Strongrivers4287

Increased activity of STAT3 is associated with progression of head and neck squamous cell carcinoma (HNSCC). Upstream activators of STAT3, such as JAKs, represent potential targets for therapy of solid tumors, including HNSCC. In this study, we investigated the anticancer effects of ruxolitinib, a clinical JAK1/2 inhibitor, in HNSCC preclinical models, including patient-derived xenografts (PDX) from patients treated on a window-of-opportunity trial.

HNSCC cell lines were treated with ruxolitinib, and the impact on activated STAT3 levels, cell growth, and colony formation was assessed. PDXs were generated from patients with HNSCC who received a brief course of neoadjuvant ruxolitinib on a clinical trial. The impact of ruxolitinib on tumor growth and STAT3 activation was assessed.

Ruxolitinib inhibited STAT3 activation, cellular growth, and colony formation of HNSCC cell lines. Ruxolitinib treatment of mice bearing an HNSCC cell line-derived xenograft significantly inhibited tumor growth compared with vehicle-treated controls. The response of HNSCC PDXs derived from patients on the clinical trial mirrored the responses seen in the neoadjuvant setting. Baseline active STAT3 (pSTAT3) and total STAT3 levels were lower, and ruxolitinib inhibited STAT3 activation in a PDX from a patient whose disease was stable on ruxolitinib, compared with a PDX from a patient whose disease progressed on ruxolitinib and where ruxolitinib treatment had minimal impact on STAT3 activation.

Ruxolitinib exhibits antitumor effects in HNSCC preclinical models. Baseline pSTAT3 or total STAT3 levels in the tumor may serve as predictive biomarkers to identify patients most likely to respond to ruxolitinib.

Ruxolitinib exhibits antitumor effects in HNSCC preclinical models. Baseline pSTAT3 or total STAT3 levels in the tumor may serve as predictive biomarkers to identify patients most likely to respond to ruxolitinib.A novel bacterium, designated strain JHSY0214T, was isolated from the gut of a Korean limpet, Cellana toreuma. Cells of strain JHSY0214T were Gram-stain-negative, strictly aerobic, yellow-pigmented, non-spore-forming, non-motile and showed a rod-coccus growth cycle. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belonged to the genus Parasphingorhabdus, and was most closely related to Parasphingorhabdus litoris KCTC 12764T (98.71 %). Strain JHSY0214T had two fluoroquinolone-resistance genes and seven multidrug-resistance efflux pump genes, but did not have beta-lactamase genes and zinc resistance genes compared with P. litoris KCTC 12764T. Strain JHSY0214T grew optimally at 30 °C, pH 7.0 and in the presence of 2 % (w/v) NaCl. The predominant cellular fatty acids of strain JHSY0214T were summed feature 8 (C18  1  ω6c and/or C18  1  ω7c; 41.2 %), summed feature 3 (C16  1  ω7c and/or C16  1  ω6c; 21 %) and C16  0 (18.9 %). The major isoprenoid quinone was ubiquinone-10. The major polar lipids were sphingoglycolipid and phosphatidylethanolamine. The genomic DNA G+C content was 52.8 mol%. Based on phylogenetic, genotypic and phenotypic data, strain JHSY0214T represents a novel species of the genus Parasphingorhabdus, for which the name Parasphingorhabdus cellanae is proposed. selleckchem The type strain is JHSY0214T (=KCTC 82387T=DSM 112279T).The structures of the crosslinks in supramolecular polymer networks play an important role on their properties and functions. Herein, emissive metallacages are used as crosslinks to prepare metallacage-cored polyurethanes. The mechanical properties including storage modulus, toughness, Young's modulus and breaking strength of polymers are greatly enhanced with the increase of crosslinking densities. Moreover, such polymers not only exhibit good fluorescence in the solid state, but also show self-healing and shape memory properties owing to the dynamic reversible non-covalent bonds in their structures. This study not only offers a convenient strategy to prepare metallacage-crosslinked networks, but also explores their applications as self-healing and shape memory materials, which will promote the study of metallacage-cored supramolecular networks as smart materials.

We hypothesized that inhibition and trapping of PARP1 alone would be sufficient to achieve antitumor activity. In particular, we aimed to achieve selectivity over PARP2, which has been shown to play a role in the survival of hematopoietic/stem progenitor cells in animal models. We developed AZD5305 with the aim of achieving improved clinical efficacy and wider therapeutic window. This next-generation PARP inhibitor (PARPi) could provide a paradigm shift in clinical outcomes achieved by first-generation PARPi, particularly in combination.

AZD5305 was tested in vitro for PARylation inhibition, PARP-DNA trapping, and antiproliferative abilities. In vivo efficacy was determined in mouse xenograft and PDX models. The potential for hematologic toxicity was evaluated in rat models, as monotherapy and combination.

AZD5305 is a highly potent and selective inhibitor of PARP1 with 500-fold selectivity for PARP1 over PARP2. AZD5305 inhibits growth in cells with deficiencies in DNA repair, with minimal/no effects inefit of nonselective PARPi, while reducing potential for hematotoxicity. AZD5305 is currently in phase I trials (NCT04644068).

