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Chaperone-mediated Autophagy Regulates Cell Growth by Targeting SMAD3 in Glioma

Neuroscience Bulletin 2022年第6期38卷 637-651页

作者： Hanqun Liu Yuxuan Yong Xingjian Li Panghai Ye Kai Tao Guoyou Peng Mingshu Mo Wenyuan Guo Xiang Chen Yangfu Luo Yuwan Lin Jiewen Qiu Ziling Zhang Liuyan Ding Miaomiao Zhou Xinling Yang Lin Lu Qian Yang Pingyi Xu department of Neurology The First Affliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China department of neurosurgery Tangdu HospitalThe Fourth Military Medical UniversityXi'an 710038China department of Neurology The Second Affliated Hospital of Xinjiang Medical UniversityUrimqi 830054China department of Experiment Surgery Tangdu HospitalThe Fourth Military Medical UniversityXi'an 710038China

Previous studies suggest that the reduction of SMAD3(mothers against decapentaplegic homolog 3)has a great impact on tumor development,but its exact pathological function remains unclear.In this study,we found that the protein level of SMAD3 was greatly reduced in human-grade IV glioblastoma tissues,in which LAMP2A(lysosome-associated membrane protein type 2A)was significantly up-regulated.LAMP2A is a key ratelimiting protein of chaperone-mediated autophagy(CMA),a lysosome pathway of protein degradation that is activated in glioma.We carefully analyzed the amino-acid sequence of SMAD3 and found that it contained a pentapeptide motif biochemically related to KFERQ,which has been proposed to be a targeting sequence for CMA.In vitro,we confirmed that SMAD3 was degraded in either serum-free or KFERQ motif deleted condition,which was regulated by LAMP2A and interacted with HSC70(heat shock cognate 71 kDa protein).Using isolated lysosomes,amino-acid residues 75 and 128 of SMAD3 were found to be of importance for this process,which affected the CMA pathway in which SMAD3 was involved.Similarly,down-regulating SMAD3 or up-regulating LAMP2A in cultured glioma cells enhanced their proliferation and invasion.Taken together,these results suggest that excessive activation of CMA regulates glioma cell growth by promoting the degradation of SMAD3.Therefore,targeting the SMAD3-LAMP2Amediated CMA-lysosome pathway may be a promising approach in anti-cancer therapy.

关键词： Glioma-SMAD3 Chaperone-mediated autophagy Cell growth

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Case report and review of the literature of primary gastrointestinal amyloidosis diagnosed with enteroscopy and endoscopic ultrasonography

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World Journal of Clinical Cases 2018年第9期6卷 284-290页

作者： Yi-Pin Liu Wei-Wei Jiang Guo-Xun Chen Yan-Qing Li department of Gastroenterology Qilu Hospital Shandong University department of Gastroenterology Yantai Affiliated Hospital of Binzhou Medical University department of Nutrition University of Tennessee

Here, we report a rare case of primary gastrointestinal amyloidosis in a stable condition after being followed up for three years. The patient was admitted to the hospital in 2014. Tests showed decreased levels of hemoglobin and ferritin. Transoral and transanal enteroscopy showed multiple nodular protuberances in the esophagus, ileum, colon and rectum. Endoscopic ultrasonography indicated the nodular protuberances stemmed from the submucosa and partially invaded the intrinsic myometrium. Pathological examinations found multiple small nodules in the submucosa and dyed structures, which were positive for special Congo red dyeing. After treatment with oral iron supplements, the levels of hemoglobin and ferritin became normal. It is concluded that the patient represents a case of primary gastrointestinal amyloidosis with multiple nodular protuberances in the digestive tract with controllable moderate abdominal discomfort and anemia and a benign course. Enteroscopy and endoscopic ultrasonography play an important role in the diagnosis of primary gastrointestinal amyloidosis.

