bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5074: Investigating the cellular uptake of liposomal delivery system using cellular models of lymphoma
Authors: Bom Joyce Edlyne Chima , Van Le Tien , Togba-Bass Tracy , Kim Erica , Campbell Robert 
Published: June 2022

Abstract
Background: Lymphoma accounts for more than 4% of cancer diagnoses in the United States. Conventional treatment strategies for lymphoma are effective, but face a multitude of challenges limiting efficacy. Nanomedicine presents a viable option to optimize the efficacy of current anti-lymphoma therapies. To achieve most selective drug targeting, optimization of liposome preparations is key. To improve the selective targeting properties of conventional liposomes, cell membrane lipid-extracted nanoliposomes (CLENs) were prepared using lipids extracted from lymphoma target cells. Reported here is results of initial design and development, including physicochemical characterization and in vitro analyses.
Methods: The CRL-1593.2 cell line was the chosen cellular model of lymphoma. CRL-1593.2 cells were cultured and expanded In vitro for cellular extraction purposes. The CRL-1593.2 cell lipid extract (LE) was included to prepare CRL-1593.2 CLENs. Conventional lipid ingredients used in preparation of CRL-1593.2-CLENs included DOPC, Cholesterol, and DPPE-Rhodamine (used as a fluorescence indicator) for fluorescence studies using a fluorescence microplate reader. Phase I studies included physicochemical characterization and cellular uptake studies of preparations of CLENs, including 0 to 40 mol% of CRL-1593.2 LE content. In Phase II, the optimal LE content as determined by Phase I was fixed, while cholesterol content varied from 0 to 40 mol%.. For in vitro studies, the control cell lines employed represented other hematological diseases, RPMI 8226 (multiple myeloma), CCRF-CEM (acute lymphoblastic leukemia), and K562-GFP (chronic myeloid leukemia).
Results: The optimized composition of CLEN preparation type consisted of DOPC: Cholesterol, lymphoma lipid extract (derived from CRL-1593.2 cells) in the ratio of 93:5:2. The mean particle size was 116 ± 10 nm (n=4) and the mean zeta potential was - 4.5 ± 5 mV (n= 4). For in vitro studies, the inclusion of 2 mol% LE in CRL-1593.2-CLENS demonstrated significant uptake when compared to 0% LE control preparations (P = 0.016). Additionally, the lymphoma cells also had a significantly higher uptake of the CRL-1593.2-CLENs when compared to the other hematological cell lines [(CCL-155; P = 0.0081), (K562-GFP; P = 0.0037) and, (CCRF-CEM; P = 0.0079)].
Conclusions: Early findings collectively suggest that the CRL-1593.2-CLENs is a highly selective drug delivery platform for the targeting of lymphoma cells.
Citation Format: Joyce Edlyne Chima Bom, Tien Van Le, Tracy Togba-Bass, Erica Kim, Robert Campbell. Investigating the cellular uptake of liposomal delivery system using cellular models of lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5074.
Abstract 5093: A predictive biomarker classififier in NSCLC treated with immunotherapy
Authors: Zhang Shixin , Wang Xintong 
Published: June 2022

Abstract
Background: Our Study have been focusing on investigating the immune components to increase immunotherapy efficacy and to assist patient stratification for immunotherapy NSCLC patients, we explored predict property of the mutations characteristics with immunotherapy survival benefit and Tumor Immune Microenvironment(TME)characteristics.
Methods: A training cohort of 344 immunotherapy NSCLC were obtained from MSK database with Clinical and biological data. intersecting Candidate genes related to survival(p_value &lt; 0.05)with immunity-related genes (IRGs), following an independent cohort of 75 patients with immunotherapy NSCLC was assessed. Applying the same patients RNA-Seq data calculated TME by CIBERSORT from TCGA database.
Results: The result divided the patients into two groups: 54 samples in the MT group ( two or more of the 18 candidate genes mutated) and 290 samples in the WT group (less two mutations in the 18 genes).The TMB status frequency in WT_H/L and MT_H/L cohort were 11.9% vs 3.8% and 21.5% vs 62.8%(MT_H vs WT_H, P &lt; 0.01 ; MT_L vs WT_L, P = 0.046 ). Discovery training cohort showed a high Overall Survial for patients with MT group which was 15.7% and 84.3% for WT group( P_value &lt; 0.0001). The genes mutation signature degree of most immune cells (such as CD4\8+ T cells and M1 macrophages \natural killer ) were higher in the MT group.
