Bone-targeted therapies to reduce skeletal morbidity in prostate cancer / 亚洲男科学杂志(英文版)

Bone metastases are the main driver of morbidity and mortality in advanced prostate cancer. Targeting the bone microenvironment, a key player in the pathogenesis of bone metastasis, has become one of the mainstays of therapy in men with advanced prostate cancer. This review will evaluate the data supporting the use of bone-targeted therapy, including (1) bisphosphonates such as zoledronic acid, which directly target osteoclasts, (2) denosumab, a receptor activator of nuclear factor-kappa B (RANK) ligand inhibitor, which targets a key component of bone stromal interaction, and (3) radium-223, an alpha-emitting calcium mimetic, which hones to the metabolically active areas of osteoblastic metastasis and induces double-strand breaks in the DNA. Denosumab has shown enhanced delay in skeletal-related events compared to zoledronic acid in patients with metastatic castration-resistant prostate cancer (mCRPC). Data are mixed with regard to pain control as a primary measure of efficacy. New data call into question dosing frequency, with quarterly dosing strategy potentially achieving similar effect compared to monthly dosing for zoledronic acid. In the case of radium-223, there are data for both pain palliation and improved overall survival in mCRPC. Further studies are needed to optimize timing and combination strategies for bone-targeted therapies. Ongoing studies will explore the impact of combining bone-targeted therapy with investigational therapeutic agents such as immunotherapy, for advanced prostate cancer. Future studies should strive to develop biomarkers of response, in order to improve efficacy and cost-effectiveness of these agents.

Experimental model of the morphological and morphometric aspects of tissue repair in skin wounds submitted to beta radiation emitted by Strontium -90 in rats

O objetivo deste trabalho é relatar o uso do modelo experimental para investigação dos efeitos da radiação Beta do Estrôncio-90 no processo de reparação tecidual de feridas provocadas em ratos. Utilizamos 48 animais da linhagem EPM-1 Wistar, distribuídos em dois grupos que receberam a radiação em dias alternados (Grupo A) e diariamente (Grupo B). Cada grupo foi subdividido em quatro, cada um com 6 ratos, para estudo no 3º, 7º, 14º e 21º dias de pós-operatório. Realizou-se duas incisões no dorso de cada animal, suturou-se em seguida, sendo que a de situação cranial foi irradiada e a caudal serviu para controle. Nas datas determinadas, as feridas controle e irradiada foram observadas macroscopicamente e retiradas para preparo do estudo histológico comparativo ao microscópico óptico. Realizou-se em seguida, análise morfométrica para contagem de leucócitos, fibroblastos e fibras colágenas, submetidos a estudo estatístico.

The role of natural killer cells in the early period of infection in murine cutaneous leishmaniasis

In order to study the role of natural killer (NK) cells during the early period of Leishmania infection, BALB/c mice were selectively and permanently depleted of NK cells by injection with 90Sr and subsequently infected with Leishmania (Leishmania) amazonensis (HSJD-1 strain). 90Sr is known to selectively deplete NK cells, leaving an intact T- and B-cell compartment and preserving the ability to produce both interferon alpha and IL-2. This method of depletion has advantages when compared with depletion using anti-NK cell monoclonal antibodies because the effect is permanent and neither activates complement nor provokes massive cell death. In the present study, after one month of treatment with 90Sr, the depletion of NK cells was shown by a more than ten-fold reduction in the cytotoxic activity of these cells: 2 x 106 spleen cells from NK-depleted animals were required to reach the same specific lysis of target cells effected by 0.15 x 106 spleen cells from normal control animals. The histopathology of the skin lesion at 7 days after Leishmania infection showed more parasites in the NK cell-depleted group. This observation further strengthens a direct role of NK cells during the early period of Leishmania infection

Estudo histológico e morfométrico da reparaçäo de feridas cutâneas, provocadas em ratos, submetidas à radiaçäo beta do estrôncio-90 / Histologic and morphometric study on the healing of skin wounds in rats subwitted to Beta irradiation of Stroncium-90

O objetivo deste trabalho foi investigar os efeitos da radiaçäo Beta do Estrôncio-90 no processo de reparaçäo tecidual de feridas provocadas em ratos. Utilizamos 24 animais da linhagem EPM-1 Wistar distribuídos em 4 grupos. Receberam a radiaçäo em dias alternados e sua análise foi feita aos 3, 7, 14 e 21 dias de pós-operátorio. Realizou-se duas incisöes no dorso de cada animal, suturou-se em seguida, sendo que a de situaçäo cranial foi irradiada e a caudal serviu para controle. Nas àreas determinadas, as feridas controle e irradiada foram observadas macroscopicamente e retiradas para preparo do estudo histológico comparativo ao microscópio óptico. Realizou-se, em seguida, análise morfométrica para contagem de leucócitos, fibroblastos e fibras colágenas, submetidas a estudo estatístico. Da análise dos resultados, pode-se concluir que, em geral, a radiaçäo Beta do Estrôncio-90 provocou um aumento no número de leucócitos, uma diminuiçäo no número de fibroblastos e näo alterou o número de fibras colágenas, quando comparou-se a ferida irradiada à controle nos tempos do experimento

Use of beta radiation to control I.O.P.

The use of ophthalmic applicator containing Strontium-90 beta ray was used to bring about a change in I.O.P. by its effect on the ciliary body. The change in I.O.P. depends on the degree of damage done to the ciliary body. The study showed that the change in I.O.P. was directly proportional to the intensity of beta rays application - higher the dose of beta radiation more was the damage and more the reduction in I.O.P.