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  • American Association for Cancer Research (AACR)  (67)
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  • 1
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 4 ( 2020-02-15), p. 870-881
    Abstract: Despite the well-known prognostic value of the tumor–immune microenvironment (TIME) in colorectal cancers, objective and readily applicable methods for quantifying tumor-infiltrating lymphocytes (TIL) and the tumor–stroma ratio (TSR) are not yet available. Experimental Design: We established an open-source software-based analytic pipeline for quantifying TILs and the TSR from whole-slide images obtained after CD3 and CD8 IHC staining. Using a random forest classifier, the method separately quantified intraepithelial TILs (iTIL) and stromal TILs (sTIL). We applied this method to discovery and validation cohorts of 578 and 283 stage III or high-risk stage II colorectal cancers patients, respectively, who were subjected to curative surgical resection and oxlaliplatin-based adjuvant chemotherapy. Results: Automatic quantification of iTILs and sTILs showed a moderate concordance with that obtained after visual inspection by a pathologist. The K-means–based consensus clustering of 197 TIME parameters that showed robustness against interobserver variations caused colorectal cancers to be grouped into five distinctive subgroups, reminiscent of those for consensus molecular subtypes (CMS1-4 and mixed/intermediate group). In accordance with the original CMS report, the CMS4-like subgroup (cluster 4) was significantly associated with a worse 5-year relapse-free survival and proved to be an independent prognostic factor. The clinicopathologic and prognostic features of the TIME subgroups have been validated in an independent validation cohort. Conclusions: Machine-learning–based image analysis can be useful for extracting quantitative information about the TIME, using whole-slide histopathologic images. This information can classify colorectal cancers into clinicopathologically relevant subgroups without performing a molecular analysis of the tumors.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 83, No. 8_Supplement ( 2023-04-14), p. LB157-LB157
    Abstract: As the third enzyme of the pentose phosphate pathway (PPP), abnormally elevated levels of 6-phosphogluconate dehydrogenase (6PGD) have been documented in various human cancers. We demonstrate that reduced cereblon (CRBN) protein expression is the underlying mechanism of elevated 6PGD expression in metastatic prostate cancer cells. We establish 6PGD as a new endogenous substrate for CRBN by demonstrating that it interacts directly with CRBN and is ubiquitinated by CRL4CRBN. In addition, CRBN negatively regulates prostate cancer cell progression and metastasis, as abnormally high 6PGD, in the absence of sufficient CRBN, enhances the metastatic potential of prostate cancer in vitro and in vivo. Our findings show convincingly that carbohydrate metabolism regulated by 6PGD is linked to prostate cancer metastasis via CRBN. Based on these data, we propose that the 6PGD-CRBN axis may be a suitable target for further research into new therapeutics for mitigating prostate cancer metastasis. Citation Format: Koushik Guchhait, Hyeon Seung Yoon, Seungheon Shin, Hyun-Su An, Hye Seung Nam, Francisco D. Yanqui-Rivera, Samara M. Oña, Miguel Á. Mendez, Seokjae Park, Eun-Kyoung Kim, Jong Yeon Hwang, Jee-Young Han, Doo Yong Chung, Daeho Park, Su-Geun Yang, Chul-Seung Park, Steve K. Cho. Cereblon inhibits prostate cancer progression and metastasis by negatively regulating 6PGD [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB157.
