Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether k...Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.展开更多
Background: Early research describing the concept of intensity-modulated conformal radiotherapy (IMRT) was based on 7 to 9 beams to reach an adequate level of modulation. Nevertheless, its implementation demands signi...Background: Early research describing the concept of intensity-modulated conformal radiotherapy (IMRT) was based on 7 to 9 beams to reach an adequate level of modulation. Nevertheless, its implementation demands significant resources. Our objective was to compare the compliance and homogeneity of target dose distribution between simplified IMRT and 3D-CRT in patients with cervical cancer and to assess the clinical value of simplified IMRT. Materials and Methods: From 2016 to 2017, 17 patients with stage IIB - IIIC cervical cancer were treated with external beam radiotherapy using simplified IMRT (12 cases) or 3DCRT (05 cases) and brachytherapy. Prior to radiotherapy, CT scans were conducted to delineate the target volume. The clinical target volume (CTV) included the uterus, primary tumor, supravaginal portion of the cervix, paracervical tissue, common iliac, internal and external iliac lymph nodes, obturator, and pre sacral lymph nodes, and the surrounding tissues. If the lower vagina was involved, the target volume included the whole vagina. The planning target volume (PTV) included the CTV with 1 cm anteriorly and 0.5 cm in all other directions. The PTV received 95% of 45 Gy (1.8 Gy/25 fraction). Dose-volume histogram, conformity index, homogeneity index, and treatment time per fraction were compared. Results: The 3D-CRT plan was more homogeneous than the simplified IMRT plan, while the simplified IMRT plan was more conformal. The volume of small bowels that received high-dose radiation significantly increased with simplified IMRT compared to 3D-CRT. Treatment time per fraction was 6 and 13 minutes for 3D-CRT and simplified IMRT, respectively. Conclusion: The simplified IMRT treatment plan is technically and dosimetrically acceptable and an alternative to the classic 3D-CRT plan for cervical cancer. It provides better dose distribution than 3D-CRT. However, the 3D-CRT treatment plan significantly reduced the overall treatment time per fraction.展开更多
Cancer remains one of the leading causes of death in the world,with more than 9 million deaths in 2022,a number that continues to rise.This highlights the urgent need for the development of new drugs,with enhanced ant...Cancer remains one of the leading causes of death in the world,with more than 9 million deaths in 2022,a number that continues to rise.This highlights the urgent need for the development of new drugs,with enhanced antitumor capabilities and fewer side effects.Metal-based drugs have been used in clinical practice since the late 1970s,beginning with the introduction of cisplatin.Later,two additional platinum-based molecules,carboplatin,and oxaliplatin,were introduced,and all three continue to be widely used in the treatment of various cancers.However,despite their significant anticancer activity,the undesirable side effects of these drugs have motivated the scientific community to explore other metal-based complexes with greater anticancer potential and fewer adverse effects.In this context,metals such as ruthenium,copper,gold,zinc,palladium,or iridium,present promising alternatives for the development of new anticancer agents.Unfortunately,although thousands of metal-based drugs have been synthesized and tested both in vitro and in animal models,only a few ruthenium-based drugs have entered clinical trials in recent years.Meanwhile,many other molecules with comparable or even greater anticancer potential have not advanced beyond the laboratory stage.In this review,we will revisit the mechanisms of action and anticancer activities of established platinum-based drugs and explore their use in recent clinical trials.Additionally,we will examine the development of potential new metal-based drugs that could one day contribute to cancer treatment worldwide.展开更多
The Chinese Society of Clinical Oncology Non-small Cell Lung Cancer(CSCO NSCLC)guidelines were first published in 2016,ranking among the earliest-released guidelines within the CSCO series.In 2020 the CSCO published s...The Chinese Society of Clinical Oncology Non-small Cell Lung Cancer(CSCO NSCLC)guidelines were first published in 2016,ranking among the earliest-released guidelines within the CSCO series.In 2020 the CSCO published separate guidelines for NSCLC and small cell lung cancer(SCLC)for the first time to improve clinical usability.展开更多
Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 ...Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.展开更多
Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely int...Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.展开更多
Cancer is one of the deadliest diseases in developing countries. In recent years, natural plant-based compounds have been used in the search for drugs to combat numerous diseases, including cancer. In this study, we e...Cancer is one of the deadliest diseases in developing countries. In recent years, natural plant-based compounds have been used in the search for drugs to combat numerous diseases, including cancer. In this study, we evaluate the cytotoxic properties of paanfo tiben 1 and paanfo tiben 2, two traditional herbal formulations from Burkina Faso used in the treatment of cancer in Burkina Faso. To this end, the recipes were infused and freeze-dried. The dry extracts obtained were used to determine total phenolics and flavonoids content, assess antioxidant activity using the DPPH, ABTS and FRAP methods, evaluate anti-inflammatory properties by inhibiting 15-LOX, COX 1 and 2, and assess cytotoxic activity on HeLa cervical cancer and HePG2 liver cancer cell lines using the MTT test. The paanfo tiben 1 recipe showed the highest levels of total phenolics and flavonoids, as well as the best antioxidant activities, with IC50 values of 21.020 ± 0.6 µg/ml and 22.94 ± 0.57 µg/ml for DPPH and ABTS, and 165.15 mM EAA/mg dry extract for FRAP. It also exhibited the best cytotoxic activity with IC50 values of 112.02 ± 0.025 µg/ml on HeLa cells and 80.67 ± 6.08 µg/ml on HepG2 cells. On the other hand, paanfo tiben 2 exhibited the best anti-inflammatory activities through inhibition of 15-LOX and COX 1, with inhibition percentages at 100 µg/ml of 32.523% and 24.717 % respectively. These results could justify the traditional use of these two recipes by traditional health practitioners in the treatment of cancer sufferers in Burkina Faso.展开更多
Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (mi...Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients’ outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.展开更多
AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from ga...AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.展开更多
AIM： To study the association between nitrite and nitrosamine intake and gastric cancer （GC）, between meat and processed meat intake, GC and oesophageal cancer （OC）, and between preserved fish, vegetable and smok...AIM： To study the association between nitrite and nitrosamine intake and gastric cancer （GC）, between meat and processed meat intake, GC and oesophageal cancer （OC）, and between preserved fish, vegetable and smoked food intake and GC. METHODS： In this article we reviewed all the published cohort and case-control studies from 1985-2005, and analyzed the relationship between nitrosamine and nitrite intake and the most important related food intake （meat and processed meat, preserved vegetables and fish, smoked foods and beer drinking） and GC or OC risk. Sixty-one studies, 11 cohorts and 50 case-control studies were included. RESULTS： Evidence from case-control studies supported an association between nitrite and nitrosamine intake with GC but evidence was insufficient in relation to OC. A high proportion of case-control studies found a positive association with meat intake for both tumours （11 of 16 studies on GC and 11 of 18 studies on OC）. A relatively large number of case-control studies showed quite consistent results supporting a positive association between processed meat intake and GC and OC risk （10 of 14 studies on GC and 8 of 9 studies on OC）. Almost all the case-control studies found a positive and significant association between preserved fish, vegetable and smoked food intake and GC. The evidence regarding OC was more limited. Overall the evidence from cohort studies was insufficient or more inconsistent than that from case-control studies.CONCLUSION： The available evidence supports a positive association between nitrite and nitrosamine intake and GC, between meat and processed meat intake and GC and OC, and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive.展开更多
BACKGROUNDLong noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastriccancer (GC) progression and metastasis. Searching for coexpressed lncRNAclusters or representative biomarkers related to malignant...BACKGROUNDLong noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastriccancer (GC) progression and metastasis. Searching for coexpressed lncRNAclusters or representative biomarkers related to malignant phenotypes of GC mayhelp to elucidate the mechanism of tumor development and predict the prognosisof GC.AIMTo investigate the prognostic value of NOTCH1 associated with lncRNA in T cellacute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of itsinvolvement in GC invasion and metastasis.METHODSRNA sequencing and corresponding clinical data were downloaded from TheCancer Genome Atlas database. The significance module was studied byweighted gene coexpression network analysis. A total of 336 clinical sampleswere included in the study. Gene silencing, reverse transcription polymerasechain reaction, western blotting, scrape motility assay, and Transwell migrationassay were used to assess the function of hub-lncRNAs.RESULTSAt the transcriptome level, 3339 differentially expressed lncRNAs were obtained.weighted gene coexpression network analysis was used to obtain 15 lncRNAclusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hublncRNAof blue module and was an independent risk factor for GC prognosis.NALT1 was overexpressed in GC and its expression was closely related toinvasion and metastasis. The mechanism may involve NALT1 regulation ofNOTCH1, which is associated with lncRNA in T cell acute lymphoblasticleukemia, through cis regulation, thereby affecting the expression of the NOTCHsignaling pathway.CONCLUSIONNALT1 is overexpressed and promotes invasion and metastasis of GC. Themechanism may be related to regulation of NOTCH1 by NALT1 and its effect onNOTCH signaling pathway expression.展开更多
Based upon studies from randomized clinical trials, the extended （D2） lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lympha...Based upon studies from randomized clinical trials, the extended （D2） lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes （PAN） in JCOG9501, the clinical benefit of D2＋ para-aortic nodal dissection （PAND） for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.l I nodes has been controversial, and however, the final results from the randomized trial ofJCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as MI stage in the current version of the Japanese classification. We propose that D2~No.14v and ＋No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients.展开更多
Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the e...Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC.The primary endpoint was clinical benefit rate(CBR).Secondary endpoints included progression-free survival(PFS),time to response(TTR),duration of response(DoR),central nervous system(CNS) as first site of relapse,and safety.The results showed that there were 23 patients with partial responses and 7 patients with stable disease,resulting in a CBR of 57.7%.The median PFS was 6.34 months(95% confidence interval,4.93-9.82 months).The median TTR and DoR were 4.07 months(range,0.03-14.78 months) and 6.93 months(range,1.45-9.72 months),respectively.Thirteen(25.0%) patients had new lesions as disease progression.Among them,2(3.8%) patients had CNS disease reported as the first relapse.The most common toxicities were palmar-plantar erythrodysesthesia(59.6%),diarrhea(48.1%),rash(48.1%),hyperbilirubinemia(34.6%),and fatigue(30.8%).Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample,baseline PIK3CA mutation status was not associated with CBR(P = 0.639) or PFS(P = 0.989).These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC,irrespective of PIK3CA status.展开更多
