BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.Howeve...BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.展开更多
目的:使用前列腺影像报告和数据系统(prostate imaging reporting and data system,PI-RADS)和中性粒细胞校正前列腺特异性抗原(prostate-specific antigen,PSA)相关指标,评估其在前列腺癌中的诊断潜力,并探讨它们在前列腺免穿刺活检中...目的:使用前列腺影像报告和数据系统(prostate imaging reporting and data system,PI-RADS)和中性粒细胞校正前列腺特异性抗原(prostate-specific antigen,PSA)相关指标,评估其在前列腺癌中的诊断潜力,并探讨它们在前列腺免穿刺活检中的潜在应用价值。方法:收集2018年1月—2023年1月陕西省人民医院收治的546例总前列腺特异性抗原(total prostate-specific antigen,tPSA)>4 ng/mL或直肠指检和经直肠前列腺穿刺活检发现异常的患者的临床资料,单因素、多因素及受试者操作特征(receiver operating characteristic,ROC)曲线分析年龄、tPSA、前列腺体积(prostate volume,PV)、中性粒细胞计数(neutrophil count,NC)、PI-RADS及对tPSA进行校正后得到的4个变量:前列腺特异性抗原密度(prostate-specific antigen density,PSAD)、tPSA-中性粒细胞比值(tPSA to neutrophil ratio,PNR)、PSAD-中性粒细胞比值(PSAD to neutrophil ratio,PDNR)、PSAD联合PI-RADS-中性粒细胞比值(PSAD combined with PI-RADS to neutrophil ratio,PDPNR)对前列腺癌的诊断价值,并分析它们在前列腺免穿刺活检中的价值。结果:tPSA通过PV、NC和PI-RADS评分的校正提高了对前列腺癌的诊断价值(PDPNR>PDNR>PSAD>PNR>tPSA)。此外,当阴性预测值到达100%时,tPSA的特异度仅为0.75%,PDNR的特异度最高,为22.39%。当阳性预测值到达100%时,tPSA的特异度仅为13.79%,PDPNR的灵敏度最高,为29.31%。结论:校正的tPSA变量提高了前列腺癌的诊断性能,减少了不必要的穿刺和患者负担(心理负担、穿刺疼痛和经济负担),为进一步的前瞻性研究提供了理论依据。展开更多
Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is uncl...Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.展开更多
Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironm...Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.展开更多
Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated signi...Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.展开更多
Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is cha...Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).展开更多
Highlights By conjugating the same anti-N monoclonal antibody(mAb4-mAb1)with colloidal gold or fluorescent microspheres,this study developed two rapid point-of-care antigen immunochromatographic strips for the detecti...Highlights By conjugating the same anti-N monoclonal antibody(mAb4-mAb1)with colloidal gold or fluorescent microspheres,this study developed two rapid point-of-care antigen immunochromatographic strips for the detection of porcine deltacoronavirus.The fluorescent microsphere-based lateral flow test strip demonstrated a sensitivity of 10^(1.7)TCID_(50)/0.1 mL,which is fourfold higher than that of the colloidal gold-based assay.Porcine deltacoronavirus(PDCoV)is a recently identified enteric coronavirus that causes an acute infectious disease in piglets,leading to diarrhea,vomiting,dehydration,and mortality(Hu et al.2015).展开更多
宫颈癌是严重威胁女性健康的恶性肿瘤,其发生与高危型人乳头瘤病毒(high-risk human papilloma virus,HR-HPV)持续感染密切相关。现行以细胞学和HPV检测为主的筛查策略虽降低了宫颈癌负担,但HR-HPV检测特异度不高导致大量一过性感染者...宫颈癌是严重威胁女性健康的恶性肿瘤,其发生与高危型人乳头瘤病毒(high-risk human papilloma virus,HR-HPV)持续感染密切相关。现行以细胞学和HPV检测为主的筛查策略虽降低了宫颈癌负担,但HR-HPV检测特异度不高导致大量一过性感染者接受了不必要的阴道镜转诊,成为临床实践的难题。p16/Ki-67双染色技术通过免疫细胞化学方法同步检测p16^(INK4a)与Ki-67蛋白共表达,可客观标识HR-HPV驱动的细胞转化状态,为HR-HPV阳性人群的分流管理提供了优质解决方案。大量证据表明,对于高级别宫颈上皮内瘤变(CIN2+)检测,双染色技术不仅敏感度可达90%以上,其特异度(约70%~85%)更显著优于细胞学分流,可减少约30%~50%的阴道镜转诊,且其阴性预测值(>97%)支持对阴性人群延长随访间隔,优化了筛查效率。p16/Ki-67双染色技术通过精准风险分层,在保障病变检出率的同时显著减少过度诊疗,已成为宫颈癌筛查策略优化中循证依据最充分的分流工具之一。展开更多
AIM To evaluate the relationship between the expression of Ki 67 antigen and the pathobiological behaviours of gastric cancers especially their distant metastases. METHODS Fifty six specimens of gastric cancer ro...AIM To evaluate the relationship between the expression of Ki 67 antigen and the pathobiological behaviours of gastric cancers especially their distant metastases. METHODS Fifty six specimens of gastric cancer routinely fixed in formalin and embedded in paraffin (FFEP) were studied by immunohistochemical method. RESULTS Expression of Ki 67 antigen was significantly related to the distant metastases to liver, ovary and adrenal gland ( P <0 005), but not related to the histological type, growth pattern, depth of invasion, histological differentiation and the metastases to local lymph nodes ( P >0 05). Furthermore, the Ki 67 antigen expression was significantly related to the DNA aneuploidy pattern, which is closely related to poor prognosis ( P <0 05). CONCLUSION Overexpression of Ki 67 can be used as an objective marker of the proliferative activity for predicting prognosis of gastric cancer and metastatic potential to distant organs.展开更多
BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and sh...BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and should be consi- dered for palliative treatment such as chemotherapy and ra- diotherapy. Unfortunately, reports of chemotherapy and radiotherapy for gallbladder carcinoma are disappointing. We investigated the influence of norcantharidin (NCTD) on proliferation, proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human gallbladder carci- noma were cultured by the cell culture technique. The ex- periment was divided into NCTD group and control group. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The streptavidin-biotin complex method was used to determine the expressions of prolifera- tion-related gene proteins PCNA and Ki-67 of human gall- bladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a dose- and time-dependent manner, with the IC50 value of 56.18 μg/ ml at 48 hours. After treatment with NCTD, the expression of PCNA (0.932 ±0.031 vs. 0.318 ±0.023, P<0.001) and Ki-67 (0.964 ±0.092 vs. 0.297 ±0.018, P<0.001) proteins were decreased significantly. CONCLUSION: NCTD inhibits the proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the expres- sion of their proliferation-related gene proteins PCNA and Ki-67.展开更多
基金Supported by the National Science and Technology Research Center(Morocco)“PhD-Associate Scholarship-PASS”Program,No.88UH2C2023.
文摘BACKGROUND Donor-specific antibodies(DSAs)against human leukocyte antigen(HLA)-DQ are increasingly recognized as major contributors to antibody-mediated rejection(AMR)and graft failure in kidney transplantation.However,their clinical impact remains understudied in Morocco.AIM To evaluate the presence and implications of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.METHODS We retrospectively analyzed the immunological profiles and clinical outcomes of kidney transplant recipients screened for anti-HLA antibodies between 2015 and 2020,who developed anti-HLA-DQ DSAs either before or after transplantation.Anti-HLA antibodies were identified using Luminex®single antigen bead technology,and clinical follow-up included graft function assessment,biopsy interpretation,and evaluation of immunosuppression.RESULTS In the pre-transplant group(n=6 with confirmed donor typing),patients with low to moderate median fluorescence intensity(MFI)anti-HLA-DQ DSAs(MFI 561-1581)underwent successful transplantation and maintained stable graft function under optimized immunosuppression.In contrast,in the post-transplant group(n=6 with confirmed donor typing),the emergence of de novo anti-HLA-DQ DSAs was consistently associated with AMR,with MFI values reaching up to 19473,with biopsy-proven AMR in 5 of 6 cases and suspicion of AMR in 1 case.Two representative cases are detailed to illustrate the clinical impact of DQ DSAs:one patient developed high-level anti-DQB1*02 de novo DSA(MFI 12029)with persistent AMR after 5 years,while another developed anti-DQA1*05:01 de novo DSA after an early AMR episode but maintained stable graft function after 5 years(creatinine 1.48 mg/dL).CONCLUSION Our findings underscore the clinical significance of anti-HLA-DQ DSAs in Moroccan kidney transplant recipients.While preformed DSAs with low immunogenicity may permit successful transplantation,de novo DSAs strongly correlate with AMR.Proactive monitoring,including routine DSA screening and HLA-DQ typing,could improve graft outcomes by enabling early intervention and better donor selection.
