bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3822: Expression of androgen receptor and CD24 correlates with improved 5-year survival in Pakistani patients with invasive breast cancer
Authors: Riaz Nazia , Idress Romana , Habib Sadia , Hussain Azhar , Lalani El-Nasir 
Published: July 2017

Abstract
Introduction: Androgen receptor (AR) expression has been shown to correlate with improved survival in luminal A, B and triple negative (TN) breast cancer (BCa). Cancer stem cells (CSC) with CD44+/CD24- and ALDH1+ phenotype is associated with pro-invasive gene signature in BCa. Aim of our study was to evaluate prognostic significance of AR expression in relation to CD44, CD24 and ALDH1 in invasive BCa.
Methodology: Immunohistochemical expression of AR, CD44, CD24 and ALDH1 was evaluated in 180 FFPE blocks of BCa cases from one institution. Clinico-pathological details and follow-up data were collected from medical charts. Data was analyzed on SPSS 19. Five-year survival was estimated by Kaplan Meier.
Results: Median age of patients was 55 years (range: 28-87). Fifteen percent of patients were diagnosed with stage I, 52.2% with stage II, 25% with stage III and 7.8% with stage IV disease. Mean duration of follow-up was 4.5 years (SD+ 2.7) and 29% mortalities were attributed to BCa. AR was expressed in 63.9%, ER in 61%, PR in 51% & HER-2/neu in 30% of tumors. CD44, CD24 and ALDH1 were expressed in 60%, 43.3% & 28.3% of tumors respectively.
AR expression was associated (p-value&lt;0.001) with grade II tumors expressing ER, PR and CD24 but lacking ALDH1. Multivariable analysis confirmed AR (adjusted HR 0.43, 95% CI 0.19-0.95) and PR (adjusted HR: 0.20, 95% CI: 0.07-0.60) to be independently associated with better outcome.
Five year survival of patients with AR+ versus AR- expressing tumors, showed that patients with AR+ tumors had significantly better outcome (p-value=0.03) with survival advantage of 39.6 months. Survival advantage decreased by 9.6 months in tumors expressing CD44+/CD24-/AR- (p-value=0.01) phenotype and by 12 months in patients whose tumors were phenotypically ALDHI+ /AR- (p-value=0.12).
We stratified TN tumors into 2 groups: A. TN/CD24+/AR+; B. TN/CD24-/AR- and found that group A tumors had a trend towards better 5 survival (p-value=0.09).
Conclusions: Three individual markers (CD44, CD24, AR) may afford prognostic information. Combinations of CD44, CD24 and AR permitted patient stratification into 3 risk categories: poor risk CD24-/AR-; intermediate risk CD44+/CD24-/AR- and good risk CD24+/AR+. Stratification of TN group showed that loss of AR and CD24 was associated with poorest outcome. These results underscore the relevance and importance of AR and CD24 as prognostic markers in invasive BCa.
Citation Format: Nazia Riaz, Romana Idress, Sadia Habib, Azhar Hussain, El-Nasir Lalani. Expression of androgen receptor and CD24 correlates with improved 5-year survival in Pakistani patients with invasive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3822. doi:10.1158/1538-7445.AM2017-3822
Abstract 3823: High intrinsic DPD activity matters too
Authors: Chamorey Emmanuel , Francois Eric , Etienne-Grimaldi Marie-Christine , Viotti Julien , Peyrade Frederic , Bozec Alexandre , Ferrero Jean-Marc , Schiappa Renaud , Milano Gerard 
Published: July 2017

