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World Journal of Clinical Cases 2020年第2期8卷 370-376页

作者： Hui-Ying Li Yu Xie Ting-Ting Yu Yong-Juan Lin Zhen-Yu Yin Department of geriatric oncology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

BACKGROUND Central nervous system(CNS) metastases are a catastrophic complication of nonsmall cell lung cancer(NSCLC), including brain and leptomeningeal carcinomatosis, and are always accompanied by a poor prognosis. Despite the continuous development of existing treatments, the therapy of CNS metastases remains *** SUMMARY We report a patient who was definitively diagnosed with brain and leptomeningeal metastases from NSCLC with a targeted mutation in epidermal growth factor receptor(EGFR). A standard dosage of icotinib(125 mg three times daily) was implemented but ineffective. CNS lesions developed despite stable systemic control, so pulsatile icotinib(1125 mg every 3 d) was administered. This new strategy for administration has lasted 25 mo so far, and resulted in complete remission of neurological symptoms, almost vanished lesions, and longer survival with no notable side *** This is the first successful example of pulsatile icotinib for treating isolated CNS progression from EGFR mutation-positive NSCLC, providing a new alternative for the local treatment of CNS metastases.

关键词： Non-small cell lung cancer Central nervous system metastases EGFR mutation Pulsatile icotinib Case report

Prevalence of Malnutrition and Frailty in Elderly Cancer Patients and Resulting Impact on Primary Treatment Recommendations in Colorectal and Breast Cancer

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Journal of Nutritional oncology 2020年第4期5卷 162-169页

作者： Vittoria Balzano Véronique Dardaine Giraud Carine Sauger Carole Lefebvre Patrick Heitzmann Thierry Lecomtef Étienne Dorvalg OncoCentre-Regional Cancerology Network 37000 ToursFrance geriatric oncology coordination unit Regional Cancerology NetworkToursFranceDepartment of Geriatrics37000 Tours University HospitalFrance Department of Gastroenterology and Digestive oncology 37000 Tour University HospitalFrance

Objectives To estimate the prevalence of malnutrition in elderly cancer patients and its association with frailty and primary cancer treatment recommendations in patients with the two most prevalent cancers(colorectal cancer,CRC and breast cancer,BC)in the Centre-Val de Loire region of *** The entire cohort of 704 patients aged 75 years or older presenting with cancer who underwent comprehensive geriatric assessment(CGA)between 2014 and 2017 was *** status,frailty(defined by the Balducci classification system based on CGA parameters and comorbidity),and pathological criteria were analyzed in terms of the cancer treatment recommendations suggested by geriatricians both in the whole cohort and in those with CRC and *** In the whole group of 704 patients(84.3+/-4.8 years),the prevalence of malnutrition was 62.9%,and was higher in CRC than in BC patients(71.1%vs 55.4%,Pgeriatricians had a greater tendency to suggest only palliative care to CRC patients presenting with malnutrition(15.4%vs 2.7%,P=0.006)than to BC patients(9.8%vs 5.4%,NS).Conclusion Malnutrition in elderly cancer patients is prevalent,especially in those with colorectal cancer,where malnutrition is frailty-related and may strongly impact on cancer treatment strategies.

关键词： Elderly adult geriatric oncology Malnutrition geriatric assessment Treatment decision

Change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer treated by sorafenib

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Asian Pacific Journal of Tropical Medicine 2016年第6期9卷 573-576页

作者： Chang-Jiang Lei Jia-Ni Liu Rong Wu Zhi-Xiong Long Jiang-Zhou Zhang Dan Tao Yan-Ping Liu Tumor Laboratory the Second Affiliated Hospital of Jianghan University geriatric Department the Central Hospital of Wuhan oncology Department the Second Affiliated Hospital of Jianghan University

Objective:To study the change of the peripheral blood immune pattern and its correlation with prognosis in patients with liver cancer after treated by ***:Patients with advanced liver cancer admitted in our hospital were enrolled and treated with *** two months of the treatment,their peripheral blood was *** immune cell subset and cytokines level were determined by flow cytometry and luminex *** to the reaction expressed by patients towards sorafenib,patients were divided into the response group and the no response *** changes of the peripheral blood immune pattern and its correlation with prognosis of patients in the two groups were ***:Before and after treatment of sorafenib,there was no significant difference in the ratios of T cells,NK cells and their subtypes in peripheral blood of patients between the two groups;while after treatment the ratio of B cells and regulatory B cells(Breg) of patients in the response group was significant higher than that of the no response group(P<0.05),and the prognosis conditions of patients with decreased ratio of Breg cells were better than other patients after undergoing *** levels of plasma cytokines IL-6,IL-10,IL-12,IL17,FIL-3L,IFN- γ,TNF-α,MCP-1 and VEGF showed no significant ***:After treatment of sorafenib,the prognosis conditions of patients of advanced liver cancer with a reduced Breg ratio are better than patients with an unaltered or increased Breg *** ratio of Breg in peripheral blood may be considered as early biological indicator for the prediction of the curative effects of sorafenib.

