Promoter polymorphisms of the PCA3 gene are not associated with its overexpression in prostate cancer patients

In male, the prostate cancer (PCa) is one of the most frequent neoplasias and the second cause of cancer deaths worldwide. In 2015, more than 6000 men died in Mexico due to this disease. In this regard, prostate cancer associated gene 3 (PCA3) has become an interesting target in PCa as is found highly overexpressed. Moreover, TAAA tandem repeats have been suggested to be associated with the regulation of PCA3 expression and, in turn, to be related with the development of the disease. The aim of the study was to understand the genetic basis of the disease in search for a better diagnosis. Expression levels of PCA3 gene were analysed in tissue of 13 patients diagnosed with PCa and six patients diagnosed with a benign prostatic disease (BPD). The absolute expression of PCA3 was quantified by real-time PCR. Genotype for TAAA tandem repeats was measured using automatic sequencing and the results were analysed to determine whether an association existed between them. We identified three alleles: 4, 5, 6 and four genotypes: 4/5, 5/5, 5/6, 6/6. Our analysis identified a mutation in the nucleotide 76764237 of the PCA3 gene that generates an extra TAAA tandem repeat. The nucleotide mutation is present in 61.53% of PCa and 66.66% of BPD patients. Our study revealed the presence of a mutation in the PCA3 gene that generates an extra TAAA tandem. We observed no association between the absolute expression of PCA3 messenger and the number of TAAA repetitions.

Ophthalmic manifestations of HIV in the highly active antiretroviral therapy era / Manifestaciones oftálmicas del VIH en la era de la terapia antiretroviral altamente activa

HIV-related eye disease can be classified as retinal HIV microangiopathy, opportunistic infections, neuro-ophthalmic manifestations and unusual malignancies. There is a 52-100% lifetime accumulative risk of HIV patients developing eye problems. Seventy-seven per cent of patients with ocular manifestations of HIV had CD4 counts < 200 cells/µL. Cytomegalovirus (CMV) is the most prevalent opportunistic infection, however, Africa has a low incidence of this, and more commonly squamous cell carcinoma, compared to the western hemisphere. Due to highly active antiretroviral therapy (HAART), the anti-CMV therapy may be discontinued if the CD4+ T cell count is > 100 cells/µL for a minimum of three months. Despite HAART, patients with a CD4 count < 50 cells/µL have a similar risk of developing CMV retinitis as compared to the pre-HAART era. Opportunistic infections include CMV, herpetic retinopathy (progressive outer retinal necrosis - PORN), less commonly toxoplasmosis, pneumocystis and cryptococcus. Malignancies associated with HIV include Kaposi's sarcoma and conjunctival squamous cell carcinoma. Cranial nerve palsies, optic disc swelling and atrophy are characteristic neuro-ophthalmic features. They usually occur secondary to meningitis/encephalitis (from cryptococcus and tuberculosis). With the advent of HAART, new complications have developed in CMV retinitis: immune recovery uveitis (IRU) and cystoid macula oedema (CMO). Immune recovery uveitis occurs in 71% of patients if HAART is started before the induction of the anti-CMV treatment. However, this is reduced to 31% if HAART is started after the induction treatment. Molluscum contagiosum and Kaposi's sarcoma can spontaneously resolve on HAART. Highly active anti-retroviral therapy has reduced the frequencies of opportunistic infections and improved the remission duration in HIV patients.

Las enfermedades oculares relacionadas con el VIH pueden clasificarse como microangiopatía retiniana por VIH, infecciones oportunistas, manifestaciones neuro-oftálmicas, y tumores inusuales. Hay un riesgo acumulativo de por vida de 52-100% de que los pacientes con VIH desarrollen problemas oculares. Setenta y siete por ciento de los pacientes con manifestaciones oculares por VIH tenían conteos de CD4 < 200 células/µL. El citomegalovirus (CMV) es la infección oportunista más frecuente. Sin embargo, África tiene una baja incidencia de CVM, siendo en cambio más común el carcinoma de células escamosas, en comparación con el hemisferio occidental. Debido a la terapia antiretroviral altamente activa (TAAA), la terapia anti-CMV puede suspenderse si el conteo de células CD4+ T es > 100 células/µL por un mínimo de tres meses. A pesar de la terapia TAAA, los pacientes con un conteo de CD4 < 50 células/µL tienen un riesgo similar de desarrollar retinitis por CMV en comparación con la era pre-TAAA. Las infecciones oportunistas incluyen CMV, retinopatía herpética (necrosis retiniana progresiva externa - PORN), y menos comúnmente toxoplasmosis, pneumocistosis, y cryptococcus. Los tumores malignos asociados con el VIH incluyen el sarcoma de Kaposi y el carcinoma de células escamosas de conjuntiva. La parálisis del nervio craneal, la inflamación del disco óptico, así como la atrofia, son características neuro-oftálmicas típicas. Generalmente se presentan de forma secundaria en los casos de meningitis, encefalitis (cryptococcus y tuberculosis). Con el advenimiento de TAAA, se han desarrollado nuevas complicaciones de la retinitis por CMV, a saber, la uveitis por recuperación inmunológica (IRU por su sigla en inglés) y el edema macular cistoide (EMC). La uveitis por recuperación inmunológica ocurre en 71% de los pacientes si la terapia TAAA se comienza antes de la inducción del tratamiento anti-CMV. Sin embargo, esta cantidad se reduce a un 31% si TAAA se inicia después del tratamiento de inducción. El molusco contagioso y el sarcoma de Kaposi pueden desaparecer espontáneamente con el TAAA. La terapia anti-retroviral altamente activa ha reducido las frecuencias de las infecciones oportunistas, y mejorado la duración de la remisión en pacientes con VIH.