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1.
Helicobacter ; 29(1): e13061, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38411303

RESUMO

BACKGROUND: Helicobacter pylori (H. pylori) is strongly associated with peptic ulcer disease and gastric cancer. We evaluated two triple therapy regimens comprising esomeprazole, high dose bismuth, and different doses of amoxicillin for first-line H. pylori eradication. MATERIALS AND METHODS: Two hundred patients with dyspepsia and naive H. pylori infection were randomly assigned into two groups (n = 100). Both groups were treated for 14 days similarly with esomeprazole (40 mg, twice daily) and bismuth subcitrate (240 mg, three times daily), but the dose of amoxicillin was varied between Groups A (750 mg) and B (1000 mg) three times daily. Treatment compliance and side effect were evaluated following the therapies and after 8 weeks, a negative test of stool H. pylori antigen confirmed eradication. RESULTS: The two groups were comparable with respect to sex and age. According to intention to treat analysis, eradication rates were 80% (95% CI: 77.2%-82.8%) and 90% (95% CI: 84.1%-95.9%) in A and B groups, respectively (p = 0.22). Per-protocol eradication rates were 87% (95% CI: 80.4%-93.6%) and 92.8% (95% CI: 87.7%-97.9%), respectively (p = 0.23). Severe adverse effects were 3% and 2%, respectively (p = 0.34). CONCLUSION: High dose esomeprazole, amoxicillin and bismuth achieved 92.8% cure rates per protocol in a country with a high background rate of resistance. Additional studies are needed to ascertain whether this therapy can be further improved. Until then, it can be recommended as a first-line H. pylori eradication in north of Iran.


Assuntos
Amoxicilina , Esomeprazol , Infecções por Helicobacter , Helicobacter pylori , Compostos Organometálicos , Humanos , Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Esomeprazol/administração & dosagem , Infecções por Helicobacter/tratamento farmacológico , Irã (Geográfico) , Compostos Organometálicos/administração & dosagem , Projetos Piloto , Masculino , Feminino
2.
Pan Afr Med J ; 40: 43, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795824

RESUMO

INTRODUCTION: an adequate bowel preparation is essential for good mucosal inspection during colonoscopy. This study aims to compare the efficacy of two validated oral lavage solutions for colonoscopy preparation in African patients. METHODS: a prospective observational study of patients undergoing colonoscopy in a referral endoscopy facility in Port Harcourt, Nigeria, using sodium picosulfate magnesium citrate (SPMC) and 4L split-dose polyethylene glycol (PEG). Variables collated were sociodemographic, primary indication, comorbidities, Aronchick bowel preparation scale, polyp/adenoma detection, caecal intubation and outcome. Statistical analysis was performed using IBM SPSS version 20. RESULTS: one hundred and twenty-four patients received PEG prior to colonoscopy and SPMC in 175 patients. The age range was from 22 to 92 years; mean age of 53.8 ± 14.2 years for PEG group and 55.3 ± 13.2 years for SPMC group (p=0.361). There were 215 males and 84 females. An excellent/good bowel preparation scale was recorded in 77 (62%) PEG group and 130 (74.3%) for SPMC group (p=0.592). PEG was predominantly used in the early years of endoscopists practice with the odds ratio (OR) of no polyp detection in the PEG vs SPMC groups as 1.64 (confidence interval CI 1.06-2.55) versus 0.76 (CI 0.62-0.92), respectively (p=0.016). For no adenoma detection, OR was 4.18 (CI 1.12-15.60) versus OR 0.63 (CI 0.52-0.75), respectively (p=0.012). CONCLUSION: there is similar efficacy profile using either split volume PEG or SPMC prior to colonoscopy in these African patients. Polyp and adenoma detection rates are highly dependent on the expertise of the endoscopist.


Assuntos
Catárticos/administração & dosagem , Citratos/administração & dosagem , Colonoscopia/métodos , Compostos Organometálicos/administração & dosagem , Picolinas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Adenoma/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Colo/diagnóstico , Pólipos do Colo/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nigéria , Estudos Prospectivos , Adulto Jovem
3.
Sci Rep ; 11(1): 19440, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593876

RESUMO

To quantify the urinary bladder wall T1 relaxation time (T1) before and after the instillation contrast mixture in rats previously subjected to water avoidance stress (WAS) and/or acute exposure to protamine sulfate (PS). Female Wistar rats were randomized to receive either sham (control) or 1 h of WAS for ten consecutive days before the evaluation of nocturnal urination pattern in metabolic cages. T1 mapping of urinary bladder wall at 9.4 T was performed pre- and post- instillation of 4 mM Gadobutrol in a mixture with 5 mM Ferumoxytol. Subsequently, either T1 mapping was repeated after brief intravesical PS exposure or the animals were sacrificed for histology and analyzing the mucosal levels of mRNA. Compared to the control group, WAS exposure decreased the single void urine volume and shortened the post-contrast T1 relaxation time of mucosa- used to compute relatively higher ingress of instilled Gadobutrol. Compromised permeability in WAS group was corroborated by the urothelial denudation, edema and ZO-1 downregulation. PS exposure doubled the baseline ingress of Gadobutrol in both groups. These findings confirm that psychological stress compromises the paracellular permeability of bladder mucosa and its non-invasive assay with MRI was validated by PS exposure.


