l-Theanine delays d-galactose-induced senescence by regulating the cell cycle and inhibiting apoptosis in rat intestinal cells.

BACKGROUND: Intestinal senescence is associated with several aging-related diseases. l-Theanine (LTA) has demonstrated strong potential as an antioxidant and antisenescence agent. This study investigated the regulatory effect of LTA on cellular senescence using an in vitro model of d-galactose (D-Gal)-induced senescence in the rat epithelial cell line, intestinal epithelioid cell-6 (IEC-6). RESULTS: Treatment of IEC-6 cells with 40 mg/mL D-Gal for 48 h resulted in the successful development of the senescent cell model. Compared with D-Gal alone, both LTA preventive and delayed intervention increased cell viability and the ratio of JC-1 monomers to aggregates, increased the antioxidant capacity, and decreased the advanced glycation end product (AGE) levels and the overall number of senescent cells. Preventive and delayed intervention with 1000 µM LTA alleviated the D-Gal-induced cell cycle arrest by regulating p38, p53, CDK4, and CDK6 expression at the mRNA and protein levels, and further induced CycD1 proteins. Moreover, LTA preventive intervention reduced apoptosis to a greater degree than delayed intervention by upregulating the expression of the receptors of AGEs, Bax, Bcl-2, and NF-κB at the mRNA and protein levels. CONCLUSION: Our findings indicate that LTA intervention could attenuate senescence in IEC-6 cells by regulating the cell cycle and inhibiting apoptosis. © 2023 Society of Chemical Industry.

L-Theanine alleviates heat stress through modulation of gut microbiota and immunity.

BACKGROUND: Heat stress (HS) damages the intestines, disrupting gut microbiota and immune balance. l-Theanine (LTA), found in tea, alleviates oxidative stress and cell apoptosis under HS; however, its effects on gut microbiota and immunity under HS remain unclear. To investigate this, we administered LTA doses of 100, 200, and 400 mg·kg-1 ·d-1 to C57BL/6J mice. On day 44, the model group and LTA intervention group were subjected to continuous 7-day HS treatment for 2 h per day. RESULTS: The results demonstrated that LTA intervention improved food intake, body weight, and intestinal epithelium, and reduced the water intake of heat-stressed mice. It increased the abundance of Turicibacter, Faecalibaculum, Bifidobacterium, and norank_f_Muribaculaceae, while reducing that of Lachnoclostridium and Desulfovibrio. LTA intervention also increased the concentrations of amino acid and lipid metabolites, regulated macrophage differentiation stimulated by gut microbiota and metabolites, reduced the antigen presentation by macrophages to the specific immune system, promoted B-cell differentiation and sIgA secretion, inhibited pro-inflammatory factors, and enhanced intestinal defense. Mechanistically, LTA downregulated heat shock protein 70 expression and the TLR4/NF-κB/p38 MAPK signaling pathway, restoring gut microbiota and immune balance. CONCLUSION: We suggest that LTA can alleviate HS by modulating gut microbiota, metabolites, and immunity, indicating its potential as a natural active ingredient for anti-HS food products. © 2023 Society of Chemical Industry.

Hepatoprotective effects and mechanisms of l-theanine and epigallocatechin gallate combined intervention in alcoholic fatty liver rats.

BACKGROUND: Chronic excessive alcohol consumption can lead to alcoholic fatty liver, posing substantial health risks. l-Theanine (LTA) and epigallocatechin gallate (EGCG) in tea exert antioxidant and hepatoprotective effects. However, the combined effects of LTA and EGCG on rats with alcoholic fatty liver, and the underlying mechanisms of such effects, remain unclear. In this study, Sprague Dawley (SD) rats were fed with alcohol for 6 weeks to induce alcoholic fatty liver. Subsequently, for another 6 weeks, the rats were administered LTA (200 mg kg-1 day-1), EGCG (200 mg kg-1 day-1), or a combination of LTA with EGCG (40 mg kg-1 day-1 l-Thea +160 mg kg-1 day-1 EGCG), respectively. RESULTS: The combined use of LTA and EGCG for alcoholic fatty liver disease had more significant effects than their individual administration. This combination reduced the activity of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) as well as the levels of hepatic triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS) in the rats. The combined intervention also increased hepatic superoxide dismutase (SOD) and glutathione peroxidase activity. Reductions in hepatic fat accumulation and inflammatory responses were observed. The mechanism underlying these effects primarily involved the inhibition of fatty acid synthesis and the alleviation of lipid peroxidation through the downregulation of the mRNA and protein expression of TNF-α, SREBP1c, and CYP2E1 and the upregulation of the mRNA and protein expression of ADH1, ALDH2, Lipin-1, PPARαPPARα, AMPK, and PGC-1α, thereby promoting the oxidative decomposition of fatty acids and reducing the synthesis of cholesterol and glucose. CONCLUSION: l-Theanine and EGCG appear to be able to alleviate alcoholic fatty liver by modulating lipid metabolism and ameliorating oxidative stress, indicating their potential as natural active ingredients in anti-alcoholic fatty liver food products. © 2024 Society of Chemical Industry.

