Abstract. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are routinely used to treat non-small cell lung cancer (NSCLC) in patients with common activating mutations of the EGFR gene. The aim of the study was to compare the efficacies of EGFR-TKIs in patients with common (exon 19 deletions and exon 21 p.Leu858Arg) and rare EGFR mutations. A retrospective analysis of 180 NSCLC patients with common (n=167) and rare (n=13) EGFR mutations treated with erlotinib (n=98), gefitinib (n=66) and afatinib (n=16) was performed. EGFR mutations were determined using RT-PCR and the EntroGen EGFR Mutations Analysis kit. Partial and complete response (PR and CR), progression-free survival (PFS), and overall survival (OS) were analyzed. Demographic and clinical factors had no impact on PFS or OS in patients treated with EGFR-TKIs. Erlotinib, gefitinib, and afatinib showed similar efficacies based on treatment response, median PFS, and OS. The type of EGFR mutation had no impact on median OS; however, median PFS was significantly longer in patients with the exon 19 deletion compared to patients with the exon 21 p.Leu858Arg substitution and rare EGFR gene mutations (P=0.013). Patients with common EGFR mutations showed significantly longer median PFS than those with rare EGFR mutations (10 vs. 5 months; P=0.009). Erlotinib, gefitinib, and afatinib show similar efficacies in NSCLC patients with both common and rare EGFR mutations. When undergoing EGFR-TKI treatment, patients with rare EGFR mutations showed similar OS but poorer PFS. Further investigation into the associations between particular rare EGFR mutations and EGFR-TKIs treatment outcomes is required.
The current review presents up-to-date knowledge on tuberculosis (TB) in diabetic patients. On the basis of available literature, there is little doubt about the close relationship between these two conditions. Diabetes mellitus in this association may still contribute substantially to the burden of TB and negatively affect control of the latter. Chronic hyperglycemia at least to some extent may alter the clinical manifestation, radiological appearance, treatment outcome and prognosis of TB. Although the pathogenesis is not clear, diabetes may impair both innate and adaptive immune responses to Mycobacterium tuberculosis. Eventually, effective screening and dual management of the diseases have to be addressed both in low- and high-income countries in order to limit the negative effects of the forthcoming global diabetes epidemic.
MicroRNAs (miRNAs), key regulators of gene expression at the post-transcriptional level, are grossly misregulated in some human cancers, including non-small-cell lung carcinoma (NSCLC). The aberrant expression of specific miRNAs results in the abnormal regulation of key components of signalling pathways in tumour cells. MiRNA levels and the activity of the gene targets, including oncogenes and tumour suppressors, produce feedback that changes miRNA expression levels and indicates the cell’s genetic activity. In this study, we measured the expression of five circulating miRNAs (miR-195, miR-504, miR-122, miR-10b and miR-21) and evaluated their association with EPIDERMAL GROWTH FACTOR RECEPTOR ( EGFR ) mutation status in 66 NSCLC patients. Moreover, we examined the discriminative power of circulating miRNAs for EGFR mutant‐positive and -negative NSCLC patients using two different data normalisation approaches. We extracted total RNA from the plasma of 66 non-squamous NSCLC patients (31 of whom had tumours with EGFR mutations) and measured circulating miRNA levels using quantitative reverse transcription polymerase chain reaction (RT-qPCR). The miRNA expression levels were normalised using two endogenous controls: miR-191 and miR-16. We found significant associations between the expression of circulating miR-504 and EGFR -activating mutations in NSCLC patients regardless of the normalisation approach used ( p = 0.0072 and 0.0236 for miR-16 and miR-191 normalisation, respectively). The greatest discriminative power of circulating miR-504 was observed in patients with EGFR exon 19 deletions versus wild-type EGFR normalised to miR-191 (area under the curve (AUC) = 0.81, p < 0.0001). Interestingly, circulating miR-504 levels were significantly reduced in the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog ( KRAS )-mutated subgroup compared to EGFR -mutated patients ( p < 0.0030) and those with EGFR/KRAS wild-type tumours ( p < 0.0359). Our study demonstrated the feasibility and potential diagnostic value of plasma miR-504 expression analysis to distinguish between EGFR -mutated and wild-type NSCLC patients. However, quality control and normalisation strategies are very important and have a major impact on the outcomes of circulating miRNA analyses.
The aim of the study was to assess changes in the anaerobic threshold of young soccer players in an annual training cycle. A group of highly trained 15-18 year old players of KKS Lech Poznań were tested. The tests included an annual training macrocycle, and its individual stages resulted from the time structure of the sports training. In order to assess the level of exercise capacities of the players, a field exercise test of increasing intensity was carried out on a soccer pitch. The test made it possible to determine the 4 millimolar lactate threshold (T LA 4 mmol · l-1) on the basis of the lactate concentration in blood [LA], to establish the threshold running speed and the threshold heart rate [HR]. The threshold running speed at the level of the 4 millimolar lactate threshold was established using the two-point form of the equation of a straight line. The obtained indicators of the threshold running speed allowed for precise establishment of effort intensity used in individual training in developing aerobic endurance. In order to test the significance of differences in mean values between four dates of tests, a non-parametric Friedman ANOVA test was used. The significance of differences between consecutive dates of tests was determined using a post-hoc Friedman ANOVA test. The tests showed significant differences in values of selected indicators determined at the anaerobic threshold in various stages of an annual training cycle of young soccer players. The most beneficial changes in terms of the threshold running speed were noted on the fourth date of tests, when the participants had the highest values of 4.01 m · s-1 for older juniors, and 3.80 m · s-1 for younger juniors. This may be indicative of effective application of an individualized programme of training loads and of good preparation of teams for competition in terms of players’ aerobic endurance.
EGFR gene mutations in ADSQ carcinoma patients may be more common than previously thought. EGFR mutation testing is appropriate in ADSQ-bearing patients, in which response for molecular-based therapy is predictable.
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