Cyclin-dependent kinase inhibitor 2A/2B(CDKN2A/2B)deletions are frequently identified in patients with biliary tract cancer;however,standard treatment options for this genetic alteration are lacking.Here,we present th...Cyclin-dependent kinase inhibitor 2A/2B(CDKN2A/2B)deletions are frequently identified in patients with biliary tract cancer;however,standard treatment options for this genetic alteration are lacking.Here,we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery.Postoperative pathology confirmed moderately differentiated adenocarcinoma.The tumor recurred during the second cycle of adjuvant chemotherapy following surgery,and the metastatic sites included the cranial region,right lung,and right adrenal gland.Genetic analysis revealed a CDKN2A/2B deletion,indicating palbociclib sensitivity.Subsequently,the patient received palbociclib plus lenvatinib as systemic therapy,along with stereotactic radiotherapy for the intracranial lesion.Notably,the right pulmonary metastasis significantly regressed after 12 months of treatment,with the complete disappearance of the intracranial tumor.However,the disease progressed at 32.2 months,with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung.The progression-free survival and overall survival were 32.2 months and 34.4 months,respectively.In conclusion,our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.展开更多
Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,s...Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.展开更多
基金funded by the National High-Level Hospital Clinical Research Funding[2022-PUMCH-B-128]CAMS Innovation Fund for Medical Sciences([2022-I2M-C&T-A-003],[2021-I2M-1-061])+3 种基金CSCO-Hengrui Cancer Research Fund([Y-HR2019-0239])CSCO-MSD Cancer Research Fund[YMSDZD2021-0213]the National Ten-thousand Talent Program.LZ is supported by the National Natural Science Foundation of China(No.81960125)the Department of Science and Technology of Guizhou Province(No.Qiankehe Foundation[2020]1Y302).
文摘Cyclin-dependent kinase inhibitor 2A/2B(CDKN2A/2B)deletions are frequently identified in patients with biliary tract cancer;however,standard treatment options for this genetic alteration are lacking.Here,we present the case of a 64-year-old woman diagnosed with intrahepatic cholangiocarcinoma and hilar lymph node metastasis who underwent radical surgery.Postoperative pathology confirmed moderately differentiated adenocarcinoma.The tumor recurred during the second cycle of adjuvant chemotherapy following surgery,and the metastatic sites included the cranial region,right lung,and right adrenal gland.Genetic analysis revealed a CDKN2A/2B deletion,indicating palbociclib sensitivity.Subsequently,the patient received palbociclib plus lenvatinib as systemic therapy,along with stereotactic radiotherapy for the intracranial lesion.Notably,the right pulmonary metastasis significantly regressed after 12 months of treatment,with the complete disappearance of the intracranial tumor.However,the disease progressed at 32.2 months,with significant enlargement of the right adrenal gland metastasis and new metastasis in the right lung.The progression-free survival and overall survival were 32.2 months and 34.4 months,respectively.In conclusion,our case demonstrates that palbociclib plus lenvatinib is a promising chemotherapy-free second-line treatment for intrahepatic cholangiocarcinoma with a CDKN2A/2B deletion.
基金supported by the National Key R&D Program of China(No.2020YFA0908004)the National Natural Science Foundation of China(Nos.82293684,82293680,82273936,82273929)+1 种基金CAMS Innovation Fund for Medical Science(No.2021-I2M-1-028,2022-I2M-2-002,2022-I2M-1-014,China)Natural Science Fund for Distinguished Young Scholars of Tianjin(No.21JCJQJC00020,China)。
文摘Tolerogenic dendritic cells(tol DCs)facilitate the suppression of autoimmune responses by differentiating regulatory T cells(Treg).The dysfunction of immunotolerance results in the development of autoimmune diseases,such as rheumatoid arthritis(RA).As multipotent progenitor cells,mesenchymal stem cells(MSCs),can regulate dendritic cells(DCs)to restore their immunosuppressive function and prevent disease development.However,the underlying mechanisms of MSCs in regulating DCs still need to be better defined.Simultaneously,the delivery system for MSCs also influences their function.Herein,MSCs are encapsulated in alginate hydrogel to improve cell survival and retention in situ,maximizing efficacy in vivo.The three-dimensional co-culture of encapsulated MSCs with DCs demonstrates that MSCs can inhibit the maturation of DCs and the secretion of pro-inflammatory cytokines.In the collagen-induced arthritis(CIA)mice model,alginate hydrogel encapsulated MSCs induce a significantly higher expression of CD39^(+)CD73^(+)on MSCs.These enzymes hydrolyze ATP to adenosine and activate A_(2A/2B)receptors on immature DCs,further promoting the phenotypic transformation of DCs to tol DCs and regulating naive T cells to Tregs.Therefore,encapsulated MSCs obviously alleviate the inflammatory response and prevent CIA progression.This finding clarifies the mechanism of MSCs-DCs crosstalk in eliciting the immunosuppression effect and provides insights into hydrogel-promoted stem cell therapy for autoimmune diseases.
文摘目的探讨应用聚乙二醇化干扰素α(Peg-ⅠFNα)联合利巴韦林(RBV)治疗基因1/6型慢性丙型肝炎(CHC)患者的临床疗效。方法随机将246例慢性丙型肝炎(CHC)患者分为观察组123例和对照组123例,分别接受Peg-ⅠFNα-2b 80μg或Peg-ⅠFNα-2a 180μg皮下注射,1次/w,两组均同时口服利巴韦林,治疗48 w,随访24 w。采用罗氏公司COBAS Taqman HCV实时定量PCR试剂检测血清HCV RNA,采用Abbott Real Time HCV Genotype Ⅱ试剂检测HCV基因型。结果观察组和对照组基线基因1型感染者分别为104例(84.6%)和108例(87.8%),基因6型感染者分别为19例(15.4%)和15例(12.2%,P>0.05),血清HCV RNA水平分别为(7.17±0.89) lg copies/ml和(7.19±0.88) lg copies/ml,白细胞计数分别为(6.6±1.3)×10~9/L和(6.6±1.5)×10~9/L,血小板计数分别为(154.1±21.1)×10~9/L和(157.2±19.2)×10~9/L,血清ALT水平分别为(83.4±26.3) U/L和(80.3±29.4)U/L,均无显著性相差(P>0.05);观察组快速病毒学应答率(RVR)、早期病毒学应答率(EVR)、治疗结束时病毒学应答率(ETVR)和持续病毒学应答率(SVR)分别为45.5%、82.1%、83.7%和85.4%,与对照组的43.1%、78.9%、79.7%和78.0%比,无显著性差异(P>0.05),两组停药后复发率分别为14.6%和22.0%,也无显著性相差(P>0.05);在治疗过程中,观察组与对照组发热(58.5%对61.0%)、肌肉酸痛(48.8%对51.2%)、乏力(41.5%对44.7%)、头痛(30.9%对34.1%)、厌食(25.2%对30.1%)、脱发(26.8%对30.9%)、失眠(20.3%对25.2%)、白细胞下降(27.6%对31.7%)、红细胞下降(23.6%对28.5%)、血小板下降(13.8%对17.9%)和血清T3/T4/TSH异常(8.9%对10.6%)等不良反应发生率比较,均无显著性差异(P>0.05)。结论应用Peg-ⅠFNα-2b或Peg-ⅠFNα-2a治疗基因1/6型CHC患者,疗效较好,且两种干扰素治疗效果相当,安全性较好,值得临床应用。