关键词： Liver cancer Sorafenib Chemotherapy Regulatory B cells Prognosis

Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer

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World Journal of Clinical oncology 2025年第1期16卷 5-9页

作者： Macarena Teja María I Garrido Abrahams Ocanto Felipe Counago Department of Radiation oncology GenesisCare-San Francisco de Asís University HospitalMadrid 28002Spain Department of Radiation oncology GenesisCare-Vithas La Milagrosa University HospitalMadrid 28010Spain National Director GenesisCare SpainMadrid 28043Spain Department of Medicine School of MedicineHealth and SportEuropean University of MadridMadrid 28670Spain

Pancreatic cancer is usually associated with a poor *** is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are *** et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 *** a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall *** meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their ***,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant *** are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.

关键词： Inflammatory biomarkers Nutritional biomarkers Pancreatic cancer Prognosis Surgical complications

Targeting p53 pathways:mechanisms,structures,and advances in therapy

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1399-1433页

作者： Haolan Wang Ming Guo Hudie Wei Yongheng Chen Department of oncology NHC Key Laboratory of Cancer ProteomicsLaboratory of Structural BiologyNational Clinical Research Center for Geriatric DisordersXiangya HospitalCentral South UniversityChangshaHunan 410008China

The TP53 tumor suppressor is the most frequently altered gene in human cancers,and has been a major focus of oncology *** p53 protein is a transcription factor that can activate the expression of multiple target genes and plays critical roles in regulating cell cycle,apoptosis,and genomic stability,and is widely regarded as the“guardian of the genome”.Accumulating evidence has shown that p53 also regulates cell metabolism,ferroptosis,tumor microenvironment,autophagy and so on,all of which contribute to tumor *** in TP53 not only impair its tumor suppressor function,but also confer oncogenic properties to p53 *** p53 is mutated and inactivated in most malignant tumors,it has been a very attractive target for developing new anti-cancer ***,until recently,p53 was considered an“undruggable”target and little progress has been made with p53-targeted ***,we provide a systematic review of the diverse molecular mechanisms of the p53 signaling pathway and how TP53 mutations impact tumor *** also discuss key structural features of the p53 protein and its inactivation by oncogenic *** addition,we review the efforts that have been made in p53-targeted therapies,and discuss the challenges that have been encountered in clinical development.

关键词： metabolism drugs mechanisms

Clinical features and survival of patients with multiple primary malignancies

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World Journal of Clinical Cases 2021年第34期9卷 10484-10493页

作者： Xin-Kun Wang Min-Hang Zhou Department of Radiology the Fourth Medical CenterChinese PLA General HospitalBeijing 100048China Department of geriatric oncology the Fourth Medical CenterChinese PLA General HospitalBeijing 100048China

BACKGROUND Multiple primary malignancies(MPM)are characterized by two or more primary malignancies in the same patient,excluding relapse or metastasis of prior *** aimed to elucidate the clinical features and survival of MPM *** To elucidate the clinical features and survival of MPM *** A retrospective study of MPM patients was conducted in our hospital between June 2016 and June *** survival(OS)was calculated using the Kaplan-Meier *** log-rank test was used to compare the survival of different *** A total of 243 MPM patients were enrolled,including 222 patients with two malignancies and 21 patients with three *** patients with two malignancies,51(23.0%)had synchronous MPM,and 171(77.7%)had metachronous *** most common first cancers were breast cancer(33,14.9%)and colorectal cancer(31,14.0%).The most common second cancers were non-small cell lung cancer(NSCLC)(66,29.7%)and gastric cancer(24,10.8%).There was no survival difference between synchronous and metachronous MPM patients(36.4 vs 35.3 mo,P=0.809).Patients aged>65 years at diagnosis of the second cancer had a shorter survival than patients≤65 years(28.4 vs 36.4 mo,P=0.038).Patients with distant metastasis had worse survival than patients without metastasis(20.4 vs 86.9 mo,P=0.000).Following multivariate analyses,age>65 years and distant metastasis were independent adverse prognostic factors for *** During follow-up of a first cancer,the occurrence of a second or more cancers should receive greater attention,especially for common concomitant MPM,to ensure early detection and treatment of the subsequent cancer.

