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Analysis of genomic heterogeneity and the mutational landscape in cutaneous squamous cell carcinoma through multi-patient-targeted single-cell DNA sequencing

Cutaneous squamous cell carcinoma (CSCC) is a prevalent skin cancer with aggressive progression that poses significant challenges, especially in metastatic cases. Single-cell DNA sequencing (scDNA-seq) has become an advanced technology for elucidating tumor heterogeneity and clonal evolution. However, comprehensive scDNA-seq studies and tailored mutation panels for CSCC are lacking.

We analyzed the genomic landscape of Chinese CSCC patients via a Multi-Patient-Targeted (MPT) scDNA-seq approach. This method combined bulk exome sequencing with Tapestri scDNA-seq. Mutations identified through bulk sequencing were used to design a targeted panel for scDNA-seq. Comparative analysis was conducted to explore the associations between specific gene mutations and clinical characteristics such as tumor stage and patient sex. Clonal evolution analysis was performed to understand the evolutionary trajectories of the tumors.

Bulk sequencing revealed a diverse spectrum of somatic mutations in CSCC tumors, with missense mutations being predominant. The top tumor mutations, such as those in NOTCH1, TP53, NOTCH2, TTN, MUC16, RYR2, PRUNE2, DMD, HRAS, and CDKN2A, presented similar frequencies to those reported in studies in Korean and Caucasian populations. However, the mutation frequencies of HRAS, TTN, MUC16 and MUC4 were significantly different from the Korean and Caucasian populations. Comparative analysis revealed associations between specific gene mutations and clinical characteristics such as tumor stage and patient sex. Clonal evolution analysis via scDNA-seq revealed distinct evolutionary trajectories and their potential correlation with tumor development and patient prognosis. Furthermore, scDNA-seq identified two low-frequency mutation clones, NLRP5 and HMMR, which play important roles in the clonal evolution of CSCC.

Peptide nanotubes show promise for overcoming chemotherapy resistance

A research team at CiQUS (University of Santiago de Compostela, Spain) has unveiled an innovative molecular approach that enables anticancer drugs to reach the nucleus of tumor cells, where they can exert their therapeutic effect. The study focused on doxorubicin, a widely used chemotherapy agent. Prolonged exposure to this drug often leads to the emergence of resistant cells, a major clinical challenge that this strategy successfully overcomes while preserving the drug’s antitumor activity.

The approach builds on a simple but powerful concept: the ability of cyclic peptides —small amino acid rings— to stack and self-assemble into hollow cylindrical structures (nanotubes) on the surface of cancer cell membranes. The system, developed by the team led by Juan R. Granja, couples doxorubicin to these peptides and directs it to the through a delivery pathway that differs from the drug’s usual mechanism. This allows the drug to bypass the cellular resistance mechanisms that would normally deactivate it.

Compared with healthy cells, cancer cell membranes contain higher levels of negatively charged lipids. The cyclic peptides used in this study display a strong affinity for these anionic surfaces, facilitating their interaction with . As a result, the peptide–drug conjugates enter resistant cells and travel towards the nucleus, where doxorubicin intercalates with DNA to trigger its cytotoxic effect.

“A Google for DNA”: Scientists Launch Groundbreaking Search Engine for Genetic Code

A new tool developed at ETH Zurich, MetaGraph, allows scientists to search through vast public DNA and RNA databases in seconds — like a “Google for DNA.” DNA sequencing has transformed biomedical research, making it possible to identify rare hereditary disorders in patients and pinpoint specific

Therapeutic strategies targeting cellular senescence for cancer and other diseases

Cellular senescence occurs in response to endogenous or exogenous stresses and is characterized by stable cell cycle arrest, alterations in nuclear morphology and secretion of proinflammatory factors, referred to as the senescence-associated secretory phenotype (SASP). An increase of senescent cells is associated with the development of several types of cancer and aging-related diseases. Therefore, senolytic agents that selectively remove senescent cells may offer opportunities for developing new therapeutic strategies against such cancers and aging-related diseases. This review outlines senescence inducers and the general characteristics of senescent cells. We also discuss the involvement of senescent cells in certain cancers and diseases. Finally, we describe a series of senolytic agents and their utilization in therapeutic strategies.