Assuntos
Cistite Intersticial/fisiopatologia , Bexiga Urinária/diagnóstico por imagem , Urotélio/patologia , Administração Intravesical , Animais , Cistite Intersticial/diagnóstico por imagem , Modelos Animais de Doenças , Feminino , Imageamento por Ressonância Magnética , Mucosa , Compostos Organometálicos/administração & dosagem , Permeabilidade , Protaminas/farmacologia , Ratos Wistar , Estresse Psicológico
4.
Eur Rev Med Pharmacol Sci ; 25(14): 4829-4834, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34337731

RESUMO

OBJECTIVE: Radiolabeled bisphosphonates have found wide clinical use in nuclear medicine for palliative therapy of bone metastases. 177Lu-EDTMP was used to relieve metastatic bone pain in patients with breast or prostate cancer. The therapeutic efficacy of 177Lu-EDTMP at 1-, 3-, 6-, and 8-weeks post-therapy was evaluated using Standard Pain Scoring Assessment Criteria. In addition, toxicity was evaluated in terms of hematological parameters using the Common Terminology Criteria for Adverse Events V4.0. PATIENTS AND METHODS: A fully automated synthesis of 177Lu-EDTMP was achieved in this study with high radiochemical efficiency and high radiochemical purity. During the study, 75 patients (57 M: 18 F, mean age: 68.0 ± 11.1 years) of breast/prostate cancer with documented skeletal metastases were included. Patients were administered intravenously with 177Lu-EDTMP at a dose rate of 22.2-37.0 MBq/kg following a fully automated synthesis of 177Lu-EDTMP using a disposable cassette system. RESULTS: Among the 75 patients all treated with 177Lu-EDTMP, 59 patients were responsive and the remaining 16 patients did not respond to the therapy. Mean pain score values in the responder group were 5.60 ± 0.5, 4.3 ± 0.1, 2.6 ± 0.4 and 1.4 ± 0.7 at weeks 1, 3, 6, and 8, respectively. Also, the mean pain score decreased from a baseline score of 7.6 ± 1.6 to 1.4 ± 0.7 at week 8 in the responder group. Statistical analysis of the pain score data showed a significant decrease in pain score after each radiopharmaceutical treatment, compared to the baseline scores (p <0.0001). Mild to severe toxicity was observed in two patients each treated with 177Lu-EDTMP. CONCLUSIONS: These findings demonstrated that the 177Lu-EDTMP radiopharmaceutical could be used safely to achieve considerable therapeutic efficacy, in metastatic bone pain palliation together with the safe clinical application and low radiation exposure during preparation.


Assuntos
Automação , Neoplasias Ósseas/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Dor/tratamento farmacológico , Compostos Radiofarmacêuticos/uso terapêutico , Idoso , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Feminino , Humanos , Injeções Intravenosas , Lutécio , Masculino , Estrutura Molecular , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Dor/patologia , Manejo da Dor , Radioisótopos , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química
5.
Br J Radiol ; 94(1126): 20210403, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34357794

RESUMO

OBJECTIVE: The aim of the present study was to perform calculation of the absorbed doses to organs at risk and to neuroendocrine tumors and to determine whether hepatic intra-arterial (IA) injection of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) would achieve higher intratumoral concentrations than standard intravenous administration of 177Lu-DOTATATE. METHODS: 29 patients with Grade I-II, inoperable, metastatic gastro-entero-pancreatic neuroendocrine tumor (GEPNET) were prospectively identified and enrolled for the study. 15 patients of GEPNETs with liver-dominant metastatic disease and less than 3 sites of extrahepatic metastatic disease were administered a single dose of 177Lu-DOTATATE therapy through the selective catheterization of the hepatic artery (IA group). The other 14 patients received a single dose of 177 Lu- DOTATATE through standard intravenous route (IV group). For dosimetry, whole-body γ (anterior and posterior planar acquisitions) and SPECT/CT scans of the abdomen at 2, 24 and 96 h post 177Lu-DOTATATE administration were acquired. Dosimetric calculations were done using the HERMES software. RESULTS: The mean dose per unit activity (DpA) in the liver and tumor lesions in the IA group differed significantly (p < 0.05) but differed insignificantly in spleen and kidneys (p > 05) with the IV group. The mean tumor/non-tumor concentration at 96 h was 76.83 ± 7.9 (range 10.2-251.3) in the IA group whereas it was 25.6 ± 5.9 (Range: 12-55) in the IV group. There was an average threefold increase in tumoral concentration over the standard intravenous group. CONCLUSION: IA administration of 177Lu-DOTATATE results in higher concentration and absorbed dose in hepatic metastases in patients of GEPNETs as compared to a single dose of PRRT administered through standard IV route, and thus seems to be a powerful tool to improve the efficacy of PRRT. ADVANCES IN KNOWLEDGE: Measurement of the dose received by the tumor lesions and the critical organs is of paramount importance for the prognostication of a radionuclide therapy. Scant data exist on the dosimetric impact of IA administration of the therapy with 177Lu-DOTATATE on the tumors and other organs, and this study would add an impact towards the better treatment outcome in patients of neuroendocrine tumor with liver-dominant metastatic disease.


