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1.
Cochrane Database Syst Rev ; 7: CD012997, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34219224

RESUMO

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for development of HUS is a gastrointestinal infection by Shiga toxin-producing Escherichia coli (STEC). This review addressed the interventions aimed at secondary prevention of HUS in patients with diarrhoea who were infected with a bacteria that increase the risk of HUS. OBJECTIVES: Our objective was to evaluate evidence regarding secondary preventative strategies for HUS associated with STEC infections. In doing so, we sought to assess the effectiveness and safety of interventions as well as their potential to impact the morbidity and death associated with this condition. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 November 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Studies were considered based on the methods, participants, and research goals. Only randomised controlled trials were considered eligible for inclusion. The participants of the studies were paediatric and adult patients with diarrhoeal illnesses due to STEC. The primary outcome of interest was incidence of HUS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified four studies (536 participants) for inclusion that investigated four different interventions including antibiotics (trimethoprim-sulfamethoxazole), anti-Shiga toxin antibody-containing bovine colostrum, Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent), and a monoclonal antibody against Shiga toxin (urtoxazumab). The overall risk of bias was unclear for selection, performance and detection bias and low for attrition, reporting and other sources of bias. It was uncertain if trimethoprim-sulfamethoxazole reduced the incidence of HUS compared to no treatment (47 participants: RR 0.57, 95% CI 0.11-2.81, very low certainty evidence). Adverse events relative to this review, need for acute dialysis, neurological complication and death were not reported. There were no incidences of HUS in either the bovine colostrum group or the placebo group. It was uncertain if bovine colostrum caused more adverse events (27 participants: RR 0.92, 95% CI 0.42 to 2.03; very low certainty evidence). The need for acute dialysis, neurological complications or death were not reported. It is uncertain whether Synsorb Pk reduces the incidence of HUS compared to placebo (353 participants: RR 0.93, 95% CI 0.39 to 2.22; very low certainty evidence). Adverse events relevant to this review, need for acute dialysis, neurological complications or death were not reported. One study compared two doses of urtoxazumab (3.0 mg/kg and 1.0 mg/kg) to placebo. It is uncertain if either 3.0 mg/kg urtoxazumab (71 participants: RR 0.34, 95% CI 0.01 to 8.14) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) reduced the incidence of HUS compared to placebo (very low certainty evidence). Low certainty evidence showed there may be little or no difference in the number of treatment-emergent adverse events with either 3.0 mg/kg urtoxazumab (71 participants: RR 1.00, 95% CI 0.84 to 1.18) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) compared to placebo. There were 25 serious adverse events reported in 18 patients: 10 in the placebo group, and 9 and 6 serious adverse events in the 1.0 mg/kg and 3.0 mg/kg urtoxazumab groups, respectively. It is unclear how many patients experienced these adverse events in each group, and how many patients experienced more than one event. It is uncertain if either dose of urtoxazumab increased the risk of neurological complications or death (very low certainty evidence). Need for acute dialysis was not reported. AUTHORS' CONCLUSIONS: The included studies assessed antibiotics, bovine milk, and Shiga toxin inhibitor (Synsorb Pk) and monoclonal antibodies (Urtoxazumab) against Shiga toxin for secondary prevention of HUS in patients with diarrhoea due to STEC. However, no firm conclusions about the efficacy of these interventions can be drawn given the small number of included studies and the small sample sizes of those included studies. Additional studies, including larger multicentre studies, are needed to assess the efficacy of interventions to prevent development of HUS in patients with diarrhoea due to STEC infection.


Assuntos
Diarreia/complicações , Infecções por Escherichia coli/terapia , Síndrome Hemolítico-Urêmica/prevenção & controle , Prevenção Secundária/métodos , Escherichia coli Shiga Toxigênica , Adulto , Animais , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Viés , Bovinos , Criança , Colostro/imunologia , Diarreia/microbiologia , Diarreia/terapia , Síndrome Hemolítico-Urêmica/epidemiologia , Humanos , Incidência , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/uso terapêutico , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Trissacarídeos/efeitos adversos , Trissacarídeos/uso terapêutico
2.
Int J Mol Sci ; 21(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321835