关键词： Enteroscopy Primary gastrointestinal amyloidosis Endoscopic ultrasonography Pathological diagnosis

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How does conserved dopamine neurotrophic factor protect against and rescue neurodegeneration of PC12 cells？

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Neural Regeneration Research 2017年第7期12卷 1145-1151页

作者： Jia-ming Mei Chao-shi Niu shandong university Jinan Shandong Province China department of neurosurgery Anhui Provincial Hospital Hefei Anhui Province China

Conserved dopamine neurotrophic factor protects and rescues dopaminergic neurodegeneration induced by 6-hydroxydopamine in vivo,but its potential value in treating Parkinson＇s disease remains controversial.Here,we used the proteasome inhibitors lactacystin and MG132 to induce neurodegeneration of PC12 cells.Afterwards,conserved dopamine neurotrophic factor was administrated as a therapeutic factor,both pretreatment and posttreatment.Our results showed that（1）conserved dopamine neurotrophic factor enhanced lactacystin/MG132-induced cell viability and morphology,and attenuated alpha-synuclein accumulation in differentiated PC12 cells.（2）Enzyme linked immunosorbent assay showed up-regulated 26S proteasomal activity in MG132-induced PC12 cells after pre-and posttreatment with conserved dopamine neurotrophic factor.Similarly,26S proteasome activity was upregulated in lactacystin-induced PC12 cells pretreated with conserved dopamine neurotrophic factor.（3）With regard proteolytic enzymes（specifically,glutamyl peptide hydrolase,chymotrypsin,and trypsin）,glutamyl peptide hydrolase activity was up-regulated in lactacystin/MG132-administered PC12 cells after pre-and posttreatment with conserved dopamine neurotrophic factor.However,upregulation of chymotrypsin activity was only observed in MG132-administered PC12 cells pretreated with conserved dopamine neurotrophic factor.There was no change in trypsin expression.We conclude that conserved dopamine neurotrophic factor develops its neurotrophic effects by modulating proteasomal activities,and thereby protects and rescues PC12 cells against neurodegeneration.

关键词： nerve regeneration conserved dopamine neurotrophic factor Parkinson＇s disease proteasomal inhibitor 26S proteasome alphasynuclein lactacystin MG-132 glutamyl peptide hydrolase chymotrypsin trypsin neural regeneration

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Impact of adding opioids to paravertebral blocks in breast cancer surgery patients:A systematic review and meta-analysis

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World Journal of Clinical Cases 2022年第6期10卷 1852-1862页

作者： Meng-Hua Chen Zheng Chen Da Zhao Lanzhou university Medical College Lanzhou 730000Gansu ProvinceChina department of Breast Shandong Second Provincial General HospitalJinan 250021Shandong ProvinceChina department of Oncology The First Hospital of Lanzhou UniversityLanzhou 730000Gansu ProvinceChina

BACKGROUND Several breast cancer studies have reported the use of adjuvant opioids with the paravertebral block(PVB)to improve outcomes.However,there is no level-1 evidence justifying its use.AIM To elucidate if the addition of opioids to PVB improves pain control in breast cancer surgery patients.METHODS We conducted an electronic literature search across PubMed,Embase,Scopus,and Google Scholar databases up to October 20,2020.Only randomized controlled trials(RCTs)comparing the addition of opioids to PVB with placebo for breast cancer surgery patients were included.RESULTS Six RCTs were included.Our meta-analysis indicated significantly reduced 24-h total analgesic consumption with the addition of opioids to PVB as compared to placebo[standardized mean difference(SMD)-1.57,95%confidence interval(CI):-2.93,-0.21,I2=94%].However,on subgroup analysis,the results were nonsignificant for studies using single PVB(SMD:-1.76,95%CI:-3.65,0.13 I2=95.09%)and studies using PVB infusion(SMD:-1.30,95%CI:-4.26,1.65,I2=95.49%).Analysis of single PVB studies indicated no significant difference in the time to first analgesic request between opioid and placebo groups(mean difference-11.28,95%CI:-42.00,19.43,I2=99.39%).Pain scores at 24 h were marginally lower in the opioid group(mean difference-1.10,95%CI:-2.20,0.00,I2=0%).There was no difference in the incidence of postoperative nausea and vomiting between the two groups.CONCLUSION Current evidence suggests a limited role of adjuvant opioids with PVB for breast cancer surgery patients.Further homogenous RCTs with a large sample size are needed to clarify the beneficial role of opioids with PVB.