关键词： Multiple primary malignancies Overall survival Prognostic factor Distant metastasis Age

Converting“cold”to“hot”:epigenetics strategies to improve immune therapy effect by regulating tumor-associated immune suppressive cells

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Cancer Communications 2024年第6期44卷 601-636页

作者： Yijia Tang Guangzu Cui Haicong Liu Ying Han Changjing Cai Ziyang Feng Hong Shen Shan Zeng Department of oncology Xiangya HospitalCentral South UniversityChangshaHunanP.R.China National Clinical Resaerch Center for geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunanChina

Significant developments in cancer treatment have been made since the advent of immune ***,there are still some patientswithmalignant tumors who do not benefit from *** without immunogenicity are called“cold”tumors which are unresponsive to immunotherapy,and the opposite are“hot”*** suppressive cells(ISCs)refer to cells which can inhibit the immune response such as tumor-associated macrophages(TAMs),myeloid-derived suppressor cells(MDSCs),regulatory T(Treg)cells and so *** more ISCs infiltrated,the weaker the immunogenicity of the tumor,showing the characteristics of“cold”*** dysfunction of ISCs in the tumor microenvironment(TME)may play essential roles in insensitive therapeutic *** studies have found that epigeneticmechanisms play an important role in the regulation of *** ISCs may be a new approach to transforming“cold”tumors into“hot”***,we focused on the function of ISCs in the TME and discussed how epigenetics is involved in regulating *** addition,we summarized the mechanisms by which the epigenetic drugs convert immunotherapy-insensitive tumors into immunotherapy-sensitive tumors which would be an innovative tendency for future immunotherapy in“cold”tumor.

关键词： DNA methylation epigenetics strategy histone modification immune suppressive cell noncoding RNA

Classification,clinicopathologic features and treatment of gastric neuroendocrine tumors

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World Journal of Gastroenterology 2014年第1期20卷 118-125页

作者： Ting-Ting Li Feng Qiu Zhi Rong Qian Jun Wan Xiao-Kun Qi Ben-Yan Wu Department of geriatric Gastroenterology Chinese People’s Liberation Army General Hospital Department of Neurology Chinese Navy General Hospital Department of Medical oncology Dana-Farber Cancer InstituteBostonMA 02215United States

Gastric neuroendocrine tumors (GNETs) are rare lesions characterized by hypergastrinemia that arise from enterochromaffin-like cells of the stomach. GNETs consist of a heterogeneous group of neoplasms comprising tumor types of varying pathogenesis, histomorphologic characteristics, and biological behavior. A classification system has been proposed that distinguishes four types of GNETs; the clinicopathological features of the tumor, its prognosis, and the patient’s survival strictly depend on this classification. Thus, correct management of patients with GNETs can only be proposed when the tumor has been classified by an accurate pathological and clinical evaluation of the patient. Recently developed cancer therapies such as inhibition of angiogenesis or molecular targeting of growth factor receptors have been used to treat GNETs, but the only definitive therapy is the complete resection of the tumor. Here we review the literature on GNETs, and summarize the classification, clinicopathological features (especially prognosis), clinical presentations and current practice of management of GNETs. We also present the latest findings on new gene markers for GNETs, and discuss the effective drugs developed for the diagnosis, prognosis and treatment of GNETs.

关键词： Gastric neuroendocrine tumor Classification Clinicopathological significance Diagnosis Prognosis Treatment

Significance of Thymidylate Synthase Expression for Resistance to Pemetrexed in Pulmonary Adenocarcinoma

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Significance of Thymidylate Synthase Expression for Resistan...

