Initial experience with 161 extraperitoneal laparoscopic radical cystectomy procedures: Comparison with transabdominal laparoscopic radical cystectomy.

OBJECTIVES: There is substantial concern about traditional transperitoneal laparoscopic radical cystectomy (TLRC) due to multiple postoperative complications. In contrast, extraperitoneal laparoscopic radical cystectomy (ELRC) appears to cause a lower rate of morbidity. The present study aimed to compare the efficacy of ELRC and TLRC for bladder cancer (BCa). METHODS: The clinical data of patients undergoing laparoscopic radical cystectomy for BCa from April 2018 to October 2021 were retrospectively analyzed, as ELRC and TLRC groups. The postoperative follow-up data of 275 patients were collected and the incidence of postoperative complications and other perioperative outcomes were compared between the two groups. RESULTS: Surgery was successfully completed in all patients without conversion to open surgery. There was no significant difference in the duration of cystectomy surgery (67.32 ± 23.53 vs 72.17 ± 25.72 min, p = 0.106), intraoperative blood loss (178.06 ± 110.4 vs. 174.56 ± 127.40 ml, p = 0.413), or the number of lymph node dissection (15.1 ± 5.7 vs. 14.5 ± 5.1, p = 0.380) between the two groups. The length of stay (11.6 ± 3.8 vs 14.7 ± 5.6 d, p < 0.001), time to resume food intake after surgery (2.3 ± 0.9 vs 3.0 ± 1.3 d, p < 0.001), and the incidence of ileus (p < 0.001) in the ELRC group were significantly lower than in the TLRC group. CONCLUSIONS: ELRC is a safe procedure that can reduce the incidence of postoperative complications, shorten postoperative hospital stay, reduce the duration of recovery of patients, and, therefore, should be promoted.

Collective analysis of the expression and prognosis for LEM-domain proteins in prostate cancer.

BACKGROUND: Mammalian LEM-domain proteins (LEMs) are encoded by seven genes, including LAP2, EMD, LEMD1, LEMD2, LEMD3, ANKLE1, and ANKLE2. Though some LEMs were involved in various tumor progression, the expression and prognostic values of LEMs in prostate adenocarcinoma (PRAD) have yet to be analyzed. METHODS: Herein, we investigated the expression, survival data, and immune infiltration levels of LEMs in PRAD patients from ATCG, TIMER, LinkedOmics, and TISIDB databases. We also further validated the mRNA and protein expression levels of ANKLE1, EMD, and LEMD2 in human prostate tumor specimens by qPCR, WB, and IHC. RESULTS: We found that all LEM expressions, except for that of LAP2, were markedly altered in PRAD compared to the normal samples. Among all LEMs, only the expressions of ANKLE1, EMD, and LEMD2 were correlated with advanced tumor stage and survival prognosis in PRAD. Consistent with the predicted computational results, the mRNA and protein expression levels of these genes were markedly increased in the PRAD group. We then found that ANKLE1, EMD, and LEMD2 expressions were markedly correlated with immune cell infiltration levels. High ANKLE1, EMD, and LEMD2 expressions predicted a worse prognosis in PRAD based on immune cells. DNA methylation or/and copy number variations may contribute to the abnormal upregulation of ANKLE1, EMD, and LEMD2 in PRAD. CONCLUSIONS: Taken together, this study implied that ANKLE1, EMD, and LEMD2 were promising prognosis predictors and potential immunotherapy targets for PRAD patients.

Exosomal miR-663b targets Ets2-repressor factor to promote proliferation and the epithelial-mesenchymal transition of bladder cancer cells.

Exosomes circulating in biological fluids have the potential to be utilized as cancer biomarkers and are associated with cancer progression and metastasis. MicroRNA (miR)-663b has been found to be elevated in plasma from patients with bladder cancer (BC). However, the functional role of exosomal miR-663b in BC processes remains unknown. Here, we isolated exosomes from plasma and found that the miR-663b level was elevated in exosomes from plasma of patients with BC compared with healthy controls. Exosomal miR-663b from BC cells promoted cell proliferation and epithelial-mesenchymal transition. Moreover, exosomal miR-663b targeted Ets2-repressor factor and acted as a tumor promoter in BC cells. Taken together, our findings suggested that exosomal miR-663b is a promising potential biomarker and target for clinical detection and therapy in BC.

