Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance pati...Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.展开更多
Human epidermal growth factor receptor 2(HER-2)is a transmembrane receptor tyrosine kinase that is overexpressed in various solid tumors and is closely related to tumor invasion,metastasis,and poor prognosis.In recent...Human epidermal growth factor receptor 2(HER-2)is a transmembrane receptor tyrosine kinase that is overexpressed in various solid tumors and is closely related to tumor invasion,metastasis,and poor prognosis.In recent years,the expression of HER-2 in colorectal cancer and its clinical significance have gradually attracted attention.This article reviews the expression of HER-2 in colorectal cancer,the clinicopathological characteristics of HER-2 positive colorectal cancer,the detection methods of HER-2,and the drug treatment targeting HER-2,to provide references for clinical diagnosis and treatment and research.展开更多
Objective:Glucocorticoid-induced osteoporosis(GIOP)is a common complication of prolonged glucocorticoid therapy.Chlorogenic acid(CGA),a polyphenol with antioxidant properties that is extracted from traditional Chinese...Objective:Glucocorticoid-induced osteoporosis(GIOP)is a common complication of prolonged glucocorticoid therapy.Chlorogenic acid(CGA),a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex,has potential anti-osteoporotic activity.This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4(MLO-Y4)cells and explore the underlying molecular mechanisms.Methods:The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone(Dex).The micro-computed tomography,hematoxylin-eosin staining,silver nitrate staining,and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo.Then,network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP.After that,2',7'-dichlorofluorescein diacetate staining,flow cytometry,real-time quantitative reverse transcription polymerase chain reaction,and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro.Results:Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice.The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase(ERBB2),which is also known as human epidermal growth factor receptor 2(HER2),caspase-3,kinase insert domain receptor,matrix metallopeptidase 9,matrix metallopeptidase 2,proto-oncogene tyrosine-protein kinase Src,and epidermal growth factor receptor as core targets.The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways(P<0.05),including the ERBB,phosphoinositide 3 kinase-AKT serine/threonine kinase 1(AKT),and mechanistic target of rapamycin kinase(mTOR)pathways.Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex,which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway.Conclusion:CGA exerted anti-osteoporotic effects against GIOP,partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway.展开更多
BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available the...BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available therapeutic options is typically low.CRC exhibiting overexpression or amplification of the human epidermal growth factor receptor 2(HER2)gene has shown responsiveness to HER2-targeted therapies.CASE SUMMARY We present the case of a 69-year-old woman diagnosed with mCRC with an NRAS p.G12V mutation and microsatellite stability,identified through tumor sequencing,along with HER2 overexpression detected by immunohistochemistry.She exhibited an excellent response to disitamab vedotin-containing therapy.To our knowledge,this is the first reported case of mCRC with HER2 overexpression and an NRAS p.G12V mutation achieving a remarkable clinical response to anti-HER2 therapy.CONCLUSION Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overex-pressing mCRC,offering patients an additional treatment option.展开更多
Background:Chimeric antigen receptor T(CAR-T)cell therapies have demonstrated significant clinical efficacy in hematological malignancies.However,their application to solid tumors remains substantially limited by mult...Background:Chimeric antigen receptor T(CAR-T)cell therapies have demonstrated significant clinical efficacy in hematological malignancies.However,their application to solid tumors remains substantially limited by multiple challenges,including the risk of off-target effects.Hence,optimizing CAR-T cells for stronger antigen binding is essential.Methods:In this study,we employed a classical anti-human endothelial growth factor receptor 2(HER2)single-chain variable fragment(scFv)derived from trastuzumab,alongside an anti-HER2-13 scFv identified from a combinatorial cellular CAR library,for the construction of a third-generation CAR-T cell.Meanwhile,the phenotypes and both in vitro and in vivo functions of CAR-T cells transduced with the two scFvs via PiggyBac transposon-mediated gene transfer were compared.Results:The optimal ratio between the PiggyBac HER2-CAR-puro transposon and the Super PiggyBac transposase plasmid differed during the construction of the two HER2-targeted CAR-T cell types.The expansion abilities,CD3^(+)CAR^(+)population,CD4^(+)CAR^(+)/CD8^(+)CAR^(+)proportions,and memory and exhaustion markers between the two CAR-T groups were similar after using the optimized proportion of plasmid.Both CAR-T cell types exhibited significant antitumor activity,with the anti-HER2-13 CAR-T cells demonstrating superior target specificity.Therapeutic effects were observed with both CAR-T cells and trastuzumab in theMDA-MB-231HER2+breast tumor xenograft model,with anti-HER2-13 CAR-T cells demonstrating slightly enhanced efficacy and no evident offtarget toxicity.Conclusion:These results highlight the potential of anti-HER2-13 CAR-T cells to serve as a safer and more efficacious alternative in HER2-targeted therapy.展开更多
BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is over...BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is overexpressed in a subset of pa-tients with colorectal cancer and has been established as a therapeutic target.CASE SUMMARY This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors(ICIs)in combination with pyrotinib.The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression.CONCLUSION ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer.Chemotherapy following disease progression could enhance efficacy synergistically.展开更多