Assuntos
Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Administração Intravenosa , Adulto , Idoso , Complexos de Coordenação , Feminino , Humanos , Injeções Intra-Arteriais , Neoplasias Hepáticas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/farmacocinética , Compostos Organometálicos/farmacocinética , Projetos Piloto , Estudos Prospectivos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Dosagem Radioterapêutica
6.
Nat Commun ; 12(1): 4310, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262026

RESUMO

Patients with primary and bone metastatic breast cancer have significantly reduced survival and life quality. Due to the poor drug delivery efficiency of anti-metastasis therapy and the limited response rate of immunotherapy for breast cancer, effective treatment remains a formidable challenge. In this work, engineered macrophages (Oxa(IV)@ZnPc@M) carrying nanomedicine containing oxaliplatin prodrug and photosensitizer are designed as near-infrared (NIR) light-activated drug vectors, aiming to achieve enhanced chemo/photo/immunotherapy of primary and bone metastatic tumors. Oxa(IV)@ZnPc@M exhibits an anti-tumor M1 phenotype polarization and can efficiently home to primary and bone metastatic tumors. Additionally, therapeutics inside Oxa(IV)@ZnPc@M undergo NIR triggered release, which can kill primary tumors via combined chemo-photodynamic therapy and induce immunogenic cell death simultaneously. Oxa(IV)@ZnPc@M combined with anti-PD-L1 can eliminate primary and bone metastatic tumors, activate tumor-specific antitumor immune response, and improve overall survival with limited systemic toxicity. Therefore, this all-in-one macrophage provides a treatment platform for effective therapy of primary and bone metastatic tumors.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Macrófagos/transplante , Fotoquimioterapia/métodos , Animais , Apoptose/efeitos dos fármacos , Antígeno B7-H1/antagonistas & inibidores , Neoplasias Ósseas/imunologia , Neoplasias Ósseas/secundário , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Portadores de Fármacos/química , Feminino , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Morte Celular Imunogênica/efeitos dos fármacos , Memória Imunológica/efeitos dos fármacos , Indóis/administração & dosagem , Indóis/química , Indóis/farmacologia , Raios Infravermelhos , Macrófagos/química , Nanomedicina , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Oxaliplatina/administração & dosagem , Oxaliplatina/química , Oxaliplatina/farmacologia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacologia
7.
AJR Am J Roentgenol ; 217(5): 1195-1205, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34133205

RESUMO

BACKGROUND. Gadobutrol and gadoterate are widely used macrocyclic gadolinium-based contrast agents. Given gadobutrol's higher T1 relaxivity, a reduced gadobutrol dose should achieve essentially equivalent diagnostic efficacy as a standard dose of gadoterate. OBJECTIVE. The purpose of our study was to show efficacy of a 25% reduced dose of gadobutrol is noninferior to 100% standard dose of gadoterate for contrast-enhanced MRI of the CNS. METHODS. In this international prospective multicenter open-label crossover trial (LEADER-75 [Lower Administered Dose With Higher Relaxivity: Gadovist vs Dotarem]), adult patients with known or suspected CNS pathology underwent contrast-enhanced brain MRI with standard-dose gadoterate (0.1 mmol/kg); if an enhancing lesion was identified, a second MRI with reduced-dose gadobutrol (0.075 mmol/kg) was performed within 15 days of the first MRI. Three radiologists independently reviewed images to score three primary efficacy measures: subjective lesion enhancement, lesion border delineation, lesion internal morphology. A noninferiority analysis used readers' mean scores of the primary efficacy measures. Noninferiority of reduced-dose gadobutrol to standard-dose gadoterate for primary efficacy measures was defined as the difference in score between reduced-dose gadobutrol images and unenhanced images achieving at least 80% of the difference in score between standard-dose gadoterate images and unenhanced images. A post hoc analysis was performed to directly compare contrast-enhanced images for equivalence. Secondary efficacy variables included the number of lesions detected, reader confidence, diagnostic performance for malignancy, and reader preference in side-by-side comparison. RESULTS. The efficacy analysis included 141 patients (78 men, 63 women; mean age, 58.5 ± 13.5 [SD] years). Improvement of reduced-dose gadobutrol over unenhanced images was noninferior to improvement of standard-dose gadoterate over unenhanced images using a 20% noninferiority margin for all three primary efficacy measures using mean readings (p ≤ .025). In the post hoc analysis, the mean reading for the three primary efficacy measures differed by less than 1% between reduced-dose gadobutrol and standard-dose gadoterate, supporting equivalence of all measures using a narrow ± 5% margin (p ≤ .025). The total number of lesions detected by mean reading was 301 for reduced-dose gadobutrol versus 291 for standard-dose gadoterate. Mean reader confidence was 3.3 ± 0.6 for reduced-dose gadobutrol versus 3.3 ± 0.6 for standard-dose gadoterate. Sensitivity (58.7%), specificity (91.8%), and accuracy (70.2%) for malignancy from majority reading were identical for reduced-dose gadobutrol and standard-dose gadoterate. Reader preference was not different (95% CI, -0.10 to 0.11). CONCLUSION. A 25% reduced dose of gadobutrol is noninferior to standard-dose gadoterate for contrast-enhanced brain MRI. CLINICAL IMPACT. Use of reduced-dose gadobutrol should be considered for brain MRI, particularly in patients undergoing multiple contrast-enhanced examinations. TRIAL REGISTRATION. ClinicalTrials.gov NCT03602339; EU Clinical Trials Register EudraCT 2018-00690-78.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Gadolínio/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Meglumina/administração & dosagem , Neuroimagem/métodos , Compostos Organometálicos/administração & dosagem , Idoso , Estudos Cross-Over , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
8.
Int J Med Sci ; 18(12): 2725-2735, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104105