Targeting the adenosine signaling pathway in macrophages for cancer immunotherapy.

One of the ways in which macrophages support tumorigenic growth is by producing adenosine, which acts to dampen antitumor immune responses and is generated by both tumor and immune cells in the tumor microenvironment (TME). Two cell surface expressed molecules, CD73 and CD39, boost catalytic adenosine triphosphate, leading to further increased adenosine synthesis, under hypoxic circumstances in the TME. There are four receptors (A1, A2A, A2B, and A3) expressed on macrophages that allow adenosine to perform its immunomodulatory effect. Researchers have shown that adenosine signaling is a key factor in tumor progression and an attractive therapeutic target for treating cancer. Several antagonistic adenosine-targeting biological therapies that decrease the suppressive action of tumor-associated macrophages have been produced and explored to transform this result from basic research into a therapeutic advantage. Here, we'll review the newest findings from studies of pharmacological compounds that target adenosine receptors, and their potential therapeutic value based on blocking the suppressive action of macrophages in tumors.

A novel extraperitoneal approach exploration for the treatment of urachal mass: a retrospective observational single-center study.

BACKGROUND: To explore the extraperitoneal laparoscopic urachal mass excision technique and its safety and efficacy in treating urachal mass. METHODS: Baseline characteristics were collected from patients who underwent surgery to diagnose a urachal cyst or abscess in our hospital between January 2020 and August 2021. The full-length of the urachus and part of the top bladder wall were completely removed through the extraperitoneal approach. Patient outcomes were collected to evaluate surgical safety and efficacy, including operation time, intraoperative blood loss, drainage tube removal time, length of stay (LOS), and postoperative complications. RESULTS: All 20 surgeries were successfully performed laparoscopically, and no case was converted to open surgery. The mean body mass index of the patients was 24.6 ± 2.2. The mean patient age was 49.3 ± 8.7 years. The mean size of the cysts was 3.0 ± 0.4 cm. The mean operation time was 56.3 ± 12.0 min. The mean intraoperative blood loss was 28.0 ± 6.4 mL. The mean drainage tube removal time was 3.0 ± 0.5 days. The mean LOS was 5.2 ± 0.4 days. The mean follow-up was 13.4 ± 2.1 months. No postoperative complications were observed during the follow-up period. The short-term follow-up and small patient cohort limited our outcome evaluation. CONCLUSION: Our results indicated that the extraperitoneal laparoscopic approach was a safe and effective method to treat urachal mass. Given the limitations of the study, further multiple and larger sample-sized trials are required to confirm our findings.

Initial Experience With Extraperitoneal Laparoscopic Radical Cystectomy With Pelvic Organ-Preserving and Orthotopic Neobladder Techniques for Bladder Cancer in Female Patients.

OBJECTIVE: To present the extraperitoneal laparoscopic radical cystectomy (ELRC) technique, and initial outcomes of organ-preserving and orthotopic neobladder (ONB) techniques for bladder cancer in selected females. MATERIALS AND METHODS: Data including patient characteristics, operative time, blood loss, transfusion rate, length of hospital stay, and pathologic outcomes, as well as 30- and 90-day complications were collected between April 2018 and May 2021 from females who underwent ONB after ELRC. Regular follow-up focused on patients' oncological and functional outcomes, and postoperative sexual function status was assessed using the Female Sexual Function Index (FSFI). RESULTS: Eleven females with a mean age of 53 years who underwent ELRC with pelvic organ-preservation and ONB were analyzed retrospectively. All procedures were completed successfully. The mean operative time was 264.82 ± 33.81 min, and the average intraoperative blood loss was 128 ± 18.19 mL. All patients had negative pathological margins and no lymph node metastases. The average hospital stay was 10.72 days. The single J ureteral stent and catheter were usually removed 3-4 weeks after the procedure. The FIFS assessment of postoperative sexual function showed that the patients were relatively satisfied. CONCLUSION: ELRC with pelvic organ preservation and ONB technology was a safe and feasible surgical strategy for the selected female patients. Preserving organs and vascular nerve bundles seemed to be safe in oncological and produced encouraging functional results. Further rigorous prospective studies with more patients and long-term follow-up data are needed to assess the oncologic and functional results.

