Knowledge mapping of alternative splicing of cancer from 2012 to 2021: A bibliometric analysis.

Background: As a processing method of RNA precursors, alternative splicing (AS) is critical to normal cellular activities. Aberrant AS events are associated with cancer development and can be promising targets to treat cancer. However, no detailed and unbiased study describes the current state of AS of cancer research. We aim to measure and recognize the current state and trends of AS cancer research in this study. Methods: The Web of Science Core Collection was used to acquire the articles. Utilizing three bibliometric tools (CiteSpace, VOSviewer, R-bibliometrix), we were able to measure and recognize the influence and collaboration data of individual articles, journals, and co-citations. Analysis of co-occurrence and burst information helped us identify the trending research areas related to AS of cancer. Results: From 2012 to 2021, the total number of papers on AS of cancer published in 766 academic journals was 3,507, authored by 20,406 researchers in 405 institutions from 80 countries/regions. Research involving AS of cancer genes was primarily conducted in the United States and China; simultaneously, the Chinese Academy of Sciences, Fudan University, and National Cancer Institute were the institutions with strong research capabilities. Scorilas Andreas is the scholar with the most publications, while the most co-citations were generated by Wang, Eric T. Plos One published the most papers on AS of cancer, while J Biol Chem was the most co-cited academic journal in this field. The results of keyword co-occurrence analysis can be divided into three types: molecular (P53, CD44, androgen receptor, srsf3, esrp1), pathological process (apoptosis, EMT, metastasis, angiogenesis, proliferation), and disease (breast cancer, colorectal cancer, prostate cancer, hepatocellular carcinoma, gastric cancer). Conclusion: Research on AS of cancer has been increasing in intensity over the past decade. Current AS of cancer studies focused on the hallmarks of AS in cancer and AS signatures including diagnostic and therapeutic targets. Among them, the current trends are splicing factors regulating epithelial-mesenchymal transition and other hallmarks, aberrant splicing events in tumors, and further mechanisms. These might give researchers interested in this field a forward-looking perspective and inform further research.

Catalytic Asymmetric Allylic Substitution with Copper(I) Homoenolates Generated from Cyclopropanols.

By using copper(I) homoenolates as nucleophiles, which are generated through the ring-opening of 1-substituted cyclopropane-1-ols, a catalytic asymmetric allylic substitution with allyl phosphates is achieved in high to excellent yields with high enantioselectivity. Both 1-substituted cyclopropane-1-ols and allylic phosphates enjoy broad substrate scopes. Remarkably, various functional groups, such as ether, ester, tosylate, imide, alcohol, nitro, and carbamate are well tolerated. Moreover, the present method is nicely extended to the asymmetric construction of quaternary carbon centers. Some control experiments argue against a radical-based reaction mechanism and a catalytic cycle based on a two-electron process is proposed. Finally, the synthetic utilities of the product are showcased by means of the transformations of the terminal olefin group and the ketone group.

Copper(I)-Catalyzed Regioselective Asymmetric Addition of 1,4-Pentadiene to Ketones.

By using commercially available 1,4-pentadiene as a pronucleophile, a copper(I)-catalyzed regioselective asymmetric allylation of ketones is achieved. A variety of chiral tertiary alcohols bearing a terminal (Z)-1,3-diene unit are generated in high (Z)/(E) ratio and high enantioselectivity. Both aromatic ketones and aliphatic ketones serve as suitable substrates. Furthermore, the reactions with (E)-C1(alkyl)-1,4-dienes proceed in moderate yields with acceptable enantioselectivity but with low (Z,E)/others ratio, which demonstrates the partial isomerization of (E)-allylcopper(I) species to (Z)-allylcopper(I) species through 1,3-migration. Subsequent Heck reaction and olefin metathesis compensate for the low efficiency with C1-1,4-dienes. The synthetic utility of the product is further demonstrated by a copper(I)-catalyzed regioselective borylation of the 1,3-diene group.

MicroRNA­197 reverses the drug resistance of fluorouracil­induced SGC7901 cells by targeting mitogen­activated protein kinase 1.