RESUMO

Rationale: Peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE (oxodotreotide) results in external radiation exposure from the patient. In the PREELU observational prospective study, we determined the equivalent dose rate at 1 m of the patient (EDR-1m) for a period following PRRT. The main objective was to predict which patients could be discharged from the hospital at approximately 3 h after the administration of 177Lu-DOTATATE, i.e. at the end of the infusion of amino-acids according to our PRRT protocol. As presenting no undue risk of radiation exposure for the public, those patients could be treated as outpatients or day patients, rather than inpatients. Methods: We sequentially measured EDR-1m facing the sternum and then the pelvis during 50 PRRT in 24 patients with metastatic neuroendocrine tumours, each 30 minutes after ending administration of Lutathera, over at least 180 minutes. Results: 180 minutes after the administration of ca. 7400 MBq of Lutathera, EDR-1m was <40 µSv/h in all cases, and <25 µSv/h in 32 cases (64%). After an overnight hospital stay, EDR-1m was <25 µSv/h in all cases. The EDR-1m value measured facing the sternum was the greatest in about one-fourth of paired measurements. In patients whose creatinine clearance was >96 mL/min/1.73m2, the EDR-1m was most likely (predictive value=90%) to drop below 25 µSv/h within 180 minutes after the administration of Lutathera. In 16 patients who benefited from several PRRT cycles, the creatinine clearance did not decrease significantly from one cycle to the next, probably due to the kidney protection by the amino-acid infusion. The patients whose EDR-1m dropped below 25 µSv/h at 180 minutes during their first PRRT cycle were unlikely (predictive value= 88%) to decease during the following two years. Conclusion: All patients could have been discharged 3 h after administration according to the criterion EDR-1m <40 µSv/h. Using EDR-1m <25 µSv/h as criterion, an extended hospital stay beyond 3 h would have been necessary in around one-third of the PRRT treatments and could be anticipated based on creatinine clearance ≤96 mL/min/1.73m2. EDR-1m <25 µSv/h at 180 min during the first PRRT yielded a strong predictive value on the patient's survival at two years, a finding that should be confirmed in future studies.


Assuntos
Tumores Neuroendócrinos/radioterapia , Octreotida/análogos & derivados , Compostos Organometálicos/efeitos adversos , Exposição à Radiação/prevenção & controle , Radiometria/estatística & dados numéricos , Compostos Radiofarmacêuticos/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Compostos Organometálicos/administração & dosagem , Estudos Prospectivos , Doses de Radiação , Compostos Radiofarmacêuticos/administração & dosagem , Fatores de Tempo
9.
Toxicol Appl Pharmacol ; 423: 115573, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33991535

RESUMO

Oxaliplatin is being used in different malignancies and several side effects are reported for patients taking Oxaliplatin, including peripheral neuropathy, nausea and vomiting, diarrhea, mouth sores, low blood counts, fatigue, loss of appetite, etc. Here we have developed a targeted anticancer drug delivery system based on folate-conjugated amine-functionalized UiO-66 for the delivery of oxaliplatin (OX). UiO-66-NH2 (U) and UiO-66-NH2-FA(FU) were pre-functionalized by the incorporation of folic acid (FA) into the structure via coordination of the carboxylate group of FA. The FTIR spectra of drug-loaded U and FU showed the presence of new carboxylic and aliphatic groups of OX and FA. Powder X-ray diffraction (PXRD) patterns were matched accordingly with the reference pattern and FESEM results showed semi-spherical particles (115-128 nm). The evaluated amounts of OX in U and FU were calculated 304.5 and 293 mg/g, respectively. The initial burst release of OX was 15.7% per hour for U(OX) and 10.8% per hour for FU(OX). The final release plateau gives 62.9% and 52.3% for U(OX) and FU(OX). To evaluate the application of the prepared delivery platform, they were tested on colorectal cancer cells (CT-26) via MTT assay, cell migration assay, and spheroid model. IC50 values obtained from MTT assay were 21.38, 95.50, and 18.20 µg/mL for OX, U(OX), and FU(OX), respectively. After three days of treatment, the CT26 spheroids at two doses of 500 and 50 µg/mL of U(OX) and FU(OX) showed volume reduction. Moreover, the oxidative behavior of the prepared systems within the cell was assessed by total thiol, malondialdehyde, and superoxide dismutase activity. The results showed that FU(OX) had higher efficacy in preventing the growth of CT-26 spheroid, and was more effective than oxaliplation in cell migration inhibition, and induced higher oxidative stress and apoptosis.


Assuntos
Neoplasias Colorretais/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Ácido Fólico/metabolismo , Compostos Organometálicos/metabolismo , Oxaliplatina/metabolismo , Ácidos Ftálicos/metabolismo , Aminoácidos/administração & dosagem , Aminoácidos/metabolismo , Animais , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Ácido Fólico/administração & dosagem , Camundongos , Camundongos Endogâmicos BALB C , Compostos Organometálicos/administração & dosagem , Oxaliplatina/administração & dosagem , Ácidos Ftálicos/administração & dosagem
10.
Pancreas ; 50(4): 513-515, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33939662

