journal
https://read.qxmd.com/read/38491381/affinity-fine-tuning-anti-caix-car-t-cells-mitigate-on-target-off-tumor-side-effects
#21
JOURNAL ARTICLE
Yufei Wang, Alicia Buck, Brandon Piel, Luann Zerefa, Nithyassree Murugan, Christian D Coherd, Andras G Miklosi, Haraman Johal, Ricardo Nunes Bastos, Kun Huang, Miriam Ficial, Yasmin Nabil Laimon, Sabina Signoretti, Zhou Zhong, Song-My Hoang, Gabriella M Kastrunes, Marion Grimaud, Atef Fayed, Hsien-Chi Yuan, Quang-De Nguyen, Tran Thai, Elena V Ivanova, Cloud P Paweletz, Ming-Ru Wu, Toni K Choueiri, Jon O Wee, Gordon J Freeman, David A Barbie, Wayne A Marasco
One of the major hurdles that has hindered the success of chimeric antigen receptor (CAR) T cell therapies against solid tumors is on-target off-tumor (OTOT) toxicity due to sharing of the same epitopes on normal tissues. To elevate the safety profile of CAR-T cells, an affinity/avidity fine-tuned CAR was designed enabling CAR-T cell activation only in the presence of a highly expressed tumor associated antigen (TAA) but not when recognizing the same antigen at a physiological level on healthy cells. Using direct stochastic optical reconstruction microscopy (dSTORM) which provides single-molecule resolution, and flow cytometry, we identified high carbonic anhydrase IX (CAIX) density on clear cell renal cell carcinoma (ccRCC) patient samples and low-density expression on healthy bile duct tissues...
March 16, 2024: Molecular Cancer
https://read.qxmd.com/read/38491348/the-m-6-a-modification-mediated-lncrna-pou6f2-as1-reprograms-fatty-acid-metabolism-and-facilitates-the-growth-of-colorectal-cancer-via-upregulation-of-fasn
#22
JOURNAL ARTICLE
Tao Jiang, Junwen Qi, Zhenyu Xue, Bowen Liu, Jianquan Liu, Qihang Hu, Yuqiu Li, Jing Ren, Hu Song, Yixin Xu, Teng Xu, Ruizhi Fan, Jun Song
BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1...
March 16, 2024: Molecular Cancer
https://read.qxmd.com/read/38486218/a-novel-pan-pi3k-inhibitor-ktc1101-synergizes-with-anti-pd-1-therapy-by-targeting-tumor-suppression-and-immune-activation
#23
JOURNAL ARTICLE
Xin Peng, Xin Huang, Talal Ben Lulu, Wenqing Jia, Shaolu Zhang, Limor Cohen, Shengfan Huang, Jindian Fan, Xi Chen, Shanshan Liu, Yongzhe Wang, Kailin Wang, Sho Isoyama, Shingo Dan, Feng Wang, Zhe Zhang, Moshe Elkabets, Dexin Kong
BACKGROUND: Phosphoinositide 3-kinases (PI3Ks) are critical regulators of diverse cellular functions and have emerged as promising targets in cancer therapy. Despite significant progress, existing PI3K inhibitors encounter various challenges such as suboptimal bioavailability, potential off-target effects, restricted therapeutic indices, and cancer-acquired resistance. Hence, novel inhibitors that overcome some of these challenges are needed. Here, we describe the characterization of KTC1101, a novel pan-PI3K inhibitor that simultaneously targets tumor cell proliferation and the tumor microenvironment...
March 14, 2024: Molecular Cancer
https://read.qxmd.com/read/38468291/the-construction-of-modular-universal-chimeric-antigen-receptor-t-mu-car-t-cells-by-covalent-linkage-of-allogeneic-t-cells-and-various-antibody-fragments
#24
JOURNAL ARTICLE
Tao Chen, Jieyi Deng, Yongli Zhang, Bingfeng Liu, Ruxin Liu, Yiqiang Zhu, Mo Zhou, Yingtong Lin, Baijin Xia, Keming Lin, Xiancai Ma, Hui Zhang
BACKGROUND: Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. METHODS: Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells...