文摘目的:使用前列腺影像报告和数据系统(prostate imaging reporting and data system,PI-RADS)和中性粒细胞校正前列腺特异性抗原(prostate-specific antigen,PSA)相关指标,评估其在前列腺癌中的诊断潜力,并探讨它们在前列腺免穿刺活检中的潜在应用价值。方法:收集2018年1月—2023年1月陕西省人民医院收治的546例总前列腺特异性抗原(total prostate-specific antigen,tPSA)>4 ng/mL或直肠指检和经直肠前列腺穿刺活检发现异常的患者的临床资料,单因素、多因素及受试者操作特征(receiver operating characteristic,ROC)曲线分析年龄、tPSA、前列腺体积(prostate volume,PV)、中性粒细胞计数(neutrophil count,NC)、PI-RADS及对tPSA进行校正后得到的4个变量:前列腺特异性抗原密度(prostate-specific antigen density,PSAD)、tPSA-中性粒细胞比值(tPSA to neutrophil ratio,PNR)、PSAD-中性粒细胞比值(PSAD to neutrophil ratio,PDNR)、PSAD联合PI-RADS-中性粒细胞比值(PSAD combined with PI-RADS to neutrophil ratio,PDPNR)对前列腺癌的诊断价值,并分析它们在前列腺免穿刺活检中的价值。结果:tPSA通过PV、NC和PI-RADS评分的校正提高了对前列腺癌的诊断价值(PDPNR>PDNR>PSAD>PNR>tPSA)。此外,当阴性预测值到达100%时,tPSA的特异度仅为0.75%,PDNR的特异度最高,为22.39%。当阳性预测值到达100%时,tPSA的特异度仅为13.79%,PDPNR的灵敏度最高,为29.31%。结论:校正的tPSA变量提高了前列腺癌的诊断性能,减少了不必要的穿刺和患者负担(心理负担、穿刺疼痛和经济负担),为进一步的前瞻性研究提供了理论依据。
文摘Objectives:B-cell maturation antigen(BCMA)-targeted antibody–drug conjugates(ADCs)have emerged as promising therapies for relapsed/refractory multiple myeloma(RRMM),but the overall efficacy and safety profile is unclear.This study aimed to synthesize the available evidence on the safety and efficacy of BCMA-ADCs in development for RRMM.Methods:A systematic search was conducted using six bibliographic databases and ClinicalTrials.gov up to November 2024.Studies were eligible if they were human clinical trials or animal studies evaluating BCMA-ADCs and reported efficacy and safety outcomes.Data extraction and quality assessments were conducted using validated tools,including ROBINS-I and SYRCLE’s risk of bias tool.Results:A total of 21 studies were included:16 clinical trials and five animal studies.Key findings included that belantamab mafodotin demonstrated variable but generally durable response rates(32%–85%)and a broad range of progression-free survival(PFS)(2.8–36.6 months),albeit with ocular toxicities in 51%–96%.Among newer candidates,MEDI2228 showed median PFS 5.1–6.6 months with 14%discontinuation for ocular symptoms,while AMG 224 had an overall response rate(ORR)of 23%(9/40)with anemia 21%,thrombocytopenia 24%,and ocular adverse events(AEs)21%.Animal studies supported the tumor-eradicating potential of all BCMA-ADC candidates,although safety signals such as hepatic and renal toxicity were noted with HDP-101.The risk of bias assessment revealed generally moderate to serious concerns in human trials,while the overall quality of the animal studies was acceptable.Conclusions:BCMA-targeted ADC candidates show encouraging efficacy in RRMM,particularly belantamab mafodotin.However,frequent AEs,especially ocular and hematologic toxicities,underscore the need for optimization in ADC design.Further research should prioritize enhancing safety while maintaining clinical benefit.
