Correlation Between Hyaluronic Acid,Hyaluronic Acid Synthase And Human Renal Clear Cell Carcinoma

Objective：To study the correlation between hyaluronic acid（HA）,hyaluronic acid synthase（HAS） and human renal clear cell carcinoma（RCCC）.Methods：The expression of three HAS isoforms＇ gene and HA in 93 RCCC tissues,27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.Results：All RCCC and adjacent normal tissues expressed three HASs＇ mRNA protein;at the mRNA level,both RCCC and adjacent normal tissues,expressed more HAS3 than HAS1 or HAS2,their differences were statistically significant（all P values 0.05）;but,at the protein level,all HAS isoforms presented the equivalent expression.Compared with the adjacent non-neoplastic kidney tissues,the expression of all HAS isoforms＇ mRNA in RCCC tissues were increased evidently and their differences were significant（all P values 0.0001）;but at the protein level,only the expression of HAS3 increased evidently（P=0.022）.In all adjacent normal tissues,more than 80% renal tubular cells strongly expressed HA,however,only the minority RCCC cases（16/93） presented weakly positive HA staining in few cancer nests（5%-30%）,the difference were significant（P0.0001）.In RCCC tissues subgrouped according to clinical stage,pathological grade,lymphatic metastasis or not and distant metastasis or not,the HASs＇ mRNA protein differential expression all had no statistical significance（all P values 0.05）.Conclusion：Different from other malignancy,HA and HASs（except for HAS3） may not play important roles in the biological progress of human RCCC.

Correlation between Cholinergic Innervation, Autophagy, and Etiopathology of Benign Prostatic Hyperplasia

Background： Whether cholinergic innervations and/or autophagy have a role in the etiopathology of benign prostatic hyperplasia （BPH） is still unknown. This study aimed to investigate the role of cholinergic innervation and autophagy in the etiopathology of BPH. Methods： Male, 13-week-old spontaneous hypertension rats （spontaneous BPH animal model） were divided into three groups： an experimental group （EG, n = 24）, a control group （CG, n = 24）, and a normal control group （NC, n = 10）. The EG animals were intragastrically injected with tolterodine （3.5 mg/kg, twice a day）, CG animals were intragastrically injected with physiological saline, and the NC animals did not receive any treatment. Rats were sacrificed every 4 weeks, and the prostatic gross morphological changes, wet weight/body weight （ww/bw）, dry weight/wet weight （dw/ww）, histological changes, ultrastructural changes, and LC3 immunohistochemistry were continuously observed and compared. Results： The gross morphological and ww/bw changes in the three groups were similar at every stage. The dw/ww （mg/mg） values of the EG at week 17, 21, 25, and 29 were 0.1478 ±0.0034, 0.1653 ± 0.0036, 0.1668 ± 0.0045, and 0.1755±0.0034, respectively, and the CG values were 0.1511 ±0.0029, 0.1734± 0.0020, 0.1837 ±0.0052, and 0.1968 ± 0.0045, respectively. The difference between EG and CG for dw/ww showed statistical significance after 21 weeks of age （week 21： P = 0.016, week 25： P = 0.008, and week 29： P = 0.001）. Both EG and CG, prostatic glandular epithelial cell proliferation, and secretory function improved with age, but in EG, these improvements were slower than those in CG, and all the differences were statistically significant after 21 weeks. An increasing number of autophagosomes in the prostatic glandular cell cytoplasm, attenuation of LC3-I immunohistochemical staining, enhancement of LC3-II staining, and the ratio of LC3-1I/LC3-1 staining were all progressive in both groups, but the rate of change in EG was faster than that in CG, and these differences gained statistical significance after 25 weeks. Comparisons with regard to the above indexes between CG and NC showed no statistical significance at any stage. Conclusions： Cholinergic innervations and activation of autophagy appear to have important functions in the etiopathology of BPH. Drug-mediated blockade of cholinergic innervations could delay the physiopathology processes. Moreover, overactivation of autophagy may also play an important role in this delay.

Efficacy and Safety of Medium-to-long-term Use of Tolterodine Extended Release with or without Tamsulosin in Patients with Benign Prostate Hyperplasia and Larger Prostate Size： A Double-blind, Placebo-controlled, Randomized Clinical Trial

Background： The medium-to-long-term use of antimuscarinics alone or in combination with an α-blocker in men with an enlarged prostate is still controversial. This double-blind, placebo-controlled, randomized clinical trial aimed to investigate the efficacy and safety of medium-to-long-term use of tolterodine extended release （ER） with or without tamsulosin in patients with benign prostate hyperplasia （BPH） and larger prostate size. Methods： Totally, 152 patients （age ≥50 years） with BPH, International Prostate Symptom Score （IPSS） ≥12, quality-of-life （QoL） score ≥3, and total prostate volume ≥25 ml were enrolled in this study. The patients were randomized into four groups （n = 38 in each） to receive tolterodine ER placebo plus tamsulosin placebo, 0.2 mg tamsulosin plus tolterodine ER placebo, 4 mg tolterodine ER plus tamsulosin placebo, or tolterodine ER plus tamsulosin once daily for 24 weeks. IPSS （total, storage, and voiding subscales）, QoL, maximum urinary flow rate （Qmax）, and postvoid residual volume （PVR） were collected at baseline, and at weeks 4, 12, and 24. Results： Compared with placebo, tolterodine ER plus tamsulosin significantly improved total IPSS （？7.15, ？12.20, and ？14.66 vs. ？3.51, ？5.78, and ？7.23）, storage IPSS （？3.56, ？5.63, and ？6.66 vs. ？1.52, ？1.21, and ？2.43）, voiding IPSS （？2.88, ？5.10, and ？6.48 vs. ？1.52, ？3.03, and ？2.97）, QoL （？1.21, ？2.40, and ？3.21 vs. ？0.39, ？1.41, and ？1.60）, Qmax （2.21, 7.97, and 9.72 ml/s vs. 2.15, 2.44, and 2.73 ml/s）, and PVR （？17.88, ？26.97, and ？27.89 ml vs. ？12.03, ？11.16, and ？16.73 ml） at weeks 4, 12, and 24, respectively; the differences were all statistically significant （P 〈 0.05）. Adverse events （AEs） were not increased with treatment progression. Tolterodine ER alone did not improve total IPSS （？4.61, ？6.79, and ？5.70）, voiding IPSS （？0.64, ？1.83, and ？1.45）, QoL （？0.69, ？1.21, and ？1.41）, or Qmax（？0.79, 2.83, and 1.11 ml/s）, compared with placebo （all P 〉 0.05）. However, a gradual increase in PVR （10.03, 10.41, and 12.89 ml） and more urinary AEs suggestive of urinary retention （11/38 vs. 4/38） were observed. Conclusion： Medium-to-long-term use of tolterodine ER plus tamsulosin should be recommended in patients with BPH and an enlarged prostate volume.