March 11, 2024: Molecular Cancer
https://read.qxmd.com/read/38461274/correction-aurora-kinase-targeting-in-lung-cancer-reduces-kras-induced-transformation
#25
Edmilson Ozorio Dos Santos, Tatiana Correa Carneiro-Lobo, Mateus Nobrega Aoki, Elena Levantini, Daniela Sanchez Bassères
No abstract text is available yet for this article.
March 9, 2024: Molecular Cancer
https://read.qxmd.com/read/38461272/bladder-cancer-derived-exosomal-circrna_0013936-promotes-suppressive-immunity-by-up-regulating-fatty-acid-transporter-protein-2-and-down-regulating-receptor-interacting-protein-kinase-3-in-pmn-mdscs
#26
JOURNAL ARTICLE
Xiaojun Shi, Shiyu Pang, Jiawei Zhou, Guang Yan, Ruxi Gao, Haowei Wu, Zhou Wang, Yuqing Wei, Xinyu Liu, Wanlong Tan
BACKGROUND: Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is one of the causes of tumor immune tolerance and failure of cancer immunotherapy. Here, we found that bladder cancer (BCa)-derived exosomal circRNA_0013936 could enhance the immunosuppressive activity of PMN-MDSCs by regulating the expression of fatty acid transporter protein 2 (FATP2) and receptor-interacting protein kinase 3 (RIPK3). However, the underlying mechanism remains largely unknown. METHODS: BCa-derived exosomes was isolated and used for a series of experiments...
March 9, 2024: Molecular Cancer
https://read.qxmd.com/read/38461268/integration-of-pan-omics-technologies-and-three-dimensional-in-vitro-tumor-models-an-approach-toward-drug-discovery-and-precision-medicine
#27
REVIEW
Anmi Jose, Pallavi Kulkarni, Jaya Thilakan, Murali Munisamy, Anvita Gupta Malhotra, Jitendra Singh, Ashok Kumar, Vivek M Rangnekar, Neha Arya, Mahadev Rao
Despite advancements in treatment protocols, cancer is one of the leading cause of deaths worldwide. Therefore, there is a need to identify newer and personalized therapeutic targets along with screening technologies to combat cancer. With the advent of pan-omics technologies, such as genomics, transcriptomics, proteomics, metabolomics, and lipidomics, the scientific community has witnessed an improved molecular and metabolomic understanding of various diseases, including cancer. In addition, three-dimensional (3-D) disease models have been efficiently utilized for understanding disease pathophysiology and as screening tools in drug discovery...
March 9, 2024: Molecular Cancer
https://read.qxmd.com/read/38459596/exosome-circatp8a1-induces-macrophage-m2-polarization-by-regulating-the-mir-1-3p-stat6-axis-to-promote-gastric-cancer-progression
#28
JOURNAL ARTICLE
Cuncan Deng, Mingyu Huo, Hongwu Chu, Xiaomei Zhuang, Guofei Deng, Wenchao Li, Hongfa Wei, Leli Zeng, Yulong He, Huashan Liu, Jia Li, Changhua Zhang, Hengxing Chen
Circular RNAs (circRNAs) play important roles in gastric cancer progression but the regulatory role of circRNAs in controlling macrophage function remains elusive. Exosomes serve as cargo for circRNAs and play a crucial role as mediators in facilitating communication between cancer cells and the tumor microenvironment. In this study, we found that circATP8A1, a previously unreported circular RNA, is highly expressed in both gastric cancer tissues and exosomes derived from plasma. Increased circATP8A1 was associated with advanced TNM stage and worse prognosis in patients with gastric cancer...
March 8, 2024: Molecular Cancer
https://read.qxmd.com/read/38459592/genetic-fusion-of-ccl11-to-antigens-enhances-antigenicity-in-nucleic-acid-vaccines-and-eradicates-tumor-mass-through-optimizing-t-cell-response
#29
JOURNAL ARTICLE
Hailong Qi, Zhongjie Sun, Tianle Gao, Yanling Yao, Yu Wang, Weiwei Li, Xudong Wang, Xiaofang Wang, Defang Liu, Jian-Dong Jiang
Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines in vivo. We found that fusion with different chemokines shifted the nature of the immune response against the antigens...