Integrative computational approach identifies immune-relevant biomarkers in ulcerative colitis.

Ulcerative colitis is a common inflammatory bowel disease with a complex genetic and immune etiology. Immune infiltration plays a vital role in the development of ulcerative colitis. To explore potential biomarkers for ulcerative colitis and analyze characteristics of immune cell infiltration, we used bioinformatic analyses, including machine learning algorithms, cell type deconvolution methods, and pathway enrichment methods. In this study, we identified 216 differentially expressed mRNAs (DEMs), of which 153 were upregulated, and 63 were downregulated genes. DEMs were mainly enriched in infiltrating neutrophils and regulation of leukocyte migration. Moreover, eight candidate biomarkers, DPP10, MST1L, DPP10-AS1, CEP55, ACSL1, MGP, OLFM4, and SGK1, were identified. Of these candidate biomarkers, MST1L, OLFM4, and DPP10 were then validated in the GSE48958 dataset and were predicted to be strongly correlated with infiltrating immune cells of ulcerative colitis. The underlying mechanism of these key genes in the development of colitis was also predicted by gene set variation analysis. To further validate these biomarkers' expression in ulcerative colitis, we determined mRNA levels of SGK1, CEP55, ACSL1, OLFM4, and DPP10 in lipopolysaccharides (LPS)-stimulated Raw264.7 cells by quantitative reverse transcription-polymerase chain reaction. We also examined SGK1, CEP55, ACSL1, OLFM4, DPP10, and MGP expression in the colon tissues of dextran sodium sulfate-induced colitis mice. Consistent with the predicted computational results, the mRNA levels of these candidate genes were markedly changed in LPS-stimulated Raw264.7 cells and inflamed colon tissues. Hence, our findings indicated that these critical genes may act as diagnostic biomarkers for ulcerative colitis and that differential immune infiltration cells may help illustrate the progression of ulcerative colitis.

Extraperitoneal Laparoscopic Radical Cystectomy With Preservation of Fertility for the Treatment of Ewing Sarcoma: The First Report of a Reliable Surgical Method.

OBJECTIVE: To improve the complications of traditional laparoscopic radical cystectomy (LRC), a novel technique of extraperitoneal laparoscopic radical cystectomy (ELRC) with preservation of fertility was described. MATERIALS AND METHODS: Selected patients with bladder cancer were treated with the ELRC technique. The seminal vesicles and the vas deferens were preserved. Patient's perioperative conditions, tumor prognosis, and follow-up data were analyzed retrospectively. RESULTS: We successfully completed ELRC surgery in dozens of patients. The orthotopic ileal neobladder was placed in the extraperitoneal area, completely preserving the peritoneum. The postoperative complications caused by postoperative peritoneal loss were reduced. Moreover, the perioperative period was strictly managed with the concept of enhanced recovery after surgery (ERAS). We described the operation process in detail through a typical case of a child. All patients were free of complication at short-term follow-up, and reported satisfied sexual function with normal erections. CONCLUSION: The ELRC technique has benefits in terms of decreased ileus, reoperation rates, hospital stay, ease of management of urinary leaks, and improves the patient quality of life. ELRC is also an oncologically safe approach with excellent significant functional outcomes in carefully selected transitional cell carcinoma (TCC) or non-TCC patients who expect to maintain sexual function and fertility, especially for young patients. In addition, more patient groups and longer follow-ups are needed to further understand the safety and practicality of the ELRC technology.

