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1.
Allergol Immunopathol (Madr) ; 51(2): 130-136, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36916098

RESUMO

Although platin desensitization is a safe and effective alternative for patients with hypersensitivity reactions (HSRs), sometimes breakthrough reactions (BTRs) can be encountered. However, data about the risk factors for BTRs are limited. The aim of this study is to define the outcomes of desensitization, the characteristics of BTRs, and to identify the risk factors for BTRs with platins in thoracic malignancies. This is a retrospective report of patients with thoracic malignancies who underwent platin desensitization. Patients' demographics, initial HSR characteristics, skin test results, desensitization outcomes, and BTR characteristics were recorded. Thirty-three lung cancer and 14 malignant pleural mesothelioma (MPM) patients were included in the study. The culprit drug was cisplatin in 29 and was carboplatin in 18 patients. Skin test positivity was 43.5% with cisplatin, 50% with carboplatin, and it was found to be higher if the interval between the initial HSR and skin testing (ST) was ˃20 days (p = 0.027). One hundred and five desensitization courses were performed. Twenty-two patients had 33 BTRs. Skin test positivity was higher in the BTR-positive group (p = 0.025). BTRs (18.2%; n = 6) were more severe than initial HSR. In the case of epinephrine administration during initial HSR, epinephrine administration during the first BTR was found to be more (p = 0.036). The target dose was achieved in 92.4% of desensitization courses. The number of previous platin infusions ≥10 was found to be an independent risk factor for BTR development (p = 0.036 OR:17.641, 95% CI: 1.211-256.971). Identification of risk factors for BTR will guide appropriate management and desensitization approaches for platin HSRs.


Assuntos
Antineoplásicos , Hipersensibilidade a Drogas , Hipersensibilidade , Neoplasias Torácicas , Humanos , Carboplatina/efeitos adversos , Cisplatino/efeitos adversos , Antineoplásicos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/epidemiologia , Estudos Retrospectivos , Dessensibilização Imunológica/métodos , Fatores de Risco , Neoplasias Torácicas/epidemiologia , Neoplasias Torácicas/induzido quimicamente , Neoplasias Torácicas/complicações , Hipersensibilidade/complicações , Testes Cutâneos/métodos , Epinefrina/uso terapêutico
2.
Ann Surg Oncol ; 20 Suppl 3: S379-88, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22941157

RESUMO

BACKGROUND: We examined whether cigarette smoking affects the degrees of oxidative damage (8-hydroxyl-2'-deoxyguanosine [8-OHdG]) on mitochondrial DNA (mtDNA), whether the degree of 8-OHdG accumulation on mtDNA is related to the increased total mtDNA copy number, and whether human 8-oxoguanine DNA glycosylase 1 (hOGG1) Ser326Cys polymorphisms affect the degrees of 8-OHdG accumulation on mtDNA in thoracic esophageal squamous cell carcinoma (TESCC). METHODS: DNA extracted from microdissected tissues of paired noncancerous esophageal muscles, noncancerous esophageal mucosa, and cancerous TESCC nests (n = 74) along with metastatic lymph nodes (n = 38) of 74 TESCC patients was analyzed. Both the mtDNA copy number and mtDNA integrity were analyzed by quantitative real-time polymerase chain reaction (PCR). The hOGG1 Ser326Cys polymorphisms were identified by restriction fragment length polymorphism PCR and PCR-based direct sequencing. RESULTS: Among noncancerous esophageal mucosa, cancerous TESCC nests, and metastatic lymph nodes, the mtDNA integrity decreased (95.2 to 47.9 to 18.6 %; P < 0.001) and the mtDNA copy number disproportionally increased (0.163 to 0.204 to 0.207; P = 0.026). In TESCC, higher indexes of cigarette smoking (0, 0-20, 20-40, and >40 pack-years) were related to an advanced pathologic N category (P = 0.038), elevated mtDNA copy number (P = 0.013), higher mtDNA copy ratio (P = 0.028), and increased mtDNA integrity (P = 0.069). The TESCC mtDNA integrity in patients with Ser/Ser, Ser/Cys, and Cys/Cys hOGG1 variants decreased stepwise from 65.2 to 52.1 to 41.3 % (P = 0.051). CONCLUSIONS: Elevated 8-OHdG accumulations on mtDNA in TESCC were observed. Such accumulations were associated with a compensatory increase in total mtDNA copy number, indexes of cigarette smoking, and hOGG1 Ser326Cys polymorphisms.


Assuntos
Carcinoma de Células Escamosas/genética , DNA Glicosilases/genética , DNA Mitocondrial/genética , Neoplasias Esofágicas/genética , Guanina/análogos & derivados , Polimorfismo Genético/genética , Fumar/efeitos adversos , Neoplasias Torácicas/genética , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/secundário , Neoplasias Esofágicas/induzido quimicamente , Neoplasias Esofágicas/patologia , Esôfago/efeitos dos fármacos , Esôfago/metabolismo , Feminino , Genótipo , Guanina/metabolismo , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias Torácicas/induzido quimicamente , Neoplasias Torácicas/patologia
3.
Toxicol Pathol ; 32(5): 558-66, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15603540

