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Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts

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Science China Life Sciences 2025年第1期 263-271页

作者： Siyi He Zhiyi Zhang Guohui Song Zhenhai Wang Chunyun Dai Shipeng Yan Kun Jiang Bingbing Song He Li Maomao Cao Dianqin Sun Fan Yang Xinxin Yan Shaoli Zhang Yi Teng Qianru Li Changfa Xia Wanqing Chen Office of cancer Screening National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College Department of Gastroenterology Gansu Wuwei Tumor Hospital Cixian cancer Institute Linzhou cancer Hospital Center for Disease Control and Prevention of Sheyang County Department of cancer Prevention and Control Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of MedicineCentral South University Luoshan Center for Disease Control and Prevention Office for cancer Control and Research Affiliated Cancer Hospital of Harbin Medical University

Surveillance recommendations for gastric cancer（GC） in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter communitybased cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015–2017 and followed-up until 2021. Cumulative incidence rates（CIRs） of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixedeffects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic（atrophic gastritis/intestinal metaplasia） and neoplastic lesions（low-grade/high-grade dysplasia）, respectively(Ptrend<0.001). Four predictors, including male, ≥60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients（≥3 risk factors） with non-neoplastic lesions showed higher GC risks（adjusted HR=7.73, 95%CI: 4.29–13.92）, and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions（aHR=3.07, 95%CI: 1.67–5.64） and high-risk patients with mild lesions（aHR=7.29, 95%CI: 3.58–14.86） showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3–5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

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Advances in ATM,ATR,WEE1,and CHK1/2 inhibitors in the treatment of PARP inhibitor-resistant ovarian cancer

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cancer Biology & Medicine 2023年第12期20卷 915-921页

作者： Qin Tang Xin Wang Haixia Wang Lin Zhong Dongling Zou Department of Gynecologic Oncology Chongqing University Cancer Hospital&Chongqing Cancer Institute&Chongqing Cancer HospitalChongqing 400030China Chongqing Specialized Medical Research Center of ovarian cancer Chongqing 400030China Organoid Transformational Research Center Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized TreatmentChongqing University Cancer HospitalChongqing 400030China

ovarian cancer(OC)poses a significant challenge in modern gynecologic oncology,both diagnostically and *** to the American cancer Society,an estimated 21,000 new cases of OC were reported in the United States alone in *** most prevalent subtype of OC87,highgrade serous(HGS),is characterized by heightened genomic instability and defects in DNA damage response(DDR)pathways,which contribute to disease development and ***,approximately 50%of HGS ovarian cancer(HGSOC)patients exhibit homologous recombination repair(HRR)defects(HRDs)3.

关键词： cancer treatment alone

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National cancer Institute’s early detection research network:a model organization for biomarker research

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Journal of the National cancer Center 2023年第2期3卷 93-99页

作者： Paul D.Wagner Sudhir Srivastava cancer Biomarkers Research group Division of Cancer PreventionNational Cancer InstituteBethesdaUSA

For many cancers a primary cause of poor survival is that they are detected at a late stage when therapies are less *** screening methods exist to detect some types of cancer at an early stage,there are currently no effective methods to screen for most types of *** have the potential to improve detection of early-stage cancers,risk stratification,and prediction of which pre-cancerous lesions are likely to progress and to make screening tests less *** thousands of research articles on biomarkers for early detection are published every year,few of these biomarkers have been validated and shown to be clinically *** reflects both the inherent difficulty in detecting early-stage cancers and a disconnect between the process of discovering biomarkers and their use in the *** overcome this limitation the US National cancer Institute created the Early Detection Research *** is a highly collaborative program that brings together biomarker discoverers,assay developers,and *** provides an infrastructure that is essential for developing and validating biomarkers and imaging methods for early cancer detection and has successfully completed several multicenter validation studies.

