Ferroptosis-inducing compounds synergize with docetaxel to overcome chemoresistance in docetaxel-resistant non-small cell lung cancer cells.

Development of resistance to therapy-induced cell death is a major hurdle in the effective treatment of advanced solid tumors. Erastin and RSL3 were originally found to induce synthetic lethality by induction of a novel form of cell death termed ferroptosis. Emerging evidence suggests that ferroptosis inducers enhance chemosensitivity of classic therapeutic agents by triggering ferroptotic cell death. In this study we evaluated the effects of erastin and RSL3 on the resistance of docetaxel, doxorubicin, and cisplatin, and revealed a mechanism whereby these ferroptosis inducers augment docetaxel efficacy in non-small cell lung cancer by regulating redox signaling to promote ferroptosis. Transcriptome analysis revealed that combination treatment modulated not only p53 signaling pathway but also immune responses and several signaling pathways including MAPK, NF-κB and PI3K/Akt. Considering that glutathione peroxidase 4 (GPX4) serves as the main effector to protect cells from ferroptosis, this study identified three novel non-covalent GPX4 inhibitors with the aid of pharmacophore-based virtual screening. The new ferroptosis-inducing compounds synergized with docetaxel to increase the cytotoxicity by promoting ferroptotic cell death in docetaxel-resistant A549/DTX cells. Collectively, the induction of ferroptosis contributed to docetaxel-induced cytotoxic effects and overcame drug resistance in A549/DTX cells. Ferroptosis has a great potential to become a new approach to attenuate resistance to some classic therapeutic drugs in cancer patients.

Enhancing Vault Prediction and ICL Sizing Through Advanced Machine Learning Models.

PURPOSE: To use artificial intelligence (AI) technology to accurately predict vault and Implantable Collamer Lens (ICL) size. METHODS: The methodology focused on enhancing predictive capabilities through the fusion of machine-learning algorithms. Specifically, AdaBoost, Random Forest, Decision Tree, Support Vector Regression, LightGBM, and XGBoost were integrated into a majority-vote model. The performance of each model was evaluated using appropriate metrics such as accuracy, precision, F1-score, and area under the curve (AUC). RESULTS: The majority-vote model exhibited the highest performance among the classification models, with an accuracy of 81.9% area under the curve (AUC) of 0.807. Notably, LightGBM (accuracy = 0.788, AUC = 0.803) and XGBoost (ACC = 0.790, AUC = 0.801) demonstrated competitive results. For the ICL size prediction, the Random Forest model achieved an impressive accuracy of 85.3% (AUC = 0.973), whereas XG-Boost (accuracy = 0.834, AUC = 0.961) and LightGBM (accuracy = 0.816, AUC = 0.961) maintained their compatibility. CONCLUSIONS: This study highlights the potential of diverse machine learning algorithms to enhance postoperative vault and ICL size prediction, ultimately contributing to the safety of ICL implantation procedures. Furthermore, the introduction of the novel majority-vote model demonstrates its capability to combine the advantages of multiple models, yielding superior accuracy. Importantly, this study will empower ophthalmologists to use a precise tool for vault prediction, facilitating informed ICL size selection in clinical practice. [J Refract Surg. 2024;40(3):e126-e132.].

Utility of enteral nutrition via percutaneous transhepatic cholangiography drainage catheterization in late-stage malignant obstructive jaundice.