Objective: The aim of the study was to investigate the level of self-image of patients after breast cancer surgery, and explore factors influencing self-image among patients who have experienced different types of sur...Objective: The aim of the study was to investigate the level of self-image of patients after breast cancer surgery, and explore factors influencing self-image among patients who have experienced different types of surgeries, and set out a foundation for the improvement of care strategies. Methods: The 538 patients with primary breast cancer who underwent surgery in the Department of Breast Surgery, First Hospital of China Medical University, Shenyang, China, from January 2004 to January 2009 were included in the study. The psychological status of the patients was evaluated by body image after breast cancer questionnaire (BIBCQ), social support rating scale (SSRS), self-rating anxiety scale (SRAS), depression rating scale (DRS), and general information questionnaire. The factors influencing the self-image were selected by a stepwise regression analysis. Results: The patients who underwent breast-conserving surgery were the most satisfied with their body image, followed by those underwent surgery of modified radical mastectomy with reconstruction. However, cases treated by modified radical mastectomy without reconstruction had negative outcomes. Regardless of operation type, the self-image was influenced by anxiety, level of abuse by husband, and sexual satisfaction after operation. Conclusion: The self-image of patients who underwent different breast cancer surgeries was influenced by different factors, and individualized nursing should be offered in accordance with the specific situation.展开更多
Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoido...Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.展开更多
AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We...AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.展开更多
Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully det...Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population.Methods:We performed the first population study investigating the germline mutation status in more than 1,000(n=1,923)Chinese patients with CRC and examined their relationship with the somatic mutational landscape.Germline alterations were examined with a 58-gene next-generation sequencing panel,and somatic alterations were examined with a 605-gene panel.Results:A total of 92 pathogenic(P)mutations were identified in 85 patients,and 81 likely pathogenic(LP)germline mutations were identified in 62 patients,accounting for 7.6%(147/1,923)of all patients.MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups,respectively.Patients with P/LP mutations had a significantly higher ratio of microsatellite instability,highly deficient mismatch repair,family history of CRC,and lower age.The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group.The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the nonLynch syndrome group.Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Population risk analysis indicated that the overall odds ratio was 11.13(95%CI:8.289–15.44)for the P group and 20.68(95%CI:12.89–33.18)for the LP group.Conclusions:Distinct features were revealed in Chinese patients with CRC with germline mutations.The Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Patients with P/LP germline mutations exhibited higher CRC risk.展开更多
Although the genetic bases of most hereditary cancer syndromes are known,and genetic tests are available for them,the incidence of the most rare of these syndromes is likely underestimated,partially because the clinic...Although the genetic bases of most hereditary cancer syndromes are known,and genetic tests are available for them,the incidence of the most rare of these syndromes is likely underestimated,partially because the clinical expression is neither fully understood nor easily diagnosed due to the variable and complex expressivity. The clinical features of a small pool of rare cancer syndromes include gastroenterological signs,though not necessarily tumors,that could require the intervention of a gastroenterologist during any of the phases of the clinical management. Herein we will attempt to spread the knowledge on these rare syndromes by summarizing the phenotype and genetic basis,and revising the peculiar gastroenterological signs whose underlying role in these rare hereditary cancer syndromes is often neglected. Close collaboration between geneticists and gastroenterologists could facilitate both the early identification of patients or relatives at-risk and the planning of multidisciplinary and tailored management of these subjects.展开更多
Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afa...Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afatinib have not been evaluated.Methods: A prognostic tool for overall survival(OS)/progression free survival(PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6(n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1(n = 390) and LUX-Lung 2(n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor treatment.Results: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk group.Conclusions: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment.展开更多
基金funded by the National Natural Science Foundation of China(No.82273704)Noncommunicable Chronic Diseases-National Science and Technology Major Project(No.2023ZD0501400-2023ZD0501402)+4 种基金Beijing Hospitals Authority’s Ascent Plan(DFL20241102)Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support(No.ZLRK202325)China Postdoctoral Science Foundation(2024M760152)Peking University Medicine Fund for World’s Leading Discipline or Discipline Cluster Development(No.BMU2022XKQ004)Science Foundation of Peking University Cancer Hospital(Nos.BJCH2024BJ02,XKFZ2410,BJCH2025CZ04,and 2022-27)。
文摘Objective:Based on multistage metabolomic profiling and Mendelian randomization analyses,the current study identified plasma metabolites that predicted the risk of developing gastric cancer(GC)and determined whether key metabolite levels modified the GC primary prevention effects.Methods:Plasma metabolites associated with GC risk were identified through a case-control study.Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial(SIT),a nested case-control study of the Mass Intervention Trial in Linqu,Shandong province(MITS),China,the UK Biobank,and the Finn Gen project.Results:A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population(SIT:HR=1.26 per 1 SD change,95%CI:1.07±1.49;MITS:HR=1.07,95%CI:1.00±1.14)and an increased gastric adenocarcinoma risk in Finn Gen(OR=1.68,95%CI:1.16±2.45).Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level(P-interaction=0.098)and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level(P-interaction=0.02).Conclusions:Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention.Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.
