Evaluation of Ficolin-3 as a Potential Prognostic Serum Biomarker in Chinese Patients with Esophageal Cancer.

Aims: Ficolin-3 is a circulating pattern recognition molecule of the lectin pathway, which participates in the host immune responses to cancer. Our study aimed to evaluate the prognostic efficacy of ficolin-3 in patients with esophageal cancer (EC). Methods: A total of 233 patients with EC were recruited for this study during a period from March 2013 to March 2016. Clinical information and pretherapeutic tumor specimens from all of the patients were analyzed. Serum ficolin-3 levels were determined by enzyme-linked immunosorbent assay. Patients were then assigned into quartiles according to their serum ficolin-3 levels. The Cox proportional hazards model was utilized to explore the correlation between ficolin-3 levels with overall survival (OS) and disease-specific survival (DSS). Results: The serum ficolin-3 level in the esophageal squamous cell carcinoma (ESCC) group was significantly higher than in the esophageal adenocarcinoma (EAC) group (19.59 ± 4.35 ng/mL vs. 18.39 ± 5.42 ng/mL, p < 0.01). There were great differences in prevalence of ESCC, tumor length, involvement of adventitia, and lymph node status among patients in different ficolin-3 groups (all p < 0.01). Both univariate analyses and further multivariate analyses revealed the close association between ficolin-3 levels and EAC (For OS and DSS, all p < 0.05). Out of 233 patients, survival information was available for 220, including 100 (45.45%) females and 120 (54.54%) males. When dividing the ficolin-3 levels into quartiles, patients with higher serum ficolin-3 levels showed a trend toward longer OS and DSS no matter whether they were diagnosed as ESCC or EAC (HR 0.21-0.55, all p < 0.05). Conclusions: Serum ficolin-3 levels were identified as an independent prognostic biomarker for DSS and OS in Chinese patients with EC, especially EAC.

Increased level of Hsp90-beta in bronchoalveolar lavage fluid correlates with lymphatic invasion and advanced stage of lung cancer patients.

BACKGROUND: The purpose of this work is to explore the correlation between Hsp90-beta level in broncheoalveolar lavage fluid (BALF) and lung cancer. METHODS: Hsp90-beta level was measured by immunohistochemistry and enzyme-linked immunosorbent assay. Sensitivity and specificity of Hsp90-beta were calculated by receiver operator characteristic curve. RESULTS: BALF in patients with lung cancer showed a higher expression of Hsp90-beta than those with benign lung disease (P<0.05). Elevated Hsp90-beta was closely related to lymphatic invasion and advanced stage of patients with lung cancer (P<0.05). The sensitivity of BALF Hsp90-beta for discerning lung cancer from patients with benign disease was 82.56% and specificity was 97.56%. CONCLUSION: Increased BALF Hsp90-beta correlates with lymphatic invasion and advanced stage of patients with lung cancer, suggesting it could be a diagnostic indicator for patients with lung cancer.

Plasma proteasomal chymotrypsin-like activity correlates with prostate cancer progression.

Previously, we demonstrated that inhibition of proteasomal chymotrypsin-like (CT-like) activity in human prostate cancer (PCa) PC-3 cultures and PC-3 xenografts results in accumulation of ubiquitinated proteins, followed by induction of cell death. Studies have shown that plasma CT-like proteasomal activity may be a powerful biomarker for risk stratification in hematologic malignancies. We hypothesized that circulating proteasomes could also be used to stratify risk for patients with PCa. A total of 109 patients with suspected PCa underwent prostatic biopsies were enrolled. Subjects were divided into non-cancer, low-risk PCa, and high-risk PCa groups. Three different proteasomal activity markers (CT-like, caspase-like, and trypsin-like) were measured and compared among the three groups. The proteasomal target proteins, Ub-prs, Hsp70, Bax, and P27 in plasma and prostate tissues were also evaluated. Multivariate analysis was used to assess whether CT-like activity was a predictor of PCa progression. Only proteasomal CT-like activity in the high-risk group was statistically higher than in the non-cancer group (P < 0.05). The expression of Ub-prs, Hsp70, Bax, and P27 protein was decreased in both plasma and PCa tissue of high-risk patients. CT-like activity was found to be an independent predictor of high-risk PCa. Subjects with CT-like activity ≥55 had a 2.15-fold higher risk of having high-risk PCa as compared to those with a CT-like activity of <55 (P = 0.021). We found CT-like activity to be an independent predictor of high-risk PCa, and as such, it may be a good candidate as a biomarker for high-risk PCa detection and stratification.

