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Is the combination of immunotherapy with conventional chemotherapy the key to increase the efficacy of colorectal cancer treatment?

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World Journal of Gastrointestinal Oncology 2023年第2期15卷 251-267页

作者： Jonadab E Olguin Monica G Mendoza-Rodriguez C Angel Sanchez-Barrera Luis I Terrazas Laboratorio Nacional en Salud Diagnóstico Molecular y Efecto Ambiental en Enfermedades Crónico-degenerativasFacultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico Unidad de Biomedicina Facultad de Estudios Superiores IztacalaUniversidad Nacional Autónoma de MéxicoTlalnepantla 54090Estado de MexicoMexico

Colorectal cancer(CRC) is among the most prevalent and deadly neoplasms worldwide. According to GLOBOCAN predictions, its incidence will increase from 1.15 million CRC cases in 2020 to 1.92 million cases in 2040. Therefore, a better understanding of the mechanisms involved in CRC development is necessary to improve strategies focused on reducing the incidence, prevalence,and mortality of this oncological pathology. Surgery, chemotherapy, and radiotherapy are the main strategies for treating CRC. The conventional chemotherapeutic agent utilized throughout the last four decades is 5-fluorouracil, notwithstanding its low efficiency as a single therapy. In contrast, combining 5-fluorouracil therapy with leucovorin and oxaliplatin or irinotecan increases its efficiency. However, these treatments have limited and temporary solutions and aggressive side effects. Additionally, most patients treated with these regimens develop drug resistance, which leads to disease progression. The immune response is considered a hallmark of cancer;thus, the use of new strategies and methodologies involving immune molecules, cells, and transcription factors has been suggested for CRC patients diagnosed in stages Ⅲ and Ⅳ. Despite the critical advances in immunotherapy, the development and impact of immune checkpoint inhibitors on CRC is still under investigation because less than 25% of CRC patients display an increased 5-year survival. The causes of CRC are diverse and include modifiable environmental factors(smoking, diet, obesity, and alcoholism), individual genetic mutations, and inflammation-associated bowel diseases. Due to these diverse causes, the solutions likely cannot be generalized. Interestingly, new strategies, such as single-cell multiomics, proteomics, genomics, flow cytometry, and massive sequencing for tumor microenvironment analysis, are beginning to clarify the way forward. Thus,the individual mechanisms involved in developing the CRC microenvironment, their causes, and their consequences need to be understood from a g

关键词： Colorectal cancer Immunotherapy checkpoint inhibitors chemotherapy Immunotherapy Immune response

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Intrathecal methotrexate in combination with systemic chemotherapy in glioblastoma patients with leptomeningeal dissemination:A retrospective analysis

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World Journal of Clinical Cases 2022年第17期10卷 5595-5605页

作者： Xun Kang Feng Chen Shou-Bo Yang Ya-Li Wang Zeng-Hui Qian Yan Li Hao Lin Parker Li Yi-Chen Peng Xiao-Min Wang Wen-Bin Li Department of Neuro-oncology Cancer CenterBeijing Tiantan HospitalCapital Medical UniversityBeijing 100070China Department of Neurosurgery Beijing Tiantan HsopitalCapital Medical UniversityBeijing 100070China Department of Oncology Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Clinical Medicine Shanghai Jiao Tong University School of MedicineShanghai 200240China

BACKGROUND Glioblastoma(GBM)is one of the most common and aggressive primary malignant brain tumors with severe symptoms and a poor prognosis.Leptomeningeal dissemination(LMD)is a serious complication of GBM that often results in dire outcomes.There is currently no effective treatment.AIM To estimate the clinical outcomes of combination therapy in GBM patients with LMD METHODS A retrospective analysis was conducted using data collected from GBM patients diagnosed with LMD from January 2012 to December 2019 at our institution.All these patients had received at least one cycle of a combination therapy consisting of intrathecal methotrexate(MTX)and systemic chemotherapy.Clinical and pathological data were analyzed to explore the outcome of GBM patients with LMD and to determine the most effective treatment.RESULTS Twenty-six patients were enrolled in this study.The median time from GBM diagnosis to LMD development was 9.3 mo(range:2-59 mo).The median overall survival of LMD patients from diagnosis to after receiving systemic chemotherapy in combination with intrathecal MTX was 10.5 mo(range:2-59 mo).In the Cox univariate analysis,gross resection of tumor(P=0.022),Karnofsky performance status(KPS)>60(P=0.002),and Ommaya reservoir implant(P60(P=0.037)and Ommaya reservoir implant(P=0.014)were positive factors correlated with survival.Myelotoxicity and gastrointestinal reactions were the common toxicities of this combination therapy.According to Common Terminology Criteria of Adverse Events 4.03,most of the patients presented with toxicity less than grade 3.CONCLUSION Intrathecal MTX administration combined with systemic chemotherapy is a potentially effective treatment for patients with GBM and LMD,with mild treatment-related side effects.

