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.     

Rapid change in height and body proportions of Maya American children

Maya families from Guatemala migrated to the United States in record numbers from the late 1970s to the early 1990s. Births to Maya immigrant women have created a sizable number of Maya American children. The height and sitting height of 5 to 12 years children (n = 431) were measured in 1999 and 2000. Leg length was estimated and the sitting height ratio was calculated. These data were compared with a sample of Maya children living in Guatemala measured in 1998 (n = 1,347). Maya American children are currently 11.54 cm taller and 6.83 cm longer‐legged, on average, than Maya children living in Guatemala. Consequently, the Maya Americans have a significantly lower average sitting height ratio (i.e., relatively longer legs in proportion to length of the head and trunk) than do the Maya in Guatemala. These results add support to the hypothesis that both the height and body proportions of human populations are sensitive indicators of the quality of the environment for growth. Am. J. Hum. Biol. 14:753–761, 2002. © 2002 Wiley‐Liss, Inc.     

Characteristics of pollinosis caused by Betula in patients from Ourense (Galicia, Spain).

A retrospective study was performed to describe the features of the pollinosis caused by Betula in the area of Ourense, Spain. The pollen count was carried out with a Lanzoni volumetric Hirts spore trap (1993-2000). The Betula pollen represented 5% over the annual total (annual mean quantity: 965 grains). It was present in the air from March to mid-May. The highest peaks took place in April (maximum values mean: 131 grains/m3). The medical records of 222 patients (mean age 25.66 years) diagnosed with pollinosis (1998-2000), who lived at less than 30 km. from the spore trap, were reviewed. In all of them, the skin-prick test (SPT) was carried out with pollen allergens. The percentages of positive SPT were: Lolium perenne, 91.89% (16.6% monosensitized); Plantago lanceolata, 71.17% (1.26% monosensitized); Betula alba, 41.89% (10.75% monosensitized); Platanus hybrida, 34.95%; Olea europea, 10.36%; and Parietaria judaica, 6.3%. The mean age of Betula monosensitized patients was 44.7 years. The majority of them had symptoms in March-April, 40% had asthma symptoms, 80% had lived in Central Europe, and 30% of them presented an oral allergy syndrome to fruits. There were 41.93% of the patients with positive SPT to Betula pollen who had asthma symptoms, in comparison with 23.25% of the patients with negative SPT to Betula (p = 0.0034). There were 20.28% of the patients with positive SPT to Betula pollen, who had lived in Central Europe, in comparison with 4.27% of the patients with negative SPT to Betula, p: 0.00049. The relative risk of sensitization was 2.05. CONCLUSIONS: Betula pollen was the second cause of clinical pollinosis in our patients, after grass, being responsible of the symptoms in the early spring, in a small number of the patients in their forties. The presence of asthma was higher in Betula sensitized patients, and the residence in Central Europe was a sensitization risk factor.