The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Role of vitamin D3 in tumor aggressiveness and radiation response for hepatocellular carcinoma.

Locoregional control is a significant prognostic factor for hepatocellular carcinoma (HCC). Historically, the use of radiotherapy (RT) for HCC was limited owing to the low radiotolerance of the liver and the need for high RT doses for disease control. We aimed to examine if 1α,25-dihydroxyvitamin D3 (calcitriol) has a role in the tumor inhibition and the radiation response of HCC in vitro and in vivo, and explore the underlying mechanisms. The human and murine liver cancer cell lines were selected for cellular and animal experiments to investigate the changes in tumor characteristics and the radiation response after calcitriol supplementation. The effects induced by calcitriol supplementation on interleukin-6 (IL-6) signaling and the tumor immune microenvironment following RT were also examined. Our data revealed that calcitriol supplementation attenuated tumor aggressive behavior, decrease IL-6 expression, and augmented radiation-induced tumor inhibition. The biological changes following calcitriol treatment included suppressed epithelial-mesenchymal transition, attenuated cancer stem cell-like properties and increased radiation-induced reactive oxygen species and cell death in vitro. Regarding immune microenvironment, calcitriol attenuated the recruitment of myeloid-derived suppressor cell (MDSC) recruitment and increased the infiltration of cytotoxic T cells in tumor following RT. Furthermore, When the primary liver tumor was irradiated with larger dose per fraction, calcitriol induced a smaller size of synchronous unirradiated tumor in mice, which linked with attenuated IL-6 signaling and MDSC recruitment. In conclusion, calcitriol treatment reduced tumor aggressiveness and enhanced the radiation response. The inhibited IL-6 signaling and subsequently enhanced antitumor immunity might be responsible to augment radiation-induced tumoricidal effect induced by calcitriol. Based on our results, we suggest that calcitriol could exert the antitumor and radiosensitization effects for HCC, especially for multifocal tumors.

Risk of major adverse cardiovascular events among second-line hormonal therapy for metastatic castration-resistant prostate cancer: A real-world evidence study.

BACKGROUND: To evaluate the possible major adverse cardiovascular events (MACE) associated with second-line hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We performed a population-based real-world cohort study of 4962 prostate cancer patients between 2014 and 2017 utilizing the Chang Gung Research Database of Taiwan. The second-line hormonal therapies included enzalutamide and abiraterone acetate. The outcomes of interest were MACE, including acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF) events that resulted in hospitalization. Cox proportional-hazards models with inverse probability of treatment weighting (IPTW) with propensity scores were used. RESULTS: After IPTW, 288 patients were prescribed second-line hormonal therapy and 1575 received first-line androgen-deprivation therapy (ADT). Of all patients diagnosed with MACE, the event rates were 2.92% in the second-line hormonal group and 2.22% in the first-line ADT group. The mean follow-up period was 9.52 months for the second-line hormonal group. Patients who received second-line hormonal therapy exhibited a significantly increased risk for MACE (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 2.03-4.89), ACS (HR: 4.94; 95% CI: 2.36-10.33), and HF (HR: 2.83; 95% CI: 1.53-5.25), compared with the first-line ADT group, but a similar risk for IS was observed in both groups (HR: 1.70; 95% CI: 0.95-3.04). CONCLUSIONS: The real-world evidence study revealed increased risks for MACE in mCRPC patients receiving second-line hormonal therapy.

Prognostic Significance of Neoadjuvant Rectal Scores in Preoperative Short-Course Radiotherapy and Long-Course Concurrent Chemoradiotherapy for Patients with Locally Advanced Rectal Cancer.