Conclusions: Our study offers genes mutation biomarker for OS prediction and potential addition development of tumor exemption, to be served as a convenient tool for identifying high relapse individuals with immunotherapy NSCLC patients.
Citation Format: Shixin Zhang, Xintong Wang. A predictive biomarker classififier in NSCLC treated with immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5093.
Abstract 5094: A pan-cancer analysis of GRIN2A as a potential biomarker for immune checkpoint therapy
Authors: Jiang Mei , Zhong Xuefeng , Huang Mengli 
Published: June 2022

Abstract
Background: GRIN2A is the encoding gene of GluN2A, which is a subunit of the N-methyl-D-aspartate receptor, and participates in the regulation of excitatory neurotransmission in the brain. GRIN2A is one of the key genes in epilepsy researches, however, only a few researches have been done on GRIN2A in cancer field. The existing studies showed that GRIN2A mutation was frequently found in melanoma and caused abnormal tumor suppressor function. Besides, GRIN2A mutation was associated with higher tumor mutation burden (TMB) in non-small-cell lung cancer, suggesting that GRIN2A-altered tumors might be more sensitive to immune checkpoint inhibitors (ICIs), but the correlation of GRIN2A mutation status with immune response in clinical remains unknown.
Methods: Next generation sequencing (NGS) and clinical data of pan-cancer patients were obtained from two MSK-IMPACT Clinical Sequencing cohorts (MSK-2017, N=10336; MSK-2019, N=1661). The MSK-2019 cohort, which was treated with ICIs, were analyzed to explore the association between GRIN2A alteration and therapeutic efficacy of ICIs. Moreover, mRNA expression data of 10201 pan-cancer patients were obtained from the Cancer Genome Atlas (TCGA) database to explore the association between GRIN2A expression level and immune cell infiltration.
Results: In total, 3.74% (387/10336) of pan-cancer patients in MSK-2017, and 7.47% (124/1661) in MSK-2019, carried GRIN2A alteration. In MSK-2017, the top three GRIN2A alteration frequency cancer types were melanoma (68/365, 18.63%), skin cancer (non-melanoma, 22/148, 14.86%) and small cell lung cancer (11/82, 13.41%), respectively. And the commonly mutation types of GRIN2A were missense mutation. In MSK-2019 treated with ICIs, the TMB level of GRIN2A-altered group was significantly higher than wild group (median TMB, altered-type vs. wild-type = 25.09 vs. 5.90 Muts/Mb, P&lt;0.0001) and the overall survival (OS) of GRIN2A-altered group were significantly longer than wild group (OS, median, 44.00 vs. 15.00 months; HR=0.5812 [95%CI: 0,4474-0.7550], P=0.0008). But in MSK-2017 without immunotherapy, there was no difference in OS between GRIN2A-altered group and wild group (OS, median, 26.00 vs. 26.13 months; HR=1.194 [95%CI: 0.9588-1.487], P=0.0849). Furthermore, the GRIN2A expression level was positively correlated with the degree of immune cell infiltration in some tumor types, such as prostate adenocarcinoma (PRAD), while some tumors did the opposite, such as sarcoma (SARC).
Conclusion: The results indicated that GRIN2A gene alteration was associated with a higher TMB level in pan-cancer patients, and patients carrying GRIN2A alteration might easily benefit from ICIs.
Citation Format: Mei Jiang, Xuefeng Zhong, Mengli Huang. A pan-cancer analysis of GRIN2A as a potential biomarker for immune checkpoint therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5094.
Abstract 5098: Genetic and immunologic characteristics of biliary tract cancer patients with LRP1B mutation
Authors: Chen Weiwei , Zhang Hushan , Dong Hongmin , Wang Gang , Li Xiaokai , Chen Wanghua , Li Guodong , Bai Saixi , Chen Juan , Wang Wenling 
Published: June 2022

Abstract
Background: Although the initial clinical results of immune checkpoint inhibitors (ICI) have been obtained in biliary tract cancer (BTC), and previous researches explored potential biomarkers for predicting response to ICI in BTC, and gene LRP1B was found as one of predictive biomarkers. Here we evaluated the mutation information of LRP1B in Chinese patients with BTC, and analyzed the potential explanation for more benefit from ICI treatment in patients with LRP1B mutation.