Laparoscopic radical cystectomy with pelvic lymph node dissection and ileal orthotopic neobladder by a total extraperitoneal approach: Our initial technique and short-term outcomes.

PURPOSE: With the increasing application of laparoscopic or robot-assisted radical cystectomy, a reliable and promising method is needed for reducing postoperative complications. We describe the short-term outcomes of totally extraperitoneal laparoscopic radical cystectomy (TELRC) with extraperitoneal pelvic lymph node dissection (EPLND) and extraperitoneal ileal orthotopic neobladder (EION) techniques. MATERIALS AND METHODS: From January 2020 to December 2021, we performed TELRC and EPLND with EION in 72 patients in our center. The accompanying video highlights our novel techniques. The patients' demographic data, intraoperative data, and perioperative complications were collected, and short-term oncological and functional results are reported. RESULTS: All procedures were technically successful without conversion to open surgery. The patients' mean body mass index was 26.22±5.71. Median age was 57.51±12.34 years. Average hospital stay was 13.78±4.62 days. Median intraoperative blood loss was 112.92±88.56 mL. No blood transfusion was needed during the operations and only one blood transfusion was performed during the perioperative period. Mean operating time was 259.44±49.84 minutes. Average cost was US$9,875.71±1,873.08. Postoperative short-term complications included short-term ileus (n=3), infection (n=13), leakage of urine (n=11), and lymph fistula (n=7). One late complication of unilateral vesicoureteral anastomotic stenosis occurred. The mean follow-up was 13.42±8.77 months, and no patient developed local or systemic recurrence. The short-term follow-up and small cohort of patients limited our evaluation of outcomes. CONCLUSIONS: TELRC with PLND and EION was technically feasible and clinically promising, with a reduced potential harm of postoperative complications. Long-term follow-up and a larger cohort of patients are needed for further study.

Endoscopic enucleation vs endoscopic vaporization procedures for benign prostatic hyperplasia: how should we choose: A protocol for systematic review and meta-analysis.

OBJECTIVE: To assess the safety and efficacy of different endoscopic procedures of the prostate techniques, by comparing endoscopic enucleation (EEP) and endoscopic vaporization procedures (EVP) of the prostate; and laser enucleation procedures (L-EEP) vs laser vaporization procedures (L-EVP) surgeries for benign prostatic hyperplasia. METHODS: A systematic literature review was performed in December 2019 using PubMed, Embase and the Cochrane Library to identify relevant studies. Two analyses were carried out: (1) EEP vs EVP; and (2) L-EEP vs L-EVP. Efficacy and safety were evaluated using perioperative data, functional outcomes, including maximum urinary flow rate (Qmax), quality of life (QoL), international prostate symptom score (IPSS), postvoiding residual urine volume (PRV), and rate of complications. Meta-analyses were conducted using RevMan5.3. RESULTS: Sixteen studies (4907 patients) evaluated EEP vs EVP, and 12 of them (4392 patients) evaluated L-EEP vs L-EVP. EEP showed improved functional outcomes compared with EVP. EEP was always presented a better Qmax at various follow-up times. EEP also associated with a reduced PRV and IPSS at 12 months postsurgery, an increased Qmax, and reduced IPSS and QoL score at both 24 and 36 months postsurgery. In addition, EEP was associated with less total energy utilized and retreatment for residual adenoma, but a longer catheterization time. Among other outcomes, there was no significant difference. L-EEP favors total energy used, retreatment for residual adenoma, and functional outcomes. L-EEP was associated with reduced PRV at 1, 6, and 12 months postsurgery, a greater Qmax at 6 and 12 months postsurgery, a lower IPSS at 12 months postsurgery, and higher Qmax and lower IPSS and QoL scores at 24 and 36 months postsurgery. However, there was no difference at 3 months postsurgery. No significant differences were observed for other perioperative data and complications. CONCLUSIONS: Both EEP and EVP displayed sufficient efficacy and safety for treating benign prostatic hyperplasia. EEP and L-EEP were favored in perioperative data, rate of complications, and functional outcomes. However, the clinical significance of those statistical differences was unclear. Hence, higher-quality randomized controlled trials may be needed to provide a clear algorithm.

