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1.
Int J Mol Sci ; 24(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37047426

RESUMO

Metabolic adaptations are a hallmark of cancer and may be exploited to develop novel diagnostic and therapeutic tools. Only about 50% of the patients who undergo thyroidectomy due to suspicion of thyroid cancer actually have the disease, highlighting the diagnostic limitations of current tools. We explored the possibility of using non-invasive blood tests to accurately diagnose thyroid cancer. We analyzed blood and thyroid tissue samples from two independent cohorts of patients undergoing thyroidectomy at the Hospital Universitario 12 de Octubre (Madrid, Spain). As expected, histological comparisons of thyroid cancer and hyperplasia revealed higher proliferation and apoptotic rates and enhanced vascular alterations in the former. Notably, they also revealed increased levels of membrane-bound phosphorylated AKT, suggestive of enhanced glycolysis, and alterations in mitochondrial sub-cellular distribution. Both characteristics are common metabolic adaptations in primary tumors. These data together with reduced mtDNA copy number and elevated levels of the mitochondrial antioxidant PRX3 in cancer tissue samples suggest the presence of mitochondrial oxidative stress. In plasma, cancer patients showed higher levels of cfDNA and mtDNA. Of note, mtDNA plasma levels inversely correlated with those in the tissue, suggesting that higher death rates were linked to lower mtDNA copy number. In PBMCs, cancer patients showed higher levels of PGC-1α, a positive regulator of mitochondrial function, but this increase was not associated with a corresponding induction of its target genes, suggesting a reduced activity in cancer patients. We also observed a significant difference in the PRDX3/PFKFB3 correlation at the gene expression level, between carcinoma and hyperplasia patients, also indicative of increased systemic metabolic stress in cancer patients. The correlation of mtDNA levels in tissue and PBMCs further stressed the interconnection between systemic and tumor metabolism. Evaluation of the mitochondrial gene ND1 in plasma, PBMCs and tissue samples, suggested that it could be a good biomarker for systemic oxidative metabolism, with ND1/mtDNA ratio positively correlating in PBMCs and tissue samples. In contrast, ND4 evaluation would be informative of tumor development, with ND4/mtDNA ratio specifically altered in the tumor context. Taken together, our data suggest that metabolic dysregulation in thyroid cancer can be monitored accurately in blood samples and might be exploited for the accurate discrimination of cancer from hyperplasia.


Assuntos
Mitocôndrias , Neoplasias da Glândula Tireoide , Humanos , Hiperplasia/metabolismo , Mitocôndrias/genética , Mitocôndrias/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Glicólise
4.
J. coloproctol. (Rio J., Impr.) ; 41(4): 411-418, Out.-Dec. 2021. tab
Artigo em Inglês | LILACS | ID: biblio-1356428

RESUMO

Introduction: Transanal total mesorectal excision (TaTME) has revolutionized the surgical techniques for lower-third rectal cancer. The aim of the present study was to analyze the outcomes of quality indicators of TaTME for rectal cancer compared with laparoscopic TME (LaTME). Methods: A cohort prospective study with 50 (14 female and 36male) patients, with a mean age of 67 (range: 55.75 to 75.25) years, who underwent surgery for rectal cancer. In total, 20 patients underwent TaTME, and 30, LaTME. Every TaTME procedure was performed by experienced colorectal surgeons. The sample was divided into two groups (TaTME and LaTME), and the quality indicators of the surgery for rectal cancer were analyzed. Results: There were no statistically significant differences regarding the patients and the main characteristics of the tumor (age, gender, American Society of Anesthesiologists [ASA] score, body mass index [BMI], tumoral stage, neoadjuvant therapy, and distance from the tumor to the external anal margin) between the two groups. The rates of: postoperativemorbidity (TaTME: 35%; LaTME: 30%; p=0.763);mortality (0%); anastomotic leak (TaTME: 10%; LaTME: 13%; p=0.722); wound infection (TaTME: 0%; LaTME: 3.3%; p=0.409); reoperation (TaTME: 5%; LaTME: 6.6%; p=0.808); and readmission (TaTME: 5%; LaTME: 0%; p=0.400), as well as the length of the hospital stay (TaTME: 13.5 days; LaTME: 11 days; p=0.538), were similar in both groups. There were no statistically significant differences in the rates of positive circumferential resection margin (TaTME: 5%; LaTME: 3.3%; p=0.989) and positive distal resection margin (TaTME: 0%; LaTME: 3.3%; p=0.400), the completeness of the TME (TaTME: 100%; LaTME: 100%), and the number of lymph nodes harvested (TaTME: 15; LaTME: 15.5; p=0.882) between two groups. Conclusion: Transanal total mesorectal excision is a safe and feasible surgical procedure for middle/lower-third rectal cancer. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Retais/cirurgia , Resultado do Tratamento , Protectomia/métodos , Neoplasias Retais/terapia , Laparoscopia
5.
J. coloproctol. (Rio J., Impr.) ; 41(3): 257-264, July-Sept. 2021. tab
Artigo em Inglês | LILACS | ID: biblio-1346426

RESUMO

Introduction: The Covid-19 pandemic has had an important impact on colorectal cancer surgery, for hospital resources had to be redistributed in favour of Covid-19 patients. The aim of the present study is to analyze our results in colorectal oncologic surgery during the Covid-19 pandemic in patients with and without perioperative SARSCoV- 2 infection. Methods: In total, 32 patients (19 male and 13 female patients), with a mean age of 64 years (range: 57.2 to 69.5 years) with colorectal cancer underwent surgery under the recommendations of surgical societies included in a protocol. Data collection included clinical characteristics (gender, age, body mass index, American Society of Anesthesiologists score, tumor location, preoperative staging, lymphopenia), data related to SARS-CoV-2 infection (postoperative symptoms, diagnostic tests), operative details (surgical procedure, approach, duration, stoma), pathological outcomes (tumor stage, number of lymph nodes harvested, distal and circumferential radial margins, quality of the total mesorectal excision), and surgical outcomes (morbidity, mortality, hospital stay, and the rates of reoperation and readmission). Results: A total of 3 (9.4%) patients who underwent colorectal surgery during the Covid-19 pandemic were infected by SARS-CoV-2 in the postoperative period. Chronic obstructive pulmonary disease was associated with Covid-19 (6.2% versus 33.3%; p=0.042), and surgical morbidity was higher among Covid-19 patients (100% versus 37.9%; p=0.039). There were not significant differences between COVID-19 patients and non-COVID-19 patients in relation to the rest of the analyzed outcomes. Conclusion: During the Covid-19 pandemic, colorectal cancer surgery should be performed according to the recommendations of surgical societies. However, Covid- 19 patients could present a higher morbidity rate. (AU)


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/terapia , Resultado do Tratamento , COVID-19
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