BACKGROUND Human epidermal growth factor receptor 2(HER2)plays pivotal roles in cellular proliferation,survival,and differentiation of several malignancies.Upper tract urothelial carcinoma(UTUC)is a relatively rare ma...BACKGROUND Human epidermal growth factor receptor 2(HER2)plays pivotal roles in cellular proliferation,survival,and differentiation of several malignancies.Upper tract urothelial carcinoma(UTUC)is a relatively rare malignancy.The clinical and molecular significance of HER2 expression level in UTUC remains poorly characterized vs bladder cancer.AIM To comprehensively evaluate HER2 expression patterns and their association with UTUC patients’clinicopathological features.METHODS Data were retrospectively collected from patients diagnosed with UTUC at The First Affiliated Hospital of Guangxi Medical University between January 2023 and December 2024.HER2 status was evaluated by immunohistochemistry in 145 UTUC patients who met the inclusion criteria.Its associations with tumor grade,tumor stage,and other clinicopathological parameters were assessed.Theχ2 test or Fisher’s exact test,along with univariate and multivariate logistic regression analyses,were performed to determine the influences of clinicopathological factors on HER2 expression.RESULTS HER2 positivity was significantly associated with high tumor grade(P=0.003),while other variables,including sex,anatomical tumor location,pathological T stage,Ki-67 proliferation index,nodal metastasis status,lymphovascular invasion,and tumor laterality failed to demonstrate statistically significant correlations.These findings were further substantiated through univariate logistic regression modeling,yielding an odds ratio of 3.56[95%confidence interval(CI):1.30-9.75;P=0.013]for the association between high tumor grade and HER2 positivity.Importantly,this relationship remained robust(hazard ratio=3.42,95%CI:1.22-9.60;P=0.019)even after implementing multivariate logistic regression analysis.With a median follow-up time of 8 months(interquartile range,4-14)months,14 patients experienced intravesical recurrence after radical nephroureterectomy.Certain patient characteristics,such as HER2-negative,male sex,high-grade tumors,and luminal phenotype,were associated with a higher risk of intravesical recurrence.CONCLUSION In UTUC,HER2 overexpression is closely associated with tumor dedifferentiation(high grade),while it does not correlate with conventional indicators of disease progression,indicating that HER2 may serve a distinct biological function in this cancer type.展开更多
BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regim...BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase Ⅲ clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.展开更多
Cholangiocarcinoma(CCA)is a fatal bile duct malignancy.CCA is intrinsically resistant to standard chemotherapy,responds poorly to it,and has a poor prognosis.Effective treatments for cholangiocarcinoma remain elusive,...Cholangiocarcinoma(CCA)is a fatal bile duct malignancy.CCA is intrinsically resistant to standard chemotherapy,responds poorly to it,and has a poor prognosis.Effective treatments for cholangiocarcinoma remain elusive,and a breakthrough in CCA treatment is still awaited.The human epidermal growth factor receptor 2(HER2)plays an oncogenic role by promoting an aggressive cancer phenotype through multiple pathways.While HER2 has shown increasing potential as an effective target for breast and gastric cancers over the last decade,this has not been the case for CCA.This review explores the possibility of targeting HER2 in CCA immunotherapy.Key findings suggest that HER2 alterations have been reported as one of the signatures associated with a poorer prognosis in liver fluke-associated CCA,the most prevalent subtype in Southeast Asia.Furthermore,we assess recent advances in HER2-targeted therapeutic approaches,presenting the current stage,rationale,and evidence supporting the use of HER2 as a promising therapeutic target for cancer immunotherapy in CCA.We also emphasize the crucial role of animal models in developing anticancer therapies.In summary,focusing on HER2 expression could provide alternative strategies for the HER2-altered CCA cluster.展开更多
The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9%between the experimental and control groups.That is to say,in the intermediate-risk hormone receptor pos...The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9%between the experimental and control groups.That is to say,in the intermediate-risk hormone receptor positive/human epidermal growth factor receptor-2 negative subgroup,there are also some patients with primary resistance to ribociclib.These patients benefit less from ribociclib,and they are unable to gain significant benefit even with the intensive adjuvant therapy of ribociclib.Considering the drug toxicity and health economic benefits,a 3-year course of ribociclib may not be appropriate for all intermediate-risk populations.Therefore,how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored.In this paper,we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.展开更多
BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of h...BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.展开更多
This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer p...This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.展开更多
BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC r...BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability.Reliable prognostic markers are critical to guide clinical management.AIM To investigate the prognostic factors,including human epidermal growth factor receptor 2(HER2)expression,associated with survival outcomes in patients with gastric SRCC.METHODS A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted,assessing demographic,clinical,and pathological data.HER2 expression was analyzed using immunohistochemistry,and survival outcomes,including overall survival and disease-free survival,were examined.RESULTS With a median follow-up of 43 months,the median patient age was 50 years,and males exhibited a higher mortality rate(P=0.0107).Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality(P=0.00149 and P=0.00163,respectively).Advanced tumornode-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes(P<0.001 and P=0.019).HER2 positivity correlated with higher mortality(P=0.00882)but was not significantly linked to recurrence(P=0.53).Surgical treatment significantly improved survival compared with non-surgical approaches(P=0.0226).CONCLUSION These findings highlight the aggressive nature of SRCC with advanced disease stage,elevated tumor markers,and lymphovascular invasion contributing to poor outcomes.HER2 expression,though infrequent,may indicate worse prognosis,reinforcing the role of surgical intervention in survival improvement.展开更多