Objective: The purpose of this study was to explore the clinical benefits of establishing an enteral nutrition (EN) pathway via percutaneous transhepatic cholangiography drainage (PTCD) catheterization in patients with late-stage malignant obstructive jaundice (MOJ).Methods: We selected 30 patients diagnosed as having late-stage MOJ with malnutrition. A dual-lumen biliary-enteral nutrition tube was placed via PTCD along with a biliary stent implantation. Postoperative EN was provided, and we observed the time taken for tube placement, its success rate, complications, and therapeutic efficacy.Results: Tube placement was successful in all 30 patients with an average procedural time of 5.7 ± 1.4 min with no tube placement complications. Compared to preoperative measures, there was a significant improvement in postoperative jaundice reduction and nutritional indicators one month after the procedure (p < 0.05). Post-placement complications included tube perileakage in 5 cases, entero-biliary reflux in 4 cases, tube blockage in 6 cases, tube displacement in 4 cases, accidental tube removal in 3 cases, and tube replacement due to degradation in 8 cases, with tube retention time ranging from 42 to 314 days, averaging 124.7 ± 37.5 days. All patients achieved the parameters for effective home-based enteral nutrition with a noticeable improvement in their quality of life.Conclusion: In this study, we found that the technique of establishing an EN pathway via PTCD catheterization was minimally invasive, safe, and effective; the tube was easy to maintain; and patient compliance was high. It is, thus, suitable for long-term tube retention in patients with late-stage MOJ.

Wip1 contributes to the adaptation of HepG2 human liver cancer cells to stress hormone-induced DNA damage.

Numerous studies have shown that the release of stress hormones resulting from repeated exposure to chronic psychological stress increases DNA damage and promotes tumorigenesis. However, the mechanisms that enable cancerous cells adapt to stress hormone-induced DNA damage and survive remain unclear. The present study aimed to investigate the impact of stress hormones on the survival of liver cancer cells and the underlying mechanism. HepG2 human liver cancer cells were treated with dexamethasone (DEX), epinephrine (EPI) and norepinephrine (NE) and subjected to the testing of DNA damage, cell survival and cell apoptosis by alkaline comet assay, CCK-8 viability assay and flow cytometry, respectively. The protein expression levels of DNA damage response factors were determined by western blotting analysis. The results revealed that treatment of HepG2 cells with DEX, EPI and NE induced DNA damage without affecting cell survival or inducing apoptosis. The protein levels of wild-type p53-induced phosphatase 1 (Wip1), a type 2C family serine/threonine phosphatase, were increased, and the dephosphorylation of DNA damage response factors, including phosphorylated (p-)ataxia-telangiectasia mutated and p-checkpoint kinase 2, occurred following treatment with DEX, EPI and NE. In addition, a cycloheximide chase assay was performed to explore the protein stability under treatment with stress hormones. Compared with vehicle-treated cells, Wip1 exhibited increased protein stability in stress hormone-treated HepG2 cells. Eventually, the depletion of Wip1 using small interfering RNA verified the role of Wip1 in the modulation of stress hormone-induced DNA damage. These findings suggest that cancerous cells likely adapt to stress hormone-induced DNA damage via Wip1 upregulation. The present study provides an insight into the underlying mechanism that links chronic psychological stress with tumor growth and progression.

Banana stem and leaf biochar as an effective adsorbent for cadmium and lead in aqueous solution.

Lead (Pb) and cadmium (Cd) are toxic heavy metals commonly found in aqueous environments. Biochar as a green adsorbent generated from biomass feedstock may be used for effective removal of these heavy metals. This study investigated the adsorption kinetics and isotherms of Pb2+ and Cd2+ in aqueous solutions at different pH by biochar prepared from banana stem and leaf (BSL-BC) at 400 °C. Characterizations using scanning electron microscope, X-ray diffraction, and Fourier-transform infrared spectroscopy showed that the synthesized BSL-BC had rough surface, porous structure, and oxygen-containing functional groups. The adsorption of Pb2+ and Cd2+ onto BSL-BC reached equilibrium in 8 h and 200 min, respectively, with faster adsorption attained at higher pH and the optimum pH occurred at 5 (Pb2+) and 8 (Cd2+). All adsorption kinetic data followed the pseudo-second-order rate model. The adsorption isotherm data of Pb2+ and Cd2+ could be well-described by the Langmuir and Freundlich models, respectively, whereas neither the Temkin or Dubinin-Radushkevich models provided satisfactory fitting results. The maximum adsorption capacities for Pb2+ and Cd2+ were 302.20 and 32.03 mg/g, respectively. The calculated mechanism contributions showed that complexation with oxygen-containing functional groups, ion exchange, mineral precipitation, and Pb2+/Cd2+-π coordination accounted for 0.1%, 8.4%, 88.8%, and 2.6% to Pb2+ adsorption, and 0.4%, 6.3%, 83.0%, and 10.4% to Cd2+ adsorption, respectively. Therefore, mineral precipitation was likely the major mechanism responsible for adsorption of both Pb2+ and Cd2+ by BSL-BC. The results suggest that the synthesized BSL-BC has great potential for adsorption of Pb2+ and Cd2+ from aqueous solutions.