RESUMO

OBJECTIVES: Positively charged amino acids (AA) such as arginine/lysine are coinfused with radiolabeled somatostatin analogs to reduce rates of nephrotoxicity. In the phase 3 NETTER-1 trial, commercial AA formulations were used in association with 177Lu-DOTA-0-Tyr3-Octreotate (DOTATATE). These formulations were also used in an early-access program (EAP) before regulatory approval of 177Lu-DOTATATE. Our program transitioned to compounded l-arginine 2.5%/l-lysine 2.5% in 0.9% NaCl after commercial approval of 177Lu-DOTATATE. We sought to compare rates of nausea/vomiting with arginine/lysine versus commercial parenteral AA formulations. METHODS: Rates of nausea/vomiting of all 20 EAP patients who received commercial AAs (15% Clinisol) were compared with the first 29 patients to receive 177Lu-DOTATATE after commercial approval and coinfused with arginine/lysine. Other parameters reviewed included infusion rates, need for PRN nausea medications, and other toxicities. RESULTS: Seventeen percent of patients who received compounded arginine/lysine experienced nausea, compared with 100% of patients in the EAP group (P < 0.0001). Infusion-related reactions occurred in 3% of the arginine/lysine cohort versus 35% in the EAP group. Infusion durations were substantially shorter in the arginine/lysine cohort (reduced by 61%). CONCLUSIONS: Coinfusions of arginine/lysine with radiolabeled somatostatin analogs result in substantially lower rates of nausea/vomiting compared with commercial AA formulations designed for parenteral nutrition.


Assuntos
Aminoácidos/uso terapêutico , Náusea/diagnóstico , Tumores Neuroendócrinos/terapia , Octreotida/análogos & derivados , Compostos Organometálicos/uso terapêutico , Nutrição Parenteral/métodos , Vômito/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aminoácidos/administração & dosagem , Aminoácidos/efeitos adversos , Arginina/administração & dosagem , Arginina/efeitos adversos , Arginina/uso terapêutico , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Feminino , Humanos , Bombas de Infusão , Lisina/administração & dosagem , Lisina/efeitos adversos , Lisina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Octreotida/uso terapêutico , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Nutrição Parenteral/efeitos adversos , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/uso terapêutico , Receptores de Peptídeos/química , Estudos Retrospectivos , Vômito/etiologia
11.
BMC Cancer ; 21(1): 579, 2021 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-34016077

RESUMO

BACKGROUND: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC. METHODS: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews. RESULTS: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported. CONCLUSION: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42019125245 .


Assuntos
Carcinoma Neuroendócrino/radioterapia , Radioisótopos do Iodo/administração & dosagem , Lesões por Radiação/epidemiologia , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias da Glândula Tireoide/radioterapia , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/secundário , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/etiologia , Humanos , Radioisótopos do Iodo/efeitos adversos , Octreotida/administração & dosagem , Octreotida/efeitos adversos , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/efeitos adversos , Lesões por Radiação/etiologia , Tolerância a Radiação , Compostos Radiofarmacêuticos/efeitos adversos , Insuficiência Renal/epidemiologia , Insuficiência Renal/etiologia , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/secundário , Resultado do Tratamento , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos
12.
Int J Med Sci ; 18(10): 2166-2175, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33859524

RESUMO

Rationale: Neuroendocrine neoplasia (NEN) of small bowel (SBNEN) frequently present with metastatic disease. Theranostics (molecular imaging followed by targeting therapy) allow for personalised medicine. Liquid biopsies enable precise identification of residual disease and real-time monitoring of therapeutic response. Our aim was to determine the clinical utility of a combination of surgery, theranostics, and a multigene blood measurement in metastasised SBNEN. Methods: Inclusion criteria were SBNEN, G1/G2 NEN, initial tumour diagnosis, stage IV NEN, positivity on 68Ga somatostatin analogue PET/CT, eligible for surgery, and 177Lu peptide receptor radionuclide therapy (PRRT). Blood samples for NETest were collected longitudinally. Progression-free survival (PFS) and overall survival (OS) were calculated. NETest results were assessed prior to surgery and during clinical follow-up. Results: A surgical cohort of 39 SBNEN patients met eligibility criteria. Thirty-two patients underwent ileal resection and 7 right hemicolectomy. The mean number of 177Lu PRRT cycles was 4. Mortality was nil. Surgical morbidity was 10.3%. Transient grade 1/2 toxicity occurred in 41% (PRRT). NETest scores (n=9 patients) decreased in 100% following treatment and correlated with diminished tumour volume and disease stabilization following surgery and PRRT. Median follow-up: 78 months. Median PFS and OS: 42.7 and 110 months, respectively. Progression-free survival at 1-, 3-, and 5-years was 79.4%, 57.1% and 40.5%, respectively. Overall survival at 1-, 3-, and 5-years was 97.4%, 97.4%, and 94.1%, respectively. Conclusions: Surgery combined with 177Lu PRRT is safe and provides favourable PFS and OS in selected patients with advanced SBNEN. Liquid biopsy (NETest) has the potential to accurately delineate disease status.


Assuntos
Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/terapia , Medicina de Precisão/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/mortalidade , Neoplasias Intestinais/patologia , Estimativa de Kaplan-Meier , Biópsia Líquida/métodos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Intervalo Livre de Progressão , Compostos Radiofarmacêuticos/administração & dosagem , Estudos Retrospectivos , Resultado do Tratamento
13.
ACS Appl Mater Interfaces ; 13(11): 12845-12856, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33709684

