Short-term treatment with cabergoline can lead to tumor shrinkage in patients with nonfunctioning pituitary adenomas.

This study was carried out to evaluate the effectiveness of cabergoline in the treatment of nonfunctioning pituitary adenomas (NFPA), in a short-term follow-up period. Nineteen patients (10 men and 9 women) followed at the University Hospital of Brasilia and harboring nonfunctioning pituitary macroadenomas were enrolled in the study. Eleven patients were previously submitted to transsphenoidal surgery, and in 8 patients no previous treatment had been instituted. Their response to the use of cabergoline (2 mg/week) by 6 months was evaluated. Significant tumor shrinkage (above 25 % from baseline tumor volume) was observed in 6 (31.6 %) of the 19 patients, and no adverse effects were observed during treatment. In 9 patients (47.4 %), a reduction in tumor volume of at least 10 % was noted, whereas tumor growth was observed in four patients (increase above 25 % was only observed in one patient). Cabergoline (2 mg/week) can lead to significant tumor shrinkage in NFPA in a considerable number of patients, and this effect can be observed early (6 months after starting medication). Thus, this therapeutic strategy may be a low cost and safe alternative for treatment of NFPA in patients with remnant or recurrent tumor after transsphenoidal surgery or in those not operated by contraindications or refusal to surgical procedure.

Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV).

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.

Control of Cytokines in Latent Cytomegalovirus Infection.

Human cytomegalovirus (HCMV) has evolved a number of mechanisms for long-term co-existence within its host. HCMV infects a wide range of cell types, including fibroblasts, epithelial cells, monocytes, macrophages, dendritic cells, and myeloid progenitor cells. Lytic infection, with the production of infectious progeny virions, occurs in differentiated cell types, while undifferentiated myeloid precursor cells are the primary site of latent infection. The outcome of HCMV infection depends partly on the cell type and differentiation state but is also influenced by the composition of the immune environment. In this review, we discuss the role of early interactions between HCMV and the host immune system, particularly cytokine and chemokine networks, that facilitate the establishment of lifelong latent infection. A better understanding of these cytokine signaling pathways could lead to novel therapeutic targets that might prevent latency or eradicate latently infected cells.

Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene.

Pendred Syndrome (PS) is an autossomal recessive disorder characterized by sensorineural deafness, goiter and iodide organification defect. The hearing loss is associated with inner ear abnormalities, ranging from an isolated enlarged vestibular aqueduct (EVA) to a typical coclear dysplasia. Mutations in the gene that encodes pendrin (SLC26A4), a chloride/iodide transporter, have been shown to be associated with PS. We describe the clinical and molecular characteristics of a large consanguineous family harboring a mutation in the SLC26A4 gene. The proband was a 26-year-old deaf Brazilian woman who presented a bulky multinodular goiter and hypothyroidism since puberty. Five other siblings were deaf: one brother had a similar phenotype, three siblings also had goiters but normal thyroid function tests, and one brother had only a subtle thyroid enlargement. Other 4 siblings had no thyroid or hearing disorder. Parents were first degree cousins and had normal hearing. The mother was healthy, except for subclinical hypothyroidism; the father was deceased. A perchlorate test in the proband showed a discharge of 21% of the incorporated iodide 2h after the administration of 1g of KClO4. Audiological examinations showed profound hearing loss in all deaf subjects; CT and MRI of the temporal bones showed EVA in all of them. Genomic DNA was isolated from whole blood, from the 6 affected and 4 unaffected siblings, the mother and control. The coding region of the PDS gene (exons 2-21), including exon/intron boundaries, were amplified by PCR and sequenced. A single base-pair (T) deletion at position 1197 of exon 10 was detected in homozygous state in the 6 deaf siblings. The mother and 2 unaffected siblings were heterozygous for this mutation, which has been described by Everett et al. The 1197delT mutation is predicted to result in a frameshift and a truncated protein. The existence of PS phenocopies and intrafamilial phenotypic variability are well documented. The definite diagnosis requires molecular analysis. Our study illustrates the value and challenges of mutational analysis in selected patients with PS.