    Type of Medium: Online Resource
    ISSN: 1538-7445
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 4525-4525
    Abstract: Purpose: Pre-operative chemoradiation therapy (CRT) is standard treatment in clinical stage T3/4 or node positive rectal cancer, however, there are no established biomarker that can predict pathological response and clinical outcome to CRT. The aim of this study was to evaluate the correlation between expression of molecular markers and pathological response and clinical outcomes in patients with rectal cancer who received 5-FU based chemoradiotherapy. Experiment design: Immunohistochemical stain was performed in tissue arrays constructed from core tissue specimens taken before treatment and from operative specimens from 120 patients who received 5-FU based pre-operative CRT and surgery between June 2003 and Dec. 2008. Expression of Ki67, TS, BAX, EpCAM, p53, p21, EGFR, CD44, CD133, CD166, HIF1a and ALDH1 were assessed and correlated with tumor regression grades and disease free survival. Results Of 120 patients (M/F 77/43, median age:63), 23 (19.2%) patients achieved pathologic complete remission; Dworak grade 1: 18 (15%), grade 2: 51 (42.5%); Grade 3: 28 (23.3%), and Grade 4: 23 (19.2%). In the analysis of association between marker expressions and tumor regression grades, low p21 expression at pretreatment biopsy was significantly associated with grade 4 (total regression) (p=0.039) and better disease free survival (5yr DFS rate - low vs high p21: 89% vs 54%, p=0.001). In the multivariate analysis, low p21 expression level in pre-treatment biopsy was significantly associated with better DFS (p=0.003, HR 0.20; 95% CI 0.72, 0.57) and the score difference of p21 expression between pre- and post treatment tissue was also significant (p=0.002, HR 0.09; 95% CI 0.02, 0.39). Low CD166 expression level at pretreatment biopsy was associated with better DFS (p=0.003; HR 0.19; 95% CI 0.07, 0.58). Low ypN stage and high tumor regression grade also have significantly a good effect on DFS as well (p= 0.001, 0.018 respectively). Conclusion Our results showed low p21 and CD166 expression at pretreatment biopsy was associated with tumor regression and good prognosis in patients treated with 5-FU based chemoradioatherapy. Larger, prospective trials and functional studies are warranted to determine the role of p21 and CD166 as predictive biomarker of response to chemoradiotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4525. doi:1538-7445.AM2012-4525
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 4
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    American Association for Cancer Research (AACR) ; 2019
    In:  Cancer Research Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3750-3750
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3750-3750
    Abstract: Background: While additional gastrectomy has not shown superiority compared to conventional systemic therapy in unresectable gastric cancer in REGATTA trial, there have been several subsequent attempts to find a role for conversion surgery with a curative intent in selected patients. The aim of this study was to analyze the conversion surgery data and to see if there was a role of cancer dormancy markers to select patients for conversion surgery. Patients and Methods: From the pathology database at Seoul National University Bundang Hospital, we identified 49 patients treated with chemotherapy followed by gastrectomy in initially unresectable gastric cancer from January 2006 to August 2016. Of these, 26 patients were analyzed to explore the role of conversion surgery with a curative intent. As cancer dormancy markers, NR2F1, nanog, mig6, and pERK were evaluated using immunohistochemistry staining. Results: Twenty-six (53%) from a total of forty-nine patients received conversion surgery. The median age was 58 years (range, 39-78) and the duration of prior chemotherapy before conversion surgery was 5.1 months (range, 3.1-13.9). Category 2 with para-aortic lymph node involvement was the most prevalent disease status (57.5%). At the time of conversion surgery, complete response, partial response, and stable disease status had been established with chemotherapy in 2, 15, and 3 patients, respectively. Of these, R0 resection was accomplished in twenty-two (85%) patients. Median overall