PSA density improves the rate of prostate cancer detection in Chinese men with a PSA between 2.5-10.0 ng ml (-1) and 10.1-20.0 ng ml (-1) : a multicenter study.

Chinese men should have a higher prostate-specific antigen (PSA) "gray zone" than the traditional value of 2.5-10.0 ng ml-1 since the incidence of prostate cancer (PCa) in Chinese men is relative low. We hypothesized that PSA density (PSAD) could improve the rate of PCa detection in Chinese men with a PSA higher than the traditional PSA "gray zone." A total of 461 men with a PSA between 2.5 and 20.0 ng ml-1 , who had undergone prostatic biopsy at two Chinese centers were included in the analysis. The men were then further divided into groups with a PSA between 2.5-10.0 ng ml-1 and 10.1-20.0 ng ml-1 . Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of PSA and PSAD for the diagnosis of PCa. In men with a PSA of 2.5-10.0 ng ml-1 or 10.1-20.0 ng ml-1 , the areas under the ROC curve were higher for PSAD than for PSA. This was consistent across both centers and the cohort overall. When the entire cohort was considered, the optimal PSAD cut-off for predicting PCa in men with a PSA of 2.5-10.0 ng ml-1 was 0.15 ng ml-1 ml-1 , with a sensitivity of 64.4% and specificity of 64.6%. The optimal cut-off for PSAD in men with a PSA of 10.1-20.0 ng ml-1 was 0.33 ng ml-1 ml-1 , with a sensitivity of 60.3% and specificity of 82.7%. PSAD can improve the effectiveness for PCa detection in Chinese men with a PSA of 2.5-10.0 ng ml-1 (traditional Western PSA "gray zone") and 10.1-20.0 ng ml-1 (Chinese PSA "gray zone").

MLN2238 synergizes BH3 mimetic ABT-263 in castration-resistant prostate cancer cells by induction of NOXA.

Patients undergoing androgen blockade therapy develop castration-resistant prostate cancer (CRPC), which is associated with Bcl-2 upregulation and results in disease progression and death. In recent years, promising therapeutic agents, such as the BH3-only mimetic ABT-263 and proteasome inhibitors, have been developed and widely evaluated against a broad spectrum of cancer types, including prostate cancer, alone or in combination with other chemotherapeutic agents. In this study, the antitumor efficacy of ABT-263 and MLN2238 were evaluated as single agents and in combination in four CRPC cell lines: PC3, C4-2B, C4-2, and DU145. The viability of the treated cells and markers of apoptosis were assayed. Protein-protein interactions were analyzed by co-immunoprecipitation in drug-treated cells. Lentivirus-mediated short hairpin RNA was used to knockdown Bax, Mcl-1, and NOXA expressions. We found that ABT-263 and MLN2238 alone exhibited a mild cytotoxicity, and in combination, they elicited a synergistic cytotoxic effect in CRPC cells. The cell apoptosis induced by the combination drug treatment was evidenced by enhanced caspase-3 and Poly (ADP-ribose) polymerase (PARP) cleavage, and annexin-V-positive staining was significantly depleted by Bax knockdown. MLN2238 treatment upregulated NOXA and Mcl-1 expression, leading NOXA/Mcl-1 complexes to disassociate Bak from its complexes with Mcl-1 and enhancing ABT263-triggered Bax activation. NOXA knockdown by short hairpin RNA significantly attenuated the cytotoxicity of ABT-263 and MLN2238 co-administration. In conclusion, MLN2238 and ABT-263 synergistically triggered apoptosis in CRPC cells by upregulating NOXA and activating Bax, indicating a promising therapeutic strategy for the treatment of CRPC.

Percent free prostate-specific antigen does not improve the effectiveness of prostate cancer detection in Chinese men with a prostate-specific antigen of 2.5-20.0 ng/ml: a multicenter study.