Important Therapeutic Considerations in T1b Penile Cancer: Prognostic Significance and Adherence to Treatment Guidelines.

BACKGROUND: The clinical implications and contemporary management of T1b penile cancer are unknown. National treatment guidelines advocate surgical lymph node examination (SLNE) for T1b disease. OBJECTIVE: The aim of this study was to evaluate the prognosis of T1b disease and adherence to corresponding treatment guidelines. METHODS: We analyzed 296 patients from two academic centers, and 1263 patients from the Surveillance, Epidemiology, and End Results (SEER) registry (median follow-up 48.3 and 21 months, respectively). Multivariate Cox and Fine-Gray regressions were applied for penile cancer-specific survival (PCSS) analyses. RESULTS: In the academic center cohort, 28.3% of T1 patients had T1b disease, all of whom underwent SLNE. Nodal metastases were detected in 86.7% of T1b patients and 13.2% of T1a patients (p < 0.001). Using T1a as a reference, PCSS was significantly poorer in the T1b patients, with an adjusted hazard ratio (aHR) of 4.10 (p = 0.03). In the SEER cohort, 16.8% of T1 patients were classified as T1b. SLNE was performed in 21.7% of the T1b patients versus 38.2% of the T2 patients (p = 0.002). The probability of nodal metastases was 2.23-fold higher in T1b patients than in T1a patients (p < 0.001). In clinical N0M0 patients without SLNE, compared with T1a disease, T1b was associated with an aHR of 4.40 and a subdistribution HR of 4.53 for PCSS (both p = 0.003). CONCLUSIONS: T1b penile cancer is strongly associated with nodal metastases and adverse PCSS, and is poorly managed according to guidelines recommended in the nationwide registry.

Evaluation of clinical staging of the American Joint Committee on Cancer (eighth edition) for prostate cancer.

OBJECTIVES: This study aimed to evaluate the eighth edition of the American Joint Committee on Cancer (AJCC) for clinical staging of prostate cancer based upon Surveillance, Epidemiology and, End Results (SEER) database. MATERIALS AND METHODS: Patients diagnosed as prostate adenocarcinoma during 2004-2009 without any surgical treatment to the primary site were selected from the SEER registry. Excluded were cases with incomplete or unavailable staging, PSA and Gleason score information. RESULTS: A total of 144,443 cases were identified. The median follow-up time was 84 months. The median age at diagnosis was 69 years, and median PSA was 7 ng/ml. CSS at 10th years was 96.2% for cT2a and 86.2% for cT2b/2c, respectively. The survival differences between clinical stage cT2a and cT2b/2c still had statistical significance (P < 0.001). For patients with grade group 1, there was no statistically significant difference for CCS between the cT2a and cT1 (P = 0.310), and between the subgroup of cT1/cT2a with 10 ng/ml ≤ PSA < 20 ng/ml and the subgroup of cT2b/2c with PSA < 20 ng/ml (P = 0.126), respectively. The CSS of IIIA (T1/2 with PSA ≥ 20 ng/ml) was less than IIC (P < 0.001), which has worst prognosis within stage I/II. The prognosis of T1/2 stage with Gleason score grade group 5 and PSA < 20 ng/ml was not only worse than AJCC IIC (P < 0.001) but also worse than AJCC IIIB (P < 0.001). CONCLUSION: It is necessary to maintain a three-tier system to subdivide T2 disease clinically. For patients with grade group 1, cT2a and cT1 could merge into one group. Organ-confined disease with PSA ≥ 20 ng/ml or grade group 5 should be separated from stage II.

Functional interaction of fibroblast growth factor 8b and androgen in prostate cancer cell proliferation.

