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Extended survival with metastatic pancreatic cancer under fruquintinib treatment after failed chemotherapy:Two case reports

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World Journal of Clinical Cases 2024年第7期12卷 1296-1304页

作者： Dan Wu Qiong Wang Shuai yan xia Sun Ya Qin Ming Yuan Nan-Yao Wang xian-Ting Huang Department of Oncology Jiangyin People's HospitalWuxi 214400Jiangsu ProvinceChina

BACKGROUND Pancreatic cancer is a highly malignant *** decades of treatment progress,the current five-year survival rate for patients is still less than 10%.For later-line treatment,the treatment options are even more ***-angiogenic drugs can improve progression-free survival in patients with advanced pancreatic *** data show that fruquintinib might improve the prognosis of advanced pancreatic cancer by targeting angiogenesis and lymphopoiesis,improving the abnormal vascular structure,and modulating the tumour immune *** SUMMARY We present two cases of third-line fruquintinib monotherapy that brought an extraprolonged progress-free survival(PFS)of 10 *** 1 took adjuvant gemcitabine-based and first-line nab-paclitaxel-based chemotherapy and then used local radiotherapy combined with programmed cell death 1 receptor(PD-1).Each line lasted approximately 7 ***,the patient took third-line fruquintinib,which was followed by stable disease for 10 months,during which no additional adverse effect was *** patient later refused to take fruquintinib due to difficulty urinating and lower abdominal pain after the coronavirus disease 2019(COVID-19)*** patient died in February *** 2 also took two prior lines of chemotherapy and then local radiotherapy combined with *** confirmed disease progression,the patient experienced a continuous partial response after using fruquintinib monotherapy in the third *** the patient had COVID-19 in December 2022,fruquintinib was *** patient died in January 2023 due to disease *** Both cases achieved a PFS benefit from later-line single-agent fruquintinib *** its better safety profile,fruquintinib may be worth exploring and studying in more depth as a later-line treatment for pancreatic cancer patients.

关键词： Pancreatic cancer Anti-vascular endothelial growth factor receptor Fruquintinib Case report

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Cell division cyclin 25C knockdown inhibits hepatocellular carcinoma development by inducing endoplasmic reticulum stress

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World Journal of Gastroenterology 2024年第19期30卷 2564-2574页

作者： yan-Fei Li Fang-Yuan Zheng Xin-Yu Miao Hai-Long Liu Yao-Yao Zhang Nai-xia Chao Fa-Rong Mo School of Basic Medical Sciences Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Biological Molecular Medicine Research(Guangxi Medical University) Education Department of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Human Development and Disease Research(Guangxi Medical University) Education Department of Guangxi Zhuang Autonomous RegionNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Cell division cyclin 25C(CDC25C)is a protein that plays a critical role in the cell cycle,specifically in the transition from the G2 phase to the M *** research has shown that CDC25C could be a potential therapeutic target for cancers,particularly for hepatocellular carcinoma(HCC).However,the specific regulatory mechanisms underlying the role of CDC25C in HCC tumorigenesis and development remain incompletely *** To explore the impact of CDC25C on cell proliferation and apoptosis,as well as its regulatory mechanisms in HCC *** Hepa1-6 and B16 cells were transduced with a lentiviral vector containing shRNA interference sequences(LV-CDC25C shRNA)to knock down ***,a xenograft mouse model was established by subcutaneously injecting transduced Hepa1-6 cells into C57BL/6 mice to assess the effects of CDC25C knockdown on HCC development in *** proliferation and migration were evaluated using a Cell Counting Kit-8 cell proliferation assays and wound healing assays,*** expression of endoplasmic reticulum(ER)stress-related molecules(glucose-regulated protein 78,X-box binding protein-1,and C/EBP homologous protein)was measured in both cells and subcutaneous xenografts using quantitative real-time PCR(qRT-PCR)and western ***,apoptosis was investigated using flow cytometry,qRT-PCR,and western *** CDC25C was stably suppressed in Hepa1-6 and B16 cells through LV-CDC25C shRNA transduction.A xenograft model with CDC25C knockdown was successfully established and that downregulation of CDC25C expression significantly inhibited HCC growth in ***25C knockdown not only inhibited cell proliferation and migration but also significantly increased the ER stress response,ultimately promoting ER stress-induced apoptosis in HCC *** The regulatory mechanism of CDC25C in HCC development may involve the activation of ER stress and the ER stress-induced apoptosis signali