MicroRNAs (miRNAs) are a group of small non­coding RNA molecules, which serve an important function in the development of multidrug resistance in cancer through the post­transcriptional regulation of gene expression and RNA silencing. In the present study, the functional effects of miR­197 were analyzed in chemo­resistant gastric cancer cells. Low expression levels of miR­197 were observed in the fluorouracil (5­FU)­resistant gastric cell line SGC7901/5­FU when compared with those in the parental gastric cell line SGC7901. Overexpression of miR­197 in SGC7901/5­FU cells was identified to partially restore 5­FU sensitivity. miRNA target prediction algorithms suggested that mitogen­activated protein kinase 1 (MAPK1) is a candidate target gene for miR­197. A luciferase reporter assay confirmed that miR­197 led to silencing of the MAPK1 gene by recognizing and then specifically binding to the predicted site of the MAPK1 mRNA 3'­untranslated region. When miR­197 was overexpressed in SGC7901 cells, the protein levels of MAPK1 were downregulated. Furthermore, MAPK1 knockdown significantly increased the growth inhibition rate of the SGC7901/5­FU cells compared with those in the control group. These results indicated that miR­197 may influence the sensitivity of 5­FU treatment in a gastric cancer cell line by targeting MAPK1.

Indirect comparison showed survival benefit from adjuvant chemoradiotherapy in completely resected gastric cancer with d2 lymphadenectomy.

Background. Little data on directly comparing chemoradiotherapy with observation has yet been published in the setting of adjuvant therapy for resected gastric cancer who underwent D2 lymphadenectomy. The present indirect comparison aims to provide more evidence on comparing the two approaches. Methods. We conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed indirect comparison to obtain the relative hazards of adjuvant chemoradiotherapy to observation on overall and disease-free survival. Results. seven randomized controlled trials were identified. Three trials compared adjuvant chemoradiotherapy with adjuvant chemotherapy, and 4 trials compared adjuvant chemotherapy with observation. Using indirect comparison, the relative hazards of adjuvant chemoradiotherapy to observation were 0.43 (95% CI: 0.33-0.55) in disease-free survival and 0.52 (95% CI: 0.38-0.71) in overall survival for completely resected gastric cancer with D2 lymphadenectomy. Conclusions. Postoperative chemoradiotherapy can prolong survival and decrease recurrence in patients with resected gastric cancer who underwent D2 gastrectomy. Molecular biomarker might be a promising direction in the prediction of clinical outcome to postoperative chemoradiotherapy, which warranted further study.

Postoperative chemoradiotherapy versus postoperative chemotherapy for completely resected gastric cancer with D2 Lymphadenectomy: a meta-analysis.

BACKGROUND: Both chemoradiotherapy and chemotherapy are used in postoperative adjuvant therapy for resected gastric cancer. However, it is controversial whether chemoradiotherapy or chemotherapy is the optimal strategy for patients with gastric cancer after D2 lymphadenectomy. The present meta-analysis aims to provide more evidence on the relative benefits of adjuvant therapies in this setting. METHODS: We conducted a systematic review of randomized controlled trials, extracted time-to-event data using Tierney methods (when not reported), and performed meta-analysis to obtain the relative hazards of adjuvant chemoradiotherapy to chemotherapy on efficacy and toxicities. RESULTS: A total of 895 patients from 3 randomized controlled trials were identified for this meta-analysis. All patients were from Asian countries. Our results showed that postoperative chemoradiotherapy significantly improved locoregional recurrence-free survival [LRRFS: hazard ratio (HR) = 0.53, 95% CI = 0.32-0.87, p = 0.01] and disease-free survival (DFS: HR = 0.72, 95% CI = 0.59-0.89, p = 0.002); however, the improvement of distant metastasis recurrence-free survival (DMRFS: HR = 0.86; 95% CI = 0.66-1.11, p = 0.25) and overall survival (OS: HR = 0.79, 95% CI = 0.61-1.03, p = 0.08) were non-significant. The main grade 3 or 4 toxicities were equivalent between the two groups. CONCLUSION: In non-selected Asian patients with resected gastric cancer who underwent D2 lymphadenectomy, postoperative chemoradiotherapy improved LRRFS and DFS but might not improve OS compared to postoperative chemotherapy.

[Indirect comparison of different adjuvant chemotherapies for stage II-III gastric cancer after D2 gastrectomy in Asian patients].

