bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2883: Theranostics nanoparticles targeting to metastatic non small cell lung cancer
Authors: LI LI-JIE , Chan Ming-Hsien , Chang Wei-Min , Hsiao Michael 
Published: July 2021

Abstract
Non-small-cell lung cancer (NSCLC) accounts for one of the most deadly cancers due to metastasis after therapy. Cancer metastasis usually results from epithelial-to-mesenchymal transition (EMT), and metabolic disorder is a key mediator of lung cancer EMT. The linkage between metabolic disorder and NSCLC EMT is still unclear. Using in silico analysis, C4ST1, a key enzyme of glycosaminoglycan synthesis pathway was up-regulation in mesenchymal type NSCLC cells. C4ST1 catalyzes chondroitin sulfate A (CsA) formation. We found both C4ST1 and CsA were up-regulation in mesenchymal type NSCLC cells. Not only C4ST1 overexpression but also CsA treatments changed NSCLC EMT balance and decreased the transcriptional activity on CDH1 promoter region. Furthermore, both treatments could promote in vitro NSCLC migration and invasion abilities in the epithelial type NSCLC cells. Up-regulation of C4ST1 cells also promoted lung cancer metastasis. Moreover, we used CsA binding peptide as a targeting ligands of metastatic NSCLC cells on theranostics nanoparticles. In summary, this study finds key gene in NSCLC EMT. Up-regulation of C4ST1 promotes NSCLC EMT and cell surface CsA content which may provide a novel theranostics niche on metastatic NSCLC cells.
Citation Format: LI-JIE LI, Ming-Hsien Chan, Wei-Min Chang, Michael Hsiao. Theranostics nanoparticles targeting to metastatic non small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2883.
Abstract 2892: Silencing cancer-neuronal crosstalk suppresses perineural invasion in colorectal cancer
Authors: Knoblich Colewyn , Rezvani Khosrow 
Published: July 2021

Abstract
Colorectal cancer (CRC) is one of the most diagnosed cancers and is a leading cause of cancer related mortality. Metastasis away from the primary site of CRC creates further complications, resulting in poor prognosis and decreased overall survival of patients. Perineural invasion (PNI) is an emerging field in cancer research that involves interactions between cancer and the nervous system as an alternative route for metastasis. Various studies have been conducted to understand the underlying mechanisms for metastasis, but PNI has been relatively understudied. Accumulating evidence indicate several signaling pathways are key players in the dynamic crosstalk between cancer cells and the nervous system portending the poor prognosis of patients facilitated by PNI. We hypothesize that colon and rectum cancer cells bi-directionally communicate with their adjacent nervous system influencing cancer progression and metastasis. We are using a combination of in vitro and animal models to define mechanisms underlying PNI in CRC. There are two set of experiments in this study as follow: Aim 1 determines whether neuron- cell lines co-cultured with diverse human colon and rectum cancer cells employed both selective soluble and exosome-based communications to have a stimulatory effect on the migration of colon and rectal cancer cells. We use a set of immunocytometry, western blot, flow-cytometry and proteomic approaches to determine key factors selectively used by colon/rectal cancer cells and neuronal cells to promote downstream metastatic pathways. Aim 2 uses a colon or rectal sciatic NIH-III immunodeficient mouse model to study the influence of the nervous system on cancer cells progression and involved signaling pathways in animal model. Completion of this study will uncover the soluble and vesicle factors released by cancer cells and nerve endings during cancer progression and their potential relevance in the treatment of CRC cancer.
Citation Format: Colewyn Knoblich, Khosrow Rezvani. Silencing cancer-neuronal crosstalk suppresses perineural invasion in colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2892.
Abstract 2893: Transmembrane Chloride Intracellular Channel 1 (tmCLIC1) protein as a potential target for colorectal cancer metastasis
Authors: Cianci Francesca , Carlini Valentina , Verduci Ivan , Ranucci Matteo , Mazzanti Michele 
Published: July 2021

