Clinical validation of the novel CLIA-CA-62 assay efficacy for early-stage breast cancer detection

BackgroundWithout organized screening programs up to 60-70% of breast cancers are diagnosed at advanced stages that have significantly lower five-year survival rate and poorer outcomes, which is a serious global public health problem. The purpose of the blind clinical study was the assessment of the novel in-vitro diagnostic chemiluminescent CLIA-CA-62 assay for early-stage breast cancer detection.MethodsBlind serum samples of 196 BC patients with known TNM staging, 85% with DCIS, Stage I & IIA, and 73 healthy control subjects were analyzed with the CLIA-CA-62 and CA 15-3 ELISA assays. Results were also compared to the pathology findings and to published data from mammography, MRI, ultrasound, and multi-cancer early detection test (MCED).ResultsThe CLIA-CA-62 overall sensitivity for BC was 92% (100% for DCIS) at 93% specificity and it decreased in invasive stages (Stage I=97%, Stage II=85% and Stage III=83%). For the CA 15-3 assay sensitivity was 27-46% at 80% specificity. Sensitivity for mammography was 63-80% at 60% specificity, depending on the stage and the parenchymal density.ConclusionThese results demonstrate that CLIA-CA-62 immunoassay could prove useful as a supplement to current mammography screening and other imaging methods, thus increasing the diagnostic sensitivity in DCIS and Stage I breast cancer detection

Chitosan Cross-Linking with Acetaldehyde Acetals

Here we demonstrate the possibility of using acyclic diethylacetal of acetaldehyde (ADA) with low cytotoxicity for the fabrication of hydrogels via Schiff bases formation between chitosan and acetaldehyde generated in situ from acetals in chitosan acetate solution. This approach is more convenient than a direct reaction between chitosan and acetaldehyde due to the better commercial availability and higher boiling point of the acetals. Rheological data confirmed the formation of intermolecular bonds in chitosan solution after the addition of acetaldehyde diethyl acetal at an equimolar NH2: acetal ratio. The chemical structure of the reaction products was determined using elemental analysis and 13C NMR and FT-IR spectroscopy. The formed chitosan-acetylimine underwent further irreversible redox transformations yielding a mechanically stable hydrogel insoluble in a broad pH range. The reported reaction is an example of when an inappropriate selection of acid type for chitosan dissolution prevents hydrogel formation

Stimuli-Responsive Dual Cross-Linked <i>N</i>-Carboxyethylchitosan Hydrogels with Tunable Dissolution Rate

Here, we discuss the applicability of (methylenebis(salicylaldehyde)—MbSA) for the fabrication of the stimuli-responsive N-carboxyethylchitosan (CEC) hydrogels with a tunable dissolution rate under physiological conditions. In comparison with non-covalent salicylimine hydrogels, MbSA cross-linking via covalent bis(‘imine clip’) and non-covalent hydrophobic interactions allowed the fabrication of hydrogels with storage moduli > 1 kPa at ten-fold lower aldehyde/CEC molar ratio with the preservation of pH- and amino-acid responsive behavior. Although MbSA-cross-linked CEC hydrogels were stable at neutral and weakly alkaline pH, their disassembly in cell growth medium (Dulbecco’s modified Eagle’s medium, DMEM) under physiological conditions was feasible due to transimination reaction with amino acids contained in DMEM. Depending on the cross-linking density, the complete dissolution time of the fabricated hydrogels varied from 28 h to 11 days. The cytotoxicity of MbSA cross-linked CEC hydrogels toward a human colon carcinoma cell line (HCT 116) and primary human dermal fibroblasts (HDF) was remarkably lower in comparison with CEC-salicylimine hydrogels. Fast gelation, relatively low cytotoxicity, and tunable stimuli-induced disassembly under physiological conditions make MbSA cross-linked CEC hydrogels promising for drug encapsulation and release, 3D printing, cell culturing, and other biomedical applications

Stimuli-Responsive Dual Cross-Linked N-Carboxyethylchitosan Hydrogels with Tunable Dissolution Rate

Here, we discuss the applicability of (methylenebis(salicylaldehyde)—MbSA) for the fabrication of the stimuli-responsive N-carboxyethylchitosan (CEC) hydrogels with a tunable dissolution rate under physiological conditions. In comparison with non-covalent salicylimine hydrogels, MbSA cross-linking via covalent bis(‘imine clip’) and non-covalent hydrophobic interactions allowed the fabrication of hydrogels with storage moduli &gt; 1 kPa at ten-fold lower aldehyde/CEC molar ratio with the preservation of pH- and amino-acid responsive behavior. Although MbSA-cross-linked CEC hydrogels were stable at neutral and weakly alkaline pH, their disassembly in cell growth medium (Dulbecco’s modified Eagle’s medium, DMEM) under physiological conditions was feasible due to transimination reaction with amino acids contained in DMEM. Depending on the cross-linking density, the complete dissolution time of the fabricated hydrogels varied from 28 h to 11 days. The cytotoxicity of MbSA cross-linked CEC hydrogels toward a human colon carcinoma cell line (HCT 116) and primary human dermal fibroblasts (HDF) was remarkably lower in comparison with CEC-salicylimine hydrogels. Fast gelation, relatively low cytotoxicity, and tunable stimuli-induced disassembly under physiological conditions make MbSA cross-linked CEC hydrogels promising for drug encapsulation and release, 3D printing, cell culturing, and other biomedical applications

Cytokine Profile in Lung Cancer Patients: Anti-Tumor and Oncogenic Cytokines

Lung cancer is currently the second leading cause of cancer death worldwide. In recent years, checkpoint inhibitor immunotherapy (ICI) has emerged as a new treatment. A better understanding of the tumor microenvironment (TMJ) or the immune system surrounding the tumor is needed. Cytokines are small proteins that carry messages between cells and are known to play an important role in the body’s response to inflammation and infection. Cytokines are important for immunity in lung cancer. They promote tumor growth (oncogenic cytokines) or inhibit tumor growth (anti-tumour cytokines) by controlling signaling pathways for growth, proliferation, metastasis, and apoptosis. The immune system relies heavily on cytokines. They can also be produced in the laboratory for therapeutic use. Cytokine therapy helps the immune system to stop the growth or kill cancer cells. Interleukins and interferons are the two types of cytokines used to treat cancer. This article begins by addressing the role of the TMJ and its components in lung cancer. This review also highlights the functions of various cytokines such as interleukins (IL), transforming growth factor (TGF), and tumor necrosis factor (TNF)

Angiogenesis in Lung Cancer: Understanding the Roles of Growth Factors

Research has shown the role of growth factors in lung cancer angiogenesis. Angiogenesis promotes lung cancer progression by stimulating tumor growth, enhancing tumor invasion, contributing to metastasis, and modifying immune system responses within the tumor microenvironment. As a result, new treatment techniques based on the anti-angiogenic characteristics of compounds have been developed. These compounds selectively block the growth factors themselves, their receptors, or the downstream signaling pathways activated by these growth factors. The EGF and VEGF families are the primary targets in this approach, and several studies are being conducted to propose anti-angiogenic drugs that are increasingly suitable for the treatment of lung cancer, either as monotherapy or as combined therapy. The efficacy of the results are encouraging, but caution must be placed on the higher risk of toxicity, outlining the importance of personalized follow-up in the management of these patients

Alcohol and cause-specific mortality in Russia : a retrospective case-control study of 48,557 adult deaths

Alcohol is an important determinant of the high and fluctuating adult mortality rates in Russia, but cause-specific detail is lacking. Our case-control study investigated the effects of alcohol consumption on male and female cause-specific mortality