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Cervical cancer:a tale from HPV infection to PARP inhibitors

Genes & Diseases 2023年第4期10卷 1445-1456页

作者： Minakshi Mann Vikram Pratap Singh Lalit Kumar Department of Medical Oncology Dr.B.R.A.Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew Delhi 110029India Department of Oncoanaesthesia and Palliative Medicine Dr.B.R.A.Institute Rotary Cancer HospitalAll India Institute of Medical SciencesNew Delhi 110029India Epigenetics Section Mouse Cancer Genetics ProgramCenter for Cancer ResearchNational Cancer InstituteFrederickMD 21702USA

Globally,cervical cancer(CxCa)ranks 4th common cancer among females and led to 569,847 incidences and 311,365 deaths in 2018.80%of CxCa cases occur due to persistent infection with a high-risk subtype of human papillomavirus(HPV-16 and 18).Smoking,high par-ity,and co-infection with type 2 herpes simplex or HIV are other known risk factors for CxCa.Major histological subtypes are squamous(70%)and adenocarcinoma(25%).Presently,concur-rent radiation plus cisplatin(CDDP)-based chemotherapy is the standard treatment for CxCa patients.However,CDDP resistance and toxic side effects limit its efficacy,leading to a poorer response rate and an expected overall survival ranging from 10 to 17.5 months.Reduced drug uptake,increased DNA damage repair,increased CDDP inactivation,and overexpressed Bcl-2 or caspase inhibition,are primarily accountable mechanisms for CDDP resistance and improving CDDP’s efficacy remains the major challenge.Poly(ADP-ribosyl)polymerase-1,an effective mediator of nucleotide excision repair pathway,is involved in DNA repair as well as maintaining genomic stability and is significantly expressed in malignant lymphomas,hepa-tocellular-,cervical-and colorectal carcinoma,which has been approved effective in mainte-nance therapy and may serve as an effective target to enhance CDDP sensitivity in CxCa.Here,we summarize the etiology and epidemiology of and treatment for CxCa,the mechanism responsible for chemotherapy resistance,PARP inhibitor as a possible therapy for CxCa,and other possible chemotherapeutic options for CxCa treatment.

关键词： Cervical cancer Chemotherapy Cisplatin Disease etiology and histology PARP inhibitors Resistance

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Transcutaneous Electrical Acupoint Stimulation Combined with Warm Acupuncture for Breast cancer Related Upper Limb Lymphedema:A Retrospective Cohort Study

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Chinese Journal of Integrative Medicine 2023年第6期29卷 534-539页

作者： LU Chao LI Guang-liang DENG De-hou BAO Wen-long WANG Yan ZHANG Ai-qin Department of Traditional Chinese Medicine the Cancer Hospital of University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Hangzhou(310022)China institute of Basic Medicine and cancer Chinese Academy of SciencesHangzhou(310022)China Department of Breast Medical Oncology the Cancer Hospital of University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Hangzhou(310022)China

Objective To observe the clinical efficacy of transcutaneous electrical acupoint stimulation(TEAS)combined with warm acupuncture in treating breast cancer associated with upper limb lymphedema(BCRL).Methods This was a retrospective cohort study using a paired control design.Fifty-two BCRL patients were assigned to the control group(27 cases)and the treatment group(25 cases).The patients in the control group were treated with lymphedema comprehensive detumescence treatment(CDT)for 4 weeks,including systematic therapy composed of manual lymphatic drainage,compression bandage,skincare,and functional exercise.The patients in the treatment group were treated with TEAS combined with warm acupuncture based on the control group methods.Each treatment lasted for 30 min and was applied twice a week for 4 weeks.The arm circumference(AC)of different positions of the affected limb and the degree of swelling of the affected limb were evaluated before the first treatment and after the last treatment.The clinical efficacy was evaluated according to the degree of edema before and after treatment.All adverse events during treatment were recorded.Results The patients’AC and the swelling feeling of the affected limb in the treatment group and the control group were both reduced compared with those before treatment.Compared with the control group,AC of the wrist joint transverse stria,the midpoint between the wrist joint transverse stria and the elbow joint transverse stria in the treatment group were significantly reduced(P<0.05).The decrease in AC diameter at the midpoint between the elbow joint transverse stria and the axillary transverse stria was the most significant(P<0.01).The swelling degree of the affected limbs in the treatment group was significantly lower than before treatment,and was significantly lower compared with the control group after treatment(P<0.01).The total effective rate was 72%in the treatment group,significantly higher than that in the control group(55.56%,P<0.05).No serious adverse events occured in either

