keyword
https://read.qxmd.com/read/38536927/activation-of-endogenous-retroviruses-and-induction-of-viral-mimicry-by-mek1-2-inhibition-in-pancreatic-cancer
#1
JOURNAL ARTICLE
Alice Cortesi, Francesco Gandolfi, Fabiana Arco, Pierluigi Di Chiaro, Emanuele Valli, Sara Polletti, Roberta Noberini, Francesco Gualdrini, Sergio Attanasio, Francesca Citron, I-Lin Ho, Rutvi Shah, Er-Yen Yen, Mara Cetty Spinella, Simona Ronzoni, Simona Rodighiero, Nico Mitro, Tiziana Bonaldi, Serena Ghisletti, Silvia Monticelli, Andrea Viale, Giuseppe Riccardo Diaferia, Gioacchino Natoli
While pancreatic ductal adenocarcinomas (PDACs) are addicted to KRAS-activating mutations, inhibitors of downstream KRAS effectors, such as the MEK1/2 kinase inhibitor trametinib, are devoid of therapeutic effects. However, the extensive rewiring of regulatory circuits driven by the attenuation of the KRAS pathway may induce vulnerabilities of therapeutic relevance. An in-depth molecular analysis of the transcriptional and epigenomic alterations occurring in PDAC cells in the initial hours after MEK1/2 inhibition by trametinib unveiled the induction of endogenous retroviruses (ERVs) escaping epigenetic silencing, leading to the production of double-stranded RNAs and the increased expression of interferon (IFN) genes...
March 29, 2024: Science Advances
https://read.qxmd.com/read/38530888/normalizing-granuloma-vasculature-and-matrix-improves-drug-delivery-and-reduces-bacterial-burden-in-tuberculosis-infected-rabbits
#2
JOURNAL ARTICLE
Meenal Datta, Laura E Via, Véronique Dartois, Danielle M Weiner, Matthew Zimmerman, Firat Kaya, April M Walker, Joel D Fleegle, Isaac D Raplee, Colton McNinch, Maksym Zarodniuk, Walid S Kamoun, Changli Yue, Ashwin S Kumar, Sonu Subudhi, Lei Xu, Clifton E Barry, Rakesh K Jain
Host-directed therapies (HDTs) represent an emerging approach for bacterial clearance during tuberculosis (TB) infection. While most HDTs are designed and implemented for immuno-modulation, other host targets-such as nonimmune stromal components found in pulmonary granulomas-may prove equally viable. Building on our previous work characterizing and normalizing the aberrant granuloma-associated vasculature, here we demonstrate that FDA-approved therapies (bevacizumab and losartan, respectively) can be repurposed as HDTs to normalize blood vessels and extracellular matrix (ECM), improve drug delivery, and reduce bacterial loads in TB granulomas...
April 2, 2024: Proceedings of the National Academy of Sciences of the United States of America
https://read.qxmd.com/read/38525011/targeted-ultrasound-nanobubbles-therapy-for-prostate-cancer-via-immuno-sonodynamic-effect
#3
JOURNAL ARTICLE
Xin Huang, Yueying Chen, Fanglu Zhong, Bin Gui, Yugang Hu, Yuxin Guo, Qing Deng, Qing Zhou
BACKGROUND: Prostate cancer (PCa) poses a significant global health threaten. Immunotherapy has emerged as a novel strategy to augment the inhibition of tumor proliferation. However, the sole use of anti-PD-L1 Ab for PCa has not yielded improvements, mirroring outcomes observed in other tumor types. METHODS: This study employed the thin film hydration method to develop lipid nanobubbles (NBs) encapsulating chlorin e6 (Ce6) and anti-PD-L1 Ab (Ce6@aPD-L1 NBs). Our experimental approach included cellular assays and mouse immunization, providing a comprehensive evaluation of Ce6@aPD-L1 NBs' impact...
