ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation of 2-chloroethyl-1,1-d2 phenyl sulfide without appreciable scramblingDouglass F. Taber and Yanong WangCite this: J. Org. Chem. 1993, 58, 23, 6470Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://pubs.acs.org/doi/10.1021/jo00075a051https://doi.org/10.1021/jo00075a051research-articleACS PublicationsRequest reuse permissionsArticle Views95Altmetric-Citations2LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value.From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated.There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P=0.00). There was significant association between bcl-2, and bax expression (P<0.05). p53 expression correlated with histological grade (P=0.01); bcl-2 expression with pathological stage (P=0.00); bax expression with male (P=0.02), histological grade (P=0.01), Borrmann type (P=0.01), tumor location (P=0.00), lymph node metastasis (P=0.03), and pathological stage (P=0.03); c-myc expression with Borrmann type (P=0.00). bcl-2 expression was related with good survival in univariate analysis (P=0.01). Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P=0.03).The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.
Proliferative activity of soft tissue sarcomas (STS) in 31 cases was estimated by histologic grading, mitotic count, DNA analysis by flow cytometry, and immuno-histochemical procedures with monoclonal antibody Ki-67. Aneuploid was found in 12 of 16 cases (75.0%) with Grade 3, and in 4 of 15 cases (26.7%) with Grade 1, 2 (P=0.0121). Tumors with more than 100 Ki-67 positive tumor cells per 10 high power fields (HPF) had a higher rate of aneuploid (81.3%) than those with less than 100 Ki-67 per 10 HPF (26.7%) (P=0.0038). There were significant correlations between Grade and DI (r=0.4901,P=0.0051), Grade and Ki-67 (r=0.4636,P=0.0086), Ki-67 and DI (r=0.6368,P=0.0001). The results indicate that DI and reactivity of tumor cells to Ki-67 may reflect proliferative activity and be helpful for clinicians to judge the biological behaviour of tumors more accurately and objectively. Supplementary to the grading of STS, DI and Ki-67 score could be useful as prognostic parameters for clinical investigation of multimodality therapy for individual patients.
The clinical importance of preoperative tumor markers remain elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of AFP, CEA, CA19-9, and CA50 in T4a stage gastric cancer.Two hundred and seventy-three T4a gastric cancer patients who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. The correlation between tumor markers and clinicopathologic characteristics and prognostic value of preoperative tumor markers were investigated.Correlation analysis showed that AFP was associated with Borrmann type (P = 0.010); CEA with sex (P = 0.029), tumors site (P = 0.014), and N stage (P = 0.001); CA19-9 with age (P = 0.047), tumor site (P = 0.011), lymphovascular invasion (P = 0.004), and N stage (P = 0.000); CA50 with age (P = 0.017), tumor site (P = 0.004), tumor size (P = 0.014), and N stage (P = 0.000). Multivariate analysis showed that the positivity of preoperative CEA, CA19-9, and CA50 were major independent poor prognostic factors of patients with T4a stage gastric cancer.Preoperative serum tumor marker might be a candidate for the staging system in addition to conventional factors.
Total gastrectomy is a very important mode of therapy for gastric cancer.Many different types of reconstruction have been proposed,but there is no definitive conclusions as to which procedure is the best because of the postoperative complications,such as dumping syndrome,regurgitant esophagitis,malnutrition and so on.In this review,the author summarized recent clinical studies addressing gastrointestinal reconstruction following total gastrectomy.There is still some debate on preserving duodenal passage and the pouch reconstruction can provide improvement of the quality of life in patients receiving total gastrectomy.
327 Background: The optimal chemotherapeutic regimen for gastric cancer with peritoneal metastasis remains undefined. We evaluated the efficacy and safety of intraperitoneal and intravenous paclitaxel plus S-1 (NIPS Group) versus paclitaxel plus S-1 (PS Group) in gastric cancer patients with peritoneal metastasis. Methods: In this multicenter, randomized, controlled, phase 3 trial, patients were recruited from 9 cancer centers in China. Eligible patients were aged 18~75 years with an Eastern Cooperative Oncology Group performance status of 0~1, histologically confirmed gastric adenocarcinoma, peritoneal metastases from gastric cancer requiring definitive diagnosis by laparoscopy, without gastric outflow tract obstruction and intestinal obstruction, no prior treatment with chemotherapy, radiation therapy, targeted therapy or immunotherapy. Eligible patients were randomly assigned (2:1) to receive either intravenous paclitaxel at 50 mg/m² and intraperitoneal paclitaxel at 20 mg/m² on days 1 and 8, along with oral S-1 at a dose of 80 mg/m² on days 1~14, or intravenous paclitaxel at 70 mg/m² on days 1 and 8, along with oral S-1 at 80 mg/m² on days 1~14. The primary endpoint was overall survival in the intention-to-treat population. Safety was assessed in all participants. A sample size of 238 patients was calculated to provide 80% power with a one-sided alpha of 0.1, accounting for a 10% dropout rate. Survival was analyzed using Kaplan-Meier curves and compared with the log-rank test. Cox regression was used for multivariate analysis. A P -value < 0.05 was considered statistically significant. Results: From May 10, 2017, to March 9, 2022, 246 patients were screened and 222 were included in the modified intention-to-treat population, of whom 148 patients were assigned to the NIPS Group and 74 to the PS group. As of data cutoff (March 9, 2024), the median survival time was 19.4 months (95% CI, 17.1~22.9), in the NIPS group and 13.9 months (95% CI, 10.3~16.1) in the PS group (HR = 0.66; 95% CI 0.49 - 0.88; P = 0.005). The 1-year and 2-year overall survival rates were 69.6% and 37.2% in the NIPS group, compared to 54.1% and 20.3% in the PS group. The most common grade 3~4 adverse events were leukopenia (21.7% in the NIPS group, and 24.7% in the PS group) and neutropenia (19.9% in the NIPS group, and 23.4% in the PS group). No treatment-related deaths were reported. Conclusions: Intraperitoneal and intravenous paclitaxel plus S-1 significantly improved the overall survival compared to intravenous paclitaxel plus S-1 in gastric cancer patients with peritoneal metastasis, with manageable toxicity. Clinical trial information: ChiCTR-IIR-16009802.
