• CD163
• Macrophage
• Radical nephroureterectomy
• Upper urinary tract
• Urothelial carcinoma

• Male
• Humans
• Female
• Nephroureterectomy/methods
• Carcinoma, Transitional Cell/pathology
• Retrospective Studies
• Urinary Bladder Neoplasms/pathology
• Kidney Neoplasms/pathology
• Ureteral Neoplasms/pathology
• Prognosis
• Urinary Tract/pathology
• Urologic Neoplasms/surgery
• Urologic Neoplasms/pathology

The prognosis of non-metastatic gallbladder adenocarcinoma (NM-GBA) patients is affected by the status of metastatic lymph nodes. The purpose of this study was to explore the prognostic value of the log odds of positive lymph nodes (LODDS) and develop a novel nomogram to predict the overall survival in NM-GBA patients. A total of 1035 patients confirmed to have NM-GBA were selected from the Surveillance, Epidemiology, and End Results (SEER) database and further divided into training and validation cohorts. The discrimination and calibration of the nomogram were evaluated using the concordance index (C-index), the area under the time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. The net benefits and clinical utility of the nomogram were quantified and compared with those of the 8th edition American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) staging system using decision curve analysis (DCA), net reclassification index (NRI), and integrated discrimination improvement (IDI). The risk stratifications of the nomogram and the TNM-staging system were compared. LODDS showed the highest accuracy in predicting OS for NM-GBA. The C-index (0.730 for the training cohort and 0.746 for the validation cohort) and the time-dependent AUC (> 0.7) indicated the satisfactory discriminative ability of the nomogram. The calibration plots showed a high degree of consistency. The DCA, NRI, and IDI indicated that the nomogram performed significantly better than the TNM-staging (P < 0.05). A novel LODDS-included nomogram was developed and validated to assist clinicians in evaluating the prognosis of NM-GBA patients.

The most common site of prostate cancer metastasis is bone tissue with many recent studies having conducted genomic and clinical research regarding bone metastatic prostate cancer. However, further work is needed to better define those patients that are at an elevated risk of such metastasis.

SEER and TCGA databases were searched to develop a nomogram for predicting prostate cancer bone metastasis.

Herein, we leveraged the Surveillance, Epidemiology, and End Results (SEER) database to construct a predictive nomogram capable of readily and accurately predicted the odds of bone metastasis in prostate cancer patients. This nomogram was utilized to assign patients with prostate cancer included in The Cancer Genome Atlas (TCGA) to cohorts at a high or low risk of bone metastasis (HRBM and LRBM, respectively). Comparisons of these LRBM and HRBM cohorts revealed marked differences in mutational landscapes between these patient cohorts, with increased frequencies of gene fusions, somatic copy number variations (CNVs), and single nucleotide variations (SNVs), particularly in the P53 gene, being evident in the HRBM cohort. We additionally identified lncRNAs, miRNAs, and mRNAs that were differentially expressed between these two patient cohorts and used them to construct a competing endogenous RNA (ceRNA) network. Moreover, three weighted gene co-expression network analysis (WGCNA) modules were constructed from the results of these analyses, with KIF14, MYH7, and COL10A1 being identified as hub genes within these modules. We further found immune response activity levels in the HRBM cohort to be elevated relative to that in the LRBM cohort, with single sample gene enrichment analysis (ssGSEA) scores for the immune checkpoint signature being increased in HRBM patient samples relative to those from LRBM patients.

We successfully developed a nomogram capable of readily detecting patients with prostate cancer at an elevated risk of bone metastasis.

When treating diseases related primarily to tissue remodeling and fibrosis, it is desirable to regulate TGFβ concentration and modulate its biological effects. The highest cellular concentrations of TGFβ are found in platelets, with about 40% of all TGFβ found in peripheral blood plasma being secreted by them. Therefore, an understanding of the mechanisms of TGFβ secretion from platelets may be of key importance for medicine. Unfortunately, despite the finding that platelets are an important regulator of TGFβ levels, little research has been carried out into the development of platelet-directed therapies that might modulate the TGFβ-dependent processes. Nevertheless, there are some very encouraging reports suggesting that platelet TGFβ may be specifically involved in cardiovascular diseases, liver fibrosis, tumour metastasis, cerebral malaria and in the regulation of inflammatory cell functions. The purpose of this review is to briefly summarize these few, extremely encouraging reports to indicate the state of current knowledge in this topic. It also attempts to better characterize the influence of TGFβ on platelet activation and reactivity, and its shaping of the roles of blood platelets in haemostasis and thrombosis.