关键词： transcutaneous electrical acupoint stimulation warm acupuncture breast cancer related upper limb lymphedema comprehensive detumescence treatment clinical efficacy

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Advances in regional nodal management of early-stage breast cancer

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Chinese Journal of cancer Research 2024年第2期36卷 215-225页

作者： Zhao Bi Yongsheng Wang Breast cancer Center Shandong Cancer Hospital and InstituteShandong First Medical University and Shandong Academy of Medical SciencesJinan 250017China

With the continuous improvement of systemic treatment, reasonable local regional control of early-stage breast cancer can be translated into survival benefits. The optimization of regional nodal management in patients with limited sentinel lymph node(SLN) metastasis needs to be weighed by surgical complications, regional recurrence risk, and lymph node status, as well as other escalating treatment(systemic/radiotherapy) that may result from deescalating surgery. With the effective support and supplementation of systemic therapy and radiotherapy, the management of axillary surgery is developing in a de-escalating trend. The widespread application of neoadjuvant therapy has contributed to optimizing the management of patients with clinically node-negative/imaging nodepositive disease. In clinical practice, it is necessary to consider the residual tumor burden of regional lymph nodes when formulating the optimal irradiation fields in patients with limited positive SLN without axillary lymph node dissection. The combined application of genomic tests and American College of Surgeons Oncology Group Z0011/AMAROS criteria could provide patients with a better strategy of dual de-escalation treatment, which includes the de-escalation of both axillary surgery and systemic treatment. In the era of sentinel lymph node biopsy(SLNB), the regional nodal management of breast cancer should adhere to the concept of “updating ideas, making bold assumptions, and carefully seeking proof”, make full use of the benefits of systemic therapy and radiotherapy to reduce the scope of surgery and complications, and expand the “net benefit” of efficacy and quality of life. This review discusses the optimization of regional nodal management in the era of SLNB, in order to provide reference information for clinicians.

关键词： Breast cancer sentinel lymph node biopsy internal mammary lymph node radiotherapy surgery

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Plasma-metabolite-based machine learning is a promising diagnostic approach for esophageal squamous cell carcinoma investigation

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Journal of Pharmaceutical Analysis 2021年第4期11卷 505-514页

作者： Zhongjian Chen Xiancong Huang Yun Gao Su Zeng Weimin Mao Laboratory of Pharmaceutical Analysis and Drug Metabolism College of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China The cancer Research institute The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou310022China

The aim of this study was to develop a diagnostic strategy for esophageal squamous cell carcinoma(ESCC)that combines plasma metabolomics with machine learning algorithms.Plasma-based untargeted metabolomics analysis was performed with samples derived from 88 ESCC patients and 52 healthy controls.The dataset was split into a training set and a test set.After identification of differential metabolites in training set,single-metabolite-based receiver operating characteristic(ROC)curves and multiple-metabolite-based machine learning models were used to distinguish between ESCC patients and healthy controls.Kaplan-Meier survival analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic significance of the plasma metabolites.Finally,twelve differential plasma metabolites(six up-regulated and six down-regulated)were annotated.The predictive performance of the six most prevalent diagnostic metabolites through the diagnostic models in the test set were as follows:arachidonic acid(accuracy:0.887),sebacic acid(accuracy:0.867),indoxyl sulfate(accuracy:0.850),phosphatidylcholine(PC)(14:0/0:0)(accuracy:0.825),deoxycholic acid(accuracy:0.773),and trimethylamine N-oxide(accuracy:0.653).The prediction accuracies of the machine learning models in the test set were partial least-square(accuracy:0.947),random forest(accuracy:0.947),gradient boosting machine(accuracy:0.960),and support vector machine(accuracy:0.980).Additionally,survival analysis demonstrated that acetoacetic acid was an unfavorable prognostic factor(hazard ratio(HR):1.752),while PC(14:0/0:0)(HR:0.577)was a favorable prognostic factor for ESCC.This study devised an innovative strategy for ESCC diagnosis by combining plasma metabolomics with machine learning algorithms and revealed its potential to become a novel screening test for ESCC.