OBJECTIVE: To compare efficacy of different adjuvant chemotherapy regimens for stage II-III gastric cancer after D2 gastrectomy in Asian patients. METHODS: Associated literatures were searched through electronic databases and hand-searching. Prospective randomized clinical trials (RCTs) comparing adjuvant chemotherapy after D2 gastrectomy with surgery alone were included in the study. Overall survival and disease-free survival were chosen as the endpoints. Relative hazard was analyzed by Bucher adjusted indirect comparison. RESULTS: Two RCTs were selected, including comparison between S-1 versus surgery alone and comparison between XELOX versus surgery alone. There was no statistical difference in overall survival between the two regimens (HR=0.94, 95%CI:0.62-1.44, P=0.79). The recurrence risk of S-1 was slightly higher as compared to XELOX, but no statistical difference was found (HR=1.11, 95%CI:0.80-1.53, P=0.54). CONCLUSION: The adjuvant chemotherapy with S-1 is similar to XELOX for stage II-III gastric cancer after D2 gastrectomy in Asian patients.

No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis.

BACKGROUND: The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies (MAbs) remains controversial in colorectal cancer (CRC). The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC) through meta-analysis. METHODS: Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO) and European Society for Medical Oncology (ESMO) were searched. Eligible studies were randomized controlled trials (RCTs) which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab) in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicities. Hazard ratios (HR) and risk ratio (RR) were used for the meta-analysis and were expressed with 95% confidence intervals. RESULTS: This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn't result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95) or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13). The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75) or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36). Patients who received combined therapy didn't have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]). Toxicities slightly increased in anti-EGFR drugs group. CONCLUSIONS: The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in survival benefit and response rate. More RCTs are warranted to evaluate the combination of chemotherapy and targeted therapy.

Overall survival of patients with advanced pancreatic cancer improved with an increase in second-line chemotherapy after gemcitabine-based therapy.

CONTEXT: In the last decade, gemcitabine-based regimen as first-line therapy has demonstrated low efficacy regarding overall survival benefit for patients with advanced pancreatic cancer. OBJECTIVE: The purpose of this study was to explore a new strategy, such as an increased second-line chemotherapy rate, in order to improve overall survival. DESIGN: Retrospective data analysis. METHODS: The data in the literature on gemcitabine-based therapy for patients with advanced pancreatic cancer were collected by searching databases, such as MEDLINE, EMBASE, the Chinese Biomedical Literature Analysis and Retrieval System, and EBM Reviews (Cochrane Database of Systematic Reviews). Linear regression was used to explore the relationship between overall survival and second-line chemotherapy. The primary endpoint was overall survival. The secondary endpoints were progression-free survival and residual survival. RESULTS: Ten randomized controlled trials, involving 2,679 patients, were included in the present study. The results indicated that overall survival was positively correlated with a combination of chemotherapy, stage of disease and second-line chemotherapy in patients with advanced pancreatic cancer (r = 0.753; P = 0.003). Meanwhile median overall survival would be prolonged about 1.56 days if second-line chemotherapy was increased by 1% (t = 4.33; P = 0.001). Progression-free survival was not significantly correlated with second-line chemotherapy (r = 0.092; P = 0.701); in contrast, residual survival was positively correlated with second-line chemotherapy (r = 0.717; P < 0.001). CONCLUSIONS: Our study indicated that overall survival closely correlated to second-line chemotherapy in patients with advanced pancreatic cancer; more attention should be paid after first-line therapy which must be administered skillfully in order to improve overall survival, and this is worthy of further study.

[Chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia: diagnosis and treatment].

