The αvβ6 integrin specific virotherapy, Ad5-A20.FCU1, selectively delivers potent "in-tumour" chemotherapy to pancreatic ductal adenocarcinoma.

Background: Pancreatic ductal adenocarcinoma (PDAC) represent an unmet clinical need. Approximately 90% of PDACs express high levels of αvβ6 integrin. We have previously described Ad5-A20, an adenovirus vector with ablated native means of cell entry and retargeted to αvβ6 integrin by incorporation of an A20 peptide.

A pseudotyped adenovirus serotype 5 vector with serotype 49 fiber knob is an effective vector for vaccine and gene therapy applications.

Adenoviruses (Ads) have demonstrated significant success as replication-deficient (RD) viral vectored vaccines, as well as broad potential across gene therapy and cancer therapy. Ad vectors transduce human cells via direct interactions between the viral fiber knob and cell surface receptors, with secondary cellular integrin interactions. Ad receptor usage is diverse across the extensive phylogeny.

Temporally resolved proteomics identifies nidogen-2 as a cotarget in pancreatic cancer that modulates fibrosis and therapy response.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by increasing fibrosis, which can enhance tumor progression and spread. Here, we undertook an unbiased temporal assessment of the matrisome of the highly metastatic KPC (, , ) and poorly metastatic KPC (, , ) genetically engineered mouse models of pancreatic cancer using mass spectrometry proteomics. Our assessment at early-, mid-, and late-stage disease reveals an increased abundance of nidogen-2 (NID2) in the KPC model compared to KPC, with further validation showing that NID2 is primarily expressed by cancer-associated fibroblasts (CAFs).

The Immune System-A Double-Edged Sword for Adenovirus-Based Therapies.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious.

Identification of cross reactive T cell responses in adenovirus based COVID 19 vaccines.

Vaccination has proven to be a valuable tool to combat SARS-CoV-2. However, reports of rare adverse reactions such as thrombosis/thrombocytopenia syndrome after ChAdOx1 nCoV-19 vaccination have caused scientific, public and media concern. ChAdOx1 was vectorised from the Y25 chimpanzee adenovirus, which was selected due to low human seroprevalence to circumvent pre-existing immunity.

Urinary Metabolite Diagnostic and Prognostic Liquid Biopsy Biomarkers of Lung Cancer in Nonsmokers and Tobacco Smokers.

Purpose: Nonsmokers account for 10% to 13% of all lung cancer cases in the United States. Etiology is attributed to multiple risk factors including exposure to secondhand smoking, asbestos, environmental pollution, and radon, but these exposures are not within the current eligibility criteria for early lung cancer screening by low-dose CT (LDCT).

Experimental Design: Urine samples were collected from two independent cohorts comprising 846 participants (exploratory cohort) and 505 participants (validation cohort).

Phase 1 study of CAR-37 T cells in patients with relapsed or refractory CD37+ lymphoid malignancies.

We report a first-in-human clinical trial using chimeric antigen receptor (CAR) T cells targeting CD37, an antigen highly expressed in B- and T-cell malignancies. Five patients with relapsed or refractory CD37+ lymphoid malignancies were enrolled and infused with autologous CAR-37 T cells. CAR-37 T cells expanded in the peripheral blood of all patients and, at peak, comprised >94% of the total lymphocytes in 4 of 5 patients.

Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism.

In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth remains underappreciated. This work sought to address this in the context of triple negative breast cancer (TNBC), a cancer type known to aggressively disseminate at all stages of disease progression.

Population divergence in nutrient-temperature interactions in .

The interaction between larval host plant quality and temperature can influence the short-term physiological rates and life-history traits of insect herbivores. These factors can vary locally, resulting in local adaptation in responses to diet and temperature, but the comparison of these interactions between populations is infrequently carried out. In this study, we examine how the macronutrient ratio of an artificial diet determines the larval growth, development, and survival of larval (Lepidoptera: Pieridae) at different temperatures between two invasive North American populations from different climatic regions.

How development and survival combine to determine the thermal sensitivity of insects.

Thermal performance curves (TPCs) depict variation in vital rates in response to temperature and have been an important tool to understand ecological and evolutionary constraints on the thermal sensitivity of ectotherms. TPCs allow for the calculation of indicators of thermal tolerance, such as minimum, optimum, and maximum temperatures that allow for a given metabolic function. However, these indicators are computed using only responses from surviving individuals, which can lead to underestimation of deleterious effects of thermal stress, particularly at high temperatures.

Carbon monoxide poisoning: A problem uniquely suited to a medicinal inorganic chemistry solution.

Carbon monoxide poisoning is one of the most common forms of poisoning in the world. Although the primary mode of treatment, oxygen therapy, is highly effective in many cases, there are instances in which it is inadequate or inappropriate. Whereas oxygen therapy relies on high levels of a low-affinity ligand (O) to displace a high-affinity ligand (CO) from metalloproteins, an antidote strategy relies on introducing a molecule with a higher affinity for CO than native proteins (K > K).

Capture and inactivation of viral particles from bioaerosols by electrostatic precipitation.

Infectious viral particles in bioaerosols generated during laparoscopic surgery place staff and patients at significant risk of infection and contributed to the postponement of countless surgical procedures during the COVID-19 pandemic causing excess deaths. The implementation of devices that inactivate viral particles from bioaerosols aid in preventing nosocomial viral spread. We evaluated whether electrostatic precipitation (EP) is effective in capturing and inactivating aerosolized enveloped and non-enveloped viruses.