关键词： Glioma Glioblastoma Leptomeningeal dissemination Intrathecal methotrexate chemotherapy

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Mature dendritic cell-derived dendrosomes swallow oxaliplatin-loaded nanoparticles to boost immunogenic chemotherapy and tumor antigen-specific immunotherapy

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Bioactive Materials 2022年第9期7卷 15-28页

作者： Xing Chen Xiang Ling Jiaxuan Xia Ying Zhu Longlong Zhang Yuwei He Anni Wang Guolong Gu Bo Yin Jianxin Wang Department of Pharmaceutics School of PharmacyFudan UniversityKey Laboratory of Smart Drug DeliveryMinistry of EducationShanghai201203China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityState Key Laboratory of Natural MedicinesNanjing210009China Department of Radiology Huashan HospitalFudan UniversityShanghai200040China Institutes of Integrative Medicine of Fudan University Shanghai200040China

The cytomembrane-derived delivery platform represents a promising biomimetic strategy in oncotherapy.To achieve durable and reliable tumor inhibition,mature dendrosomes(mDs),which were isolated from bone marrow-derived dendritic cells undergoing CT26 tumor antigen(TA)stimulation,were fused with redox-responsive nanoparticles(NPs)that were composed of poly(disulfide ester amide)polymers with an intensified disulfide density and hydrophobic oxaliplatin(OXA)prodrugs with the ability to potentiate immunogenicity.In vitro and in vivo results revealed that NP/mDs could induce tumor cell death through mitochondrial pathway and thus created immunogenic microenvironments,but also elicited immunocyte differentiation by TA cross-dressing and infiltration by direct presentation.By further neutralizing immune-regulatory interaction,the administration of PD-L1 antibody(αPD-L1)greatly improved antitumor efficiency of NP/mDs.Furthermore,the effectors of host immune systems effectively inhibited the growth and metastasis of distal tumors,likely because the autologous TA evoked by OXA and allogeneic TA delivered by mDs acted as additional stimuli to reinforce the immune response of tumor-specific T cells and immunosurveillance toward oncogenesis.These results demonstrated that NP/mDs could simultaneously realize immunogenic chemotherapeutics and specific TA delivery.In combination withαPD-L1,the antitumor effect was further enhanced.Therefore,NP/mDs provide a promising strategy for the comprehensive treatment of malignancy.

关键词： Dendritic cell Dendrosome Antigen delivery Immunotherapy chemotherapy

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Continuous intravenous infusion of recombinant human endostatin using infusion pump plus chemotherapy in non-small cell lung cancer

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World Journal of Clinical Cases 2022年第4期10卷 1164-1171页

作者： Zhi-Quan Qin Si-Fu Yang Yun Chen Chao-Jin Hong Tong-Wei Zhao Guo-Rong Yuan Liu Yang Liang Gao Xiao Wang Li-Qin Lu Department of Medical Oncology Zhejiang Provincial People’s Hospital(People’s Hospital of Hangzhou Medical College)Hangzhou 310014Zhejiang ProvinceChina