Abstract
Colorectal cancer (CRC) is the third most common tumor worldwide and the fourth cause of cancer-related death. The presence of distal metastasis at the time of the first diagnosis represents a worst prognosis factor for patients' long-term survival. Therefore, finding new targets to arrest the metastatic process is a main challenge for successful CRC therapy. Our laboratory focused its attention on the Chloride Intracellular Channel 1 (CLIC1), a metamorphic protein able to switch from a cytoplasmic to a transmembrane form associated to ion channel activity. Previous experiments demonstrated that transmembrane CLIC1 (tmCLIC1) functional activity is negligible in normal colon cells, while increases proportionally to CRC cells' aggressiveness. Moreover, we also revealed that tmCLIC1 supports CRC cells abnormal proliferation rate. Here, we show that tmCLIC1 pharmacological inhibition or its stable knock-down by gene silencing led to a significative reduction of CRC cells migrative and invasive potential, in vitro. To further confirm our hypothesis, we assessed in CLIC1 knock-down cells the downregulation of metalloproteinase-7 (MMP-7) protein and p38 mitogen-activated protein kinase (MAPK) signaling, both involved in migration and metastatic processes. Moreover, by injecting subcutaneously transfected cell lines in nude mice, we demonstrate that CLIC1 knock-down impairs tumor growth and limits cancer cells dissemination to lung. Our results suggest a role for tmCLIC1 in promoting CRC metastasis, making this protein a promising pharmacological target to arrest or slow-down CRC metastasis development. Moreover, thanks to its functional expression exclusively associated with malignant progression, tmCLIC1 could allow to limit side effects on healthy cell population.
Citation Format: Francesca Cianci, Valentina Carlini, Ivan Verduci, Matteo Ranucci, Michele Mazzanti. Transmembrane Chloride Intracellular Channel 1 (tmCLIC1) protein as a potential target for colorectal cancer metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2893.
Abstract 2897: The metastatic potential of high-grade serous ovarian cancer cells along disease progression
Authors: Ritch Sabrina J. , Goyeneche Alicia A. , Noman Abu S. , Telleria Carlos M. 
Published: July 2021

Abstract
Epithelial ovarian cancer (EOC) represents 90% of all ovarian tumors and is considered to be the deadliest gynecological disease. High grade serous ovarian cancer (HGSOC) is the most aggressive form of EOC and represents 70% of all deaths from the disease. Due to a lack of early symptoms and valid screening methods, HGSOC is often diagnosed at late stages, when metastasis has already occurred. HGSOC disseminates from the primary tumor as single cells or clusters that typically adheres to the peritoneal organs and wall. The purpose of this study was to characterize the migratory, invasive, and adhesive abilities of HGSOC cells representing different stages of disease evolution. Both wound healing (WH) and Boyden chamber (BC) assays were performed to study the migratory capacity of five HGSOC cell lines; PEO1, PEO4 and PEO6, from a first patient, and PEO14 and PEO23, from a second patient. The cell lines were generated along different stages of the disease (e.g. at presentation, recurrence, and before death), thus representing disease evolution. To study the invasive capacity of each cell line, a layer of extracellular matrix was added to the BC assays. Adhesion assays were performed on fibronectin coated plates. It was found that the migratory and invasive capacities of the HGSOC cell lines decreased along disease evolution in both cellular series. PEO1 and PEO14, two chemo-sensitive cell lines, were found to have the highest migratory and invasive capacities, while their chemoresistant counterparts, PEO4, PEO6 and PEO23, showed a decrease in migration and invasion. Moreover, a distinct migration pattern was found to be conserved in both WH and BC assays. Cell lines representing an early stage disease had a tendency to migrate as individual cells, while cells representing a late stage disease were observed migrating in clusters. Adhesion rates were found to be similar between all cells lines. The results suggest that HGSOC disease progression seems to be associated with reduced migratory and invasive capacities, contradicting the idea that advanced stage EOC cancers have higher metastatic potential.
Citation Format: Sabrina J. Ritch, Alicia A. Goyeneche, Abu S. Noman, Carlos M. Telleria. The metastatic potential of high-grade serous ovarian cancer cells along disease progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2897.
Abstract 2902: Beneficial effect of vactosertib combined with nal-IRI5-FU/LV in pancreatic cancer treatment
Authors: Hong Eunji , Park Sujin , Oshima Akira , Heo Jinsun , Park Jinah , Lee Jihee , Pang Kyoungwha , Han Songee , Park Hyeyeon , Kim Seong-Jin 
Published: July 2021