Pendred syndrome in a large consanguineous Brazilian family caused by a homozygous mutation in the SLC26A4 gene / Síndrome de Pendred causada por mutação em homozigoze no gene SLC26A4 em uma família brasileira consangüínea

Pendred Syndrome (PS) is an autossomal recessive disorder characterized by sensorineural deafness, goiter and iodide organification defect. The hearing loss is associated with inner ear abnormalities, ranging from an isolated enlarged vestibular aqueduct (EVA) to a typical coclear dysplasia. Mutations in the gene that encodes pendrin (SLC26A4), a chloride/iodide transporter, have been shown to be associated with PS. We describe the clinical and molecular characteristics of a large consanguineous family harboring a mutation in the SLC26A4 gene. The proband was a 26-year-old deaf Brazilian woman who presented a bulky multinodular goiter and hypothyroidism since puberty. Five other siblings were deaf: one brother had a similar phenotype, three siblings also had goiters but normal thyroid function tests, and one brother had only a subtle thyroid enlargement. Other 4 siblings had no thyroid or hearing disorder. Parents were first degree cousins and had normal hearing. The mother was healthy, except for subclinical hypothyroidism; the father was deceased. A perchlorate test in the proband showed a discharge of 21 percent of the incorporated iodide 2h after the administration of 1g of KClO4. Audiological examinations showed profound hearing loss in all deaf subjects; CT and MRI of the temporal bones showed EVA in all of them. Genomic DNA was isolated from whole blood, from the 6 affected and 4 unaffected siblings, the mother and control. The coding region of the PDS gene (exons 2-21), including exon/intron boundaries, were amplified by PCR and sequenced. A single base-pair (T) deletion at position 1197 of exon 10 was detected in homozygous state in the 6 deaf siblings. The mother and 2 unaffected siblings were heterozygous for this mutation, which has been described by Everett et al. The 1197delT mutation is predicted to result in a frameshift and a truncated protein. The existence of PS phenocopies and intrafamilial phenotypic variability are...

A syndrome de Pendred (SP) é uma doença autossômica recessiva caracterizada por surdez neurossensorial, bócio e defeito de organificação do iodo. A perda auditiva está associada a anormalidades do ouvido interno, desde a dilatação isolada do aqueduto vestibular (DAV) até uma típica displasia coclear. Mutações no gene que codifica a pendrina (SLC26A4), um transportador de cloreto/iodeto, têm sido associadas à SP. Descrevemos as características clínicas e moleculares de uma grande família consangüínea portadora de uma mutação no gene SLC26A4. O caso-índice era uma paciente do sexo feminino, brasileira, 26 anos, portadora de surdez congênita, que apresentava um volumoso bócio multinodular e hipotireoidismo desde a puberdade. Outros cinco irmãos eram surdos: um irmão tinha fenotipo semelhante, três também tinham bócio, porém com função tiroideana normal e um irmão tinha apenas um discreto aumento da tiróide. Outros quatro irmãos não apresentavam alteração tiroideana ou auditiva. Os pais eram primos de primeiro grau e tinham audição normal. A mãe era saudável, exceto por hipotireoidismo subclínico; o pai era falecido. O teste do perclorato no caso-índice revelou a liberação de 21 por cento do iodo incorporado duas horas após a administração de 1 g de KClO4. Os exames audiológicos mostraram perda auditiva profunda em todos os indivíduos afetados; TC e RMN dos ossos temporais mostraram DAV em todos eles. O DNA genômico foi isolado do sangue total dos seis irmãos afetados e dos quatro não-afetados, da mãe e do controle. A região codificante do gene PDS (éxons 2-21), incluindo as junções éxon/íntron, foram amplificadas por PCR e seqüenciadas. Foi detectada a deleção de uma base (T) na posição 1197 do éxon 10, em homozigoze, nos seis irmãos afetados. A mãe e dois irmãos não-afetados eram heterozigotos para a mutação, que foi descrita inicialmente por Everett e cols. A mutação 1197delT provavelmente resulta em um erro de fase de leitura (frameshift)...