Rami Shoukrun

Despite the widespread utilization of Patient-Derived Xenografts (PDXs) as preclinical platforms in lung cancer research, there are concerns regarding their capability to accurately represent the tumor's clinical and molecular features across sequential passages. In this study, we established a Non-Small Cell Lung Cancer (NSCLC) PDX model in NSG-SGM3 mice and assessed clinical and preclinical factors throughout subsequent passages. Our cohort consisted of 40 NSCLC patients, which were used to successfully create 20 patient-specific PDX models in NSG-SGM3 mice. We found that the main factors that contributed to the growth of the engrafted PDX in mice were a higher grade or stage of disease, in contrast to a long duration of chemotherapy treatment which was negatively correlated with PDX propagation. Successful PDX growth was also linked to poorer prognosis and overall survival, while growth pattern variability was affected by the tumor's aggressiveness, primarily affecting the first passage. Pathology analysis showed preservation of histological type and grade; however, Whole Exome Sequence (WES) analysis revealed genomic instability in advanced passages, leading to the inconsistency of clinically relevant alterations between PDXs and biopsies. Multiple clinical and preclinical factors affect the engraftment success, growth kinetics, and tumor stability of patient-specific NSCLC PDXs; thus, their use for prolonged treatment evaluation studies remains questionable.

Background: The incidence of thyroid nodules is increasing among patients in North America. Few of these nodules harbour malignancy, thus further research is required to identify predictive markers of malignant thyroid disease. This study set out to understand the relationship between the levels of fT4 and fT3 and differentiated thyroid cancer. Methods: A case-control study was conducted with 142 cases and 86 controls from the McGill University Teaching Hospitals. All patients underwent thyroid surgery. Cases were defined as patients with malignant nodules confirmed on final pathology and controls were defined as patients with benign nodules. The serological levels of TSH, fT4 and fT3 were measured preoperatively. Odds ratios were determined for each parameter and logistic regressions were calculated between markers and probability of malignancy. Additionally, fT4 values were divided by fT3 values (fT4/fT3 quotient) for each patient and an odds ratio was calculated. Results: Amongst cases, the mean TSH was 2.25 ± 0.360U/mL, fT4 was 14.8 ± 0.689pmol/L, and fT3 was 4.65 ± 0.463pmol/L. Amongst controls, the mean TSH was 2.36 ± 1.68U/mL, fT4 was 14.3 ± 1.71pmol/L, and fT3 was 5.27 ± 0.957pmol/L. Patients in the control group were more likely to have low TSH, while patients in the case group would have high fT4 and patients in the control group were more likely to have a low fT4. The OR for patients with TSH >4.4U/mL was 2.13 (0.97, 4.65), and for patients with TSH 16pmol/L was 2.10 (1.09, 4.06), and for patients with fT4 < 10pmol/L was 0.45 (0.20, 0.98). The OR for patients with fT3 > 5.5pmol/L was 0.39 (0.14, 1.28). The OR for patients with fT3 < 3pmol/L was 1.83 (0.25, 13.69). The average fT4/fT3 was 3.39 ± 0.206 for cases and 2.93 ± 0.467 for controls. The fT4/fT3 quotient was considered high if it was >3.3 (OR =6.00 (2.94, 12.25)). Conclusion: In this study, a direct relationship between high levels of fT4 and malignancy was uncovered. Furthermore, low levels of TSH and fT4 increased the likelihood that a nodule was benign. In this study a fT4/fT3 ratio >3.3 increased the risk of malignancy by 3.6 times ( p-value =0.0013).