基金supported by the Kazan Federal University Strategic Academic Leadership Program(PRIORITY-2030).
文摘Classical Hodgkin lymphoma(cHL)is characterized by rare Hodgkin/Reed-Sternberg(HRS)tumor cells that uniformly express cluster of differentiation(CD)30 molecules and orchestrate an immunosuppressive tumor microenvironment,making CD30 an attractive and selective therapeutic target.We summarize the biological rationale for CD30 as a therapeutic target and the preclinical and clinical evidence across major platforms:antibody-drug conjugates(brentuximab vedotin),monoclonal antibodies(including acimtamig and its combinations with Natural Killer cells),second-and third-generation chimeric antigen receptor(CAR)-T cells,and alternative modalities.Particular attention is given to standardized response assessment(IWG,Lugano,RECIL criteria),which enables appropriate cross-trial comparisons.Taken together,the data indicate that beyond the established role of brentuximab vedotin,CD30-directed CAR-T cells and bispecific antibodies demonstrate high activity in refractory cHL,especially when used with fludarabine-containing lymphodepletion,combined with programmed cell death 1(PD-1)receptor blockade as a strategy to eradicate minimal residual disease.Key challenges include durable effector-cell persistence and optimization of sequencing and combinations;notably,loss of CD30 as an escape mechanism appears uncommon.Integrating mechanistic insights into HRS biology with clinical trial data highlights strategies to enhance the efficacy,safety,and accessibility of CD30-directed immunotherapy.This review aims to provide a concise overview of CD30-targeted approaches in cHL,emphasizing therapeutic outcomes and the evolution of CAR-T technologies.
文摘Prostate-specific membrane antigen(PSMA)is a surface membrane antigen that is highly overexpressed in prostate cancer,with heterogenous expression throughout the natural history of the disease.This has generated significant interest as a potential biomarker for use in early diagnosis and treatment of prostate cancer.We reviewed the literature surrounding PSMA and its current clinical applications in diagnosing and managing early prostate cancer that is confined to the prostate and local lymph nodes.A search on PubMed,Medline,and Web of Science was performed using the following keywords:“PSMA”,“Prostate Specific Membrane Antigen”,“Prostate cancer”,“Biomarker”,“Diagnosis”.We considered all available articles relevant to the topic of PSMA as a biomarker in early prostate cancer when developing this narrative review.Key articles assessing the biology of PSMA,as well as its use as a potential diagnostic and therapeutic target in early prostate cancer,were assessed.The role of PSMA PET as a potential diagnostic and risk stratification tool was assessed.The current use of antibody-drug conjugates and radioligand therapy targeting PSMA was assessed,along with any current evidence to support their use in early prostate cancer.PSMA is heavily expressed throughout the early stages of prostate cancer,and this has significant therapeutic implications.There is a growing body of evidence that shows PSMA PET can play a role in the diagnosis,risk stratification,and prognostication of localised prostate cancer.PSMA-targeted therapies such as Lu-177 currently do not have any proven benefit in treating early prostate cancer;however,this remains an area of ongoing research.
文摘Loss of immune tolerance to central nervous system(CNS)antigens lies at the heart of multiple sclerosis(MS),the most common chronic autoimmune disease of the CNS.MS affects nearly2 million people wo rldwide and is chara cterized by focal areas of demyelination,inflammation,axonal injury,and neurodegeneration(Bronge et al.,2022;Magliozzi et al.,2023).