RESUMO

Tumor immunotherapy like immune checkpoint blockade (ICB) shows great success nowadays but is severely limited by low response rates and immune-related adverse events (IRAEs). While photodynamic therapy (PDT) could efficiently eradicate tumor cells and further induce immune responses to promote activating of T lymphocytes. Herein a nanodrug hierarchically incorporating photosensitizer and PD-L1 antibody was developed for synergistic tumor immuno-photodynamic therapy. A pH/enzyme dual-sensitive polymeric micelle with sheddable PEG coating was designed for codelivery of PD-L1 antibody and zinc phthalocyanine (ZnPc) in the tumor. The tumor microenvironment featuring low pH and high matrix metallopeptidase 2 (MMP-2) sequentially triggered the shedding of PEG and the release of PD-L1 antibody to exert local ICB in tumor tissue, after which the remaining nanodrug with ZnPc undergoing charge reversal was readily delivered into tumor cells. With light irradiation, the photodynamic therapy effect of sAMPc induced immunogenic cell death of tumor cells and further promoted intratumor recruitment of CD8+ T cells, thus resulting in a synergistic immuno-photodynamic therapy with ICB. Moreover, the PEG-sheddable strategy endowed the nanodrug with stealth properties in blood circulation, making the IRAEs of PD-L1 antibody significantly reduced. This pH/MMP-2 dual-sensitive PEG sheddable nanodrug provids a promising strategy for well-combined ICB therapy and PDT to achieve improved anticancer immuno-photodynamic therapy with reduced adverse effects.


Assuntos
Antineoplásicos Imunológicos/administração & dosagem , Antígeno B7-H1/antagonistas & inibidores , Preparações de Ação Retardada/química , Indóis/administração & dosagem , Compostos Organometálicos/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Polietilenoglicóis/química , Antineoplásicos Imunológicos/uso terapêutico , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Indóis/uso terapêutico , Isoindóis , Masculino , Neoplasias/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Microambiente Tumoral/efeitos dos fármacos , Compostos de Zinco
14.
Sci Rep ; 11(1): 4727, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649421

RESUMO

To present the feasibility of a dynamic whole-body (DWB) 68Ga-DOTATOC-PET/CT acquisition in patients with well-differentiated neuroendocrine tumors (WD-NETs). Sixty-one patients who underwent a DWB 68Ga-DOTATOC-PET/CT for a histologically proven/highly suspected WD-NET were prospectively included. The acquisition consisted in single-bed dynamic acquisition centered on the heart, followed by the DWB and static acquisitions. For liver, spleen and tumor (1-5/patient), Ki values (in ml/min/100 ml) were calculated according to Patlak's analysis and tumor-to-liver (TLR-Ki) and tumor-to-spleen ratios (TSR-Ki) were recorded. Ki-based parameters were compared to static parameters (SUVmax/SUVmean, TLR/TSRmean, according to liver/spleen SUVmean), in the whole-cohort and according to the PET system (analog/digital). A correlation analysis between SUVmean/Ki was performed using linear and non-linear regressions. Ki-liver was not influenced by the PET system used, unlike SUVmax/SUVmean. The regression analysis showed a non-linear relation between Ki/SUVmean (R2 = 0.55,0.68 and 0.71 for liver, spleen and tumor uptake, respectively) and a linear relation between TLRmean/TLR-Ki (R2 = 0.75). These results were not affected by the PET system, on the contrary of the relation between TSRmean/TSR-Ki (R2 = 0.94 and 0.73 using linear and non-linear regressions in digital and analog systems, respectively). Our study is the first showing the feasibility of a DWB 68Ga-DOTATOC-PET/CT acquisition in WD-NETs.


Assuntos
Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/diagnóstico , Cintilografia/métodos , Baço/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Octreotida/administração & dosagem , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Baço/patologia , Tomografia Computadorizada por Raios X/métodos
15.
Breast Cancer ; 28(4): 927-936, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33625722

RESUMO

BACKGROUND: The high concentration of gadolinium in gadobutrol, which is widely used in Japan, helps visualize signal enhancement of neoplastic lesions, however, there was concern that high T1 relaxivity could decrease the contrast between the lesion and the background mammary gland. We evaluate the effect of gadobutrol on background parenchymal enhancement (BPE) and differential diagnosis between benign and malignant lesions in dynamic MRI of the breast. METHODS: Ninety-nine patients were enrolled prospectively. Measurements of the following signal intensities (SIs) were obtained: breast tissue on a pre-contrast image (SIpre) and an early-phase image (SIearly); and the SIs of breast cancer on a pre-contrast image (SIpre-cancer) and an early-phase image (SIearly-cancer). We calculated the BPE ratio, i.e., (SIearly - SIpre)/SIpre and the cancer/BPE ratio, i.e., (SIearly-cancer - SIpre-cancer)/(SIearly on the affected side - SIpre on the affected side). These quantitative assessments were compared with the data from the recently published multicenter study (reference study without use of gadobutrol). In addition, two radiologists reinterpreted each of the MR images, and a third radiologist set the ROIs in the lesions and performed kinetic analysis as a Reader 3. RESULTS: While there was no significant difference in the SI of breast cancer in the premenopausal patients between the two studies, that in postmenopausal patients was significantly higher in the present study than in the reference study (p = 0.002). Although there was no significant difference in the cancer/BPE ratio in the postmenopausal patients between the two studies, the cancer/BPE ratio in the premenopausal patients was significantly higher in the reference study than in the present study (p = 0.028). For differentiation between benign and malignant masses, the mass margin was found to be the most important term (p < 0.001). According to the data of Reader 3, visual washout was observed in all 18 patients in whom the interpretation was changed from "plateau" to "washout". CONCLUSIONS: Gadobutrol may decrease the contrast between breast cancer and background parenchyma in premenopausal patients, and it may have a characteristic that "washout" does not easily occur, leading to "plateau" in patients with breast cancer.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Meios de Contraste/administração & dosagem , Aumento da Imagem/métodos , Compostos Organometálicos/administração & dosagem , Tecido Parenquimatoso/patologia , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Mamografia/métodos , Pessoa de Meia-Idade , Estudos Prospectivos
16.
Clin Cancer Res ; 27(8): 2216-2225, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33526423

