Các bài báo tiêu biểu
The technique for radical retropubic prostatectomy has been modified to avoid injury to the branches of the pelvic plexus that innervate the corpora cavernosa. The surgical procedure is based on an understanding of the anatomical relationships between the branches of the pelvic plexus that innervate the corpora cavernosa, the capsular branches of the prostatic vessels that provide the scaffolding for these nerves, and the lateral pelvic fascia. The modifications involve two steps in the procedure: 1) the incision in the lateral pelvic fascia is placed anterior to the neurovascular bundle, which is located dorsolateral to the prostate along the pelvic sidewall; 2) the lateral pedicle is divided close to the prostate to avoid injury to the branches of the pelvic plexus that accompany the capsular vessels of the prostate. Pathologic evaluation of 16 prostatic specimens removed by this modified procedure demonstrated no compromise in the adequacy of the surgical margins. Postoperative sexual function was evaluated in 12 men who underwent the procedure 2‐10 months previously. All have experienced erections and six have achieved successful vaginal penetration and orgasm. Of the six patients with sexual partners who have been followed 6 months or longer, five (83%) are fully potent. These data indicate that it is possible to cure localized prostatic cancer with surgery and maintain postoperative sexual function.
Histone deacetylase 1 (HDAC1) là một co-ức chế có vai trò trong việc điều chỉnh quá trình phân hóa và tăng trưởng tế bào. HDAC1 được điều chỉnh tăng lên trong các mô ác tính so với mô lành tính, và nhắm đến một số yếu tố phiên mã bao gồm cả p53.
Bằng phương pháp nhuộm miễn dịch mô học, sự biểu hiện protein HDAC1 đã được nghiên cứu trong các mẫu mô tuyến tiền liệt của người và mô hình xenograft chuột CWR22. Cũng đã tiến hành phân tích bằng dòng tế bào và huỳnh quang phân giải.
HDAC1 đã được điều chỉnh tăng trong các tổn thương tiền ác tính và ác tính, với mức tăng biểu hiện cao nhất trong các loại ung thư kháng hormoon (HR). Sử dụng mô hình xenograft CWR22, chúng tôi đã chỉ ra rằng điều chỉnh HDAC1 phụ thuộc vào androgen. Sự biểu hiện quá mức của HDAC1 dẫn đến tăng trưởng tế bào đáng kể và sự chuyển hướng về kiểu biểu hiện cytokeratin (CK) không phân hóa trong một dòng clone PC3M liên tục biểu hiện HDAC1.
Nghiên cứu này nhấn mạnh tầm quan trọng của HDAC1 trong quá trình phân chia tế bào và sự phát triển của ung thư tuyến tiền liệt (CaP) và đề xuất một cơ chế cho việc tuyển mộ HDAC1 vào nhân tế bào. HDAC1 có thể là một mục tiêu điều trị quan trọng, đặc biệt trong giai đoạn độc hại nhất của tình trạng độc lập với androgen. © 2004 Wiley‐Liss, Inc.
The majority of the prostatic cancers are adenocarcinomas characterized by glandular formation and the expression of luminal differentiation markers androgen receptor (AR) and prostate‐specific antigen (PSA). Most adenocarcinomas are indolent and androgen‐dependent. Hormonal therapy that inhibits AR signaling produces symptomatic relief in patients with advanced and metastatic adenocarcinomas. Prostatic small cell neuroendocrine carcinoma (SCNC) is a variant form of prostate cancer (PC). In contrast to adenocarcinoma, the tumor cells of SCNC do not form glands and are negative for AR and PSA. SCNC is extremely aggressive and does not respond to hormonal therapy. The purpose of this study was to compare the important and relevant features of two most commonly used PC cell lines, LNCaP and PC3, with prostatic adenocarcinoma and SCNC.
Xenograft tumors of LNCaP and PC3 were prepared and compared with human prostatic adenocarcinoma and SCNC for the expression of key signaling molecules by immunohistochemistry and Western blot analysis.
LNCaP cells express AR and PSA and their growth is inhibited by androgen withdrawal, similar to human prostatic adenocarcinoma. PC3 cells do not express AR and PSA and their proliferation is independent of androgen, similar to SCNC. Adenocarcinoma cells and LNCaP cells are negative for neuroendocrine markers and stem cell‐associated marker CD44 while SCNC and PC3 cells are positive. LNCaP cells have identical cytokeratin profiles to adenocarcinoma while PC3 cells have cytokeratin profiles similar to SCNC.
LNCaP cells share common features with adenocarcinoma while PC3 cells are characteristic of SCNC. Prostate 71:1668–1679, 2011. © 2011 Wiley‐Liss, Inc.
Androgen, besides having the well‐established agonistic ability to stimulate prostate cell proliferation, also has an antagonistic ability to inhibit prostatic cell death. This statement is based upon the observations that 1) only 2.1% of the total prostatic cells die per day when serum testosterone level is sufficient for chronic maintenance of the gland; 2) 3 days following castration, when serum testosterone level is less than 10% of the intact value, the percentage of total prostatic cells now dying per day is increased tenfold to a value of 20.8%; and 3) this high rate of prostatic cell death can be inhibited following castration if serum androgen level is appropriately maintained by exogenous testosterone treatment. The serum testosterone level needed to antagonistically inhibit prostatic cell death (ie, 1.4 ± 0.1 ng/ml) is more than twofold lower than that needed to antagonistically stimulate prostatic cell proliferation (3.3 ± 0.4 ng/ml). Due to this dose difference, it is experimentally possible in castrated rats to inhibit prostatic cell death selectively without simultaneously stimulating cell proliferation and still completely prevent the rapid involution of the prostate following castration. These results suggest that the rapid involution of the prostate following castration is predominantly due to a decreased antagonistic effect of androgen on prostatic cell death rather than to a decreased agonistic effect of androgen on prostatic cell proliferation and that these two androgenic effects are distinct processes in the prostate.