基金financially supported by the National Key Research and Development Program of China(2021YFF0703600)。
文摘Highlights By conjugating the same anti-N monoclonal antibody(mAb4-mAb1)with colloidal gold or fluorescent microspheres,this study developed two rapid point-of-care antigen immunochromatographic strips for the detection of porcine deltacoronavirus.The fluorescent microsphere-based lateral flow test strip demonstrated a sensitivity of 10^(1.7)TCID_(50)/0.1 mL,which is fourfold higher than that of the colloidal gold-based assay.Porcine deltacoronavirus(PDCoV)is a recently identified enteric coronavirus that causes an acute infectious disease in piglets,leading to diarrhea,vomiting,dehydration,and mortality(Hu et al.2015).
文摘宫颈癌是严重威胁女性健康的恶性肿瘤,其发生与高危型人乳头瘤病毒(high-risk human papilloma virus,HR-HPV)持续感染密切相关。现行以细胞学和HPV检测为主的筛查策略虽降低了宫颈癌负担,但HR-HPV检测特异度不高导致大量一过性感染者接受了不必要的阴道镜转诊,成为临床实践的难题。p16/Ki-67双染色技术通过免疫细胞化学方法同步检测p16^(INK4a)与Ki-67蛋白共表达,可客观标识HR-HPV驱动的细胞转化状态,为HR-HPV阳性人群的分流管理提供了优质解决方案。大量证据表明,对于高级别宫颈上皮内瘤变(CIN2+)检测,双染色技术不仅敏感度可达90%以上,其特异度(约70%~85%)更显著优于细胞学分流,可减少约30%~50%的阴道镜转诊,且其阴性预测值(>97%)支持对阴性人群延长随访间隔,优化了筛查效率。p16/Ki-67双染色技术通过精准风险分层,在保障病变检出率的同时显著减少过度诊疗,已成为宫颈癌筛查策略优化中循证依据最充分的分流工具之一。
文摘AIM To evaluate the relationship between the expression of Ki 67 antigen and the pathobiological behaviours of gastric cancers especially their distant metastases. METHODS Fifty six specimens of gastric cancer routinely fixed in formalin and embedded in paraffin (FFEP) were studied by immunohistochemical method. RESULTS Expression of Ki 67 antigen was significantly related to the distant metastases to liver, ovary and adrenal gland ( P <0 005), but not related to the histological type, growth pattern, depth of invasion, histological differentiation and the metastases to local lymph nodes ( P >0 05). Furthermore, the Ki 67 antigen expression was significantly related to the DNA aneuploidy pattern, which is closely related to poor prognosis ( P <0 05). CONCLUSION Overexpression of Ki 67 can be used as an objective marker of the proliferative activity for predicting prognosis of gastric cancer and metastatic potential to distant organs.
文摘BACKGROUND: Gallbladder carcinoma is a highly lethal and aggressive disease with early metastasis, strong invasion and poor prognosis. Most patients with this disease are at the advanced and un-resectable stage and should be consi- dered for palliative treatment such as chemotherapy and ra- diotherapy. Unfortunately, reports of chemotherapy and radiotherapy for gallbladder carcinoma are disappointing. We investigated the influence of norcantharidin (NCTD) on proliferation, proliferation-related gene proteins PCNA and Ki-67 of human gallbladder carcinoma GBC-SD cells in vitro. METHODS: GBC-SD cell lines of human gallbladder carci- noma were cultured by the cell culture technique. The ex- periment was divided into NCTD group and control group. The tetrazolium-based colorimetric assay was used to evaluate cell growth. The streptavidin-biotin complex method was used to determine the expressions of prolifera- tion-related gene proteins PCNA and Ki-67 of human gall- bladder carcinoma GBC-SD cells. RESULTS: NCTD inhibited the growth and proliferation of GBC-SD cells from 10 mg/L or after 6 hours in a dose- and time-dependent manner, with the IC50 value of 56.18 μg/ ml at 48 hours. After treatment with NCTD, the expression of PCNA (0.932 ±0.031 vs. 0.318 ±0.023, P<0.001) and Ki-67 (0.964 ±0.092 vs. 0.297 ±0.018, P<0.001) proteins were decreased significantly. CONCLUSION: NCTD inhibits the proliferation of human gallbladder carcinoma GBC-SD cells in vitro and the expres- sion of their proliferation-related gene proteins PCNA and Ki-67.