ABSTRACT: The purpose of this study was to investigate the clinical and hormonal features of patients with incidentally discovered adrenal adenomas in relation to corticotropin releasing hormone (CRH) testing and the clinical outcome of adrenalectomy.
Twenty-three consecutive patients with incidentally detected adrenal adenomas were included in this retrospective study. All the patients underwent abdominal computed tomography scans and hormonal assays, including assessment of circadian rhythms of plasma cortisol and corticotropin (adrenocorticotropic hormone, ACTH), a corticotropin stimulation test, and low-dose and high-dose dexamethasone tests. The patients were reevaluated at regular intervals (6, 12, and 24 months) for a median period of 24 months. Subclinical Cushing's syndrome (SCS) was diagnosed in patients with subtle hypercortisolism who did not present clinical signs of Cushing's syndrome.
We calculated the responsive index (peak value of ACTH in CRH test/baseline value of ACTH in CRH test). Of 23 patients, 6 had Cushing's syndrome, 8 had SCS, and 9 had a non-functioning tumor. All patients underwent laparoscopic adrenalectomy. Several patients (5 of 6 with Cushing's syndrome and 2 of 8 with SCS) required cortisol replacement therapy after surgery. The remaining patients required no hormonal replacement after surgery. Those who required hormone replacement had a responsive index of less than 1.2. Those who did not need hormone replacement therapy had a responsive index of more than 2.0.
In our limited experience, the responsive index of the CRH test might be a valuable tool for predicting the need for cortisol replacement after surgery in patients with SCS.
Korean journal of urology 06/2012; 53(6):414-8.
ABSTRACT: Sustained chronic inflammation and oxidative stress in the prostate promote prostate carcinogenesis. The process of oncogenic transformation leads to enhanced DNA damage and activates the checkpoint network that functions as an inducible barrier against cancer progression. Here, we analyzed the effects of testosterone on the DNA damage response in prostate cancer cells to assess whether testosterone functions a barrier to cancer progression under the oxidative stress.
We examined the effects of testosterone on components of the DNA damage response pathway, including ATM (ataxia-telangiectasia-mutated kinase), H2AX (histone H2AX variant), and Chk2 (checkpoint kinase2) in prostate cancer cell lines, treated with various concentration of hydrogen peroxide (H(2) O(2) ). Cellular apoptosis was quantified by poly (ADP-ribose) polymerase (PARP) cleavage and flow cytometry.
H(2) O(2) induced apoptosis and phosphorylation of ATM, Chk2, and H2AX in LNCaP cells. An ATM inhibitor, Ku55933, reduced H(2) O(2) -induced apoptosis in LNCaP and 22Rv1 cells. Androgen treatments increased H(2) O(2) -induced activation of the DNA damage response and PARP cleavage, but not when the H(2) O(2) -treated cells were also treated with the anti-androgen flutamide. The ATM inhibitor Ku55933 inhibited androgen-induced phosphorylation of ATM and PARP cleavage.
DNA damage responses play important roles in the maintenance of the cell homeostasis in response to oxidative stress. Our results indicated that under oxidative stress androgen signaling may induce apoptosis by activating the DNA damage response.
The Prostate 01/2012; 72(13):1407-11. · 3.48 Impact Factor
ABSTRACT: Recently, we reported that combined ingestion of soy isoflavones and curcumin significantly decreased the serum level of prostate-specific antigen based on a randomized placebo-controlled double-blind clinical study. We investigated whether these polyphenols inhibited the proliferation of prostate cancer cells by activating a DNA damage response. The effects of isoflavones and curcumin on the expression and phosphorylation of ataxia-telangiectasia-mutated kinase (ATM), histone H2AX variant (H2AX) and checkpoint kinase2 (Chk2) were examined in LNCaP cells. The induction of apoptosis in LNCaP cells was evaluated by poly(ADP-ribose) polymerase (PARP) cleavage. Furthermore, the effects of a testosterone supplement on modulation of the DNA damage response were examined. Combined treatment of isoflavones and curcumin additively suppressed cellular proliferation and induced phosphorylation of ATM, histone H2AX, Chk2 and p53. Testosterone augmented the activation of the DNA damage response and PARP cleavage induced by curcumin. Our results indicate that activation of the DNA damage response by polyphenols might suppress the malignant transformation of prostate cancer. In addition, testosterone, when combined with curcumin, may have suppressive effects on the progression of prostate cancer.
Cancer Science 02/2011; 102(2):468-71. · 3.33 Impact Factor