Cell-to-cell contact induces human adipose tissue-derived stromal cells to differentiate into urothelium-like cells in vitro.

Human adipose-derived stromal cells (hASCs) are capable of multi-lineage differentiation. Co-culture of stem cells with mature cells or tissues can drive their differentiation toward required lineages. We investigated whether direct cell-to-cell contact between hASCs and human UCs, or soluble signaling molecules, could induce the differentiation of hASCs into urothelium-like cells in vitro. hASCs were isolated from human subcutaneous adipose tissue and amplified in vitro. After labeled by green fluorescent protein, hASCs were cultured with human UCs in direct co-culture, indirect co-culture and conditioned culture, respectively. Two weeks later, expressions of specific urothelial differentiation markers were analyzed by RT-PCR and immunofluorescence. We found that hASCs in direct co-culture expressed urothelial-specific genes uroplakin Ib, uroplakin II and cytokeratin 18. However, uroplakin III gene was not detected during the experimental period. Additionally, uroplakin Ib and cytokeratin 18 were observed in differentiated hASCs by immunofluorescence. Notably, none of these markers were detected in hASCs cultured in indirect co-culture and conditioned culture. These findings suggest that direct cell-to-cell contact between hASCs and human UCs can induce the differentiation of hASCs along urothelial lineage.

Laparoscopic radical cystectomy with orthotopic ileal neobladder: a report of 85 cases.

PURPOSE: The preliminary results of laparoscopic radical cystectomy in 85 patients are presented in this study. The functional and oncologic outcomes of this procedure in these patients are discussed. PATIENTS AND METHODS: Between December 2002 and May 2006, we performed 85 laparoscopic radical cystectomies with orthotopic ileal neobladder for bladder cancer in 77 men and 8 women. A 5-port transperitoneal approach was applied. The standard bilateral pelvic lymphadenectomy was performed first, then radical cystectomy was completed laparoscopically. The construction of the ileal neobladder and the anastomosis of ureter-neobladder were performed extracorporeally. The neobladder was anastomosed to the urethral stump under laparoscopy. A nerve-sparing procedure was performed for eight patients. RESULTS: The median operative time was 320 min, and the median blood loss was 280 mL. Conversion to open surgery was not necessary in any of the patients. The average time to oral intake after operation was 3.9 days. There were no perioperative mortalities. The complication rate was 14.1% (12/85), including such complications as three uretero-pouch anastomotic strictures, one vesicourethral anastomotic stricture, one pouch-vaginal fistula, one colonic pouch fistula, one ileo-pouch fistula, three ileus, one pneumonia, and one pyelonephritis. The daytime continence rate was 91.2%, and the nighttime continence rate was 82.4% at 6 months postoperatively. The neobladder capacity was about 343 mL. Surgical margins were tumor free for all patients. Of the eight patients who underwent a nerve-sparing procedure, four patients had potency for intercourse. During a follow-up period of 1 to 41 months (average 21.3 months), three patients had local recurrence, one patient had trocar site seeding, and five patients had distant metastasis, of whom four died. CONCLUSIONS: Laparoscopic radical cystectomy with extracorporeal formation of a neobladder is a feasible procedure with low morbidity and acceptable neobladder function. Long-term follow-up is needed to confirm the oncologic outcomes.

Laparoscopic radical cystectomy with orthotopic ileal neobladder in the female: report of 14 cases.

