BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.Howev...BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.展开更多
BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and ...BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.展开更多
Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RN...Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.展开更多
This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal sube...This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.展开更多
Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of sufferin...Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.展开更多
BACKGROUND Colorectal anastomotic occlusion is a serious complication of colorectal cancer surgery.Although several treatment strategies have been proposed,the mana-gement of anastomotic occlusion remains challenging....BACKGROUND Colorectal anastomotic occlusion is a serious complication of colorectal cancer surgery.Although several treatment strategies have been proposed,the mana-gement of anastomotic occlusion remains challenging.In this report,we present a case of anastomotic occlusion recanalization performed using a novel technique involving two endoscopes,one for radial incision and the other serving as a guide light.This novel technique offers significant advantages in terms of operational feasibility,reduced invasiveness,rapid recovery,and shortened hospital stay.CASE SUMMARY A 37-year-old man underwent low anterior resection and prophylactic double-lumen ileostomy for rectal cancer in June,2023.Two months later,complete anastomotic occlusion was observed on colonoscopy.Therefore,we developed a novel atresia recanalization technique.Two endoscopes were placed,one through the colonic anastomosis and the other through the anus.A radial incision was successfully made from the colonic side,guided by the light of the endoscope from the anal side.Atresia recanal-ization was performed within 20 minutes.Three weeks after recanalization,colonoscopy revealed that the diameter of the colorectal anastomosis was approximately 16 mm and the patient therefore underwent stoma reversal in September.During the follow-up period of approximately one year,the patient remained well and no stenosis or obstruction symptoms were observed.CONCLUSION Endoscopic atresia recanalization of colorectal anastomotic occlusion assisted by an opposing light source is safe and effective.展开更多
The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a st...The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.展开更多
BACKGROUND With the widespread use of hemocoagulase in patients with gastrointestinal bleeding,clinicians have become increasingly concerned about coagulation dis-orders associated with this medication.Risk factors fo...BACKGROUND With the widespread use of hemocoagulase in patients with gastrointestinal bleeding,clinicians have become increasingly concerned about coagulation dis-orders associated with this medication.Risk factors for hypofibrinogenemia asso-ciated with hemocoagulase are poorly understood.AIM To determine risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding.METHODS We performed a retrospective analysis of the medical documentation of hospit-alized patients treated with hemocoagulase for gastrointestinal bleeding.Hypofib-rinogenemia was defined as a decrease in plasma fibrinogen concentration to less than 2.0 g/L.The included patients were divided into two groups:acquired hypofibrinogenemia group and non-hypofibrinogenemia group.We used logistic regression analysis to identify potential risk factors and established risk assess-RESULTS There were 36 patients in the acquired hypofibrinogenemia group and 73 patients in the non-hypofibrinogenemia group.The hypofibrinogenemia group showed higher rates of intensive care unit admissions(P=0.021),more female patients(P=0.005),higher in-hospital mortality(P=0.027),larger hemocoagulase doses(P=0.026),more Packed Red Cells transfusions(P=0.024),and lower baseline fibrinogen levels(P<0.000).Binary logistic regression was employed to examine the risk factors associated with acquired hypofibrinogenemia.The analysis revealed that baseline fibrinogen[odds ratio(OR)0.252,95%CI:0.137-0.464,P<0.000],total hemocoagulase doses(OR 1.074,95%CI:1.015-1.137,P=0.014),and female gender(OR 2.856,95%CI:1.015–8.037,P=0.047)were statist-ically significant risk factors.CONCLUSION Higher doses of total hemocoagulase,female gender,and a lower baseline fibrinogen level were risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding.展开更多
Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor(EGFR)signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy.In this phase 3 study(Clin...Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor(EGFR)signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy.In this phase 3 study(ClinicalTrial.gov:NCT04028778),315 patients with treatment-naïve,EGFR-mutated,advanced non-small cell lung cancer(NSCLC)were randomized(1:1)to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle.At the prespecified final analysis of progression-free survival(PFS),a significant improvement in PFS was observed for the anlotinib arm over the placebo arm(hazards ratio[HR]=0.64,95%CI,0.48–0.80,P=0.003).Particularly,patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib.The incidence of grade 3 or higher treatment-emergent adverse events was 49.7%of the patients receiving gefitinib plus anlotinib versus 31.0%of the patients receiving gefitinib plus placebo.Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve,EGFR-mutated,advanced NSCLC,with a manageable safety profile.展开更多