• Smad
• TGFβ
• cardiovascular
• fibrosis
• granules
• platelets
• preeclampsia
• secretion

• Blood Platelets/metabolism
• Cardiovascular Diseases/physiopathology
• Hemostasis/physiology
• Humans
• Inflammation/physiopathology
• Liver Cirrhosis/physiopathology
• Malaria, Cerebral/physiopathology
• Neoplasm Metastasis/physiopathology
• Platelet Activation/physiology
• Thrombosis/physiopathology
• Transforming Growth Factor beta/blood
• Transforming Growth Factor beta/metabolism

• Adverse pathology
• Biomarkers
• Cell cycle progression
• Genomic Evaluators of Metastatic Prostate Cancer
• Prostate cancer
• Prostatectomy

Transforming growth factor β (TGFβ) is overexpressed in advanced cancers and promotes tumorigenesis by inducing epithelial–mesenchymal transition (EMT), which enhances invasiveness and metastasis. Although we previously reported that EMT could be induced by increasing CK2 activity alone, it is not known whether CK2 also plays an essential role in TGFβ‐induced EMT. Therefore, in the present study, we investigated whether TGFβ signaling could activate CK2 and, if so, whether such activation is required for TGFβ‐induced EMT. We found that CK2 is activated by TGFβ treatment, and that activity peaks at 48 h after treatment. CK2 activation is dependent on TGFβ receptor (TGFBR) I kinase activity, but independent of SMAD4. Inhibition of CK2 activation through the use of either a CK2 inhibitor or shRNA against CSNK2A1 inhibited TGFβ‐induced EMT. TGFβ signaling decreased CK2β but did not affect CK2α protein levels, resulting in a quantitative imbalance between the catalytic α and regulatory β subunits, thereby increasing CK2 activity. The decrease in CK2β expression was dependent on TGFBRI kinase activity and the ubiquitin–proteasome pathway. The E3 ubiquitin ligases responsible for TGFβ‐induced CK2β degradation were found to be CHIP and WWP1. Okadaic acid (OA) pretreatment protected CK2β from TGFβ‐induced degradation, suggesting that dephosphorylation of CK2β by an OA‐sensitive phosphatase might be required for CK2 activation in TGFβ‐induced EMT. Collectively, our results suggest CK2 as a therapeutic target for the prevention of EMT and metastasis of cancers.

• Epithelial-mesenchymal transition
• TGFβ
• WW domain containing E3 ubiquitin protein ligase 1
• carboxyl terminus of Hsc70-interacting protein
• protein kinase CK2

• Antisense oligonucleotide
• cancer
• epithelial-mesenchymal transition
• monoclonal antibody
• transforming growth factor-β

Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ≥ 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ≥ 320 pg/mL and PSA ≥ 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.

• CCL2
• androgen deprivation therapy
• biomarker
• prostate cancer
• risk classification

• Biochemical recurrence
• Circulating tumor cells
• Prostate cancer
• Prostatectomy

• Aged
• Analysis of Variance
• Humans
• Kaplan-Meier Estimate
• Logistic Models
• Male
• Middle Aged
• Neoplasm Recurrence, Local/blood
• Neoplasm Staging
• Neoplastic Cells, Circulating/pathology
• Preoperative Period
• Prognosis
• Prostate-Specific Antigen/blood
• Prostatectomy/methods
• Prostatic Neoplasms/blood
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/surgery
• Time Factors
• Treatment Outcome

• Female
• Hospice Care
• Humans
• Male
• Middle Aged
• Models, Statistical
• Neoplasms/mortality
• Neoplasms/therapy
• Prognosis
• Prospective Studies
• Survival Analysis
• Taiwan/epidemiology