关键词： Cell division cyclin 25C Hepatocellular carcinoma Endoplasmic reticulum stress Proliferation Apoptosis

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Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish

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Zoological Research 2024年第2期45卷 355-366页

作者： Jing-Yi Jia Guang-Hui Chen Ting-Ting Shu Qi-Yong Lou xia Jin Jiang-yan He Wu-Han xiao Gang Zhai Zhan Yin College of Fisheries Huazhong Agriculture UniversityWuhanHubei 430070China State Key Laboratory of Freshwater Ecology and Biotechnology Institute of HydrobiologyChinese Academy of SciencesWuhanHubei 430072China College of Advanced Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China Hubei Key Laboratory of Three Gorges Project for Conservation of Fishes Chinese Sturgeon Research InstituteChina Three Gorges CorporationYichangHubei 443100China Hubei Hongshan Laboratory Huazhong Agriculture UniversityWuhanHubei 430070China Innovative Academy of Seed Design Chinese Academy of SciencesBeijing 100049China

Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in ***,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in *** this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)*** assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-*** androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis *** Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd ***,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally ***,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts.

关键词： Cyp17a1 Testosterone Androgen receptor De novo lipogenesis Fatty acid synthesis

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Si-Miao-Yong-An Decoction alleviates thromboangiitis obliterans by regulating miR-548j-5p/IL-17A signaling pathway

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Chinese Journal of Natural Medicines 2024年第6期22卷 541-553页

作者： CHU Chu SUN Shangwen ZHANG Zhen WU Qi LI Haoyang LIANG Gang MIAO Xiuming JIANG Haiqiang GAO yan ZHANG Yunhong WANG Bin LI xia Innovative Institute of Chinese Medicine and Pharmacy Shandong University of Traditional Chinese MedicineJinan 250355China National Key Laboratory for Innovation and Transformation of Luobing Theory The Key Laboratory of Cardiovascular Remod-eling and Function ResearchChinese Ministry of EducationChinese National Health Commission and Chinese Academy of Medical SciencesDepartment of CardiologyQilu Hospital of Shandong UniversityJinan 250012China School of Clinical and Basic Medical Sciences Shandong First Medical University&Shandong Academy of Medical SciencesJinan 271016China Affiliated Hospital of Shandong University of Traditional Chinese Medicine Jinan 250014China International Business School Tianjin Foreign Studies UniversityTianjin 300204China Institute of Pharmaceutical Research Shandong University of Traditional Chinese MedicineJinan 250355China

Thromboangiitis obliterans(TAO)is a rare,chronic,progressive,and segmental inflammatory disease characterized by a high rate of amputation,significantly compromising the quality of life of ***-Miao-Yong-An decoction(SMYA),a tradition-al prescription,exhibits anti-inflammatory,anti-thrombotic,and various other pharmacological ***,it was fully proved to be effective for TAO therapy,but the specific therapeutic effect of SMYA on TAO has been ***,deep unveiling the mechanism of SMYA in TAO for identifying clinical therapeutic targets is extremely *** this study,we observed elev-ated levels of IL-17A in the peripheral blood mononuclear cells(PBMCs)of TAO patients,whereas the expression of miR-548j-5p was significantly decreased.A negative correlation between the levels of miR-548j-5p and IL-17A was also *** vitro ex-periments showed that overexpression of miR-548j-5p led to a decrease in IL-17A levels,whereas downregulation of miR-548j-5p showed the opposite *** a dual luciferase assay,we confirmed that miR-548j-5p directly targets ***,serum containing SMYA effectively decreased IL-17A levels by increasing the expression of *** importantly,the results of in vivo tests indicated that SMYA mitigated the development of TAO by inhibiting IL-17A through the upregulation of miR-548j-5p in vascular *** conclusion,SMYA significantly enhances the expression of miR-548j-5p,thereby reducing the levels of the target gene IL-17A and alleviating *** research not only identifies novel targets and pathways for the clinical diagnosis and treatment of TAO but also advances the innovation in traditional Chinese medicine through the elucidation of the SMYA/miR-548j-5p/IL-17A regulatory axis in the pathogenesis of TAO.