Methods: The formalin-fixed paraffin-embedded specimens of 1324 cancer patients who have underwent next-generation sequencing (NGS) from 2016 to 2021, were included in this study. NGS was performed to detect gene mutation, and tumor mutational burden (TMB) measured by a 733 gene panel. PD-L1 expression detected by using Dako PD-L1 IHC 22C3 pharmDx.
Result: The NGS results revealed that 12.76% (169/1324) patients with BTC have LRP1B mutation. Among these 1324 patients, 931 (patients with or without LRP1B mutations were 129 and 802, respectively) patients were available for analysis of TMB level, 820 ((patients with or without LRP1B mutations were 114 and 706, respectively)) patients for analysis of PD-L1 expression, and 1163 (patients with or without LRP1B mutations were 172 and 991, respectively) patients for analysis of MSI-H. TMB level and PD-L1 expression level were compared between groups with and without LRP1B mutation, and results showed that both these two biomarkers were higher in group with LRP1B mutation than without LRP1B mutation, especially TMB level was significantly higher (p&lt;0.001).Further analysis revealed that the median TMB level, proportion of strong positive PD-L1 expression, and proportion of MSI-H were all higher in group of LRP1B mutation than wild type.
Conclusion:These results suggest that LRP1B can be considered as one of effective biomarkers for ICI treatment in BTC, the underly mechanism may be related to the high TMB level.
Citation Format: Weiwei Chen, Hushan Zhang, Hongmin Dong, Gang Wang, Xiaokai Li, Wanghua Chen, Guodong Li, Saixi Bai, Juan Chen, Wenling Wang. Genetic and immunologic characteristics of biliary tract cancer patients with LRP1B mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5098.
Abstract 5101: Urine based dynamically monitoring reflect pathologic response in MIBC patients with neoadjuvant immunotherapy
Authors: Yang Xiao , Cai Lingkai , Cao Qiang , Shi Min , Liang Yiming , Qu Yurong , Lu Qiang 
Published: June 2022

Abstract
Background: The recommended standard of care treatment for nonmetastatic muscle-invasive bladder cancer (MIBC) is radical cystectomy (RC). Even with urinary diversion, radical cystectomy has a major impact on patients' quality of life. Although high rates of overall and disease-specific survival were observed in patients managed with bladder preservation, who achieved a clinically complete response to neoadjuvant therapy. Frequent evaluation of tumor response based cystoscopy implementing personalized bladder-sparing treatment paradigms.
Case Presentation: Here, we report on a case of urine-based dynamically monitoring during neoadjuvant immunotherapy in a MIBC patient treated with RC. A 57-year-old male presented macrohematuria and was diagnosed with bladder urothelial carcinoma by transurethral resection of bladder tumor (TURBT) with clinical stage IIIA (high-grade, multiple, cT2N0M0). He received 3 cycles of Tislelizumab monotherapy and sequential radical cystectomy. The RC specimen showed a complete pathological response (pCR). Four urine samples were collected prior to TURBT, on a day after TURBT, at beginning of neoadjuvant immunotherapy, and on the day of CR. Mutations status in 17 genes and methylation level of ONECUT2 were analyzed by a high-throughput sequencing-based urine test panel (genetron-uro-V1). In urine sediment DNA, which was collected before TURBT, the TERT promoter mutations C228T, TP53 D281H, and ERBB2 D277Y were detected in urine sediment DNA at variant allele frequencies (VAF) of 31.8%, 10.5%, and 0.5%, respectively. After removing in most parts of tumor, the VAF of TERT C228T decreased to 19.6% and mutation in TP53 and ERBB2 could not be detected. Without neoadjuvant immunotherapy, the VAF of TERT C228T still stayed above 12%. After 3 cycles of Tislelizumab monotherapy on the day of CR, all mutation was below the detection limit in urine sediment DNA, which was consistent with pCR in the pathological report of RC specimen.
Conclusions: This case suggested that urine-based dynamically monitoring reflected pathologic response, which could support personalized care and help select patients for bladder-sparing treatment.
Citation Format: Xiao Yang, Lingkai Cai, Qiang Cao, Min Shi, Yiming Liang, Yurong Qu, Qiang Lu. Urine based dynamically monitoring reflect pathologic response in MIBC patients with neoadjuvant immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5101.