RESUMO

PURPOSE: PET with somatostatin receptor ligand [68Ga]Ga-DOTA-D-Phe1-Tyr3-octreotide ([68Ga]Ga-DOTA-TOC) is an established method in radiotherapy planning because of the improved detection and delineation of meningioma tissue. We investigated the diagnostic accuracy of supplementary [68Ga]Ga-DOTA-TOC PET in patients with a 3-month postoperative MRI reporting gross-total resection (GTR). EXPERIMENTAL DESIGN: Thirty-seven patients with a histologically proven meningioma and GTR on postoperative MRI were prospectively referred to [68Ga]Ga-DOTA-TOC PET. Detection and volume measurements of [68Ga]Ga-DOTA-TOC-avid lesions in relation to the primary tumor site were recorded. Residual tumor in suspicious lesions suggested by [68Ga]Ga-DOTA-TOC PET was verified by (i) tumor recurrence/progression on subsequent MRI scans according to the Response Assessment of Neuro-Oncology criteria, (ii) subsequent histology, and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scan. RESULTS: Twenty-three PET scans demonstrated [68Ga]Ga-DOTA-TOC-avid lesions suspicious of residual meningioma, where 18 could be verified by (i) tumor progression on subsequent MRI scans (n = 6), (ii) histologic confirmation (n = 3), and (iii) follow-up [68Ga]Ga-DOTA-TOC PET scans confirming the initial PET findings (n = 9) after an overall median follow-up time of 17 months (range, 9-35 months). In contrast, disease recurrence was seen in only 2 of 14 patients without [68Ga]Ga-DOTA-TOC-avid lesions (P < 0.0001). The sensitivity, specificity, and diagnostic accuracy of [68Ga]Ga-DOTA-TOC PET in detecting meningioma residue was 90% [95% confidence interval (CI), 67-99], 92% (95% CI, 62-100), and 90% (95% CI, 74-98; P < 0.0001), respectively. CONCLUSIONS: The majority of patients with GTR on 3-month postoperative MRI may have small unrecognized meningioma residues that can be detected using [68Ga]Ga-DOTA-TOC PET.


Assuntos
Neoplasias Meníngeas/diagnóstico , Meninges/diagnóstico por imagem , Meningioma/diagnóstico , Tomografia por Emissão de Pósitrons/métodos , Adulto , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Meníngeas/cirurgia , Meninges/patologia , Meninges/cirurgia , Meningioma/cirurgia , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasia Residual , Octreotida/administração & dosagem , Octreotida/análogos & derivados , Compostos Organometálicos/administração & dosagem , Período Pós-Operatório , Compostos Radiofarmacêuticos/administração & dosagem
17.
Pharm Res ; 38(2): 335-346, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33604784

RESUMO

PURPOSE: Melanoma is an invasive and very aggressive skin cancer due to its multi-drug resistance that results in poor patient survival. There is a need to test new treatment approaches to improve therapeutic efficacy and reduce side effects of conventional treatments. METHODS: PLA/PVA nanoparticles carrying both Dacarbazine and zinc phthalocyanine was produced by double emulsion technique. The characterization was performed by dynamic light scattering and atomic force microscopy. In vitro photodynamic therapy test assay using MV3 melanoma cells as a model has been performed. In vitro cell viability (MTT) was performed to measure cell toxicity of of nanoparticles with and without drugs using human endothelial cells as a model. The in vivo assay (biodistribution/tissue deposition) has been performed using radiolabeled PLA/PVA NPs. RESULTS: The nanoparticles produced showed a mean diameter of about 259 nm with a spherical shape. The in-vitro photodynamic therapy tests demonstrated that the combination is critical to enhance the therapeutic efficacy and it is dose dependent. The in vitro cell toxicity assay using endothelial cells demonstrated that the drug encapsulated into nanoparticles had no significant toxicity compared to control samples. In-vivo results demonstrated that the drug loading affects the biodistribution of the nanoparticle formulations (NPs). Low accumulation of the NPs into the stomach, heart, brain, and kidneys suggested that common side effects of Dacarbazine could be reduced. CONCLUSION: This work reports a robust nanoparticle formulation with the objective to leveraging the synergistic effects of chemo and photodynamic therapies to potentially suppressing the drug resistance and reducing side effects associated with Dacarbazine. The data corroborates that the dual encapsulated NPs showed better in-vitro efficacy when compared with the both compounds alone. The results support the need to have a dual modality NP formulation for melanoma therapy by combining chemotherapy and photodynamic therapy.