The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can ...The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.展开更多
The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years,leading to numerous researches on cancer microbiome entering clinical evaluation.As promising biomarkers...The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years,leading to numerous researches on cancer microbiome entering clinical evaluation.As promising biomarkers and therapeutic targets,the critical involvement of microbiota in cancer clinical practice has been increasingly appreciated.Here,recent progress in this field is reviewed.We describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers,respectively.In addition,we highlight the relationship between microbiota and the therapeutic efficacy,toxicity,or side effects of commonly utilized treatments for cancer,including chemotherapy,radiotherapy,and immunotherapy.Given that microbial factors influence the cancer treatment outcome,we further summarize some dominating microbial interventions and discuss the hidden risks of these strategies.This review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.展开更多
Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regress...Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regression and overall survival benefit in many types of cancer.With the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for immunotherapy.Small molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively investigated.Monotherapy of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance.Here,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.展开更多
There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and th...There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.展开更多
Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusiv...Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.展开更多
Cancer has emerged as the leading cause of mortality worldwide and is driven by numerous intricate factors1.The tropomyosin receptor kinase (TRK) proto-oncogene family consists of the TRKA,TRKB,and TRKC transmembrane ...Cancer has emerged as the leading cause of mortality worldwide and is driven by numerous intricate factors1.The tropomyosin receptor kinase (TRK) proto-oncogene family consists of the TRKA,TRKB,and TRKC transmembrane receptors,which are encoded by the NTRK1,NTRK2,and NTRK3 genes,respectively,and are widely expressed in the nervous system and many non-neuronal tissue types2.TRK signaling plays crucial roles in neuronal development,differentiation,and diverse neuronal functions,such as neuronal survival,synapse formation and plasticity,and axon and dendrite formation,in physiologic processes3.展开更多
In recent years,cryotherapy has gained increasing acceptance as a treatment for prostate cancer,offering complementary therapeutic benefits when combined with radical surgery and radiotherapy.Despite the potential for...In recent years,cryotherapy has gained increasing acceptance as a treatment for prostate cancer,offering complementary therapeutic benefits when combined with radical surgery and radiotherapy.Despite the potential for surgical complications,it stands as a safe and viable therapeutic modality.Cryotherapy provides an efficient approach for elderly patients,especially those with compromised physical conditions and individuals experiencing recurrence after initial treatment.It has shown promise in extending survival periods and improving the overall quality of life for these patients.This article aims to comprehensively examine the developmental trajectory,surgical techniques,indications,therapeutic outcomes,and potential complications associated within prostate cancer treatment.展开更多
The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments.Therefore,to aid scientists in making informed ...The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments.Therefore,to aid scientists in making informed choices,a community-based platform that indexes and rates bioinformatics tools is urgently needed.In this study,we introduce Bio Treasury(http://biotreasury.rjmart.cn),an integrated communitybased repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics tools.Bio Treasury offers a comprehensive collection of well-indexed bioinformatics software,tools,and databases,totaling over 10,000 entries.In the past two years,we have continuously improved and maintained Bio Treasury,adding several exciting features,including creating structured homepages for every tool and user,a hierarchical category of bioinformatics tools and classifying tools using large language model(LLM).Bio Treasury streamlines the tool submission process with intelligent auto-completion.Additionally,Bio Treasury provides a wide range of social features,for example,enabling users to participate in interactive discussions,rate tools,build and share tool collections for the public.We believe Bio Treasury can be a valuable resource and knowledge-sharing platform for the biomedical community.It empowers researchers to effectively discover and evaluate bioinformatics tools,fostering collaboration and advancing bioinformatics research.展开更多
