41 research outputs found
Genetic Analysis of Prostate Cancer
__Abstract__
The human prostate has the size of a chestnut and envelops the urethra as it
exits the bladder, below the bladder neck. It is the largest of the male accessory sex
glands, which also include the seminal vesicles, and bulbourethral gland. The prostate
is composed of glandular structures, which are tightly fused within a common capsule.
The prostate can be subdivided in a transitional, a central, and a peripheral zone(McNeal 1997). Histologically, the glandular structures are complex arrays
of luminal structures. Except for the larger ducts near the urethra, the ductal-acinar
system is lined by highly differentiated secretory columnar epithelial cells layered on
undifferentiated nonsecretory basal epithelial cells, thus forming a continuous layer
adjacent to the basement membrane. The glandular structures are
supported by stroma. The stromal compartment encompasses all cellular and extracellular
elements outside the epithelial basement membrane and includes smooth
muscle cells, blood vessels, lymphatic tissues, nerves, and fibroblasts embedded in a
loose collagenous matrix (reviewed by Cunha et al. 1987)(McNeal 1997)
Characterization of a zinc-finger protein and its association with apoptosis in prostate cancer cells
BACKGROUND: The transition from androgen-dependent to androgen-independent
prostate cancer is not fully understood but appears to involve multiple
genetic changes. We have identified a gene, GC79, that is more highly
expressed in androgen-dependent LNCaP-FGC human prostate cancer cells than
in androgen-independent LNCaP-LNO human prostate cancer cells. Physiologic
levels (0.1 nM:) of androgens repress expression of GC79 messenger RNA
(mRNA) in LNCaP-FGC cells. To determine the role of GC79, we cloned its
complementary DNA (cDNA) and functionally characterized its product.
METHODS: The differentially expressed GC79 gene was cloned from human
prostate cDNA libraries, sequenced, and transfected into mammalian cells
to study its function. Expression of GC79 was analyzed in various adult
and fetal human tissues and in prostate glands of castrated rats. The
association of GC79 expression and apoptosis was investigated in COS-1 and
LNCaP cells transfected with GC79 cDNA. All statistical tests are
two-sided. RESULTS: Sequence analysis indicates that GC79 encodes a large,
complex, multitype zinc-finger protein, containing nine C(2)H(2)-type
zinc-finger domains, a cysteine-rich region, and a GATA C(4)-type
zinc-finger domain. Castration-induced androgen withdrawal increased the
expression of GC79 mRNA in the regressing rat ventral prostate, suggesting
that the expression of GC79 mRNA is associated with the process of
apoptotic cell death in the rat ventral prostate. Transfection and
induction of GC79 cDNA in both COS-1 and LNCaP prostate cancer cells led
to an apoptotic index that was eightfold higher (P:<.001, two-sided
Student's t test) than that observed in uninduced transfected cells.
CONCLUSIONS: We have cloned an androgen-repressible gene, GC79, that is
potentially involved in apoptosis. This finding may have implications for
the development of androgen-independent prostate cancer and, ultimately,
for the treatment of prostate cancer
Pharmacodynamic Effects of Topical Omiganan in Patients With Mild to Moderate Atopic Dermatitis in a Randomized, Placebo-Controlled, Ph
Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (â18.5%; 95% confidence interval, â32.9 to â1.0; P = 0.04; and â8.2; 95% confidence interval, â16.3 to â0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials
Inter-and intra-patient variability over time of lesional skin microbiota in adult patients with atopic dermatitis
No effect of topical digoxin and furosemide gel for patients with external anogenital warts
Drug Delivery Technolog
Results of phase 2 trials exploring the safety and efficacy of omiganan in patients with human papillomavirus-induced genital lesions
AIMS\nMETHODS\nRESULTS\nCONCLUSION\n To assess safety and tolerability and explore pharmacodynamics and efficacy of omiganan in external anogenital warts (AGW) and vulvar high-grade squamous intraepithelial lesions (HSIL).\nTwo randomized controlled trials in patients with external AGW and vulvar HSIL were conducted. Patients received topical omiganan 2.5% or placebo gel once daily for 12 weeks with a follow-up of 12 weeks. Safety and tolerability were monitored and pharmacodynamics and clinical efficacy of omiganan were assessed by analysing lesion count, size and viral load. Self-reported pain, itch and quality of life were assessed by an electronic diary and questionnaire.\nTwenty-four AGW and 12 vulvar HSIL patients were enrolled. All patients had a high treatment adherence (99%). No serious adverse events occurred and all adverse events (n = 27) were mild, transient and self-limiting. The treatment groups were not different in terms of safety and tolerability, lesion count and size, and patient-reported outcomes pain, itch and quality of life. Human papillomavirus load significantly reduced after 12 weeks of treatment with omiganan compared to placebo (-96.6%; 95% confidence interval -99.9 to -7.4%; P = .045) in AGW patients only.\nTopical omiganan appears to be safe in patients with AGW and vulvar HSIL and reduced human papillomavirus load after 12 weeks of treatment in AGW patients.Drug Delivery Technolog
Pharmacodynamic effects of topical Omiganan in patients with mild to moderate atopic dermatitis in a randomized, placebo-controlled, phase II trial
Omiganan is an indolicidin analog with antimicrobial properties that could be beneficial for patients with atopic dermatitis. In this randomized, double-blind, placebo-controlled, phase II trial we explored the efficacy, pharmacodynamics, and safety of topical omiganan once daily in 36 patients with mild to moderate atomic dermatitis. Patients were randomized to apply topical omiganan 1%, omiganan 2.5%, or vehicle gel to one target lesion once daily for 28 consecutive days. Small but significant improvements in local objective SCORing Atopic Dematitis index and morning itch were observed in the omiganan 2.5% group compared with the vehicle gel group (-18.5%; 95% confidence interval, -32.9 to -1.0; P = 0.04; and -8.2; 95% confidence interval, -16.3 to -0.2; P = 0.05, respectively). A shift from lesional to nonlesional skin microbiota was observed in both omiganan treatment groups, in contrast to the vehicle group. Thus, treatment with topical omiganan improved dysbiosis in patients with mild to moderate atopic dermatitis, and small but statistically significant improvements in clinical scores were detected. Our findings warrant further exploration in future clinical trials.Drug Delivery Technolog
Human papillomavirus 16 is an aetiological factor of scrotal cancer
Background: Squamous cell scrotal carcinoma (SCSC) is an infrequent skin cancer associated historically with occupational carcinogens. Human papillomavirus (HPV) DNA has been associated with SCSC but there is no definitive proof of its oncogenic role. Methods: Human papillomavirus-DNA and -E6*I mRNA were analysed in six invasive histologically typed SCSC. LCM-PCR was used to localise HPV DNA to tumour cells. P16(INK4a)and p53 expression were studied by immunohistochemistry. Results: In three warty or basaloid SCSC HPV16-DNA and E6*I-mRNA were detected. LCM-PCR confirmed HPV16 was in p16(INK4a)-positive malignant cells. However, of three usual-type SCSC, all were HPV-negative and two expressed p53 protein but not p16(INK4a). Conclusions: Human papillomavirus 16 was present in tumour cells and oncogenically active in basaloid and warty SCSC, whereas usual SCSC was HPV-negative and showed immunostaining, suggesting p53 mutation. The dual pathways of oncogenesis and relation between histological type of SCSC and HPV are similar to that in penile cancers