Laser-detected magnetic resonance spectra dressed by a radio-frequency field.

We theoretically and experimentally investigate the laser-detected magnetic resonance spectra dressed by a radio-frequency magnetic field in Fg = 4 of D1 line of cesium atoms. The analytical expression of the transmission spectrum for magnetic resonance dressed by a radio-frequency magnetic field is derived and has substantial agreement with the transmission spectra observed in the experiment. The theoretical prediction of the ratio of the amplitudes of the two sidebands with the detuning is basically consistent with the experimental data, which confirms the validity of the analytical expression. The separation between the two sidebands under resonance shows a highly linear proportion to the amplitude of the dressing field, which may provide a useful scheme for the measurement of radio-frequency magnetic field and magnetic imaging.

Ultranarrow spectral line of the radiation in double qubit-cavity ultrastrong coupling system.

The ultrastrongly coupling (USC) system has very important research significance in quantum simulation and quantum computing. In this paper, the ultranarrow spectrum of a circuit QED system with two qubits ultrastrongly coupled to a single-mode cavity is studied. In the regime of USC, the JC model breaks down and the counter-rotating terms in the quantum Rabi Hamiltonian leads to the level anti-crossing in the energy spectrum. Choosing a single-photon driving field at the point of avoided-level crossing, we can get an equivalent four-level dressed state model, in which the dissipation of the two intermediate states is only related to the qubits decay. Due to the electron shelving of these two metastable states, a narrow peak appears in the cavity emission spectrum. Furthermore, we find that the physical origin for the spectral narrowing is the vacuum-induced quantum interference between two transition pathways. And this interference effect couples the slowly decaying incoherent components of the density matrix into the equations of the sidebands. This result provides a possibility for the study of quantum interference effect in the USC system.

Chronic restraint stress promotes the mobilization and recruitment of myeloid-derived suppressor cells through ß-adrenergic-activated CXCL5-CXCR2-Erk signaling cascades.

Myeloid-derived suppressor cells (MDSCs) play an important role in tumor immune escape. Recent studies have shown that MDSCs contribute to tumor progression under psychological stress, but the underlying mechanism of MDSCs mobilization and recruitment remains largely unknown. In the present study, a chronic restraint stress paradigm was applied to the H22 hepatocellular carcinoma (HCC) bearing mice to mimic the psychological stress. We observed that chronic restraint stress significantly promoted HCC growth, as well as the mobilization of MDSCs to spleen and tumor sites from bone marrow. Meanwhile, chronic restraint stress enhanced the expression of C-X-C motif chemokine receptor 2 (CXCR2) and pErk1/2 in bone marrow MDSCs, together with elevated chemokine (C-X-C motif) ligand 5 (CXCL5) expression in tumor tissues. In vitro, the treatments of MDSCs with epinephrine (EPI) and norepinephrine (NE) but not corticosterone (CORT)-treated H22 conditioned medium obviously inhibited T-cell proliferation, as well as enhanced CXCR2 expression and extracellular signal-regulated kinase (Erk) phosphorylation. In vivo, ß-adrenergic blockade with propranolol almost completely reversed the accelerated tumor growth induced by chronic restraint stress and inactivated CXCL5-CXCR2-Erk signaling pathway. Our findings support the crucial role of ß-adrenergic signaling cascade in the mobilization and recruitment of MDSCs under chronic restraint stress.

Clinical activity of abiraterone plus prednisone in docetaxel-naοve and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer.