The spreading of cancer cells from the primary tumor site to other parts of the body,known as metastasis,is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer(TNBC).Ove...The spreading of cancer cells from the primary tumor site to other parts of the body,known as metastasis,is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer(TNBC).Overexpression of epidermal growth factor receptor(EGFR)is observed in approximately 70%of TNBC patients.EGFR is crucial for promoting tumor metastasis and associated with poor prognosis.Therefore,it is vital to identify effective therapeutic strategies targeting EGFR inhibition.Ononin,an isoflavonoid found in various plants,such as clover and soybeans,has been shown to have anticancer properties in several cancers.In the present study,we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways.We used various assays,including cell viability,colony formation,Transwell,wound healing,ELISA,Western blotting,and staining techniques,to achieve this objective.The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis,as evidenced by the cell viability assay,colony formation assay,and expression of apoptosis markers,and reduced the metastatic capabilities of TNBC cells.These effects were achieved through the direct suppression of cell adhesion,invasiveness and motility.Furthermore,in TNBC xenograft lung metastatic models,ononin treatment significantly reduced tumor growth and lung metastasis.Additionally,ononin reversed the epithelial-mesenchymal transition(EMT)by downregulating the expression of EMT markers and matrix metalloproteinases,as confirmed by Western blot analysis.Furthermore,ononin treatment reduced EGFR phosphorylation and suppressed the PI3K,Akt,and m TOR signaling pathways,which was further confirmed using EGFR agonists or inhibitors.Importantly,ononin treatment did not exert any toxic effects on liver or kidney function.In conclusion,our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFRmediated PI3K/Akt/m TOR pathway.Further studies are warranted to validate its efficacy and explore its potential clinical applications.展开更多
PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as ti...PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.展开更多
There is still room for improvement in first-line treatment of advanced small cell lung cancer(SCLC).This trial firstly investigated efficacy and safety of antiangiogenic therapy(surufatinib)(200 mg,qd,po)plus anti-PD...There is still room for improvement in first-line treatment of advanced small cell lung cancer(SCLC).This trial firstly investigated efficacy and safety of antiangiogenic therapy(surufatinib)(200 mg,qd,po)plus anti-PD-1 treatment(toripalimab)(240 mg,d1,ivdrip)combined with etoposide(100 mg/m²,d1-d3,iv,drip)and cisplatin(25 mg/m²,d1-d3,ivdrip)for advanced SCLC as first-line treatment,which has been registered on ClinicalTrials.gov under the identifier NCT04996771.The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab.The primary endpoint was progression-free survival(PFS).The secondary end points included objective response rate(ORR),disease control rate(DCR),overall survival(OS)and safety.All of the 38 patients were enrolled for safety analysis,while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment.After a median follow-up of 21.3 months,the ORR was 97.1%(34/35),and the DCR and the tumor shrinkage rate were both 100%(35/35).The median PFS was 6.9 months(95%CI:4.6 m–9.2 m)and the median OS was 21.1 months(95%CI:12.1 m–30.1 m).The 12-month,18-month,and 24-month OS rates were 66.94%,51.39%and 38.54%.The occurrence rate of grade≥3 treatment-emergent adverse events(TEAEs)was 63.2%(24/38),including neutrophil count decreased(31.6%,12/38),white blood cell count decreased(23.7%,9/38)and platelet count decreased(10.5%,4/38).No unexpected adverse events occurred.This novel four-drug regimen(surufatinib,toripalimab,etoposide plus cisplatin)revealed impressive therapeutic efficacy and tolerable toxicities.展开更多
基金Supported by Natural Science Foundation of Guangdong Province,No.2020A1515011539.
文摘BACKGROUND Hepatic arterial infusion chemotherapy(HAIC)has been proven to be an ideal choice for treating unresectable hepatocellular carcinoma(uHCC).HAIC-based treatment showed great potential for treating uHCC.However,large-scale studies on HAIC-based treatments and meta-analyses of first-line treatments for uHCC are lacking.AIM To investigate better first-line treatment options for uHCC and to assess the safety and efficacy of HAIC combined with angiogenesis inhibitors,programmed cell death of protein 1(PD-1)and its ligand(PD-L1)blockers(triple therapy)under real-world conditions.METHODS Several electronic databases were searched to identify eligible randomized controlled trials for this meta-analysis.Study-level pooled analyses of hazard ratios(HRs)and odds ratios(ORs)were performed.This was a retrospective single-center study involving 442 patients with uHCC who received triple therapy or angiogenesis inhibitors plus PD-1/PD-L1 blockades(AIPB)at Sun Yat-sen University Cancer Center from January 2018 to April 2023.Propensity score matching(PSM)was performed to balance the bias between the groups.The Kaplan-Meier method and cox regression were used to analyse the survival data,and the log-rank test was used to compare the suvival time between the groups.RESULTS A total of 13 randomized controlled trials were included.HAIC alone and in combination with sorafenib were found to be effective treatments(P values for ORs:HAIC,0.95;for HRs:HAIC+sorafenib,0.04).After PSM,176 HCC patients were included in the analysis.The triple therapy group(n=88)had a longer median overall survival than the AIPB group(n=88)(31.6 months vs 14.6 months,P<0.001)and a greater incidence of adverse events(94.3%vs 75.4%,P<0.001).CONCLUSION This meta-analysis suggests that HAIC-based treatments are likely to be the best choice for uHCC.Our findings confirm that triple therapy is more effective for uHCC patients than AIPB.
