1,720,967 research outputs found
Analysis and Characterization of Mitochondrial DNA Mutations in The Cancer Genome Atlas Hepatocellular Carcinoma Cohort
Full text linkHepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and represents the second cause of cancer related death worldwide, characterized by high recurrence rates and poor survival, even when detected and treated at its early stages.
Mitochondrial mutations have been known to play a role in carcinogenesis, but to date, few studies correctly prioritize and interpret the variants discovered. Thus, we aimed to identify and analyze the occurrence and clinical impact of mtDNA mutations in the HCC dataset from The Cancer Genome Atlas (TCGA) consortium - National Cancer Institute.
Whole exome sequencing fastq files from 377 TCGA-HCC patients (paired tumor, non- tumor tissues) were processed to reconstruct the mtDNA genomes using the MToolBox automated pipeline. Pairwise comparison between blood/normal solid tissue and tumor was performed in order to identify the potentially germline and tumor-specific somatic mtDNA variants. Information regarding the variability and pathogenicity of the variants were obtained from HmtVar database.
The assembly of the mitochondrial reads showed an adequate coverage and quality for 104 patients. Variants were classified as pathogenic based on the allele frequency and disease score using the HmtVar criteria. After discarding the germline variants used in haplogroup classification, fixing the heteroplasmic fraction (HF) at 0.4 and prioritizing the variants we found 13 pathogenic/likely-pathogenic missense mutations and three tRNA pathogenic mutations in tRNA genes. HCC tumors presented a total of 302 somatic variants. After applying the same criteria, we found 24 pathogenic mutations in 22 patients. The burden of pathogenic mtDNA mutations resulted associated with a poorer survival of these patients.
We found 21% of HCC patients to harbor somatic pathogenic mtDNA mutations in their tumors. We found that these patients had a poorer survival than those harbouring non-pathogenic variants. mtDNA mutations could cause mitochondrial dysfunction and impact the prognosis and survival of HCC patients
Primary or Interval Debulking Surgery for Advanced Endometrial Cancer with Carcinosis: A Systematic Review and Individual Patient Data Meta-Analysis of Survival Outcomes
Full text linkObjective: To compare the survival outcomes of primary debulking surgery and platinum-based adjuvant chemotherapy versus interval debulking surgery after platinum-based neoadjuvant chemotherapy in patients with stage IVb endometrial cancer and peritoneal carcinosis. Methods: The online search included the following data sources: PubMed, Scopus, WOS, and the Cochrane Library from 1990 to 2024 (PROSPERO registration code: CRD42023438602). A total of 3230 studies were identified, with the inclusion of 16. Individual patient data on survival outcomes, disease distribution, and residual tumors, as well as details of neoadjuvant chemotherapy and adjuvant treatment, were extracted. Results: A total of 285 patients were included: 197 (69%) underwent primary debulking surgery and 88 (31%) underwent interval debulking surgery. The pooled analysis revealed a median progression-free survival in the primary debulking surgery group of 18.0 months compared to 12.0 months in the interval debulking surgery group (p = 0.028; log-rank test), and a median overall survival of 30.92 months versus 28.73 months (p = 0.400; log-rank test). Among the 134 patients with available information on the residual tumor after primary debulking surgery or interval debulking surgery, 110 (82%) had no macroscopic residual tumor (residual tumor = 0). The median progression-free survival was 18.9 months in the residual tumor = 0 group compared to 6.19 months in the residual tumor > 0 group (p < 0.001; log-rank test); the median overall survival was 40.6 months versus 21 months (p = 0.028; log-rank test). Conclusions: These results indicate that primary debulking surgery should be considered the preferred treatment approach for advanced endometrial cancer with carcinosis, especially in carefully selected patients where complete cytoreduction is achievable. Further prospective studies are warranted to confirm these results and to establish standardized criteria for patient selection, incorporating molecular-integrated risk profiles for endometrial cancer
Post-operative residual disease and number of cycles of neoadjuvant chemotherapy in advanced epithelial ovarian carcinoma
Full text linkBackgroundThe optimal number of neoadjuvant chemotherapy cycles in patients with advanced ovarian cancer is still disputed. ObjectiveTo evaluate the impact of the number of neoadjuvant chemotherapy cycles and role of optimal cytoreduction on the prognosis of patients with advanced ovarian cancer. MethodsClinical and pathological details were examined. Patients were evaluated combining the number of cycles of neoadjuvant chemotherapy-namely, 'interval debulking surgery' after up to four neoadjuvant chemotherapy cycles, and 'delayed debulking surgery' after more than four cycles of therapy. ResultsA total of 286 patients were included in the study. Complete cytoreduction with no residual peritoneal disease (CC0) was achieved in 74 (74%) patients with interval debulking surgery and 124 (66.7%) patients with delayed interval debulking. Of those with residual disease, there were 26/88 (29.5%) patients in the interval debulking surgery group and 62/88 (70.5%) patients in the delayed debulking surgery group. Comparison of patients with delayed debulking-CC0 and interval debulking-CC0 showed no difference in progression-free survival (p=0.3) or overall survival (p=0.4), while significantly worse outcomes were observed in patients with interval debulking-CC1 (p=0.02 and p=0.04, respectively). Specifically, patients with interval debulking-CC1 had an approximately 67% increased risk of disease progression (p=0.04; HR=2.01 (95% CI 1.04 to 4.18)) and a 69% higher risk of death than patients with delayed debulking-CC0 (p=0.03; HR=2.34 (95% CI 1.11 to 4.67)). ConclusionIncreasing the number of neoadjuvant chemotherapy cycles does not worsen patient outcomes if complete resection is achieved. Nevertheless, additional prospective trials are necessary to establish the optimum number of neoadjuvant chemotherapy cycles
miRNA levels are associated with body mass index in endometrial cancer and may have implications for therapy
Full text linkEndometrial cancer (EC) is the most prevalent gynecological cancer in high-income countries. Its incidence is skyrocketing due to the increase in risk factors such as obesity, which represents a true pandemic. This study aimed to evaluate microRNA (miRNA) expression in obesity-related EC to identify potential associations between this specific cancer type and obesity. miRNA levels were analyzed in 84 EC patients stratified based on body mass index (BMI; >= 30 or <30) and nine noncancer women with obesity. The data were further tested in The Cancer Genome Atlas (TCGA) cohort, including 384 EC patients, 235 with BMI >= 30 and 149 with BMI <30. Prediction of miRNA targets and analysis of their expression were also performed to identify the potential epigenetic networks involved in obesity modulation. In the EC cohort, BMI >= 30 was significantly associated with 11 deregulated miRNAs. The topmost deregulated miRNAs were first analyzed in 84 EC samples by single miRNA assay and then tested in the TCGA dataset. This independent validation provided further confirmation about the significant difference of three miRNAs (miR-199a-5p, miR-449a, miR-449b-5p) in normal-weight EC patients versus EC patients with obesity, resulting significantly higher expressed in the latter. Moreover, the three miRNAs were significantly correlated with grade, histological type, and overall survival. Analysis of their target genes revealed that these miRNAs may regulate obesity-related pathways. In conclusion, we identified specific miRNAs associated with BMI that are potentially involved in modulating obesity-related pathways and that may provide novel implications for the clinical management of obese EC patients
Mir-30e-3p/CXCL3 axis is involved in sorafenib resistance of hepatocellular carcinoma through the modulation of the tumor immune microenvironment
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