Abstract
Introduction: Fluoropyrimidines (FP) are of major use in treating cancer. Dihydropyrimidine dehydrogenase (DPD) is the main enzyme responsible for FP catabolism. Low DPD activity screening has proven its predictive clinical value in identifying patients at risk for toxicity. However, high DPD activity may translate to decreased FP activation and efficacy.
Patients and methods: One hundred and forty-three patients (monocentric retrospective study) underwent a pretreatment assessment of DPD activity in lymphocytes between 01/01/2004 and 20/04/2016. Included patients were male or female, &gt;18 years, FP-treatment-based. Cut-off for DPD activity was assessed using smoothing spline curves.
Results: Median patient follow-up was 30 months [CI95%: 27.3-36.2], mean age 63+/-3 years, females accounted for 53%, 90% of patients had a good performance status (0 or 1). Fifty-eight percent of FP indications (65% 5-FU and 35% capecitabine) were adjuvant or neoadjuvant and 42% were prescribed for local or metastatic recurrences. Tolerance was poor for 43% of patients and 49% needed dose reduction. Objective response (complete and partial) was observed in 50% of patients, stable disease in 38% and progression in 12%. No significant correlation was observed between DPD activity and response to treatment. Mean DPD activity (pmol min−1 mg−1 protein) was 0.21+/-0.1 (quartile: [0.001-0.14-0.20-0.28-0.48]). DPD activity analyzed as a continuous variable was significantly linked to overall survival (OS) (p=0.042) but not with progression-free survival (PFS). The higher the DPD activity, the lower the OS. DPD activity analyzed as a binary variable (cut-off at 0.30) was significantly linked to overall survival (p=0.012) but also with PFS (p=0.016). A Cox regression model for OS and PFS adjusted for age, sex, type of cancer, type of administered FP, and associated surgical or radiotherapy treatment was performed. After adjustment, DPD activity remained significantly linked to OS (p=0.03) and PFS (p=0.021).
Conclusions: DPD activity screening could lead to a two-pronged approach: FP dose reduction in the event of low DPD and dose increase for high DPD. Such a strategy needs to be prospectively validated under personalized DPD-based treatment.
Note: This abstract was not presented at the meeting.
Citation Format: Emmanuel Chamorey, Eric Francois, Marie-Christine Etienne-Grimaldi, Julien Viotti, Frederic Peyrade, Alexandre Bozec, Jean-Marc Ferrero, Renaud Schiappa, Gerard Milano. High intrinsic DPD activity matters too [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3823. doi:10.1158/1538-7445.AM2017-3823
Abstract 3829: TCIRG1, T-cell immune regulator 1, functions as a metastatic enhancing gene in liver tumorigenesis
Authors: Yang Hee Doo , Eun Jung Woo , Shen Qingyu , Kim Hyung Seok , Kim Sang Yean , Nam Suk Woo 
Published: July 2017

Abstract
Recurrence and metastasis are a major challenge in the management of hepatocellular carcinoma (HCC) patients after HCC resection. In order to identify metastatic molecular signature, we performed comparative gene expression profiling analysis with recurred HCC tissues from HCC patients who underwent partial or total hepatectomy and non-metastatic primary HCC. From this, we were able to recapitulate molecular signatures associate with HCC recurrence, and found that TCIRG1 (T-Cell Immune Regulator 1) was one of the aberrantly overexpressed gene elements in recurred HCC patients with total hepatectomy. We then observed that TCIRG1 is significantly overexpressed in TCGA-LIHC (Liver Hepatocellular Carcinoma Dataset of The Cancer Genome Atlas), and high expression of TCIRG1 was significantly associated with poor prognosis of HCC patients in 5-year disease-free. TCIRG1 knockdown suppressed tumor cell growth and proliferation in Huh7 and SNU475, liver cancer cell lines. From flow cytometric analysis for cell cycle analysis and cell death, we observed that TCIRG1 knockdown caused a significant increase of G1/S phase, and also induced programmed cell death processing in liver cancer cells. TCIRG1 knockdown also reduced the metastatic potential of HCC cells by selectively regulating epithelial-mesenchymal transition (EMT) regulatory proteins, E-cadherin, N-cadherin, Vimentin, Fibronectin, Snail and Slug, in liver cancer cells. In addition, sustained expression of TCIRG1 in liver cancer cell line reduced tumor growth rate in mouse xenograft model. Moreover, targeted-disruption of TCIRG1 significantly attenuated the metastatic potential of ras-transformed NIH-3T3 cells in vitro and in vivo. In conclusion, our findings suggest that TCIRG1 functions as metastatic enhancing gene by modulating cellular growth, death, and EMT in liver cancer cells providing TCIRG1 as a therapeutic target for the treatment of liver malignancy and metastasis.
Citation Format: Hee Doo Yang, Jung Woo Eun, Qingyu Shen, Hyung Seok Kim, Sang Yean Kim, Suk Woo Nam. TCIRG1, T-cell immune regulator 1, functions as a metastatic enhancing gene in liver tumorigenesis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3829. doi:10.1158/1538-7445.AM2017-3829
Abstract 3843: Autologous resconstitution of human cancer and immune system in vivo
Authors: Fu Juan , Sen Rupashree , Masica David L , Karchin Rachel , Pardoll Drew , Kim Young 
Published: July 2017

