1. An insulin-producing cell line, RINm5F, derived from a rat insulinoma was studied. 2. The cellular content of immunoreactive insulin was 0.19 pg/cell, which represents approx. 1% of the insulin content of native rat beta-cells, whereas that of immunoreactive glucagon and somatostatin was five to six orders of magnitude less than that of native alpha- or delta-cells respectively. 3. RINm5F cells released 7-12% of their cellular immunoreactive-insulin content at 2.8 mM-glucose during 60 min in Krebs-Ringer bicarbonate buffer. 4. Glucose utilization was increased by raising glucose from 2.8 to 16.7 mM. There was, however, no stimulation of immunoreactive-insulin release even when glucose was increased from 2.8 to 33.4 mM. A small stimulation of release was, however, found when glucose was raised from 0 to 2.8 mM. 5. Glyceraldehyde stimulated the release of immunoreactive insulin in a dose-dependent manner. 6. At 20 mM, leucine or arginine stimulated release at 2.8 mM-glucose. 7. Raising intracellular cyclic AMP by glucagon or 3-isobutyl-1-methylxanthine stimulated release at 2.8 mM-glucose with no additional stimulation at 16.7 mM-glucose. 8. Stimulation of immunoreactive-insulin release by K+ was dose-related between 2 and 30 mM. Another depolarizing agent, ouabain, also stimulated release. 9. Adrenaline (epinephrine) inhibited both basal (2.8 mM-glucose) release and that stimulated by 30 mM-K+. 10. Raising Ca2+ from 1 to 3 mM stimulated immunoreactive-insulin release, whereas a decrease from 1 to 0.3 or to 0.1 mM-Ca2+ lowered the release. 11. These findings could reflect a relatively specific impairment in glucose handling by RINm5F cells, contrasting with the preserved response to other modulators of insulin release.
BACKGROUND. The first evaluation of pelvic extended lymph node dissection (pLND) in oligometastatic prostate cancer (PCa) detected by 68 Ga-PSMA PET/CT. METHODS. Retrospective analysis of 35 PCa patients underwent 68 Ga-PSMA PET/CT affected by biochemical recurrence (BCR) after curative treatment (n ¼ 23) or before primary therapy of high-risk PCa (n ¼ 12). We performed pLND associated with pathologic imaging in 17 men with nodal oligometastatic PCa. RESULTS. Indicative lesions for PCa in PET/CT were detected in 91.4% (32 of 35) of patients. Nodal, bone, visceral (pulmonary), and within the prostate suspected disease were detected in 72% (23 of 32), 16% (5 of 32), 6% (2 of 32), and 47% (15 of 32) of patients, respectively. Median serum PSA in patients with pathological radiotracer uptake in recurrent and high-risk PCa patients was 2.9 ng/ml (range 0.18-30) and 19.5 ng/ml (range 6-90), respectively. The median number of removed lymph nodes with pLND in recurrent and high-risk PCa was 10 (range 4-17) and 12 (range 8-29) per patient and the median number of positive lymph nodes was 1 (range 1-2) and 3 (2-3) per patient, respectively. In total, two false positive and one false-negative lymph node were found. Diagnostic accuracies per nodal lesion in total of 213 removed nodes: sensitivity, 94%; specificity, 99%; positive predictive value (PPV), 89%, and negative predictive value (NPV), 99.5%. After pLND, 53% (9 of 17) of patients received androgen deprivation therapy and/or radiation therapy and hormonal therapy, while 47% (8 of 17) of patients remained free of any post-surgery therapy. Follow-up PSA remained less than 0.2 ng/ml in 82% (14 of 17) of patients. After pLND, immediate BCR (PSA never measured less than 0.2 ng/ml) in 18% (3 of 17) of patients was recorded. CONCLUSIONS. This represents the first study of pLND in the setting of nodal oligometastatic PCa detected by 68 Ga-PSMA PET/CT. The use of 68 Ga-PSMA PET/CT could be to improve the accuracy for the detection of nodal micrometastases. These promising findings need validation in larger studies.
ObjectiveTo date, only few studies have evaluated the impact of ureteral stenting prior to ureterorenoscopy. This study is to clarify the role of preoperative ureteral stenting in the treatment for ureteral stones.MethodsWe retrospectively reviewed 550 ureterorenoscopies from 1998 to 2008. Patients were classified into two groups depending on whether they had a stent placed before URS. Baseline characteristics of patients and stone properties, stone-free rates, complications, and operation times were compared between both groups. Subanalysis was performed regarding stone localization. We retrospectively reviewed data from patient documentation, X-ray imagery, intravenous urography, and operation reports.ResultsBaseline characteristics of patients were similar in both groups. The majority of patients underwent stent placement before the ureteroscopic stone treatment (88.4%). The mean operation time in the prestented group was longer (43.3 vs. 38.4 min). Stone-free rate of patients with stent was 72.2%, compared to 59.4% without preoperative stenting. The rate of minor complications was 4.7% with stent versus 9.4% without stent, major complications 0.6% versus 1.6%, respectively. Patients with distal ureter stones had similar stone-free rates regardless of a stent placement (90.1% with stent vs. 87.6% without), and no difference in complication rates was observed (3.5% with stent vs. 3.1% without), respectively.ConclusionsStent placement prior to ureteroscopic stone treatment in distal ureter is not reasonable and does not considerably improve stone-free rates.
In the prostate, estrogen receptor B (ERB), the preferred receptor for phytoestrogens, has features of a tumor suppressor. To investigate the mechanisms underlying the beneficial effects on prostate cancer of histone deacetylase inhibitor valproic acid (VPA) and phytoestrogen tectorigenin, we analyzed the expression of ERB after tectorigenin or VPA treatment. For further functional analysis, we knocked down ERB expression by RNA interference. LNCaP prostate cancer cells were treated with 5 mmol/L VPA or 100 Mmol/L tectorigenin and transfected with small interfering RNA (siRNA) against ERB. Control transfections were done with luciferase (LUC) siRNA. Expression of ERB was assessed by Western blot. mRNA expression was quantitated by real-time reverse transcription-PCR. Expression of ERB mRNA and protein markedly increased after VPA or tectorigenin treatment. When ERB was knocked down by siRNA, the expression of prostatederived Ets factor, prostate-specific antigen, prostate cancer -specific indicator gene DD3 PCA3 , insulin-like growth factor-1 receptor, the catalytic subunit of the telomerase, and ERA was up-regulated and the tectorigenin effects were abrogated. ERB levels were diminished in prostate cancer and loss of ERB was associated with proliferation. Here, we show that siRNA-mediated knockdown of ERB increases the expression of genes highly relevant to tumor cell proliferation. In addition, we show that one prominent result of treatment with VPA or tectorigenin is the up-regulation of ERB resulting in antiproliferative effects. Thus, these drugs, by restoring the regulatory function of ERB in tumor cells, could become useful in the intervention of prostate cancer. [Mol Cancer Ther 2007;6(10):2626 -33]
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