March 8, 2024: Molecular Cancer
https://read.qxmd.com/read/38459558/activation-of-the-pi3k-akt-signaling-pathway-by-arntl2-enhances-cellular-glycolysis-and-sensitizes-pancreatic-adenocarcinoma-to-erlotinib
#30
JOURNAL ARTICLE
Weiyu Ge, Yanling Wang, Ming Quan, Tiebo Mao, Evelyne Y Bischof, Haiyan Xu, Xiaofei Zhang, Shumin Li, Ming Yue, Jingyu Ma, Haiyan Yang, Lei Wang, Zhengyuan Yu, Liwei Wang, Jiujie Cui
BACKGROUND: Pancreatic adenocarcinoma (PC) is an aggressive malignancy with limited treatment options. The poor prognosis primarily stems from late-stage diagnosis and when the disease has become therapeutically challenging. There is an urgent need to identify specific biomarkers for cancer subtyping and early detection to enhance both morbidity and mortality outcomes. The addition of the EGFR tyrosine kinase inhibitor (TKI), erlotinib, to gemcitabine chemotherapy for the first-line treatment of patients with advanced pancreatic cancer slightly improved outcomes...
March 8, 2024: Molecular Cancer
https://read.qxmd.com/read/38459511/circnox4-activates-an-inflammatory-fibroblast-niche-to-promote-tumor-growth-and-metastasis-in-nsclc-via-fap-il-6-axis
#31
JOURNAL ARTICLE
Yan Zhao, Yunlong Jia, Jiali Wang, Xiaolin Chen, Jingya Han, Shuman Zhen, Shuxian Yin, Wei Lv, Fan Yu, Jiaqi Wang, Fan Xu, Xinming Zhao, Lihua Liu
BACKGROUND: Cancer-associated fibroblasts (CAFs) orchestrate a supportive niche that fuels cancer metastatic development in non-small cell lung cancer (NSCLC). Due to the heterogeneity and plasticity of CAFs, manipulating the activated phenotype of fibroblasts is a promising strategy for cancer therapy. However, the underlying mechanisms of fibroblast activation and phenotype switching that drive metastasis remain elusive. METHODS: The clinical implications of fibroblast activation protein (FAP)-positive CAFs (FAP+ CAFs) were evaluated based on tumor specimens from NSCLC patients and bioinformatic analysis of online databases...
March 8, 2024: Molecular Cancer
https://read.qxmd.com/read/38424621/correction-circular-rna-circmet-drives-immunosuppression-and-anti-pd1-therapy-resistance-in-hepatocellular-carcinoma-via-the-mir-30-5p-snail-dpp4-axis
#32
Xiao-Yong Huang, Peng-Fei Zhang, Chuan-Yuan Wei, Rui Peng, Jia-Cheng Lu, Chao Gao, Jia-Bing Cai, Xuan Yang, Jia Fan, Ai-Wu Ke, Jian Zhou, Guo-Ming Shi
No abstract text is available yet for this article.
February 29, 2024: Molecular Cancer
https://read.qxmd.com/read/38424542/targeted-deletion-of-cd244-on-monocytes-promotes-differentiation-into-anti-tumorigenic-macrophages-and-potentiates-pd-l1-blockade-in-melanoma
#33
JOURNAL ARTICLE
Jeongsoo Kim, Tae-Jin Kim, Sehyun Chae, Hyojeong Ha, Yejin Park, Sunghee Park, Chul Joo Yoon, Seon Ah Lim, Hyemin Lee, Jiyoung Kim, Jungwon Kim, Kyungtaek Im, Kyunghye Lee, Jeongmin Kim, Daham Kim, Eunju Lee, Min Hwa Shin, Serk In Park, Inmoo Rhee, Keehoon Jung, Jeewon Lee, Keun Hwa Lee, Daehee Hwang, Kyung-Mi Lee
BACKGROUND: In the myeloid compartment of the tumor microenvironment, CD244 signaling has been implicated in immunosuppressive phenotype of monocytes. However, the precise molecular mechanism and contribution of CD244 to tumor immunity in monocytes/macrophages remains elusive due to the co-existing lymphoid cells expressing CD244. METHODS: To directly assess the role of CD244 in tumor-associated macrophages, monocyte-lineage-specific CD244-deficient mice were generated using cre-lox recombination and challenged with B16F10 melanoma...
