Polymerase alpha components associate with telomeres to mediate overhang processing

Telomeres consist of TTAGGG repeats, which end with a 3\u27 G-overhang and are bound by a six-protein complex, known as Shelterin. In humans, telomeres shorten at each cell division, unless telomerase is expressed and able to add telomeric repeats to the 3\u27 G-overhang. However, for effective telomere maintenance, the DNA strand complementary to that made by telomerase must be synthesized. In this study, I focused on the Polα/primase complex, in particular the subunits p68 (POLA2, the regulatory subunit) and p180 (Polα, the catalytic subunit), and their potential roles at telomeres. I was able to detect p180, p68 and OBFC1, a subunit in the CST complex, at telomeres in S phase using chromatin immunoprecipitations. I could also show that OBFC1, Shelterin and Polα/primase interact, revealing contacts occurring at telomeres. Finally, depletion of p68 by shRNA and p68 and p180 by siRNA, led to increased overhang amounts at telomeres. I propose a model in which Polα-primase is important for proper telomeric overhang processing, perhaps through fill-in synthesis. These results shed light on important events necessary for efficient telomere maintenance and protection

Telomeric and Sub-Telomeric Structure and Implications in Fungal Opportunistic Pathogens

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity levels. In this review, telomere structure, as well as functional implications, will be examined in opportunistic fungal pathogens, including Aspergillus fumigatus, Candida albicans, Candida glabrata, and Pneumocystis jirovecii

Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis

BackgroundJCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer.MethodsWe reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size <20 mm; wedge resections or lobectomies with or without lymph node dissection; NSCLC as the only primary tumor during the follow-up period. We excluded: multiple invasive lung cancer; positive resection margin; preoperative evidence of nodal disease; distant metastasis at presentation; follow-up time <5 years. The reverse Kaplan – Meier method estimated the median OS and PFS and compared them by the log-rank test. The stratified backward stepwise Cox regression model was employed for multivariable survival analyses.Results539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 – 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23).ConclusionsLobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC <20 mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection

Telomeric and Sub-Telomeric Structure and Implications in Fungal Opportunistic Pathogens

Telomeres are long non-coding regions found at the ends of eukaryotic linear chromosomes. Although they have traditionally been associated with the protection of linear DNA ends to avoid gene losses during each round of DNA replication, recent studies have demonstrated that the role of these sequences and their adjacent regions go beyond just protecting chromosomal ends. Regions nearby to telomeric sequences have now been identified as having increased variability in the form of duplications and rearrangements that result in new functional abilities and biodiversity. Furthermore, unique fungal telomeric and chromatin structures have now extended clinical capabilities and understanding of pathogenicity levels. In this review, telomere structure, as well as functional implications, will be examined in opportunistic fungal pathogens, including Aspergillus fumigatus, Candida albicans, Candida glabrata, and Pneumocystis jirovecii

DataSheet_1_Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis.docx

BackgroundJCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer.MethodsWe reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size Results539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 – 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23).ConclusionsLobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC <20 mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection.</p

Image_1_Real-world survival outcomes of wedge resection versus lobectomy for cT1a/b cN0 cM0 non-small cell lung cancer: a single center retrospective analysis.jpeg

BackgroundJCOG0802/WJOG4607L showed benefits in overall survival (OS) of segmentectomy. CALGB 140503 confirmed that sublobar resection was not inferior to lobectomy concerning recurrence-free survival (RFS) but did not provide specific OS and RFS according to the techniques of sublobar resections. Hence, we retrospectively analyze the survival differences between wedge resection and lobectomies for stage IA lung cancer.MethodsWe reviewed the clinical records of patients with clinical stage IA NSCLC over 20 years. The inclusion criteria were: preoperative staging with CT scan and whole body CT/PET; tumor size Results539 patients were identified: 476 (88.3%) lobectomies and 63 (11.7%) wedge resections. The median OS time for the whole cohort was 189.7 months (range: 173.7 – 213.9 months). The 5-year wedge resection and lobectomy OS were 82.2% and 87.0%. The 5-year RFS of wedge resection and lobectomy were 17.8% and 28.9%. The log-rank test showed no significant differences (p = 0.39) between wedge resections and lobectomies regarding OS and RFS (p = 0.23).ConclusionsLobectomy and wedge resection are equivalent oncologic treatments for individuals with cN0/cM0 stage IA NSCLC <20 mm. Validating the current findings requires a prospective, randomized comparison between wedge resection and standard lobectomy to establish the prognostic significance of wedge resection.</p