基金This study was reviewed and approved by the Ethics Committee of Sun Yat-sen University Cancer Center(Approval No.B2023-219-03).
文摘BACKGROUND Gastric cancer(GC)is the most common malignant tumor and ranks third for cancer-related deaths among the worldwide.The disease poses a serious public health problem in China,ranking fifth for incidence and third for mortality.Knowledge of the invasive depth of the tumor is vital to treatment decisions.AIM To evaluate the diagnostic performance of double contrast-enhanced ultrasonography(DCEUS)for preoperative T staging in patients with GC by comparing with multi-detector computed tomography(MDCT).METHODS This single prospective study enrolled patients with GC confirmed by preoperative gastroscopy from July 2021 to March 2023.Patients underwent DCEUS,including ultrasonography(US)and intravenous contrast-enhanced ultrasonography(CEUS),and MDCT examinations for the assessment of preoperative T staging.Features of GC were identified on DCEUS and criteria developed to evaluate T staging according to the 8th edition of AJCC cancer staging manual.The diagnostic performance of DCEUS was evaluated by comparing it with that of MDCT and surgical-pathological findings were considered as the gold standard.RESULTS A total of 229 patients with GC(80 T1,33 T2,59 T3 and 57 T4)were included.Overall accuracies were 86.9%for DCEUS and 61.1%for MDCT(P<0.001).DCEUS was superior to MDCT for T1(92.5%vs 70.0%,P<0.001),T2(72.7%vs 51.5%,P=0.041),T3(86.4%vs 45.8%,P<0.001)and T4(87.7%vs 70.2%,P=0.022)staging of GC.CONCLUSION DCEUS improved the diagnostic accuracy of preoperative T staging in patients with GC compared with MDCT,and constitutes a promising imaging modality for preoperative evaluation of GC to aid individualized treatment decision-making.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515220184).
文摘Breast cancer has surpassed lung cancer to become the most common malignancy worldwide.The incidence rate and mortality rate of breast cancer continue to rise,which leads to a great burden on public health.Circular RNAs(circRNAs),a new class of noncoding RNAs(ncRNAs),have been recognized as important oncogenes or suppressors in regulating cancer initiation and progression.In breast cancer,circRNAs have significant roles in tumorigenesis,recurrence and multidrug resistance that are mediated by various mechanisms.Therefore,circRNAs may serve as promising targets of therapeutic strategies for breast cancer management.This study reviews the most recent studies about the biosynthesis and characteristics of circRNAs in diagnosis,treatment and prognosis evaluation,as well as the value of circRNAs in clinical applications as biomarkers or therapeutic targets in breast cancer.Understanding the mechanisms by which circRNAs function could help transform basic research into clinical applications and facilitate the development of novel circRNA-based therapeutic strategies for breast cancer treatment.
基金Supported by Basic and Applied Basic Research Foundation of Guangzhou,No.202201011331National Natural Science Foundation of China,No.82373118Natural Science Foundation of Guangdong Province,No.2023A1515010828.
文摘This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography(EUS)in the context of small rectal neuroendocrine neoplasms(NENs).A total of 108 patients with rectal subepithelial lesions(SELs)with a diameter of<20 mm were included in the analysis.The diagnosis and depth assessment of EUS was compared to the histology findings.The prevalence of NENs in rectal SELs was 78.7%(85/108).The sensitivity of EUS in detecting rectal NENs was 98.9%(84/85),while the specificity was 52.2%(12/23).Overall,the diagnostic accuracy of EUS in identifying rectal NENs was 88.9%(96/108).The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9%(78/84).Therefore,EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs,with good sensitivity but inferior specificity.EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.
