant tumors in terms of incidence,and related morbidity and mortality1.In the past 20 years,China has made the most outstanding achievements in the diagnosis and treatment of gastric cancer among countries worldwide.The overall 5-year survival rate of patients in China has increased by nearly 10%2.However,early gastric cancer accounts for only 20%of clinically confirmed cases,the overall effects of therapies for gastric cancer still must be improved3.The REGATTA study has confirmed that palliative surgery cannot improve the long-term survival of patients with stage IV gastric cancer4.展开更多
Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC...Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.展开更多
Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively high.Especially for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of...Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively high.Especially for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of lung cancer patients are diagnosed at an advanced stage.The traditional treatment for advanced non-small cell lung cancer(NSCLC)is chemotherapy.In recent years,with the rapid development of molecular pathology,we have a deeper understanding of the underlying pathological mechanism and heterogeneity of lung cancer,especially NSCLC.Molecular targeted therapy is more accurate because of its anti-tumor effect,and the incidence of adverse drug reactions is low.Compared with chemotherapy in the traditional sense,the degree of damage to normal tissues is also significantly reduced.Therefore,it has become a research hotspot in recent years.This article reviews the research progress of various molecular targeted drugs for the treatment of lung cancer based on domestic and foreign research literature and related data.展开更多
Currently,there is the extremely poor prognosis for pancreatic cancer.Despite the continuous development of various technologies,the long-term survival rate is not improved well.With the rapid development of genomics ...Currently,there is the extremely poor prognosis for pancreatic cancer.Despite the continuous development of various technologies,the long-term survival rate is not improved well.With the rapid development of genomics and biotechnology,the concept of tumor precision treatment has attracted much attention.Gene sequencing technology and biomarker detection have been used to deeply explore the mechanism of the occurrence and development of pancreatic cancer and applied it to clinical diagnosis and treatment,making it possible for patients to carry out individualized precision treatment for pancreatic cancer.Multiple-factor analysis combined with meaningful biological indicators is more helpful to determine individualized diagnosis and treatment measures.This paper summarizes the research results in the above aspects.展开更多
Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer ...Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer of a cancer hospital in Tianjin were selected as the research objects by the convenience sampling method.The general data questionnaire,spouse fear of disease progression scale and self-efficacy scale were used to investigate.Multiple linear regression was used to analyze the influencing factors of the fear of the disease progression in the postoperative pa tients’spouse of bladder cancer.Results:The score of fear of disease progression was(35.75±9.86).The results of multiple linear regression analysis showed that the spouse’s age,medical payment method,occupational status and self-efficacy were the main influencing factors for the spouse’s fear of disease progression after bladder cancer(P<0.05),which accounted for 55%of the total variation.Conclusion:The spouse’s fear of disease progression in patients with bladder cancer is at a moderate lev el,and age,medical payment method,occupational status and self-efficacy are the main influencing factors.It is suggested that clinical medical staff focus on young,rural cooperative medical care,self-financed,in-service,and unemployed,low self-eff icacy of postoperative bladder cancer patients'spouses.A series of psychological counseling and health education should be given to help the patient spouse correctly understand and deal with diseases,reduce the patients’spouses of negative emotions,im prove the patients’spouses of self-efficacy,and reduce the spouse fear level of disease progression.展开更多