关键词： Opioids Pain Surgery Breast cancer Nerve block Paravertebral block

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Risk factors and outcomes of postoperative stroke in surgical treatment for giant intracranial aneurysms

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Chinese Neurosurgical Journal 2023年第2期9卷 105-113页

作者： Hao Wang Junlin Lu Xin Chen Qiang Hao department of neurosurgery Fengtai DistrictBeijing Tiantan HospitalCapital Medical UniversityNo.119 South Fourth Ring Rd WestBeijing 100070China department of neurosurgery West China HospitalSichuan UniversityChengduSichuanChina

Background:Giant intracranial aneurysms(GIAs)are challenges for surgical treatment.Risk factors of postoperative stroke remain unclear.This study aims to investigate the predictors of postoperative stroke in GIAs and the impact of stroke on outcomes.Methods:We performed a retrospective medical record review of patients with GIAs who received microsurgery at our institution between 2011 and 2018.Multivariate logistic regression analyses were carried out to identify risk factors for postoperative stroke.The clinical and angiographic outcomes were compared between patients with and without stroke.Results:A total of 97 patients were included in this study.Surgical modalities included direct aneurysm neck clipping in 85 patients(87.7%),trapping with the bypass in 8(8.2%),proximal artery ligation in 1(1%),and bypass alone in 3(3.1%).Postoperative stroke was found in 26 patients(26.8%).Independent factors that affect postoperative stroke were recurrent aneurysm(OR,10.982;95%CI,1.976-61.045;P=0.006)and size≥3.5 cm(OR,3.420;95%CI,1.133-10.327;P=0.029).Combined perioperative mortality and morbidity was 26.8%.Follow-up was achieved from 89 patients(91.8%),with a mean follow-up period of 39 months(range 19 to 94 months).Good outcomes were observed in 75 patients(84.3%)and poor outcomes were observed in 14 patients(15.7%).Conclusions:Postoperative stroke was significantly associated with clinical outcome.Favorable outcomes can be achieved in most patients with GIAs after appropriate microsurgical modality.Recurrent aneurysm and size≥3.5 cm are risk factors of postoperative stroke.

关键词： Giant intracranial aneurysms Microsurgery Outcome Stroke Complication

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Clinical significance of SQSTM1/P62 and nuclear factor-κB expression in pancreatic carcinoma

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World Journal of Gastrointestinal Oncology 2020年第7期12卷 719-731页

作者： Zhao-Yang Zhang Sen Guo Rui Zhao Zhi-Peng Ji Zhuo-Nan Zhuang department of Emergency Surgery Qilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina department of General Surgery Qilu HospitalShandong UniversityJinan 250012Shandong ProvinceChina department of General Surgery Second Affiliated Hospital of Shandong UniversityJinan 250033Shandong ProvinceChina department of Gastrointestinal Surgery Beijing Tsinghua Changgung HospitalSchool of Clinical MedicineTsinghua UniversityBeijing 102200China

BACKGROUND Overexpression of SQSTM1(sequestosome 1,P62)and nuclear factor-κB(NF-κB)plays an important role in the invasion and metastasis of a variety of malignant tumors.AIM To explore the expression of P62 and NF-κB in pancreatic cancer and their relationship with clinicopathological features.METHODS The expression levels of P62 and NF-κB were analyzed by immunohistochemistry with a tissue chip containing 40 cases of human pancreatic carcinoma.Then we analyzed the correlation among P62 expression,phospho-P65 expression,and clinicopathological features of pancreatic carcinoma samples.RESULTS P62 expression was mainly observed in the cytoplasm of pancreatic carcinoma cells.Phosphorylated P65(phospho-P65)was mainly expressed in the nucleus and cytoplasm of pancreatic carcinoma cells.There was a significant difference in P62 expression among T stages.And a significant difference in phosphor-P65 expression among pathology types was noted.In the cases with strongly positive P62 expression,significant differences were found in age.And there were significant differences in T stage and tumor-node-metastasis stage in the cases with strongly positive phosphor-P65 expression.CONCLUSION In pancreatic carcinoma,P62 expression is significantly correlated with T stage.It may be a valuable malignant indicator for human pancreatic carcinoma.

