Acrylic-melamine latex with controlled crosslinking capability

Crosslinkable polymers are highly demanded in applications where improved thermal, mechanical, and chemical strengths are required. Among crosslinkable polymers, those with film forming capability are of high technological interest, as in coatings and adhesives. In a scenario of increasing concern for sustainability and stricter environmental legislation, coatings industry has switched to water based products, like acrylic latexes. Crosslinkable latexes aim to improve the physical properties of coalesced latex films, over the levels attainable with thermoplastic latexes, which lack hardness, toughness and solvent resistance. Please click Additional Files below to see the full abstract

Chemo-Protective Effects of Dl-Limonene Unaided and in-Blend with 6-Methyleneandrosta-1, 4-Diene-3, 17-Dione on N-Nitroso-N-Methylurea and Estrogen Sulfotransferase Breast Cancer-Induced Albino Female Rat

Breast cancer is a serious prime hassle commonly diagnosed in women worldwide and it is currently the leading cause of cancer-related mortality. In N-nitroso-N-methylurea (NMU) and estrogen sulfotransferase (EST) breast cancer-induced female rat, the study evaluates the chemo-protective possibilities of DL-limonene (1:1) and its combination with 6-Methyleneandrosta-1, 4, Diene- 3, 17-Dione using standard techniques. Amongst others, data obtained reveals mild areas of clogged blood vessels and pulmonary inflammation revealed in the histopathology section. Interestingly, it's possible that DL-limonene alone at a concentration of 10% could be an effective breast cancer treatment. The findings also revealed that combining DL-limonene with 6-ADD at 5% and 12.5mg/kg could reduce the risk of toxicity associated with higher chemotherapeutic dosages in long-term treatment. Furthermore, at a modest dose, this combination may increase the use of aromatase inhibitors in premenopausal women. Despite the medicinal and therapeutic benefits of DL-limonene, it is best to take it in moderation due to its possible harmful effects on the blood vessels

Deciding logics of linear Kripke frames with scattered end pieces

We show that logics based on linear Kripke frames – with or without constant domains – that have a scattered end piece are not recursively enumerable.This is done by reduction to validity in all finite classical models

Film-forming thermoresponsive nanogels for dermal protein delivery

Thermoresponsive nanogels (NGs) have great potential as nanocarriers because of their high in aqueous solutions, elevated biocompatibility, high loading capacity, controlled release of an active component, fast response to temperature change, and design flexibility. In this scenario, a NG dispersion with a film forming ability could be useful for designing a dermal platform for drugs delivery, where the delivering film/patch could be previously obtained or directly formed onto the surface where the release is required. Please click Additional Files below to see the full abstract

Producción de látex híbridos acrílicos/alquídicos

In this work, the production of high solids content hybrid acrylic/alkyd latexes by miniemulsion polymerization is discussed. First, the miniemulsification procedure to achieve colloidally stable hybrid nanodroplets is presented. Next, the efficient nucleation of most nanodroplets during the polymerization, avoiding other nucleation mechanisms is presented. Finally, the key aspects to control the polymer architecture as well as the particle morphology are analyzed.Fil: Goikoetxea, Monika. Universidad del País Vasco; EspañaFil: Minari, Roque Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Beristain, Itxaso. Universidad del País Vasco; EspañaFil: Paulis, María. Universidad del País Vasco; EspañaFil: Asua, José M.. Universidad del País Vasco; EspañaFil: Barandiaran, María J.. Universidad del País Vasco; Españ

Modulating Tumor Microenvironment: A Review on STK11 Immune Properties and Predictive vs Prognostic Role for Non-small-cell Lung Cancer Immunotherapy

The quest for immunotherapy (IT) biomarkers is an element of highest clinical interest in both solid and hematologic tumors. In non-small-cell lung cancer (NSCLC) patients, besides PD-L1 expression evaluation with its intrinsic limitations, tissue and circulating parameters, likely portraying the tumor and its stromal/immune counterparts, have been proposed as potential predictors of IT responsiveness. STK11 mutations have been globally labeled as markers of IT resistance. After a thorough literature review, STK11 mutations condition the prognosis of NSCLC patients receiving ICI-containing regimens, implying a relevant biological and clinical significance. On the other hand, waiting for prospective and solid data, the putative negative predictive value of STK11 inactivation towards IT is sustained by less evidence. The physiologic regulation of multiple cellular pathways performed by STK11 likely explains the multifaceted modifications in tumor cells, stroma, and tumor immune microenvironment (TIME) observed in STK11 mutant lung cancer, particularly explored in the molecular subgroup of KRAS co-mutation. IT approaches available thus far in NSCLC, mainly represented by anti-PD-1/PD-L1 inhibitors, are not promising in the case of STK11 inactivation. Perceptive strategies aimed at modulating the TIME, regardless of STK11 status or specifically addressed to STK11-mutated cases, will hopefully provide valid therapeutic options to be adopted in the clinical practice

Phase II, Open-label, Single-arm, Multicenter Study to Assess the Activity and Safety of Alectinib as Neoadjuvant Treatment in Surgically Resectable Stage III ALK-positive NSCLC: ALNEO Trial