This report summarizes the presentations and discussions that took place at the Seventh Joint Meeting of the Korea–Japan Study Group of Prostate Cancer (K-J-CaP) and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) held in Seoul, Korea, in September 2013. The original J-CaP and CaPSURE Joint Initiative has now been established since 2007 and since the initial collaboration between research teams in the United States (US) and Japan, the project has expanded to include several other Asian countries. The objective of the initiative is to analyze and compare data for prostate cancer patients in the participating countries, looking at similarities and differences in patient management and outcomes. Until now the focus has been primarily on data generated within J-CaP and CaPSURE, both large-scale, longitudinal, observational databases of prostate cancer patients in Japan and the US, respectively. This year’s meeting was hosted for the first time in Korea which has recently established its own national database–K-CaP–to add to the wealth of data generated by J-CaP and CaPSURE. As a newly-developed database, K-CaP has also provided a valuable ‘template’ for other countries, such as China and Indonesia, planning to establish their own national databases and this will ultimately allow greater opportunities for international data comparisons. A range of topics was discussed at this Seventh Joint Meeting including comparison of outcomes following androgen deprivation therapy or radical prostatectomy in patients with localized prostate cancer, the use of active surveillance as a treatment option and the triggers for intervention when employing this regimen, patient quality of life during treatment, the impact of comorbidities on outcomes, and a comparison of recent outcomes data between J-CaP and CaPSURE. The participants recognized that prostate cancer was now a global disease and therefore major insights into understanding and improving the management of this condition would arise from global interactions such as this joint initiative.

• Comorbidity
• Drug therapy for prostate cancer
• Prostatectomy
• Prostatic neoplasms
• Quality of life

Although the incidence of prostate cancer (PCa) is rapidly increasing in Korea, there are few suitable prediction models for disease recurrence after radical prostatectomy (RP). We established pre- and post-operative nomograms estimating biochemical recurrence (BCR)-free probability after RP in Korean men with clinically localized PCa.

Our sampling frame included 3,034 consecutive men with clinically localized PCa who underwent RP at our tertiary centers from June 2004 through July 2011. After inappropriate data exclusion, we evaluated 2,867 patients for the development of nomograms. The Cox proportional hazards regression model was used to develop pre- and post-operative nomograms that predict BCR-free probability. Finally, we resampled from our study cohort 200 times to determine the accuracy of our nomograms on internal validation, which were designated with concordance index (c-index) and further represented by calibration plots.

Over a median of 47 months of follow-up, the estimated BCR-free rate was 87.8% (1 year), 83.8% (2 year), and 72.5% (5 year). In the pre-operative model, Prostate-Specific Antigen (PSA), the proportion of positive biopsy cores, clinical T3a and biopsy Gleason score (GS) were independent predictive factors for BCR, while all relevant predictive factors (PSA, extra-prostatic extension, seminal vesicle invasion, lymph node metastasis, surgical margin, and pathologic GS) were associated with BCR in the post-operative model. The c-index representing predictive accuracy was 0.792 (pre-) and 0.821 (post-operative), showing good fit in the calibration plots.

In summary, we developed pre- and post-operative nomograms predicting BCR-free probability after RP in a large Korean cohort with clinically localized PCa. These nomograms will be provided as the mobile application-based SNUH Prostate Cancer Calculator. Our nomograms can determine patients at high risk of disease recurrence after RP who will benefit from adjuvant therapy.

• Aged
• Disease-Free Survival
• Humans
• Lymphatic Metastasis
• Male
• Middle Aged
• Neoplasm Grading
• Nomograms
• Postoperative Period
• Preoperative Period
• Probability
• Proportional Hazards Models
• Prostate-Specific Antigen
• Prostatectomy
• Prostatic Neoplasms/epidemiology
• Prostatic Neoplasms/surgery
• Republic of Korea

• U54 CA149233 NCI NIH HHS

• active surveillance
• nomograms
• prediction
• progression
• prostate cancer

The objective was to validate an online nomogram developed based on the French collaborative national database on upper urinary tract urothelial carcinoma (UUT-UC) using a different cohort.

The study comprised 328 patients with UUT-UC who underwent radical nephroureterectomy. The discrimination of models was quantified using Harrell's concordance index. The relationship between the model-derived and actuarial cancer-specific mortality was graphically explored within calibration plots. Calibration was also assessed using the quartiles of the predicted survival at 3 and 5 years and calculation of the corresponding observed Kaplan–Meier estimates. Clinical net benefit was evaluated constructing decision curve analysis.

The discrimination accuracy of the nomograms at 3 and 5 years was 71.6% and 71.8%, respectively. Although nomograms discriminated well by Kaplan–Meier curves, and log-rank tests were all highly significant, the calibration plots tended to exaggerate the overestimation of mortality between predicted and observed probabilities at 3 and 5 years for survival. When compared with the AJCC/UICC staging system, the nomograms performed well across a wide range of threshold probabilities using decision curve analysis.