Novel predictors of tumor growth by exploratory quantitative analysis of radiomics features from MRI data for incidentally discovered meningioma

Predicting future tumor growth from initial imaging of incidentally discovered meningioma (IDM) could inform treatment decisions. However, most factors identified in prior studies on meningioma growth are qualitative. The aim of this study is to identify factors associated with tumor growth using quantitative radiomics features from MRI data.

MRI T2 features from initial imaging of 24 tumor growth cases were compared with those of 25 cases without growth. An in-house program was developed to reduce the time required for data analysis. This program is based on the open-source software 3D Slicer 5.6.2 and PyRadiomics 3.1.0. It enables semi-automatic batch t-test analyses for each feature to compare tumor growth and non-growth groups. Regions of interest (ROIs) were placed in the tumor, outer tumor edge, whole brain, and white matter contralateral to the tumor. A total of 107 features were analyzed across seven classifications: First Order, Shape, Gray Level Co-occurrence Matrix, Gray Level Run Length Matrix, Gray Level Size Zone Matrix, Gray Level Dependence Matrix, and Neighboring Gray Tone Difference Matrix. A t-test was used to identify significant predictors.

Ten features across five classifications showed significant differences (p 0.05): 2 First Order statistics, 2 Shape features, 4 Gy Level Co-occurrence Matrices, 1 Gy Level Size Zone Matrix, and 1 Neighboring Gray Tone Difference Matrix.

P53 in the DNA-Damage-Repair Process

The cells in the human body are continuously challenged by a variety of genotoxic attacks. Erroneous repair of the DNA can lead to mutations and chromosomal aberrations that can alter the functions of tumor suppressor genes or oncogenes, thus causing cancer development. As a central tumor suppressor, p53 guards the genome by orchestrating a variety of DNA-damage-response (DDR) mechanisms. Already early in metazoan evolution, p53 started controlling the apoptotic demise of genomically compromised cells. p53 plays a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability. In addition, p53 took on diverse roles to also directly impact the activity of various DNA-repair systems. It thus appears as if p53 is multitasking in providing protection from cancer development by maintaining genome stability.

Nasal spray with gold nanoparticles delivers targeted treatment to the brain

Tiny gold particles that act as carriers for lithium can be delivered directly to the brain in the form of a nasal spray. Developed by scientists at the Università Cattolica Rome campus/Fondazione Policlinico Universitario A. Gemelli IRCCS, the new nanotechnological device can be used for the treatment and prevention of neuropsychiatric and neurodegenerative diseases.

Lithium is already in for manic-depressive syndrome, but in oral formulation it is not free of side effects. It is used to combat neuropsychiatric diseases such as bipolar disorder, neurodegenerative diseases such as Alzheimer’s disease, and brain infections such as those caused by Herpes Simplex Virus type 1, which several recent studies have linked to an increased risk of neurological diseases.

Published in the journal Advanced Materials and already patented, the idea is the result of a study that demonstrated that it is possible to directly inhibit the activity of an enzyme that plays a key role in the development of these diseases (glycogen synthase kinase-3 beta, GSK-3β) directly in the brain by using lithium delivered by intranasally administered .

Molecular motors drive new non-invasive cancer therapies

Imagine tiny machines, smaller than a virus, spinning inside cancer cells and rewiring their behavior from within. No surgery, no harsh chemicals, just precision at the molecular level.

Two researchers from the Artie McFerrin Department of Chemical Engineering at Texas A&M University are investigating light-activated molecular motors—nanometer-sized machines that can apply from within cells to target and selectively disrupt cancerous activity.

Chemical engineering professor Dr. Jorge Seminario and postdoctoral associate Dr. Diego Galvez-Aranda have contributed to pioneering research by demonstrating a new frontier in non-invasive cancer therapies. The recently published manuscript in the Journal of the American Chemical Society continues this line of investigation.

What’s The Biochemistry Of Fitness In 80yr Olds?

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