Assuntos
Antineoplásicos Alquilantes/administração & dosagem , Portadores de Fármacos/química , Melanoma/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular , Dacarbazina/administração & dosagem , Dacarbazina/farmacocinética , Composição de Medicamentos/métodos , Células Endoteliais , Humanos , Isoindóis/administração & dosagem , Isoindóis/farmacocinética , Masculino , Melanoma/patologia , Camundongos , Nanopartículas/química , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/farmacocinética , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacocinética , Poliésteres/química , Álcool de Polivinil/química , Neoplasias Cutâneas/patologia , Distribuição Tecidual , Compostos de Zinco/administração & dosagem , Compostos de Zinco/farmacocinética
18.
Theranostics ; 11(7): 3527-3539, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33537102

RESUMO

To investigate the utility of noninvasive µPET-CT with 64Cu-DOTA-anti-CD11b (64Cu-αCD11b) in assessing bone marrow status after anticancer therapies, and the protective role of anti-CSF-1 (αCSF-1) against bone marrow suppression induced by Abraxane. Methods: MDA-MB-435 tumor-bearing mice were treated with Abraxane, αCSF-1, or αCSF-1 plus Abraxane. µPET-CT and biodistribution of 64Cu-αCD11b were performed after intravenous injection of the radiotracer. Cells from mouse bone marrow and MDA-MB-435 tumor were analyzed by flow cytometry. A humanized αCSF-1 was investigated for its role in protecting bone marrow cells, using a transgenic mouse model that expresses functional human CSF-1. Results: µPET-CT showed that 64Cu-αCD11b had high uptake in the bone marrow and spleen of both normal and tumor-bearing mice. Abraxane significantly reduced 64Cu-αCD11b uptake in the bone marrow and spleen of treated mice compared to untreated mice. Interestingly, 64Cu-αCD11b µPET-CT revealed that αCSF-1 alleviated the depletion of bone marrow cells by Abraxane. These changes in the bone marrow population of CD11b+ myeloid cells were confirmed by flow cytometry. Moreover, αCSF-1 potently enhanced tolerance of bone marrow granulocytic myeloid cells to Abraxane, decreased cell migration, and suppressed recruitment of myeloid cells to the tumor microenvironment. The humanized αCSF-1 also alleviated the effects of Abraxane on bone marrow cells in transgenic mice expressing human CSF-1, suggesting clinical relevance of αCSF-1 in prevention of bone marrow suppression in addition to its role in reducing tumor-infiltrating myeloid cells. Conclusions: Abraxane-induced bone marrow CD11b+ myeloid cell depletion in tumor-bearing mice could be noninvasively assessed by µPET-CT with 64Cu-αCD11b and prevented by αCSF-1.


Assuntos
Paclitaxel Ligado a Albumina/toxicidade , Anticorpos/farmacologia , Antineoplásicos/toxicidade , Medula Óssea/diagnóstico por imagem , Neoplasias/diagnóstico por imagem , Baço/diagnóstico por imagem , Paclitaxel Ligado a Albumina/antagonistas & inibidores , Animais , Anticorpos/química , Medula Óssea/efeitos dos fármacos , Medula Óssea/imunologia , Medula Óssea/patologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/imunologia , Células da Medula Óssea/patologia , Antígeno CD11b/genética , Antígeno CD11b/imunologia , Linhagem Celular Tumoral , Radioisótopos de Cobre , Feminino , Expressão Gênica , Compostos Heterocíclicos com 1 Anel/química , Xenoenxertos , Humanos , Fator Estimulador de Colônias de Macrófagos/genética , Fator Estimulador de Colônias de Macrófagos/imunologia , Camundongos , Camundongos Nus , Células Mieloides/efeitos dos fármacos , Células Mieloides/imunologia , Células Mieloides/patologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Neoplasias/patologia , Compostos Organometálicos/administração & dosagem , Compostos Organometálicos/química , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/química , Baço/efeitos dos fármacos , Baço/imunologia , Baço/patologia , Microambiente Tumoral/efeitos dos fármacos
19.
Nanomedicine ; 33: 102368, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33548477

RESUMO

The photodynamic anticancer activity of a photosensitizer can be further increased by co-administration of a flavonoid. However, this requires that both molecules must be effectively accumulated at the tumor site. Hence, in order to enhance the activity of zinc phthalocyanine (ZnPc, photosensitizer), it was co-encapsulated with quercetin (QC, flavonoid) in lipid polymer hybrid nanoparticles (LPNs) developed using biodegradable & biocompatible materials and prepared using a single-step nanoprecipitation technique. High stability and cellular uptake, sustained release, inherent fluorescence, of ZnPC were observed after encapsulation in the LPNs, which also showed a higher cytotoxic effect in breast carcinoma cells (MCF-7) compared to photodynamic therapy (PDT) alone. In vivo studies in tumor-bearing Sprague Dawley rats demonstrated that the LPNs were able to deliver ZnPc and QC to the tumor site with minimal systemic toxicity and increased antitumor effect. Overall, the photodynamic effect of ZnPc was synergized by QC. This strategy could be highly beneficial for cancer management in the future while nullifying the side effects of chemotherapy.


Assuntos
Antineoplásicos/química , Materiais Biocompatíveis/química , Isoindóis/química , Lipossomos/química , Nanopartículas/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Quercetina/química , Compostos de Zinco/química , Animais , Antineoplásicos/administração & dosagem , Materiais Biocompatíveis/administração & dosagem , Permeabilidade da Membrana Celular , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Humanos , Isoindóis/administração & dosagem , Células MCF-7 , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia , Compostos Organometálicos/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Quercetina/administração & dosagem , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Compostos de Zinco/administração & dosagem
20.
Invest New Drugs ; 39(1): 89-97, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32833137

RESUMO

Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.


Assuntos
Indóis/farmacologia , Metaloporfirinas/farmacologia , Compostos Organometálicos/farmacologia , Oxigênio/farmacologia , Fotoquimioterapia/métodos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células HeLa , Humanos , Indóis/administração & dosagem , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Metaloporfirinas/administração & dosagem , Mitocôndrias/efeitos dos fármacos , Compostos Organometálicos/administração & dosagem , Oxigênio/administração & dosagem , Pressão Parcial , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/análise
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