Abstract
Pancreatic cancer is one of leading causes of cancer-related mortality in the world. Treatment of pancreatic cancer is difficult due to aggressiveness, distal metastasis, and genetic and epigenetic alterations. Especially, TGF-β is highly expressed in the pancreatic cancer patients, and it leads aggressive tumor metastasis. Regulation of TGF-β signaling is essential for controlling tumor progression and metastasis because TGF-β is involved in cell proliferation, epithelial-to-mesenchymal transition, angiogenesis, metastasis, and immune responses in cancer. Therefore, inhibition of TGF-β signaling may be the key concept of effective chemotherapies for metastatic pancreatic cancer. Recently, nanoliposomal iriotecan (nal-IRI), 5-flourouracil (5-FU) and leucovorin (LV) adjuvant therapy has been applied for pancreatic cancer patients' treatment. Vactosertib, one of the leading TGF-β inhibitor, has been used for clinical trials in many chemotherapy strategies. In this study, we investigated the combination treatment effect of nal-IRI/5-FU/LV and vactosertib on pancreatic cancer in syngeneic orthotopic pancreatic mouse model. The combination treatment significantly increased survival rate compare with control or single treatment of vactosertib or nal-IRI/5-FU/LV. In the histological analysis showed that cancer cell invasion to surrounding tissues was markedly reduced in vactosertib and combination treatment groups. In the RNA-sequencing analysis of tumor RNA, the apoptotic process are positively regulated in vactosertib plus nal-IRI/5-FU/LV group. Furthermore, we found the up-regulated differentially expressed gene (DEG), CCDC80, involved in cell migration, invasion and apoptosis. We ectopically overexpressed CCDC80 on pancreatic cancer cell lines and demonstrated the tumor suppressive role of CCDC80. In conclusion, the combination treatment with vactosertib with nal-IRI/5-FU/LV improved pancreatic cancer survival by inhibiting tumor invasion and inducing apoptosis. These results indicate that combination therapy can be applied to clinical trials in pancreatic cancer patient. This study supported by KHIDI grant (HI14C2640) and National R&D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (HA17C0037).
Citation Format: Eunji Hong, Sujin Park, Akira Oshima, Jinsun Heo, Jinah Park, Jihee Lee, Kyoungwha Pang, Songee Han, Hyeyeon Park, Seong-Jin Kim. Beneficial effect of vactosertib combined with nal-IRI5-FU/LV in pancreatic cancer treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2902.
Abstract 2909: Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients
Authors: Li Fangyu , White Michael G. , Davis Jennifer , Hoffman Kristi L. , Menter David , Ajami Nadim , Zhang Xiaotao , Morris Jeffrey S. , Jenq Robert R. , Petrosino Joseph , Wargo Jennifer A. , Kopetz Scott , Daniel Carrie R. 
Published: July 2021