February 29, 2024: Molecular Cancer
https://read.qxmd.com/read/38413951/correction-comprehensive-review-of-crispr%C3%A2-based-gene-editing-mechanisms-challenges-and-applications-in-cancer-therapy
#34
Mohammad Chehelgerdi, Matin Chehelgerdi, Milad Khorramian-Ghahfarokhi, Marjan Shafieizadeh, Esmaeil Mahmoudi, Fatemeh Eskandari, Mohsen Rashidi, Asghar Arshi, Abbas Mokhtari-Farsani
No abstract text is available yet for this article.
February 27, 2024: Molecular Cancer
https://read.qxmd.com/read/38402205/activation-induced-cytidine-deaminase-causes-recurrent-splicing-mutations-in-diffuse-large-b-cell-lymphoma
#35
LETTER
Maria S Benitez-Cantos, Carlos Cano, Marta Cuadros, Pedro P Medina
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma. A major mutagenic process in DLBCL is aberrant somatic hypermutation (aSHM) by activation-induced cytidine deaminase (AID), which occurs preferentially at RCH/TW sequence motifs proximal to transcription start sites. Splice sequences are highly conserved, rich in RCH/TW motifs, and recurrently mutated in DLBCL. Therefore, we hypothesized that aSHM may cause recurrent splicing mutations in DLBCL. In a meta-cohort of > 1,800 DLBCLs, we found that 77...
February 24, 2024: Molecular Cancer
https://read.qxmd.com/read/38395864/small-cells-big-issues-biological-implications-and-preclinical-advancements-in-small-cell-lung-cancer
#36
REVIEW
Anna Solta, Büsra Ernhofer, Kristiina Boettiger, Zsolt Megyesfalvi, Simon Heeke, Mir Alireza Hoda, Christian Lang, Clemens Aigner, Fred R Hirsch, Karin Schelch, Balazs Döme
Current treatment guidelines refer to small cell lung cancer (SCLC), one of the deadliest human malignancies, as a homogeneous disease. Accordingly, SCLC therapy comprises chemoradiation with or without immunotherapy. Meanwhile, recent studies have made significant advances in subclassifying SCLC based on the elevated expression of the transcription factors ASCL1, NEUROD1, and POU2F3, as well as on certain inflammatory characteristics. The role of the transcription regulator YAP1 in defining a unique SCLC subset remains to be established...
February 24, 2024: Molecular Cancer
https://read.qxmd.com/read/38383439/the-therapeutically-actionable-long-non-coding-rna-t-recs-is-essential-to-cancer-cells-survival-in-nras-mapk-driven-melanoma
#37
JOURNAL ARTICLE
Valentin Feichtenschlager, Linan Chen, Yixuan James Zheng, Wilson Ho, Martina Sanlorenzo, Igor Vujic, Eleanor Fewings, Albert Lee, Christopher Chen, Ciara Callanan, Kevin Lin, Tiange Qu, Dasha Hohlova, Marin Vujic, Yeonjoo Hwang, Kevin Lai, Stephanie Chen, Thuan Nguyen, Denise P Muñoz, Yoshinori Kohwi, Christian Posch, Adil Daud, Klemens Rappersberger, Terumi Kohwi-Shigematsu, Jean-Philippe Coppé, Susana Ortiz-Urda
Finding effective therapeutic targets to treat NRAS-mutated melanoma remains a challenge. Long non-coding RNAs (lncRNAs) recently emerged as essential regulators of tumorigenesis. Using a discovery approach combining experimental models and unbiased computational analysis complemented by validation in patient biospecimens, we identified a nuclear-enriched lncRNA (AC004540.4) that is upregulated in NRAS/MAPK-dependent melanoma, and that we named T-RECS. Considering potential innovative treatment strategies, we designed antisense oligonucleotides (ASOs) to target T-RECS...