关键词： Thromboangiitis obliterans IL-17A Inflammation miR-548j-5p Si-Miao-Yong-An Decoction

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Cholic acid mitigates osteoarthritis by inhibiting the NF-κB/PERK/ SIRT1 signaling pathway

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BIOCELL 2024年第7期48卷 1095-1104页

作者： JIAOE SHENG ZUMIN YI SANSHAN HE QINGCHAO WU xia HUANG GUOQING yan YUFANG Dai LINCHONG SU The Minda Hospital of Hubei Minzu University Hubei Provincial Key Laboratory of Occurrence and Intervention of Rheumatic DiseaseEnshi445000China The Obstetrics and Gynecology of Jianshi County Hospital of Traditional Chinese Medicine Enshi445300China

Introduction:Cholic acid(CA)is a natural steroid useful in treating chronic bronchitis and *** the other hand,its potential impact on osteoarthritis(OA)is ***:Using an in vitro and in vivo osteoarthritis model,we sought to assess the chondroprotective properties of ***:We employed the Cell Counting Kit-8 to measure the impact of CA on chondrocyte activity to assess the toxicity of the *** molecular biology experimental techniques were used to investigate potential signaling pathways that CA may use to prevent inﬂammation and give chondrocytes ***,how CA affects the OA model in Sprague-Dawley(SD)rats was ***:CA signiﬁcantly suppressed the up-regulation of the interleukin-1β(IL-1β),cyclooxygenase-2(COX-2),and matrix metalloproteinase 13(MMP-13)and the downregulation of aggrecan and type II collagen A1(COL2A)in chondrocytes treated tumor necrosis factor-alpha(TNF-α).Differentially expressed genes(DEG)enrichment revealed IL-17,TNF,chemokine,cytokine-cytokine receptor,toll-like receptor,and nucleotide oligomerization domain-like receptor were the primary signaling *** enriched DEGs included CXCL6,CCL20,MMP3,CXCL3,CXCL11,CCL5,CXCL10,MMP9,MMP13,and CXCL2;these DEGs are involved in inﬂammatory responses and their expression induced by TNF-αwas reversed by CA *** inhibits p65 nuclear translocation and inhibitory subunit kappa B alpha(IκBα)phosphorylation induced by TNF-α.Furthermore,CA attenuated protein expression of protein kinase RNA-like endoplasmic reticulum kinase(PERK),inositol-requiring transmembrane kinase/endoribonuclease 1α(IRE1α),glucose regulatory protein 78(GRP78),and sirtuin 1(SIRT1),and down-regulation of phosphorylation of AMP-activated protein kinase-α(p-AMPKα)in TNF-α-treated ***:CA signiﬁcantly ameliorated cartilage degradation in the OA rat *** alleviated the inﬂammatory response through the nuclear factor kappa B/PERK/SIRT1 axis and

关键词： Cholic acid Cartilage Inﬂammation RNA sequencing Differentially expressed genes

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Establishing VIGS and CRISPR/Cas9 techniques to verify RsPDS function in radish

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Journal of Integrative Agriculture 2024年第5期23卷 1557-1567页

作者： Jiali Ying yan Wang Liang Xu Tiaojiao Qin Kai xia Peng Zhang Yinbo Ma Keyun Zhang Lun Wang Junhui Dong Lianxue Fan Yuelin Zhu Liwang Liu National Key Laboratory of Crop Genetics&Germplasm Enhancement and Utilization/Key Laboratory of Horticultural Crop Biology and Genetic Improvement(East China)of Ministry of Agriculture and Rural Affairs/College of Horticulture Nanjing Agricultural UniversityNanjing210095China College of Horticulture and Landscape Architecture Yangzhou UniversityYangzhou 225009China College of Life Sciences Nanjing Agricultural UniversityNanjing 210095China