Abstract
Background: The intestinal microbiome is intimately involved in the pathogenesis of colorectal cancer and likely holds further insights to improve the treatment and management of this deadly disease. In a clinical cohort of patients with colon and rectal cancers, we characterized the tumor microbiota of surgical specimens and evaluated associations with prognostic factors, consensus molecular subtypes (CMS), and survival.
Methods: In 167 patients diagnosed with stage II through IV colon and/or rectal cancer who underwent evaluation and surgical resection (no prior systemic therapy) at The University of Texas MD Anderson Cancer, we characterized the tumor microbiome via 16S rRNA gene sequencing. Each patient's tumor was classified via CMS, a gene expression-based colorectal cancer classification system; and all patients were prospectively followed for disease progression, recurrence, or death. Microbiota diversity and composition were assessed with regard to clinicopathologic and tumor features; and associations with survival were further evaluated in multivariable Cox proportional hazards models.
Results: Left- vs. right-sided colon tumors were characterized by higher microbial diversity, distinct community features, and increased abundance of Bacteroides and Fusobacterium. CMS1 (microsatellite instability immune) vs. CMS2 (canonical) tumors were characterized by higher Bacteroides and Fusobacterium and lower Escherichia (all P&lt;0.05). Fusobacterium-positive and Escherichia-positive tumors were associated with improved 5-year overall survival [presence vs. absence, multivariable-adjusted HR and 95% CI: 0.43 (0.20-0.93) and 0.32 (0.19-0.78), respectively]. Bacteroides was enriched among stage II/III patients who progressed within 2-years (log-rank p&lt;0.001).
Conclusions: Our findings are consistent with those of other groups suggesting the landscape of the tumor microbiome differs by sidedness and molecular subtype, holding important clues and exploitable targets to improve outcomes in colorectal cancer patients.
Citation Format: Fangyu Li, Michael G. White, Jennifer Davis, Kristi L. Hoffman, David Menter, Nadim Ajami, Xiaotao Zhang, Jeffrey S. Morris, Robert R. Jenq, Joseph Petrosino, Jennifer A. Wargo, Scott Kopetz, Carrie R. Daniel. Tumor microbiota profiles are associated with molecular subtype and survival in colorectal cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2909.
Abstract 2919: Novel pre-clinical model to identify genetic modifiers of triple negative breast cancer
Authors: Sipe Laura M. , Korba Emily B. , Lu Lu , Williams Robert W. , Ashbrook David G. , Makowski Liza 
Published: July 2021

Abstract
Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype with poor outcomes. This is a grave clinical challenge for the ~30,000 patients diagnosed with this disease every year. Discovering genetic modifiers of differential TNBC vulnerability and disease progression is critical to improving predictive and personalized treatments. We hypothesized that using a well-established recombinant inbred strain, novel genetic modifiers of TNBC risk and aggression will be identified. The C3(1)-T antigen (C3Tag) genetically engineered mouse model (GEMM) recapitulates many facets of human basal-like TNBC to demonstrate promoting effects of exposures on tumor phenotypes. However, GEMM are highly constrained by their inbred genotype and do not allow a robust interrogation of the manner in which individual genetic variation might impact tumor initiation, progression, and response to therapy. Therefore, we developed a novel murine model of TNBC in the background of the largest and best characterized genetic reference population. Systems genetics is used to identify gene candidates. Cross-species comparison of our findings with publicly available human GWAS and genomic databases is an effective approach to validate conserved biologically relevant and targetable pathways. To our knowledge, this is the first study to explore modifier genes for TNBC phenotypes using a systems genetics approach in a GEMM for TNBC. Our results will contribute to significant advances in understanding risk and improving outcomes for breast cancer.
Citation Format: Laura M. Sipe, Emily B. Korba, Lu Lu, Robert W. Williams, David G. Ashbrook, Liza Makowski. Novel pre-clinical model to identify genetic modifiers of triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2919.
Abstract 2930: Characterization based on therapeutic target biomarkers of patients-driven xenografts model of gastric-type cervical adenocarcinoma
Authors: Kojima Yuki , Yoshida Hiroshi , Okuya Toshihiro , Okuma Hitomi S. , Nishikawa Tadaaki , Tanioka Maki , Sudo Kazuki , Noguchi Emi , Shimoi Tatsunori , Tanase Yasuhito , Uno Masaya , Ishikawa Mitsuya , Fujiwara Yasuhiro , Yonemori Kan , Kato Tomoyasu 
Published: July 2021