Fibroblast growth factor 8b and androgen play important roles in cell proliferation of prostate cancer. We investigated the effects of fibroblast growth factor 8b and androgen on the proliferation of prostate cell lines and the corresponding intracellular mechanisms. It is found that dihydrotestosterone and fibroblast growth factor 8b stimulated Lncap cell mitosis in a concentration-responsive manner, with 30 ng/mL as the most suitable concentration, respectively. Dihydrotestosterone treatment alone did not enhance the expression and phosphorylation level of fibroblast growth factor receptor but significantly enhanced the level of fibroblast growth factor receptor phosphorylation elicited by fibroblast growth factor 8b. Phosphorylations of extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal kinase were stimulated by dihydrotestosterone or fibroblast growth factor 8b. Among these major downstream pathways for mitogen-activated protein kinase, c-Jun NH2-terminal kinase signaling was most significantly enhanced. Protein kinase C phosphorylation was higher than AKT by the combined stimulation of dihydrotestosterone and fibroblast growth factor 8b. The phosphorylation of CDC2 was significantly induced by dihydrotestosterone and fibroblast growth factor 8b synergetically, and Smad underwent the same induction as CDC2. So the promoting effect of fibroblast growth factor 8b on cell cycle might contribute to the G2/M transition. This study indicated that the functional interaction between fibroblast growth factor 8b and androgen was essential for the prostate cancer cell proliferation.

Assessment of survival of patients with metastatic clear cell renal cell carcinoma after radical cytoreductive nephrectomy versus no surgery: a seer analysis.

PURPOSES: To examine the factors related to the choice of cytoreductive nephrectomy (CN) for patients with metastatic clear cell renal cell carcinoma (mCCRCC), and compare the population-based survival rates of patients treated with or without surgery in the modern targeted therapy era. MATERIALS AND METHODS: From 2006 to 2009, patients with mCCRCC were identified from SEER database. The factors that affected patients to be submitted to CN were examined and propensity scores for each patient were calculated. Then patients were matched based upon propensity scores. Univariable and multivariable cox regression models were used to compare survival rates of patients treated with or without surgery. Finally, sensitivity analysis for the cox model on a hazard ratio scale was performed. RESULTS: Age, race, tumor size, T stage and N stage were associated with nephrectomy univariablely. After the match based upon propensity scores, the 1-, 2-, and 3-year cancer-specific survival rate estimates were 45.1%, 27.9%, and 21.7% for the no-surgery group vs 70.6%, 52.2%, and 41.7% for the surgery group, respectively (hazard ratio 0.42, 95%CI: 0.35-0.52, log-rank P<0.001). In multivariable Cox proportional hazard regression model, race, T stage, N stage and median household income were significantly associated with survival. Sensitivity analysis on a hazard ratio scale indicated that the hazard ratio might be above 1.00 only when the unknown factor had an opposite effect on survival which was 3-fold than CN. CONCLUSION: The results of our study showed that CN significantly improves the survival of patients with metastatic CCRCC even in the targeted therapy era.

Genetic diversity revealed by morphological traits and ISSR markers in 48 Okras (Abelmoschus escullentus L.).

Okra is a widely distributed crop in the tropics, subtropics, and warmer areas of the temperate zones. Its major potential uses as a vegetable, oil and protein source, and source of paper pulp and fuel, or biomass are compatible. It is expected to have high value of exploitation and application. Due to the limited number of molecular studies focused on okras, the methods of morphological and ISSR markers were used to analysis the genetic diversity of 48 okras in the present study. The 22 primers were picked for ISSR-PCR, and a total of 154 fragments were amplified with an overall average polymorphism of 54.55 %. We used the 154 markers to construct the dendrogram based on the unweighted pair group method with arithmetic means (UPGMA). A high level of genetic diversity was found among 48 individuals. The 48 Okras was divided into four clusters at Dice's coefficient of 0.19 with clustering analysis. Based on these data of the genetic diversity, it will be possible to exploit the available resources of okra in more valuable ways.

Visceral fat accumulation is associated with different pathological subtypes of renal cell carcinoma (RCC): a multicentre study in China.