Abstract 5125: Biological and clinical value of OCT4A/SPP1C axis in endometrial and lung adenocarcinoma
Authors: Irie Kyohei , Mizuno Nobuhiko , Miyamoto Tomoyuki , Ohtsuka Aiji , Yamamoto Hiromasa , Toyooka Shinichi , Masuyama Hisashi , Kosaka Mitsuko 
Published: June 2022

Abstract
Background: It is largely unclear whether octamer-binding transcription factor 4A (OCT4A, OCT3/4A) functions physiologically or pathologically in adult somatic tissues and related cancers. We have recently identified OCT4A translation in a human cancer cell subpopulation that might exacerbate cell migration and invasion. Here, we focus on biological and clinical features of OCT4A and its relationship with secreted phosphoprotein 1(SPP1), which is strongly related to the malignant progression of numerous tumors.
Methods: RT-PCR or qPCR analysis was used to identify full-length spliced forms of OCT4A and SPP1 transcripts in non-tumor and tumor human cells. An OCT4A-FLAG-tagged genomic transgene identified OCT4A-positive cancer cells. Cell-ablation of OCT4A-positive cells using promoter-driven diphtheria toxin A was used to examine the potential role of OCT4A in lung and endometrial adenocarcinoma cells. OCT4A and SPP1 transcripts in early-stage lung adenocarcinoma (stage I, fifty-eight cases) were analyzed and compared with pathohistological and prognostic features.
Results: We found that OCT4A and SPP1C are co-expressed in highly aggressive human lung and endometrial adenocarcinoma cell lines but not in mesothelioma or non-tumor cell lines. Ablation of OCT4A-positive cells significantly decreased cancer-cell migration and SPP1C mRNA levels. The OCT4A/SPP1C axis was found in primary, early-stage, lung adenocarcinomas, and all four cases of recurrence and/or metastasis out of 58 cases were included in the OCT4A and SPP1C positive group.
Conclusions: Co-expression of OCT4A and SPP1C may correlate with human cancer cell migration and the OCT4A/SPP1C axis may have a prognostic value in high-risk, early-stage lung adenocarcinomas. References: Stem Cells (2018), 36:1341-54. BMC Cancer (2020), 20:521.
Gene expression of OCT4A and SPP1 variants in 58 cases of early-stage lung adenocarcinoma OCT4A(-) OCT4A(+) OCT4A(++) SPP1A(+),SPP1C(+) 0 cases 9 cases 17cases(including 4 cases of recurrence or metastasis ) SPP1A(+),SPP1C(-) 3 cases 6 cases 7 cases SPP1A(-),SPP1C(-) 13cases 3 cases 0 cases
Citation Format: Kyohei Irie, Nobuhiko Mizuno, Tomoyuki Miyamoto, Aiji Ohtsuka, Hiromasa Yamamoto, Shinichi Toyooka, Hisashi Masuyama, Mitsuko Kosaka. Biological and clinical value of OCT4A/SPP1C axis in endometrial and lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5125.