Abstract
Correlative studies from checkpoint inhibitor trials have indcated that better understanding of human leukocytic trafficking into the human tumor microenvironment can expedite the translation of future immune-oncologic agents. In order to directly characterize signaling pathways that can regulate human leukocytic trafficking into the tumor, we have developed a completely autologous xenotransplanation method to reconstitute the human tumor immune microenvironment in vivo. When we analyzed the TCGA database of human head and neck squamous cell carcinoma(HNSCC), we found that STAT3 signaling was associated with worse prognostic mesenchymal subtye. We silenced STAT3 signaling in the tumor compartment in these autologously reconstituted humanized mice, and we noted increased tumor infiltrating lymphocytes and slower tumor growth rate. We also used this novel agents that can alter endogenous leukocytic infiltration into the tumor. Taken together, we present a valuable method to study individialized human tumor microenvironments in vivo without confound allgeneic responses.
Citation Format: Juan Fu, Rupashree Sen, David L Masica, Rachel Karchin, Drew Pardoll, Young Kim. Autologous resconstitution of human cancer and immune system in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3843. doi:10.1158/1538-7445.AM2017-3843
Abstract 3845: Establishment and characterization of patient-derived xenografts of clear cell carcinoma of the ovary
Authors: Watari Hidemichi , Endo Daisuke , Honda Kouhei , Kunitomo Mihoko , Nomura Toshiyuki , Sakuragi Noriaki 
Published: July 2017

Abstract
Background; The patient-derived xenograft (PDX) model is likely to reflect original human cancer biology compared to cultured cell lines, since tumor tissues are directly implanted into animals. PDX models of ovarian cancer have been developed, but were not fully characterized at the molecular level, especially for clear cell carcinoma (CCC), which is more prevalent in Japan than western countries, exhibits chemoresistant phenotype and poor survival. The development of new treatment strategies and the better understanding of biology of CCC both depend on clinically relevant animal models. In particular, molecular annotated PDX models are useful for the preclinical investigation of anticancer drugs and individualized anticancer therapy. Methods; We transplanted 19 parent (primary or metastatic) tumors directly into NOG mice. The histologic characteristics were compared between parental tumors and PDX ones. Among CCC pairs, gene expression analysis, gene mutation analysis were conducted on parental tumors and corresponding PDX tumors. Response to chemotherapeutic agents was analyzed using PDX tumors of CCC, and correlated with clinical outcome. Results; Six of nineteen (31.6%) transplanted tumors could be passaged. Gene expression profiles revealed that engrafted tumors expressed more proliferation-related genes than those of non-englafted ones. Among six PDX models established, two were found to be CCC. Two PDX tumors of CCC maintained the histologic characteristics of parental CCC tumors. Gene expression profile revealed similar results between primary CCC and PDX tumors of CCC except that PDXs lost expression of immune-related genes.. Gene mutational analysis showed similar pattern between primary CCC and PDX of CCC. Drug-sensitivity test showed resistance to carboplatin in two PDX tumors of CCC, which is consistent with their clinical outcomes. Conclusions. PDXs of CCC were established and found to retain histologic and clinical features of original tumors, and can be utilized to screen new target drugs for platinum-resistant CCC.
Citation Format: Hidemichi Watari, Daisuke Endo, Kouhei Honda, Mihoko Kunitomo, Toshiyuki Nomura, Noriaki Sakuragi. Establishment and characterization of patient-derived xenografts of clear cell carcinoma of the ovary [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3845. doi:10.1158/1538-7445.AM2017-3845
Abstract 3851: Targeting HER2 in gastric cancer: Hints from a gastric PDX platform
Authors: Corso Simona , Migliore Cristina , Apicella Maria , Menegon Silvia , Pectasides Eirini , Capeloa Tania , Durando Stefania , Cargnelutti Marilisa , Cassoni Paola , Sapino Anna , Giuli Maurizio de , Bass Adam , Giordano Silvia 
Published: July 2017