CDK11 negatively regulates Wnt/β-catenin signaling in the endosomal compartment by affecting microtubule stability

2013华东胸部肿瘤论坛暨第六届浙江省胸部肿瘤论坛

作者： Yang Min Fan Wei-Fei Pu Xiao-Lin Liu Fu-Yin Meng Li-Juan Wang Ju Department of oncology Jiangsu Province Geriatric Institute

Pemetrexed(PEM),a multi-targeted antifolate,is promising clinical activity in non-squamous nonsmall cell lung ***,most patients eventually acquire resistance to *** evaluate the resistant mechanism,we exposed the lung adenocarcinoma cell line A549 to stepwise-increasing pemetrexed concentrations of 1.6,6.4 and 16μm,and established three pemetrexed-resistant lung cancer cell lines;A549/PEM-1.6,A549/PEM-6.4,and A549/PEM-I6 *** inhibition was determined by the 3-[4,5- dimethyl-thizol-2-yl]-2,5-diphenyltetrazolium bromide *** of the genes encoding thymidylate synthase(TS),reduced folate carrier(RFC),and folypoly-7-glutamate synthetase(FPGS) were analyzed by quantitative real-time reverse transcriptase polymerase chain *** three A549 cell lines showed more resistance to PEM(3.7-,17.3-,and 38.0- fold,respectively) than the parental cell line,which also showed cross-resistance to cisplatin,but not to docetaxel,vinorelbine,and *** gene expression was significantly increased in three pemetrexed-resistant cells relative to parental cells in a pemetrexed dose dependent *** knockdown TS expression with siRNA enhanced cytotoxicity of pemetrexed in A549/ PEM-16 *** contrast,the levels of HFC and FPGS genes expression in A549/PEM-1.6 cells and A549/ PEM-6.4 cells were significantly decreased,whereas the levels of both genes were restored in A549/PEM-16 *** summary,pemetrexed-resistant A549 cells remained sensitive to docetaxel,vinorelbine,and 5-fluorouracil .TS expression appeared to be associated with resistance to pemetrexed,which may be a predictive marker for pemetrexed sensitivity in lung adenocarcinoma.

关键词： Non-small cell lung cancer Pemetrexed Resistance Thymidylate synthase Reduced folate carrier Folypoly-γ-glutamate synthetase

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Cancer Biology & Medicine 2020年第2期17卷 328-342页

作者： Danmin Ou Lin Chen Jiang He Zhuoxian Rong Jie Gao Liyu Liu Feiyu Tang Jiang Li Yuezhen Deng Lunquan Sun Department of oncology Center for Molecular MedicineXiangya HospitalCentral South UniversityChangsha 410008China international Cooperation Base of Cancer Precision Therapy Department of Science and Technology of Hunan ProvinceChangsha 410008China Key Laboratory of Molecular Radiation oncology of Hunan Province Changsha 410008China National Clinical Research Center for geriatric Disorders Changsha 410008China

Objectives:Improper activation of Wnt/β-catenin signaling has been implicated in human *** the well-studied glycogen synthase kinase 3p(GSK3p)and casein kinase 1(CK1),other kinases affecting Wnt/β-catenin signaling remain to be ***:To identify the kinases that modulate Wnt/β-catenin signaling,we applied a kinase small interfering RNA(siRNA)library screen *** assays,immunoblotting,and real-time polymerase chain reaction(PCR)were performed to confirm the regulation o f the Wnt/β-catenin signaling pathway by cyclin-dependent kinase 11(CDK11)and to investigate the underlying *** immunofluorescence,coimmunoprecipitation(co-IP),and scratch wound assays were used to demonstrate colocalization,detect protein interactions,and explore the function of ***:CDK11 was found to be a significant candidate kinase participating in the negative control of Wnt/P-catenin ***-regulation of CDK11 led to the accumulation of Wnt/β-catenin signaling receptor complexes,in a manner dependent on intact adenomatosis polyposis coli(APC)*** analysis showed that CDK11 modulation of Wnt/P-catenin signaling engaged the endolysosomal machinery,and CDK11 knockdown enhanced the colocalization of Wnt/β-catenin signaling receptor complexes with early endosomes and decreased colocalization with ***,CDK11 was found to function in Wnt/β-catenin signaling by regulating microtubule *** of CDK11 down-regulated ***,co-IP assays demonstrated that CDK11 interacts with the a-tubulin deacetylase SIRT2,whereas SIRT2 down-regulation in CDK11-depleted cells reversed the accumulation of Wnt/(3-catenin signaling receptor ***11 was found to suppress cell migration through altered W nt/β-catenin ***:CDK11 is a negative modulator of Wnt/β-catenin signaling that stabilizes microtubules,thus resulting in the dysregulation of receptor complex trafficking

关键词： Wnt/β-catenin signaling CDK11 endosome microtubule SIRT2