关键词： Pancreatic carcinoma Phosphorylated P65 P62 SQSTM1 Nuclear factor-κB Malignant

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Successful treatment of breast metastasis from primary transverse colon cancer:A case report

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World Journal of Clinical Cases 2023年第11期11卷 2559-2566页

作者： Xin Jiao Fang-Zhou Xing Mi-Mi Zhai Peng Sun department of Gastrointestinal Surgery Affiliated Hospital of Weifang Medical UniversityWeifang 261041Shandong ProvinceChina department of Digestive System Weifang People’s HospitalWeifang 261041Shandong ProvinceChina

BACKGROUND The incidence of colon cancer is increasing worldwide.Treatments for colon cancer include surgery and surgery combined with chemotherapy and radiotherapy,but the median survival rate is still poor.Colon cancer most commonly metastasizes to the lymph nodes,lungs,liver,peritoneum,and brain,but breast metastasis is rare.There is no agreement on its treatment.CASE SUMMARY A 23-year-old woman was admitted to our hospital for further treatment with a history of acute abdominal pain,nausea,and vomiting.Her physical examination and computed tomography scan revealed an abdominal tumor.Transverse colectomy was successfully performed.Histopathological examination revealed that the tumor was a mucosecretory adenocarcinoma with signet ring cells.The patient inadvertently found a mass in the outer upper quadrant of the right breast after four cycles of XELOX chemotherapy[oxaliplatin 130 mg/m^(2),d1,intravenous(iv)drip for 2 h;capecitabine 1000 mg/m^(2),po,bid,d1–d14].After discussion with the patient,we performed a lumpectomy and frozen biopsy.The latter revealed that the breast tumor was intestinal metastasis.Genetic testing showed wild-type RAS and BRAF.So we replaced the original chemotherapy with FOLFIRI[irinotecan 180 mg/m^(2),d1,iv drip for 3–90 min;leucovorin 400 mg/m^(2),d1,iv drip for 2 h;5-fluorouracil(5-FU)400 mg/m^(2),d1 and 5-FU 1200 mg/(m^(2)d)×2 d,continuous iv drip for 46–48 h]+cetuximab(500 mg/m^(2),d1,iv drip for 2 h).Serum levels of tumor markers returned to normal after several treatment cycles,and there was no evidence of tumor recurrence or metastasis.CONCLUSION Breast metastasis from colon cancer is rare.Radical breast surgery should be avoided unless needed for palliation.Chemotherapy combined with targeted therapy should be the first choice.

关键词： Colon cancer Breast metastasis Tumor markers FOLFIRI Cetuximab Prognosis Case report

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Effect of Yiqi Bushen prescription on hippocampal neuronal apoptosis in diabetic rats

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Neural Regeneration Research 2011年第21期6卷 1628-1634页

作者： Deshan Liu Weiwei Lin Wei Gao Ping Chang Wei Li department of Traditional Chinese Medicine Qilu Hospital of Shandong University Jinan 250012 Shandong Province China

This study investigated the neuroprotective effect of Yiqi Bushen prescription （YQBS, supplementing qi and tonifying kidney） on neuronal cell apoptosis. Following YQBS treatment, the number of surviving hippocampal neurons increased, anti-apoptotic Bcl-2 expression increased and pro-apoptotic Bax expression decreased. In addition, diabetic rats exhibited improved learning and memory. YQBS treatment also increased Bcl-2 mRNA expression and the ratio of Bcl-2/Bax, but decreased levels of hypoxia-inducible factor-1α mRNA and Bax mRNA expression after high-glucose/hypoxia-induced injury. Results demonstrated that YQBS inhibited hippocampal neuronal apoptosis by decreasing hypoxia-inducible factor-1α expression and increasing Bcl-2 expression, thereby improving cognitive impairment in diabetic rats.

