Intratumoral concentration of sex steroids and expression of sex steroid-producing enzymes in ductal carcinoma in situ of human breast

It is well known that sex steroids play important roles in the development of invasive ductal carcinoma (IDC) of the human breast. However, biological significance of sex steroids remains largely unclear in ductal carcinoma in situ (DCIS), regarded as a precursor lesion of IDC, which is partly due to the fact that the intratumoral concentration of sex steroids has not been examined in DCIS. Therefore, in this study, we first examined the intratumoral concentrations of estradiol and 5alpha-dihydrotestosterone (DHT) using liquid chromatography/electrospray tandem mass spectrometry in DCIS. Intratumoral concentrations of both estradiol and DHT were threefold higher in DCIS than non-neoplastic breast tissues and estrogen-producing enzymes (aromatase, steroid sulfatase, and 17beta-hydroxysteroid dehydrogenase type 1 (17betaHSD1)), and androgen-producing enzymes (17betaHSD5 and 5alpha-reductase type 1 (5alphaRed1)) were abundantly expressed in DCIS by real-time PCR and immunohistochemical analyses. The intratumoral concentration of DHT was significantly lower in IDC than DCIS, while the expression of aromatase mRNA in carcinoma cells and intratumoral stromal cells was significantly higher in IDC than those in DCIS. Immunohistochemistry for sex steroid-producing enzymes in DCIS demonstrated that 5alphaRed1 immunoreactivity was positively correlated with Ki-67 labeling index and histological grade and was also associated with an increased risk of recurrence in patients with DCIS examined. Results of our study suggest that intratumoral concentrations of estradiol and DHT are increased in DCIS, which is possibly due to intratumoral production of these steroids. Therefore, estradiol and DHT may play important roles in the development of DCIS of the human breast.     

Pre-admission antithrombotic use is associated with 3-month mRS score after thrombectomy for acute ischemic stroke

Journal of Thrombosis and Thrombolysis - In patients who undergo thrombectomy for acute ischemic stroke, the relationship between pre-admission antithrombotic (anticoagulation or antiplatelet) use...     

Efficacy of temozolomide combined with capecitabine (CAPTEM) on refractory prolactinomas as assessed using an ex vivo 3D spheroid assay

Pituitary - Refractory prolactinomas resistant to dopamine agonists (DAs) pose a clinical challenge. Temozolomide (TMZ) is a recommended treatment option, but its effects are difficult to predict,...     

Acute renal failure due to adenovirus-associated obstructive uropathy and necrotizing tubulointerstitial nephritis in a bone marrow transplant recipient

Management of post-transplant complications caused by severe adenoviral infection remains a major therapeutic challenge. A 17-year-old male who had undergone bone marrow transplantation for the treatment of acute lymphoblastic leukemia developed complete anuria following hemorrhagic cystitis 34 days after the transplant procedure. The computed tomogram scan revealed bilateral hydronephrosis, indicating acute renal failure because of obstructive uropathy. The emergency procedure of percutaneous nephrostomy caused massive bleeding in the left kidney, which eventually required a nephrectomy. Adenovirus-positive severe necrotizing tubulointerstitial nephritis was the histopathological diagnosis. Post-transplant acute renal failure because of hydronephrosis, which could be complicated by adenovirus-induced renal parenchymal disease, is of great concern and may cause significant problems with interventional treatment.     

Effect of angiotensin blockade and converting enzyme inhibition on renovascular hypertension: comparison between unilateral and bilateral renal artery stenosis

The response to angiotensin II analog infusion during sodium deletion and the effects of a one-month captopril treatment were compared between 15 renovascular hypertensive patients with unilateral and 6 with bilateral renal artery stenosis. Plasma renin activity, its response to sodium depletion, and the renal vein renin ratio during sodium depletion were greater in unilateral than in bilateral stenosis. A fall in diastolic blood pressure induced by analog infusion during sodium depletion was correlated with the preinfusion plasma renin activity and with the renal vein renin ratio. Treatment with captopril showed a comparable hypotensive effect in unilateral and bilateral stenosis. The reduction in blood pressure was not correlated with the pretreatment renin levels or changes in blood pressure observed during analog infusion. Plasma renin activity rose and plasma aldosterone level fell in all patients. These results indicate that the mechanism maintaining high blood pressure is more renin dependent in unilateral than in bilateral stenosis and that the long-term effect of captopril does not depend solely on the suppression of the renin-angiotensin-aldosterone system.