关键词： Biomarkers Early detection Validation Collaboration Data sharing

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Helicobacter pylori CagA protein polymorphisms and their lack of association with pathogenesis

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World Journal of Gastroenterology 2010年第31期16卷 3936-3943页

作者： Nicole Acosta Andrés Quiroga Pilar Delgado María Mercedes Bravo Carlos Jaramillo Molecular Diagnostics and Bioinformatics Laboratory Biological Sciences DepartmentLos Andes University Infectious Agents and cancer Research group National Cancer Institute(Colombia)

AIM: To investigate Helicobacter pylori (H. pylori) CagA diversity and to evaluate the association between protein polymorphisms and the occurrence of gastric pathologies. METHODS: One hundred and twenty-two clinical isolates of H. pylori cultured from gastric biopsies obtained from Colombian patients with dyspepsia were included as study material. DNA extracted from isolates was used to determine cagA status, amplifying the C-terminal cagA gene region by polymerase chain reaction. One hundred and six strains with a single amplicon were sequenced and results were used to characterize the 3' variable region of the cagA gene. To establish the number and type of tyrosine phosphorylation motifs Glutamine acid-Proline-Isoleucine-Tyrosine-Alanine (EPI-YA) bioinformatic analysis using Amino Acid Sequence Analyzer-Amino Acid Sequence Analyzer software was conducted. Analysis of the association between the number of EPIYA motifs and the gastric pathology was performed using χ2 test and analysis of the presence of EPIYA-C motifs in relation to the pathology was made by logistic regression odds ratios. Comparisons among EPIYA types found and those reported in GenBank were performed using a proportion test in Statistix Analytical Software version 8.0. RESULTS: After amplification of the 3' of the cagA gene, 106 from 122 isolates presented a single amplicon and 16 showed multiple amplicons. As expected, diversity in the size of the cagA unique fragments among isolates was observed. The 106 strains that presented a single amplicon after 3' cagA amplification came from patients with gastritis (19 patients), atrophic gastritis (21), intestinal metaplasia (26), duodenal ulcer (22) and gastric cancer. DNA sequence analysis showed that the differences in size of 3' cagA unique fragments was attributable to the number of EPIYA motifs: 1.9% had two EPIYA motifs, 62.3% had three, 33.0% had four and 2.8% had five motifs. The majority of tested clinical strains (62.3%) were found to harbor

关键词： Helicobacter pylori CagA-protein polymorphisms Molecular characterization Bioinformatic analysis Pathogenesis cancer

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Molecular mechanisms of metastasis in prostate cancer

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Asian Journal of Andrology 2009年第1期11卷 57-67页

作者： Noel W. Clarke Claire A. Hart Mick D. Brown Genito-Urinary cancer Research group School of Cancer and lmaging Sciences Paterson Institute for Cancer ResearchChristie Hospital University of Manchester Manchester M20 4BX UK

Prostate cancer （PCa） preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is currently unknown, although considerable progress has been made in determining the key players in this process. In this review, we present the current understanding of the molecular processes driving PCa metastasis to the bone.

关键词： bone bone marrow stroma metastasis prostate cancer

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Predicting the physiological relevance of in vitro cancer preventive activities of phytochemicals

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Acta Pharmacologica Sinica 2007年第9期28卷 1274-1304页

作者： Lynne M HOWELLS Elena P MOISEEVA Christopher PNEAL Bethany EFOREMAN Catherine KANDREADI Yi-yang SUN E Ann HUDSON Margaret M MANSON cancer Biomarkers and Prevention group University of LeicesterLeicester LE1 7RHUK

There is growing interest in the ability of phytochemicals to prevent chronicdiseases,such as cancer and heart ***,some of these agents havepoor bioavailability and many of the in-depth studies into their mechanisms ofaction have been carried out in vitro using doses which are unachievable *** order to optimize the design of chemopreventive treatment,it is impor-tant to determine which of the many reported mechanisms of action are *** this review we consider the physiologically achievable doses for afew of the best studied agents (indole-3-carbinol,diindolylmethane,curcumin,epigallocatechin-3-gallate and resveratrol) and summarize the data derived fromstudies using these low concentrations in cell *** then cite examples of invitro effects which have been observed in ***,the ability of agentcombinations to act synergistically or antagonistically is *** con-clude that each of the compounds shows an encouraging range of activities invitro at concentrations which are likely to be physiologically *** arealso many examples of in vivo studies which validate in vitro *** consideration is that combinations of agents can result in significantactivity at concentrations where any single agent is ***,for each of thecompounds reviewed here,in vitro studies have provided useful insights intotheir mechanisms of action in ***,data are lacking on the full rangeof activities at low doses in vitro and the benefits or otherwise of combinations invivo.