Abstract
Introduction: Gastric cancer is the 3rd leading cause of cancer mortality worldwide. Surgery is the only curative treatment strategy and conventional chemotherapy has shown limited efficacy. Trastuzumab (a HER2 mAb), is the only therapy targeting molecular alterations approved so far in gastric cancer, for HER2+ patients with advanced disease. However only a fraction (&lt;20%) of HER2 amplified patients benefits from treatment.
Methods: We have recently generated a molecularly annotated colony of gastro-esophageal PDXs (at the moment, &gt; 70 PDXs). The platform also comprises primary cell lines and 3D-cultured organoids derived from gastric cancer PDXs.
Results and Discussion: At present, we have identified several HER2+ PDXs and generated the corresponding in vitro derivatives. Four HER2+ PDXs, showing 3+ HercepTest score and HER2 amplification &gt; 8 copies (thus theoretically sensitive to Trastuzumab), were selected to undergo ‘xenotrials’ with the following anti-HER2 drugs/combos: Trastuzumab (T); Pertuzumab (P, anti-HER2 mAb); Lapatinib (L, a dual HER2-EGFR tyrosine kinase inhibitor). According to RECIST-like criteria, T induced tumor regression in only 1 out of 4 HER2+ PDXs. Interestingly, in all the tumors but one the combos T+P and T+L were able to bypass resistance to T monotherapy and to induce tumor regression. One tumor was resistant to all the tested therapeutic approaches.
Conclusion: We identified PDXs displaying HER2 gene amplification. Only a minor fraction of them benefited from the anti-HER2 mono-therapy, despite the presence of a strong HER2 gene amplification, while the association of two HER2 inhibiting drugs resulted in intense and prolonged response. This suggests that monotherapy with T might not be the most effective therapeutic approach in gastric cancer patients. We are currently investigating the cause of resistance to anti-HER2 drugs to identify mutations/CNV in tumors showing resistance to Trastuzumab.
Note: This abstract was not presented at the meeting.
Citation Format: Simona Corso, Cristina Migliore, Maria Apicella, Silvia Menegon, Eirini Pectasides, Tania Capeloa, Stefania Durando, Marilisa Cargnelutti, Paola Cassoni, Anna Sapino, Maurizio de Giuli, Adam Bass, Silvia Giordano. Targeting HER2 in gastric cancer: Hints from a gastric PDX platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3851. doi:10.1158/1538-7445.AM2017-3851
Abstract 3882: Identification of targetable EMT markers in cancer stem-like cells derived from therapeutic resistant melanoma
Authors: Crosson William P. , Berlinberg Elyse , Nazarian Ramin 
Published: July 2017

Abstract
Melanoma is the deadliest form of skin cancer, expected to claim approximately 10,000 lives in 2016. An activating mutation in BRAF(V600E) occurs in 50-60% of melanomas and 7% of all cancers. Despite an unprecedented initial response, patients treated with a highly effective BRAF inhibitor, vemurafenib (FDA approved 2011), acquire drug resistance within 6-9 months. Vemurafenib-resistant sub-lines, derived from BRAFV600E isogenic parental melanoma cells, have altered cell morphology and upregulated PDGFRβ expression. Epithelial-to-mesenchymal transition (EMT), a hallmark of cancer-stem-like cells (CSC), is a potential mechanism that melanomas employ to evade targeted therapy. Through immunocytochemical, immunoblot, and flow cytometric analysis, we investigated the expression profile of EMT biomarkers within parental and resistant melanoma cell lines. Our findings indicate CSCs within melanoma populations may serve as progenitor cells for therapy-resistant melanoma sublines through differential expression of key EMT-related biomarkers. Furthermore, resistant cell lines were significantly more invasive in migration assays. Our results implicate notable EMT biomarkers in CSCs that can be used as novel targets for diagnosis and treatment of tumor resistance in melanoma patients.
Citation Format: William P. Crosson, Elyse Berlinberg, Ramin Nazarian. Identification of targetable EMT markers in cancer stem-like cells derived from therapeutic resistant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3882. doi:10.1158/1538-7445.AM2017-3882
Abstract 3883: Transcriptome analysis reveals mitochondrial gene signature upregulation in gastric cancers expressing the stem cell marker CD133
Authors: Lee Han Hong , Ko Yoon Ho , Kim Tae-Min , Park Won-Sang 
Published: July 2017

