Kevin C. Johnson, Avishay Spitzer, Frederick S. Varn, Masashi Nomura, Luciano Garofano, Tamrin Chowdhury, Anuja Lipsa, Linbin Zhang, Ester Calvo Fernández, Tanyeri Barak, A. Gulhan Ercan-Sencicek, Ayse Buket Peksen, Kevin J. Anderson, C. Mircea S. Tesileanu, Samirkumar B. Amin, Emre Kocakavuk, Dacheng Zhao, Fulvio D’Angelo, Simona Migliozzi, Lillian Bussema, Simon Gritsch, Hyo-Eun Moon, Sun Ha Paek, Franck Bielle, Roel G. W. Verhaak

Acquired genetic and cell-state changes in IDH-mutant glioma progression

Gliomas with mutant isocitrate dehydrogenase (IDH) are malignant brain tumours that typically arise in early to mid-adulthood and nearly always recur following treatment1,2. However, the genetic and cellular-state changes that drive IDH-mutant glioma progression under treatment remain incompletely understood. Here we integrated single-nucleus transcriptomic profiles, chromatin accessibility profiles and bulk DNA and RNA sequencing from 75 temporally separated gliomas across 35 patients comprising both the oligodendroglioma and astrocytoma IDH-mutant glioma tumour types.

Casey Hudson, Robert P. Krattli Jr., Sanad M. El-Khatib, Arya R. Vagadia, An H. Do, Shreya Madan, Manal T. Usmani, Tracy Nguyen, Devyani Swami, Katja M. Piltti, Leslie M. Thompson, Brian J. Cummings, Aileen J. Anderson

Human neural stem cell-derived extracellular vesicles improve cognitive function following glioma chemoradiation therapy

Cranial radiation therapy (RT) with concomitant and adjuvant temozolomide (TMZ; Stupp protocol) prolongs glioma survival but frequently results in persistent cognitive impairment. Human neural stem cell (hNSC)-derived extracellular vesicles (EVs) are a promising acellular therapy whose bioactive cargo can modulate neuroinflammation and synaptic integrity. We evaluated two EVs derived from GMP-grade hNSCs (Shef6 and UCI-191) in syngeneic glioma-bearing and non-tumor adult mice treated with fractionated cranial RT (3 × 8.67 Gy) together with concomitant low-dose (25 mg/kg) and adjuvant high-dose (66.7 mg/kg, intraperitoneal) TMZ. EV administration improved memory performance in RT-TMZ–exposed mice and, notably, Shef6-EVs also extended survival in glioma-bearing mice in the absence of chemoradiotherapy.

Bethany Veo, Ph.D., Dong Wang, John DeSisto, Angela Pierce, Breauna Brunt, Pradeep Chandra Bompada, Andrew Donson, Andrew Goodspeed, PhD, Kiara Smart, Nicholas Foreman, Nathan Dahl & Rajeev Vibhakar. ​

Single-cell multi-omics identifies metabolism-linked epigenetic reprogramming as a driver of therapy-resistant medulloblastoma

Medulloblastoma (MB) is the most prevalent malignant brain tumor in children, exhibiting clinical and genomic heterogeneity. Of the four major subgroups, Group 3 tumors (MYC-MB), display high levels of MYC and metastasis rates. Despite treatment with surgery, radiation, and chemotherapy, patients with Group 3 MB are more likely to develop aggressive recurrent tumors with poor survival. To examine resistance mechanisms in this study, we perform single nuclei multiome analysis of matched primary and recurrent tumors.

Vladimir Wischnewski, Paola Guerrero Aruffo, Matteo Massara, Roeltje Maas, Klara Soukup, and Johanna Joyce

The local microenvironment suppresses the synergy between irradiation and anti-PD1 therapy in breast-to-brain metastasis

Wischnewski et al. demonstrate suppressed CD8+ T cell cytotoxicity in breast cancer brain metastases, contrasting with genetically identical extracranial tumors.