BACKGROUND Over 150000 new diagnoses of colorectal cancer(CRC)are diagnosed yearly,and 1 in 5 patients have distant metastases on diagnosis.Previous estimates approximate that brain metastases(BM)occur in 0.6%to 3.2%o...BACKGROUND Over 150000 new diagnoses of colorectal cancer(CRC)are diagnosed yearly,and 1 in 5 patients have distant metastases on diagnosis.Previous estimates approximate that brain metastases(BM)occur in 0.6%to 3.2%of patients with CRC.AIM To describe the updated literature about the incidence and risk factors of BM in CRC as well as their treatment with surgery,chemotherapy,and radiation.METHODS We systematically searched the literature published between January 1,2010 and April 1,2025 in PubMed,Cochrane,Scopus,and EMBASE.All studies about BM from CRC were included.Studies only containing information about the treatment of primary CRC or primary brain tumors were not included.Articles were categorized and described as incidence,surgery,chemotherapy,or radiation to provide an overview of the state of research on BM from CRC.RESULTS Our primary search resulted in 1648 articles that were eventually screened to 147.These articles were analyzed to provide the state of current literature on incidence and risk factors of BM from CRC as well as how these metastases are treated with chemotherapy,radiation,and surgery.CONCLUSION Prognosis is influenced by tumor burden,performance status,and emerging molecular markers.Stereotactic radiotherapy and surgical resection provide favorable outcomes for select patients,whereas chemotherapy and immunotherapy remain areas of limited evidence.Continued research is needed to identify highrisk patients and optimize multidisciplinary treatment approaches.展开更多
Background:The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors.In such cancer cells,oncogenic receptors,including human epiderma...Background:The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors.In such cancer cells,oncogenic receptors,including human epidermal growth factor receptor 2(HER2),are activated,and their targeted inhibition represents an attractive therapeutic strategy.The study aimed to develop small-molecule potential dual heat shock protein 90(HSP90)-HER2 inhibitors and evaluate them as anticancer agents in HER2-positive cells.Methods:The research project involved obtaining a series of compounds with potential dual inhibitory activity against HSP90 and HER2 by targeted organic synthesis,which was preliminarily assessed using molecular modelling and calculation of key parameters of molecular dynamics.The potential therapeutic benefit of the obtained molecules was studied using basic molecular biological methods,including assessment of cytotoxic activity in vitro using the MTT test,as well as determination of a possible mechanism of action based on the expression of key participants in intracellular signaling(western blotting).Additionally,therapeutic combinations were developed and tested on a cellularmodel of the disease,including a lead compound and chemotherapeutic drugs used in clinical practice,in order to find synergistic pairs and improve the effectiveness of the treatment.Results:In this work,novel dual HSP90-HER2 inhibitors,based on the fused thiazole-dihydrobenzisoxazole polycyclic scaffold,were designed and synthesized.The resulting compounds exhibited strong antiproliferative activity against HER2-positive breast cancer cells with high selectivity.Among them,ATF-2 demonstrated antiproliferative activity comparable to HER2 inhibitor lapatinib and significantly suppressed HER2 expression and activity,epidermal growth factor receptor(EGFR)activity,and cyclin-dependent kinase 6(CDK6)expression in HCC1954 breast cancer cells.Conclusion:These findings highlight ATF-2 as a promising dual HSP90-HER2 inhibitor with broader inhibitory effects on the HER2,EGFR,and CDK6 pathways.展开更多
Objective To evaluate the effects of transforming growth factor β(TGF-β) and recombinant human bone morphogenetic protein 2 (rhBMP2) on human periodontal ligament fibroblasts (HPDLFs). Methods HPDLFs were done prima...Objective To evaluate the effects of transforming growth factor β(TGF-β) and recombinant human bone morphogenetic protein 2 (rhBMP2) on human periodontal ligament fibroblasts (HPDLFs). Methods HPDLFs were done primary culture to detect the distinct concentrations of TGF-P and rhBMF2 on its proliferation, alkaline phosphatase (ALP) activity, osteocalcin (OC) synthesis and formation of the minerali-zed nodules, respectively. Results TGF-β (5～100ng/ml) significantly stimulated the proliferation of HPDLFs. The ALP activity of HPDLFs was evaluated evidently by 5ng/ml TGF-β. TGF-β( 0. 5 ～ 100ng/ml) had no effects on OC synthesis and formation of the mineralized nodules of HPDLFs. rhBMP2 (0. 25～2mg/ ml) had no remarkable effect on the proliferation of HPDLFs. The ALP activity, OC synthesis and forma-tion of the mineralized nodules of HPDLFs were significantly stimulated by 0. 5～ 2mg /ml rhBMP2. Conclusion The effects of TGF-β and rhBMP2 on HPDLFs are dose-dependent. TGF-P can stimulate HPDLFs to express the early marker of osteoblastic phenotype, and it lacks the ability to promote maturation of the osteogenic phenotype. rhBMP2 can not only stimulate the expression but also promote the maturation of osteoblas-tic phenotype of HPDLFs.展开更多
Objective： To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and its significance for establishing a solid foundation for further study of the relationship between...Objective： To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods： The expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and human pancreatic carcinoma cell lines （MIAPaCa-2） was detected by using RT-PCR. Results： The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion： The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines （Hep-2） is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.展开更多
The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus.Here,we present a Human Angiotensin-converting-enzyme 2(ACE2)-functionalized gold“virus traps”nanostructure as an ...The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus.Here,we present a Human Angiotensin-converting-enzyme 2(ACE2)-functionalized gold“virus traps”nanostructure as an extremely sensitive SERS biosensor,to selectively capture and rapidly detect S-protein expressed coronavirus,such as the current SARS-CoV-2 in the contaminated water,down to the single-virus level.Such a SERS sensor features extraordinary 106-fold virus enrichment originating from high-affinity of ACE2 with S protein as well as“virus-traps”composed of oblique gold nanoneedles,and 109-fold enhancement of Raman signals originating from multi-component SERS effects.Furthermore,the identification standard of virus signals is established by machine-learning and identification techniques,resulting in an especially low detection limit of 80 copies mL^(−1) for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min,which is of great significance for achieving real-time monitoring and early warning of coronavirus.Moreover,here-developed method can be used to establish the identification standard for future unknown coronavirus,and immediately enable extremely sensitive and rapid detection of novel virus.展开更多
