PubMed Health⌕ Search

Biomedical subjects

M Gleave

Publications and source records attributed to M Gleave.

24 records · Page 2Linked to original sources
PubMed1996

[Hormone release and intermittent hormonal therapy in the LN CaP model of human prostate cancer].

Androgen-independent progression invariably occurs following castration of patients with prostate cancer. Animal model data suggest that androgen resistance may result from adaptive cell survival mechanisms activated by androgen withdrawal. If this is true, then re-exposure to, or low levels of, androgens may suppress or downregulate these mechanisms. The objective of this study is to determine whether intermittent androgen suppression (IAS) delays the onset of nonandrogen-regulated PSA production in the LNCaP prostate tumour model, when compared to continuous androgen suppression (CAS). Serum PSA levels correlate highly with LNCaP tumour volume and decrease rapidly following castration; beginning 3-4 weeks post-castration LN CaP tumours become androgen-independent with respect to PSA gene expression and produce PSA in amounts similar to precastrate state. In this study, IAS-treated mice were implanted with testosterone pellets beginning two weeks post-castration; cycles of testosterone replacement for 1 week and withdrawal for 2 weeks were repeated until serum PSA levels no longer returned to baseline. IAS therapy prolonged time to androgen-independent PSA production 3-fold, from an average of 26 days in the CAS group to 77 days in the IAS group. Serum and LNCaP tumour mRNA PSA levels remained below precastrate levels by 60 days post-castration in 75% of the IAS group, while serum PSA in all mice in the CAS group exceeded precastrate PSA by 28 days post-castration. Following castration, serum PSA levels increased 9-fold faster with CAS compared to IAS therapy. Observations using IAS in the LNCaP tumour model suggest that the onset of androgen-independent PSA gene regulation is prolonged 3-fold, perhaps due to androgen-induced differentiation and/or downregulation of androgen-suppressed gene expression.

Androgens↗
PubMed1995

[Theoretical considerations and initial clinical results of intermittent hormone treatment of patients with advanced prostatic carcinoma].

Androgen suppression is the routine approach to the treatment of advanced prostate cancer. Using intermittent androgen suppression by taking the advantage of the reversible action of medical castration results in the maintenance of apoptotic potential. The experiments in the androgen-dependent androgen-dependent Shionogi carcinoma tumor model as well as clinical experience in a group of men with prostate malignancy are presented in this report. These consecutive cycles of androgen withdrawal and replacement afford an improved quality of life when the patient is off therapy. It is possible to reduce toxicity, cost of treatment and to delay tumor progression. Whether survival is affected in a beneficial or adverse way still remains to be studied.

Androgen Antagonists↗
PubMed1991

Acceleration of human prostate cancer growth in vivo by factors produced by prostate and bone fibroblasts.

Prostate cancer, the most prevalent cancer affecting men, frequently metastasizes to the axial skeleton where it produces osteoblastic lesions with growth rates often exceeding that of the primary tumor. To evaluate the role of tumor cell-host stromal interaction and stromal specific growth factors (GFs) in prostate cancer growth and progression, we coinoculated athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts s.c. LNCaP tumor formation was most consistently induced by human bone (MS) fibroblasts (62%), followed by embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney, or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. The human prostate component of these tumors was confirmed with immunohistochemical staining for prostate-specific antigen (PSA), Northern analysis for PSA expression, and Southern analysis for human repetitive Alu sequences. Elevations in serum PSA paralleled the histomorphological and biochemical findings. LNCaP and fibroblast cell-conditioned media (CM) was used to determine whether autocrine and paracrine mitogenic pathways exist between LNCaP and fibroblast cells in vitro, and various defined GFs were tested to identify possible active factors. Mitogenic assays revealed a 200-300% bidirectional stimulation between LNCaP and bone or prostate fibroblast-derived CM. Lung, normal rat kidney, and 3T3 fibroblast CM were not mitogenic for LNCaP cells. Among the purified GFs tested basic fibroblast growth factor (bFGF) was the most potent mitogen, stimulating LNCaP growth 180% in a concentration-dependent manner. Transforming growth factor alpha and epidermal growth factor were both minimally mitogenic. Coinoculation of LNCaP cells with a slowly absorbed matrix (Gelfoam) absorbed with bFGF or dialyzed and concentrated rUGM or MS CM was also capable of inducing LNCaP tumor formation in vivo. These observations illustrate that fibroblasts differentially modulate prostate cancer growth through the release of paracrine-mediated GFs, possibly including bFGF, and that tumor-stromal cell interactions play an important role in prostate cancer growth and progression.

Androgens↗
PubMed1987

Neonatal renomegaly.

A retrospective clinical review was done to study the value of ultrasound and renography in the investigation of 100 neonates with renomegaly. Abnormalities in 73 patients were detected antenatally with ultrasonography. Of the neonates 47 had lower urinary tract pathological conditions and ultrasound was more than 90 per cent accurate in identifying the accompanying ureteral dilatation. A total of 53 neonates had upper tract anomalies (ureteropelvic junction obstruction or cystic dysplasia). With ultrasonography the degree of pyelocaliectasis in patients with ureteropelvic junction obstruction was classified as mild (22 units), moderate (13) or severe (7). Initial treatment and followup were reviewed to study the clinical course of neonates with mild to moderate degrees of pyelocaliectasis followed nonoperatively, and to determine whether the diuretic renogram had a predictive role in identifying which kidneys were most likely to deteriorate.

Dilatation, Pathologic↗
PubMedDate not supplied

Breaststroker's knee. An analysis of epidemiological and biomechanical factors.

Competitive swimmers have a high incidence of breaststroke-related knee injuries. Although previous investigators have implicated the terminal phase of the kick in the injury mechanism, athletes often complain of pain during the initial phase of rearward thrust. Disagreement in the current literature surrounds the precise anatomical derangement(s) constituting "breaststroker's knee." The purpose of this investigation was to delineate the epidemiology, anatomy, and pathobiomechanics of breaststroke knee injuries. Descriptive data were obtained by surveying 391 athletes. An extremely high incidence of knee pain was documented both among breaststroke specialists (73%) and nonbreaststrokers (48%). Age, years of competitive swimming, and specific training characteristics were positively correlated with knee pain. Both the medial collateral ligament and the inferomedial patellar border were involved. A further 21 swimmers were assessed in detail using four methods: interview, physical examination, Cybex II isokinetic quadriceps and hamstring testing, and cinematographic analyses. The interview and physical examination data supported the conclusions derived from the descriptive data, while Cybex testing and kinematic film analyses failed to demonstrate statistical differences between the injured and noninjured groups. Although kinematic film analyses did not demonstrate statistical differences between cases and controls, dramatic differences in the injury rate were noted when hip abduction angles at kick initiation were less than 37 degrees or greater than 42 degrees. This bimodal increase in injury rates suggests that modification of hip abduction at kick initiation, in conjunction with altered training regimens, will lead to a reduction in medial knee joint stress and hence fewer breastroke injuries.

Adolescent↗