Background: Alectinib is a potent anaplastic lymphoma kinase (ALK)-tyrosine kinase inhibitor (TKI) which is currently used in the first-line setting of advanced ALK+ non-small cell lung cancer (NSCLC). Despite favorable results in the metastatic setting, the activity of alectinib in locally-advanced ALK+ NSCLC as a neoadjuvant treatment remains to be assessed. We report the case of a patient with stage IIIA ALK+ NSCLC (cT2aN2) who received alectinib as neoadjuvant treatment, achieving major pathological response (MPR) at pathologic examination. Hence we present the treatment rationale and study design of a phase II, open-label, single-arm, multicenter clinical trial (ALNEO study, EUDRACT number 2020-003432-25). Materials and Methods: Patients with potentially resectable stage III ALK+ NSCLC (any T with N2, T4N0-1) will be registered to receive oral alectinib 600 mg twice daily for 2 cycles of 4 weeks each (8 weeks totally) during the neoadjuvant phase. After definitive surgery, patients will enter in the adjuvant setting, during which they will receive alectinib 600 mg twice daily for 24 cycles (96 weeks). The primary endpoint is MPR, defined as ≤10% residual viable tumor cells histologically detected in the resected primary tumor and all resected lymph nodes after surgery. Secondary endpoints include pathological complete response, objective response, event-free survival, disease-free survival, overall survival, adverse events. Conclusions: Our case report supports the feasibility of alectinib as neoadjuvant treatment. ALNEO study will further explore the activity and safety of this novel treatment strategy

Dynamic evaluation of circulating mirna profile in egfr‐ mutated nsclc patients treated with egfr‐tkis

Background: Resistance to EGFR‐TKIs constitutes a major challenge for the management of EGFR‐mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR‐21, miR‐27a and miR‐181a) as a surrogate for predicting EGFR‐TKI performance in EGFR‐mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR‐mutated NSCLC patients treated with EGFR‐TKIs were collected at different points in time and miRNA levels were assessed by RT‐PCR. Results: Higher basal values of miR‐21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR‐21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR‐TKI treatment showed that patients who experienced SD had an increase in miR‐21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR‐27a (FC = 3.1) and miR‐181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR‐21 levels in NSCLC cells that became resistant after exposure to EGFR‐TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR‐21, and their dynamic change over time in predicting EGFR‐TKI response in EGFR‐mutated NSCLC

Small Cell Lung Cancer Transformation as a Resistance Mechanism to Osimertinib in Epidermal Growth Factor Receptor-Mutated Lung Adenocarcinoma: Case Report and Literature Review

Introduction: Small cell lung cancer (SCLC) transformation represents a mechanism of resistance to osimertinib in EGFR-mutated lung adenocarcinoma, which dramatically impacts patients' prognosis due to high refractoriness to conventional treatments. Case Description: We present the case of a patient who developed a SCLC phenotypic transformation as resistance mechanism to second-line osimertinib for T790M-positive EGFR-mutated NSCLC. Our patient received platinum–etoposide doublet following SCLC switch and achieved a modest clinical benefit which lasted 4 months. NGS and IHC analyses for p53 and Rb were performed on subsequent liver biopsies, revealing baseline TP53 mutation and complete absence of p53 and Rb expression. Primary cell cultures were established following a liver biopsy at the time of SCLC transformation, and drug sensitivity assays showed meaningful cell growth inhibition when osimertinib was added to platinum–etoposide compared with control (p < 0.05). A review of the current literature regarding SCLC transformation after failure of osimertinib was performed. Conclusions: Based on retrospective data available to date, platinum–etoposide chemotherapy is the preferred treatment choice in the occurrence of SCLC transformation after osimertinib failure. The extension of osimertinib in combination with chemotherapy in the occurrence of SCLC transformation as resistance mechanism to osimertinib is a matter of debate. The combination of osimertinib and platinum–etoposide was effective in inhibiting cell growth in our primary cell cultures. Clinical studies are needed to further explore this combination in the occurrence of SCLC transformation as a resistance mechanism to osimertinib

Efficacy of the cdk4/6 dual inhibitor abemaciclib in egfr-mutated nsclc cell lines with different resistance mechanisms to osimertinib

Abemaciclib is an inhibitor of cyclin-dependent kinases (CDK) 4 and 6 that inhibits the transition from the G1 to the S phase of the cell cycle by blocking downstream CDK4/6-mediated phosphorylation of Rb. The effects of abemaciclib alone or combined with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib were examined in a panel of PC9 and HCC827 osimertinib-resistant non-small cell lung cancer (NSCLC) cell lines carrying EGFR-dependent or-independent mechanisms of intrinsic or acquired resistance. Differently from sensitive cells, all the resistant cell lines analyzed maintained p-Rb, which may be considered as a biomarker of osimertinib resistance and a potential target for therapeutic intervention. In these models, abemaciclib inhibited cell growth, spheroid formation, colony formation, and induced senes-cence, and its efficacy was not enhanced in the presence of osimertinib. Interestingly, in osimertinib sensitive PC9, PC9T790M, and H1975 cells the combination of abemaciclib with osimertinib significantly inhibited the onset of resistance in long-term experiments. Our findings provide a preclinical support for using abemaciclib to treat resistance in EGFR mutated NSCLC patients progressed to osimertinib either as single treatment or combined with osimertinib, and suggest the combination of osimertinib with abemaciclib as a potential approach to prevent or delay osimertinib resistance in first-line treatment