survival (OS) in all patients that underwent conversion surgery, defined as the time from initiation of chemotherapy to death by any cause, was 36.1 months (95% CI, 29.6-51.4). In patients that underwent R0 resection, disease free survival (DFS) from conversion surgery and OS from initial chemotherapy was 15.1 months (95% CI, 13.9-43.8) and 37.8 months (95% CI, 31.7-57.1), respectively. Patients with a shorter duration of prior chemotherapy were associated with both longer OS and DFS from conversion surgery (p & lt; 0.001, both). Less advanced pathologic stage at the time of conversion surgery was also associated with longer OS from conversion surgery (p=0.045). Regarding cancer dormancy markers from initial biopsy specimens, stronger expression (moderate to strong) of NR2F1, nanog, and mig6 showed a tendency for longer DFS after conversion surgery (p=0.018, p=0.834, p=0.344, respectively) and also longer OS after conversion surgery (p=0.027, p=0.225, p=0.359, respectively). Conclusion: When advanced gastric cancer showed a favorable response after chemotherapy, a survival of over 3 years was observed in patients who received a curative conversion surgery, despite the initial unresectability. We may expect survival benefits from conversion surgery in certain subgroups, with better initial response to palliative chemotherapy and higher levels of specific cancer dormancy proteins in the tumor. Citation Format: Hun Jee Choe, Jin Won Kim, Song-Hee Han, Kui-Jin Kim, Jeong-Min Kim, Koung Jin Suh, Ji-Won Kim, Keun-Wook Lee, Hye Seung Lee. Conversion surgery in unresectable advanced gastric cancer and cancer dormancy as a prognostic marker [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3750.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 5
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    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Research Vol. 76, No. 14_Supplement ( 2016-07-15), p. 5136-5136
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 5136-5136
    Abstract: Background: Agents targeting HER2 or EGFR have been applied in several cancer types. Tumor microenvironment including tumor-infiltrating lymphocytes could be a predictive marker in HER2- or EGFR- targeted therapy, although there are some controversies. However, the effects of HER2 and EGFR inhibition on tumor microenvironment are unclear. Method: We screened HER2, EGFR, and PD-L1 expression in gastric cancer cell lines by western blot (SNU216, SNU668, SNU719, AGS, N87, YCC3, and YCC10). HER2 and EGFR was inhibited by using dual inhibitor (afatinib, lapatinib). After HER2 and EGFR inhibition, the change of PD-L1 expression was evaluated in HER2 overexpressed cell lines (SNU216, N87, SKBR3) at western blot, FACS, PCR, and qPCR. Selective blockade for down-steam molecules of HER2 and EGFR was conducted by using pictilisib (PI3K inhibitor) and trametinib (MEK inhibitor). The change of chemokines such as CXCL1, CCL2, and CCL21 was evaluated after HER2 and EGFR inhibition by PCR. In clinical data, PD-L1 expression and HER2 expression in resected gastric cancer were also evaluated by immunohistochemistry analysis. Results: EGFR-overexpressed or HER2-overexpressed gastric cancer cell lines (SNU216, SNU668, N87) showed higher protein expression of PD-L1. PD-L1 expression decreased with dose-dependent manner in afatinib- or lapatinib- treated cell lines (SNU216, N87, SKBR3). In pictilisib-treated cell lines, PD-L1 was also down-regulated. However, trametinib-treated cell lines did not show down-regulation of PD-L1. After lapatinib treatment in HER2 overexpressed cell lines, CXCL1, CCL21, and CCL2 decreased with dose-dependent manner. In 289 patients with resected gastric cancer, there was a significant association between HER2 and PD-L1 expression (p = 0.03). Conclusions: PD-L1 is associated with HER2 and EGFR expression. PD-L1 is regulated by inhibition of PI3K pathway. Therefore, HER2 or EGFR inhibition could interact with tumor microenvironment by down-regulation of expression of PD-L1 and chemokines. Citation Format: Jin Won Kim, Ji Hea Sung, Mi Hyun Kang, Ji-Won Kim, Se-Hyun Kim, Keun-Wook Lee, Hye Seung Lee, Jee Hyun Kim. HER2 or EGFR inhibition interacts with tumor microenvironment by downregulation of PD-L1 and chemokines. [abstract] . In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5136.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 6