BACKGROUND: Bladder carcinoma is the most common malignant urological tumor in China. We present our preliminary experience and results of laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder in female patients with bladder carcinoma. METHODS: From February 2003 to February 2008, 14 female patients with bladder carcinoma underwent LRC with orthotopic ileal neobladder. Nine of these patients underwent hysterectomy and ovariectomy, and the other 5 had preservation of the uterus and ovarian appendage. Standard bilateral pelvic lymphadenectomy was followed by radical cystectomy that was completed laparoscopically with hysterectomy and ovariectomy when needed. The tumor was removed by a 4 - 5 cm lower midline abdominal incision, followed by the construction of ileal neobladder and the extracorporeal anastomosis of ureter-neobladder. The neobladder was anastomosed to the urethral stump under a laparoscope. RESULTS: The mean operative time and blood loss in the 14 patients were 350.2 minutes and 349.8 ml, respectively. Postoperative complications included uretero-pouch anastomotic stricture in 1 patient and pouch-vaginal fistula in 1 patient. Follow-up time of all patients ranged from 3 to 60 months, and 12 patients were followed up for more than 6 months and achieved micturition in half a year. One patient had occasional day-time urinary incontinence and 2 had night-time incontinence. Two patients who had undergone hysterectomy and ovariectomy had voiding difficulties after one year, which was treated by intermittent self-catheterization. The mean volume of the neobladder and the residual urine were 333.6 ml and 31.2 ml, respectively. Surgical margins were tumor free for all patients. One patient had bone metastasis and died 11 months after the operation. CONCLUSIONS: LRC with orthotopic ileal neobladder in female patients is a technically feasible, safe and mini-invasive procedure with a low morbidity and acceptable neobladder function. Long-term follow-up is required to confirm the neobladder function and oncological outcomes.

[Laparoscopic radical cystectomy with orthotopic ileal neobladder: report of 108 cases].

OBJECTIVE: To analyze the effects, complication, and outcome of laparoscopic radical cystectomy. METHODS: 108 patients with bladder cancer, 96 males and 12 females, aged 61 (36 - 81) underwent laparoscopic radical cystectomy with orthotopic ileal neobladder. Five-port transperitoneal approach was applied. The surgical procedure included standard laparoscopic pelvic lymphadenectomy, radical resection of bladder, extracorporeal formation of ileal pouch; extracorporeal implantation of ureters; and laparoscopic urethra-neobladder anastomosis. Erectile nerve sparing procedure was performed for 26 cases. The patients were followed up for 1 - 53 months. RESULTS: The median operation time was 330 min, and the median blood loss was 320 ml. Conversion to open surgery was not necessary in any of the patients. There was no peri-operative mortality. The complication rate was 18.5% (20/108). Surgical margins were tumor free for all cases. The day-time and night-time continence rates were 90.7% and 82.6% respectively in 6 months postoperatively. 10 of the 26 patients undergoing erectile nerve-sparing procedure had potency for intercourse. Follow-up showed 5 cases with local recurrence, 1 case with trocar site seeding and 6 cases with distant metastasis, 8 of the patients died of tumor-related disease and 3 died of diseases not related to tumor. CONCLUSION: Laparoscopic radical cystectomy with extracorporeal formation of orthotopic ileal neobladder is a feasible technique with low morbidity and acceptable neobladder function.

[Compare of laparoscopic and open surgery for radical cystectomy with orthotopic ileal neobladder].

OBJECTIVE: To compare the clinical therapeutic effect and complications of laparoscopic radical cystectomy with orthotopic ileal neobladder (LRC-INB) with open radical cystectomy with orthotopic ileal neobladder (ORC-INB). METHODS: A total of 171 patients were evaluated, including 63 cases with ORC-INB and 108 cases with LRC-INB from June 1994 to May 2007 at our institution. The parameters analyzed included perioperative data, postoperative complications, new bladder function and effect of tumor control. RESULTS: There was no significant difference in demographic characteristics of patients between these 2 groups. The mean operating time was 330 min in the LRC group and 310 min in the ORC group (P > 0.05). The mean blood loss was 320 ml in the LRC group and 1100 ml in ORC group (P < 0.001). The mean oral intake after operation was 2.4 days for LRC group and 4.5 days for ORC group (P < 0.001). No perioperative death was occurred in both groups. The complication rate was 18.5% in LRC group, while 30.0% in ORC group (P < 0.05). Twelve months after operation, the day-time and night-time continence rate were 90.7% and 82.6% for the LRC group, 88.3% and 81.6% for the ORC group respectively (P > 0.05). There was no significant difference of VOL, pressure and residual urine volume (RUV) of neobladder between these 2 groups. Surgical margin were tumor free for 107 cases except one T4 case in laparoscopic group had positive margin (P > 0.05). The mean number of removed lymph node were 12 and 8 in LRC and ORC group respectively (P < 0.05). The 2 years tumor free survival rate of the same stage or grade was no significant different (P > 0.05). CONCLUSIONS: LCR had advantages of less blood loss, shorter oral intake time, less postoperative complications, comparable continent rate and short-term tumor control with ORC. Long-term follow up is needed to confirm the oncological outcome.