关键词： bioavailability cancer chemoprevention curcumin diet diindolylmethane epigallo catechin-3-gallate indole-3-carbinolresveratrol

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Circulating cancer stem cells:the importance to select

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Chinese Journal of cancer Research 2015年第5期27卷 437-449页

作者： Ming-Hsin Yang Ahmet Imrali Christopher Heeschen Centre for Stem Cells in cancer & Ageing Barts Cancer InstituteQueen Mary University of London Division of Urology Department of SurgeryTri-Service General HospitalNational Defense Medical Center Stem Cells & cancer group Molecular Pathology ProgrammeSpanish National Cancer Research Centre(CNIO)

It has been demonstrated that even localized tumors withottt chnically apparent metastasis give rise to circulating tumor cells （CTCs）. A growing number of technically diverse platforms are being developed for detecting/isolating CTCs in the circulating blood. Despite the technical challenges of isolating rare CTCs from blood, recent studies have already shown the predictive value of CTCs enumeration. Thus, it is becoming increasingly accepted that CTC numbers are linked to patients＇ outcome and may also be used to monitor treatment response and disease relapse, respectively. Further CTCs provide a non-invasive source for tumor material, ＇liquid biopsy＇, which is particularly important for patients, where no biopsy material can be obtained or where serial biopsies of the tumor, e.g., following treatment, are practically impossible. On the other hand the molecular and biological characterization of CTCs has still remained at a rather experimental stage. Future studies are necessary to define CTC heterogeneity to establish the crucial role of circulating cancer stem cells for driving metastasis, which represent a distinct subpopulation of CTCs that bear metastasis-initiating capabilities based on their sternness properties and invasiveness and thus are critical for the patients＇ clinical outcome. As compared to non-tumorigenic/metastatic bulk CTCs, circulating cancer stem cells may not only be capable of evading from the primary tumor, but also escape from immune surveillance, survive in the circulating blood and subsequently form metastases in distant organs. Thus, circulating cancer stem cells represent a subset of exclusively tumorigenic cancer stem cells characterized by their invasive characteristics and are potential therapeutic targets for preventing disease progression. To date, only a few original reports and reviews have been published focusing on circulating cancer stem cells. This review discusses the potential importance of isolating and characterizing th

关键词： cancer stem cells circulating tumor cells (CTCs) drug resistance

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CagA EPIYA polymorphisms in Colombian Helicobacter pylori strains and their influence on disease-associated cellular responses

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World Journal of Gastrointestinal Oncology 2013年第3期5卷 50-59页

作者： Carlos Alberto Fajardo Andrés Javier Quiroga Andrea Coronado Karen Labrador Nicole Acosta Pilar Delgado Carlos Jaramillo María Mercedes Bravo cancer and Infectious Agents Research group National Cancer Institute Molecular Diagnostics and Bioinformatics Laboratory Biological Sciences Department Los Andes University