The online nomogram is a highly accurate prognostic tool for patients with UUT-UC treated with radical nephroureterectomy. The model can provide an accurate estimate of the individual risk of cancer-specific mortality. Further improvement and implementation of novel molecular marker is needed.

• Diagnosis
• Disease management
• Prostate neoplasms

• Aged
• Antigens, Surface/blood
• Antigens, Surface/genetics
• Biomarkers, Tumor/blood
• Biomarkers, Tumor/genetics
• Disease-Free Survival
• Follow-Up Studies
• Glutamate Carboxypeptidase II/blood
• Glutamate Carboxypeptidase II/genetics
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local/blood
• Neoplasm Recurrence, Local/genetics
• Neoplasm Recurrence, Local/mortality
• Neoplastic Cells, Circulating/pathology
• Nomograms
• Predictive Value of Tests
• Prostate-Specific Antigen/blood
• Prostate-Specific Antigen/chemistry
• Prostate-Specific Antigen/genetics
• Prostatectomy
• Prostatic Neoplasms/genetics
• Prostatic Neoplasms/mortality
• Prostatic Neoplasms/surgery
• RNA, Messenger/blood
• RNA, Messenger/genetics
• Real-Time Polymerase Chain Reaction/methods
• Recurrence

Owing to the scarcity of upper urinary tract urothelial carcinoma (UUT-UC) it is often necessary for investigators to pool data. A patient-specific survival nomogram based on such data is needed to predict cancer-specific survival (CSS) post nephroureterectomy (NU). Herein, we propose and validate a nomogram to predict CSS post NU.

Twenty-one French institutions contributed data on 1120 patients treated with NU for UUT-UC. A total of 667 had full data for nomogram development. Study population was divided into the nomogram development cohort (397) and external validation cohort (270). Cox proportional hazards regression models were used for univariate and multivariate analyses and to build a nomogram. A reduced model selection was performed using a backward step-down selection process, and Harrell's concordance index (c-index) was used for quantifying the nomogram accuracy. Internal validation was performed by bootstrapping and the reduced nomogram model was calibrated.

Of the 397 patients in the nomogram development cohort, 91 (22.9%) died during follow-up, of which 66 (72.5%) died as a consequence of UUT-UC. The actuarial CSS probability at 5 years was 0.76 (95% CI, 71.62-80.94). On multivariate analysis, T stage (P<0.0001), N status (P=0.014), grade (P=0.026), age (P=0.005) and location (P=0.022) were associated with CSS. The reduced nomogram model had an accuracy of 0.78. We propose a nomogram to predict 3 and 5-year CSS post NU for UUT-UC.

We have devised and validated an accurate nomogram (78%), superior to any single clinical variable or current model, for predicting 5-year CSS post NU for UUT-UC.

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in prostate regulation and in prostate cancer (PC) development/progression. IL-6 acts as a paracrine and autocrine growth stimulator in benign and tumor prostate cells. The levels of IL-6 and respective receptors are increased during prostate carcinogenesis and tumor progression. Several studies reported that increased serum and plasma IL-6 and soluble interleukin-6 receptor levels are associated with aggressiveness of the disease and are associated with a poor prognosis in PC patients. In PC treatment, patients diagnosed with advanced stages are frequently submitted to hormonal castration, although most patients will eventually fail this therapy and die from recurrent castration-resistant prostate cancer (CRPC). Therefore, it is important to understand the mechanisms involved in CRPC. Several pathways have been proposed to be involved in CRPC development, and their understanding will improve the way to more effective therapies. In fact, the prostate is known to be dependent, not exclusively, on androgens, but also on growth factors and cytokines. The signaling pathway mediated by IL-6 may be an alternative pathway in the CRPC phenotype acquisition and cancer progression, under androgen deprivation conditions. The principal goal of this review is to evaluate the role of IL-6 pathway signaling in human PC development and progression and discuss the interaction of this pathway with the androgen recepto pathway. Furthermore, we intend to evaluate the inclusion of IL-6 and its receptor levels as a putative new class of tumor biomarkers.The IL-6/IL-6R signaling pathway may be included as a putative molecular marker for aggressiveness in PC and it may be able to maintain tumor growth through the AR pathway under androgen-deprivation conditions. The importance of the IL-6/IL-6R pathway in regulation of PC cells makes it a good candidate for targeted therapy.