关键词： Yiqi Bushen prescription hippocampal neuron hypoxia-inducible factor-1α apoptosis diabetes learning and memory neural regeneration

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Correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2

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Chinese Medical Journal 2013年第10期126卷 1925-1929页

作者： ZHOU Shao-fei HU San-yuan MA Lei MIAO Lei MAO Wei-zheng department of (Jeneral Surgery Qilu Hospital Shandong UniversityJinan Shandong 250012 China department o1: General Surgery Qingdao Municipal HospitalQingdao Shandong 266071 China

Background The relationship between the presence of metalloproteinases and thyroid cancer remains unknown, and many controversies still exist in this field. The objective of this study was to investigate the correlations between papillary thyroid cancer and peripheral blood levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metall0Proteinase-2. Methods The correlations were studied bY detecting the levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloProteinase-1, and tissue inhibitor of metalloproteinase-2 by enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the peripheral blood of 30 patients with papillary thyroid carcinoma, 27 patients with benign thyroid disease, and 25 hea !hy vo!unteers. Results The leve!s of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood of patients with papillary thyroid carcinoma were significantly higher than those in the peripheral blood of patients with benign thyroid disease and healthy volunteers （P 〈0.05）. However, there were no significant differences between patients with benign thyroid disease and healthy volunteers （P 〉0.05）. The accuracy of detection by both enzyme-linked immunosorbant assay and reverse-transcription polymerase chain reaction in the papillary thyroid cancer group was 83.33%. Conclusions The levels of matrix metalloproteinase-2, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, and tissue inhibitor of metalloproteinase-2 in the peripheral blood are helpful in identifying thyroid carcinoma and aid in preoperative assessment.

关键词： thyroid carcinoma matrix metalloproteinase-2 matrix metalloproteinase-9 tissue inhibitor of metalloproteinase-1 tissue inhibitor of metalloproteinase-2

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Simultaneously metastatic cholangiocarcinoma and small intestine cancer from breast cancer misdiagnosed as primary cholangiocarcinoma:A case report

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World Journal of Clinical Cases 2023年第18期11卷 4446-4453页

作者： Xin Jiao Mi-Mi Zhai Fang-Zhou Xing Xiao-Ling Wang department of Gastrointestinal Surgery Affiliated Hospital of Weifang Medical UniversityWeifang 261041Shandong ProvinceChina department of Digestive System Weifang People’s HospitalWeifang 261041Shandong ProvinceChina

BACKGROUND Cholangiocarcinoma and small intestine cancer are common clinical malignancies,but metastatic cholangiocarcinoma and small intestine cancer are rare,especially simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer.Since the clinical presentation of metastatic cholangiocarcinoma and small intestine cancer does not differ from primary tumor,it may lead to misdiagnosis preoperatively.CASE SUMMARY A 66-year-old woman was admitted to our hospital for further treatment due to abdominal pain and jaundice.Abdominal magnetic resonance imaging and magnetic resonance cholangiopancreatography showed an occupying lesion of the bile duct,considering a high possibility of primary bile duct tumor.Therefore,we performed a radical bile duct cancer surgery and cholecystectomy,and multiple tumors in the small intestine were found and removed during the surgery process.Postoperative pathology showed metastatic bile duct cancer and small intestine cancer from tumors in other parts.The patient underwent a right total mastectomy and axillary lymph node dissection because of right breast cancer 2 years ago.Combining with the immunohistochemical results,the patient was finally diagnosed as metastatic cholangiocarcinoma and metastatic small intestine cancer from breast cancer.Postoperatively,the patient received four cycles of chemotherapy and targeted therapy with docetaxel,capecitabine and trastuzumab.Unfortunately,the patient eventually died from tumor progression,thoracoabdominal infection,and sepsis 5 mo after surgery.CONCLUSION Simultaneous metastatic cholangiocarcinoma and small intestine cancer from breast cancer are rare and the prognosis is extremely poor.Improving preoperative diagnostic accuracy is beneficial to avoid excessive surgical treatment.Treatment should be aimed at relieving biliary obstruction and abdominal pain,and then supplemented with chemotherapy and targeted therapy to control tumor progression and prolong the patient’s life.

关键词： Breast cancer Metastatic cholangiocarcinoma Metastatic small intestine cancer Misdiagnosis Prognosis Case report

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