OBJECTIVE: To investigate the features of chronic prostatitis with non-neurogenic detrusor sphincter dyssynergia (NNDSD) and the effects of pelvic floor biofeedback in the treatment of the disease. METHODS: We included in this study 113 male patients, aged 15 - 48 (mean 36) years and diagnosed as having chronic prostatitis for 1 -2 (mean 1.2) years based on such typical symptoms as frequent micturition, urgent micturition, voiding pain, difficult void, etc, that lasted over 3 months, and the score > or = 1 on the first and second parts of NIH-CPSI. Urethritis, interstitial cystitis, urethral stricture and neurogenic bladder were excluded. All the patients underwent urodynamic examinations for the uroflow curve, Q(max), Pdet. max and MUCP. Biofeedback was carried out for those with non-neurogenic detrusor sphincter dyssynergia, and the effects were evaluated at 10 weeks. RESULTS: Twenty-one (18.6%) of the 113 cases were found to be NNDSD. Biofeedback treatment achieved obvious decreases in Q(max) (8.2 +/- 4.1), Pdet. max (125.1 +/- 75.3), MUP (124.3 +/- 23.3) and MUCP (101.5 +/- 43.6), as compared with 15.1 +/- 7.3, 86.3 +/- 54.2, 65.4 +/- 23.0 and 43.5 +/- 16.7 before the treatment (P < 0.05). Statistically significant differences were observed between pre- and post-treatment scores on voiding pain (4.0 +/- 2.0 vs 2.2 +/- 1.7), urination (7.9 +/- 2.1 vs 2.2 +/- 1.9), life impact (9.6 +/- 2.7 vs 2.9 +/- 2.6) and total scores (21.7 +/- 4.8 vs 8.4 +/- 4.6) (P < 0.05). CONCLUSION: Chronic prostatitis patients with LUTS may have NNDSD, which is urodynamically characterized by low Q(max), high intra-bladder pressure and increased urethral pressure in some patients. Urodynamic examinations may contribute to definite diagnosis and appropriate choice of treatment. Pelvic floor biofeedback has satisfactory short-term effects in the treatment of these patients.

[Clinical features and minimally invasive treatment of prostatic utricle cyst].

OBJECTIVE: To investigate the clinical characteristics, diagnostic methods and minimally invasive treatment of prostatic utricle cyst. METHODS: We retrospectively analyzed the clinical data of 9 cases of prostatic utricle cyst, of whom 5 presented with frequent or urgent micturition, 3 with difficult urination or thinning urinary stream, and the other 1 with hemospermia. All the cases underwent ultrasonography and MRI. Transurethral cyst deroofing was performed for 3 of the patients with smaller cysts close to the prostatic urethra, and laparoscopic excision of the prostatic utricle was conducted for the other 6 with bigger cysts behind the prostatic urethra. RESULTS: The duration of transurethral cyst deroofing ranged from 30 to 50 min and intraoperative bleeding was 20 -70 ml; the mean time of laparoscopic excision of the prostatic utricle was 100 - 150 min and intraoperative bleeding was 30 -50 ml. All the patients were followed up for 3 - 12 months, which revealed normal penile erection and ejaculation, and no urinary tract irritation or difficult urination. CONCLUSION: Ultrasonography and MRI are excellent imaging modalities for accurate depiction of prostatic utricle cyst. Transurethral cyst deroofing is valuable for prostatic utricle cyst close to the prostatic urethra. Laparoscopic excision of the prostatic utricle, owing to its safety, effectiveness, minimal invasiveness, fewer complications and rapid recovery, can be used as the first option for the treatment of prostatic utricle cyst.

[Effects of B7-H1 blockade on biologic activity of CD3AK cells in vitro].

AIM: To investigate the effect of B7-H1 blockade on proliferation, activation, and antitumor immunity of CD3AK cells. METHODS: CD3AK cells were induced by stimulation of normal human peripheral blood lymphocytes with CD3 mAbs. Then the cells were cultured with anti-B7-H1 mAbs to block B7-H1 pathway. The proliferation efficiency of CD3AK cells was measured by 3H-thymidine incorporation assay and the concentrations of IFN-gamma, TNF-alpha and IL-10 were measured by ELISA method. Meanwhile the killing activity of CD3AK cells on bladder cancer cell line BIU-87 was measured by MTT method. RESULTS: Blockade of B7-H1 greatly promoted the proliferation of CD3AK cells and extended the survival time of CD3AK cells in vitro. It also enhanced IFN-gamma, TNF-alpha secretion but suppressed IL-10 secretion. And the cytotoxic effect of CD3AK cells on BIU-87 cells were significantly enhanced. CONCLUSION: Blockade of B7-H1 can promote and retain the proliferation and activation of CD3AK cells. It can also improve the antitumor immunity mediated by CD3AK cells. The manipulation of B7-H1 may become a beneficial target for immunotherapy in tumors.