2024: International Journal of Nanomedicine
https://read.qxmd.com/read/38523872/late-stage-ovarian-cancer-with-systemic-multiple-metastases-shows-marked-shrinkage-using-a-combination-of-wilms-tumor-antigen-1-wt1-dendritic-cell-vaccine-natural-killer-nk-cell-therapy-and-nivolumab
#4
Hisashi Nagai, Ryusuke Karube
A patient with bilateral ovarian cancer, peritoneal dissemination, and multiple liver and lung metastases was found with a sudden accumulation of ascites six months after delivery. Chemotherapy was started, but the prognosis was judged to be poor, so immuno-cell therapy was combined with chemotherapy. After multiple cycles of Wilms' tumor antigen 1 (WT1) dendritic cell vaccine therapy and highly activated natural killer (NK) cell therapy, the patient showed a disappearance of ascites and a remarkable reduction of multiple cancers in the whole body...
March 2024: Curēus
https://read.qxmd.com/read/38519913/an-international-phase-ii-trial-and-immune-profiling-of-sbrt-and-atezolizumab-in-advanced-pretreated-colorectal-cancer
#5
JOURNAL ARTICLE
Antonin Levy, Daphné Morel, Matthieu Texier, Roger Sun, Jerome Durand-Labrunie, Maria E Rodriguez-Ruiz, Severine Racadot, Stéphane Supiot, Nicolas Magné, Stacy Cyrille, Guillaume Louvel, Christophe Massard, Loic Verlingue, Fanny Bouquet, Alberto Bustillos, Lisa Bouarroudj, Clément Quevrin, Céline Clémenson, Michele Mondini, Lydia Meziani, Lambros Tselikas, Rastilav Bahleda, Antoine Hollebecque, Eric Deutsch
BACKGROUND: Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the colorectal (CRC) cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in advanced cancer patients. METHODS: Eligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint)...
March 23, 2024: Molecular Cancer
https://read.qxmd.com/read/38516453/acute-cytomegalovirus-infection-associated-with-erythema-multiforme-like-eruption-a-case-report
#6
Luca Pipitò, Antonio Cascio
Human cytomegalovirus infection usually proceeds asymptomatically in immunocompetent patients. In symptomatic forms, mononucleosis syndrome is the most common manifestation. However, atypical cases of cytomegalovirus infections in immunocompetent subjects are reported in the literature. Here, we describe a case of cytomegalovirus-related mononucleosis syndrome that presented with an atypical erythema multiforme-like skin rash and high fever. Very few cases have been described in the literature previously. In our case, the diagnosis was supported by specific serology, and human cytomegalovirus DNA was detected in the blood sample...
February 2024: Curēus
https://read.qxmd.com/read/38511984/implications-of-an-altered-gut-microbiome-in-rat-experimental-vascularized-composite-transplantation
#7
JOURNAL ARTICLE
Ashti M Shah, Ali M Aral, Derek A Barclay, Jinling Yin, Ruben Zamora, Vijay Gorantla, Yoram Vodovotz
OBJECTIVES: Vascularized composite allotransplantation is a reconstructive option after severe injury but is fraught with complications, including transplant rejection due to major histocompatibility complex mismatch in the context of allogeneic transplant, which in turn is due to altered immuno-inflammation secondary to transplant. The immunosuppressant tacrolimus can prevent rejection. Because tacrolimus is metabolized predominantly by the gut, this immunosuppressant alters the gut microbiome in multiple ways, thereby possibly affecting immunoinflammation...