BACKGROUND Lung cancer is one of the deadliest cancers in the world with the highest incidence and mortality rate among all cancers.Non-small cell lung cancer(NSCLC)accounts for approximately 80%of primary lung cancer.However,efficacy and safety of the current regimens for NSCLC is unsatisfactory.Therefore,there has been an increasing urgency for development of potential therapeutic therapies for NSCLC.AIM To investigate the therapeutic outcomes and safety of continuous intravenous infusion of recombinant human endostatin(Rh-endostain)using an infusion pump in retreated advanced NSCLC.METHODS Patients with retreated advanced NSCLC who were admitted to Zhejiang Provincial People's Hospital from October 2017 to April 2019 were recruited.These patients received continuous intravenous infusion of Rh-endostain using an infusion pump.Objective response rate(ORR),clinical benefit rate(CBR),median progression-free survival(mPFS),and incidences of adverse events(AEs)were analyzed after treatment.RESULTS A total of 45 patients with retreated advanced NSCLC were included,and all of them were evaluated.In these patients,ORR was 22.2%,CBR was 84.4%,and mPFS was 5.3 mo.The following AEs were observed,decreased hemoglobin(34 cases,75.6%),nausea/vomiting(32 cases,71.1%),elevated transaminase(24 cases,53.3%),leukopenia(16 cases,35.6%),thrombocytopenia(14 cases,31.1%),and constipation(1 case,3.4%).None of the patients had leukopenia,nausea/vomiting,and constipation of grade III and above.CONCLUSION The patients showed improved adherence to 5-d continuous intravenous infusion of Rh-endostain using an infusion pump.Favorable efficacy and safety of this treatment regimen were achieved in retreated advanced NSCLC.

关键词： Non-small cell lung cancer chemotherapy Recombinant human endostatin Continuous intravenous infusion

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Toripalimab combined with targeted therapy and chemotherapy achieves pathologic complete response in gastric carcinoma:A case report

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World Journal of Clinical Cases 2022年第18期10卷 6184-6191页

作者： Rui Liu Xia Wang Zhi Ji Ting Deng Hong-Li Li Yan-Hui Zhang Yu-Chong Yang Shao-Hua Ge Le Zhang Ming Bai Tao Ning Yi Ba National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300000China

BACKGROUND Neoadjuvant or perioperative chemotherapy combined with surgery can reduce postoperative recurrence and improve the long-term survival rate of patients with locally advanced resectable gastric carcinoma.Nivolumab combined with chemotherapy has been recommended by the National Comprehensive Cancer Network guidelines as a first-line therapy for advanced gastric carcinoma/adenocarcinoma of the gastroesophageal junction and serves as the basis for immunotherapy combined with chemotherapy to become a neoadjuvant therapy.Herein,we report a case in which pathologic complete response was achieved by neoadjuvant administration of toripalimab,Herceptin,and docetaxel,oxaliplatin,calcium folinate,and fluorouracil(FLOT)chemotherapy followed by surgery for human epidermal growth factor receptor 2(HER2)-and programmed deathligand 1(PD-L1)-positive locally advanced gastric carcinoma.We hope that this case will shed some light on neoadjuvant therapy for gastric carcinoma.CASE SUMMARY The patient was diagnosed with locally advanced adenocarcinoma of the cardia.Immunohistochemistry of the baseline tissues suggested that the tissues were HER2-(fluorescent in situ hybridization)and PD-L1-positive(combined positive score=1).The patient underwent surgery following a four-cycle neoadjuvant therapy comprising Herceptin,toripalimab,and FLOT chemotherapy.The postoperative pathological findings showed mild atypical hyperplasia of the local glands with chronic mucosal inflammation(proximal stomach),no clear residual tumor(tumor regression grade 0),no regional lymph node metastasis,and negative upper and lower cut ends.The levels of tumor markers were reduced to normal levels after re-examination.With good postoperative recovery,the four-cycle preoperative chemotherapy was continued at the same dosage as that previously administered.After the treatment,the patient was monitored every 3 mo with a follow-up of 12 mo(4 times).As of February 27,2022,he was in a good condition without disease progression.The clinical trial registration

关键词： Toripalimab Targeted therapy chemotherapy Perioperative management Gastric carcinoma Case report

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A smart nanoprobe based on luminescent terbium metal-organic framework coated gold nanorods for monitoring and photo-stimulated combined thermal-chemotherapy

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Journal of Rare Earths 2022年第9期40卷 1371-1381,I0002页

作者： Tong Zhang Liying Qin Liangliang Liu Meina Zhang Tianyi Du Yifan Fan Huicheng Yan Pingru Su Ping Zhou Yu Tang Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province College of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China School/Hospital of Stomatology Lanzhou UniversityLanzhou 730000China