Hematopoietic cells home to bone by means of chemo‐attraction to marrow chemokines, and interaction of chemokines with their receptors leads to the expression/activation of adhesion molecules and proteases. Recent evidence suggests that similar mechanisms may be active in cancer metastasis. Previously, we showed that metalloproteases (MMPs), and in particular MMP‐9, play a role in prostate cancer (PC) expansion in bone.
We used a variety of methods including RT‐PCR, immunohistochemistry, ELISA, gelatin zymography, cellular motility and invasion, and subcellular fractionation of PC cells applied to in vivo and in vitro models.
Here we showed that (a) CXCL12/CXCR4 axis is expressed in PC bone metastasis; (b) exogenous CXCL12 induced MMP‐9 expression by PC cells; (c) bone stromal cells and bone tissue conditioned media induced the migration of PC cells in a CXCR4‐dependent manner; (d) pharmacological inhibition of PI3 kinase and MAP kinase pathways abrogated CXCL12‐induced MMP‐9 expression and invasion of PC cells; (e) exogenous CXCL12 induced Akt1 phosphorylation is indispensable for proMMP‐9 secretion, migration, and invasion of PC cells; (f) CXCR4 was localized to lipid rafts in PC cells and initiated Akt phosphorylation.
These data suggest that chemoattractive mechanisms involve migration of cancer cells towards bone tissue, and that cell signaling induced by binding of the chemokine to its receptor leads to the activation of multiple signaling pathways and subsequent secretion of MMP‐9 into the local environment. These findings provide a link between chemoattractive mechanisms, growth of tumor cells in bone, and tumor‐enhanced bone matrix turnover. © 2005 Wiley‐Liss, Inc.
Adenocarcinoma of the prostate produces specific ultrasonic findings that can be used in diagnosis. We have examined 211 patients using transrectal ultrasound in both the sagittal and axial planes. Thirty‐three carcinomas were detected, and 31 histologically confirmed; 24 by needle biopsy, six by transurethral resection, one by total prostatectomy, and two by the demonstration of distant metatases. On ultrasound, all of the carcinomas were less echogenic than normal prostate. All appeared to originate in the peripheral zone of the prostate and produced asymmetry of the gland. The majority of carcinomas in this series showed capsular involvement and ten penetrated and extended beyond the prostatic capsule.
The results of this series indicate that transrectal ultrasound can be used to detect cancer of the prostate gland. Ultrasound demonstrated the extent of tumor involvement and enabled accurate staging of these cancers.
Estrogen signaling mediated by the estrogen receptor beta (ERβ) has potential implications in normal and abnormal prostate growth. Few studies have addressed this issue in human prostate tissue leaving conflicting results on the immunolocalization of the ERβ in benign and neoplastic lesions.
Using a new monoclonal antibody, the current study reports on the differential expression of the ERβ in tissue sections from 132 patients with prostate cancer.
The prostatic epithelium expressed the ERβ extensively in secretory luminal cell types and at lower levels in basal cells. Atrophic changes of the peripheral zone (PZ) were more immunoreactive than hyperplastic lesions of the transition zone (TZ). When compared with glandular tissue of the PZ, high‐grade prostatic intraepithelial neoplasia (HGPIN) revealed decreased levels of the ERβ in 30 of 47 cases and was unreactive in six lesions. In informative cases with suitable internal controls, all primary tumors (n = 60), lymph node (n = 7), and bone metastases (n = 5) expressed the ERβ at variable degree. No correlation was found between the ERβ status, the primary Gleason grade (
The secretory epithelium is a major target of ERβ‐mediated estrogen signaling in the human prostate. Its downregulation in HGPIN is consistent with chemopreventive effects that the ERβ may exert on the prostatic epithelium. The continuous expression of the receptor protein at significant levels in untreated primary and metastatic adenocarcinoma indicates that these tumors can use estrogens through an ERβ‐mediated pathway. The partial loss of the ERβ in recurrent tumors after androgen‐deprivation may reflect the androgen‐dependence of ERβ gene expression in human prostate cancer. Prostate 54: 79–87, 2003. © 2002 Wiley‐Liss, Inc.
Analyses of the proteins of azoospermic ejaculates from subjects with defective seminal vesicles demonstrated that three prostatic‐secreted proteins were predominant. Prostatic acid phosphatase (PAP), prostate‐specific antigen (PSA; or γ‐seminoprotein), and β‐microsemi‐noprotein (β‐MSP; or β‐inhibin), were identified as the three predominant proteins secreted by the normal human prostate gland. Immunohistochemical localization of these proteins, in the epithelium of normal prostatic acini and ducts, with the avidin‐biotin complex procedure demonstrated that each PAP‐immunoreactive cell was invariably immunoreactive both with PSA‐and β‐MSP‐monospecific antisera as well.