February 22, 2024: Molecular Cancer
https://read.qxmd.com/read/38378518/resistance-of-hnscc-cell-models-to-pan-fgfr-inhibition-depends-on-the-emt-phenotype-associating-with-clinical-outcome
#38
JOURNAL ARTICLE
Felix Broghammer, Irina Korovina, Mahesh Gouda, Martina Celotti, Johan van Es, Inga Lange, Cornelia Brunner, Jovan Mircetic, Robert P Coppes, Olivier Gires, Andreas Dahl, Michael Seifert, Nils Cordes
BACKGROUND: Focal adhesion signaling involving receptor tyrosine kinases (RTK) and integrins co-controls cancer cell survival and therapy resistance. However, co-dependencies between these receptors and therapeutically exploitable vulnerabilities remain largely elusive in HPV-negative head and neck squamous cell carcinoma (HNSCC). METHODS: The cytotoxic and radiochemosensitizing potential of targeting 10 RTK and β1 integrin was determined in up to 20 3D matrix-grown HNSCC cell models followed by drug screening and patient-derived organoid validation...
February 21, 2024: Molecular Cancer
https://read.qxmd.com/read/38378555/reshaping-the-tumor-microenvironment-of-cold-soft-tissue-sarcomas-with-oncolytic-viral-therapy-a-phase-2-trial-of-intratumoral-jx-594-combined-with-avelumab-and-low-dose-cyclophosphamide
#39
LETTER
Maud Toulmonde, Jean-Philippe Guegan, Mariella Spalato-Ceruso, Florent Peyraud, Michèle Kind, Lucile Vanhersecke, François Le Loarer, Raul Perret, Coralie Cantarel, Carine Bellera, Alban Bessede, Antoine Italiano
Most soft-tissue sarcomas (STS) exhibit an immunosuppressive tumor microenvironment (TME), leading to resistance against immune checkpoint inhibitors (ICIs) and limited therapeutic response. Preclinical data suggest that oncolytic viral therapy can remodel the TME, facilitating T cell accumulation and enhancing the immunogenicity of these tumors.We conducted the METROMAJX, a phase II clinical trial, to investigate the combination of JX-594, an oncolytic vaccinia virus engineered for selective tumor cell replication, with metronomic cyclophosphamide and the PD-L1 inhibitor avelumab in patients with advanced, 'cold' STS, characterized by an absence of tertiary lymphoid structures...
February 20, 2024: Molecular Cancer
https://read.qxmd.com/read/38374062/impact-of-metronomic-trabectedin-combined-with-low-dose-cyclophosphamide-on-sarcoma-microenvironment-and-correlation-with-clinical-outcome-results-from-the-tarmic-study
#40
LETTER
Cheng-Ming Sun, Maud Toulmonde, Mariella Spalato-Ceruso, Florent Peyraud, Alban Bessede, Michèle Kind, Sophie Cousin, Xavier Buy, Jean Palussiere, Antoine Bougouin, Catherine Sautès-Fridman, Hervé Wolf Fridman, Marina Pulido, Antoine Italiano
Soft tissue sarcomas (STS) are diverse mesenchymal tumors with few therapeutic options in advanced stages. Trabectedin has global approval for treating STS patients resistant to anthracycline-based regimens. Recent pre-clinical data suggest that trabectedin's antitumor activity extends beyond tumor cells to influencing the tumor microenvironment (TME), especially affecting tumor-associated macrophages and their pro-tumoral functions. We present the phase I/II results evaluating a combination of metronomic trabectedin and low-dose cyclophosphamide on the TME in patients with advanced sarcomas...
February 19, 2024: Molecular Cancer
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