RNA interference-mediated silencing of the PAR gene inhibits the growth of PC3 cells via the induction of G2/M cell cycle arrest and apoptosis.

BACKGROUND: The prostate androgen-regulated (PAR) gene is ubiquitously overexpressed in prostate cancer (PCa) cells and is involved in proliferation of PCa. However, the mechanism by which the modulation of PAR gene expression elicits its biological effects on PCa cells is not well documented. Here, we investigate the mechanism of PAR depletion inhibiting PCa cell growth. METHODS: PAR expression was depleted by small interfering RNA (siRNA) and its subsequent effects on proliferation of PC3 cells were determined by the trypan blue exclusion assay. Flow cytometric analysis provided the evidence for the progression of cell cycle and the induction of apoptosis which was further confirmed by the observation of cleavage of poly(ADP-ribose) polymerase. Western blot analysis was performed to investigate the involvement of critical molecular events known to regulate the cell cycle and the apoptotic machinery. RESULTS: siRNA transfection results in a dose-dependent inhibition of cell growth in PC3 cells by causing G2/M phase cell cycle arrest and apoptosis. The G2/M arrest by PAR depletion was associated with decreased levels of cyclin B1, pCdc2 (Tyr15), Cdc2 and Cdc25C. PAR depletion also was found to result in inhibition of procaspases 9, 8, 6 and 3 with significant increase in the ratio of Bax : Bcl-2. CONCLUSIONS: Our data indicate that PAR depletion induces G2/M arrest via the Cdc25C-Cdc2/cyclin B1 pathway. Furthermore, the results of the present study point toward involvement of pathways mediated by both caspase 8 and caspase 9 in apoptosis induction by PAR depletion.

[Effects of small interfering RNA magnetic nanoparticles combination with external magnetic fields on survivin gene expression of bladder cancer cells and apoptosis].

OBJECTIVE: To investigate the effects of the small interfering RNA plasmid-dextran magnetic nanoparticles (siRNA-DMN) combination with external magnetic fields on silencing survivin gene expression of bladder cancer cells and apoptosis when DMN used as gene carrier to transfer siRNA-survivin recombinant plasmid in vivo. METHODS: The siRNA-survivin recombinant plasmid specific targeted survivin was synthesized in previous experiment. DMN were prepared by chemical coprecipitation method and used as gene carrier. The siRNA-DMN were constructed by static electricity of polylysine and transferred into human bladder cancer BIU-87 cells with the help of external magnetic fields. The growth inhibiting rate (IR) of BIU-87 cells was observed by 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide's test and the apoptosis index (AI) was detected by transferase-mediated dUTP nick end labeling method. The relatively transcription levels of survivin mRNA and protein expression were respectively detected by semi-quantitive reverse transcription polymerase chain reaction and Western Blotting techniques. RESULTS: The diameter, effective diameter and saturation magnetization of DMN-siRNA were about 10 - 12 nm, 94.8 nm and 0.19 emu/g, respectively. The IR (39.60%) and AI (28.72%), the relative expression of survivin mRNA and protein of siRNA-DMN combination with external magnetic fields on BIU-87 cells were significantly higher and lower than those in the control group and single siRNA-DMN group, respectively (P < 0.05). CONCLUSIONS: The siRNA-survivin plasmid-DMN combination with external magnetic fields could effectively inhibit survivin expression and induce BIU-87 cells apoptosis which provided experimental basis for the magnetic targeting gene therapy of bladder tumor.

Prostate androgen-regulated gene: a novel potential target for androgen-independent prostate cancer therapy.