AIM: To investigate the influence of the CagA diversity in Helicobacter pylori (H. pylori ) strains from Colombia on the host cell biology. METHODS: Eighty-four H. pylori-cagA positive strains with different Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs patterns, isolated from patients with gastritis (n=17), atrophic gastritis (n=17), duodenal ulcer (n=16), intestinal metaplasia (n=16) and gastric cancer (n=18), were included. To determine the integrity of the cag pathogenicity island (cag PAI) we evaluated the presence of cagA, cagT, cagE, and cag10 genes by polymerase chain reaction. AGS gastric epithelial cellswere infected with each strain and assayed for translo-cation and tyrosine phosphorylation of CagA by western blot, secretion of interleukin-8 (IL-8) by enzyme-linked immuno sorbent assay after taking supernatants from cocultures and cell elongation induction. For cell elongation quantification, coculture photographs were taken and the proportion of "hummingbird" cells (>15 μm) was determined. RESULTS: Overall 72% (60/84) of the strains were found to harbor a functional cag PAI. Levels of phos-phorylated CagA were significantly higher for isolates from duodenal ulcer than the ones in strains from gas-tritis, atrophic gastritis, intestinal metaplasia and gastric cancer (49.1% ± 23.1% vs 21.1% ± 19.5%, P < 0.02; 49.1% ± 23.1% vs 26.2%±14.8%, P<0.045; 49.1% ± 23.1% vs 21.5% ± 19.5%, P<0.043 and 49.1% ± 23.1% vs 29.5% ± 27.1%, P < 0.047 respectively). We observed variable IL-8 expression levels ranging from 0 to 810 pg/mL and from 8.8 to 1442 pg/mL at 6 h and 30 h post-infection, respectively. cagPAI-defective strains did not induce detectable levels of IL-8 at 6 h post-infection. At 30 h post-infection all strains induced IL-8 expression in AGS cells, although cagPAI-defective strains induced significantly lower levels of IL-8 than strains with a functional cagPAI (57.1 ± 56.6 pg/mL vs 513.6 ± 338.6 pg/mL,P < 0.0001). We did not observe differences in the extent of cell

关键词： Helicobacter pylori cagA 3’region CagA protein Interleukin 8 Cell elongation Glu-Pro-Ile-Tyr-Ala

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Risk factors for bleeding after endoscopic submucosal dissection of colorectal neoplasms

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World Journal of Gastroenterology 2014年第7期20卷 1839-1845页

作者： Sho Suzuki Akiko Chino Teruhito Kishihara Naoyuki Uragami Yoshiro Tamegai Takanori Suganuma Junko Fujisaki Masaaki Matsuura Takao Itoi Takuji Gotoda Masahiro Igarashi Fuminori Moriyasu Department of Gastroenterology Cancer Institute HospitalJapanese Foundation for Cancer ResearchTokyo 135-8550Japan Fuminori Moriyasu Department of Gastroenterology and HepatologyTokyo Medical UniversityTokyo 160-0023Japan Bioinformatics group Genome Centerand Division of Cancer GenomicsCancer InstituteJapanese Foundation for Cancer ResearchTokyo 135-8550Japan

AIM: To investigate the risk factors for delayed bleeding following endoscopic submucosal dissection (ESD) treatment for colorectal neoplasms.

关键词： Adverse event Bleeding Colorectal neoplasms Endoscopic submucosal dissection Hemorrhage

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Molecular signaling in cancer stem cells of tongue squamous cell carcinoma:Therapeutic implications and challenges

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World Journal of Stem Cells 2023年第5期15卷 438-452页

作者： Priyanka Joshi Sanjeev Waghmare Stem Cell Biology group Cancer Research InstituteAdvanced Centre for Treatment Research and Education in CancerTata Memorial CentreNavi Mumbai 410210India

Head and neck squamous cell carcinoma is the seventh most common cancer worldwide with high mortality *** oral cavity cancers,tongue carcinoma is a very common and aggressive oral cavity *** the implementation of a multimodality treatment regime including surgical intervention,chemo-radiation as well as targeted therapy,tongue carcinoma shows a poor overall 5-year survival pattern,which is attributed to therapy resistance and recurrence of the *** presence of a rare population,i.e.,cancer stem cells(CSCs)within the tumor,are involved in therapy resistance,recurrence,and distant metastasis that results in poor survival *** agents targeting CSCs have been in clinical trials,although they are unable to reach into therapy stage which is due to their failure in trials.A more detailed understanding of the CSCs is essential for identifying efficient *** signaling pathways,which are differentially regulated in the CSCs,are one of the promising targets to manipulate the CSCs that would provide an improved *** this review,we summarize the current understanding of molecular signaling associated with the maintenance and regulation of CSCs in tongue squamous cell carcinoma in order to emphasize the need of the hour to get a deeper understanding to unravel novel targets.

关键词： Head and neck squamous cell carcinoma cancer stem cells Signaling Tongue squamous cell carcinoma

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