Outcomes of patients with non-small cell lung cancer and poor performance status treated with immune checkpoint inhibitors in the real-world setting

International Journal of Clinical Oncology - Immune-checkpoint inhibitors (ICIs) are standard treatments for metastatic non-small cell lung cancer (NSCLC). Patients with poor performance status...     

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.     

Extraction of phenolic components from an Aloe vera (Aloe barbadensis Miller) crop and their potential as antimicrobials and textile dyes

The present work focuses on the use of solid and agricultural residues from Aloe vera crops, as a source of antimicrobial agents and textile dyes. The roots from an A. vera plantation post-harvest were extracted with ethyl acetate, purified and phytochemically characterized to obtain five metabolites: aloesaponarin-I (1), deoxyerythrolaccin (2), lacaic acid D methyl ester (3), aloesaponarin-II (4), and aloesaponol-I (5). Acid hydrolysis of the solid industrial residue gave aloe-emodin (6) as the main product with a good yield. All of the components were tested for the first time against phytopathogenic bacteria strains, and deoxyerythrolaccin and lacaic acid D methyl ester were active against Xanthomonas campestris with MIC values of 46.86 and 93.75 μg/mL, respectively. Aloesaponarin-I and aloe-emodin, the main products, were tested as dyes for polyester fabrics using different mordants and pH bath conditions. The colour of each material was investigated in terms of the CIELAB L*, a* and b* values, and the colour fastness to light and washing was investigated according to the Mexican standard methods (NMX-A-074-INNTEX-2005; NMX-A-105-B02-INNTEX-2010). Aloesaponarin-I dyed polyester bright yellow but the final colour was very sensitive to the pH of the dye bath. Aloe-emodin dyed polyester deep yellow, and the fabrics showed good colour fastness to light and to domestic laundering. This study provides evidence that the phenolic components obtained from agricultural residues of the aloe industry can be useful organic alternatives as antimicrobial agents and textile dyes.