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Phototherapies are promising for noninvasive treatment of aggressive tumors, especially when combining heat induction and oxidative processes. Herein, we show enhanced phototoxicity of gold shell-isolated nanorods conjugated with toluidine blue-O (AuSHINRs@TBO) against human colorectal tumor cells (Caco-2) with synergic effects of photothermal (PTT) and photodynamic therapies (PDT). Mitochondrial metabolic activity tests (MTT) performed on Caco-2 cell cultures indicated a photothermal effect from AuSHINRs owing to enhanced light absorption from the localized surface plasmon resonance (LSPR). The phototoxicity against Caco-2 cells was further increased with AuSHINRs@TBO where oxidative processes, such as hydroperoxidation, were also present, leading to a cell viability reduction from 85.5 to 39.0%. The molecular-level mechanisms responsible for these effects were investigated on bioinspired tumor membranes using Langmuir monolayers of Caco-2 lipid extract. Polarization-modulation infrared reflection-absorption spectroscopy (PM-IRRAS) revealed that the AuSHINRs@TBO incorporation is due to attractive electrostatic interactions with negatively charged groups of the Caco-2 lipid extract, resulting in the expansion of surface pressure isotherms. Upon irradiation, Caco-2 lipid extract monolayers containing AuSHINRs@TBO (1:1 v/v) exhibited ca. 1.0% increase in surface area. This is attributed to the generation of reactive oxygen species (ROS) and their interaction with Caco-2 lipid extract monolayers, leading to hydroperoxide formation. The oxidative effects are facilitated by AuSHINRs@TBO penetration into the polar groups of the extract, allowing oxidative reactions with carbon chain unsaturations. These mechanisms are consistent with findings from confocal fluorescence microscopy, where the Caco-2 plasma membrane was the primary site of the cell death induction process.
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AIM: Assess biocompatibility, uptake and photodynamic therapy (PDT) mechanism of metallated porphyrin doped conjugated polymer nanoparticles (CPNs) in human brain and colorectal tumor cells and macrophages. MATERIALS & METHODS: CPNs were developed employing 9,9-dioctylfluorene-alt-benzothiadiazole, an amphiphilic polymer (PS-PEG-COOH), and platinum octaethylporphyrin. T98G, SW480 and RAW 264.7 cell lines were exposed to CPNs to assess uptake and intracellular localization. Additionally, a PDT protocol using CPNs was employed for the in vitro killing of cancer and macrophage cell lines. RESULTS & CONCLUSION: CPNs were well incorporated into glioblastoma and macrophage cells with localization in lysosomes. SW480 cells were less efficient incorporating CPNs with localization in the plasma membrane. In all cell lines PDT treatment was efficient inducing oxidative stress that triggered apoptosis.
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Neoplasias Colorretais/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Porfirinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/patologia , Humanos , Macrófagos/efeitos dos fármacos , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Polímeros/química , Poliestirenos/química , Poliestirenos/farmacologia , Porfirinas/química , Células RAW 264.7RESUMO
PURPOSE: Annexin-A1 (ANXA1) has been implicated in various tumor types, but few studies have investigated its involvement in colorectal cancer. The study aimed to analyze ANXA1 expression in the normal margin and colorectal tumor tissues of 104 patients who underwent surgery for colorectal cancer and to associate the ANXA1 expression with predictive clinicopathological variables. METHODS: Hematoxylin-eosin and immunohistochemical staining were used for the analysis. RESULTS: ANXA1 expression was higher in colorectal cancer than in normal margin tissue (p = 0.0001). However, no differences were observed when we analyzed the ANXA1 expression in colon and rectal tumors (p = 0.830). Also, this protein positivity was associated with increased carcinoembryonic antigen levels (p = 0.004). Our data in the DNA-mismatch repair proteins expression was in accordance to the literature. And their positivity was not associated with ANXA1 presence in colorectal cancer. CONCLUSION: The high incidence of ANXA1 positive expression in colorectal cancer and its association with carcinoembryonic antigen levels might indicate the importance of this protein in the colorectal cancer biology.