Acute intermittent porphyria presenting with seizures and posterior reversible encephalopathy syndrome: Two case reports and a literature review.

INTRODUCTION: Acute intermittent porphyria (AIP) is a rare and challenging hereditary neurovisceral disease with no specific symptoms. Posterior reversible encephalopathy syndrome (PRES) is a clinicoradiological syndrome with bilateral reversible posterior gyriform lesions that can be associated with many different conditions, including AIP. Usually, peripheral neuropathy is considered the most common neurological manifestation of AIP. However, AIP should also be considered when seizures and PRES are associated with unexplained abdominal pain. CASE PRESENTATION: Both the patients were presented with seizures and PRES on brain magnetic resonance imaging (MRI). Unexplained abdominal pain occurred before the onset of seizures. The AIP diagnosis was made after repeated Watson-Schwartz tests. Hematin was not available for these 2 patients. However, supportive treatment including adequate nutrition and fluid therapy as well as specific antiepileptic drugs aided the patient's recovery and no acute attacks had occurred by the 3-year follow-up. CONCLUSION: In contrast to other causes of PRES patients, seizure is the most common symptom in AIP patients with PRES. This is a strong diagnostic clue for AIP when ambiguous abdominal pain patients presented with seizures and PRES on brain MRI. A positive prognosis can be achieved with the combination of early recognition, supportive and intravenous hematin therapy, and withdrawal of precipitating factors, including some antiepileptic drugs.

SnoN suppresses TGF-ß-induced epithelial-mesenchymal transition and invasion of bladder cancer in a TIF1γ-dependent manner.

The transcriptional regulator SnoN (also known as SKI-like proto-oncogene, SKIL), a member of the Ski family, has been reported to influence epithelial-mesenchymal transition (EMT) in response to TGF-ß. In the present study, we investigated the role of SnoN in bladder cancer (BC). Differential expression of SnoN was not detected in BC tissues compared with that noted in adjacent non-cancerous tissues. SnoN was upregulated in response to TGF-ß treatment, but had no effect on the TGF-ß pathway, which may be explained by the low level of SnoN SUMOylation. TIF1γ, which catalyzes the SUMOylation of SnoN, was downregulated in BC tissues. Overexpression of TIF1γ restored the ability of SnoN to suppress the TGF-ß pathway. Furthermore, TGF-ß-induced EMT and invasion of BC cells were suppressed by TIF1γ in the presence of SnoN. Collectirely, our data suggest that SnoN suppresses TGF-ß­induced EMT and invasion of BC cells in a TIF1γ­dependent manner and may serve as a novel therapeutic option for the treatment of BC.

[Identification of response element gene sequence for non-steroid hormone transcription factors for the activation and up-regulation of L-plastin expression in prostate cancer].