基金supported by the Shenzhen Key Laboratory of Drug Addiction (ZDSYS20190902093601675)CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024)+2 种基金National Natural Science Foundation of China (82274358)Shenzhen-Hong Kong Institute of Brain ScienceGuangdong Basic and Applied Basic Research Foundation (2023B1515040009)
文摘Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
文摘BACKGROUND Colorectal anastomotic occlusion is a serious complication of colorectal cancer surgery.Although several treatment strategies have been proposed,the mana-gement of anastomotic occlusion remains challenging.In this report,we present a case of anastomotic occlusion recanalization performed using a novel technique involving two endoscopes,one for radial incision and the other serving as a guide light.This novel technique offers significant advantages in terms of operational feasibility,reduced invasiveness,rapid recovery,and shortened hospital stay.CASE SUMMARY A 37-year-old man underwent low anterior resection and prophylactic double-lumen ileostomy for rectal cancer in June,2023.Two months later,complete anastomotic occlusion was observed on colonoscopy.Therefore,we developed a novel atresia recanalization technique.Two endoscopes were placed,one through the colonic anastomosis and the other through the anus.A radial incision was successfully made from the colonic side,guided by the light of the endoscope from the anal side.Atresia recanal-ization was performed within 20 minutes.Three weeks after recanalization,colonoscopy revealed that the diameter of the colorectal anastomosis was approximately 16 mm and the patient therefore underwent stoma reversal in September.During the follow-up period of approximately one year,the patient remained well and no stenosis or obstruction symptoms were observed.CONCLUSION Endoscopic atresia recanalization of colorectal anastomotic occlusion assisted by an opposing light source is safe and effective.
文摘The prevalence of colorectal cancer(CRC) is increasing annually and metastasis is the principal cause of death in patients with CRC, with the liver being the most frequently affected site. Many studies have shown a strong interplay between the gut flora, particularly Fusobacterium nucleatum(F. nucleatum), Escherichia coli, and Bacteroides fragilis, and the development of gut tumors. Some strains can induce gut inflammation and produce toxins that directly harm gut epithelial cells, ultimately accelerating the onset and progression of CRC. However,little clinical evidence exists on the specific interplay between the gut microflora and colorectal cancer liver metastasis(CRLM). Some research showed the existence of viable F. nucleatum in distant metastasis of CRC.Subsequently, gut microbiota products, such as lipopolysaccharides, sodium butyrate, and protein cathepsin K, were also found to affect the development of CRC. This article summarizes the mechanism and research status of the interplay between gut microflora and CRLM, discusses the importance of gut microflora in the treatment of CRLM, and proposes a new approach to understanding the mechanism of CRLM and potential treatments for the microbiome. It is anticipated that the gut microbiota will be a formidable therapeutic and prophylactic tool for treating and preventing CRLM.
文摘BACKGROUND With the widespread use of hemocoagulase in patients with gastrointestinal bleeding,clinicians have become increasingly concerned about coagulation dis-orders associated with this medication.Risk factors for hypofibrinogenemia asso-ciated with hemocoagulase are poorly understood.AIM To determine risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding.METHODS We performed a retrospective analysis of the medical documentation of hospit-alized patients treated with hemocoagulase for gastrointestinal bleeding.Hypofib-rinogenemia was defined as a decrease in plasma fibrinogen concentration to less than 2.0 g/L.The included patients were divided into two groups:acquired hypofibrinogenemia group and non-hypofibrinogenemia group.We used logistic regression analysis to identify potential risk factors and established risk assess-RESULTS There were 36 patients in the acquired hypofibrinogenemia group and 73 patients in the non-hypofibrinogenemia group.The hypofibrinogenemia group showed higher rates of intensive care unit admissions(P=0.021),more female patients(P=0.005),higher in-hospital mortality(P=0.027),larger hemocoagulase doses(P=0.026),more Packed Red Cells transfusions(P=0.024),and lower baseline fibrinogen levels(P<0.000).Binary logistic regression was employed to examine the risk factors associated with acquired hypofibrinogenemia.The analysis revealed that baseline fibrinogen[odds ratio(OR)0.252,95%CI:0.137-0.464,P<0.000],total hemocoagulase doses(OR 1.074,95%CI:1.015-1.137,P=0.014),and female gender(OR 2.856,95%CI:1.015–8.037,P=0.047)were statist-ically significant risk factors.CONCLUSION Higher doses of total hemocoagulase,female gender,and a lower baseline fibrinogen level were risk factors for hemocoagulase-associated hypofibrinogenemia in patients with gastrointestinal bleeding.