AIM: To clarify the mechanism underlying the anti-mutagenic and anti-cancer activities of Scorpio water extract (SWE). METHODS: Human hepatoma HepG2 cells were incubated with various concentrations of SWE. After 24-h ...AIM: To clarify the mechanism underlying the anti-mutagenic and anti-cancer activities of Scorpio water extract (SWE). METHODS: Human hepatoma HepG2 cells were incubated with various concentrations of SWE. After 24-h incubation, cytotoxicity and apoptosis evaluations were determined by MTT and DNA fragmentation assay, respectively. After treatment with SWE, mitochondrial membrane potential (MMP) was determined by measuring the retention of the dye 3,3'-dihexyloxacarbocyanine (DiOC6(3)) and the protein expression including cytochrome C and poly-(ADPribose) polymerase (PARP) were measured by Western blotting. Caspase-3 and -9 enzyme activities were measured using specific fluorescence dyes such as Ac-DEVD-AFC and Ac-LEHD-AFC. RESULTS: We found that treatment with SWE induced apoptosis as confirmed by discontinuous DNA fragmentation in cultured human hepatoma HepG2 cells. Our investigation also showed that SWE-induced apoptosis of HepG2 cells were associated with intracellular events including disruption of MMP, increased translocation of cytochrome C from mitochondria to cytosol, activation of caspase-3, and PARP. Pre-treatment of N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), a caspase-3 specific inhibitor, or cyclosporin A (CsA), an inhibitor of MMP disruption, completely abolished SWE-induced DNA fragmentation. CONCLUSION: These results suggest that SWE possibly causes mitochondrial damage, leading to cytochrome C release into cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic cell death in HepG2 cells. These results further suggest that Scorpio may be a valuable agent of therapeutic intervention of human hepatomas.展开更多
文摘Background:Cyclin-dependent kinase 4/6(CDK4/6)inhibitors have transformed the management of hormone receptor–positive/HER2–negative(HR+/HER2–)advanced breast cancer,yet evidence for elderly or poor-performance patients remains limited.This study examined real-world outcomes of palbociclib plus endocrine therapy in Asian patients,with additional subgroup analyses by age and performance status.Methods:We retrospectively analyzed 46 consecutive Asian patients with recurrent or de novo HR+/HER2−breast cancer treated with first-line palbociclib plus ET between April 2021 and March 2025.The primary endpoint was progression-free survival(PFS).Secondary endpoints included overall response rate(ORR),disease control rate(DCR),and safety.Subgroup analyses were performed by age(<70 vs.≥70 years)and performance status(PS;0–1 vs.2–3).Results:The median PFS was 26.6 months(range,1.4–69.5).Stratified by age,median PFS was 26.9 months in patients<70 years and 26.2 months in those≥70 years(p=0.760).By PS,PFS was 26.9 months for PS 0–1 and 17.8 months for PS 2–3(p=0.099).ORR was 60.9%and DCR 93.5%;notably,all PS 2–3 patients achieved disease control.Hematologic toxicities were common,with neutropenia(80.4%)and leukopenia(86.7%)predominating,but grade≥3 anemia was rare(2.2%).Elderly patients experienced anemia more frequently,while overall toxicity remained manageable.Dose reductions occurred in 47.8%without loss of efficacy.Conclusions:In routine Japanese practice,palbociclib plus ET provided prolonged PFS and high disease control consistent with pivotal trials and international real-world evidence.Importantly,elderly patients tolerated treatment well,and selected PS 2–3 patients also derived clinical benefit.These findings indicate that neither age nor PS alone should preclude the use of palbociclib in carefully monitored real-world patients.
文摘Human epidermal growth factor receptor 2(HER-2)is a transmembrane receptor tyrosine kinase that is overexpressed in various solid tumors and is closely related to tumor invasion,metastasis,and poor prognosis.In recent years,the expression of HER-2 in colorectal cancer and its clinical significance have gradually attracted attention.This article reviews the expression of HER-2 in colorectal cancer,the clinicopathological characteristics of HER-2 positive colorectal cancer,the detection methods of HER-2,and the drug treatment targeting HER-2,to provide references for clinical diagnosis and treatment and research.
基金National Natural Science Foundations of China(No.81873318 and 82374474)the Medical and Nursing Combination Scientific Innovative Project of Shanghai University of Traditional Chinese Medicine(No.YYKC-2021-01-010)。
文摘Objective:Glucocorticoid-induced osteoporosis(GIOP)is a common complication of prolonged glucocorticoid therapy.Chlorogenic acid(CGA),a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex,has potential anti-osteoporotic activity.This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4(MLO-Y4)cells and explore the underlying molecular mechanisms.Methods:The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone(Dex).The micro-computed tomography,hematoxylin-eosin staining,silver nitrate staining,and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo.Then,network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP.After that,2',7'-dichlorofluorescein diacetate staining,flow cytometry,real-time quantitative reverse transcription polymerase chain reaction,and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro.Results:Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice.The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase(ERBB2),which is also known as human epidermal growth factor receptor 2(HER2),caspase-3,kinase insert domain receptor,matrix metallopeptidase 9,matrix metallopeptidase 2,proto-oncogene tyrosine-protein kinase Src,and epidermal growth factor receptor as core targets.The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways(P<0.05),including the ERBB,phosphoinositide 3 kinase-AKT serine/threonine kinase 1(AKT),and mechanistic target of rapamycin kinase(mTOR)pathways.Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex,which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway.Conclusion:CGA exerted anti-osteoporotic effects against GIOP,partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway.
文摘BACKGROUND Colorectal cancer(CRC)is a leading cause of cancer-related mortality worldwide.In cases of metastatic CRC(mCRC)that are resistant to conventional chemo-therapy-based treatments,the efficacy of available therapeutic options is typically low.CRC exhibiting overexpression or amplification of the human epidermal growth factor receptor 2(HER2)gene has shown responsiveness to HER2-targeted therapies.CASE SUMMARY We present the case of a 69-year-old woman diagnosed with mCRC with an NRAS p.G12V mutation and microsatellite stability,identified through tumor sequencing,along with HER2 overexpression detected by immunohistochemistry.She exhibited an excellent response to disitamab vedotin-containing therapy.To our knowledge,this is the first reported case of mCRC with HER2 overexpression and an NRAS p.G12V mutation achieving a remarkable clinical response to anti-HER2 therapy.CONCLUSION Disitamab vedotin demonstrates promising anti-tumor effects in HER2-overex-pressing mCRC,offering patients an additional treatment option.