This study investigated the clinical activity of abiraterone plus prednisone in docetaxel-naïve and docetaxel-resistant Chinese patients with metastatic castration-resistant prostate cancer (mCRPC). A total of 146 patients with docetaxel-naïve group (103 cases) and docetaxel-resistant group (43 cases) were enrolled from the Shanghai Cancer Center (Shanghai, China) in this retrospective cohort study. The efficacy endpoints were prostate-specific antigen response rate, prostate-specific antigen progression-free survival, clinical/radiographic progression-free survival, and overall survival in response to abiraterone plus prednisone. Significantly higher prostate-specific antigen response rate was found in docetaxel-naïve group (54.4%, 56/103) compared to docetaxel-resistant group (34.9%, 15/43) (P = 0.047). In addition, significantly higher median prostate-specific antigen progression-free survival (14.0 vs 7.7 months, P = 0.005), clinical or radiographic progression-free survival (17.0 vs 12.5 months, P = 0.003), and overall survival (27.0 vs 18.0 months, P = 0.016) were found in docetaxel-naïve group compared to docetaxel-resistant group, respectively. The univariate and multivariate analyses indicated that lower albumin and visceral metastases were independent significant predictors for shorter overall survival. To sum up, our data suggested that abiraterone plus prednisone was efficient in both docetaxel-naïve and docetaxel-resistant Chinese patients. Moreover, higher PSA response rate and longer overall survival were observed in the docetaxel-naïve group, which suggested that abiraterone was more effective for docetaxel- naïve patients than for docetaxel failures.

Phenotypes of circulating tumour cells predict time to castration resistance in metastatic castration-sensitive prostate cancer.

OBJECTIVES: To identify biomarkers that predict the response to standard androgen deprivation therapy (ADT) of patients newly diagnosed with metastatic castration-sensitive prostate cancer (CSPC) in order to improve therapeutic decision-making, and to investigate whether the characterization of baseline circulating tumour cells (CTCs) would predict the effective period of standard ADT. MATERIALS AND METHODS: The study included 108 patients newly diagnosed with high-volume metastatic CSPC. Enumeration and characterization of patients' baseline CTCs (CTCs+ and CTCs-, indicating detectable and undetectable CTCs, respectively) were performed using the CanPatrol technique, which detects markers of the epithelial to mesenchymal transition (EMT) in CTCs, and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes. RESULTS: After a median follow-up of 24 months, 90 patients (83.3%) progressed to castration-resistant prostate cancer (CRPC), 93 patients (86.1%) had detectable CTCs, and the median number of CTCs was 4. The rate of progression to CRPC was significantly higher for patients with mesenchymal CTCs+ than for patients with CTCs+/mesenchymal CTCs- and CTCs- (93.1% vs 71.4% and 73.3%; P = 0.013). The median time to CRPC for patients with mesenchymal CTCs+ was significantly shorter than for those with CTCs+/mesenchymal CTCs- and CTCs- (10.5 months vs 18.0 and 14.0 months; P = 0.003). Multivariate Cox regression analysis suggested that the CTC phenotype was the only independent prognostic factor influencing the progression of disease from CSPC to CRPC. CONCLUSIONS: Characterization of baseline CTCs according to the EMT phenotype predicted the effective period of standard ADT for patients newly diagnosed with metastatic CSPC. These findings are important for counselling patients and designing clinical trials.

Controllable radiation properties of a driven exciton-biexciton quantum dot couples to a graphene sheet.

We investigate the radiation properties of a driven exciton-biexciton structure quantum dot placed close to a graphene sheet. The study of the Purcell factor then demonstrates the tunability of light-matter coupling, which in turn provides the possibility to control the steady-state populations. As the result, dipole transitions can be selectively enhanced and asymmetry in the resonance fluorescence can be observed. Meanwhile, both quadratures can exhibit two-mode squeezing at the Rabi sideband frequencies. A further study shows that although the increase in the environment temperature has a destructive influence on the population imbalance, squeezing occurs even at room temperature. Due to the flexibility in controlling the resonance fluorescence spectrum and producing two-mode squeezed states, our proposal would have potential applications in quantum information and other quantum research fields.