Hwanju Lim, Yujeong Moon, Sangheon Han, Hanhee Cho, Sunejeong Song, Jinseong Kim, Jagyeong Goo, Nayeon Shim, Lili Guo, Tae-il Kim, Won Seok Chang, Won-Gun Koh, Kwangmeyung Kim

Low-dose radiation generated ROS-activatable doxorubicin prodrug loaded liposome nanoparticles for triple-negative breast cancer treatment

Triple-negative breast cancer (TNBC) treatment is frequently limited by both intrinsic resistance and normal tissue toxicity in radiation therapy (RT) and chemotherapy. Herein, we report reactive oxygen species (ROS)- activatable DOX prodrug loaded liposome nanoparticles (ROS-LNPs) for precision therapy against TNBC.

Irma Telarovic, Carmen S. M. Yong, Lisa Kurz, Irene Vetrugno, Sabrina Reichl, Alba Sanchez Fernandez, Hung-Wei Cheng, Rona Winkler, Matthias Guckenberger, Anja Kipar, Burkhard Ludewig & Martin Pruschy

Delayed tumor-draining lymph node irradiation preserves the efficacy of combined radiotherapy and immune checkpoint blockade in models of metastatic disease

Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion and to improve treatment response. However, clinical benefits of radiotherapy-immunotherapy combinations have been modest. Routine concomitant tumor-draining lymph node irradiation (DLN IR) might be the culprit.

Hwanju Lim, Yujeong Moon, Sangheon Han, Hanhee Cho, Sunejeong Song, Jinseong Kim, Jagyeong Goo, Nayeon Shim, Lili Guo, Tae-il Kim, Won Seok Chang, Won-Gun Koh, and Kwangmeyung Kim

Low-dose radiation generated ROS-activatable doxorubicin prodrug loaded liposome nanoparticles for triple-negative breast cancer treatment

Triple-negative breast cancer (TNBC) treatment is frequently limited by both intrinsic resistance and normal tissue toxicity in radiation therapy (RT) and chemotherapy. Herein, we report reactive oxygen species (ROS)- activatable DOX prodrug loaded liposome nanoparticles (ROS-LNPs) for precision therapy against TNBC.

Lei Li (李磊) et al.

Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade

Tardigrades, commonly known as water bears, are small ecdysozoans renowned for their tolerance to extreme environments, including ultrahigh radiation. They exhibit exceptional resistance to ionizing radiation, withstanding doses as high as 3000 to 5000 grays (Gy) of gamma rays, which is ∼1000 times the lethal dose for humans. The mechanism of radiotolerance in tardigrades remains largely unclear.

Keiji Kawatani, Genesis Omana Suarez, Ralph B. Perkerson III, Ephraim E. Parent, Toshihiko Nambara, Joshua A. Knight, Tammee M. Parsons, Kshama Gupta, Francis Shue, Alla Alnobani, Prasanna Vibhute, Hancheng Cai, Hugo Guerrero-Cázares, John A. Copland III, Alfredo Quiñones-Hinojosa, and Takahisa Kanekiyo

Human iPSC-Derived MSCs Induce Neurotrophic Effects and Improve Metabolic Activity in Acute Neuronal Injury Models

While preclinical studies highlight the significant potential of MSC therapy in mitigating neurological damage from stroke and traumatic brain injury, the variability in clinical trial outcomes may stem from the inherent heterogeneity of somatic MSCs. Accumulating evidence has demonstrated that induced pluripotent stem cells (iPSCs) are an ideal alternative resource for the unlimited expansion and biomanufacturing of MSCs. Thus, we investigated how iPSC-derived MSCs (iMSCs) influence properties of iPSC-derived neurons. Our findings demonstrate that the secretome from iMSCs possesses neurotrophic effects, improving neuronal survival and promoting neuronal outgrowth and synaptic activity in vitro. Additionally, the iMSCs enhance metabolic activity via mitochondrial respiration in neurons, both in vitro and in mouse models.

Sky News

Deadly flesh-eating parasite found in person in US for first time

The importance of the Sterile Insect Technique (SIT) has never been clearer. The first case of screwworm infection has now been reported in Maryland, USA. Read more here.