基金supported by the Yunnan Fundamental Research Projects,China(Grant No.202201AS070068)Central Funds Guiding the Local Science and Technology Development,China(202207AB110017)+1 种基金The Science and Technology Fund of Kunming City,China(No.2019-1-N-25318000002027)The Scientific and Technological Innovation Team in Kunming Medical University,China(CXTD202215).
文摘Background:Chimeric antigen receptor T(CAR-T)cell therapies have demonstrated significant clinical efficacy in hematological malignancies.However,their application to solid tumors remains substantially limited by multiple challenges,including the risk of off-target effects.Hence,optimizing CAR-T cells for stronger antigen binding is essential.Methods:In this study,we employed a classical anti-human endothelial growth factor receptor 2(HER2)single-chain variable fragment(scFv)derived from trastuzumab,alongside an anti-HER2-13 scFv identified from a combinatorial cellular CAR library,for the construction of a third-generation CAR-T cell.Meanwhile,the phenotypes and both in vitro and in vivo functions of CAR-T cells transduced with the two scFvs via PiggyBac transposon-mediated gene transfer were compared.Results:The optimal ratio between the PiggyBac HER2-CAR-puro transposon and the Super PiggyBac transposase plasmid differed during the construction of the two HER2-targeted CAR-T cell types.The expansion abilities,CD3^(+)CAR^(+)population,CD4^(+)CAR^(+)/CD8^(+)CAR^(+)proportions,and memory and exhaustion markers between the two CAR-T groups were similar after using the optimized proportion of plasmid.Both CAR-T cell types exhibited significant antitumor activity,with the anti-HER2-13 CAR-T cells demonstrating superior target specificity.Therapeutic effects were observed with both CAR-T cells and trastuzumab in theMDA-MB-231HER2+breast tumor xenograft model,with anti-HER2-13 CAR-T cells demonstrating slightly enhanced efficacy and no evident offtarget toxicity.Conclusion:These results highlight the potential of anti-HER2-13 CAR-T cells to serve as a safer and more efficacious alternative in HER2-targeted therapy.
基金Supported by the Jiangsu Provincial Health and Family Planning Commission Personnel Talent Project,No.R2017005.
文摘BACKGROUND Although targeted therapy provides survival benefits for patients with metastatic colorectal cancer,some patients develop resistance to these treatments.Human epidermal growth factor receptor 2(HER2)is overexpressed in a subset of pa-tients with colorectal cancer and has been established as a therapeutic target.CASE SUMMARY This case report describes a Chinese patient with HER2-amplified advanced rectal cancer who showed no response to chemotherapy and targeted therapies against epidermal growth factor receptor and vascular endothelial growth factor but achieved a remarkable response following treatment with immune checkpoint inhibitors(ICIs)in combination with pyrotinib.The combination of oxaliplatin and ICIs with pyrotinib demonstrates synergistic effects after late-stage disease progression.CONCLUSION ICIs and pyrotinib may be effective in treating HER2-amplified advanced rectal cancer.Chemotherapy following disease progression could enhance efficacy synergistically.
基金Supported by Scientific Research Project of Health Commission of Guangxi Zhuang Autonomous Region,No.Z-A20240546Undergraduate Education and Teaching Reform Project of Guangxi Medical University,No.2025XJGYC38and Key Textbook Construction Project of Guangxi Medical University,No.Gxmuzdjc2417。
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2)plays pivotal roles in cellular proliferation,survival,and differentiation of several malignancies.Upper tract urothelial carcinoma(UTUC)is a relatively rare malignancy.The clinical and molecular significance of HER2 expression level in UTUC remains poorly characterized vs bladder cancer.AIM To comprehensively evaluate HER2 expression patterns and their association with UTUC patients’clinicopathological features.METHODS Data were retrospectively collected from patients diagnosed with UTUC at The First Affiliated Hospital of Guangxi Medical University between January 2023 and December 2024.HER2 status was evaluated by immunohistochemistry in 145 UTUC patients who met the inclusion criteria.Its associations with tumor grade,tumor stage,and other clinicopathological parameters were assessed.Theχ2 test or Fisher’s exact test,along with univariate and multivariate logistic regression analyses,were performed to determine the influences of clinicopathological factors on HER2 expression.RESULTS HER2 positivity was significantly associated with high tumor grade(P=0.003),while other variables,including sex,anatomical tumor location,pathological T stage,Ki-67 proliferation index,nodal metastasis status,lymphovascular invasion,and tumor laterality failed to demonstrate statistically significant correlations.These findings were further substantiated through univariate logistic regression modeling,yielding an odds ratio of 3.56[95%confidence interval(CI):1.30-9.75;P=0.013]for the association between high tumor grade and HER2 positivity.Importantly,this relationship remained robust(hazard ratio=3.42,95%CI:1.22-9.60;P=0.019)even after implementing multivariate logistic regression analysis.With a median follow-up time of 8 months(interquartile range,4-14)months,14 patients experienced intravesical recurrence after radical nephroureterectomy.Certain patient characteristics,such as HER2-negative,male sex,high-grade tumors,and luminal phenotype,were associated with a higher risk of intravesical recurrence.CONCLUSION In UTUC,HER2 overexpression is closely associated with tumor dedifferentiation(high grade),while it does not correlate with conventional indicators of disease progression,indicating that HER2 may serve a distinct biological function in this cancer type.
基金Supported by CAMS Innovation Fund for Medical Sciences CIFMS,No.2023-I2M-3-012.