BACKGROUND: This study aimed to investigate the prognostic factors and the utility of the neoadjuvant rectal (NAR) score for patients who have locally advanced rectal cancer (LARC) treated with preoperative short-course radiotherapy (SRT) or long-course concurrent chemoradiotherapy (CRT). METHODS: Of 314 consecutive stage 2 or 3 rectal cancer patients enrolled from January 2006 to December 2017, 205 underwent preoperative SRT (2500 cGy/5 fractions), and 109 underwent preoperative CRT (4200-5080 cGy/21-28 fractions) after total mesorectal excision (TME). The study calculated NAR scores using the following equation: [5 pN - 3(cT - pT) + 12]2/9.61. RESULTS: The multivariate analysis showed that age above 65 years, pT4, pN2, NAR scores higher than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for overall survival (OS), whereas, pN2, NAR scores lower than 16, and distance from anal verges (< 8 cm) were significant prognostic factors for disease-free survival (DFS) and distant metastasis (DM). The patients with an NAR score higher than 16, had a 5-year OS rate of 67.6%, a DFS rate of 56.9%, a locoregional recurrence (LRR) rate of 7.7%, and a DM rate of 35% compared with corresponding rates of 87.6%, 76.7%, 5.4%, and 7.2% for the patients with an NAR score of 16 or lower (p < 0.001 for OS, < 0.001 for DFS, 0.25 for LRR, and < 0.001 for DM). CONCLUSIONS: For patients who undergo SRT or CRT for LARC, a higher NAR score is associated with worse OS and DFS and higher DM rates at 5 years. The NAR score could be used as a short-term surrogate end point after neoadjuvant therapy for LARC.

The Predictive Value of Pretreatment Neutrophil-To-Lymphocyte Ratio in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) has been reported to be both a prognostic biomarker for cancer and associated with inflammation, but its predictive role in tumor immunity is not clear. The present study examined the correlations of the NLR and immune suppression with the prognoses in patients with esophageal squamous cell carcinoma (ESCC). METHODS: We performed a retrospective review of 1168 patients who were newly diagnosed with stage T1N(+) and T2-T4 ESCC at our hospital. The NLR of each ESCC patient prior to treatment was calculated, and the associations of the NLR with various clinicopathological parameters and prognoses were then examined. In addition, correlations of the proportion of myeloid-derived suppressor cells (MDSCs) and level of interleukin (IL)-6 with the NLR were assessed in 242 ESCC patients. RESULTS: An elevated NLR was significantly correlated with advanced-stage disease and reduced overall survival (OS) of ESCC patients. Furthermore, the levels of IL-6 in tumors and MDSCs in the peripheral circulation were significantly correlated with the prognoses of ESCC, and the NLR was positively correlated with MDSC levels in the circulation and IL-6 staining intensity in tumor specimens. Moreover, a high NLR was significantly associated with reduced OS in the 926 patients treated with concomitant chemoradiotherapy, but not in the 242 patients who underwent surgical intervention. CONCLUSION: The NLR may represent a clinically useful biomarker to guide ESCC treatment decisions. Patients with a higher NLR may be an optimal subgroup for IL-6- and MDSC-targeted therapy.

Long-Term Taste Impairment after Intensity-Modulated Radiotherapy to Treat Head-and-Neck Cancer: Correlations with Glossectomy and the Mean Radiation Dose to the Oral Cavity.

We explored the effects of various parameters on taste impairments (TIs) in head-and-neck (H&N) cancer patients receiving intensity-modulated radiotherapy (IMRT). From January 2014 to September 2017, 88 H&N cancer patients subjected to curative or postoperative IMRT were enrolled in this prospective study. All patients underwent at least 1 year of follow-up after IMRT. Quality-of-life assessments in terms of patient-reported gustatory function were measured using the taste-related questions of the European Organization for Research and Treatment of Cancer H&N35 questionnaires. At a median follow-up time of 27 months, 27 of 88 patients (30.7%) reported long-term TIs. In multivariate analyses, glossectomy most significantly predicted TIs (P = 0.04). The percentage of TIs (61.5%) was significantly (P = 0.03) higher in patients who underwent partial or total glossectomy than in patients who did not undergo surgery (28.0%) and those who underwent radical surgery without glossectomy (20.0%). When we excluded surgical patients from analyses, the mean radiation dose to the oral cavity was of borderline significance in terms of TI prediction (P = 0.05). Only 10.5% of patients suffered from TIs when the mean radiation dose was <5000 cGy compared with 38.7% when the mean dose was ≥5000 cGy. In conclusion, glossectomy is the major cause of long-term TIs in H&N cancer patients receiving IMRT. In patients who do not undergo glossectomy, reduction of the mean radiation dose to the oral cavity may reduce TIs after IMRT.

