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.     

Bladder cancer and asbestos in Spain

The relationship between bladder cancer and occupational exposure to asbestos was investigated between 1978 and 1982 at La Paz Hospital in Madrid in a case-control study conducted among 353 male patients and 53 women with a diagnosis of urothelium carcinoma, and among an equal number of controls matched in age (decade of life), sex and date of admission to the hospital. The results showed that bladder cancer is associated with occupational exposure to asbestos.     

Association between the occurrence of antibodies to simian vacuolating virus 40 and bladder cancer in male smokers

An association between the occurrence of antibodies to simian vacuolating virus 40 and bladder cancer in male smokers was found in a case-control study conducted in 200 male patients with bladder cancer and 400 control men. The risk of bladder cancer increases with the years of cigarette smoking.     

Glucocorticoid-dependent complementation of a hepatoma cell variant defective in viral glycoprotein sorting.

We have utilized the rat hepatoma (HTC) cell sorting variant CR4 to examine the glucocorticoid-regulated pathways that localize mouse mammary tumor virus glycoproteins to the cell surface. The defective sorting of cell surface mouse mammary tumor virus glycoproteins in CR4 cells was complemented after fusion with either normal rat hepatocytes or uninfected HTC cells. Indirect immunofluorescence of transient heterokaryons revealed that the regulated localization of mouse mammary tumor virus glycoproteins was dependent upon glucocorticoid treatment and required de novo RNA and protein synthesis. Thus, a glucocorticoid-regulated trafficking activity, unrelated to mouse mammary tumor virus sequences, which is induced in both adult rat liver and cultured hepatoma cells, can act in trans to mediate an intracellular sorting pathway for membrane glycoproteins.     

P01Contact dermatitis from textile colours in three Spanish towns

Objective:  Prevalence of textile dye contact dermatitis (TD‐CD) are lacking in many countries. Our aim is to know the frequency of TD‐CD in three different areas of Spain.
Methods:  100 patients were tested with Spanish standard series and the five most frequent TD in each city. D. Orange 1, D. Orange 3, D. Blue 35, D. Blue 106, D. Blue 124 were included in Murcia and Seville, and the three last and D. Red 1, D. Red 17 in Santiago.
Results:  23/300 (15 women and 8 men) were positives to one or more TD. D. Blue 124 was the most frequent allergen (18/300), followed by D. Blue 106 (17/300). D. Red 1, D. Red 17 and D. Orange 1 were positives in 2/200. D. Orange 3 and D. Blue 35 were positives in 1/200. Eczema was located on hands in 13 cases. Clinical picture was variable. Origin of sensitization was clothing and occupational. Relevance was obtained in 20/23 cases.
Conclusions:  The study confirm an high frequency of disperse dye allergy in Spain with a very different prevalence in the three areas: Seville 14%, Murcia 5% and Santiago 4%, that are probably due to social and cultural factors. We recommend the inclusion of D. Blue 106, D. Blue 124, D. Blue 35, D. Red 1, D. Red 17, D. Orange 1 and D. Orange 3 in standard series in order to detect sensitivity to textile colours that is most frequent than previously suspected.