文摘BACKGROUND Human epidermal growth factor receptor 2(HER2)-positive gastric cancer(GC)represents a distinct molecular cancer subtype that is often associated with a poor prognosis.While perioperative chemotherapy regimens are currently the primary recommendation for locally advanced HER2-positive GC,combination therapies incorporating immune checkpoint inhibitors are under active investigation.CASE SUMMARY The present case describes a patient with locally advanced HER2-positive GC who underwent perioperative treatment with chemotherapy combined with trastuzumab.Although significant tumor shrinkage was observed,surgical pathology results did not confirm the achievement of a pathological complete response.The current treatment strategies for advanced GC were also reviewed.Relevant case reports,retrospective studies,and prospective clinical trials were retrieved for analysis after searching the PubMed/MEDLINE,EMBASE,Cochrane Library,Web of Science,and American Society of Clinical Oncology/European Society for Medical Oncology conference abstracts between 2014 and 2024.CONCLUSION Large-scale phase Ⅲ clinical trials are needed to verify the efficacy of combined neoadjuvant treatment application for GC.
基金supported in part by the e-ASIA Joint Research Program from the Japan Agency for Medical Research and Development(AMED)(grant number:21jm0210062h0004).
文摘Cholangiocarcinoma(CCA)is a fatal bile duct malignancy.CCA is intrinsically resistant to standard chemotherapy,responds poorly to it,and has a poor prognosis.Effective treatments for cholangiocarcinoma remain elusive,and a breakthrough in CCA treatment is still awaited.The human epidermal growth factor receptor 2(HER2)plays an oncogenic role by promoting an aggressive cancer phenotype through multiple pathways.While HER2 has shown increasing potential as an effective target for breast and gastric cancers over the last decade,this has not been the case for CCA.This review explores the possibility of targeting HER2 in CCA immunotherapy.Key findings suggest that HER2 alterations have been reported as one of the signatures associated with a poorer prognosis in liver fluke-associated CCA,the most prevalent subtype in Southeast Asia.Furthermore,we assess recent advances in HER2-targeted therapeutic approaches,presenting the current stage,rationale,and evidence supporting the use of HER2 as a promising therapeutic target for cancer immunotherapy in CCA.We also emphasize the crucial role of animal models in developing anticancer therapies.In summary,focusing on HER2 expression could provide alternative strategies for the HER2-altered CCA cluster.
基金supported by China Postdoctoral Science Foundation(No.2022M721987)Natural Science Foundation of Shandong Province(No.ZR2024QH058).
文摘The latest data from the NATALEE trial showed the absolute 3-year invasive disease-free survival benefit was 4.9%between the experimental and control groups.That is to say,in the intermediate-risk hormone receptor positive/human epidermal growth factor receptor-2 negative subgroup,there are also some patients with primary resistance to ribociclib.These patients benefit less from ribociclib,and they are unable to gain significant benefit even with the intensive adjuvant therapy of ribociclib.Considering the drug toxicity and health economic benefits,a 3-year course of ribociclib may not be appropriate for all intermediate-risk populations.Therefore,how to screen out the prime population for intensive adjuvant therapy of ribociclib needs to worth explored.In this paper,we discussed that the adaptive neoadjuvant endocrine therapy can screen out the prime population for intensive adjuvant therapy of ribociclib.
基金This study was approved by the ethics committee of the First People’s Hospital of Fuzhou City(No.FZ202103).
文摘BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,with its incidence and mortality rates ranking among the highest in gastrointestinal cancers.The overexpression or gene amplification of human epidermal growth factor receptor 2(HER-2)occurs in approximately 15%-20%of gastric cancers and serves as a critical molecular target influencing prognosis and treatment out-comes.For patients with HER-2-positive gastric cancer,trastuzumab combined with platinum-based chemotherapy has been established as the standard first-line treatment.However,despite the demonstrated clinical benefits in prolonging survival,the overall efficacy remains limited.In recent years,with the successful application of immune checkpoint inhibitors(ICIs)in various malignant tumors,combining ICIs with existing standard treatment regimens has emerged as a promising approach to enhance the therapeutic efficacy of HER-2-positive gastric cancer.Nevertheless,the efficacy and prognostic factors of ICIs combined with trastuzumab and chemotherapy in HER-2-positive gastric cancer remain unclear.AIM To analyze the efficacy of ICIs combined with standard treatment regimens and the prognostic factors in patients with advanced HER-2-positive gastric cancer.METHODS Clinical data from 104 patients with advanced HER-2-positive gastric cancer who were treated at our hospital between March 2021 and May 2023 were retrospectively analyzed.Patients were divided into a control group(n=54,treated with trastuzumab combined with platinum-based chemotherapy as the standard regimen)and an observation group(n=50,treated with ICIs in addition to the standard regimen).The therapeutic efficacy,survival outcomes,and adverse reactions were compared between the two groups.Univariate and Cox multivariate analyses were performed to identify factors influencing patient prognosis.RESULTS With a median follow-up time of 14.6 months,there were no significant differences between the two groups in terms of objective response rate or disease control rate(P>0.05).The median progression-free survival(mPFS)and mPFS for patients with immunohistochemistry 3+in the observation group were significantly higher than those in the control group(P<0.05).Among patients in the observation group,those with positive programmed death-ligand 1(PD-L1)expression had a significantly higher mPFS than those with negative PD-L1 expression(P<0.05).Regarding adverse events,significant differences were observed between the two groups in hypothyroidism and neutropenia(P<0.05).Cox multivariate analysis showed that Eastern Cooperative Oncology Group(ECOG)performance status,peritoneal metastasis,positive programmed death-1 expression,and treatment regimen were independent factors influencing PFS(hazard ratio>1,P<0.05).CONCLUSION ICIs combined with standard treatment regimens for patients with advanced HER-2-positive gastric cancer demonstrate favorable clinical efficacy,significantly prolonging PFS with manageable safety.ECOG performance status,peritoneal metastasis,positive PD-L1 expression,and treatment regimen are independent factors influ-encing PFS,warranting increased clinical attention to patients exhibiting these factors.
