An elevated AST/ALT ratio was significantly associated with worse postoperative survival in patients surgically treated for localized clear-cell RCC. Further prospective studies are needed to understand the prognostic value of preoperative AST/ALT ratio.
PurposeLocalised prostate cancer diagnosis and management is increasingly complex due to its heterogeneous progression and prognostic subgroups. Pitfalls in current screening and diagnosis have prompted the search for accurate and invasive molecular and genetic biomarkers for prostate cancer. Such tools may be able to distinguish clinically significant cancers from less aggressive variants to assist with prostate cancer risk stratification and guide decisions and healthcare algorithms. We aimed to provide a comprehensive review of the current prostate cancer biomarkers available and in development.MethodsMEDLINE and EMBASE databases searches were conducted to identify articles pertaining to the use of novel biomarkers for prostate cancer.ResultsA growing number of novel biomarkers are currently under investigation. Such markers include urinary biomarkers, serology-based markers or pathological tissue assessments of molecular and genetic markers. While limited clinical data is present for analysis, early results appear promising. Specifically, a combination of serum and urinary biomarkers (Serum PSA + Urinary PCA3 + Urinary TMPRSS2-ERG fusion) appears to provide superior sensitivity and specificity profiles compared to traditional diagnostic approaches (AUC 0.88).ConclusionThe accurate diagnosis and risk stratification of prostate cancer is critical to ensure appropriate intervention. The development of non-invasive biomarkers can add to the information provided by current screening practices and allows for individualised risk stratification of patients. The use of these biomarkers appears to increase the sensitivity and specificity of diagnosis of prostate cancer. Further studies are necessary to define the appropriate use and time points of each biomarker and their effect on the management algorithm of prostate cancer.
BackgroundTo compare the oncological and perioperative outcomes of different nephroureterectomy approaches in patients with non-metastatic upper tract urothelial carcinoma (UTUC).MethodsWe retrospectively analyzed the data of 422 patients who underwent open, laparoscopic, or robotic nephroureterectomy for non-metastatic UTUC. Perioperative and postoperative survival outcomes were compared using Kaplan-Meier analyses and Cox-proportional hazard models.ResultsOf the patients, 161, 137, and 124 were treated with an open, laparoscopic, and robotic approach, respectively. Laparoscopic and robotic approaches involved significantly less blood loss (p = 0.001), shorter hospital stay (p < 0.001), and longer operation time (p < 0.001) compared with the open approach. There were no significant differences in intraoperative complications (open, 8.1%; laparoscopic, 5.1%; robotic, 7.3%; p = 0.363) or early postoperative complications (open, 14.9%; laparoscopic, 14.6%; robotic, 13.7%; p = 0.880). The laparoscopic and robotic groups showed significantly less postoperative analgesic use (p = 0.015). The robotic group showed significantly longer progression-free, cancer-specific, and overall survivals than the open approach group on univariate Kaplan-Meier analysis, but surgery type was not significantly associated with survival outcomes per multivariate Cox proportional tests (all p-values > 0.05).ConclusionThe laparoscopic and robotic approaches yielded better perioperative outcomes, such as less intraoperative bleeding, shorter hospital stays, less analgesic usage, and non-inferior oncological outcomes, compared with the open approach. Further prospective studies are needed to compare these surgical techniques.
The PI3K/Akt/mTOR pathway is a prototypic survival pathway and constitutively activated in many malignant conditions. Moreover, activation of the PI3K/Akt/mTOR pathway confers resistance to various cancer therapies and is often associated with a poor prognosis. In this study, we explored the antitumor effect of NVP-BEZ235, a dual PI3K/mTOR inhibitor in cisplatin-resistant human bladder cancer cells and its synergistic interaction with cisplatin. A human bladder cancer cell line with cisplatin resistance was exposed to escalating doses of NVP-BEZ235 alone or in combination with cisplatin and antitumor effects was determined by the CCK-8 assay. Based on a dose-response study, synergistic interaction between NVP-BEZ235 and cisplatin was evaluated by combination index (CI), three-dimensional model and clonogenic assay. The combination of NVP-BEZ235 and cisplatin caused significant synergistic antitumor effect in cisplatin-resistant bladder cancer cells over a wide dose range and reduced the IC50 of NVP-BEZ235 and cisplatin by 5.6- and 3.6-fold, respectively. Three-dimensional synergy analysis resulted in a synergy volume of 388.25 μM/ml2% indicating a strong synergistic effect of combination therapy. The combination therapy caused cell cycle arrest and caspase-dependent apoptosis. Although NVP-BEZ235 suppressed PI3K/mTOR signaling without any paradoxical induction of Akt activity, it caused MEK/ERK pathway activation. The present study demonstrated that the PI3K/mTOR dual inhibitor NVP-BEZ235 can synergistically potentiate the antitumor effects of cisplatin in cisplatin-resistant bladder cancer cells though the suppression of cell cycle progression and the survival pathway as well as induction of caspase-dependent apoptosis.
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