关键词： Diagnostic Esophageal squamous cell carcinoma(ESCC) Metabolomics Machine learning Prognostic

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National guidelines for diagnosis and treatment of gastric cancer 2022 in China(English version)

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Chinese Journal of cancer Research 2022年第3期34卷 207-237页

作者：无 Jiafu Ji Zhaode Bu Jiahui Chen National Health Commission of the People's Republic of China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Peking University Cancer Hospital&Institute The cancer Hospital of the University of Chinese Academy of sciences(Zhejiang cancer Hospital) Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of Sciences

Contents 1.Overview 2.Diagnosis 2.1 Symptoms 2.2 Signs 2.3 Imaging 2.3.1 X-ray gas-barium double-contrast imaging 2.3.2 Ultrasonography(US)2.3.3 CT 2.3.4 MRI 2.3.5 Positron emission tomography(PET)-CT 2.3.6 Emission c... 详细信息

关键词： diagnosis gastric treatment

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Quantitative characterization of cell physiological state based on dynamical cell mechanics for drug efficacy indication

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Journal of Pharmaceutical Analysis 2023年第4期13卷 388-402页

作者： Shuang Ma Junfeng Wu Zhihua Liu Rong He Yuechao Wang Lianqing Liu Tianlu Wang Wenxue Wang State Key Laboratory of Robotics Shenyang Institute of AutomationChinese Academy of SciencesShenyang 110016China institutes for Robotics and Intelligent Manufacturing Chinese Academy of SciencesShenyang 110169China University of Chinese Academy of sciences Beijing 100049China Department of Thoracic Surgery Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang 110042China Department of Radiotherapy Cancer Hospital of China Medical UniversityLiaoning Cancer Hospital and InstituteShenyang 110042China

Cell mechanics is essential to cell development and function,and its dynamics evolution reflects the physiological state of cells.Here,we investigate the dynamical mechanical properties of single cells under various drug conditions,and present two mathematical approaches to quantitatively characterizing the cell physiological state.It is demonstrated that the cellular mechanical properties upon the drug action increase over time and tend to saturate,and can be mathematically characterized by a linear timeinvariant dynamical model.It is shown that the transition matrices of dynamical cell systems significantly improve the classification accuracies of the cells under different drug actions.Furthermore,it is revealed that there exists a positive linear correlation between the cytoskeleton density and the cellular mechanical properties,and the physiological state of a cell in terms of its cytoskeleton density can be predicted from its mechanical properties by a linear regression model.This study builds a relationship between the cellular mechanical properties and the cellular physiological state,adding information for evaluating drug efficacy.

关键词： Cellular mechanical properties Cytoskeleton Drug efficacy evaluation Cell system modelling Linear regression

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Prognostic factors affecting long-term outcomes in patients with brain metastasis from esophageal carcinoma

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Chinese Journal of cancer Research 2020年第6期32卷 768-777页

作者： Peng Zhang Lejing Yao Ming Chen Wei Feng Department of Radiology Physics The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology The Cancer Hospital of the University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China

Objective: The incidence of brain metastasis from esophageal cancer(BMEC) has increased in recent years.Thus, it is necessary to identify factors that affect long-term outcomes for such patients.Methods: From January 1997 to July 2018, consecutive patients(10,043 patients, 31 with brain metastasis) with esophageal cancer(EC) treated at Zhejiang cancer Hospital were recruited for retrospective analysis.Demographic, clinical, and pathological variables and the survival data were retrieved.Results: The median time from diagnosis of EC to diagnosis of brain metastases was 7.67(range, 0.43-55.20)months. The median survival time of BMEC patients from diagnosis of primary esophageal tumor was 16.7(range,2.33-163.30) months and the median survival time from the point of diagnosis of brain metastasis was 6.47(range,0.43-148.13) months. Univariate and multivariate analyses showed that the pathology type, EC without chemotherapy, and bone metastasis history were significantly associated with a shorter time interval between the first treatment of EC and brain metastasis. Chemotherapy history after brain metastasis, whole brain radiation therapy(WBRT) history, and surgery were significant predictors for better long-term survival outcomes.Conclusions: Our findings indicate that the use of surgery, WBRT, and chemotherapy can achieve the best therapeutic effects for BMEC patients.

关键词： Brain metastasis from esophageal cancer time to brain metastasis(TTBM) prognosis factors survival time radiotherapy chemotherapy

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pH-triggered cancer-targeting polymers:From extracellular accumulation to intracellular release

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Nano Research 2023年第4期16卷 5155-5168页

作者： Rizwan Ullah Khan Jinning Shao Jia-Yu Liao Linghui Qian institute of Drug Metabolism and Pharmaceutical Analysis Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical SciencesCancer Center&Hangzhou Institute of Innovative MedicineZhejiang UniversityHangzhou 310058China

Stimuli-responsive polymers are promising to achieve targeted delivery,improved stability during circulation,and controlled release of therapeutic and diagnostic agents.Among them,pH-responsive polymeric nanocarriers have attracted significant attention as pH varies in different body fluids(e.g.,stomach,intestine,and colon)and intracellular organelles(e.g.,endosome,lysosome,and mitochondria)to maintain homeostasis,while distinctive pH changes are also found in certain pathological states.For example,the extracellular environment of the tumor is acidic,which can be employed to drive selective delivery.During the internalization process,since most nanocarriers enter cells upon endocytosis where a drop of pH from 6.5 to 5.0 can occur from endosome to lysosome,pH-sensitive groups have been developed for enhanced cargo release.In this review,both non-covalent and covalent interactions responsive to pH changes are introduced,with a focus on the structure-property relationship and their applications in cancer targeting and endosomal escape.