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    American Association for Cancer Research (AACR) ; 2007
    In:  Clinical Cancer Research Vol. 13, No. 14 ( 2007-07-15), p. 4154-4163
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 13, No. 14 ( 2007-07-15), p. 4154-4163
    Abstract: Purpose: Gastric cancer is heterogeneous clinically and histologically, and prognosis prediction by tumor grade or type is difficult. Although previous studies have suggested that frozen tissue–based molecular classifications effectively predict prognosis, prognostic classification on formalin-fixed tissue is needed, especially in early gastric cancer. Experimental Design: We immunostained 659 consecutive gastric cancers using 56 tumor-associated antibodies and the tissue array method. Hierarchical cluster analyses were done before and after feature selection. To optimize classifier number and prediction accuracy for prognosis, a supervised analysis using a support vector machine algorithm was used. Results: Of 56 gene products, 27 survival-associated proteins were selected (feature selection), and hierarchical clustering identified two clusters: cluster 1 and cluster 2. Cluster 1 cancers were more likely to have intestinal type, earlier stage, and better prognosis than cluster 2 (P & lt; 0.05). In 187 early gastric cancers (pT1), cluster 2 was associated with the presence of metastatic lymph nodes (P = 0.026). Kaplan-Meier survival curves stratified by pathologic tumor-lymph node metastasis revealed that cluster 2 was associated with poor prognosis in stage I or II cancer (P & lt; 0.05). Support vector machines and genetic algorithms selected nine classifiers from the whole data set, another nine classifiers for stage I and II, and eight classifiers for stage III and IV. The prediction accuracies for patient outcome were 73.1%, 88.1%, and 76%, respectively. Conclusions: Protein expression profiling using the tissue array method provided a useful means for the molecular classification of gastric cancer into survival-predictive subgroups. The molecular classification predicted lymph node metastasis and prognosis in early stage gastric cancer.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2007
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  • 7
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    Online Resource
    American Association for Cancer Research (AACR) ; 2013
    In:  Cancer Research Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2383-2383
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 73, No. 8_Supplement ( 2013-04-15), p. 2383-2383
    Abstract: Aim: To evaluate the clinical significance of intratumoral HER2 heterogeneity in gastric cancer (GC). Methods: A total of 322 GC tissues were evaluated by HER2 immunohistochemistry (IHC), of which 73 with IHC 2+ or 3+ were subjected to fluorescence in situ hybridization (FISH). Also, 3-5 distinct spots in each case showing different HER2 staining intensity were evaluated individually for comparing IHC staining intensity with gene copy number (GCN). Minimum, average, and maximum FISH scores were generated for each case. Results: Intratumoral heterogeneity of HER2 overexpression and gene amplification were 54 and 30 of 73 cases with IHC 2+ or 3+, respectively. These cases were characterised by diffuse or mixed Lauren type, HER2 IHC 2+, and low-level amplification. Kaplan-Meier survival analysis revealed that the heterogeneous overexpression was significantly associated with longer disease-free survival times than the homogeneous, and the high average GCN was most associated with poor outcome. Also, there was a strong correlation between the IHC and FISH results for each spot. Quantitative PCR analysis of the cancer tissues and the cell-free plasma showed that HER2 gene copy by quantitative PCR on tissue correlated well with those by FISH, but plasma HER2 level was not.Conclusions: Considering the high incidence of intratumoral HER2 heterogeneity in GC, accurate HER2 assessment would require larger tissues and more detailed guidelines. The guidelines should include the recommendation that FISH-scoring areas be selected with reference to a corresponding IHC slide. Also, the definition of HER2-positive tumours should be reassessed considering the intratumoral heterogeneity. Citation Format: Hye Seung Seung Lee, Hee Eun Lee, Kyoung Un Park, Soo Kyung Nam, Do Joong Park, Hyung-Ho Kim. Clinical significance of intratumoral HER2 heterogeneity in gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2383. doi:10.1158/1538-7445.AM2013-2383