RESUMO

Phentolamine is a reversible competitive alpha-adrenergic antagonist with similar affinities for alphal and alpha2 receptors. It has a long history of safe clinical use, and was developed as a potential therapy for male erectile dysfunction because of its capacity to increase the arteriolar blood flow to the corpora cavernosa. Phentolamine mesylate was administered to rats by oral gavage at daily doses of 10, 50, and 150 mg/kg for 24 months. A dose-related increase in mortality, ascribed to an exaggerated pharmacologic effect, was seen at high doses. Systemic exposure as measured by plasma drug concentration increased with dose and duration of dosing and slight drug accumulation occurred, particularly in high-dose males. In the treated groups, 10 males and 1 female were diagnosed with hibernomas, neoplasms of brown adipose tissue, which appeared in the thoracic cavity or retroperitoneal area as circumscribed, tan to reddish-brown lobulated masses. Histologically, the masses were well circumscribed with variably sized lobules defined by a rich capillary network and consisted of closely apposed oval to polygonal cells with large amounts of cytoplasm and a centrally located nucleus. The cytoplasm's appearance varied from multivacuolated to univacuolated to granular eosinophilic. In a few cases, neoplastic emboli were observed in capsular vessels. Ultrastructurally, the neoplastic cells contained numerous mitochondria with transverse parallel cristae that occupied over 60% of the cytoplasm and lipid droplets. This study documents the previously unreported development of hibernomas in rats treated with phentolamine mesylate.


Assuntos
Antagonistas Adrenérgicos alfa/toxicidade , Carcinógenos/toxicidade , Lipoma/induzido quimicamente , Fentolamina/toxicidade , Neoplasias Retroperitoneais/induzido quimicamente , Neoplasias Torácicas/induzido quimicamente , Administração Oral , Antagonistas Adrenérgicos alfa/administração & dosagem , Antagonistas Adrenérgicos alfa/sangue , Animais , Testes de Carcinogenicidade , Carcinógenos/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Lipoma/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/ultraestrutura , Fentolamina/administração & dosagem , Fentolamina/sangue , Ratos , Ratos Sprague-Dawley , Neoplasias Retroperitoneais/patologia , Neoplasias Torácicas/patologia
5.
Med Cutan Ibero Lat Am ; 16(6): 497-501, 1988.
Artigo em Espanhol | MEDLINE | ID: mdl-3073276

RESUMO

Presently exist only four regions where the supply of drinking water with an abnormally high content of arsenic and/or its salts, produces cutaneous signs generically termed "arsenical toxidermias" or "chronic arsenism"; they are: Mexico, Taiwan, Chile and Argentina. In this paper details are given of the typical skin lesions of hydroarsenism and the generally multiple epitheliomas of varied histological and clinical pattern in 340 patients; the diseases characterized for not being acute but chronic and the relanodermia holds a secondary place. Among histologically diagnosed carcinomas, deep basal-cell (276) and superficial multiple basal-cell (130) carcinomas predominate over the squamous-cell carcinomas (239) and Bowen disease (113); 18 mixed carcinomas were found. In these 340 patients, 51 carcinomas of the internal organs (15%), 34 of lungs, 8 of larynx, 3 of stomach, 2 of liver and 1 of pharynx, trachea, esophagus and breast in a man were diagnosed, which evolved in a similar manner to that of not arsenical patients.


Assuntos
Intoxicação por Arsênico , Neoplasias do Sistema Digestório/induzido quimicamente , Neoplasias Cutâneas/induzido quimicamente , Neoplasias Torácicas/induzido quimicamente , Poluentes Químicos da Água/efeitos adversos , Poluentes da Água/efeitos adversos , Abastecimento de Água , Adulto , Idoso , Argentina , Neoplasias do Sistema Digestório/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Cutâneas/complicações , Neoplasias Torácicas/complicações
6.
Exp Pathol ; 26(3): 179-83, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6542873

RESUMO

After intratracheal instillation of glass fibres and crocidolite in male Syrian golden hamsters, besides lung carcinomas a number of mesotheliomas of the epitheloid type occurred. These were examined with light microscopy (LM) and scanning electron microscopy (SEM); the characteristics of the tumours are described.


Assuntos
Poeira/efeitos adversos , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Sarcoma Experimental/patologia , Animais , Cricetinae , Neoplasias Pulmonares/etiologia , Masculino , Mesocricetus , Mesotelioma/etiologia , Mesotelioma/ultraestrutura , Microscopia Eletrônica de Varredura , Neoplasias Torácicas/induzido quimicamente , Neoplasias Torácicas/patologia
9.
Ann Anat Pathol (Paris) ; 21(2): 237-46, 1976.
Artigo em Francês | MEDLINE | ID: mdl-970688

RESUMO

The results after intraperitoneal injection of fibrous and granular dusts in rats suggest, that the fibrous shape of asbestos is the cause of its cancerogenicity. Fibrous dusts other than asbestos (for example glass fibers) may induce tumours, when their diameters are like that of asbestos and the fibres are invariable in tissue. It is supposed, that a fibre with a diameter less than 1 mum and a length greater than 3 mum has a cancerogenic effect. The interpretation of the experimental results considering the cancerogenesis in humans is discussed, especially concerning the effect of fibrous glass.


Assuntos
Amianto/efeitos adversos , Vidro , Neoplasias Abdominais/induzido quimicamente , Animais , Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Poeira , Exposição Ambiental , Feminino , Humanos , Injeções Intraperitoneais , Neoplasias Experimentais , Tamanho da Partícula , Ratos , Neoplasias Torácicas/induzido quimicamente
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