Abstract 5304: A promising combination partner for paclitaxel in triple-negative breast cancer (TNBC) therapy
Authors: Lee Youl-Nam , Han Yun-hee , Kim Won-Sam , Lee Cheol-Min , Moon Eun-Joung , Kim Hae-Jin 
Published: June 2022

Abstract
Cytotoxic chemotherapy is initially effective in patients with metastatic triple-negative breast cancer (mTNBC). However, most of the TNBC patients have high risk of recurrence after chemotherapy and metastatic tumor recurrence indicates rapid tumor proliferation and drug resistance. In TNBC cells, treatment with the chemotherapeutic drug paclitaxel (PTX) induces Transforming growth factor (TGF)-β signaling pathway. TGF-β is a master regulator of tumor angiogenesis and epithelial-mesenchymal transition (EMT), which are limiting the efficacy of cancer therapies and suppressing the anti-tumor immune response. TGF-β induces autophagy in tumor cells and autophagy is closely associated with cancer cell survival and contributing to resistance to therapies. The targeting of TGF-β pathway is possibly an effective strategy to inhibit drug resistance and increase the sensitivity of cancer treatment. Charis 1000 (C1K), which is currently under development, is a synthetic peptide that targets TGF-β1. As C1K partially inhibits TGF-β1-induced Smad2 phosphorylation in TNBC cells, there is no risk of side effects unlike small molecules or antibodies that completely inhibit the TGF-β1 signaling pathway. Combination therapies including chemotherapy are actively investigated as effective treatments for various cancers. PTX, one of frequently used drugs in combination therapies, increases phosphorylation of Smad2, a TGF- β1 downstream signaling pathway and induces autophagy in TNBC cells, but PTX in combination with C1K increases apoptosis while reducing Smad2 phosphorylation and autophagy. The combination of C1K with PTX in the mouse TNBC model showed significant tumor size reduction in comparison to the PTX alone group. In addition, the combination of C1K with PTX confirmed the increased apoptosis and decreased autophagy in the tumor tissues. Furthermore, the combination of C1K with PTX increased the survival rate of mice that was reduced due to the side effects of PTX. These data indicate that the drug resistance induced by TGF-β signaling pathway can be suppressed by C1K combination through TGF-β signaling modulation. C1K may be a promising combination partner for cancer treatment by reducing drug resistance and increasing apoptotic potential of anticancer drugs. Currently, a phase1 clinical trial of the C1K combination therapy with PTX is ongoing and the preclinical studies of the C1K combination with immune checkpoint inhibitors (ICIs) are actively investigated as well.
Citation Format: Youl-Nam Lee, Yun-hee Han, Won-Sam Kim, Cheol-Min Lee, Eun-Joung Moon, Hae-Jin Kim. A promising combination partner for paclitaxel in triple-negative breast cancer (TNBC) therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5304.
Abstract 5338: Pamiparib as a non-P-glycoprotein substrate PARP inhibitor can overcome ABCB1-mediated multidrug resistance in ovarian cancer cells
Authors: Deng Minjuan , Qin Kang , Li Yang , Jiang Yu , Jin Wei , Shen Zhirong 
Published: June 2022

Abstract
Ovarian cancer is commonly treated with debulking surgery followed by platinum-taxane based chemotherapy and targeted therapy (PARP inhibitors). However, a key challenge facing these therapies is drug resistance caused by various mechanisms, one of which is the P-glycoprotein (P-gp, encoded by the ABCB1 gene) mediated multidrug resistance. Tumor cells with high P-gp protein expression extrude P-gp substrate drugs from intracellular space and reduce drug efficacy. Since Paclitaxel and some PARP inhibitors such as Olaparib are P-gp substrates, their clinical benefit may be compromised in primary or acquired P-gp positive patients. Pamiparib, on the other hand, is PARP inhibitor that is not P-gp substrate, therefore, it is reasonable to hypothesize that Pamiparib will have better efficacy in P-gp high ovarian tumors.
To test this hypothesis, Paclitaxel or Olaparib acquired resistant cell lines were developed through prolonged in vitro culture of sensitive A2780 cells (P-gp negative) with stepwise increased concentrations of individual drug. Both Paclitaxel and Olaparib resistant cells (A2780pacR and A2780olaR, respectively) highly express P-gp protein and are cross-resistant to each other, indicating this acquired resistance is mediated by P-gp protein upregulation. Indeed, P-gp protein inhibitor Verapamil can largely restore sensitivity to Paclitaxel and Olaparib in A2780pacR and A2780olaR cells, while over-expression of P-gp protein into parental A2780 cell line recapitulated the resistant phenotype. In contrast to Paclitaxel and Olaparib, Pamiparib as non P-gp substrate, is equally sensitive to parental A2780, A2780pacR and A2780olaR cell lines and not affected by P-gp expression. Consistently, intracellular drug concentration of Pamiparib is equivalent in A2780 and A2780olaR cells, however, decreased cellular Olaparib was detected in resistant cell line. These findings have been further confirmed in Olaparib resistant CDX model, in which Pamiparib showed tumor growth inhibition while Olaparib did not. The results highly suggest that Pamiparib as a non-P-gp substrate PARP inhibitor can overcome ABCB1-mediated drug resistance in tumors and may provide additional clinical benefits to ovarian cancer patients.
Citation Format: Minjuan Deng, Kang Qin, Yang Li, Yu Jiang, Wei Jin, Zhirong Shen. Pamiparib as a non-P-glycoprotein substrate PARP inhibitor can overcome ABCB1-mediated multidrug resistance in ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5338.