Role of ALDH1 in the prognosis of esophageal cancer and its relationship with tumor microenvironment.

Aldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and significantly increased in cancer stem-like cells. In the present study, the role of ALDH1 in esophageal squamous cell carcinoma (ESCC) was investigated. We retrospectively analyzed the clinical outcomes of 148 ESCC and examined its correlation with ALDH1 levels. Furthermore, we preformed cellular and animal experiments to investigate the role of ALDH1 in tumor progression and microenvironment. Our data revealed that ALDH1 staining was positively linked to a higher clinical stage, higher loco-regional failure rate, and shorter survival time. Furthermore, there was a positive link between ALDH1 expression and IL-6 signaling according to the data of clinical specimens and cellular experiments. Using animal model, ALDH1-positive tumors were associated with aggressive tumor growth, increased IL-6, augmented epithelial-mesenchymal transition (EMT), and activation of myeloid-derived suppressor cells (MDSCs). Blockade of COX-2 attenuated the aggressive tumor growth of ALDH1-positive cancer cells. In conclusion, our findings suggested that ALDH1 played an important role in tumor aggressiveness and associated with a tumor-promoting microenvironment in esophageal cancer. Directly targeting ALDH1 or using a COX-2 inhibitor could be a promising strategy for the treatment of ESCC.

Predictive Value of CD44 in Muscle-Invasive Bladder Cancer and Its Relationship with IL-6 Signaling.

BACKGROUND: CD44, a cancer stem cell surface marker, is associated with treatment resistance and prognosis in some cancers. In the present study, we examined the predictive value of CD44 in muscle-invasive bladder cancer (MIBC). METHODS: We retrospectively analyzed the clinical outcomes of 105 MIBC patients and correlated these outcomes with the expression of CD44. Furthermore, the bladder cancer cell lines HT1197 and MB49 were selected for cellular and animal experiments to investigate the correlation between CD44 and tumor aggressiveness. RESULTS: Analysis of clinical specimens indicated that CD44 staining was significantly associated with a higher clinical stage, higher locoregional failure rate, and lower disease-specific survival rate for MIBC patients. Using cellular experiments and orthotopic tumor models, we showed that CD44+ bladder cancer cells had a higher invasion ability and augmented epithelial-mesenchymal transition (EMT) compared with CD44 cells. There was a significant correlation between interleukin (IL)-6 and CD44 levels noted by in vitro testing, and clinical samples. Blockade of IL-6 attenuated the expression of CD44, cancer stem-cell-like properties, and aggressive tumor behavior in vitro and in vivo. The related changes included the attenuated STAT3 activation and EMT, and decreased programmed death ligand 1-mediated T-cell suppression. CONCLUSION: Our findings suggest that CD44 expression is positively associated with tumor aggressiveness in bladder cancer, and activated IL-6 signaling provides a suitable microenvironment for the induction of CD44 expression.

The Efficacy of Postoperative Adjuvant Chemotherapy for Patients with pT3N0M0 Upper Tract Urothelial Carcinoma.