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Anexina A1/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , Neoplasias Colorretais/metabolismo , Enzimas Reparadoras do DNA/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida , Análise Serial de Tecidos , Adulto JovemRESUMO
OBJECTIVE: Endoscopic submucosal dissection is a technique developed in Japan for en bloc resection with a lower rate of recurrence. It is considered technically difficult and performed only in specialized centers. This study sought to report the initial experience from the Gastrocentro - Campinas State University for the treatment of gastric and colorectal lesions by endoscopic submucosal dissection. MATERIALS AND METHODS: The guidelines of the Japanese Association of Gastric Cancer were used as evaluative criteria. For colorectal lesions, the recommended standards proposed by Uraoka et al. and Saito et al. were employed. The practicability of the method, the development of complications and histological analysis of the specimens were evaluated. RESULTS: Sixteen patients underwent endoscopic submucosal dissection from June 2010 to April 2011; nine patients were treated for gastric lesions, and seven were treated for colorectal lesions. The average diameter of the gastric lesions was 28.6 mm, and the duration of resection was 103 min without complications. All lesions presented lesion-free margins. Of the seven colorectal tumors, four were located in the rectum and three were located in the colon. The average size was 26 mm, and the average procedure time was 163 min. Two complications occurred during the rectal resection procedures: perforation, which was treated with an endoscopic clip, and controlled bleeding. One of the lesions presented a compromised lateral margin without relapse after 90 days. Depth margins were all free of lesions. CONCLUSION: Endoscopic submucosal dissection at our institution achieved high success rates, with few complications in preliminary procedures. The procedure also made appropriate lesion staging possible.
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Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias do Colo/cirurgia , Dissecação/métodos , Mucosa Gástrica/cirurgia , Hospitais Especializados , Mucosa Intestinal/cirurgia , Neoplasias Retais/cirurgia , Neoplasias Gástricas/cirurgia , Biópsia , Brasil , Neoplasias do Colo/patologia , Estudos de Viabilidade , Mucosa Gástrica/lesões , Mucosa Gástrica/patologia , Mucosa Intestinal/lesões , Mucosa Intestinal/patologia , Reprodutibilidade dos Testes , Neoplasias Retais/patologia , Resultado do TratamentoRESUMO
We determined the effect of fish oil (FO) ingestion on colonic carcinogenesis in rats. Male Wistar rats received 4 subcutaneous injections (40 mg/kg body weight each) of 1,2-dimethylhydrazine (DMH) at 3-day intervals and were fed a diet containing 18 percent by weight FO (N = 10) or soybean oil (SO, N = 10) for 36 weeks. At sacrifice, the colon was removed, aberrant crypt foci were counted and the fatty acid profile was determined. Intestinal tumors were removed and classified as adenoma or carcinoma. Liver and feces were collected and analyzed for fatty acid profile. FO reduced the mean (± SEM) number of aberrant crypt foci compared to SO (113.55 ± 6.97 vs 214.60 ± 18.61; P < 0.05) and the incidence of adenoma (FO: 20 percent vs SO: 100 percent), but carcinoma occurred equally in FO and SO rats (2 animals per group). The polyunsaturated fatty acid (PUFA) profile of the colon was affected by diet (P < 0.05): total ù-3 (FO: 8.18 ± 0.97 vs SO: 1.71 ± 0.54 percent) and total ù-6 (FO: 3.83 ± 0.59 vs SO: 10.43 ± 1.28 percent). The same occurred in the liver (P < 0.05): total ù-3 (FO: 34.41 ± 2.6 vs SO: 6.46 ± 0.59 percent) and total ù-6 (FO: 8.73 ± 1.37 vs SO: 42.12 ± 2.33 percent). The PUFA profile of the feces and liver polyamine levels did not differ between groups (P > 0.05). In conclusion, our findings indicate that chronic FO ingestion protected against the DMH-induced preneoplastic colon lesions and adenoma development, but not against carcinoma in rats.