Virus-induced gene silencing(VIGS)and clustered regularly interspaced short palindromic repeats/CRISPR-associated protein(CRISPR/Cas)systems are effective technologies for rapid and accurate gene function verification in modern plant ***,the investigation of gene silencing and editing in radish remains *** this study,a bleaching phenotype was generated through the knockdown of RsPDS using tobacco rattle virus(TRV)-and turnip yellow mosaic virus(TYMV)-mediated gene silencing *** TYMV-mediated gene silencing efficiency was higher than the TRV-based VIGS system in *** expression level of RsPDS was significantly inhibited using VIGS in'NAU-067'radish *** rootless seedlings of‘NAU-067'were infected with Agrobacterium rhizogenes using the 2300GN-Ubi-RsPDS-Cas9 vector with two target *** adventitious roots were blue with GUs staining,and four of these adventitious roots were edited at target sequence 1 of the RsPDS gene as indicated by Sanger ***,albino lines were generated with ***-mediated transformation of radish *** base substitutions and three base deletions occurred at target sequence 2 in Line 1,and three base insertions and three base substitutions occurred at target sequence 1 in Line *** study shows that VIGS and CRISPR/Cas9 techniques can be employed to precisely verify the biological functions of genes in radish,which will facilitate the genetic improvement of vital horticultural traits in radish breeding programs.

关键词： Raphanus sativus L. VIGS CRISPR/Cas9 Agrobacterium rhizogenes A.tumefaciens RsPDS

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快速城镇化地区生态环境质量时空格局演变及对土地利用变化响应——以廊坊市北三县为例

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西北林学院学报 2024年第1期39卷 169-176页

作者：武爱彬程林赵艳霞河北省科学院地理科学研究所/河北省地理信息开发应用工程技术研究中心河北石家庄050011 北京林业大学水土保持学院北京100083

对生态环境质量时空格局及其对土地利用变化的响应进行研究可为区域制定生态保护修复政策提供参考。通过构建遥感生态指数,对廊坊市北三县2000-2020年生态环境质量分布格局分析评价,利用地理加权回归模型探索生态环境质量变化对土地利... 详细信息

对生态环境质量时空格局及其对土地利用变化的响应进行研究可为区域制定生态保护修复政策提供参考。通过构建遥感生态指数,对廊坊市北三县2000-2020年生态环境质量分布格局分析评价,利用地理加权回归模型探索生态环境质量变化对土地利用变化的响应。结果表明,北三县2000-2020年生态环境质量等级以“良”和“一般”为主,整体呈下降趋势,等级“较差”面积呈快速增长趋势。建设用地变化、土地利用强度变化和生态环境质量变化呈负相关关系,回归系数在空间上呈现较大的异质性;生态用地变化与生态环境质量变化呈正相关关系,回归系数在空间上异质性不强。城镇快速扩张的区域生态环境质量变化对建设用地变化和土地利用强度变化响应最显著。大量耕地向建设用地转变是区域生态环境变化的最主要影响因素,在国土空间规划中应划定城市边界,严格控制建设用地规模,提高集约节约利用水平,确保区域可持续发展。

关键词：生态环境质量遥感生态指数土地利用变化地理加权回归廊坊北三县

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Evaluation of microRNA expression profiles in human sperm frozen using permeable cryoprotectant-free droplet vitrification and conventional methods

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Asian Journal of Andrology 2024年第4期26卷 366-376页

作者： Li-Xin Zhang Jing Mao yan-Dong Zhou Guang-Yao Mao Run-Fa Guo Hong-Shan Ge xia Chen Department of Histology and Embryology Medical SchoolNantong UniversityNantong 226001China Department of Reproductive Medicine The Affiliated Taizhou People’s Hospital of Nanjing Medical UniversityTaizhou School of Clinical MedicineNanjing Medical UniversityTaizhou 225300China.

For sperm cryopreservation,the conventional method,which requires glycerol,has been used for a long *** addition,the permeable cryoprotectant-free vitrification method has been continuously *** the differences of cryopreservation effects between the two methods have being studied,differences in microRNA(miRNA)profiles between them remain *** this study,we investigated the differences in miRNA expression profiles among conventional freezing sperm,droplet vitrification freezing sperm and fresh human *** also analyzed the differences between these methods in terms of differentially expressed miRNAs(DEmiRs)related to early embryonic development and paternal *** results showed no significant differences between the cryopreservation methods in terms of sperm motility ratio,plasma membrane integrity,DNA integrity,mitochondrial membrane potential,acrosome integrity,and ultrastructural ***,sperm miRNA-sequencing showed differences between the two methods in terms of the numbers of DEmiRs(28 and 19 with vitrification using a nonpermeable cryoprotectant and the conventional method,respectively)in postthaw and fresh sperm *** related to early embryonic development and paternal epigenetics mainly included common DEmiRs between the *** results showed that the differences between conventional freezing and droplet vitrification were minimal in terms of miRNA expression related to embryonic development and *** in sperm miRNA expression due to freezing are not always detrimental to embryonic *** study compared differences in miRNA expression profiles before and after cryopreservation between cryopreservation by conventional and vitrification *** offers a new perspective to evaluate various methods of sperm cryopreservation.