PURPOSE: Nephroureterectomy with bladder cuff excision may not be sufficient as monotherapy for patients with pT3N0M0 upper tract urothelial carcinoma. The efficacy of postoperative adjuvant chemotherapy in this setting remains controversial. We evaluated the efficacy of adjuvant chemotherapy for patients with pT3N0M0 upper tract urothelial carcinoma in overall, cancer specific and recurrence-free survival. MATERIALS AND METHODS: We retrospectively reviewed records on 171 consecutive patients with pT3N0M0 upper tract urothelial carcinoma treated with radical nephroureterectomy between 2004 and 2014 at 2 branches of the same institution. Postoperative adjuvant chemotherapy was gemcitabine/cisplatin or cisplatin/fluorouracil/leucovorin. Overall, cancer specific and recurrence-free survival rates were estimated using the Kaplan-Meier method. The values of prognostic factors were evaluated by Cox regression analysis. RESULTS: Postoperative adjuvant chemotherapy was administered in 60 patients vs nonadjuvant therapy in 111 patients. Median followup was 35.8 months. Between the adjuvant and nonadjuvant treatment groups there were statistically significant differences in 5-year cancer specific (80.5% vs 57.6%, p = 0.010) and recurrence-free (74.4% vs 52.9%, p = 0.026) survival rates. Although there was no statistically significant difference in overall survival (71.9% vs 49.0%, p = 0.072), there was a trend of better overall survival in the patients who received postoperative chemotherapy. On multivariable analysis age (p = 0.018), tumor location (p = 0.003) and adjuvant chemotherapy (p = 0.001) were predictors of cancer specific survival. CONCLUSIONS: Adjuvant chemotherapy improves cancer specific and recurrence-free survival in patients with pT3N0M0 upper tract urothelial carcinoma after radical nephroureterectomy.

TGF Beta1 Expression Correlates with Survival and Tumor Aggressiveness of Prostate Cancer.

BACKGROUND: Although biopsy Gleason score and clinical stage can be used to inform treatment decisions for prostate cancer, identifying molecular markers of tumor aggressiveness could lead to a more tailored approaches to therapy. In the present study, we investigated the association of transforming growth factor (TGF)-ß1 levels and various markers of tumor aggressiveness and explore some potential mechanisms underlying the associations. METHODS: We used human and murine prostate cancer cell lines and their respective hormone resistance sub-lines, in vitro and in vivo to examine the changes in tumor aggressiveness, as well as the pathway responsible for these changes. Furthermore, 105 prostate cancer biopsy specimens were analyzed to correlate the level of TGF-ß1 with the clinical characteristics of patients. RESULTS: Our data revealed that activated TGF-ß1 signaling resulted in more aggressive tumor growth and augmented the epithelial-mesenchymal transition. Activated IL-6 signaling was associated with TGF-ß1 levels and the aggressive tumor features noted in TGF-ß1-positive prostate cancers in vitro and in vivo. Furthermore, the TGF-ß1 levels significantly correlated with Tregs accumulation in vivo. The clinical data indicated that TGF-ß1 immunoreactivity had a moderate positive correlation with IL-6 staining, advanced clinical stage, higher Gleason score, and pretreatment PSA in patients with prostate cancer. CONCLUSIONS: TGF-ß1 levels are significantly associated with aggressive prostate features. In vitro and in vivo alternations of TGF-ß1 expression impacts tumor invasiveness, tumor growth rate and recruitment of immunosuppressive Treg cells in the tumor microenvironment. TGF-ß1 expression may represent a clinical useful biomarker to guide prostate cancer treatment decisions.

Thrombomodulin mediates the migratory ability of hormone-independent prostate cancer cells through the regulation of epithelial-to-mesenchymal transition biomarkers.

Thrombomodulin (TM) is highly expressed in endothelial cells and plays the key role in maintaining physical homeostasis. In addition, many pieces of evidence also show that TM contains the diagnostic value for malignant diseases. TM has been found to correlate with metastatic status in multiple cancers, but its role in prostate cancer progression remains unclear. TM expression was determined in prostate cancer cells (DU-145 and PC-3 cells) using real-time PCR and Western blotting. TM expression was manipulated in prostate cancer cells using TM-specific shRNA and an overexpression system. The proliferation, adhesion, and migratory ability of prostate cancer cells expressing various TM levels were determined using the x'Celligence biosensor system and a transwell migration assay. Higher levels of TM transcription and translation were found in DU-145 cells and were negatively correlated with the low migratory ability of DU-145 cells. After silencing TM expression in DU-145 cells, cell growth decreased, but cell adhesion and migration dramatically increased. TM overexpression in PC-3 cells reduced their metastatic ability. We investigated the possible mechanisms of this phenomenon and determined that the enhanced cell migration was mediated through the expression of E-cadherin and vimentin. TM may be a modulator of hormone-independent prostate cancer (HIPC) metastasis. The downregulation of TM expression enhanced the migratory ability of these cells via an increase in vimentin expression and a decrease in E-cadherin expression.