Real-time monitoring and accurate treatment are of great significance for reducing the side effects during the cancer therapy.In this work,we rationally prepared a smart nanoprobe based on core-shell terbium metal-organic gramework(MOF)with highly effective photothermal conversion capacity and drug release efficiency under near-infrared light irradiation for real-time fluorescence imaging-guided multimodal therapy.The nanoprobe can achieve prominent photothermal therapy and controllable drug release,act as a fluorescence thermometer,and also real-time feedback of temperature is expected to be achieved.At the same time,the two-photon ligand design significantly improves the tissue penetration ability of the nanoprobe.Our work is expected to provide a reference for precise treatment and real-time monitoring of tumors and at the same time provide new ideas for the formulation of individualized treatment plans.

关键词： Lanthanide metal-organic frameworks(LnMOFs) Fluorescence thermometer Two-photon ligand Photothermal therapy chemotherapy Rare earths

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Adjuvant chemotherapy versus Radiotherapy in High-risk,Early-stage Endometrioid Endometrial Carcinoma

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Current Medical Science 2022年第1期42卷 185-191页

作者： Min WU Ya-nan YANG Yu-hui HUANG Jing CAI Xiao-qi HE Ze-hua WANG Department of Obstetrics and Gynecology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China

Objective:The present study was designed to evaluate the effects of adjuvant chemotherapy(CT)vs.radiotherapy(RT,alone or combined with CT)on the prognosis of patients with high-risk,early-stage(stage I and stage II)endometrioid endometrial carcinoma.Methods:This single-center retrospective clinical study was conducted in Union Hospital,Tongji Medical College,Huazhong University of Science and Technology between 2010 and 2019.

关键词： endometrioid endometrial carcinoma chemotherapy radiotherapy

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Surgical management of monomorphic epitheliotropic intestinal Tcell lymphoma followed by chemotherapy and stem-cell transplant:A case report and review of the literature

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World Journal of Gastrointestinal Oncology 2022年第11期14卷 2273-2287页

作者： Abdul Saad Bissessur Ji-Chun Zhou Ling Xu Zhao-Qing Li Si-Wei Ju Yun-Lu Jia Lin-Bo Wang Department of Surgical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina Department of Medical Oncology First Affiliated HospitalZhejiang University School of MedicineHangzhou 310006Zhejiang ProvinceChina

BACKGROUND Monomorphic epitheliotropic intestinal T-cell lymphoma(MEITL)is a rare and rapidly progressive intestinal T-cell non-Hodgkin lymphoma associated with a very poor prognosis and a median survival of 7 mo.Advances in the identification of MEITL over the last two decades have led to its recognition as a separate entity.MEITL patients,predominantly male,typically present with vague and nonspecific symptoms and diagnosis is predominantly confirmed at laparotomy.Currently,there are no standardized treatment protocols,and the optimal therapy remains unclear.CASE SUMMARY We report a case of MEITL that was initially considered to be gastrointestinal stromal tumor(GIST)and Imatinib was administered for one cycle.The 62-yearold man presented with abdominal pain,abdominal distension,and weight loss of 20 pounds.Within 2 wk,the size of the mass considerably increased on computed tomography scans.The patient underwent surgery followed by chemotherapy with CHOP(cyclophosphamide,doxorubicin,vincristine,and prednisone)and stem-cell transplant.A correct diagnosis of MEITL was established based on postoperative pathology.Immunophenotypically,the neoplastic cells fulfilled the diagnostic criteria for MEITL as they were CD3+,CD4+,CD8+,CD56+,and TIA-1+.CONCLUSION Given that MEITL has no predisposing factor and presents with vague symptoms with rapid progression,the concomitant presence of abdominal symptoms and B symptoms(weight loss,fever,and night sweats)with hypoalbuminemia,anemia,low lymphocytic count and endoscopic findings of diffuse infiltrating type lesions should alert physicians to this rare disease,especially when it comes to Asian patients.Immediate laparotomy should then be carried out followed by chemotherapy and stem-cell transplant.