文摘Background: Early research describing the concept of intensity-modulated conformal radiotherapy (IMRT) was based on 7 to 9 beams to reach an adequate level of modulation. Nevertheless, its implementation demands significant resources. Our objective was to compare the compliance and homogeneity of target dose distribution between simplified IMRT and 3D-CRT in patients with cervical cancer and to assess the clinical value of simplified IMRT. Materials and Methods: From 2016 to 2017, 17 patients with stage IIB - IIIC cervical cancer were treated with external beam radiotherapy using simplified IMRT (12 cases) or 3DCRT (05 cases) and brachytherapy. Prior to radiotherapy, CT scans were conducted to delineate the target volume. The clinical target volume (CTV) included the uterus, primary tumor, supravaginal portion of the cervix, paracervical tissue, common iliac, internal and external iliac lymph nodes, obturator, and pre sacral lymph nodes, and the surrounding tissues. If the lower vagina was involved, the target volume included the whole vagina. The planning target volume (PTV) included the CTV with 1 cm anteriorly and 0.5 cm in all other directions. The PTV received 95% of 45 Gy (1.8 Gy/25 fraction). Dose-volume histogram, conformity index, homogeneity index, and treatment time per fraction were compared. Results: The 3D-CRT plan was more homogeneous than the simplified IMRT plan, while the simplified IMRT plan was more conformal. The volume of small bowels that received high-dose radiation significantly increased with simplified IMRT compared to 3D-CRT. Treatment time per fraction was 6 and 13 minutes for 3D-CRT and simplified IMRT, respectively. Conclusion: The simplified IMRT treatment plan is technically and dosimetrically acceptable and an alternative to the classic 3D-CRT plan for cervical cancer. It provides better dose distribution than 3D-CRT. However, the 3D-CRT treatment plan significantly reduced the overall treatment time per fraction.
文摘Cancer remains one of the leading causes of death in the world,with more than 9 million deaths in 2022,a number that continues to rise.This highlights the urgent need for the development of new drugs,with enhanced antitumor capabilities and fewer side effects.Metal-based drugs have been used in clinical practice since the late 1970s,beginning with the introduction of cisplatin.Later,two additional platinum-based molecules,carboplatin,and oxaliplatin,were introduced,and all three continue to be widely used in the treatment of various cancers.However,despite their significant anticancer activity,the undesirable side effects of these drugs have motivated the scientific community to explore other metal-based complexes with greater anticancer potential and fewer adverse effects.In this context,metals such as ruthenium,copper,gold,zinc,palladium,or iridium,present promising alternatives for the development of new anticancer agents.Unfortunately,although thousands of metal-based drugs have been synthesized and tested both in vitro and in animal models,only a few ruthenium-based drugs have entered clinical trials in recent years.Meanwhile,many other molecules with comparable or even greater anticancer potential have not advanced beyond the laboratory stage.In this review,we will revisit the mechanisms of action and anticancer activities of established platinum-based drugs and explore their use in recent clinical trials.Additionally,we will examine the development of potential new metal-based drugs that could one day contribute to cancer treatment worldwide.
文摘The Chinese Society of Clinical Oncology Non-small Cell Lung Cancer(CSCO NSCLC)guidelines were first published in 2016,ranking among the earliest-released guidelines within the CSCO series.In 2020 the CSCO published separate guidelines for NSCLC and small cell lung cancer(SCLC)for the first time to improve clinical usability.
基金supported by grants from the National Natural Science Foundation of China(Grant Nos.82172635,82272686,and 82203628)Natural Science Foundation of Tianjin(Grant No.23JCZDJC00200)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-010A).
文摘Introduction Small cell lung cancer(SCLC)is a highly aggressive malignancy with limited treatment options.Despite advances in immunotherapy,response rates remain low,and the efficacy of current molecular subtyping1,2 is insufficient to predict therapeutic outcomes3,4.A recently identified vulnerability in SCLC involves the dysregulation of nuclear-cytoplasmic transport,particularly through exportin 1(XPO1)5-7.
基金support by grants from Capital’s Funds for Health Improvement and Research(Grant No.2024-2-1024)Beijing Natural Science Foundation(Grant No.7232018).