基金supported by the Science and Technology Council,Taiwan,China(NSTC 112-2320-B-039-057 and MOST 111-2320-B-039-067-MY3)the China Medical University,Taiwan,China(CMU112-S-18),awarded to Yuan-Soon Ho+1 种基金the China Medical University,Taiwan,China(CMU112-N-02),awarded to Li-Ching Chenthe Science and Technology Council,Taiwan,China(MOST 110-2320B-039-079)。
文摘This study presents novel findings on the potential of phloretin,an apple polyphenol,to enhance the effectiveness of anti-human epidermal growth factor receptor-2(HER2)antibody therapy in HER2-positive breast cancer patients.Our research reveals that phloretin inhibits typeⅡglucose transporter(GLUT2)activity,significantly reducing cancer cell glucose uptake.We confirmed the overexpression of GLUT1 and GLUT2 mRNA in paired human breast tumor tissues,with GLUT2 overexpression associated explicitly with poorer survival rates in breast cancer patients.Treatment with phloretin was observed to increase the interaction between GLUT2 and HER2 proteins,attenuate glycolysis,and enhance the binding affinity of anti-HER2 antibody drugs to target human breast cancer cells.Furthermore,the efficacy of the combination therapy involving phloretin and antibody drugs was reaffirmed in a cell-derived xenograft tumor animal model,particularly in suppressing the growth of trastuzumab-resistant HER2-positive(HER2+)breast cancer.These significant findings suggest that targeting GLUT2 activity with phloretin in combination with anti-HER2 antibody drugs may help mitigate the development of drug-resistant breast cancer,offering valuable insights for enhancing tumor treatment strategies and contributing to developing more effective therapies.
文摘BACKGROUND Gastric signet ring cell carcinoma(SRCC)is a rare,aggressive subtype of gastric cancer characterized by poor prognosis and distinctive biological behavior.Despite advances in gastric cancer treatment,SRCC remains difficult to diagnose early and manage effectively due to its infiltrative pattern and molecular variability.Reliable prognostic markers are critical to guide clinical management.AIM To investigate the prognostic factors,including human epidermal growth factor receptor 2(HER2)expression,associated with survival outcomes in patients with gastric SRCC.METHODS A retrospective analysis of 100 cases diagnosed between 2015 and 2019 was conducted,assessing demographic,clinical,and pathological data.HER2 expression was analyzed using immunohistochemistry,and survival outcomes,including overall survival and disease-free survival,were examined.RESULTS With a median follow-up of 43 months,the median patient age was 50 years,and males exhibited a higher mortality rate(P=0.0107).Elevated serum carbohydrate antigen 19-9 and carcinoembryonic antigen levels were significantly associated with increased mortality(P=0.00149 and P=0.00163,respectively).Advanced tumornode-metastasis stage and lymphovascular invasion were strong predictors of poor outcomes(P<0.001 and P=0.019).HER2 positivity correlated with higher mortality(P=0.00882)but was not significantly linked to recurrence(P=0.53).Surgical treatment significantly improved survival compared with non-surgical approaches(P=0.0226).CONCLUSION These findings highlight the aggressive nature of SRCC with advanced disease stage,elevated tumor markers,and lymphovascular invasion contributing to poor outcomes.HER2 expression,though infrequent,may indicate worse prognosis,reinforcing the role of surgical intervention in survival improvement.
文摘BACKGROUND Over 150000 new diagnoses of colorectal cancer(CRC)are diagnosed yearly,and 1 in 5 patients have distant metastases on diagnosis.Previous estimates approximate that brain metastases(BM)occur in 0.6%to 3.2%of patients with CRC.AIM To describe the updated literature about the incidence and risk factors of BM in CRC as well as their treatment with surgery,chemotherapy,and radiation.METHODS We systematically searched the literature published between January 1,2010 and April 1,2025 in PubMed,Cochrane,Scopus,and EMBASE.All studies about BM from CRC were included.Studies only containing information about the treatment of primary CRC or primary brain tumors were not included.Articles were categorized and described as incidence,surgery,chemotherapy,or radiation to provide an overview of the state of research on BM from CRC.RESULTS Our primary search resulted in 1648 articles that were eventually screened to 147.These articles were analyzed to provide the state of current literature on incidence and risk factors of BM from CRC as well as how these metastases are treated with chemotherapy,radiation,and surgery.CONCLUSION Prognosis is influenced by tumor burden,performance status,and emerging molecular markers.Stereotactic radiotherapy and surgical resection provide favorable outcomes for select patients,whereas chemotherapy and immunotherapy remain areas of limited evidence.Continued research is needed to identify highrisk patients and optimize multidisciplinary treatment approaches.
基金funded by the Belarusian Republican Foundation for Fundamental Research(BRFFR project X22MC-030,chemical synthesis)the Russian Science Foundation(grant number 24-15-00273,in vitro investigation of HSP90 signaling).
文摘Background:The most aggressive forms of breast cancer are characterized by independence from steroid hormones but a strong dependence on growth factors.In such cancer cells,oncogenic receptors,including human epidermal growth factor receptor 2(HER2),are activated,and their targeted inhibition represents an attractive therapeutic strategy.The study aimed to develop small-molecule potential dual heat shock protein 90(HSP90)-HER2 inhibitors and evaluate them as anticancer agents in HER2-positive cells.Methods:The research project involved obtaining a series of compounds with potential dual inhibitory activity against HSP90 and HER2 by targeted organic synthesis,which was preliminarily assessed using molecular modelling and calculation of key parameters of molecular dynamics.The potential therapeutic benefit of the obtained molecules was studied using basic molecular biological methods,including assessment of cytotoxic activity in vitro using the MTT test,as well as determination of a possible mechanism of action based on the expression of key participants in intracellular signaling(western blotting).Additionally,therapeutic combinations were developed and tested on a cellularmodel of the disease,including a lead compound and chemotherapeutic drugs used in clinical practice,in order to find synergistic pairs and improve the effectiveness of the treatment.Results:In this work,novel dual HSP90-HER2 inhibitors,based on the fused thiazole-dihydrobenzisoxazole polycyclic scaffold,were designed and synthesized.The resulting compounds exhibited strong antiproliferative activity against HER2-positive breast cancer cells with high selectivity.Among them,ATF-2 demonstrated antiproliferative activity comparable to HER2 inhibitor lapatinib and significantly suppressed HER2 expression and activity,epidermal growth factor receptor(EGFR)activity,and cyclin-dependent kinase 6(CDK6)expression in HCC1954 breast cancer cells.Conclusion:These findings highlight ATF-2 as a promising dual HSP90-HER2 inhibitor with broader inhibitory effects on the HER2,EGFR,and CDK6 pathways.