Prognostic value of D-lactate dehydrogenase in patients with clear cell renal cell carcinoma.

Lactate dehydrogenase (LDH) is an enzyme involved in anaerobic glycolysis and is associated with the prognosis of patients with renal cell carcinoma (RCC). The human genome has four LDH genes: LDHA, LDHB, LDHC and LDHD. In order to determine which of these four LDH genes may predict clear cell RCC (ccRCC), a total of 509 patients with ccRCC from The Cancer Genome Atlas (TCGA) cohort and 192 patients with ccRCC from the Fudan University Shanghai Cancer Centre (FUSCC) cohort were enrolled in the present study. The expression profiles of LDHD genes in the TCGA cohort were obtained from the TCGA RNAseq database. The Cox proportional hazards regression model and Kaplan-Meier curves were used to assess relative factors. The LDH family genes that were revealed to have an association with overall survival (OS) were further validated in the FUSCC cohort. In the TCGA cohort, following Cox proportional hazards analysis, LDHD expression (P=0.0400; hazard ratio, 0.872; 95% confidence interval, 0.764-0.994) was revealed to be predictive of the prognosis of patients with ccRCC. Further analysis revealed that low LDHD expression (P<0.0001) was significantly associated with a poor prognosis in terms of OS. Additionally, the expression of LDHD (P<0.0001) was significantly different in patients with ccRCC compared with paired controls. In the FUSCC cohort, low LDHD expression was also associated with a poor OS (P=0.0103), and the tumour pathological T stage was a factor that influenced the expression of LDHD (P=0.0120). Furthermore, the expression of LDHD influenced the serum LDH level (P=0.0126). The downregulation of LDHD expression may be a predictor of poor prognosis in patients with ccRCC.

B4GALT1 expression predicts prognosis and adjuvant chemotherapy benefits in muscle-invasive bladder cancer patients.

BACKGROUND: The expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC). METHODS: There were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results. RESULTS: B4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression. CONCLUSIONS: Our evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

A single nucleotide polymorphism in CYP1B1 leads to differential prostate cancer risk and telomere length.

BACKGROUND: Cytochrome P450 1B1 (CYP1B1) is a key enzyme in its oestrogen metabolism pathway, giving rise to hydroxylation and conjugation. Functionally relevant genetic variants within CYP1B1 may affect the telomere length and subsequently lead to prostate carcinogenesis. METHODS: We evaluated 8 CYP1B1 tag single nucleotide polymorphisms (SNPs) in 1015 men with prostate cancer (PCa) and 1052 cancer-free controls, and calculated odds ratios (ORs) and 95% confidence intervals (CIs) to estimate their association with risk of PCa. The influence of CYP1B1 SNPs on the relative telomere lengths was then appraised in peripheral blood leukocytes using real-time PCR. RESULTS:CYP1B1 rs1056836 variant was associated with decreased risk of PCa [odds ratio (OR): 0.80; 95% confidence interval (CI): 0.68-0.99, P = 0.041]. Longer telomere length showed a significantly higher proportion of the CYP1B1 rs1056836 CG/GG genotypes, compared with that of the CC genotype (OR: 1.60, 95% CI: 1.04-2.45). CONCLUSION: Our findings suggest that genetic variants within CYP1B1 may confer genetic susceptibility to PCa by altering telomere length.

External validation and newly development of a nomogram to predict overall survival of abiraterone-treated, castration-resistant patients with metastatic prostate cancer.