Objective:Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignancy.CD8^(+)T cells,cancer stem cells(CSCs),and tumor budding(TB)have been significantly correlated with the outcome of patients with PDAC,but the...Objective:Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignancy.CD8^(+)T cells,cancer stem cells(CSCs),and tumor budding(TB)have been significantly correlated with the outcome of patients with PDAC,but the correlations have been independently reported.In addition,no integrated immune-CSC-TB profile for predicting survival in patients with PDAC has been established.Methods:Multiplexed immunofluorescence and artificial intelligence(AI)-based comprehensive analyses were used for quantification and spatial distribution analysis of CD8^(+)T cells,CD133^(+)CSCs,and TB.In vivo humanized patient-derived xenograft(PDX)models were established.Nomogram analysis,calibration curve,time-dependent receiver operating characteristic curve,and decision curve analyses were performed using R software.Results:The established‘anti-/pro-tumor’models showed that the CD8^(+)T cell/TB,CD8^(+)T cell/CD133^(+)CSC,TB-adjacent CD8^(+)T cell,and CD133^(+)CSC-adjacent CD8^(+)T cell indices were positively associated with survival of patients with PDAC.These findings were validated using PDX-transplanted humanized mouse models.An integrated nomogram-based immune-CSC-TB profile that included the CD8^(+)T cell/TB and CD8^(+)T cell/CD133^(+)CSC indices was established and shown to be superior to the tumor-nodemetastasis stage model in predicting survival of patients with PDAC.Conclusions:‘Anti-/pro-tumor’models and the spatial relationship among CD8^(+)T cells,CSCs,and TB within the tumor microenvironment were investigated.Novel strategies to predict the prognosis of patients with PDAC were established using AI-based comprehensive analysis and machine learning workflow.The nomogram-based immune-CSC-TB profile can provide accurate prognosis prediction for patients with PDAC.展开更多
Historically,axillary lymph node dissection(ALND)was the standard management for axillary sentinel lymph node(SLN)-positive patients,because it enables full assessment of overall axillary lymph node(ALN)metastasis sta...Historically,axillary lymph node dissection(ALND)was the standard management for axillary sentinel lymph node(SLN)-positive patients,because it enables full assessment of overall axillary lymph node(ALN)metastasis status and favorable local-regional control1,2.展开更多
Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-c...Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.展开更多
The rapidly evolving realm of single-cell transcriptomics offers vital new perspectives into the understanding of intra-and inter-cellular molecular dynamics governing development,physiology,and pathogenesis.Deep lear...The rapidly evolving realm of single-cell transcriptomics offers vital new perspectives into the understanding of intra-and inter-cellular molecular dynamics governing development,physiology,and pathogenesis.Deep learning,a recent artificial intelligence advance with a promising application for big data,has demonstrated potential in the field of single-cell analysis1.展开更多
Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances withi...Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.展开更多
文摘Cancer stands as one of the major threats to human life.Ensuring the safety of drugs is paramount,and the impact of adverse reactions on patients’quality of life and prognosis should not be underestimated.Diarrhea is a common clinical adverse event,and despite the absence of specific anti-diarrhea drugs,there is a pressing need for improvement.This article aims to provide a valuable reference for researchers in clinical drug use and scientific tumor treatment.It summarizes recent advancements in drug mechanisms and adverse reactions,whether in preclinical research or clinical diagnosis and therapy.
基金supported by the National Natural Science Foundation of China (U20A20375,82372779,82373279,and 82373283)the Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A)。
文摘Introduction Neutrophils,a crucial component of the innate immune system,are the most abundant bone marrow-derived eukaryotic cell in human blood.The functional importance of neutrophils is often overlooked because neutrophils are short-lived,terminally differentiated,and do not proliferate.Although traditionally considered anti-bacterial cells,research has demonstrated the multifaceted roles of neutrophils in cancer.Studies have suggested that neutrophils with normal functions co-exist with pathologically activated neutrophils that support tumorprogression and metastasis in the context of cancer.