RESUMO

Development of new, safe, and effective microbicides to prevent human immunodeficiency virus HIV sexual transmission is needed. Unfortunately, most microbicides proved ineffective to prevent the risk of HIV-infection in clinical trials. We are working with G2-S16 polyanionic carbosilane dendrimer (PCD) as a new possible vaginal topical microbicide, based on its short reaction times, wide availability, high reproducibility, and quantitative yields of reaction. G2-S16 PCD exerts anti-HIV activity at an early stage of viral replication, by blocking gp120/CD4/CCR5 interaction, and providing a barrier against infection for long periods of time. G2-S16 PCD was stable at different pH values, as well as in the presence of seminal fluids. It maintained the anti-HIV activity against R5/X4 HIV over time, did not generate any type of drug resistance, and retained the anti-HIV effect when exposed to semen-enhanced viral infection. Importantly, G2-S16 PCD did not modify vaginal microbiota neither in vitro or in vivo. Histopathological examination did not show vaginal irritation, inflammation, lesions, or damage in the vaginal mucosa, after administration of G2-S16 PCD at different concentrations and times in female mice and rabbit animal models. Based on these promising data, G2-S16 PCD could become a good, safe, and readily available candidate to use as a topical vaginal microbicide against HIV.


Assuntos
Alcanossulfonatos/uso terapêutico , Fármacos Anti-HIV/uso terapêutico , Dendrímeros/uso terapêutico , Infecções por HIV/prevenção & controle , Compostos de Organossilício/uso terapêutico , Administração Intravaginal , Alcanossulfonatos/administração & dosagem , Alcanossulfonatos/efeitos adversos , Animais , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Dendrímeros/administração & dosagem , Dendrímeros/efeitos adversos , Avaliação Pré-Clínica de Medicamentos , Feminino , Infecções por HIV/transmissão , Humanos , Masculino , Compostos de Organossilício/administração & dosagem , Compostos de Organossilício/efeitos adversos
3.
Biochem Pharmacol ; 107: 29-40, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26920250

RESUMO

Poly (ADP-ribose) polymerases (PARPs) facilitate repairing of cancer cell DNA damage as a mean to promote cancer proliferation and metastasis. Inhibitors of PARPs which interfering DNA repair, in context of defects in other DNA repair mechanisms, can thus be potentially exploited to inhibit or even kill cancer cells. However, nondiscriminatory inhibition of PARPs, such as PARP2, may lead to undesired consequences. Here, we demonstrated the design and development of the Zj6413 as a potent and selective PARP1 catalytic inhibitor. It trapped PARP1/2 at damaged sites of DNA. As expected, the Zj6413 showed notable anti-tumor activity against breast cancer gene (BRCA) deficient triple negative breast cancers (TNBCs). Zj6413 treated breast cancers (BCs) showed an elevated level of DNA damage evidenced by the accumulation of γ-H2AX foci and DNA damaged related proteins. Zj6413 also induced G2/M arrest and cell death in the MX-1, MDA-MB-453 BC cells, exerted chemo-sensitizing effect on BRCA proficient cancer cells and potentiated Temozolomide (TMZ)'s cytotoxicity in MX-1 xenograft tumors mice. In conclusion, our study provided evidence that a new PARP inhibitor strongly inhibited the catalytic activity of PARPs, trapped them on nicked DNA and damaged the cancer cells, eventually inhibiting the growth of breast tumor cells in vitro and in vivo.


Assuntos
Desenho de Fármacos , Compostos de Organossilício/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Quinazolinonas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Animais , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Alquilantes/química , Antineoplásicos Alquilantes/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dacarbazina/efeitos adversos , Dacarbazina/agonistas , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Agonismo de Drogas , Feminino , Fase G2/efeitos dos fármacos , Humanos , Camundongos Nus , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Poli(ADP-Ribose) Polimerase-1 , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos , Inibidores de Poli(ADP-Ribose) Polimerases/química , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/química , Poli(ADP-Ribose) Polimerases/genética , Quinazolinonas/efeitos adversos , Quinazolinonas/química , Quinazolinonas/farmacologia , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Temozolomida , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Cancer Chemother Pharmacol ; 74(1): 45-54, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24807458