基金funded by the Chinese National Natural Science Foundation Project(Grant No.82173101,82373262,82241232,82272789,82102864)Guangzhou Basic and Applied Basic Research Foundation(2024A04J4082)partly funded by the 308 Clinical Research Foundation of Sun Yat-sen University Cancer Center.
文摘Dual inhibition of vascular endothelial growth factor and epidermal growth factor receptor(EGFR)signaling pathways offers the prospect of improving the effectiveness of EFGR-targeted therapy.In this phase 3 study(ClinicalTrial.gov:NCT04028778),315 patients with treatment-naïve,EGFR-mutated,advanced non-small cell lung cancer(NSCLC)were randomized(1:1)to receive anlotinib or placebo plus gefitinib once daily on days 1–14 per a 3-week cycle.At the prespecified final analysis of progression-free survival(PFS),a significant improvement in PFS was observed for the anlotinib arm over the placebo arm(hazards ratio[HR]=0.64,95%CI,0.48–0.80,P=0.003).Particularly,patients with brain metastasis and those harboring EGFR amplification or high tumor mutation load gained significant more benefits in PFS from gefitinib plus anlotinib.The incidence of grade 3 or higher treatment-emergent adverse events was 49.7%of the patients receiving gefitinib plus anlotinib versus 31.0%of the patients receiving gefitinib plus placebo.Anlotinib plus gefitinib significantly improves PFS in patients with treatment-naïve,EGFR-mutated,advanced NSCLC,with a manageable safety profile.
文摘The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.
基金supported by grants from the Guangzhou Science and Technology Project(202206010013 to N.Liu)the Guangdong Basic and Applied Basic Research Foundation(2022A1515220010 to N.Liu)the Fundamental Research Funds for the Central Universities,Sun Yat-sen University(22yklj07 to N.Liu).
文摘The profound influence of microbiota in cancer initiation and progression has been under the spotlight for years,leading to numerous researches on cancer microbiome entering clinical evaluation.As promising biomarkers and therapeutic targets,the critical involvement of microbiota in cancer clinical practice has been increasingly appreciated.Here,recent progress in this field is reviewed.We describe the potential of tumor-associated microbiota as effective diagnostic and prognostic biomarkers,respectively.In addition,we highlight the relationship between microbiota and the therapeutic efficacy,toxicity,or side effects of commonly utilized treatments for cancer,including chemotherapy,radiotherapy,and immunotherapy.Given that microbial factors influence the cancer treatment outcome,we further summarize some dominating microbial interventions and discuss the hidden risks of these strategies.This review aims to provide an overview of the applications and advancements of microbes in cancer clinical relevance.
基金supported by the National Natural Science Foundation of China(Nos.U21A20421,82073882,82073317,81772540 and 82272996)the Key Project of Science Technology Program of Guangzhou(No.2023B03J0029,China)+1 种基金the National Key R&D Program of China(No.2022YFE0209700)the Science and Technology Program of Guangzhou(Nos.202201010819 and 202206010081,China)。
文摘Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer therapy.They induce long-term tumor regression and overall survival benefit in many types of cancer.With the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for immunotherapy.Small molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively investigated.Monotherapy of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor resistance.Here,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.
基金supported by grants from the National Natural Science Foundation of China (81972531, 82373175, 82102775, and 82002466)the Major Scientific and Technological Projects of Guangdong Province (2019B020202002)the Young Talents Program of Sun Yat-sen University Cancer Center (YTP-SYSUCC-0067)
文摘There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease progression.The targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and D-substitution.Herein,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating CNS-ALL.The self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different experiments.Our results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious toxicity.Moreover,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.
基金supported by the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010403,Ning Lyu)Natural Science Foundation of Guangdong Province,China(No.1914050001553,Dong Chen).