基金supported by grants from the China Postdoctoral Science Foundation(Grant No.2022M712387)。
文摘Objective:To assess the clinical outcomes and toxicities of once daily(QD)simultaneous dose reduction intensity-modulated radiotherapy(SDR-IMRT-QD;SDR-QD)versus conventional QD IMRT(C-QD)and twice daily(BID)IMRT in patients with limited-stage small cell lung cancer(LS-SCLC).Methods:After propensity score matching(PSM),a retrospective analysis involving 300 patients with LS-SCLC treated using SDR-QD,C-QD,or BID was performed from January 1,2014 to December 31,2019.The prescribed irradiation dose in the SDR-QD cohort was 60 Gy/PGTV and 54 Gy/PTV QD.The radiation dose was 60 Gy for both PGTV and PTV QD in the C-QD cohort.The radiation dose was 45 Gy for both PGTV and PTV in the BID cohort.Toxicities,short-term effects,and survival outcomes were recorded.A meta-analysis on the protective effects of pharmaceuticals for cardiac toxicities induced by anti-tumor therapy was performed.Results:The median overall survival time(MST)in the 3 cohorts were 32.7 months(SDR-QD),26.3 months(C-QD),and 33.6 months(BID);the differences between groups were statistically significant.Lower toxicities and doses to organs-at-risk(OARs)occurred in the SDR-QD and BID cohorts.Further,the cardiac dose dosimetric parameter Vheart40 was negatively associated with survival(r=-0.35,P=0.007).A Vheart40 value of 16.5%was recommended as a cut-off point,which yielded 54.7%sensitivity and 85.7%specificity for predicting negative survival outcomes.The meta-analysis indicated that pharmaceuticals significantly reduced the cardiac toxicities induced by chemotherapy,but not radiotherapy.Conclusions:SDR-QD was shown to have similar toxicities and survival compared with BID,but fewer toxicities and better survival than C-QD.In addition,cardiac dose exposure was negatively associated with survival.Thus,16.5%of the cardiac dosimetric parameter Vheart40 is recommended as the cut-off point,and a Vheart40>16.5%predicts poor survival.
文摘Gastric cancer (GC) is a major health concern globally,ranking fifth in frequency and fourth in cancer-associated mortality1.In China,an estimated 396,500 new cases are diagnosed each year,and late-stage disease comprises more than 80%of cases2.Because of late diagnosis and heterogeneous characteristics,the prognosis of GC remains poor.For patients with advanced disease,traditional chemotherapy has been the mainstay of treatment,but its clinical outcomes are far from satisfactory,with a 5-year survival rate below 10%.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2021YFC2500400)the National Natural Science Foundation of China(Grant Nos.81974439&82204121)+2 种基金the Beijing-Tianjin-Hebei Basic Research Cooperation Special Project(20JCZXJC00090)the Tianjin Health Committee Foundation(Grant No.TJWJ2021MS008)the Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Given the rapid changes in social structure(urbanization),economic structure(industrialization),and demographic structure(population aging)in China,cancer has become a major public health problem1.Extensive evidence has indicated that screening can decrease cancer mortality,particularly among high-risk groups,and several representative national and regional cancer screening programs have been launched in China to cope with the increasing burden of cancer.
基金supported by the Construction Project of Cancer Precision Diagnosis and Drug Treatment Technology(Grant No. ZLJZZDYYWZL04)the Clinical Oncology Research Fund of CSCO(Grant No. Y-SY2021MS-0240)+2 种基金the Haihe Yingcai(Tianjin)Project(Grant No. TJSJMYXYC-D2-039)the Tianjin Key Medical Discipline(Specialty)Construction Project grant(Grant No. TJYXZDXK-009A)the CACA-BeiGene Lymphoma Research Foundation(Grant No.CORP-117)。
文摘Mature T-and natural killer(NK)-cell lymphomas are heterogeneous groups of malignant lymphoid neoplasms arising from T and NK cells. The incidence of mature T-and NK-cell lymphomas is 2.1 per 100,000 people, according to a US report~1.