AIM: To investigate the involvement of the prostate androgen-regulated (PAR) gene in the androgen receptor (AR) signaling pathway and the malignant phenotype of androgen-independent prostate cancer (PCa) cells. METHODS: The difference in PAR expression between LNCaP and PC3 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). Androgen and anti-androgen effects on PAR expression were evaluated by RT-PCR in LNCaP, PC3 cells and PC3 cells stably transfected with vector containing wild-type AR. To determine the importance of PAR in the malignant proliferation of androgen-independent PCa cells, we used small interfering RNA (siRNA) transfection to knock down the expression of the gene in PC3 cells. The changes in the malignant phenotype of PCa cells after transfection were analyzed by cell count, colony formation in soft agar and flow cytometry. RESULTS: PAR expression was 3-fold higher in PC3 cells than that in LNCaP cells. Dihydrotestosterone (DHT) regulated PAR mRNA expression in LNCaP cells and the effect was inhibited by the AR antagonist, flutamide. By contrast, DHT did not affect PAR expression in PC3 cells. The reintroduction of AR into PC3 cells by stable transfection restored the androgen effect on PAR upregulation. After the knockdown of the PAR gene by siRNA, PC3 cells exhibited a reversal of the malignant phenotype. CONCLUSION: Because of the possibility that PAR is downstream from the AR, and because of its contribution to malignant proliferation in androgen-independent PCa cells, the gene could be a potential therapeutic target for androgen-independent PCa with AR signaling pathway alteration.

[Effects of different immunodepressants on the sperm parameters of kidney transplant recipients].

OBJECTIVE: To study the effects of different immunodepressants on the sperm parameters of kidney transplant recipients. METHODS: In 15 healthy fertile men and 37 kidney transplant recipients, ejaculates were aseptically obtained by masturbation. Thirty-seven patients were divided into two groups, 20 patients were treated with Prograf (FK506) combination with mycophenolate mofetil (MMF) and prednisone; 17 patients were treated with cyclosporine (CsA) combination with azathioprine with prednisone. The sperm viability, mobility parameters such as prorsad percentage motility, straight line velocity (VSL), curve line velocity (VCL), velocity of average path (VAP) and morph were estimated with a computer-assisted sperm analyzer (CASA) provided with a multiple-exposure photography system. RESULTS: There were no significant difference in sperm viability rate [(81.7 +/- 5.7)%, (79.4 +/- 6.8)% and (83.8 +/- 6.0)%], VCL [(24.1 +/- 8.6)%, (23.9 +/- 4.4)%, (24.8 +/- 4.2)% ] and VAP [(19.7 +/- 6.6)%, (18.6 +/- 2.9)%, (21.0 +/- 4.0)%] among groups of FK506, CsA and control, respectively (P > 0.05). The rate of anomaly [(67.8 +/- 5.7)%], the prorsad percentage motility [(46.4 +/- 8.1)%] and VSL [(15.4 +/- 4.6)%] in the group of FK506 were respectively significantly lower and higher than those in the group of CsA [(80.1 +/- 5.6%, (33.3 +/- 6.4)%, (10.2 +/- 2.4)%] (P < 0.05). CONCLUSION: The application of FK506 combined with MMF could help recover the mobility and morphology of the sperm in kidney transplantation recipients.

[Effects of PTEN gene transfection on proliferation and invasion of human bladder cancer cell line BIU87].

BACKGROUND & OBJECTIVE: PTEN (phosphatase and tensin homologue deleted from chromosome 10) is the first antioncogene with phosphatase activity till now, and was found absent or mutational in many primary malignant tumors and cell lines. Its inactivation is correlated to tumor development and prognosis. This study was to investigate the effects of PTEN transfection on proliferation and invasion of human bladder cancer cell line BIU87. METHODS: A eukaryotic expression plasmid containing PTEN, pBp-PTEN, was introduced into E. coli DH5alpha and amplified. The plasmid was prepared and purified, and then identified by restrictive enzyme digestion. pBp-PTEN was transfected into BIU87 cells, and positive cell clones (pBp-PTEN-BIU87) were selected and amplified. Empty plasmid-transfected BIU87 cells (pBp-BIU87) and normal BIU87 cells were set as control. The expression of PTEN was detected by reverse transcription-polymerase chain reaction (RT-PCR). Proliferation and invasion ability of BIU87 cells were measured before and after transfection by MTT assay and cell invasion assay. RESULTS: Plasmid pBp-PTEN containing PTEN was successfully constructed and transfected into BIU87 cells. After transfection, the inhibitory rates of cell growth at the first, second, third, and fourth days were 4.27%, 18.92%, 19.54%, and 17.69%, respectively. The penetrating cells were significantly less in pBp-PTEN-BIU87 group than in pBp-BIU87 and BIU87 groups (39.3+/-7.7 vs. 48.1+/-13.2 and 48.9+/-11.0, P<0.05). CONCLUSION: Transfection with PTEN might suppress proliferation and invasive ability of bladder cancer BIU87 cells.

