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2.
Cureus ; 15(8): e43248, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37692620

RESUMEN

Introduction The association of acute appendicitis with caecal or colorectal cancer is known. One of the proposed theories for acute appendicitis is luminal blockage by mass at the base of the appendix. There have been no national recommendations or guidelines for follow-up with patients aged 40 and older after an emergency appendicectomy. The purpose of this study was to evaluate the prevalence of caecal and colonic cancer or polyps in patients over the age of 40 who have undergone an appendicectomy. This shall enable us to develop the necessary strategies to investigate and diagnose associated caecal and colonic pathology in acute appendicitis to prevent delayed diagnosis of colon cancer. Methods All patients who underwent appendicectomy between October 2011 and October 31, 2021, and who were 40 years of age or older were included in this retrospective cohort study. Patients aged 40 to 54 years old and patients 55 years or older underwent subgroup analyses. We looked at any investigations of the colon (CT pneumocolon or colonoscopy) within three years before the appendicectomy or three years after an appendicectomy. All colorectal cancers diagnosed within five years of the index episode of appendicitis were included in the analysis. Results A total of 1076 appendicectomies were performed on patients aged 40 and older during the study period of 10 years. A total of 769 patients were confirmed to have appendicitis on histology. One hundred and fifty-seven patients had colonic investigations within three years of the diagnosis of acute appendicitis. In our study, 51 of the 769 patients (6.63%) were found to have colorectal neoplasms. Eight patients (8/769, 1.04%) were diagnosed with colorectal cancers, and the occurrence of caecal cancer was 0.26% (2/769). The mortality rate was 75% (6/8) in these patients diagnosed with colorectal cancer. Four out of six died due to advanced metastatic colonic cancer. In comparison to patients aged 40 to 54, patients over the age of 55 had a statistically significant increased risk of caecal pathology (polyp and cancer) (p = 0.07). Conclusion There seems to be an increased risk of significant colorectal neoplasm in patients over the age of 55 who are admitted with acute appendicitis, and there appears to be an increased severity with a poor prognosis of cancer in these individuals. We recommend the use of routine colonoscopy or CT pneumocolon, particularly for those over the age of 55 who present with acute appendicitis or the histology of appendicular neoplasms.

3.
J Med Chem ; 59(19): 8924-8940, 2016 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-27592633

RESUMEN

Sulfonic acid analogues of 4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2-naphthyl)ethynyl]benzoic acid (bexarotene, 1) as well as seven novel and two reported analogues of 6-(ethyl(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalen-2-yl)amino)nicotinic acid (NEt-TMN) were synthesized and assessed for selective retinoid X receptor (RXR) agonism. Compound 1 is FDA-approved for treatment of cutaneous T-cell lymphoma (CTCL); however, 1 can provoke side effects by impacting RXR-dependent receptor pathways. All of the analogues in this study were evaluated for their potential to bind RXR through modeling and then assayed in an RXR-RXR mammalian-2-hybrid (M2H) system and in RXR-responsive element (RXRE)-mediated transcriptional experiments. The EC50 profiles for these unique analogues and their analogous effectiveness to inhibit proliferation in CTCL cells relative to 1 suggest that these compounds possess similar or even enhanced therapeutic potential. Several compounds also displayed more selective RXR activation with minimal cross-signaling of the retinoic acid receptor. These results suggest that modifications of potent RXR agonists such as NEt-TMN can lead to improved biological selectivity and potency compared with the known therapeutic.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/farmacología , Receptores X Retinoide/agonistas , Tetrahidronaftalenos/química , Tetrahidronaftalenos/farmacología , Bexaroteno , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células HEK293 , Histona Desacetilasa 1/genética , Humanos , Linfoma Cutáneo de Células T/tratamiento farmacológico , Linfoma Cutáneo de Células T/genética , Linfoma Cutáneo de Células T/metabolismo , Modelos Moleculares , Niacina/análogos & derivados , Niacina/farmacología , Receptores X Retinoide/metabolismo , Proteínas de Unión a los Elementos Reguladores de Esteroles/genética
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