OBJECTIVE: To investigate whether visceral obesity is associated with certain histological subtypes of renal cell carcinoma (RCC) ina multicentre Chinese cohort. PATIENTS AND METHODS: A kidney tumour database was created using three tertiary centres in China; 487 patients were enrolled presenting with localised RCC and complete computer tomography(CT)/magnetic resonance imaging (MRI) information. A single-slice CT image was used to measure the area of visceral and subcutaneous adipose tissues in each patient. Statistical methods were used to analyse clear-cell RCC (ccRCC) and non-clear-cell RCC (non-ccRCC) as they relate to visceral fat area (VFA) and other risk factors, such as age, gender, tumour size, diabetes, hypertension, total fat area (TFA) and body mass index (BMI). RESULTS: In all, 418 patients had a ccRCC subtype and 69 had a non-ccRCC subtype. For all the patients with RCC, the mean VFA was 102 cm2, while mean BMI was 24 kg/m2. The mean VFA was greater in ccRCC than non-ccRCC patients by 25 cm2. There were significant differences in the mean VFA and TFA between patients with ccRCC and those with non-ccRCC.Multivariate analysis showed that the presence ofVFA was more important than the effects of BMI and Type 2 diabetes on pathology prediction. In patients with a normal BMI, those with a higher quartile of VFA were more likely to develop ccRCC than those with a low VFA. CONCLUSIONS: Increased visceral fat was found to be associated with ccRCC and the significance of VFA outweighed the effects of BMI and Type 2 diabetes for the prediction of RCC pathology in multivariate analyses. As a result, VFA could constitute a primary explanation for the link between obesity and ccRCC.

A Phase II trial of dosage escalation of sorafenib in Asian patients with metastatic renal cell carcinoma.

AIM: To investigate the role of sorafenib dosage escalation in Asian patients with metastatic renal cell carcinoma that had progressed after routine dosages. PATIENTS & METHODS: Sorafenib dosage escalation to 600 or 800 mg twice a day was offered to 41 patients with metastatic renal cell carcinoma who had progressed on normal dosages. Clinical outcome, toxicity and favorable clinical covariables for progression-free survival (PFS) were evaluated. RESULTS: The median PFS with dosage-escalated therapy was 7 months. Drug-related adverse events were tolerable. The pre-escalation Karnofsky performance status, serum calcium concentration, neutrophil/lymphocyte ratio, PFS and the highest toxicity grade at the routine dosage were associated with a longer PFS in the dosage-escalation period. CONCLUSION: Sorafenib dosage escalation was efficacious and tolerable in Asian patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (no. ChiCTR-ONRC-12002088).

Comparison of three versions of Partin tables to predict final pathologic stage in a Chinese cohort: a decision curve analysis.

PURPOSE: To compare Partin tables (PTs) 1997, 2001, and 2007 for their clinical applicability in a Chinese cohort based upon a decision curve analysis (DCA). METHODS: Clinical and pathologic data of 264 consecutive Chinese patients with clinically localized prostate cancer were used. These patients underwent open radical prostatectomy between 2005 and 2011. DCA quantified the net benefit of different PT versions relating to specific threshold probabilities of established capsular penetration (ECP), seminal vesicle involvement (SVI), and lymph node involvement (LNI). RESULTS: Overall, ECP, SVI, and LNI were recorded in 23.1, 10.2, and 6.1%, respectively. When the threshold probability was below the prevalence for LNI and ECP predictions, the DCA favored the 2007 version versus the 1997 version for SVI. CONCLUSIONS: DCA indicates that for low threshold probability, decision models are useful to discriminate the performance differences of three PT versions, although net benefit differences were not apparent. For high threshold probability, there may not be an important benefit from the use of PTs and the current analysis cannot translate into meaningful net gains differences.

[Hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib].