Glucose-regulated protein 78 mediates hormone-independent prostate cancer progression and metastasis through maspin and COX-2 expression.

Glucose-regulated protein 78 (GRP78) plays an essential role in embryonic development and in the progression and therapeutic resistance of many cancers. However, little is known about the function of GRP78 in hormone-independent prostate cancer. Here, we found that the expression levels of GRP78 were higher in PC-3 cells than in DU-145 cells. When the expression of GRP78 was silenced using a GRP78-specific small interfering RNA in PC-3 cells, the growth rate and adhesive ability were reduced. Cell migration was dramatically decreased in GRP78-depleted cells. Dissection of the involved signal pathways revealed that maspin expression was upregulated after silencing GRP78 expression. The upregulation of maspin and downregulation of COX-2 may cause the decrease in cell proliferation and migration observed after silencing GRP78 expression. Silencing GRP78 expression may suppress the proliferation, adhesion, and migration of prostate cancer cells via maspin and COX-2 regulation.

Thrombomodulin expression regulates tumorigenesis in bladder cancer.

BACKGROUND: The identification of potential tumor markers will help improve therapeutic planning and patient management. Thrombomodulin (TM) is a sensitive urothelial marker. TM was reported to be one of the endogenous anti-metastatic factors and has diagnostic and prognostic values for the progression of carcinoma. In the present study, we examine the role of TM in bladder cancer. METHODS: We studied the role of TM in tumor behavior and related signaling pathways in vitro using the human bladder cancer cell lines HT1376, HT1197, J82 and T24, and in vivo using animal models. We also selected clinical specimens from 100 patients with bladder cancer for immunohistochemical staining to evaluate the predictive capacity of TM in tumor invasiveness. RESULTS: The data revealed that positive immunoreactivity for TM was inversely correlated with clinical stage and DNA methyltransferase 1 immunoreactivity. Decreased TM expression could predict the aggressive tumor growth and advanced clinical stage in bladder cancer. When TM was inhibited, tumor growth rate and invasion ability were augmented in vitro and in vivo. The underlying changes included increased cell proliferation, enhanced epithelial-mesenchymal transition (EMT) and angiogenesis. Moreover, inhibition of NF-κB activation significantly increased TM expression and attenuated tumor aggressiveness in bladder cancer. CONCLUSIONS: TM plays an important role in bladder cancer tumor aggressiveness in vitro and in vivo and is a clinically significant predictor that may represent a suitable therapeutic target for bladder cancer.

Clinical characteristics and treatment outcome in a Taiwanese population of patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma.