关键词： cryopreservation cryoprotectant-free vitrification early embryonic development paternal epigenetic inheritance sperm miRNAs sucrose

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基于信息扩散理论的淄博市高影响天气关注度研究

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陕西气象 2023年第2期 74-80页

作者：孙燕玲闫爱霞王健山东省气象防灾减灾重点实验室济南250031 淄博市气象局山东淄博255048 正镶白旗气象局内蒙古锡林郭勒013800

基于2016—2019年淄博市气象台发布的预报预警信息与气象服务信息,运用信息扩散理论分析社会公众对高影响天气事件的关注度,重点对比研究高影响天气在声讯电话和微信方式下的关注度,并对高影响天气关注度的理论值与统计值进行相关性检... 详细信息

基于2016—2019年淄博市气象台发布的预报预警信息与气象服务信息,运用信息扩散理论分析社会公众对高影响天气事件的关注度,重点对比研究高影响天气在声讯电话和微信方式下的关注度,并对高影响天气关注度的理论值与统计值进行相关性检验。结果表明:社会公众对高影响天气的关注方式正从传统的声讯电话拨打向新媒体的微信阅读转变。声讯电话方式下,公众对高影响天气的关注度从高到低依次为一般性降水、大雾、大风、暴雪、暴雨、雷暴、寒潮、高温、台风;微信方式下,公众对高影响天气的关注度由高到低依次为一般性降水、大雾、暴雪、雷暴、大风、暴雨、寒潮、高温、台风;社会公众对高影响天气的关注度在微信方式下比声讯电话方式下高。基于信息扩散理论计算出社会公众对高影响天气的关注度可信度高,经检验,高影响天气关注度理论值与统计值的相关性在声讯电话方式下比微信方式更显著,拟合效果更好。

关键词：信息扩散理论高影响天气风险关注度

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Trametinib boosts palbociclib’s efficacy in breast cancer via autophagy inhibition

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Oncology Research 2024年第7期32卷 1197-1207页

作者： ANGUO WU JIAO yan TING SU CHI FENG XIN LONG YIRU PAN RUPEI YE TIAN xia HANAN LONG JIANMING WU XIULI xiaO Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou646000China The Department of Pathology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China The Department of Pathology Mianyang Central HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaMianyang621000China The Department of Pathology Yongchuan Hospital of Chongqing Medical UniversityChongqing402160China School of Basic Medical Sciences Southwest Medical UniversityLuzhou646000China School of Clinical Medical Sciences Southwest Medical UniversityLuzhou646000China

Breast cancer,a predominant global health issue,requires ongoing exploration of new therapeutic ***(PAL),a well-known cyclin-dependent kinase(CDK)inhibitor,plays a critical role in breast cancer *** its efﬁcacy is recognized,the interplay between PAL and cellular autophagy,particularly in the context of the RAF/MEK/ERK signaling pathway,remains insufﬁciently *** study investigates PAL’s inhibitory effects on breast cancer using both in vitro(MCF7 and MDA-MB-468 cells)and in vivo(tumor-bearing nude mice)*** at elucidating the impact of PAL on autophagic processes and exploring the potential of combining it with trametinib(TRA),an MEK inhibitor,our research seeks to address the challenge of PAL-induced drug ***ﬁndings reveal that PAL signiﬁcantly decreases the viability of MCF7 and MDA-MB-468 cells and reduces tumor size in mice while showing minimal cytotoxicity in MCF10A ***,PAL also induces protective autophagy,potentially leading to drug resistance via the RAF/MEK/ERK pathway *** TRA effectively neutralized this autophagy,enhancing PAL’s anti-tumor efﬁcacy.A combination of PAL and TRA synergistically reduced cell viability and proliferation,and in vivo studies showed notable tumor size *** conclusion,the PAL and TRA combination emerges as a promising strategy for overcoming PAL-induced resistance,offering a new horizon in breast cancer treatment.

关键词： Palbociclib Trametinib Protective autophagy RAF/MEK/ERK MCF7 MDA-MB-468

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