• Androgen receptor
• Castration-resistant prostate cancer
• Hormonal castration
• Inteuleukin-6
• Inteuleukin-6 receptor
• Prostate cancer
• Tumor biomarker

Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of the prostate cancer diagnosed. Since cytokines have been associated with the biology of cancer and its prognosis, we determined whether transforming growth factor beta 1 (TGFβ1), interleukin-7 (IL-7) receptor and IL-7 levels add additional prognostic information with regard to prostate cancer-specific survival.

Retrospective survival analysis of forty-four prostate cancer patients, that underwent radical prostatectomy, was performed (1989–2001). Age, Gleason score and pre-treatment PSA levels were collected. IL-7, IL-7 receptor and TGFβ1 levels in prostate cancer tissue were determined by quantitative real-time RT-PCR and their additional prognostic value analyzed with regard to prostate cancer survival. Hazard ratios and their confidence intervals were estimated, and Akaike’s information criterion was calculated for model comparison.

The predictive ability of a model for prostate cancer survival more than doubled when TGFβ1 and IL-7 were added to a model containing only the Gleason score and pre-treatment PSA (AIC: 18.1 and AIC: 6.5, respectively).

IL-7 and TGFβ1 are promising markers to indicate those at risk for poor prostate cancer survival. This additional information may be of interest with regard to the biological aggressiveness of the diagnosed prostate cancer, especially for those patients screened for prostate cancer and their considered therapy.

• Disease Progression
• Humans
• Interleukin-7/genetics
• Interleukin-7/immunology
• Male
• Middle Aged
• Predictive Value of Tests
• Prognosis
• Prostatectomy
• Prostatic Neoplasms/diagnosis
• Prostatic Neoplasms/immunology
• Prostatic Neoplasms/surgery
• Real-Time Polymerase Chain Reaction
• Receptors, Interleukin-7/genetics
• Receptors, Interleukin-7/immunology
• Retrospective Studies
• Survival Analysis
• Transforming Growth Factor beta1/genetics
• Transforming Growth Factor beta1/immunology

• bladder cancer
• nomogram
• prediction
• prognosis
• risk

• prostate neoplasms
• molecular markers
• prostate specific antigen

• Biomarkers, Tumor/blood
• Disease Progression
• Humans
• Male
• Monitoring, Physiologic
• Prognosis
• Prostatic Neoplasms/blood
• Prostatic Neoplasms/diagnosis
• Prostatic Neoplasms/therapy

• P50 CA092629 NCI NIH HHS
• R33 CA127768 NCI NIH HHS
• T32 CA082088 NCI NIH HHS

• prostate cancer
• radical prostatectomy
• prediction tools
• nomograms

• Evidence-Based Medicine
• Humans
• Male
• Models, Statistical
• Predictive Value of Tests
• Prostatectomy/mortality
• Prostatic Neoplasms/mortality
• Prostatic Neoplasms/pathology
• Prostatic Neoplasms/surgery

• P50 CA092629 NCI NIH HHS
• T32 CA082088 NCI NIH HHS

• high-resolution magic angle spinning
• magnetic resonance spectroscopy
• prostatectomy
• prostate cancer recurrence

• Adult
• Aged
• Analysis of Variance
• Case-Control Studies
• Humans
• Magnetic Resonance Spectroscopy
• Male
• Metabolomics
• Middle Aged
• Neoplasm Recurrence, Local/metabolism
• Principal Component Analysis
• Prostate/metabolism
• Prostate/surgery
• Prostate-Specific Antigen/blood
• Prostatectomy
• Prostatic Neoplasms/metabolism
• Prostatic Neoplasms/surgery
• ROC Curve
• Retrospective Studies

• CA115746 NCI NIH HHS
• R01 CA115746 NCI NIH HHS
• R01 CA095624 NCI NIH HHS
• R01 CA115746-04 NCI NIH HHS
• CA095624 NCI NIH HHS
• R01 CA095624-04 NCI NIH HHS

• Anorexia/diagnosis
• Anorexia/epidemiology
• Anorexia/therapy
• Cachexia/diagnosis
• Cachexia/epidemiology
• Cachexia/therapy
• Cytokines/metabolism
• Depressive Disorder/diagnosis
• Depressive Disorder/drug therapy
• Depressive Disorder/epidemiology
• Humans
• Neoplasms/complications
• Neoplasms/metabolism
• Neoplasms/pathology