Abstract
The majority of cervical adenocarcinomas are associated with human papillomavirus (HPV) mainly HPV types 18 and 16. Patients with gastric-type endocervical adenocarcinoma (GAS) have an aggressive clinical behavior, resulting in poor prognosis compared to those with HPV-associated usual type adenocarcinoma. Chemotherapy resistance to taxane and carboplatin-based regimen has also been reported, which poses a difficulty in managing GAS patients with metastatic lesion. We established patient-driven xenografts (PDX) of two GAS patients and evaluated protein biomarkers for drug development using immunohistochemistry staining. The pathological findings of the established PDX were confirmed by HE staining and special staining to be similar to the pathological findings obtained from the patients' surgical specimens. PDX was established 78 and 48 days after transplantation of patient tumor tissue into immunodeficient mice, respectively. HER2, HER3, PMS2, MSH6, PanTrk, and ARID1A were stained for both PDX and patient-tumor samples to evaluate biomarkers for therapeutic targets. All staining results were consistent between patient tumor samples and PDX for both patients. Staining results for HER3 showed that both patients' tumors and the corresponding PDXs were 3+. Staining for HER2 was 1+ in both cases. In all PDX and patient-tumor samaples, PMS2, MSH6 and ARID1A showed no loss of protein expression, and PanTrk showed no protein expression. In addition, nine additional tumor tissue specimens from GAS patients diagnosed at our institution were stained for HER3 and HER2. HER3 was 3+ in 3 cases and 2+ in 6 cases, and HER2 was 3+ in 1 case, 2+ in 3 cases and 1+ in 5 cases. The present study showed overexpression of HER2 and HER3, suggesting a therapeutic potential of targeting HER2 and/or HER3 in GAS patients. We are next planning an in vivo study to develop therapies in GAS patients.
Citation Format: Yuki Kojima, Hiroshi Yoshida, Toshihiro Okuya, Hitomi S. Okuma, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Emi Noguchi, Tatsunori Shimoi, Yasuhito Tanase, Masaya Uno, Mitsuya Ishikawa, Yasuhiro Fujiwara, Kan Yonemori, Tomoyasu Kato. Characterization based on therapeutic target biomarkers of patients-driven xenografts model of gastric-type cervical adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2930.
Abstract 2938: APOBEC3B and TKI resistance in EGFR mutant lung cancer
Authors: Caswell Deborah , Mayekar Manasi , Law Emily , Hill William , Gronroos Eva , Harris Reuben , Bivona Trever , Swanton Charles 
Published: July 2021

Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. EGFR mutations, which account for about 25% of lung cancer cases, are more commonly associated with lung cancer in never smokers. Although response rates to EGFR tyrosine kinase inhibitors (TKI) used as a first line therapy are high, acquired resistance inevitably occurs. Elevated tumor mutation burden in EGFR mutant lung cancer is associated with a shorter progression free survival, and worse overall survival with both first and second generation TKIs. Increasing our understanding of drivers of mutagenesis in lung cancer is critical in our efforts to prevent tumor reoccurrence and resistance. APOBEC-driven mutagenesis has been shown to occur in multiple cancer types including lung adenocarcinoma. Using the TCGA and TRACERx datasets we have demonstrated that APOBEC3B is significantly upregulated when compared with other APOBEC family members in EGFR mutant lung adenocarcinoma, and that the APOBEC mutation signature is enriched in a subset of patients with EGFR mutant lung adenocarcinoma. To model APOBEC mutagenesis in lung cancer, we have developed a novel lung cancer mouse model, by crossing the ROSA26LSL-APOBEC3B (A3B) mouse model with several different EGFR mutant mouse models. Using these models, we find that APOBEC3B expression is selected for post-TKI and contributes to resistance to TKI therapy.
Citation Format: Deborah Caswell, Manasi Mayekar, Emily Law, William Hill, Eva Gronroos, Reuben Harris, Trever Bivona, Charles Swanton. APOBEC3B and TKI resistance in EGFR mutant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2938.