Objective Although a subset of genetic loci have been associated with gastric cancer (GC) risk, the underlying mechanisms are largely unknown. We aimed to identify new susceptibility genes and elucidate their mechanisms in GC development. Design We conducted a meta-analysis of four genome-wide association studies (GWASs) encompassing 3771 cases and 5426 controls. After targeted sequencing and functional annotation, we performed in vitro and in vivo experiments to confirm the functions of genetic variants and candidate genes. Moreover, we selected 33 promising variants for two-stage replication in 7035 cases and 8323 controls from other five studies. Results The meta-analysis of GWASs identified three loci at 1q22, 5p13.1 and 10q23.33 associated with GC risk at p<5×10 − 8 and replicated seven known loci at p<0.05. At 5p13.1, the risk rs59133000[C] allele enhanced the binding affinity of NF-κB1 (nuclear factor kappa B subunit 1) to the promoter of PRKAA1 , resulting in a reduced promoter activity and lower expression. The knockout of PRKAA1 promoted both GC cell proliferation and xenograft tumour growth in nude mice. At 10q23.33, the rs3781266[C] and rs3740365[T] risk alleles in complete linkage disequilibrium disrupted and created, respectively, the binding motifs of POU2F1 and PAX3, resulting in an increased enhancer activity and expression of NOC3L , while the NOC3L knockdown suppressed GC cell growth. Moreover, two new loci at 3q11.2 (OR=1.21, p=4.56×10 − 9 ) and 4q28.1 (OR=1.14, p=3.33×10 − 11 ) were associated with GC risk. Conclusion We identified 12 loci to be associated with GC risk in Chinese populations and deciphered the mechanisms of PRKAA1 at 5p13.1 and NOC3L at 10q23.33 in gastric tumourigenesis.
We aimed to identify nutritional, inflammatory and clinical indicators associated with stage II/III gastric cancer in patients, and construct a nomogram model for accurate prediction of prognosis of patients.We retrospectively recruited stage II/III gastric cancer (GC) patients who underwent radical gastrectomy at Fudan University Shanghai Cancer Center, from 2012 to 2019. The patients were randomly divided into training and internal validation sets, and then the Maximum log-rank statistic method was used to determine the optimal cut-off value. Next, we performed univariate and multivariate Cox regression analyses to identify independent risk factors associated with overall survival (OS). These were subsequently used to develop a nomogram model. We validated this model in patients with stage II/III gastric cancer (from 2010 to 2019) at Guangxi Medical University Affiliated Tumor Hospital.A total of 2,443 patients met our inclusion criteria and were therefore included in our study. Patients from Fudan University Shanghai Cancer Center were randomly divided into training (n=1725) and internal validation (n=430) sets, while those from Guangxi Medical University Affiliated Tumor Hospital were used as the external validation set (n=288). Results from univariate and multivariate Cox regression analyses revealed that age (adjusted HR, 1.23; 95% CI, 1.05-1.44; P=0.012), TNM stage (adjusted HR, 3.62; 95% CI, 2.79-4.68; P<0.001), CEA (adjusted HR, 1.40; 95% CI, 1.14-1.71; P<0.001), CA199 (adjusted HR, 1.47; 95% CI, 1.21-1.79; P<0.001), and Prognostic Nutritional Index (PNI, adjusted HR, 0.81; 95% CI, 0.67-0.98; P=0.026) were independent prognostic factors for OS in the training set. The established nomogram model, with a C-index of 0.67, had 3- and 5-year Area under Curve (AUC) values of 0.719 and 0.714, respectively. Notably, the model effectively distinguished patients' OS in both the internal (P<0.001) and external (P<0.001) datasets.PNI is an independent prognostic factor for stage II/III GC patients after radical resection. The established novel nomogram model, based on nutritional, inflammatory and clinical indicators, can accurately and efficiently predict prognosis of stage II/III GC patients.
e15519 Background: Peri-operative treatment of locally advanced gastric cancer (LAGC) has always been argued. We aim to compare the survival benefit and safety for SOX as peri-opertative therapy versus SOX or XELOX as postoperative therapy after D2 dissection. Methods: RESOLVE is a phase III trial investigating effects of post-operative SOX and XELOX, and peri-operative SOX on LAGC. RESOLVE is the first RCT investigating different therapeutic timeframes in gastric cancer patients with stratification by Lauren classification. Clinical trials JCOG 0501 and RESOLVE exploring optimal chemotherapy modalities are compared in the table below. Results: The study enrolled the first patient in Aug 2012. By Dec 31, 2016, a total of 1061 patients were recruited. Currently 136 patients have died (arm A: 54; arm B: 44; arm C: 37) and 187 patients are under treatment (arm A: 60; arm B: 61; arm C: 66). Conclusions: The patient recruitment has completed and events of DFS will be achieved in 2 years. Clinical trial information: NCT01534546. [Table: see text]
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