[Chronic prostatitis related sexual dysfunction and its psychologic treatment].

OBJECTIVE: To explore the relationship between sexual dysfunction and chronic prostatitis and investigate the effect of psychologic treatment. METHODS: A total number of 346 patients with chronic prostatitis complicated by sexual dysfunction were randomized into two groups, one treated with routine medication (antibiotic, indomethacin, alpha1 receptor blocker and Chinese traditional medicine), and the other with both routine medication and psychologic treatment. Results were analyzed by comparing NIH-CPSI and IIEF-5 between pre- and post-treatment groups. RESULTS: The prostatitis symptoms and sexual dysfunction were improved obviously after treatment in the two groups, but compared with the control, more marked improvement was observed in the combined psychologic treatment group (P <0.01). The degree of chronic prostatitis related sexual dysfunction was not correlated with that of prostatitis symptoms. CONCLUSION: Psychology plays a very important role in chronic prostatitis related sexual dysfunction. Psychologic treatment not only works on the sexual dysfunction, but also improves prostatitis symptoms.

[Expression of MUC1 and distribution of tumor-infiltrating dentritic cells in human bladder transitional cell carcinoma].

OBJECTIVE: To study MUC1 expression and distribution of tumor-infiltrating dentritic cells (TIDCs) in human bladder transitional cell carcinoma (BTCC). METHODS: Immunohistochemical staining was employed to detect MUC1 expression and TIDC distribution in 69 surgical specimens of BTCC. MUC1 expression was also detected immunohistochemically in BIU-87, T-24 and drug-resistant BIU87/A cells. Flow cytometry was performed for determining the apoptosis rates of these 3 cells after a 48-hour treatment with adriamycin, vincristine and cisplatin, respectively. RESULTS: MUC1 expression was detected in the BTCC tissues of all stages and the immunohistochemical staining patterns were significantly associated with the pathological grade and clinical stage of the tumors (P<0.001). The number of TIDCs in the tumors was inversely correlated with tumor pathological grades and clinical stages (P<0.005). MUC1 expressed weakly in the cytoplasm and on the membrane of BIU-87 cells and T-24 cells, but strongly in the cytoplasm and membrane of BIU-87/A cells, showing significant differences between the drug-sensitive and -resistant cells (P<0.05). The apoptosis rates of BIU-87 cells and T-24 cells increased obviously after treatment with adriamycin, vincristine and cisplatin, but no significant differences were noted between the two cells or between the 3 drugs. The apoptosis rate of BIU87/A cells, however, exhibited no obvious increase after adriamycin or vincristine treatment, but showed significant increase in response to cisplatin treatment (P<0.05). CONCLUSIONS: The expression pattern of MUC1 and distribution of TIDCs can be useful markers to evaluate the degree of malignancy and prognosis of BTCC. The decrease in the number of TIDCs may have important relation to tumor immune evasion and immune tolerance, and MUC1 over-expression may lead to drug resistance of BTCC, indicating its involvement in tumor infiltration and metastasis.

[Value of quantitative examination of urine MUC1 in bladder transitional cell carcinoma].

OBJECTIVE: To evaluate the value of quantitative examination of MUC 1 in the urine of patients with bladder transitional cell carcinoma (BTCC). METHODS: Urine samples were obtained from 31 patients with BTCC for quantification of MUC 1 content by immunoradiometric analysis. The urine samples were also examined in 10 patients with cystitis glandularis, 10 with benign urine disease and 10 healthy volunteers. The differences in urine MUC1 content were statistically measured between the groups, between cancer patients of different clinical stages and classes, between primary and recurrent cancer patients, and between measurements taken before and after operation. RESULTS: Urine MUC 1 was detected in all the patients. No significant differences were found between the groups, nor between patients with BTCC in all stages (P>0.05), or between primary and recurrent cancer patients (P>0.05). But MUC 1 contents showed significant difference before and after the operation in the cancer patients (P<0.05). CONCLUSIONS: Urine MUC 1 can not serve as the marker to screen and diagnose BTCC, but it can be useful in therapeutic effect and prognostic evaluation. Specific oncogene markers are more significant than oncogene phenotype markers in clinical diagnosis and screen of BTCC.