RESUMO
A phase I-II study to evaluate gene-mediated cytotoxic immunotherapy in newly diagnosed prostate cancer before radical prostatectomy was conducted in Monterrey, Mexico. First, to investigate delivery of adenovirus to the prostate, fluorescently labeled vector was injected into fresh prostatectomy specimens and distribution was visually analyzed. The optimal volume and site instillation was then used for transrectal ultrasound guided intraprostatic injection in 10 patients with adenocarcinoma scheduled for radical prostatectomy. Each received two apical and two basal 0.5 ml injections of AdV-tk for a total of 1 × 10(11) vp followed by 14 days of prodrug. Nine patients continued to tumor resection: six high risk, one intermediate and two low risk. In vivo vector distribution was analyzed from the resected tissue of four patients. Patients were monitored for tumor progression and acute and long-term safety. For vector delivery, two apical and two basal injections of 0.5 ml led to optimal organ-wide distribution ex vivo and in vivo. Cytotoxicity was evidenced by transient rise in PSA and tumor histology. There were no significant adverse events deemed related to the treatment and no late toxicities after median follow-up of 11.3 years. All six high-risk patients had positive surgical margins and one had seminal vesicle involvement. Despite slow PSA rise post surgery in three of these patients, none developed metastases. The intermediate- and low-risk patients had complete resections and none have progressed. In conclusion, in vivo transrectal ultrasound guided instillation of an adenoviral vector into four sites in the prostate was practical as an outpatient procedure, well tolerated and led to distribution throughout the intraprostatic tumor mass. AdV-tk demonstrated no significant acute or late toxicities. Trends in PSA and disease progression conveyed the possibility of a sustained immune response against residual disease.
Assuntos
Adenoviridae/fisiologia , Terapia Viral Oncolítica/métodos , Neoplasias da Próstata/terapia , Adenoviridae/genética , Adenoviridae/imunologia , Idoso , Seguimentos , Técnicas de Transferência de Genes , Terapia Genética/métodos , Vetores Genéticos/genética , Vetores Genéticos/imunologia , Vetores Genéticos/farmacocinética , Humanos , Imunoterapia/métodos , Calicreínas/metabolismo , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/virologia , Simplexvirus/enzimologia , Simplexvirus/genética , Timidina Quinase/genéticaRESUMO
The entire coding regions of BRCA1 and BRCA2 were screened for mutations by heteroduplex analysis in 51 Mexican breast cancer patients. One BRCA1 and one BRCA2 truncating mutation each was identified in the group of 32 (6%) early-onset breast cancer patients (< or =35 years). Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case. No mutations or rare sequence variants have been identified in two additional families including each an early-onset breast cancer case and an ovarian cancer patient. The two truncating mutations (BRCA1 3857delT; BRCA2 2663-2664insA) and six of the rare variants have never been reported before and may be of country-specific origin. The majority of the alterations appeared to be distinct, with only one of them being observed in more than one family.
Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Adulto , Idade de Início , Análise Mutacional de DNA , DNA de Neoplasias/química , DNA de Neoplasias/genética , Saúde da Família , Feminino , Humanos , México , MutaçãoRESUMO
OBJECTIVE: To investigate the association between family history (FH) of neoplasia, gyneco-obstetric factors and breast cancer (BC) in a case-control study. In cases, to analyze those variables in relation with early onset of BC, the manner of detection (self-examination, prompted by pain, or casual), the size of tumor, and the elapsed time to seek medical attention. MATERIAL AND METHODS: Data from 151 prevalent BC cases and 235 age-matched controls were analyzed by multiple logistic regression, to assess the influence of BC risk factors. RESULTS: Ten per cent of patients and 1% of controls had first-degree relatives (FDR) with BC. Family history of FDR with BC (OR, 11.2; 95% CI 2.42-51.92) or with gastric or pancreatic cancer (OR, 17.7; 95% CI 2.2-142.6) was associated with BC risk. Breastfeeding at or under 25 years of age was protective against BC (OR, 0.40; 95% CI 0.24-0.66). The manner of tumor detection did not influence its size at the time of diagnosis. CONCLUSIONS: Our study confirms that FH of BC and/or of gastric or pancreatic carcinoma are risk factors for BC, while lactation at 25 years of age or earlier is protective.
Assuntos
Neoplasias da Mama/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/epidemiologia , Autoexame de Mama/estatística & dados numéricos , Estudos de Casos e Controles , Saúde da Família , Feminino , Humanos , México/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Tamanho da Amostra , Fatores SocioeconômicosRESUMO
A patient with granulosa cell tumor recurrence 14 years after primary resection, was treated with partial hepatectomy and adjuvant chemotherapy (vinblastine, cisplatin and bleomycin). She achieved complete remission and is free of disease 18 months after treatment.