OBJECTIVE: To explore the hematologic adverse effects in patients with renal cell carcinoma treated with sunitinib. METHODS: A total of 136 patients with advanced renal cell carcinoma were treated with sunitinib at our hospital from 2008 to 2011. There were 91 males and 45 females with an average age of 55.5 years. They received sunitinib in repeated 6-week cycles consisting of 4 weeks of sunitinib 50 mg per day followed by 2 weeks of treatment (schedule 4/2). The hematologic toxicities, collected at baseline and 14, 28, 42 (after a 2-week rest period) days, were graded according to the National Cancer Institute common terminology criteria for adverse events version 3.0. The paired Wilcoxon test was used to evaluate the kinetics of hematologic adverse effects at days 14, 28, and 42 post-treatment. RESULTS: The hematologic toxicities included leukopenia (n = 91, 66.9%), neutropenia (n = 95, 69.8%), lymphopenia (n = 58, 46.2%), thrombopenia (n = 89, 65.4%) and hypohemoglobinemia (n = 48, 35.3%). Among them, 31 cases (22.8%) had the high-grade (including grades 3 and 4) toxicity of thrombopenia. There were depressions in hematopoietic cell populations including leukocytes, neutrophils, and platelets at days 14, 28 and 42 versus the baseline level (all P < 0.05). The median hemoglobin level transiently increased at days 14 and 28 (both P < 0.01) and returned to the level of baseline at days 42 (P = 0.754). CONCLUSIONS: The incidence of hematologic adverse effects of sunitinib slightly varies with what have been observed in previous studies. And the incidence of high-grade toxicity of thrombocytopenia is higher than that reported in studies conducted in the US and Europe.

[Exploratory analysis of the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma].

OBJECTIVE: To explore the effect of toxicity of sunitinib on the clinical outcome of patients with advanced renal cell carcinoma (RCC) . METHODS: A total of 136 patients with advanced RCC were treated with sunitinib from 2008 to 2011. There were 91 males and 45 females with an average age of 56 years. Their 6-week therapy cycle was 4 weeks of sunitinib 50 mg daily followed by 2-week off-treatment (schedule 4/2). The median follow-up time was 15 months. Correlation between toxicities and overall survival (OS) was evaluated in a Cox model using log-transformed levels after adjusting for MSKCC model.Log-rank test and Cox proportional hazard model were used to assess the value of drug toxicity as the prognostic factors. RESULTS: The increased hemoglobin on cycle 1 day 14 (HR:0.950, 95%CI:0.923-0.978) and the increased lymphocytes on cycle 1 days 28 and 42 (HR:0.405, 95%CI:0.203-0.809, HR:0.394, 95%CI:0.179-0.867) were significantly associated with OS (P adj = 0.001, 0.014 and 0.022 respectively). Hypertension class III/IV (HR:0.066, 95%CI:0.008-0.582), and the number of neutrophils screening and lymphocyte count ratio (HR:2.537, 95%CI:1.182-5.404) were the survival prognosis independent predictors. CONCLUSION: Early hematopoietic toxicities may potentially predict the outcomes of advanced RCC after a therapy of sunitinib.

[Efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer].

OBJECTIVE: To assess the efficacy of low dose ketoconazole therapy for Chinese patients with castration resistant prostate cancer (CRPC) and explore possible prognosis factors. METHODS: From August 2006 to August 2011, 71 patients with CRPC were analyzed retrospectively, who received oral ketoconazole 200 mg, three times a day with prednisone 5 mg, twice a day. Prostate specific antigen (PSA) response rate was defined as the percentage of patients with PSA decline ≥ 50% compared to baseline PSA level during low dose ketoconazole therapy. Multivariate Logistic regression analysis and receiver operating characteristic curve were used to assess the prognostic factors and their accuracy. RESULTS: The mean initial serum PSA level was (205 ± 38) ng/ml for these patients with mean age (69 ± 1) years old. After first androgen deprivation therapy failure, the prostate cancer progressed into castration resistant stage. The baseline PSA was (93 ± 24) ng/ml and the baseline serum testosterone was (0.13 ± 0.02) ng/ml. During the low dose ketoconazole therapy, 31 patients (43.7%) had PSA decrease and 22 cases (31.0%) were effective with PSA decline more than 50%. PSA doubling time and baseline serum testosterone were positive correlation with PSA response rate by multivariate Logistic regression analysis. Patients with PSA doubling time of ≥ 3.0 months had a PSA response rate of 64.3% and the PSA response rate in those with < 3.0 months decreased to 22.8%, hazard rate (HR) = 0.149 (95% confidence interval [CI] 0.029 - 0.766), P = 0.023, area under the curve (AUC) = 0.707. The PSA response rate for patients with baseline serum testosterone ≥ 0.1 and < 0.1 µg/L were 55.6% and 5.7%, respectively, HR = 0.068 (95%CI 0.012 - 0.380), P = 0.002, AUC = 0.749. The common adverse reactions included liver dysfunction (17.9%), renal dysfunction (16.4%), fatigue (11.9%), nausea (6.0%) and anorexia (4.5%) and so on. CONCLUSIONS: Low dose ketoconazole therapy was a moderate, low toxicity hormonal therapy option for patients with CRPC. PSA doubling time ≥ 3 months and baseline serum testosterone ≥ 0.1 µg/L were predictors of desired effect for low dose ketoconazole therapy.