RESUMO

PURPOSE: Although preclinical studies on camptothecin antitumor effect have demonstrated the superiority of low-dose protracted dosing, these findings were not replicated in the clinic. 7-t-butyldimethylsilyl-10-hydroxycamptothecin (AR-67) is a camptothecin analogue currently under investigation in early phase clinical trials. To maximize the therapeutic potential of AR-67, we sought to identify factors that affect response to treatment. METHODS: After determining the maximum tolerated dose using neutropenia as a toxicity endpoint, xenografts received AR-67 under varying dosing schedules and were monitored for survival. On the last treatment day, tumor tissue was collected and topoisomerase 1 (Top1), γH2AX, caspase 3 and PARP protein content was evaluated. AR-67 plasma and tumor pharmacokinetics were also studied in mice and cancer patients who were administered AR-67 as a 1-h intravenous infusion on days 1, 4, 8, 12 and 15 every 21 days. RESULTS: Low-dose protracted dosing schedules increased animal survival compared to less frequent, but higher-dose courses and the expression of Top1 and γH2AX were schedule dependent. Fatigue and neutropenia were the dose-limiting toxicities identified in patients receiving AR-67. Finally, elimination of AR-67 from the tumor site was slower in both xenografts and tumor of a patient enrolled in the pilot clinical trial. CONCLUSIONS: We demonstrated that low-dose protracted dosing schedules of AR-67 are therapeutically effective and Top1 reflects the biological activity of AR-67 in xenografts. Moreover, the tumor pharmacokinetics as well as the efficacy and safety of AR-67 given intermittently to cancer patients warrant further investigation.


Assuntos
Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Pulmão/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Compostos de Organossilício/administração & dosagem , Inibidores da Topoisomerase I/administração & dosagem , Adulto , Animais , Biópsia com Agulha de Grande Calibre , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Esquema de Medicação , Estudos de Viabilidade , Feminino , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/metabolismo , Masculino , Camundongos , Camundongos Nus , Metástase Neoplásica , Neoplasias/sangue , Neoplasias/metabolismo , Neoplasias/patologia , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/farmacocinética , Compostos de Organossilício/uso terapêutico , Projetos Piloto , Distribuição Aleatória , Análise de Sobrevida , Distribuição Tecidual , Inibidores da Topoisomerase I/efeitos adversos , Inibidores da Topoisomerase I/farmacocinética , Inibidores da Topoisomerase I/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
5.
ACS Chem Neurosci ; 5(7): 525-32, 2014 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-24738473

RESUMO

Neuropathic pain is a chronic condition resulting from neuronal damage. Pregabalin, the (S)-isomer of 3-isobutyl-γ-aminobutyric acid (GABA), is widely used to treat neuropathic pain, despite the occurrence of central nervous system (CNS)-related side effects such as dizziness and somnolence. Here we describe the pharmacology of novel GABA derivatives containing silicon-carbon bonds, silagaba compounds. Silagaba131, 132, and 161 showed pregabalin-like analgesic activities in animal models of neuropathic pain, but in contrast to pregabalin they did not impair neuromuscular coordination in rotarod tests. Pharmacokinetic studies showed that brain exposure to silagaba compounds was lower than that to pregabalin. Surprisingly, despite their potent analgesic action in vivo, silagaba compounds showed only weak binding to α2-δ protein. These compounds may be useful to study mechanisms of neuropathic pain. Our results also indicate that silagaba132 and 161 are candidates for orally effective treatment of neuropathic pain without CNS-related side effects.


Assuntos
Analgésicos/farmacologia , Neuralgia/tratamento farmacológico , Compostos de Organossilício/farmacologia , Ácido gama-Aminobutírico/análogos & derivados , Administração Oral , Analgésicos/efeitos adversos , Analgésicos/farmacocinética , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Hiperalgesia/tratamento farmacológico , Hiperalgesia/fisiopatologia , Masculino , Camundongos , Neuralgia/fisiopatologia , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/farmacocinética , Limiar da Dor/efeitos dos fármacos , Pregabalina , Desempenho Psicomotor/efeitos dos fármacos , Ensaio Radioligante , Ratos Sprague-Dawley , Ratos Wistar , Teste de Desempenho do Rota-Rod , Tato , Ácido gama-Aminobutírico/efeitos adversos , Ácido gama-Aminobutírico/farmacocinética , Ácido gama-Aminobutírico/farmacologia
6.
J Cosmet Laser Ther ; 13(4): 142-53, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21718184