February 2024: Experimental and Clinical Transplantation
https://read.qxmd.com/read/38507505/conserved-immuno-collagenic-subtypes-predict-response-to-immune-checkpoint-blockade
#8
JOURNAL ARTICLE
Jie Mei, Yun Cai, Rui Xu, Qing Li, Jiahui Chu, Zhiwen Luo, Yaying Sun, Yuxin Shi, Junying Xu, Di Li, Shuai Liang, Ying Jiang, Jiayu Liu, Zhiwen Qian, Jiaofeng Zhou, Mengyun Wan, Yunlong Yang, Yichao Zhu, Yan Zhang, Yongmei Yin
BACKGROUND: Immune checkpoint blockade (ICB) has revolutionized the treatment of various cancer types. Despite significant preclinical advancements in understanding mechanisms, identifying the molecular basis and predictive biomarkers for clinical ICB responses remains challenging. Recent evidence, both preclinical and clinical, underscores the pivotal role of the extracellular matrix (ECM) in modulating immune cell infiltration and behaviors. This study aimed to create an innovative classifier that leverages ECM characteristics to enhance the effectiveness of ICB therapy...
March 20, 2024: Cancer Communications
https://read.qxmd.com/read/38504137/behav3d-a-3d-live-imaging-platform-for-comprehensive-analysis-of-engineered-t-cell-behavior-and-tumor-response
#9
REVIEW
Maria Alieva, Mario Barrera Román, Sam de Blank, Diana Petcu, Amber L Zeeman, Noël M M Dautzenberg, Annelisa M Cornel, Cesca van de Ven, Rob Pieters, Monique L den Boer, Stefan Nierkens, Friso G J Calkoen, Hans Clevers, Jürgen Kuball, Zsolt Sebestyén, Ellen J Wehrens, Johanna F Dekkers, Anne C Rios
Modeling immuno-oncology by using patient-derived material and immune cell co-cultures can advance our understanding of immune cell tumor targeting in a patient-specific manner, offering leads to improve cellular immunotherapy. However, fully exploiting these living cultures requires analysis of the dynamic cellular features modeled, for which protocols are currently limited. Here, we describe the application of BEHAV3D, a platform that implements multi-color live 3D imaging and computational tools for: (i) analyzing tumor death dynamics at both single-organoid or cell and population levels, (ii) classifying T cell behavior and (iii) producing data-informed 3D images and videos for visual inspection and further insight into obtained results...
March 19, 2024: Nature Protocols
https://read.qxmd.com/read/38502012/ferritin-significance-in-viral-infections
#10
REVIEW
Xia Zhao, Yuntao Zhou, Yong Zhang, Yan Zhang
As an indispensable trace element, iron is essential for many biological processes. Increasing evidence has shown that virus infection can perturb iron metabolism and play a role in the occurrence and development of viral infection-related diseases. Ferritin plays a crucial role in maintaining the body's iron homoeostasis. It is an important protein to stabilise the iron balance in cells. Ferritin is a 24-mer hollow iron storage protein composed of two subunits: ferritin heavy chain and ferritin light chain...
March 2024: Reviews in Medical Virology
https://read.qxmd.com/read/38499572/making-drugs-from-t-cells-the-quantitative-pharmacology-of-engineered-t-cell-therapeutics
#11
JOURNAL ARTICLE
Daniel C Kirouac, Cole Zmurchok, Denise Morris
Engineered T cells have emerged as highly effective treatments for hematological cancers. Hundreds of clinical programs are underway in efforts to expand the efficacy, safety, and applications of this immuno-therapeutic modality. A primary challenge in developing these "living drugs" is the complexity of their pharmacology, as the drug product proliferates, differentiates, traffics between tissues, and evolves through interactions with patient immune systems. Using publicly available clinical data from Chimeric Antigen Receptor (CAR) T cells, we demonstrate how mathematical models can be used to quantify the relationships between product characteristics, patient physiology, pharmacokinetics and clinical outcomes...
March 18, 2024: NPJ Systems Biology and Applications
https://read.qxmd.com/read/38496701/dual-immuno-oncology-agents-as-neoadjuvant-therapy-for-patients-with-resectable-non-small-cell-lung-cancer
#12
EDITORIAL
Hiroyuki Adachi, Hiroyuki Ito, Takuya Nagashima, Tetsuya Isaka, Aya Saito
No abstract text is available yet for this article.