The prostate-specific antigen (PSA) "gray zone" in Chinese men is likely higher than the traditional value (2.5-10.0 ng/ml) since the incidence of prostate cancer in Chinese men is relative low. The utility of percent free PSA in predicting prostate cancer is based on Western populations and may introduce sizable bias when applied to a Chinese cohort. We assessed the efficacy of percent free PSA in predicting prostate cancer in Chinese men with a PSA of 2.5-10.0 and 10.1-20.0 ng/ml. A total of 558 men with a PSA of 2.5-20.0 ng/ml who had undergone prostatic biopsy to detect prostate cancer from two Chinese centers were included. The rates of prostate cancer in different percent free PSA ranges were evaluated. Receiver operating characteristic curve (ROC) was used to evaluate and compare the efficiency of PSA and percent free PSA in the diagnosis of prostate cancer. The areas under ROC (AUCs) for percent free PSA for predicting prostate cancer were not higher than those for PSA, although prostate cancer detection rates increased with decreased percent free PSA in men with a PSA of 2.5-10.0, 10.1-20.0, and 2.5-20.0 ng/ml. Similarly, for men aged <70 and ≥ 70 years and with prostate volume <40 and ≥ 40 ml, AUCs showed percent free PSA was not better than PSA in predicting prostate cancer. By analyzing multicenter data, we first found that percent free PSA does not improve detection of prostate cancer in Chinese men with a PSA of 2.5-10.0 or 10.1-20.0 ng/ml.

Nanoscale dynamic behavior of surface magnetic domains on a La0.7Sr0.3MnO3 thin film.

An oscillating magnetic tip can be used to induce the striped magnetic ripple pattern with alternating up-and-down striped magnetic domains on a ferromagnetic La0.7Sr0.3MnO3 (LSMO) thin film surface. Magnetic force microscopy (MFM) images show that the surface magnetic domains (SMDs) can be aligned in a well-ordered alternating up-and-down c(2 x 2) structure on the stripe magnetic domains, indicating that the oscillating magnetic tip turns the ferromagnetic LSMO surface into a canted antiferromagnetic state. The orientation of the SMDs is determined by their discrete phase distribution. A three-dimensional (3D) SMD orientation model is built to understand dynamic behavior of the SMDs.

Prostate volume as an independent predictor of prostate cancer in men with PSA of 10-50 ng ml(-1).

Prostate volume (PV) has been shown to be associated with prostate cancer (PCa) detection rates in men with a prostate-specific antigen (PSA) in the 'grey zone' (2.0-10.0 ng ml(-1)). However, the PSA 'grey zone' in Asian men should be higher because the incidence of PCa in Asian men is relatively low. Therefore, we evaluated the association between PV and PCa detection rates in men with PSAs measuring 10-50 ng ml(-1). Men who underwent a 13-core prostatic biopsy with PV documentation participated in the study. A multivariate stepwise regression was used to evaluate whether the PV at time of prostate biopsy could predict the risk of PCa. The rates of PCa among men in different PSA ranges, stratified by PV medians (<60 and ≥60 ml), were calculated. There were 261 men included in the final analysis. PV was the strongest predictor of PCa risk (odds ratio, 0.02; P<0.001) compared to other variables. The PCa rates in men with PVs measuring <60 and ≥60 ml in the 10-19.9 ng ml(-1) PSA group were 40.6% and 15.1%, respectively, while the rates for men with PSAs measuring 20-50 ng ml(-1) were 65.1% and 26.8%. PV is an independent predictor of PCa in men with PSA measuring 10-50 ng ml(-1). In clinical practice, particularly for those countries with lower incidences of PCa, PV should be considered when counselling patients with PSAs measuring 10-50 ng ml(-1) regarding their PCa risks.

A nomogram based on age, prostate-specific antigen level, prostate volume and digital rectal examination for predicting risk of prostate cancer.

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen (PSA), prostate volume (PV), digital rectal examination (DRE) status, % free PSA and transrectal ultrasound (TRUS) findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% (223/535). The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.

[2-deoxyglucose enhances chemosensitivity of androgen-independent prostate cancer cells to docetaxel].