关键词： cancer targeting pH-responsive structure-property relationship charge shifting acid-labile linkage

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The impact of lipids on the cancer—immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

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Acta Pharmaceutica Sinica B 2023年第4期13卷 1488-1497页

作者： Mingming Zheng Wenxin Zhang Xi Chen Hongjie Guo Honghai Wu Yanjun Xu Qiaojun He Ling Ding Bo Yang Zhejiang Province Key Laboratory of Anti-cancer Drug Research Institute of Pharmacology and ToxicologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Department of Medical Thoracic Oncology the Cancer Hospital of University of Chinese Academy of Sciences(Zhejiang Cancer Hospital)Chinese Academy of SciencesHangzhou 310022China The Innovation institute for Artificial Intelligence in Medicine Zhejiang UniversityHangzhou 310018China cancer Center of Zhejiang University Hangzhou 310058China

Lipids have been found to modulate tumor biology,including proliferation,survival,and metastasis.With the new understanding of tumor immune escape that has developed in recent years,the influence of lipids on the cancer—immunity cycle has also been gradually discovered.First,regarding antigen presentation,cholesterol prevents tumor antigens from being identified by antigen presenting cells.Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells,impairing antigen presentation to T cells.Prostaglandin E2(PGE2)reduce the accumulation of tumor-infiltrating dendritic cells.Regarding T-cell priming and activation,cholesterol destroys the structure of the T-cell receptor and reduces immunodetection.In contrast,cholesterol also promotes T-cell receptor clustering and relative signal transduction.PGE2 represses T-cell proliferation.Finally,regarding T-cell killing of cancer cells,PGE2 and cholesterol weaken granule-dependent cytotoxicity.Moreover,fatty acids,cholesterol,and PGE2 can improve the activity of immunosuppressive cells,increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines.Given the regulatory role of lipids in the cancer—immunity cycle,drugs that modulate fatty acids,cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy.These strategies have been studied in both preclinical and clinical studies.

关键词： Lipids Fatty acids Cholesterol Prostaglandin E2 Tumor immune escape cancer—immunity cycle Immunotherapy Combination therapy

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Detecting circulating tumor material and digital pathology imaging during pancreatic cancer progression

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World Journal of Gastrointestinal Oncology 2017年第6期9卷 235-250页

作者： Radim Moravec Rao Divi Mukesh Verma Surveillance Research Program Division of Cancer Control and Population SciencesNational Cancer InstituteNational Institutes of Health Methods and Technologies Branch Division of Cancer Control and Population SciencesNational Cancer InstituteNational Institutes of Health

Pancreatic cancer(PC) is a leading cause of cancerrelated death worldwide. Clinical symptoms typically present late when treatment options are limited and survival expectancy is very short. Metastatic mutations are heterogeneous and can accumulate up to twenty years before PC diagnosis. Given such genetic diversity, detecting and managing the complex states of disease progression may be limited to imaging modalities and markers present in circulation. Recent developments in digital pathology imaging show potential for early PC detection, making a differential diagnosis, and predicting treatment sensitivity leading to long-term survival in advanced stage patients. Despite large research efforts, the only serum marker currently approved for clinical use is CA 19-9. Utility of CA 19-9 has been shown to improve when it is used in combination with PC-specific markers. Efforts are being made to develop early-screening assays that can detect tumor-derived material, present in circulation, before metastasis takes a significant course. Detection of markers that identify circulating tumor cells and tumor-derived extracellular vesicles(EVs) in biofluid samples offers a promising non-invasive method for this purpose. Circulating tumor cells exhibit varying expression of epithelial and mesenchymal markers depending on the state of tumor differentiation. This offers a possibility for monitoring disease progression using minimally invasive procedures. EVs also offer the benefit of detecting molecular cargo of tumor origin and add the potential to detect circulating vesicle markers from tumors that lack invasive properties. This review integrates recent genetic insights of PC progression with developments in digitalpathology and early detection of tumor-derived circulating material.

关键词：传播肿瘤房间数字病理早察觉 Exosomes 胰腺的癌症

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