文摘Advances in the identification of molecular biomarkers and the development of targeted therapies have enhanced the prognosis of patients with advanced gastric cancer.Several established biomarkers have been widely integrated into routine clinical diagnostics of gastric cancer to guide personalized treatment.Human epidermal growth factor receptor 2(HER2)was the first molecular biomarker to be used in gastric cancer with trastuzumab being the first approved targeted therapy for HER2-positive gastric cancer.Programmed death-ligand 1 positivity and microsatellite instability can guide the use of immunotherapies,such as pembrolizumab and nivolumab.More recently,zolbetuximab has been approved for patients with claudin 18.2-positive diseases in some countries.More targeted therapies,including savolitinib for MET-positive patients,are currently under clinical investigation.However,the clinical application of these diagnostic approaches could be hampered by many existing challenges,including invasive and costly sampling methods,variability in immunohistochemistry interpretation,high costs and long turnaround times for next-generation sequencing,the absence of standardized and clinically validated diagnostic cut-off values for some biomarkers,and tumor heterogeneity.Novel testing and analysis techniques,such as artificial intelligence-assisted image analysis and multiplex immunohistochemistry,and emerging therapeutic strategies,including combination therapies that integrate immune checkpoint inhibitors with targeted therapies,offer potential solutions to some of these challenges.This article reviews recent progress in gastric cancer testing,outlines current challenges,and explores future directions for biomarker testing and targeted therapy for gastric cancer.
文摘Cancer is one of the deadliest diseases in developing countries. In recent years, natural plant-based compounds have been used in the search for drugs to combat numerous diseases, including cancer. In this study, we evaluate the cytotoxic properties of paanfo tiben 1 and paanfo tiben 2, two traditional herbal formulations from Burkina Faso used in the treatment of cancer in Burkina Faso. To this end, the recipes were infused and freeze-dried. The dry extracts obtained were used to determine total phenolics and flavonoids content, assess antioxidant activity using the DPPH, ABTS and FRAP methods, evaluate anti-inflammatory properties by inhibiting 15-LOX, COX 1 and 2, and assess cytotoxic activity on HeLa cervical cancer and HePG2 liver cancer cell lines using the MTT test. The paanfo tiben 1 recipe showed the highest levels of total phenolics and flavonoids, as well as the best antioxidant activities, with IC50 values of 21.020 ± 0.6 µg/ml and 22.94 ± 0.57 µg/ml for DPPH and ABTS, and 165.15 mM EAA/mg dry extract for FRAP. It also exhibited the best cytotoxic activity with IC50 values of 112.02 ± 0.025 µg/ml on HeLa cells and 80.67 ± 6.08 µg/ml on HepG2 cells. On the other hand, paanfo tiben 2 exhibited the best anti-inflammatory activities through inhibition of 15-LOX and COX 1, with inhibition percentages at 100 µg/ml of 32.523% and 24.717 % respectively. These results could justify the traditional use of these two recipes by traditional health practitioners in the treatment of cancer sufferers in Burkina Faso.
文摘Colorectal cancer (CRC) is the third most common malignancy and the third leading cause of cancer related deaths in the United States. Almost 90% of the patients diagnosed with CRC die due to metastases. MicroRNAs (miRNAs) are evolutionarily conserved molecules that modulate the expression of their target genes post-transcriptionally, and they may participate in various physiological and pathological processes including CRC metastasis by influencing various factors in the human body. Recently, the role miRNAs play throughout the CRC metastatic cascade has gain attention. Many studies have been published to link them with CRC metastasis. In this review, we will briefly discuss metastatic steps in the light of miRNAs, along with their target genes. We will discuss how the aberration in the expression of miRNAs leads to the formation of CRC by effecting the regulation of their target genes. As miRNAs are being exploited for diagnosis, prognosis, and monitoring of cancer and other diseases, their high tissue specificity and critical role in oncogenesis make them new biomarkers for the diagnosis and classification of cancer as well as for predicting patients’ outcome. MiRNA signatures have been identified for many human tumors including CRC, and miRNA-based therapies to treat cancer have been emphasized lately. These will also be discussed in this review.
文摘AIM: To analyze the risk factors for interval time, number and pattern of hepatic metastases from gastric cancer after radical gastrectomy, and provide evidence for predicting and preventing hepatic metastasis from gastric cancer after radical gastrectomy. METHODS: A retrospective study of 87 patients with hepatic metastasis who underwent radical gastrectomy for gastric cancer from 1996 to 2001. The data was analyzed to evaluate significant risk factors for interval time, number and pattern of hepatic metastases originating from gastric cancer after radical gastrectomy. RESULTS: The size of gastric cancer and lymph node metastases were independently correlated with the interval time of hepatic metastases; the depth of invasion was independently correlated with the number of hepatic metastases; while the depth of invasion and Lauren classification were independently correlated with the pattern of hepatic metastases. CONCLUSION: We evaluated the interval time of hepatic metastases with the size of gastric cancer and lymph node metastases. The depth of invasion could be used to evaluate the number of hepatic metastases, while the depth of invasion and the Lauren classification could be used to evaluate the pattern of hepatic metastases in patients who underwent radical gastrectomy.