关键词： Monomorphic epitheliotropic intestinal T-cell lymphoma Gastrointestinal stromal tumor Immunophenotypically chemotherapy Stem-cell transplant Case report

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Efficacy Differences of First-line EGFR-TKIs Alone vs in Combination with chemotherapy in Advanced Lung Adenocarcinoma Patients with Sensitive EGFR Mutation and Concomitant Non-EGFR Genetic Alterations

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中国肺癌杂志 2022年第9期25卷 651-657页

作者： Guowei ZHANG Ruirui CHENG Yuanyuan NIU Huijuan WANG Xiangtao YAN Mina ZHANG Xiaojuan ZHANG Jinpo YANG Chunhua WEI Zhiyong MA Department of Internal Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Respiratory Medicine The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China

Background and objective:Epidermal growth factor receptor(EGFR)mutations are often associated with non-EGFR genetic alterations,which maybe a reason for the poor efficacy of EGFR tyrosine kinase inhibitors(TKIs).Here we conducted this study to explore whether EGFR-TKIs combined with chemotherapy would benefit advanced lung adenocarcinoma patients with both sensitive EGFR mutation and concomitant non-EGFR genetic alterations.Materials and methods:Cases of advanced lung adenocarcinoma with EGFR mutation combined with concomitant nonEGFR genetic alterations were retrospectively collected.And the patients were required to receive first-line EGFR-TKIs and chemotherapy combination or EGFR-TKIs monotherapy.Demographic,clinical and pathological data were collected,and the electronic imaging data were retrieved to evaluate the efficacy and time of disease progression.Survival data were obtained through face-to-face or telephone follow-up.The differences between the two groups in objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS)and overall survival(OS)were investigated.Results:107 patients were included,including 63 cases in the combination group and 44 cases in the monotherapy group.The ORR were 78%and 50%(P=0.003),and DCR were 97%and 77%(P=0.002),respectively.At a median follow-up of 13.7 mon,a PFS event occurred in 38.1%and 81.8%of patients in the two groups,with median PFS of18.8 mon and 5.3 mon,respectively(Pchemotherapy was significantly superior to EGFR-TKIs monotherapy,which should be the preferred treatment option.

关键词： Lung neoplasms EGFR mutation Concomitant genetic alteration Targeted therapy chemotherapy

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Empathetic nursing with mindful cognitive therapy for fatigue,depression,and negative emotions in leukemia patients undergoing long-term chemotherapy

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World Journal of Clinical Cases 2022年第6期10卷 1826-1833页

作者： Ying-Ying Lu Xiao-Min Lu Chun-Yan Shao Chen-Chen Wang Ting-Ting Xu Bei-Lei Zhang Department of Medical Oncology Affiliated Haian Hospital of Nantong UniversityHaian 226600Jiangsu ProvinceChina

BACKGROUND Leukemia is a broad term for blood cell cancer.Leukemia is divided into acute or chronic,depending on cell differentiation.Leukemia patients are prone to adverse reactions during chemotherapy,such as anxiety,depression,and even suicide,affecting prognosis.As a nursing model developed by three well-known cognitive psychologists,empathetic nursing with mindfulness cognitive therapy(ENMCT)can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease.AIM To explore the effect of ENMCT on cancer-induced fatigue,hope level,and negative emotions in patients with long-term leukemia chemotherapy.METHODS A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach.Fifty-one patients in the control group received routine nursing,while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy.After three months of nursing care,cancerinduced fatigue was measured with the Piper Fatigue Scale(PFS),hope level with the Herth Hope Index(HHI),and negative emotion with the Hamilton Anxiety Scale(HAMA)/Hamilton Depression Scale(HAMD).Self-management(Chinese Strategies Used by People to Promote Health)was also recorded.RESULTS The observation group’s total scores in behavior,cognition,emotion,feeling,and PFS were lower than the control group after the intervention(P<0.05).Keeping close contact with others,the attitude of taking positive actions,the attitude toward reality and future,and the total HHI score were higher in the observation group than the control group(P<0.05).The observation group’s HAMA and HAMD scores were lower than the control group(P<0.05).The observation group’s positive attitude,self-decision,and self-relief scores were greater than the control group(P<0.05).CONCLUSION Empathetic nursing with cognitive mindfulness therapy is beneficial in im

关键词： Mindfulness-based cognitive therapy Empathetic nursing Leukemia chemotherapy Cancerinduced fatigue Hope level Negative emotions

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