文摘Bod et al.1 recently published a study in Nature that garnered attention to B cell-associated anti-tumor immunity and immunotherapy of melanoma and other tumors1.As a promising supplemental immunotherapy to mainstream methods that target T and natural killer(NK)cells,B cell-associated anti-tumor immunotherapy is promising。
文摘A postmenopausal patient with a diagnosis of estrogen receptor(ER)(+), progesterone receptor(PR)(+), and human epidermal growth factor receptor-2(HER2)(-) breast cancer was reported. The patient refused surgery and was resistant to conventional chemotherapy regimens. Computed tomography and the circulating tumor cell test indicated that the patient's tumor burden increased rapidly even after several chemotherapy sessions. Multiple genetic aberrances in the phosphatidylinositol3-kinases(PI3 K) signaling pathway were detected via next-generation sequencing(NGS)-based liquid biopsy, including a p. G1007 R missense mutation in exon 21 of PIK3 CA(33.61%), a p.L70 fs frameshift mutation in exon 3 of phosphatase and tension homolog deleted on chromosome ten(PTEN)(49.14%), and a p. D1542 Y missense mutation in exon 32 of mammalian target of rapamycin(m TOR)(1.66%). Therefore, only the m TOR inhibitor everolimus was administered to the patient. Partial remission(PR) was observed after 2 months, and sustained stable disease(SD) was observed after a year and a half. Subsequent sequencing showed that the mutation ratio of PIK3 CA decreased to 4.17%, and that the PTEN and m TOR mutations disappeared, which revealed the significant curative effect of everolimus. We report the first case of successful monotherapy treatment using everolimus in a patient with advanced breast cancer bearing mutations in genes involved in the PI3 K/ARK/m TOR signaling pathway. The success of this case highlights the invaluable clinical contribution of NGS-based liquid biopsy, as it successfully provided an optimal therapeutic target for the patient with advanced breast cancer.
基金the Guangzhou Key Medical Discipline Construction Project Fundthe Guangzhou High-Level Clinical Key Specialty Construction+2 种基金the Clinical Research Promotion Project of Guangzhou Medical University for Building High Level Universitythe National Natural Science Foundation of China(No.81972918)the Guangzhou Major Clinical Technology Program(No.2019ZD16)。
文摘Objective:Systemic chemotherapy has limited efficacy in the treatment of peritoneal metastasis(PM)in gastric cancer(GC).Hyperthermic intraperitoneal chemotherapy(HIPEC)combined with complete cytoreductive surgery(CRS)has shown promising outcomes but remains controversial.The present study aimed to evaluate the safety and efficacy of HIPEC without CRS in GC patients with PM.Methods:This retrospective propensity score-matched multicenter cohort study included GC patients with PM treated with either chemotherapy alone(Cx group)or with HIPEC combined with chemotherapy(HIPEC-Cx group)in four Chinese high-volume gastric medical centers between 2010 and 2017.The primary outcomes were median survival time(MST)and 3-year overall survival(OS).Propensity score matching was performed to compensate for controlling potential confounding effects and selection bias.Results:Of 663 eligible patients,498 were matched.The MST in the Cx and HIPEC-Cx groups was 10.8 and 15.9 months,respectively[hazard ratio(HR)=0.71,95%confidence interval(95%CI),0.58-0.88;P=0.002].The 3-year OS rate was 10.1%(95%CI,5.4%-14.8%)and 18.4%(95%CI,12.3%-24.5%)in the Cx and HIPEC-Cx groups,respectively(P=0.017).The complication rates were comparable.The time to first flatus and length of hospital stay for patients undergoing HIPEC combined with chemotherapy was longer than that of chemotherapy alone(4.6±2.4 d vs.2.7±1.8 d,P<0.001;14.2±5.8 d vs.11.4±7.7 d,P<0.001),respectively.The median follow-up period was 33.2 months.Conclusions:Compared with standard systemic chemotherapy,HIPEC combined with chemotherapy revealed a statistically significant survival benefit for GC patients with PM,without compromising patient safety.
基金supported by the Program for Changjiang Scholars and Innovative Research Team in University in China(Grant No.IRT_14R40)National Key Research and Development Program of China(Grant No.2021YFC2500400)+4 种基金National Science and Technology Major Project(Grant No.2017ZX10203207)National Human Genetic Resources Sharing Service Platform(Grant No.2005DKA21300)National Key Research and Development Program of ChinaNet Construction of Human Genetic Resource Bio-bank in North China(Grant No.2016YFC1201703)and National Key R&D Program of China(Grant No.2017YFC0908300).