Determine the safety and specificity of a tumor-targeted radiotracer (89Zr-pan) in combination with 18F-FDG PET/CT to improve diagnostic accuracy in head and neck squamous cell carcinoma (HNSCC).

Adult patients with biopsy-proven HNSCC scheduled for standard-of-care surgery were enrolled in a clinical trial and underwent systemic administration of 89Zirconium-panitumumab and panitumumab-IRDye800 followed by preoperative 89Zr-pan PET/CT and intraoperative fluorescence imaging. The sensitivity, specificity, and AUC were evaluated.

A total of fourteen patients were enrolled and completed the study. Four patients (28.5%) had areas of high 18F-FDG uptake outside the head and neck region with maximum standardized uptake values (SUVmax) greater than 2.0 that were not detected on 89Zr-pan PET/CT. These four patients with incidental findings underwent further workup and had no evidence of cancer on biopsy or clinical follow-up. Forty-eight lesions (primary tumor, LNs, incidental findings) with SUVmax ranging 2.0-23.6 were visualized on 18F-FDG PET/CT; 34 lesions on 89Zr-pan PET/CT with SUVmax ranging 0.9-10.5. The combined ability of 18F-FDG PET/CT and 89Zr-pan PET/CT to detect HNSCC in the whole body was improved with higher specificity of 96.3% [confidence interval (CI), 89.2%-100%] compared to 18F-FDG PET/CT alone with specificity of 74.1% (CI, 74.1%-90.6%). One possibly related grade 1 adverse event of prolonged QTc (460 ms) was reported but resolved in follow-up.

89Zr-pan PET/CT imaging is safe and may be valuable in discriminating incidental findings identified on 18F-FDG PET/CT from true positive lesions and in localizing metastatic LNs.

89Zr-pan PET/CT imaging is safe and may be valuable in discriminating incidental findings identified on 18F-FDG PET/CT from true positive lesions and in localizing metastatic LNs.Icing imposes a significant burden on those living in cold climates, with negative impacts on infrastructure, transportation, and energy systems. Over the past few decades, a wide range of materials with ice-shedding characteristics have been developed, including surfaces that are non-wetting/hydrophobic, liquid-infused, stress-localized, and those with low interfacial toughness. Although many of these materials have demonstrated low ice adhesion in a laboratory setting, none have achieved widespread practical adoption. This is primarily a result of the fact that they tend to have very low durability, limiting their applicability. Thus, the primary challenge in developing ice-shedding materials is finding materials with both low ice adhesion AND good durability. Here, we introduce the concept of a so-called "fracture-controlled surface." Through coordinated mechanical and chemical heterogeneity in the material structure, we affect the interfacial crack nucleation and growth on these surfaces. Through this controlled process, fracture-controlled surfaces exhibit both low ice adhesion and very high mechanical durability. Measurements of the durability of these surfaces indicate performance that is three orders of magnitude greater than other state-of-the-art ice-shedding materials. Physically, via mechanical heterogeneity of the material, we pre-specified the crack nucleation coordinates at the interface and guided the crack growth in an interfacial plane, with no kinking in other directions. This helps to maximize the energy that goes towards crack nucleation and growth. A detailed mathematical model is developed to predict adhesion of external solid objects on these materials. The model suggests that an elastic matching criterion is required to achieve minimal adhesion of solid objects on these materials. Fracture-controlled surfaces provide a rich material platform to guide future innovation of materials with minimal adhesion while having very high durability.

Ultrasound-guided percutaneous cryoneurolysis is an analgesic technique in which a percutaneous probe is used to reversibly ablate a peripheral nerve(s) using exceptionally low temperature, and has yet to be evaluated with randomized, controlled trials. Pain after mastectomy can be difficult to treat, and the authors hypothesized that the severity of surgically related pain would be lower on postoperative day 2 with the addition of cryoanalgesia compared with patients receiving solely standard-of-care treatment.

Preoperatively, participants at one enrolling center received a single injection of ropivacaine, 0.5%, paravertebral nerve block at T3 or T4, and perineural catheter. Participants subsequently underwent an active or sham ultrasound-guided percutaneous cryoneurolysis procedure of the ipsilateral T2 to T5 intercostal nerves in a randomized, patient- and observer-masked fashion. Participants all received a continuous paravertebral block with ropivacaine, 0.2%, until the early morning of discharge (usy.

Percutaneous cryoneurolysis markedly improved analgesia without systemic side effects or complications after mastectomy.Isolated fallopian tubal torsion is rare among women of reproductive age, and it is even rarer during pregnancy. Despite its rare incidence, it is important to consider this diagnosis to facilitate prompt and effective intervention. We present the case of a pregnant woman in her third trimester who presented with acute right abdominal pain. A 32-year-old primigravida woman at 29 weeks and four days of gestation visited the emergency department with acute right flank and abdominal pain. Sonography and MRI revealed the presence of a right adnexal cystic mass. Exploratory laparoscopy revealed isolated right tubal torsion and a normal ovary. To avoid torsion recurrence, we performed laparoscopic right salpingectomy. The remainder of her gestation was uneventful. Histopathological examination revealed serous cystadenoma with haemorrhagic infarction. We reviewed the literature for cases of isolated tubal torsion in the past 11 years. Twenty-three case reports were included in this study, and the average time from presentation to surgical intervention was 35.