RESUMO

BACKGROUND: There has been significant interest recently in the technique of mesotherapy as a method of 'melting fat' for body contouring. OBJECTIVE: The aim of this study was to evaluate the safety, efficacy and lipolytic potential of several compounds commonly used in cosmetic mesotherapy. METHODS: A total of 75 women (mean age: 33 years) were separated randomly into three mesotherapy groups. Injections were performed for 15 treatments once a week. The main component of each cocktail was phosphatidylcholine/deoxycholic acid for group 1, caffeine for group 2, and Conjonctyl® for group 3. Outcome was evaluated by weight, body fat percentage (BFP), circumference measurements, and patient questionnaires. RESULTS: Seventy-two of all the patients (96%) showed a circumference loss. An average circumference reduction of 4.41 cm per site for group 1, 2.99 cm for group 2, and 2.10 cm for group 3 was achieved. Mean body circumference loss was statistically significant, with p < 0.00. Weight loss was 5.33 ± 1.09 kg for group 1, 3.74 ± 1.51 kg for group 2, and 2.82 ± 1.43 kg for group 3. Seventy-four subjects (98.7%) showed a BFP decrease. A questionnaire indicated high patient satisfaction (63%). No patient showed irregularities, dimples or any serious side effects after treatment. CONCLUSION: Mesotherapy is a well-tolerated and effective alternative treatment modality for reducing the diameter of body circumference.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Cafeína/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Ácido Hialurônico/uso terapêutico , Extremidade Inferior/anatomia & histologia , Mesoterapia/efeitos adversos , Adulto , Peso Corporal , Cafeína/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Ácido Hialurônico/efeitos adversos , Pessoa de Meia-Idade , Tamanho do Órgão , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/uso terapêutico , Satisfação do Paciente , Fosfatidilcolinas/efeitos adversos , Fosfatidilcolinas/uso terapêutico , Salicilatos/efeitos adversos , Salicilatos/uso terapêutico , Circunferência da Cintura , Adulto Jovem
7.
Clin Cancer Res ; 16(2): 673-80, 2010 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-20068096

RESUMO

PURPOSE: 7-t-Butyldimethylsilyl-10-hydroxycamptothecin (AR-67) is a novel third generation camptothecin selected for development based on the blood stability of its pharmacologically active lactone form and its high potency in preclinical models. Here, we report the initial phase I experience with i.v. AR-67 in adults with refractory solid tumors. EXPERIMENTAL DESIGN AND METHODS: AR-67 was infused over 1 hour daily five times, every 21 days, using an accelerated titration trial design. Plasma was collected on the 1st and 4th day of cycle 1 to determine pharmacokinetic parameters. RESULTS: Twenty-six patients were treated at nine dosage levels (1.2-12.4 mg/m(2)/d). Dose-limiting toxicities were observed in five patients and consisted of grade 4 febrile neutropenia, grade 3 fatigue, and grade 4 thrombocytopenia. Common toxicities included leukopenia (23%), thrombocytopenia (15.4%), fatigue (15.4%), neutropenia (11.5%), and anemia (11.5%). No diarrhea was observed. The maximum tolerated dosage was 7.5 mg/m(2)/d. The lactone form was the predominant species in plasma (>87% of area under the plasma concentration-time curve) at all dosages. No drug accumulation was observed on day 4. Clearance was constant with increasing dosage and hematologic toxicities correlated with exposure (P < 0.001). A prolonged partial response was observed in one subject with non-small cell lung cancer. Stable disease was noted in patients with small cell lung cancer, non-small cell lung cancer, and duodenal cancer. CONCLUSIONS: AR-67 is a novel, blood-stable camptothecin with a predictable toxicity profile and linear pharmacokinetics. The recommended phase II dosage is 7.5 mg/m(2)/d five times every 21 days.