文摘Biobanks bridge the gap between basic and translational research.Traditional cancer biobanks typically contain normal and tumor tissues,and matched blood.However,biospecimens in traditional biobanks are usually nonrenewable.In recent years,increased interest has focused on establishing living biobanks,including organoid biobanks,for the collection and storage of viable and functional tissues for long periods of time.The organoid model is based on a 3D in vitro cell culture system,is highly similar to primary tissues and organs in vivo,and can recapitulate the phenotypic and genetic characteristics of target organs.Publications on cancer organoids have recently increased,and many types of cancer organoids have been used for modeling cancer processes,as well as for drug discovery and screening.On the basis of the current research status,more exploration of cancer organoids through technical advancements is required to improve reproducibility and scalability.Moreover,given the natural characteristics of organoids,greater attention must be paid to ethical considerations.Here,we summarize recent advances in cancer organoid biobanking research,encompassing rectal,gastric,pancreatic,breast,and glioblastoma cancers.Living cancer biobanks that contain cancerous tissues and matched organoids with different genetic backgrounds,subtypes,and individualized characteristics will eventually contribute to the understanding of cancer and ultimately facilitate the development of innovative treatments.
文摘Gastric cancer is one of the most common malignant tumors worldwide.China is a large country in which gastric cancer ranks among the top 3 malignant tumors in terms of incidence,and related morbidity and mortality1.In the past 20 years,China has made the most outstanding achievements in the diagnosis and treatment of gastric cancer among countries worldwide.The overall 5-year survival rate of patients in China has increased by nearly 10%2.However,early gastric cancer accounts for only 20%of clinically confirmed cases,the overall effects of therapies for gastric cancer still must be improved3.The REGATTA study has confirmed that palliative surgery cannot improve the long-term survival of patients with stage IV gastric cancer4.
基金supported by the Science and Technology Support Plan Key Projects of Tianjin(Grant No.20YFZCSY00070)the National Natural Science Foundation of China(Grant Nos.82073276,82273100)+1 种基金the China Digestive Tumor Clinical Scientific Research Public Welfare Project(Grant No.P014-058)Science and Technology project of Health Commission of Tianjin Binhai New Area(Grant No.2022BWKY016).
文摘Aberrant activation of the WNT signaling pathway is a joint event in colorectal cancer(CRC),but the molecular mechanism is still unclear.Recently,RNA-splicing factor LSM12(like-Sm protein 12)is highly expressed in CRC tissues.This study aimed to verify whether LSM12 is involved in regulating CRC progression via regulating the WNT signaling pathway.Here,we found that LSM12 is highly expressed in CRC patient-derived tissues and cells.LSM12 is involved in the proliferation,invasion,and apoptosis of CRC cells,similar to the function of WNT signaling in CRC.Furthermore,protein interaction simulation and biochemical experiments proved that LSM12 directly binds to CTNNB1(also known asβ-Catenin)and regulates its protein stability to affect the CTTNB1-LEF1-TCF1 transcriptional complex formation and the associated WNT downstream signaling pathway.LSM12 depletion in CRC cells decreased the in vivo tumor growth through repression of cancer cell growth and acceleration of cancer cell apoptosis.Taken together,we suggest that the high expression of LSM12 is a novel factor leading to aberrant WNT signaling activation,and that strategies targeting this molecular mechanism may contribute to developing a new therapeutic method for CRC.