February 29, 2024: Translational Lung Cancer Research
https://read.qxmd.com/read/38495713/assessing-cell-viability-with-dynamic-optical-coherence-microscopy
#13
JOURNAL ARTICLE
Chao J Liu, Jason T Smith, Yuanbo Wang, Jonathan N Ouellette, Jeremy D Rogers, Jonathan D Oliner, Michael Szulczewski, Eric Wait, William Brown, Adam Wax, Kevin W Eliceiri, John Rafter
Assessing cell viability is important in many fields of research. Current optical methods to assess cell viability typically involve fluorescent dyes, which are often less reliable and have poor permeability in primary tissues. Dynamic optical coherence microscopy (dOCM) is an emerging tool that provides label-free contrast reflecting changes in cellular metabolism. In this work, we compare the live contrast obtained from dOCM to viability dyes, and for the first time to our knowledge, demonstrate that dOCM can distinguish live cells from dead cells in murine syngeneic tumors...
March 1, 2024: Biomedical Optics Express
https://read.qxmd.com/read/38492894/targeting-ese3-ehf-with-nifurtimox-inhibits-cxcr2-neutrophil-infiltration-and-overcomes-pancreatic-cancer-resistance-to-chemotherapy-and-immunotherapy
#14
JOURNAL ARTICLE
Yongjie Xie, Tianxing Zhou, Xueyang Li, Kaili Zhao, Weiwei Bai, Xupeng Hou, Ziyun Liu, Bo Ni, Zhaoyu Zhang, Jingrui Yan, Yifei Wang, Wenna Jiang, Hongwei Wang, Antao Chang, Song Gao, Tiansuo Zhao, Shengyu Yang, Chongbiao Huang, Jing Liu, Jihui Hao
BACKGROUND & AIMS: Since pancreatic cancer responds poorly to chemotherapy and immunotherapy, it is necessary to identify novel targets and compounds to overcome resistance to treatment. METHODS: This study analyzed genomic SNP sequencing, single-cell RNA sequencing, and spatial transcriptomics. Ehf-knockout mice, KPC (LSL-KrasG12D/+ , LSL-Trp53R172H/+ and Pdx1-Cre) mice, CD45.1+BALB/C nude mice, and CD34+humanized mice were also used as subjects. Multiplexed immunohistochemistry and flow cytometry were performed to investigate the proportion of tumor-infiltrated CXCR2+neutrophils...
March 14, 2024: Gastroenterology
https://read.qxmd.com/read/38481544/qingguang-an-induced-autophagy-in-tfs-inhibits-scar-formation-a-follow-up-in%C3%A2-vivo-mechanistic-investigation
#15
JOURNAL ARTICLE
Rong Hu, Xian-Jing Wang, Shu Chen, Yun Huang, Juan Yu
PURPOSE: To investigate the mechanism by which Qingguang'an inhibits scar formation in rabbits administered glaucoma filtering surgery (GFS). METHODS: Combined trabeculectomy was performed in 100 rabbits diagnosed with glaucoma, which were assigned to five groups, including the no surgery, surgery only, mitomycin C (MMC; positive control), Qingguang'an (experimental) and PBS (negative control) groups. The animals were followed up at postoperative days 1-28. Ultrastructure was observed under a transmission electron microscope (TEM)...
March 2024: Journal of Traditional and Complementary Medicine
https://read.qxmd.com/read/38477219/tumor-microenvironment-activatable-nanosystem-capable-of-overcoming-multiple-therapeutic-obstacles-for-augmenting-immuno-metal-ion-therapy
#16
JOURNAL ARTICLE
Qian Cheng, Xiaolei Shi, Yuzhe Chen, Qilin Li, Jiawei Wang, Heli Li, Lin Wang, Zheng Wang
Abnormal tumor microenvironment (TME) imposes barriers to nanomedicine penetration into tumors and evolves tumor-supportive nature to provide tumor cell protection, seriously weakening the action of antitumor nanomedicines and posing significant challenges to their development. Here, we engineer a TME-activatable size-switchable core-satellite nanosystem (Mn-TI-Ag@HA) capable of increasing the effective dose of therapeutic agents in deep-seated tumors while reversing tumor-supportive microenvironment for augmenting immuno/metal-ion therapy...