Abiraterone acetate is approved for the treatment of castration-resistant prostate cancer (CRPC); however, its effects vary. An accurate prediction model to identify patient groups that will benefit from abiraterone treatment is therefore urgently required. The Chi model exhibits a good profile for risk classification, although its utility for the chemotherapy-naive group is unclear. This study aimed to externally validate the Chi model and develop a new nomogram to predict overall survival (OS). We retrospectively analyzed a cohort of 110 patients. Patients were distributed among good-, intermediate-, and poor-risk groups, according to the Chi model. The good-, intermediate-, and poor-risk groups had a sample size of 59 (53.6%), 34 (30.9%), and 17 (15.5%) in our dataset, and a median OS of 48.4, 29.1, and 10.5 months, respectively. The C-index of external validation of Chi model was 0.726. Univariate and multivariate analyses identified low hemoglobin concentrations (<110 g l-1), liver metastasis, and a short time interval from androgen deprivation therapy to abiraterone initiation (<36 months) as predictors of OS. Accordingly, a new nomogram was developed with a C-index equal to 0.757 (95% CI, 0.678-0.836). In conclusion, the Chi model predicted the prognosis of abiraterone-treated, chemotherapy-naive patients with mCRPC, and we developed a new nomogram to predict the overall survival of this group of patients with less parameters.

High CXC chemokine receptor 1 level represents an independent negative prognosticator in non-metastatic clear-cell renal cell carcinoma patients.

CXC chemokine receptor 1 (CXCR1) signaling has been shown as an essential molecular nexus regarding cancer cell proliferation, tumor inflammation, and angiogenesis in clear cell renal cell carcinoma (ccRCC). The aim of this study was to investigate the prognostic significance of CXCR1 in patients with non-metastatic ccRCC. Data from 446 consecutive non-metastatic ccRCC patients, operated between 2003 and 2008 at a single institution, were evaluated retrospectively. The cohort was split into a training set (n = 223) and a validation set (n = 223). CXCR1 expression was assessed by immunohistochemistry staining and its association with clinicopathologic features and prognosis were evaluated. High CXCR1 epithelial expression presented prognostic value, and indicated poor overall survival (OS) (P = 0.010 and P = 0.015, respectively) and recurrence-free survival (P = 0.011 and P = 0.019, respectively) in the training and validation sets. The incorporation of CXCR1 into the T stage and SSIGN score would help to refine individual risk stratification. Multivariate analysis identified increased epithelial CXCR1 was statistically significantly associated with a poor outcome for OS (HR [95% CI] 1.808 [1.184-2.761]; P = 0.006) and RFS (HR [95% CI] 1.570 [1.076-2.290]; P = 0.019) in all non-metastatic ccRCC patients. Predictive nomograms were generated with identified independent prognosticators to assess patient overall survival and recurrence-free survival at 3, 5 and 10 y. Furthermore, high CXCR1 expression were correlated with elevated infiltrated neutrophils and enriched MMP family gene expression. To conclude, high CXCR1 level within epithelial area represented a potential independent negative prognostic factor regarding OS and RFS in non-metastatic ccRCC patients after nephrectomy.

Prognostic value of granulocyte colony-stimulating factor in patients with non-metastatic clear cell renal cell carcinoma.

Granulocyte colony-stimulating factor is a well-known cytokine to stimulate inflammatory cells. We sought to investigate the prognostic value of its expression in patients with non-metastatic clear cell renal cell carcinoma. Enrolled in this study were 228 eligible patients treated with curative nephrectomy for clear cell renal cell carcinoma during 2008. Granulocyte colony-stimulating factor expression was detected by immunohistochemistry in patient specimens, and was divided into three groups according to the distribution of its immunohistochemistry score. Subgroup analyses were performed to evaluate its risk stratification ability. Cox regression models were applied to analyze the impact of prognostic factors. We found that high granulocyte colony-stimulating factor expression was associated with diminished recurrence-free survival (P<0.001). Its expression had stronger stratification ability in late disease patients, and was further identified as an independent prognosticator for recurrence-free survival. Moreover, nomogram based on granulocyte colony-stimulating factor expression presented a better prognostic ability compared with current prognostic systems (the concordance index = 0.874). To conclude, intratumoal granulocyte colony-stimulating factor expression could be a potential prognosticator for recurrence-free survival in non-metastatic clear cell renal cell carcinoma patients. Incorporating its expression into other pathologic factors provided a finer individual model for non-metastatic clear cell renal cell patients.