L-Theanine Modulates Intestine-Specific Immunity by Regulating the Differentiation of CD4+ T Cells in Ovalbumin-Sensitized Mice.

Ovalbumin (OVA), a common food protein, can cause deadly allergies with intestine-specific immune reactions. L-Theanine (LTA) shows great potential for regulating intestinal immunity. To investigate the regulatory effect of LTA intervention on intestine-specific immunity, a 41 day experiment was performed on BALB/c OVA-sensitized mice. The results show that injecting female mice intraperitoneally with 50 µg of OVA and administering 30 mg of OVA 4 times can successfully establish an OVA-sensitized mouse model. LTA intervention significantly increased weight gain and thymus index (p < 0.05), decreased allergy and diarrhea scores (p < 0.05), and improved jejunum structure. Meanwhile, the histological score and degranulation of mast cells decreased. LTA intervention increased Clostridiales, Lachnospiraceae, Lactobacillus, Prevotella, and Ruminococcus abundance while decreasing Helicobacter abundance. Flow cytometry and Western blotting results indicated that 200 and 400 mg/kg of LTA upregulated the expression of T-bet and Foxp3 proteins (p < 0.05), thus promoting the differentiation of jejunum CD4+ T cells to Th1 and Tregs and increasing the cytokines IFN-γ, IL-10, and TGF-ß (p < 0.05). We found that 200 and 400 mg/kg of LTA downregulated the expression of RORγt and GATA3, thus inhibiting the differentiation of Th2 and Th17 cells and decreasing cytokines IL-4, IL-5, IL-13 TNF-α, IL-6, and IL-17A (p < 0.05). LTA inhibited the degranulation of mast cells and significantly decreased the serum levels of OVA-IgE, HIS, and mouse MCPT-1 (p < 0.05). Therefore, LTA intervention alleviated OVA allergy by improving intestine-specific immunity.

Comparison of accuracy among three generations of Partin tables in a Chinese cohort.

INTRODUCTION: To perform a head to head comparison among three generations of Partin tables, namely from 1997, 2001 and the last updated version of 2007, in a Chinese cohort of prostate cancer. MATERIAL AND METHODS: Clinical and pathological data of 198 consecutive Chinese patients were retrospectively analyzed, who underwent radical prostatectomy for clinically localized prostate cancer between January 2005 and May 2010. Three versions of the Partin tables were compared for their accuracy and performance to predict final pathological stage using receiver operating characteristic (ROC) curve. RESULTS: Of the whole cohort 58.6% were presented with organ-confined disease (OCD), 10.1% had lymph node involvement (LNI), and 31.3% had locally advanced disease (LAD), while 21.2% had extraprostatic extension (ECE) and 10.1% showed seminal vesicle involvement (SVI). The area under the ROC curve (AUC) of the Partin Tables 1997, 2001 and 2007 was 0.732, 0.722 and 0.695 for OCD; 0.647, 0.594 and 0.577 for LAD; 0.856, 0.872 and 0.829 for LNI, respectively. CONCLUSION: All three generations of the Partin tables showed a good accuracy to predict OCD, and LNI. However, the predictive accuracy for LAD was more limited. Overall, the newer versions of the Partin tables could not exceed the version of 1997 in their predictive accuracy for the present Chinese cohort. Our results suggest caution when using newly introduced predictive tools that are not supported by population-specific accuracy tests.

Yolk sac tumor in a patient with transverse testicular ectopia.

Transverse testicular ectopia (TTE) is a rare anomaly in which both testes descend through a single inguinal canal. We report a case of yolk sac tumor in the ectopic testis of a patient with TTE. A 24-year-old man presented to our hospital with a left inguinal-mass, right cryptorchidism and elevated alpha-fetoprotein (AFP). A left herniotomy 3 years earlier demonstrated both testes in the left scrotum, one above another positionally. Four months ago, a left scrotal mass appeared and radical orchiectomy of both testes revealed testicular yolk sac tumor of the ectopic testis. An enlarging left inguinal-mass appeared 2 months ago and he was referred to our hospital. Laboratory data showed an elevation of AFP (245.5 ng/ml) and a 46 XY karyotype. He underwent bilateral retroperitoneal lymph node dissection and simultaneous left inguinal mass dissection. Histopathologic examination revealed a diagnosis of recurrent yolk sac tumor in the left inguinal mass. The retroperitoneal lymph node was not enlarged and, on histopathology, was not involved. The patient has now been followed up for 8 months without evidence of biochemical or radiological recurrence.

