Background: Reverse transcription followed by real-time PCR is widely used for quantification of specific mRNA, and with the use of double-stranded DNA binding dyes it is becoming a standard for microarray data validation. Despite the kinetic information generated by real-time PCR, most popular analysis methods assume constant amplification efficiency among samples, introducing strong biases when amplification efficiencies are not the same.
Abstract:Background: Tumor progression is characterized by high mutation rates, each mutation potentially generating an "alarm" signal. The brain is the main integrator of signals arising in the periphery from changes in homeostasis. We hypothesized that tumors growing at a distant site might be a stimulus strong enough to be molecularly sensed and integrated by the brain.Results: Transcriptome analysis of the mouse hypothalamus, midbrain, and pre-fontal cortex at different time points following administration at a distant site of mammary, lung and colon cancer cells evidenced cancer-type and brain-region specific changes in gene expression. On the contrary, no significant gene expression changes were detected in the liver. The hypothalamus was the region with the largest number of differentially expressed genes. On the array and off the array analysis of hypothalamic samples using real time PCR confirmed changes in genes associated with synaptic activity and sickness response, respectively. Gene clustering allowed the discrimination between each cancer model and between the cancer models and arthritis.
Conclusions:The present data provides evidence of changes in gene expression in the brain during progression of distal tumors and arthritis highlighting a potential link between distal pathological processes and the brain.
Background
The efficacy and safety of secukinumab in patients with psoriasis has been established in randomised clinical trials. However, data on effectiveness and safety of secukinumab in Latin American real-world settings are scarce.
Objectives
To evaluate the effectiveness and safety of secukinumab in real-world settings in patients with psoriasis in Latin America.
Methods
PURE is an ongoing multinational, prospective, observational study in patients with moderate-to-severe chronic plaque psoriasis in Canada and Latin America assessing the real-world safety and effectiveness of secukinumab and other approved therapies. The study enrolled (1:1) patients treated with secukinumab versus other approved therapies (other Tx) per local standard of care from 81 community- and hospital-based speciality sites (21 in Latin America). Here, we report effectiveness and safety outcomes with secukinumab and other Tx for plaque psoriasis for up to 12 months in a Latin American population.
Results
Overall, 187 patients were included in the analysis, 89 of whom initiated secukinumab treatment and 98 of whom received other Tx. At month 12, 84.4%, 71.1% and 53.3% of patients treated with secukinumab achieved Psoriasis Area and Severity Index (PASI) 75/90/100, respectively, compared with 66.7%, 47.9% and 29.2% of patients who received other Tx. Investigator Global Assessment (IGA) 0/1 responders in secukinumab versus other Tx were 78.3% versus 36.7% at month 3 and 81.8% versus 66.7% at month 12, respectively. Overall, the proportion of patients achieving Dermatology Life Quality Index (DLQI) 0/1 improved from 6.9% at baseline to 76.5% at month 12 in patients treated with secukinumab versus 5.6% at baseline to 54.5% at month 12 in patients on other Tx. No unexpected adverse events were reported during the 12-month observation period.
Conclusion
Secukinumab demonstrated real-world effectiveness and improved dermatology quality-of-life in chronic plaque psoriasis patients from Latin America.
Trial Registration
PURE: NCT02786186.
Supplementary Information
The online version contains supplementary material available at 10.1007/s13555-022-00849-0.
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