基金Supported by a fellowship of the 'FundacióPrivada Institut D' investigacio Biomédica de Bellvitge (IDIBELL) partially funded by the ISCⅢnetwork (RCESP C03/09) Spain and ECNIS Network from the 6FP of the EC
文摘AIM： To study the association between nitrite and nitrosamine intake and gastric cancer （GC）, between meat and processed meat intake, GC and oesophageal cancer （OC）, and between preserved fish, vegetable and smoked food intake and GC. METHODS： In this article we reviewed all the published cohort and case-control studies from 1985-2005, and analyzed the relationship between nitrosamine and nitrite intake and the most important related food intake （meat and processed meat, preserved vegetables and fish, smoked foods and beer drinking） and GC or OC risk. Sixty-one studies, 11 cohorts and 50 case-control studies were included. RESULTS： Evidence from case-control studies supported an association between nitrite and nitrosamine intake with GC but evidence was insufficient in relation to OC. A high proportion of case-control studies found a positive association with meat intake for both tumours （11 of 16 studies on GC and 11 of 18 studies on OC）. A relatively large number of case-control studies showed quite consistent results supporting a positive association between processed meat intake and GC and OC risk （10 of 14 studies on GC and 8 of 9 studies on OC）. Almost all the case-control studies found a positive and significant association between preserved fish, vegetable and smoked food intake and GC. The evidence regarding OC was more limited. Overall the evidence from cohort studies was insufficient or more inconsistent than that from case-control studies.CONCLUSION： The available evidence supports a positive association between nitrite and nitrosamine intake and GC, between meat and processed meat intake and GC and OC, and between preserved fish, vegetable and smoked food intake and GC, but is not conclusive.
基金Supported by Liaoning S&T Project,No.20180550971 and No.20170520447CSCO-MERCK SERNO oncology research fund,No.Y-MX2016-031
文摘BACKGROUNDLong noncoding RNAs (lncRNAs) are aberrant and play critical roles in gastriccancer (GC) progression and metastasis. Searching for coexpressed lncRNAclusters or representative biomarkers related to malignant phenotypes of GC mayhelp to elucidate the mechanism of tumor development and predict the prognosisof GC.AIMTo investigate the prognostic value of NOTCH1 associated with lncRNA in T cellacute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of itsinvolvement in GC invasion and metastasis.METHODSRNA sequencing and corresponding clinical data were downloaded from TheCancer Genome Atlas database. The significance module was studied byweighted gene coexpression network analysis. A total of 336 clinical sampleswere included in the study. Gene silencing, reverse transcription polymerasechain reaction, western blotting, scrape motility assay, and Transwell migrationassay were used to assess the function of hub-lncRNAs.RESULTSAt the transcriptome level, 3339 differentially expressed lncRNAs were obtained.weighted gene coexpression network analysis was used to obtain 15 lncRNAclusters and observe their coexpression. Pearson’s correlation showed that blue module was correlated with tumor grade and survival. NALT1 was the hublncRNAof blue module and was an independent risk factor for GC prognosis.NALT1 was overexpressed in GC and its expression was closely related toinvasion and metastasis. The mechanism may involve NALT1 regulation ofNOTCH1, which is associated with lncRNA in T cell acute lymphoblasticleukemia, through cis regulation, thereby affecting the expression of the NOTCHsignaling pathway.CONCLUSIONNALT1 is overexpressed and promotes invasion and metastasis of GC. Themechanism may be related to regulation of NOTCH1 by NALT1 and its effect onNOTCH signaling pathway expression.
文摘Based upon studies from randomized clinical trials, the extended （D2） lymph node dissection is now recommended as a standard procedure for local advanced gastric cancer worldwide. However, the rational extent lymphadenectomy for local advanced gastric cancer has remained a topic of debate in the past decades. Due to the limitation of low metastatic rate in para-aortic nodes （PAN） in JCOG9501, the clinical benefit of D2＋ para-aortic nodal dissection （PAND） for patients with stage T4 and/or stage N3 disease, which is very common in China and other countries except Japan and Korea, cannot be determined. Furthermore, the role of splenectomy for complete resection of No.10 and No.l I nodes has been controversial, and however, the final results from the randomized trial ofJCOG0110 have yet to be completed. Gastric cancer with the No.14 and No.13 lymph node metastasis is defined as MI stage in the current version of the Japanese classification. We propose that D2~No.14v and ＋No.13 lymphadenectomy may be an option in a potentially curative gastrectomy for tumors with apparent metastasis to the No.6 nodes or infiltrate to duodenum. The examined lymph node and extranodal metastasis are significantly associated with the survival of gastric cancer patients.