OBJECTIVE: To search and identify the non-steroid receptor binding cis-acting elements in the L-plastin promoter in prostate cancer, and the correlative regulation pathway and transcription factors. METHODS: On the basis of construction of the L-plastin promoter luciferase vectors which were removed the steroid hormone receptor AR and ER binding elements, the promoter on the vector was nest-deleted by Exonuclease III and the relative luciferase plasmids were constructed. Transfected these twelve plasmids into prostate cancer cell line LNCaP under dihydrotestosterone-stimulated situation or not and test the intensity of luciferase, then we got the regulation message of every 200 bp part of the promoter in prostate cancer. After the analysis of relative programme, we got the possible regu- lation pathway of non-steroid hormone transcription factors. After removing the possible transcription factors binding site sequence by site-specific mutagenesis, the changes luciferase of activities proved our reasoning. RESULTS: We succeed in segmental deletion of the L-plastin promoter, and constructing the relative plasmids containing part L-plastin promoter on luciferase vector pGL3-basic. After testing the luciferase activities of constructed plasmids, we found the sequence from 206 to 1 of L-plastin promoter had significant luciferase activity. The software TRANSFECT showed that there were binding elements for transcription factors AP-4 at seq-198 to 192 and SP-1 at seq-54 to 41 on the short part promoter (206 to 1). The recombinant plasmids deleted the AP-4 and SP-1 binding elements had lower luciferase activity than the wild-type. CONCLUSION: There are some other non-steroid hormone pathway to regulate the expression of L-plastin except the steroid hormone pathway in prostate cancer. The main binding sites of the non-steroid hormone regulator lies in the sequence from 206 to 1. Transcription factors AP4 and SP-1 may up-regulated the expression of L-plastin by binding these sites.

[Preliminary study of inhibition of human Tenon's capsule fibroblasts in vitro by RNA interference targeting IKK-beta].

OBJECTIVE: To determine whether small interference RNA (siRNA) targeting the inhibitor of kappaB kinase-beta (IKK-beta) could be used to suppress the IKK-beta expression, and inhibit the proliferation of human Tenon's capsule fibroblasts in vitro. METHODS: IKK-beta specific siRNA designed from the human gene sequence was transfected into the cultured human Tenon's capsule fibroblasts, and a non-targeted siRNA was transfected as a negative control. The mRNA of IKK-beta was assessed by reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression was determined by Western blotting. Cell viability of the cultured human Tenon's capsule fibroblasts with series of RNA interference at 5, 10, 25, 50, 100, and 200 nmol/L was evaluated by MTT assay 48 hours after transfection. RESULTS: The expression of IKK-beta was significantly (P < 0.05) suppressed at both mRNA and protein levels after transfection. The proliferation of the cultured human Tenon's capsule fibroblasts was inhibited at all the transfected concentrations at different rates (10.72%, 23.35%, 30.84%, 51.25%, 50.06% and 49.63% respectively). The highest level of inhibition was observed at 50 nmol/L of siRNA concentration. CONCLUSIONS: IKK-beta specific siRNA is effective in suppressing the IKK-beta expression and inhibiting the proliferation of the cultured human Tenon's capsule fibroblasts. RNA interference may offer a new alternative to post-operational management of scar tissue formation.

13-Methyltetradecanoic acid induces mitochondrial-mediated apoptosis in human bladder cancer cells.

OBJECTIVE: 13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, is known to induce apoptosis in many types of human cancer cells. This study was designed to investigate the molecular mechanisms involved in 13-MTD-induced apoptosis in human bladder cancer cells. METHODS AND MATERIALS: MTT assay was used to investigate the potential effects of 13-MTD on the growth and viability of human bladder cancer cells. To find out whether anti-proliferation and cell death were associated with apoptosis, we used flow cytometry to quantify the extent of apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to measures DNA degradation of apoptotic cells. The proteins involved in the 13-MTD induced apoptosis were examined using Western blot. RESULTS: We show that 13-MTD inhibits cellular proliferation and viability in human bladder cancer cells, which has been attributed to apoptosis. 13-MTD down-regulates Bcl-2 and up-regulates Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the proteolytic activation of caspases. Moreover, 13-MTD down-regulates AKT phosphorylation and activates phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Up-regulating AKT phosphorylation and down-regulating JNK and P38 phosphorylation could attenuate the13-MTD-induced apoptosis. CONCLUSION: Taken together, these data indicate that 13-MTD induces mitochondrial-mediated apoptosis through regulation of the AKT and MAPK pathways, suggesting 13-MTD is a potential candidate for treatment of human bladder cancer.