文摘Lung cancer is one of the most common malignant tumors,and its morbidity and mortality are relatively high.Especially for small cell lung cancer(SCLC),the mortality rate is between 80-90%.Unfortunately,more than 50%of lung cancer patients are diagnosed at an advanced stage.The traditional treatment for advanced non-small cell lung cancer(NSCLC)is chemotherapy.In recent years,with the rapid development of molecular pathology,we have a deeper understanding of the underlying pathological mechanism and heterogeneity of lung cancer,especially NSCLC.Molecular targeted therapy is more accurate because of its anti-tumor effect,and the incidence of adverse drug reactions is low.Compared with chemotherapy in the traditional sense,the degree of damage to normal tissues is also significantly reduced.Therefore,it has become a research hotspot in recent years.This article reviews the research progress of various molecular targeted drugs for the treatment of lung cancer based on domestic and foreign research literature and related data.
文摘Currently,there is the extremely poor prognosis for pancreatic cancer.Despite the continuous development of various technologies,the long-term survival rate is not improved well.With the rapid development of genomics and biotechnology,the concept of tumor precision treatment has attracted much attention.Gene sequencing technology and biomarker detection have been used to deeply explore the mechanism of the occurrence and development of pancreatic cancer and applied it to clinical diagnosis and treatment,making it possible for patients to carry out individualized precision treatment for pancreatic cancer.Multiple-factor analysis combined with meaningful biological indicators is more helpful to determine individualized diagnosis and treatment measures.This paper summarizes the research results in the above aspects.
文摘Objective:To investigate the status quo of fear of disease progressi on in postoperative patients’spouse of bladder cancer and analyze its influencing factors.Methods:Postoperative patients’spouse of bladder cancer of a cancer hospital in Tianjin were selected as the research objects by the convenience sampling method.The general data questionnaire,spouse fear of disease progression scale and self-efficacy scale were used to investigate.Multiple linear regression was used to analyze the influencing factors of the fear of the disease progression in the postoperative pa tients’spouse of bladder cancer.Results:The score of fear of disease progression was(35.75±9.86).The results of multiple linear regression analysis showed that the spouse’s age,medical payment method,occupational status and self-efficacy were the main influencing factors for the spouse’s fear of disease progression after bladder cancer(P<0.05),which accounted for 55%of the total variation.Conclusion:The spouse’s fear of disease progression in patients with bladder cancer is at a moderate lev el,and age,medical payment method,occupational status and self-efficacy are the main influencing factors.It is suggested that clinical medical staff focus on young,rural cooperative medical care,self-financed,in-service,and unemployed,low self-eff icacy of postoperative bladder cancer patients'spouses.A series of psychological counseling and health education should be given to help the patient spouse correctly understand and deal with diseases,reduce the patients’spouses of negative emotions,im prove the patients’spouses of self-efficacy,and reduce the spouse fear level of disease progression.
基金supported by The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2017KJ198)。
文摘Objective:Pancreatic ductal adenocarcinoma(PDAC)is an aggressive malignancy.CD8^(+)T cells,cancer stem cells(CSCs),and tumor budding(TB)have been significantly correlated with the outcome of patients with PDAC,but the correlations have been independently reported.In addition,no integrated immune-CSC-TB profile for predicting survival in patients with PDAC has been established.Methods:Multiplexed immunofluorescence and artificial intelligence(AI)-based comprehensive analyses were used for quantification and spatial distribution analysis of CD8^(+)T cells,CD133^(+)CSCs,and TB.In vivo humanized patient-derived xenograft(PDX)models were established.Nomogram analysis,calibration curve,time-dependent receiver operating characteristic curve,and decision curve analyses were performed using R software.Results:The established‘anti-/pro-tumor’models showed that the CD8^(+)T cell/TB,CD8^(+)T cell/CD133^(+)CSC,TB-adjacent CD8^(+)T cell,and CD133^(+)CSC-adjacent CD8^(+)T cell indices were positively associated with survival of patients with PDAC.These findings were validated using PDX-transplanted humanized mouse models.An integrated nomogram-based immune-CSC-TB profile that included the CD8^(+)T cell/TB and CD8^(+)T cell/CD133^(+)CSC indices was established and shown to be superior to the tumor-nodemetastasis stage model in predicting survival of patients with PDAC.Conclusions:‘Anti-/pro-tumor’models and the spatial relationship among CD8^(+)T cells,CSCs,and TB within the tumor microenvironment were investigated.Novel strategies to predict the prognosis of patients with PDAC were established using AI-based comprehensive analysis and machine learning workflow.The nomogram-based immune-CSC-TB profile can provide accurate prognosis prediction for patients with PDAC.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82172873)Start-up fund of Shandong Cancer Hospital(Grant No.2020PYA08)+2 种基金National Natural Science Foundation of Shandong Province(Grant No.ZR2021QH002)China Postdoctoral Science Foundation(Grant No.2022M721987)Bethune Foundation Project(Grant No.G-X-2019-0101-12)。
文摘Historically,axillary lymph node dissection(ALND)was the standard management for axillary sentinel lymph node(SLN)-positive patients,because it enables full assessment of overall axillary lymph node(ALN)metastasis status and favorable local-regional control1,2.