OBJECTIVE: To explore the antitumor effects of 2-deoxyglucose (2-DG) plus docetaxel (Doc) on PC3 and DU145 cells and its mechanism. METHODS: The proliferation of cells was detected by methyl thiazolyl tetrazolium (MTT) assay. Then propidium iodide (PI) staining measured apoptotic cells on flow cytometry. ATP assay kit was used to detect ATP content. The expressions of proteins ubiquitinated protein (Ub) and Hsp70 were measured by Western blot. RESULTS: 2-DG could inhibit proliferation of PC3 and DU145 cells in a dose- and time-dependent manner. However, it could not induce apoptosis in PC3 or DU145. The inhibition rates for PC3 proliferation at 48 h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 10.71%, 25.32% and 56.46% respectively. The inhibition rates for DU145 cell proliferation at 48h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 12.28%, 23.94% and 63.43% respectively. The inhibition rates for PC3 cell proliferation by Doc plus 2-DG with a concentration of 1.0 g/L were 27.15%, 58.74% and 87.95% respectively and 29.53%, 59.41%, and 90.48% for DU145 respectively. 2-DG could enhance the effectiveness of inhibition to PC3 and DU145 proliferation by Doc with a synergistic manner (all q>1.15). The apoptotic rates for PC3 and DU145 induced by Doc 0.5 nmol/L plus 2-DG 1.0 g/L at 48 h were 46.49% and 53.64% respectively. The apoptotic rates were significantly higher than Doc 0.5 nmol/L alone (21.30% for PC3 and 18.92% for DU145 respectively) (P < 0.05). The ATP relative concentration for PC3 in 2-DG 1.0 g/L at 0, 12, 24, 48, and 72 h were 13.75, 11.23, 10.19, 9.81 and 9.02 and for DU145 15.00, 12.59, 11.38, 10.54 and 10.37 respectively. Simultaneously, Western blot showed that Ub and Hsp70 protein were expressed intensively. CONCLUSIONS: 2-DG can enhance the sensitivity of androgen-independent prostate cancer cells to docetaxel. Its mechanism may be associated with the decrease of proteasome function.

Scanning photoemission spectromicroscopic study of 4-nm ultrathin SiO(3.4) protrusions probe-induced on the native SiO(2) layer.

Atomic force microscopy probe-induced large-area ultrathin SiO(x) (x ≡ O/Si content ratio and x > 2) protrusions only a few nanometers high on a SiO(2) layer were characterized by scanning photoemission microscopy (SPEM) and X-ray photoemission spectroscopy (XPS). SPEM images of the large-area ultrathin SiO(x) protrusions directly showed the surface chemical distribution and chemical state specifications. The peak intensity ratios of the XPS spectra of the large-area ultrathin SiO(x) protrusions provided the elemental quantification of the Si 2p core levels and Si oxidation states (such as the Si(4+), Si(3+), Si(2+), and Si(1+) species). The O/Si content ratio (x) was evidently determined by the height of the large-area ultrathin SiO(x) protrusions.

Study of differential proteins in lung adenocarcinoma using laser capture microdissection combined with liquid chip-mass spectrometry technology.

BACKGROUND: In recent years the proportion of lung adenocarcinoma (adCA) which occurs in lung cancer patients has increased. Using laser capture microdissection (LCM) combined with liquid chip-mass spectrometry technology, we aimed to screen lung cancer biomarkers by studying the proteins in the tissues of adCA. METHODS: We used LCM and magnetic bead based weak cation exchange (MB-WCX) to separate and purify the homogeneous adCA cells and normal cells from six cases of fresh adCA and matched normal lung tissues. The proteins were analyzed and identified by matrix assisted laser desorption/ionization time-of-fight mass spectrometry (MALDI-OF-MS). We screened for the best pattern using a radial basic function neural network algorithm. RESULTS: About 2.895 × 10(6) and 1.584 × 10(6) cells were satisfactorily obtained by LCM from six cases of fresh lung adCA and matched normal lung tissues, respectively. The homogeneities of cell population were estimated to be over 95% as determined by microscopic visualization. Comparing the differentially expressed proteins between the lung adCA and the matched normal lung group, 221 and 239 protein peaks, respectively, were found in the mass-to-charge ration (M/Z) between 800 Da and 10 000 Da. According to t test, the expression of two protein peaks at 7521.5 M/Z and 5079.3 M/Z had the largest difference between tissues. They were more weakly expressed in the lung adCA compared to the matched normal group. The two protein peaks could accurately separate the lung adCA from the matched normal lung group by the sample distribution chart. A discriminatory pattern which can separate the lung adCA from the matched normal lung tissue consisting of three proteins at 3358.1 M/Z, 5079.3 M/Z and 7521.5 M/Z was established by a radial basic function neural network algorithm with a sensitivity of 100% and a specificity of 100%. CONCLUSIONS: Differential proteins in lung adCA were screened using LCM combined with liquid chip-mass spectrometry technology, and a biomarker model was established. It is possible that this technology is going to become a powerful tool in screening and early diagnosis of lung adCA.