基金the National Natural Science Foundation of China (30000191), China Postdoctoral Science Foundation (1999- 17) and S
文摘Objective To evaluate the effects of transforming growth factor β(TGF-β) and recombinant human bone morphogenetic protein 2 (rhBMP2) on human periodontal ligament fibroblasts (HPDLFs). Methods HPDLFs were done primary culture to detect the distinct concentrations of TGF-P and rhBMF2 on its proliferation, alkaline phosphatase (ALP) activity, osteocalcin (OC) synthesis and formation of the minerali-zed nodules, respectively. Results TGF-β (5～100ng/ml) significantly stimulated the proliferation of HPDLFs. The ALP activity of HPDLFs was evaluated evidently by 5ng/ml TGF-β. TGF-β( 0. 5 ～ 100ng/ml) had no effects on OC synthesis and formation of the mineralized nodules of HPDLFs. rhBMP2 (0. 25～2mg/ ml) had no remarkable effect on the proliferation of HPDLFs. The ALP activity, OC synthesis and forma-tion of the mineralized nodules of HPDLFs were significantly stimulated by 0. 5～ 2mg /ml rhBMP2. Conclusion The effects of TGF-β and rhBMP2 on HPDLFs are dose-dependent. TGF-P can stimulate HPDLFs to express the early marker of osteoblastic phenotype, and it lacks the ability to promote maturation of the osteogenic phenotype. rhBMP2 can not only stimulate the expression but also promote the maturation of osteoblas-tic phenotype of HPDLFs.
基金This work was supported by a grant from the National Natural Science Foundation of China(No. 30070809).
文摘Objective： To investigate the expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and its significance for establishing a solid foundation for further study of the relationship between human laryngeal squamous cell carcinoma and K-ras gene point mutations. Methods： The expression of K-ras in human laryngeal squamous cell carcinoma cell lines （Hep-2） and human pancreatic carcinoma cell lines （MIAPaCa-2） was detected by using RT-PCR. Results： The expression of K-ras mRNA in Hep-2 and MIAPaCa-2 was strong and positive. Conclusion： The expression of K-ras mRNA in human laryngeal squamous cell carcinoma cell lines （Hep-2） is positive. Development of laryngeal carcinoma might be related to the activation of K-ras gene point mutation.
基金the National Natural Science Foundation of China(No.51471182)this work is also supported by Shanghai international science and Technology Cooperation Fund(No.17520711700)the National Key Research and Development Project(No.2017YFB0310600).
文摘The current COVID-19 pandemic urges the extremely sensitive and prompt detection of SARS-CoV-2 virus.Here,we present a Human Angiotensin-converting-enzyme 2(ACE2)-functionalized gold“virus traps”nanostructure as an extremely sensitive SERS biosensor,to selectively capture and rapidly detect S-protein expressed coronavirus,such as the current SARS-CoV-2 in the contaminated water,down to the single-virus level.Such a SERS sensor features extraordinary 106-fold virus enrichment originating from high-affinity of ACE2 with S protein as well as“virus-traps”composed of oblique gold nanoneedles,and 109-fold enhancement of Raman signals originating from multi-component SERS effects.Furthermore,the identification standard of virus signals is established by machine-learning and identification techniques,resulting in an especially low detection limit of 80 copies mL^(−1) for the simulated contaminated water by SARS-CoV-2 virus with complex circumstance as short as 5 min,which is of great significance for achieving real-time monitoring and early warning of coronavirus.Moreover,here-developed method can be used to establish the identification standard for future unknown coronavirus,and immediately enable extremely sensitive and rapid detection of novel virus.
文摘AIM: To clarify the mechanism underlying the anti-mutagenic and anti-cancer activities of Scorpio water extract (SWE). METHODS: Human hepatoma HepG2 cells were incubated with various concentrations of SWE. After 24-h incubation, cytotoxicity and apoptosis evaluations were determined by MTT and DNA fragmentation assay, respectively. After treatment with SWE, mitochondrial membrane potential (MMP) was determined by measuring the retention of the dye 3,3'-dihexyloxacarbocyanine (DiOC6(3)) and the protein expression including cytochrome C and poly-(ADPribose) polymerase (PARP) were measured by Western blotting. Caspase-3 and -9 enzyme activities were measured using specific fluorescence dyes such as Ac-DEVD-AFC and Ac-LEHD-AFC. RESULTS: We found that treatment with SWE induced apoptosis as confirmed by discontinuous DNA fragmentation in cultured human hepatoma HepG2 cells. Our investigation also showed that SWE-induced apoptosis of HepG2 cells were associated with intracellular events including disruption of MMP, increased translocation of cytochrome C from mitochondria to cytosol, activation of caspase-3, and PARP. Pre-treatment of N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), a caspase-3 specific inhibitor, or cyclosporin A (CsA), an inhibitor of MMP disruption, completely abolished SWE-induced DNA fragmentation. CONCLUSION: These results suggest that SWE possibly causes mitochondrial damage, leading to cytochrome C release into cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic cell death in HepG2 cells. These results further suggest that Scorpio may be a valuable agent of therapeutic intervention of human hepatomas.
