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1.
Arch Pathol Lab Med ; 138(7): 896-902, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24978915

RESUMO

CONTEXT: Pancreatic neuroendocrine tumors (Panc-NETs) are rare and tend to get overshadowed by their more prevalent and aggressive ductal adenocarcinoma counterparts. The biological behavior of PancNETs is unpredictable, and thus management is controversial. However, the new World Health Organization classification has significantly contributed to the prognostic stratification of these patients. Concurrently, there have been advances in surgical techniques for benign or low-grade pancreatic tumors. These procedures include minimally invasive and parenchyma-sparing operations such as laparoscopy and enucleation. OBJECTIVE: To report on the utility and limitations of fine-needle aspiration in the preoperative evaluation and management of PancNETs. DESIGN: This was a retrospective review of our institutional tumor database from 2002 to 2012. There were 25 cases of PancNETs that were localized and staged by medical imaging and diagnosed by fine-needle aspiration. RESULTS: Fourteen patients underwent laparotomy, with some requiring only limited surgery; 4 had laparoscopic resections; 4 were serially observed without surgical intervention; and another 3 were inoperable. After a mean follow-up of 37 months, more than half of the patients had no evidence of disease, including most of those who underwent minimally invasive surgery. CONCLUSIONS: Fine-needle aspiration is a useful diagnostic adjunct to medical imaging in the preoperative evaluation and management of PancNETs. However, there are limitations with regard to grading PancNETs using this technique.


Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Laparoscopia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/classificação , Pancreatectomia , Neoplasias Pancreáticas/classificação , Pancreaticoduodenectomia , Estudos Retrospectivos , Esplenectomia , Organização Mundial da Saúde
2.
Anticancer Res ; 28(4B): 2175-80, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18751392

RESUMO

BACKGROUND: 5-Fluorouracil (5-FU) is an antineoplastic drug that targets thymidylate synthase (TS). Tumour cells can develop resistance to anti-TS drugs by a variety of mechanisms including up-regulation of TS protein and alterations in drug uptake and degradation. The possible mechanisms of the observed rapid development of resistance to the pyrimidine analogs 5-FUdR and 5-FU in cultured HCT116 colon cancer cells were investigated. MATERIALS AND METHODS: Cell survival was determined in resistant and control HCT116 cells treated with 5-FUdR and 5-FU for 7 days. The ability of the cells to take up and metabolize these drugs was determined by Western blotting and [3H]thymidine incorporation. RESULTS AND CONCLUSION: Resistant HCT116 cells were 5- and 100-fold more resistant to killing by 5-FU and 5-FUdR, respectively, than the parental cells and exhibited impaired uptake. Although the HCT116R cells were initially Mycoplasma free, a low level of Mycoplasma contamination was found in these cells after several weeks in culture. Sensitivity to 5-FUdR was restored by treatment with an anti-Mycoplasma antibiotic. Our observations emphasize the need for frequent testing for Mycoplasma contamination in any cell line under investigation for resistance to anti-TS drugs.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/microbiologia , Floxuridina/farmacologia , Fluoruracila/farmacologia , Infecções por Mycoplasma/metabolismo , Aminopterina/metabolismo , Aminopterina/farmacologia , Neoplasias Colorretais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Células HCT116 , Células HT29 , Células HeLa , Humanos , Hipoxantina/metabolismo , Hipoxantina/farmacologia , Infecções por Mycoplasma/tratamento farmacológico , Timidina/metabolismo , Timidina/farmacologia , Timidina Quinase/metabolismo , Timidilato Sintase/antagonistas & inibidores , Timidilato Sintase/metabolismo , Trítio
3.
J Histochem Cytochem ; 54(1): 19-29, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15956025

RESUMO

Thymidylate synthase (TS) [TYMS; OMIM reference number (188,350)] is normally considered to be a cytoplasmic enzyme. However, a few reports have suggested it may also be present in the nucleus. To explore this in more detail, we used a highly specific polyclonal antibody to TS and a combination of techniques, including immunocytochemistry, confocal microscopy, cell fractionation, and Western blotting. We developed cell line HeLa-55, a HeLa derivative that grossly overexpresses TS. Although the vast majority of TS was in the cytoplasm, some TS also was seen in the nucleus. TS in parental HeLa cells and in normal human fibroblasts was seen exclusively in the cytoplasm. HeLa-55 cells exposed to 5-fluorodeoxyuridine were fractionated and examined by Western blotting. Interestingly, both free TS and the ternary complex of TS were seen in the cytoplasmic fraction but only free TS was detected in the nuclear fraction. Amongst different cell lines examined, HCT-15 and normal fibroblasts showed no nuclear TS, HCC-2998 and SW-620 showed a small amount of nuclear TS, and HT-29, RKO, and HCT-116 showed a strong nuclear TS signal. Nuclear staining was clearly evident in some clinical colorectal specimens, both normal and malignant. This staining was definitively shown to be TS by competition with recombinant TS protein. A putative leucine-rich nuclear export sequence was identified but its function could not be confirmed. We conclude that small amounts of TS protein is present in the nucleus of some cell types but further work is needed to determine the significance of this observation.


Assuntos
Núcleo Celular/enzimologia , Neoplasias Colorretais/enzimologia , Timidilato Sintase/biossíntese , Transporte Ativo do Núcleo Celular , Especificidade de Anticorpos , Fracionamento Celular , Linhagem Celular Tumoral , Fibroblastos/enzimologia , Humanos , Soros Imunes , Imuno-Histoquímica , Microscopia Confocal , Timidilato Sintase/genética
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