基金supported by funds from the National Natural Science Foundation of China(Grant Nos.81830002,81830004,82070168,and 32070951)the Translational Research grant of NCRCH(Grant No.2020ZKZC04)National Key R&D Program of China(Grant No.2021YFA1100800)。
文摘Adoptive cellular immunotherapy with chimeric antigen receptor(CAR)T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma(B-NHL).With increasing approval of CAR T-cell products and advances in CAR T cell therapy,CAR T cells are expected to be used in a growing number of cases.However,CAR T-cell-associated toxicities can be severe or even fatal,thus compromising the survival benefit from this therapy.Standardizing and studying the clinical management of these toxicities are imperative.In contrast to other hematological malignancies,such as acute lymphoblastic leukemia and multiple myeloma,anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features,most notably local cytokine-release syndrome(CRS).However,previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL.Consequently,we developed this consensus for the prevention,recognition,and management of these toxicities,on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions.This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management,and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.
基金supported by the National Natural Science Foundation of China (Grant No.32270688 and 31801117)National Key Research and Development Program of China (Grant No.2021YFC2500400)+1 种基金Program for Changjiang Scholars and Innovative Research Team in University in China (Grant No.IRT_14R40)Tianjin Key Medical Discipline (Specialty) Construction Project (Grant No.TJYXZDXK-009A)。
文摘The rapidly evolving realm of single-cell transcriptomics offers vital new perspectives into the understanding of intra-and inter-cellular molecular dynamics governing development,physiology,and pathogenesis.Deep learning,a recent artificial intelligence advance with a promising application for big data,has demonstrated potential in the field of single-cell analysis1.
基金supported by grants from the National Clinical Research Center Cancer Fundthe Haihe Laboratory of Synthetic Biology(22HHSWSS00004)。
文摘Immunotherapy represents a promising strategy for cancer treatment that utilizes immune cells or drugs to activate the patient's own immune system and eliminate cancer cells.One of the most exciting advances within this field is the targeting of neoantigens,which are peptides derived from non-synonymous somatic mutations that are found exclusively within cancer cells and absent in normal cells.Although neoantigen-based therapeutic vaccines have not received approval for standard cancer treatment,early clinical trials have yielded encouraging outcomes as standalone monotherapy or when combined with checkpoint inhibitors.Progress made in high-throughput sequencing and bioinformatics have greatly facilitated the precise and efficient identification of neoantigens.Consequently,personalized neoantigen-based vaccines tailored to each patient have been developed that are capable of eliciting a robust and long-lasting immune response which effectively eliminates tumors and prevents recurrences.This review provides a concise overview consolidating the latest clinical advances in neoantigen-based therapeutic vaccines,and also discusses challenges and future perspectives for this innovative approach,particularly emphasizing the potential of neoantigen-based therapeutic vaccines to enhance clinical efficacy against advanced solid tumors.