March 13, 2024: ACS Nano
https://read.qxmd.com/read/38473428/immuno-molecular-targeted-therapy-use-and-survival-benefit-in-patients-with-stage-ivb-cervical-carcinoma-in-commission-on-cancer-%C3%A2-accredited-facilities-in-the-united-states
#17
JOURNAL ARTICLE
Collin A Sitler, Chunqiao Tian, Chad A Hamilton, Michael T Richardson, John K Chan, Daniel S Kapp, Charles A Leath, Yovanni Casablanca, Christina Washington, Nicole P Chappell, Ann H Klopp, Craig D Shriver, Christopher M Tarney, Nicholas W Bateman, Thomas P Conrads, George Larry Maxwell, Neil T Phippen, Kathleen M Darcy
PURPOSE: To investigate IMT use and survival in real-world stage IVB cervical cancer patients outside randomized clinical trials. METHODS: Patients diagnosed with stage IVB cervical cancer during 2013-2019 in the National Cancer Database and treated with chemotherapy (CT) ± external beam radiation (EBRT) ± intracavitary brachytherapy (ICBT) ± IMT were studied. The adjusted hazard ratio (AHR) and 95% confidence interval (CI) for risk of death were estimated in patients treated with vs...
March 6, 2024: Cancers
https://read.qxmd.com/read/38473265/hepatocellular-carcinoma-old-and-emerging-therapeutic-targets
#18
REVIEW
Greta Pessino, Claudia Scotti, Maristella Maggi, Immuno-Hub Consortium
Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third in cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, and genetic factors. No specific genetic alterations are unequivocally linked to HCC tumorigenesis. Current standard therapies include surgical options, systemic chemotherapy, and kinase inhibitors, like sorafenib and regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue...
February 23, 2024: Cancers
https://read.qxmd.com/read/38473244/advances-in-3d-culture-models-to-study-exosomes-in-triple-negative-breast-cancer
#19
REVIEW
Neelum Aziz Yousafzai, Lamyae El Khalki, Wei Wang, Justin Szpendyk, Khalid Sossey-Alaoui
Breast cancer, a leading cause of cancer-related deaths globally, exhibits distinct subtypes with varying pathological, genetic, and clinical characteristics. Despite advancements in breast cancer treatments, its histological and molecular heterogeneity pose a significant clinical challenge. Triple-negative breast cancer (TNBC), a highly aggressive subtype lacking targeted therapeutics, adds to the complexity of breast cancer treatment. Recent years have witnessed the development of advanced 3D culture technologies, such as organoids and spheroids, providing more representative models of healthy human tissue and various malignancies...
February 22, 2024: Cancers
https://read.qxmd.com/read/38470541/what-patients-with-advanced-cancer-experience-as-helpful-in-navigating-their-life-with-a-long-term-response-a-qualitative-study
#20
JOURNAL ARTICLE
Laura C Zwanenburg, Marije L van der Lee, José J Koldenhof, Karijn P M Suijkerbuijk, Melanie P J Schellekens
PURPOSE: Despite improved survival for people with advanced cancer due to new medical treatments, a growing group of long-term responders (LTRs) has to learn to live with uncertainties that affect several life domains. At the core of their experience, they neither feel like a patient nor feel healthy. Despite growing awareness of LTRs' experiences, learning more about how they cope with their long-term response can provide insight into how to best support them. Our study aimed to gain a deeper understanding what LTRs experience as helpful in navigating life with a long-term response...
March 12, 2024: Supportive Care in Cancer
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