文摘Overexpression of human epidermal growth factor receptor-2(HER2) in metastatic breast cancer(MBC) is associated with poor prognosis.This single-arm open-label trial(EGF109491;NCT00508274) was designed to confirm the efficacy and safety of lapatinib in combination with capecitabine in 52 heavily pretreated Chinese patients with HER2-positive MBC.The primary endpoint was clinical benefit rate(CBR).Secondary endpoints included progression-free survival(PFS),time to response(TTR),duration of response(DoR),central nervous system(CNS) as first site of relapse,and safety.The results showed that there were 23 patients with partial responses and 7 patients with stable disease,resulting in a CBR of 57.7%.The median PFS was 6.34 months(95% confidence interval,4.93-9.82 months).The median TTR and DoR were 4.07 months(range,0.03-14.78 months) and 6.93 months(range,1.45-9.72 months),respectively.Thirteen(25.0%) patients had new lesions as disease progression.Among them,2(3.8%) patients had CNS disease reported as the first relapse.The most common toxicities were palmar-plantar erythrodysesthesia(59.6%),diarrhea(48.1%),rash(48.1%),hyperbilirubinemia(34.6%),and fatigue(30.8%).Exploratory analyses of oncogenic mutations of PIK3CA suggested that of 38 patients providing a tumor sample,baseline PIK3CA mutation status was not associated with CBR(P = 0.639) or PFS(P = 0.989).These data confirm that the lapatinib plus capecitabine combination is an effective and well-tolerated treatment option for Chinese women with heavily pretreated MBC,irrespective of PIK3CA status.
文摘Objective: The aim of the study was to investigate the level of self-image of patients after breast cancer surgery, and explore factors influencing self-image among patients who have experienced different types of surgeries, and set out a foundation for the improvement of care strategies. Methods: The 538 patients with primary breast cancer who underwent surgery in the Department of Breast Surgery, First Hospital of China Medical University, Shenyang, China, from January 2004 to January 2009 were included in the study. The psychological status of the patients was evaluated by body image after breast cancer questionnaire (BIBCQ), social support rating scale (SSRS), self-rating anxiety scale (SRAS), depression rating scale (DRS), and general information questionnaire. The factors influencing the self-image were selected by a stepwise regression analysis. Results: The patients who underwent breast-conserving surgery were the most satisfied with their body image, followed by those underwent surgery of modified radical mastectomy with reconstruction. However, cases treated by modified radical mastectomy without reconstruction had negative outcomes. Regardless of operation type, the self-image was influenced by anxiety, level of abuse by husband, and sexual satisfaction after operation. Conclusion: The self-image of patients who underwent different breast cancer surgeries was influenced by different factors, and individualized nursing should be offered in accordance with the specific situation.
文摘Colorectal cancer(CRC)is one of the most prevalent cancers in developed countries.On the other hand,CRC is also one of the most curable cancers if it is detected in early stages through regular colonoscopy or sigmoidoscopy.Since CRC develops slowly from precancerous lesions,early detection can reduce both the incidence and mortality of the disease.Fecal occult blood test is a widely used non-invasive screening tool for CRC.Although fecal occult blood test is simple and cost-effective in screening CRC,there is room for improvement in terms of the accuracy of the test.Genetic dysregulations have been found to play an important role in CRC development.With better understanding of the molecular basis of CRC,there is a growing expectation on the development of diagnostic tests based on more sensitive and specific molecular markers and those tests may provide a breakthrough to the limitations of current screening tests for CRC.In this review,the molecular basis of CRC development,the characteristics and applications of different non-invasive molecular biomarkers,as well as the technologies available for the detection were discussed.This review intended to provide a summary on the current and future molecular diagnostics in CRC and its pre-malignant state,colorectal adenoma.