A first-in-class pan-lysyl oxidase inhibitor impairs stromal remodeling and enhances gemcitabine response and survival in pancreatic cancer.

The lysyl oxidase family represents a promising target in stromal targeting of solid tumors due to the importance of this family in crosslinking and stabilizing fibrillar collagens and its known role in tumor desmoplasia. Using small-molecule drug-design approaches, we generated and validated PXS-5505, a first-in-class highly selective and potent pan-lysyl oxidase inhibitor. We demonstrate in vitro and in vivo that pan-lysyl oxidase inhibition decreases chemotherapy-induced pancreatic tumor desmoplasia and stiffness, reduces cancer cell invasion and metastasis, improves tumor perfusion and enhances the efficacy of chemotherapy in the autochthonous genetically engineered KPC model, while also demonstrating antifibrotic effects in human patient-derived xenograft models of pancreatic cancer.

Oncolytic Viruses and Immune Checkpoint Inhibitors: The "Hot" New Power Couple.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumour microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically "cold" tumours.

Engineering Adenoviral Vectors with Improved GBM Selectivity.

Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of the many human adenoviral serotypes described to date, adenovirus 5 (HAdV-C5) has been the most utilised clinically and experimentally.

The laryngopharyngeal nerve: a comprehensive review.

The laryngopharyngeal nerve has received much less attention that the other contributions to the pharyngeal plexus , glossopharyngeal and vagus nerves. Often, in descriptions and depictions, the nerve is simply labeled as the sympathetic contribution to the pharyngeal plexus. As there is such scant information available regarding this nerve, the present review was performed.

Predicting age and mass at maturity from feeding behavior and diet in : An empirical test of a life history model.

Feeding for most animals involves bouts of active ingestion alternating with bouts of no ingestion. In insects, the temporal patterning of bouts varies widely with resource quality and is known to affect growth, development time, and fitness. However, the precise impacts of resource quality and feeding behavior on insect life history traits are poorly understood.

Broad sialic acid usage amongst species D human adenovirus.

Human adenoviruses (HAdV) are widespread pathogens causing usually mild infections. The Species D (HAdV-D) cause gastrointestinal tract infections and epidemic keratoconjunctivitis (EKC). Despite being significant pathogens, knowledge around HAdV-D mechanism of cell infection is lacking.

Extracellular matrix profiles determine risk and prognosis of the squamous cell carcinoma subtype of non-small cell lung carcinoma.

Background: Squamous cell carcinoma (SqCC) is a subtype of non-small cell lung cancer for which patient prognosis remains poor. The extracellular matrix (ECM) is critical in regulating cell behavior; however, its importance in tumor aggressiveness remains to be comprehensively characterized.

Methods: Multi-omics data of SqCC human tumor specimens was combined to characterize ECM features associated with initiation and recurrence.

Engineering Cancer Selective Virotherapies: Are the Pieces of the Puzzle Falling into Place?

Advances in gene therapy, synthetic biology, cancer genomics, and patient-derived cancer models have expanded the repertoire of strategies for targeting human cancers using viral vectors. Novel capsids, synthetic promoters, and therapeutic payloads are being developed and assessed through approaches such as rational design, pooled library screening, and directed evolution. Ultimately, the goal is to generate precision-engineered viruses that target different facets of tumor cell biology, without compromising normal tissue and organ function.

Pseudotyping Bacteriophage P2 Tail Fibers to Extend the Host Range for Biomedical Applications.

Bacteriophages (phages) represent powerful potential treatments against antibiotic-resistant bacterial infections. Antibiotic-resistant bacteria represent a significant threat to global health, with an estimated 70% of infection-causing bacteria being resistant to one or more antibiotics. Developing novel antibiotics against the limited number of cellular targets is expensive and time-consuming, and bacteria can rapidly develop resistance.

Synthesis and Functionalization of Challenging -Substituted Aryl Bis-pocket Porphyrins Accessed via Suzuki-Miyaura Cross-Coupling.

Herein we report an investigation into the synthesis, metalation, and functionalization of bis-pocket porphyrins using the Suzuki-Miyaura cross-coupling reaction. Steric limitations to accessing bis-pocket porphyrins were overcome by using this Pd-catalyzed C-C-bond-forming strategy to introduce steric bulk macrocyclization: 2,6-dibromo-4-trimethylsilybenzaldehyde was condensed with pyrrole, and a variety of boronic acids were coupled to the resulting porphyrin in up to 95% yield. Furthermore, we show that these porphyrins can be metalated with a variety of metals and sulfonated to create water-soluble bis-pocket porphyrins.

Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis.

The tumour stroma, and in particular the extracellular matrix (ECM), is a salient feature of solid tumours that plays a crucial role in shaping their progression. Many desmoplastic tumours including breast cancer involve the significant accumulation of type I collagen. However, recently it has become clear that the precise distribution and organisation of matrix molecules such as collagen I is equally as important in the tumour as their abundance.

Creatine riboside is a cancer cell-derived metabolite associated with arginine auxotrophy.

The metabolic dependencies of cancer cells have substantial potential to be exploited to improve the diagnosis and treatment of cancer. Creatine riboside (CR) is identified as a urinary metabolite associated with risk and prognosis in lung and liver cancer. However, the source of high CR levels in patients with cancer as well as their implications for the treatment of these aggressive cancers remain unclear.