Assuntos
Antineoplásicos/uso terapêutico , Camptotecina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Área Sob a Curva , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/farmacocinética , Camptotecina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/patologia , Compostos de Organossilício/administração & dosagem , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/farmacocinética , Compostos de Organossilício/uso terapêutico , Recidiva
9.
Drug Discov Today ; 8(12): 551-6, 2003 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-12821303

RESUMO

During the lead optimization phase of drug discovery projects, the factors contributing to subsequent failure might include poor portfolio decision-making and a sub-optimal intellectual property (IP) position. The pharmaceutical industry has an ongoing need for new, safe medicines with a genuine biomedical benefit, a clean IP position and commercial viability. Inherent drug-like properties and chemical tractability are also essential for the smooth development of such agents. The introduction of bioisosteres, to improve the properties of a molecule and obtain new classes of compounds without prior art in the patent literature, is a key strategy used by medicinal chemists during the lead optimization process. Sila-substitution (C/Si exchange) of existing drugs is an approach to search for new drug-like candidates that have beneficial biological properties and a clear IP position. Some of the fundamental differences between carbon and silicon can lead to marked alterations in the physicochemical and biological properties of the silicon-containing analogues and the resulting benefits can be exploited in the drug design process.


Assuntos
Compostos de Organossilício/química , Preparações Farmacêuticas/química , Silício/química , Química Farmacêutica/tendências , Ensaios Clínicos como Assunto , Técnicas de Química Combinatória , Bases de Dados Factuais , Desenho de Fármacos , Indústria Farmacêutica/tendências , Humanos , Mimetismo Molecular , Estrutura Molecular , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/uso terapêutico
10.
Chembiochem ; 3(4): 341-7, 2002 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-11933235

RESUMO

In the search for new compounds that might, once incorporated into biomaterials, stimulate the natural processes of bone regeneration, a new series of silicon-containing alkyl nucleobase analogues has been synthesized. An active hypoxanthine transport process in human osteoblasts was demonstrated, with an apparent Michaelis constant of 2.3 microM and a maximum possible rate of 0.47 pmol s(-1) x 10(6) cell. The synthesized analogues were tested for toxicity in human osteoblasts. Nontoxic analogues were tested in competition transport studies with [(14)C]hypoxanthine. Two of them were found to inhibit the active transport of hypoxanthine in human osteoblasts, with IC(50) values of 6.5 and 11.6 microM.


Assuntos
Materiais Biocompatíveis/química , Compostos de Organossilício/química , Osteoblastos/metabolismo , Purinas/metabolismo , Adulto , Idoso , Materiais Biocompatíveis/efeitos adversos , Materiais Biocompatíveis/síntese química , Transporte Biológico Ativo/efeitos dos fármacos , Células Cultivadas , Humanos , Pessoa de Meia-Idade , Compostos de Organossilício/efeitos adversos , Compostos de Organossilício/síntese química , Osteoblastos/efeitos dos fármacos
11.
Photochem Photobiol ; 70(1): 72-7, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10420845

RESUMO

The purpose of this study was to determine if silicon phthalocyanine 4 (Pc 4), a second-generation photosensitizer being evaluated for the photodynamic therapy (PDT) of solid tumors, was immunosuppressive. Mice treated with Pc 4 PDT 3 days before dinitrofluorobenzene sensitization showed significant suppression of their cell-mediated immune response when compared to mice that were not exposed to PDT. The response was dose dependent, required both Pc 4 and light and occurred at a skin site remote from that exposed to the laser. The immunosuppression could not be reversed by in vivo pre-treatment of mice with antibodies to tumor necrosis factor-alpha or interleukin-10. These results provide evidence that induction of cell-mediated immunity is suppressed after Pc 4 PDT. Strategies that prevent PDT-mediated immunosuppression may therefore enhance the efficacy of this therapeutic modality.


Assuntos
Tolerância Imunológica/efeitos dos fármacos , Indóis/uso terapêutico , Compostos de Organossilício/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/uso terapêutico , Silanos , Animais , Feminino , Indóis/efeitos adversos , Camundongos , Camundongos Endogâmicos C3H , Compostos de Organossilício/efeitos adversos , Fármacos Fotossensibilizantes/efeitos adversos
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