Involvement of microRNA-21 in mediating chemo-resistance to docetaxel in androgen-independent prostate cancer PC3 cells.

AIM: To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel. METHODS: A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3'UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot. RESULTS: A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be up-regulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC(50) values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells. CONCLUSION: Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment.

[Establishment of regression model predicting the probability of the capsular penetration of prostate cancer].

OBJECTIVE: To establish the regression model predicting the probability of the capsular penetration according to the Chinese prostate cancer samples. METHODS: Men enrolled in the Fudan University Shanghai Cancer Centre and undergoing radical prostatectomy between January 2006 and April 2010 were used to establish the predicting model. According to the pathology after radical prostatectomy, all cases were divided into two groups: organ confined disease group and locally advanced disease group, the difference of which were whether had the capsular penetration. The cases with regional lymph node metastasis were excluded. Serum prostate specific antigen level, Gleason grade, clinical stage were collected. Multiple Logistic regression model was established according to preoperative clinical data and postoperative pathological data to predict the incidence of capsular penetration. Receiver operating characteristic curve was used for the internal validation of the model. RESULTS: 83 Chinese men were identified in the organ confined disease group with the age of 66.8 ± 5.8 years, and 36 in the locally advanced disease group with the age of 66.0 ± 6.8 years. The difference of the age between the two groups were of no statistic significance (t = 0.650, P = 0.517). The serum prostate specific antigen level (Wilcoxon W = 4562.0, P = 0.016), Gleason score (Wilcoxon W = 4586.5, P = 0.016), and clinical stage (Wilcoxon W = 4444.5, P = 0.001) of the locally advanced disease group were higher than the other group. The equation of the multiple Logistic regression model was Logit P = 0.488 × Gleason score + 0.104 × clinical stage -6.187, with the freedom degree of two and the likelihood ratio χ(2) test of 11.263 (P = 0.001). The area under the ROC curve (AUC) for capsular penetration was 0.696 (P = 0.001), with the 95% confidence interval of 0.598 - 0.793. CONCLUSION: The multiple Logistic regression model based on the Chinese population can accurately predict the probability of capsular penetration of the prostate cancer and work on well with high internal accuracy when clinical decisions are made.

[Experiences of open transperitoneal radical nephrectomy for large renal masses].

OBJECTIVE: To evaluate the effect of technical improvements of transperitoneal radical nephrectomy on the patients with large renal cell carcinoma. METHODS: From May 2002 until May 2009, 45 patients with large (> 12 cm) renal cell carcinoma underwent transperitoneal radical nephrectomy. A subcostal incision was selected to expose the extraperitoneal area. The modified operative methods included exposing the operative field via a liver retractor and initially ligating renal artery to block the blood supply of kidney and tumor. The method of tumor-free tissue dissociation was applied. Hem-o-lock was employed for clipping so as to avoid hemorrhage. This modified technique was evaluated in respects of operating time, estimated blood loss, intra-operative complications, postoperative complications, length of hospital stay and pathological diagnoses. RESULTS: The tumor diameter was from 12.2 cm to 28.3 cm with a mean of 14.5 cm. The mean operative time was (150 +/- 58) min and the average estimated blood loss (350 +/- 180) ml. Three cases received blood transfusion. The average length of hospital stay was (12 +/- 6) days. Three cases developed complications, including spleen injury in 2 and pancreatic injury in 1. The treatment modalities were splenectomy and resection of pancreatic tail respectively. The pathological diagnoses were all of renal cell carcinoma. The pathological stage included T(2)N(0 approximately 1)M(0 approximately 1)(n = 13), T(3)N(0 approximately 1)M(0 approximately 1)(n = 23), T(4)N(0 approximately 1)M(0 approximately 1)(n = 9). After a follow-up period of 3 - 63 months, 3 cases of tumor recurrence were found in primary renal clutch. CONCLUSION: Improved radical nephrectomy is feasible for large renal cell carcinoma. And it can reduce the volume of blood loss and decrease the occurrence of complications.