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2013
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 76, No. 14_Supplement ( 2016-07-15), p. 4931-4931
    Abstract: Although HER2 immunohistochemistry (IHC) is widely used to assess the HER2 status, not all patients could be clarified with HER2 IHC positivity for Trastuzumab treatment. Here, we introduce a novel IHC method utilizing Trastuzumab itself; compared to conventional HER2 IHC, the new method evaluates the extracellular epitope which is the target of action for Trastuzumab. The purpose of this study is to test whether this new method has better performance in predicting treatment outcome of Trastuzumab therapy, and whether it is the significant prognostic factor in consecutive gastric cancer patients. From two individual institutions, 37 and 32 GC patients treated with Trastuzumab were enrolled respectively, the former as the training cohort and the latter for validation, and progression free survivals (PFS) were compared according to the results of Trastuzumab IHC. To validate the prognostic significance of Trastuzumab IHC in consecutive GC, we constructed tissue microarrays (TMA) from 536 consecutive cases and Trastuzumab IHC, HER2 IHC, and HER2 silver in situ hybridization (SISH) were performed. In training cohort (n = 37), all cases were HER2 IHC 2+ (n = 11) or 3+ (n = 26), but 2+ in 3 cases (8.1%) and 3+ in 10 cases (27.0%) by Trastuzumab IHC. Similar results were observed in validation cohort, 17 of 32 cases (53.1%) were 2+ or 3+ by Trastuzumab IHC. Trastuzumab ≥2+ group in the training cohort had significantly better PFS than Trastuzumab & lt;2+ group (p = 0.016), and survival analysis of PFS in validation cohort and combined cohort also showed favorable PFS in Trastuzumab ≥2+ group (p = 0.031 and 0.001, respectively). By Cox regression analysis in training cohort, Trastuzumab IHC ≥2+ was proved to be the independent predictive factor for PFS in patients receiving Trastuzumab. Of 536 consecutive cases of GC, 23 (4.3%) were HER2 IHC 3+, and among these patients, only 5 (21.7%) were also 3+ by Trastuzumab IHC. Disease specific survival (DSS) and overall survival (OS) in Trastuzumab IHC ≥2+ group were shorter compared to Trastuzumab IHC & lt;2 group (p = 0.015 and 0.063, respectively), while both HER2 IHC and HER2 SISH failed to discriminate significant survival differences between subgroups. In this study, we demonstrated that Trastuzumab IHC is a significant predictive factor for PFS in Trastuzumab-treated GC patients, and poor prognostic factor of DSS in consecutive GC, even better than conventional HER2 IHC and HER2 SISH. We believe that Trastuzumab IHC is a very promising, relatively easy-to-implement, novel method to assess HER2 status in routine clinical practice. Citation Format: Jiwon Koh, Soo Kyung Nam, Younwoo Lee, Chan-Young Ock, Jin Won Kim, Keun-Wook Lee, Do-Youn Oh, Do Joong Park, Hyung-Ho Kim, Keon-Wook Kang, Woo Ho Kim, Ho-Young Lee, Hye Seung Lee. Validation of Trastuzumab immunohistochemistry as a predictive and prognostic biomarker in gastric cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4931.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 9
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    American Association for Cancer Research (AACR) ; 2012
    In:  Cancer Research Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5576-5576
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 5576-5576