文摘Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain elusive.We sought to unveil the expression profile and biological role of circMYBL2 in HCC.Initial microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of circMYBL2.Subsequent experiments were conducted to evaluate the biological function of circMYBL2 in HCC progression.Furthermore,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and E2F1.CircMYBL2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell lines.Elevated expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting effects.Mechanistically,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging miR-1205.Our findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.
基金supported by grants from the National Key Research and Development Program of China (Grant No.2022YFC2705005)the National Natural Science Foundation of China (Grant No.82203303)the Basic and Applied Basic Research Foundation of Guangdong Province (Grant No.2021A1515110234)。
文摘Cancer has emerged as the leading cause of mortality worldwide and is driven by numerous intricate factors1.The tropomyosin receptor kinase (TRK) proto-oncogene family consists of the TRKA,TRKB,and TRKC transmembrane receptors,which are encoded by the NTRK1,NTRK2,and NTRK3 genes,respectively,and are widely expressed in the nervous system and many non-neuronal tissue types2.TRK signaling plays crucial roles in neuronal development,differentiation,and diverse neuronal functions,such as neuronal survival,synapse formation and plasticity,and axon and dendrite formation,in physiologic processes3.
基金supported by the National Natural Science Foundation of China(No.82203320).
文摘In recent years,cryotherapy has gained increasing acceptance as a treatment for prostate cancer,offering complementary therapeutic benefits when combined with radical surgery and radiotherapy.Despite the potential for surgical complications,it stands as a safe and viable therapeutic modality.Cryotherapy provides an efficient approach for elderly patients,especially those with compromised physical conditions and individuals experiencing recurrence after initial treatment.It has shown promise in extending survival periods and improving the overall quality of life for these patients.This article aims to comprehensively examine the developmental trajectory,surgical techniques,indications,therapeutic outcomes,and potential complications associated within prostate cancer treatment.
基金supported by the National Key Research and Development Program of China(2021YFA1302100)the National Natural Science Foundation of China(82172861,32200542)+2 种基金the Young Elite Scientists Sponsorship Program by Guangzhou Association for Science and Technology(QT-2023-045)the Youth Talent Support Program of Guangdong Provincial Association for Science and Technology(SKXRC202313)the Young Talents Program of Sun Yat-sen University Cancer Center(YTP-SYSUCC-0033)。
文摘The exponential growth of bioinformatics tools in recent years has posed challenges for scientists in selecting the most suitable one for their data analysis assignments.Therefore,to aid scientists in making informed choices,a community-based platform that indexes and rates bioinformatics tools is urgently needed.In this study,we introduce Bio Treasury(http://biotreasury.rjmart.cn),an integrated communitybased repository that provides an interactive platform for users and developers to share their experiences in various bioinformatics tools.Bio Treasury offers a comprehensive collection of well-indexed bioinformatics software,tools,and databases,totaling over 10,000 entries.In the past two years,we have continuously improved and maintained Bio Treasury,adding several exciting features,including creating structured homepages for every tool and user,a hierarchical category of bioinformatics tools and classifying tools using large language model(LLM).Bio Treasury streamlines the tool submission process with intelligent auto-completion.Additionally,Bio Treasury provides a wide range of social features,for example,enabling users to participate in interactive discussions,rate tools,build and share tool collections for the public.We believe Bio Treasury can be a valuable resource and knowledge-sharing platform for the biomedical community.It empowers researchers to effectively discover and evaluate bioinformatics tools,fostering collaboration and advancing bioinformatics research.