文摘AIM:To compare the performance of three commercially available anti-human epidermalgrowth factor receptor 2(HER2)antibodies in whole-tissue sections and tissue microarrays(TMAs)of a series of gastric tumors.METHODS:We present a comparative analysis of three anti-HER2 antibodies(HercepTest,4B5 and SP3)using TMA and whole-tissue sections prepared from the same paraffin blocks of 199 gastric adenocarcinomas operated upon between January 2004 and December2008 at a Brazilian cancer hospital.The data on the patients’age,sex,the anatomical location of the tumor and the Lauren’s histological classification were collected from clinical and pathological records.The immunohistochemical(IHC)results were examined by two pathologists and the cases were classified as positive(3+),equivocal(2+)and negative(0 or 1+),according to the criteria of the IHC scoring system of gastric cancer.TMAs and whole-tissue sections were evaluated separately and independently.All cases yielding discordant IHC results and/or scored as 2+were subjected to dual-color in situ hybridization in order to determine the final HER2 status.Besides determining the sensitivity and predictive value for HER2-positive status,we measured the accuracy of each antibody by calculating the area under the receiver operating characteristic(ROC)curve.The agreement between the results obtained using the TMAs and those obtained using the whole-tissue sections was assessed by means of Kappa coefficient.RESULTS:Intratumoral heterogeneity of HER2 expression was observed with all antibodies.HER2-positive expression(3+)in the whole-tissue sections was observed in 23 cases(11.6%)using the 4B5 antibody,in 18 cases(9.1%)using the SP3 antibody and in 10 cases(5.1%)using the HercepTest antibody.In the TMAs,11 positive cases(5.6%)were identified using SP3 antibody,9(4.6%)using the 4B5 antibody and 6(3%)using the HercepTest antibody.The sensitivity using whole-tissue sections and TMA,respectively,was 95.2%and 42.9%with 4B5,90.5%and 66.7%with SP3 and 47.6%and42.9%with HercepTest.The accuracy,calculated from the area under the ROC curve,using whole-tissue sections and TMA,respectively,was 0.91 and 0.79 by 4B5,0.86 and 0.80 by SP3 and 0.73 and 0.71 by HercepTest.The concordance of the results obtained using wholetissue sections and TMA was 97.4%(Kappa 0.75)using HercepTest,85.6%(Kappa 0.56)using SP3 and 84.1%(Kappa 0.38)using 4B5.CONCLUSION:The use of the 4B5 antibody on wholetissue sections was the most accurate IHC method for evaluating HER2 expression in gastric adenocarcinoma.
基金This study was supported by the Special Funds for Strategic Emerging Industry Development of Shenzhen(Grant No.20170922151538732)the Science and Technology Project of Shenzhen(Grant No.JSGG20180703164202084)+2 种基金the Natural Science Foundation Project of China(Grant No.71573022)the National Natural Science Foundation Regional Projects(Grant No.82060440)the special health research projects of 2019 funded by the Chinese PLA General Hospital(Grant No.NLBJ-2019003).
文摘Objective:Hereditary colorectal cancer(CRC)accounts for approximately 5%–10%of all CRC cases.The full profile of CRC-related germline mutations and the corresponding somatic mutational profile have not been fully determined in the Chinese population.Methods:We performed the first population study investigating the germline mutation status in more than 1,000(n=1,923)Chinese patients with CRC and examined their relationship with the somatic mutational landscape.Germline alterations were examined with a 58-gene next-generation sequencing panel,and somatic alterations were examined with a 605-gene panel.Results:A total of 92 pathogenic(P)mutations were identified in 85 patients,and 81 likely pathogenic(LP)germline mutations were identified in 62 patients,accounting for 7.6%(147/1,923)of all patients.MSH2 and APC was the most mutated gene in the Lynch syndrome and non-Lynch syndrome groups,respectively.Patients with P/LP mutations had a significantly higher ratio of microsatellite instability,highly deficient mismatch repair,family history of CRC,and lower age.The somatic mutational landscape revealed a significantly higher mutational frequency in the P group and a trend toward higher copy number variations in the non-P group.The Lynch syndrome group had a significantly higher mutational frequency and tumor mutational burden than the nonLynch syndrome group.Clustering analysis revealed that the Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Population risk analysis indicated that the overall odds ratio was 11.13(95%CI:8.289–15.44)for the P group and 20.68(95%CI:12.89–33.18)for the LP group.Conclusions:Distinct features were revealed in Chinese patients with CRC with germline mutations.The Notch signaling pathway was uniquely clustered in the Lynch syndrome group,and the MAPK and cAMP signaling pathways were uniquely clustered in the non-Lynch syndrome group.Patients with P/LP germline mutations exhibited higher CRC risk.
基金Supported by Grants from the Italian Ministry of Health,5 per 1000,AIRC 15460 and Genoa Atheneum 2014(to Ghiorzo P)
文摘Although the genetic bases of most hereditary cancer syndromes are known,and genetic tests are available for them,the incidence of the most rare of these syndromes is likely underestimated,partially because the clinical expression is neither fully understood nor easily diagnosed due to the variable and complex expressivity. The clinical features of a small pool of rare cancer syndromes include gastroenterological signs,though not necessarily tumors,that could require the intervention of a gastroenterologist during any of the phases of the clinical management. Herein we will attempt to spread the knowledge on these rare syndromes by summarizing the phenotype and genetic basis,and revising the peculiar gastroenterological signs whose underlying role in these rare hereditary cancer syndromes is often neglected. Close collaboration between geneticists and gastroenterologists could facilitate both the early identification of patients or relatives at-risk and the planning of multidisciplinary and tailored management of these subjects.
基金supported by a grant from Cancer Council South Australia’s Beat Cancer Project on behalf of its donors and the State Government through the Department of Health (Grant No.1159924 and 1127220)funded by a Postdoctoral Fellowship from the National Breast Cancer Foundation, Australia (Grant No.PF-17-007)
文摘Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afatinib have not been evaluated.Methods: A prognostic tool for overall survival(OS)/progression free survival(PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6(n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1(n = 390) and LUX-Lung 2(n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor treatment.Results: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk group.Conclusions: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment.