Chemokine Receptors CXCR4 and CXCR7 are Associated with Tumor Aggressiveness and Prognosis in Extramammary Paget Disease.

Chemokines are involved in many aspects of oncogenesis, including regulation of cancer cell growth, dissemination and host-tumor response. However, the potential of the chemokine receptors, CXCR4 and CXCR7, in serving as biomarkers in extramammary Paget's disease (EMPD) has been rarely examined. Expressions of CXCR4 and CXCR7 were evaluated in 92 EMPD specimens by immunohistochemistry. High expression of CXCR4 and CXCR7 were both correlated with regional lymph node metastasis and presence of lymphovascular invasion. High expression of CXCR7 also correlated with the depth of invasion. The prognostic value of these two chemokines were also investigated in progression-free survival (PFS) and cancer-specific survival (CSS). Both high expression of CXCR4 and CXCR7 were indicative of shorter PFS and CSS. In the combined prognostic model, concomitant high expression of CXCR4 and CXCR7 were suggestive of poor prognosis compared with the other two groups. In the multivariate analysis, depth of invasion, combined prognostic model and regional lymph node metastasis at diagnosis were the independent prognostic factors for EMPD patients for PFS, and the former two factors independently impacted CSS. Our results demonstrated that CXCR4 and CXCR7 can be used as prognostic biomarkers and prediction of aggressiveness of EMPD. Therapy targeting CXCR4 and CXCR7 may helpful to prevent EMPD progression and improve the prognosis of EMPD.

Combination of circulating tumor cell enumeration and tumor marker detection in predicting prognosis and treatment effect in metastatic castration-resistant prostate cancer.

Although circulating tumor cell (CTC) enumeration in peripheral blood has already been validated as a reliable biomarker in predicting prognosis in metastatic castration-resistant prostate cancer (mCRPC), patients with favorable CTC counts (CTC < 5/7.5 ml) still experience various survival times. Assays that can reduce patients' risks are urgently needed. In this study, we set up a real-time quantitative polymerase chain reaction (RT-qPCR) method to detect epithelial-mesenchymal transition (EMT) and stem cell gene expression status in peripheral blood to validate whether they could complement CTC enumeration. From January 2013 to June 2014 we collected peripheral blood from 70 mCRPC patients and enumerated CTC in these blood samples using CellSearch system. At the same time, stem cell-related genes (ABCG2, PROM1 and PSCA) and EMT-related genes (TWIST1 and vimentin) were detected in these peripheral blood samples using an RT-qPCR assay. Patient overall survival (OS) and treatment methods were recorded in the follow-up. For patients who received first-line chemotherapy, docetaxel plus prednisone, PSA progression-free survival (PSA-PFS) and PSA response rate were recorded. At the time of analysis, 35 patients had died of prostate cancer with a median follow-up of 16.0 months. Unfavorable CTC enumerations (CTC ≥5/7.5 ml) were predictive of shorter OS (p = 0.01). Also, positive stem cell gene expression indicated poor prognosis in mCRPC patients (p = 0.01). However, EMT gene expression status failed to show any prognostic value in OS (p = 0.78). A multivariate analysis indicated that serum albumin (p = 0.04), ECOG performance status (p < 0.01), CTC enumeration (p = 0.02) and stem cell gene expression status (p = 0.01) were independent prognostic factors for OS. For the 40 patients categorized into the favorable CTC enumeration group, positive stem cell gene expression also suggested poor prognosis (p < 0.01). A combined prognostic model consisting of stem cell gene expression and CTC enumeration increased the concordance probability estimated value from 0.716 to 0.889 in comparison with CTC enumeration alone. For patients who received docetaxel plus prednisone as first-line chemotherapy, positive stem cell gene expression suggested a poor PSA-PFS (p = 0.01) and a low PSA response rate (p = 0.008). However, CTC enumeration and EMT gene expression status did not affect PSA-PFS or PSA response rates. As a result, detection of peripheral blood stem cell gene expression could complement CTC enumeration in predicting OS and docetaxel-based treatment effects in mCRPC patients.