基金supported by the Guangxi Science and Technology Key Research and Development Program(AB16450012)。
文摘The spreading of cancer cells from the primary tumor site to other parts of the body,known as metastasis,is the leading cause of cancer recurrence and mortality in patients with triple-negative breast cancer(TNBC).Overexpression of epidermal growth factor receptor(EGFR)is observed in approximately 70%of TNBC patients.EGFR is crucial for promoting tumor metastasis and associated with poor prognosis.Therefore,it is vital to identify effective therapeutic strategies targeting EGFR inhibition.Ononin,an isoflavonoid found in various plants,such as clover and soybeans,has been shown to have anticancer properties in several cancers.In the present study,we aimed to investigate the effects of ononin on TNBC lung metastasis and the associated molecular pathways.We used various assays,including cell viability,colony formation,Transwell,wound healing,ELISA,Western blotting,and staining techniques,to achieve this objective.The results demonstrated that ononin effectively suppressed cellular proliferation and induced apoptosis,as evidenced by the cell viability assay,colony formation assay,and expression of apoptosis markers,and reduced the metastatic capabilities of TNBC cells.These effects were achieved through the direct suppression of cell adhesion,invasiveness and motility.Furthermore,in TNBC xenograft lung metastatic models,ononin treatment significantly reduced tumor growth and lung metastasis.Additionally,ononin reversed the epithelial-mesenchymal transition(EMT)by downregulating the expression of EMT markers and matrix metalloproteinases,as confirmed by Western blot analysis.Furthermore,ononin treatment reduced EGFR phosphorylation and suppressed the PI3K,Akt,and m TOR signaling pathways,which was further confirmed using EGFR agonists or inhibitors.Importantly,ononin treatment did not exert any toxic effects on liver or kidney function.In conclusion,our findings suggest that ononin is a safe and potentially therapeutic treatment for TNBC metastasis that targets the EGFRmediated PI3K/Akt/m TOR pathway.Further studies are warranted to validate its efficacy and explore its potential clinical applications.
基金supported by the Basic and Applied Basic Research Foundation of Guangdong Province(2022A1515220184)the Natural Science Foundation of Guangdong Province(2021A1515010547)。
文摘PIWI-interacting RNAs(pi RNAs)are a class of small noncoding RNA molecules that specifically bind to piwi protein family members to exert regulatory functions in germ cells.Recent studies have found that pi RNAs,as tissue-specific molecules,both play oncogenic and tumor suppressive roles in cancer progression,including cancer cell proliferation,metastasis,chemoresistance and stemness.Additionally,the atypical manifestation of pi RNAs and PIWI proteins in various malignancies presents a promising strategy for the identification of novel biomarkers and therapeutic targets in the diagnosis and management of tumors.Nonetheless,the precise functions of pi RNAs in cancer progression and their underlying mechanisms have yet to be fully comprehended.This review aims to examine current research on the biogenesis and functions of pi RNA and its burgeoning importance in cancer progression,thereby offering novel perspectives on the potential utilization of pi RNAs and piwi proteins in the management and treatment of advanced cancer.
基金Chinese National Natural Science Foundation Project(Grant No.82173101,82373262,82241232,82272789,82102872,82102864)Guangzhou Basic and Applied Basic Research Foundation(2024A04J4082).
文摘There is still room for improvement in first-line treatment of advanced small cell lung cancer(SCLC).This trial firstly investigated efficacy and safety of antiangiogenic therapy(surufatinib)(200 mg,qd,po)plus anti-PD-1 treatment(toripalimab)(240 mg,d1,ivdrip)combined with etoposide(100 mg/m²,d1-d3,iv,drip)and cisplatin(25 mg/m²,d1-d3,ivdrip)for advanced SCLC as first-line treatment,which has been registered on ClinicalTrials.gov under the identifier NCT04996771.The four-drug regimen was conducted q3w for 4 cycles with maintenance therapy of surufatinib and toripalimab.The primary endpoint was progression-free survival(PFS).The secondary end points included objective response rate(ORR),disease control rate(DCR),overall survival(OS)and safety.All of the 38 patients were enrolled for safety analysis,while only 35 patients were enrolled for efficacy analysis since loss of efficacy evaluation in 3 cases after treatment.After a median follow-up of 21.3 months,the ORR was 97.1%(34/35),and the DCR and the tumor shrinkage rate were both 100%(35/35).The median PFS was 6.9 months(95%CI:4.6 m–9.2 m)and the median OS was 21.1 months(95%CI:12.1 m–30.1 m).The 12-month,18-month,and 24-month OS rates were 66.94%,51.39%and 38.54%.The occurrence rate of grade≥3 treatment-emergent adverse events(TEAEs)was 63.2%(24/38),including neutrophil count decreased(31.6%,12/38),white blood cell count decreased(23.7%,9/38)and platelet count decreased(10.5%,4/38).No unexpected adverse events occurred.This novel four-drug regimen(surufatinib,toripalimab,etoposide plus cisplatin)revealed impressive therapeutic efficacy and tolerable toxicities.