    Abstract: The mammalian target of rapamycin (mTOR) plays a key role in cellular growth and homeostasis and its regulation is frequently altered in tumors. Vascular endothelial growth factor (VEGF) is known to mediate its biological functions via activation of the protein tyrosine kinase receptors, VEGF receptor 1 (VEGFR-1/Flt1) and VEGFR-2 (KDR/Flk1). Recently, mTOR inhibitors and multi-targeted kinase inhibitors have entered late-phase clinical trials in a heterogenous set of neuroendocrine neoplasms. To identify new biomarkers to predict patient outcome, we studied the expressions of AKT-mTOR pathway and VEGFR-2 in 290 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). We performed immunoshistochemistry of phospho-Akt (pAkt), phospho-mTOR (pmTOR), VEGFR-2, Chromogranin A (Chr A), and Somatostatin receptors (SSTRs) 1, 2, and 5 and analyzed the association with AJCC stage and WHO grade. All cases were re-graded and re-staged according to WHO 2010 classification and AJCC 7th edition. The cases were composed of 131 foregut (49 stomach, 32 duodenum, and 50 pancreas) and 159 hindgut (20 colon and 139 rectum); 204 (70%) Stage I, 40 (14%) Stage II, 33 (12%) Stage III, and 13 (4%) Stage IV; 179 (62%) NET G1, 61 (21%) NET G2, 20 (7%) NEC, 16 (5%) mixed adenoneuroendocrine carcinoma, and 14 (5%) grade not available. We found that 43%, 41%, and 72% of GEP-NET were positive for pAkt, pmTOR, and VEGFR-2 respectively. In hindgut tumors, the frequencies of pAkt, pmTOR, and VEGFR-2 were significantly higher than foregut tumors (P & lt;0.001, 64%, 54%, and 85% in hindgut vs. 18%, 24%, and 56% in foregut). The activated status of mTOR pathway was proved by the strong correlation of pmTOR with pAkt and SSTRs (P & lt;0.001). There was a strong intercorrelation between pmTOR and VEGFR-2 expressions (P & lt;0.001). The expression of pmTOR were inversely associated with AJCC stage and WHO grade (P & lt;0.05), however the expression of VEGFR-2 was not associated with them. The expressions of pmTOR and VEGFR-2 showed a significant correlation with expression Chr A (P & lt;0.05). Inverse association between pmTOR with AJCC stage or WHO grade was noted in hindgut tumors, but no association was noted in foregut tumors. Regarding to VEGFR-2, in hindgut tumors, there was a positive correlation between VEGFR-2 with Chr A. None of pAkt, pmTOR or VEGFR-2 had an impact on survival. In foregut tumors, VEGFR-2 was associated with N stage. In conclusion, pmTOR and VEGFR-2 were inversely associated with AJCC stage or WHO grade. Our results showed that pmTOR and VEGFR-2 showed considerable variations in expression in GEP-NET in dependence of tumor location. These differences in expressions of pmTOR and VEGFR-2 might possibly influence response to mTOR inhibitiors or multi-targeted receptor tyrosine kinase inhibitors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5576. doi:1538-7445.AM2012-5576
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 1340-1340
    Abstract: Background: It has been reported that the frequency of FOXP3+ regulatory T cells (Tregs) among tumor-infiltrating lymphocytes is increased in cancer-bearing patients. We designed the study to determine the prognostic significance of FOXP3+ Tregs in gastric cancer. Methods: Tissue microarray and immunohistochemistry were used to assess the densities of FOXP3+ T regs in primary tumor tissue (n=216) and unmatched metastatic tumor tissue of regional lymph nodes (n=149) from gastric cancer patients. Numbers of FOXP3+ Tregs were counted using an image analysis program. FOXP3+ Treg densities were evaluated for correlation with clinicopathologic characteristics and overall survival. Results: With respect to primary tumor, low density of FOXP3+ Tregs was associated with advanced T stage (p = 0.028), but not with any other clinicopathologic features. Kaplan-Meier survival analysis revealed that the high density group of FOXP3+ Tregs had longer survival time than the low density group (p = 0.001, log-rank test). In multivariate analysis, FOXP3+ Treg density remained an independent prognostic factor with hazard ratio (95% CI) of 0.651 (0.435-0.975). In addition, it was found that FOXP3+ Treg density in metastatic tumor of lymph nodes was an independent prognostic indicator, i.e., high density of FOXP3+ Tregs was significantly associated with improved survival (hazard ratio (95% CI) = 0.519 (0.318-0.848)). Conclusions: FOXP3+ Treg densities in not only primary tumor, but also metastatic loci of regional lymph nodes were significantly associated with patient survival in gastric cancer. As our finding that high density of FOXP3+ Tregs was related to favorable prognosis contrasts with several previous studies, further investigation will be needed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1340.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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