Abstract
Gastric cancers expressing the stem cell marker CD133 are more aggressive than those that do not express the marker, and are associated with more unfavorable clinical outcomes. The CD133-associated aggressive behavior of gastric cancer remains poorly understood at the molecular level. In the present study, we performed gene expression profiling of bead-sorted CD133+ and CD133- KATO III cell lines to derive in vitro molecular signatures of CD133 expression in gastric cancer. Three expression signatures associated with CD133 expression ('Mitochondria', 'Cell cycle', and 'Lipid metabolism') were inferred upon study of a module association map of the key molecular signatures associated with CD133 expression in gastric cancer. Using the public gene expression profiles, we show that the patients with overexpression of CD133 show unfavorable clinical outcomes compared to CD133- patients in the context of up-regulation of 'Mitochondria' expression signature. We further showed that CD133+ KATO III cells had a higher mitochondrial function and were more susceptible to the mitochondrial inhibitors rotenone, antimycin A, and NaN3, than were CD133- cells. Together, our findings suggest that transcriptional up-regulation of the 'Mitochondria' gene signature may identify CD133+ gastric cancers; such data are of clinical and pharmacological relevance.
Note: This abstract was not presented at the meeting.
Citation Format: Han Hong Lee, Yoon Ho Ko, Tae-Min Kim, Won-Sang Park. Transcriptome analysis reveals mitochondrial gene signature upregulation in gastric cancers expressing the stem cell marker CD133 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3883. doi:10.1158/1538-7445.AM2017-3883
Abstract 3887: GNA13 is a theranostic target that drives drug resistance and cancer stem-like phenotypes in solid tumors
Authors: Rasheed Suhail Ahmed Kabeer , Leong Hui Sun , Lakshmanan Manikandan , Raju Anandhkumar , Dadlani Dhivya , Chong Fui-Teen , Rajarethinam Ravisankar , Skanthakumar Thakshayeni , Tan Ern Yu , Hwang Jacqueline Siok Gek , Lim Kok Hing , Tan Daniel Shao-Weng , Ceppi Paolo , Wang Mei , Tergaonkar Vinay , Casey Patrick J. , Iyer N. Gopalakrishna 
Published: July 2017

Abstract
Treatment failure in solid tumors occurs due to the survival of specific subpopulations of cells that possess stem cell-like (CSC) phenotypes. Studies have implicated G protein-coupled-receptors (GPCRs) in cancer progression and the acquisition of aggressive phenotypes. Many of the implicated GPCRs signal through the G12 subfamily, comprised of GNA12 and GNA13. In this study, we demonstrate that GNA13 is upregulated in many solid tumors and impacts survival and metastases in these patients. Consistent with this, we show that GNA13 expression modulates drug resistance through its effect on the CSC sub-population in a panel of patient-derived head and neck (HNSCC) and breast cancer cells. These data were validated in vivo, where GNA13 over-expression in patient-derived xenografts increased tumor initiating capacity, tumorigenicity and drug resistance, with no effect on growth or proliferation. Signaling through NFKB and MAPK pathways appear to be critical to the observed phenotype. Importantly, blockade of GNA13 expression, or select downstream pathways using small-molecule inhibitors, abrogates GNA13-induced CSCs, rendering cells vulnerable to standard-of-care cytotoxic therapy for these cancers. Taken together, these data indicate that GNA13 expression is a potential prognostic biomarker, and interfering with GNA13-induced signaling provides a novel strategy to block CSCs and drug resistance in solid tumors.
Citation Format: Suhail Ahmed Kabeer Rasheed, Hui Sun Leong, Manikandan Lakshmanan, Anandhkumar Raju, Dhivya Dadlani, Fui-Teen Chong, Ravisankar Rajarethinam, Thakshayeni Skanthakumar, Ern Yu Tan, Jacqueline Siok Gek Hwang, Kok Hing Lim, Daniel Shao-Weng Tan, Paolo Ceppi, Mei Wang, Vinay Tergaonkar, Patrick J. Casey, N. Gopalakrishna Iyer. GNA13 is a theranostic target that drives drug resistance and cancer stem-like phenotypes in solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3887. doi:10.1158/1538-7445.AM2017-3887