OBJECTIVE: Epstein-Barr virus-positive diffuse large B-cell lymphoma is a provisional entity in the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues. Reports on the characteristics and clinical outcome of this disease in different geographic regions showed great disparities. METHODS: To define the clinical characteristics as well as the prognostic impact of Epstein-Barr virus infection on diffuse large B-cell lymphoma in Taiwan, we retrospectively investigated the Epstein-Barr virus status of 89 patients with newly diagnosed diffuse large B-cell lymphoma in our institute. RESULTS: Using a cutoff point of positive nuclear staining of Epstein-Barr virus-encoded RNA-1-in situ hybridization in ≥20% of the examined cells, we identified 15 cases (16.9%) of the entire study cohort as Epstein-Barr virus-positive diffuse large B-cell lymphoma. The clinical and laboratory features were not different between Epstein-Barr virus-positive and -negative diffuse large B-cell lymphoma patients. Univariate analysis showed patients with diffuse large B-cell lymphoma that were either Epstein-Barr virus-positive or had activated B-cell-like features had an inferior overall survival. Older age, advanced stage and lymphoma with activated B-cell-like features or Epstein-Barr virus-encoded RNA positivity were independent prognostic factors affecting overall survival on multivariate analysis. Patients with two or three of these adverse-risk factors were considered high risk and fared far worse than patients with no or only one adverse factor. CONCLUSIONS: Taken together, we demonstrated that a higher frequency of Epstein-Barr virus association was detected in a Taiwanese cohort of diffuse large B-cell lymphoma patients, and Epstein-Barr virus-encoded RNA positivity was shown to add important prognostic value in these patients.

Spheroids Generated from Malignant Pleural Effusion as a Tool to Predict the Response of Non-Small Cell Lung Cancer to Treatment.

BACKGROUND: Spheroids generated by tumor cells collected from malignant pleural effusion (MPE) were shown to retain the characteristics of the original tumors. This ex vivo model might be used to predict the response of non-small cell lung cancer (NSCLC) to anticancer treatments. METHODS: The characteristics, epidermal growth factor receptor (EGFR) mutation status, and clinical response to EGFR-TKIs treatment of enrolled patients were recorded. The viability of the spheroids generated from MPE of enrolled patients were evaluated by visualization of the formazan product of the MTT assay. RESULTS: Spheroids were generated from 14 patients with NSCLC-related MPE. Patients with EGFR L861Q, L858R, or Exon 19 deletion all received EGFR-TKIs, and five of these seven patients responded to treatment. The viability of the spheroids generated from MPE of these five patients who responded to EGFR-TKIs treatment was significantly reduced after gefitinib treatment. On the other hand, gefitinib treatment did not reduce the viability of the spheroids generated from MPE of patients with EGFR wild type, Exon 20 insertion, or patients with sensitive EGFR mutation but did not respond to EGFR-TKIs treatment. CONCLUSION: Multicellular spheroids generated from NSCLC-related MPE might be used to predict the response of NSCLC to treatment.

A meta-analysis comparing efficacy and safety between proton beam therapy versus carbon ion radiotherapy.

BACKGROUND: This study aimed to compare the outcomes of proton beam therapy (PBT) and carbon ion radiotherapy (CIRT) by a systematic review and meta-analysis of the existing clinical evidence. METHODS: A systematic literature search was performed to identify studies comparing the clinical outcomes of PBT and CIRT. The included studies were required to report oncological outcomes (local control [LC], progression-free survival [PFS], or overall survival [OS]) or adverse events. RESULTS: Eighteen articles comprising 1857 patients (947 treated with PBT and 910 treated with CIRT) were included in the analysis. The pooled analysis conducted for the overall population yielded average hazard ratios of 0.690 (95% confidence interval (CI), 0.493-0.967, p = 0.031) for LC, 0.952 (95% CI, 0.604-1.500, p = 0.590) for PFS, and 1.183 (0.872-1.607, p = 0.281) for OS with reference to CIRT. The subgroup analyses included patients treated in the head and neck, areas other than the head and neck, and patients with chordomas and chondrosarcomas. These analyses revealed no significant differences in most outcomes, except for LC in the subgroup of patients treated in areas other than the head and neck. Adverse event rates were comparable in both groups, with an odds ratio (OR) of 1.097 (95% CI, 0.744-1.616, p = 0.641). Meta-regression analysis for possible heterogeneity did not demonstrate a significant association between treatment outcomes and the ratio of biologically effective doses between modalities. CONCLUSION: This study highlighted the comparability of PBT and CIRT in terms of oncological outcomes and adverse events.

IL-6 expression predicts treatment response and outcome in squamous cell carcinoma of the esophagus.

BACKGROUND: The identification of potential tumor markers can improve therapeutic planning and patient management. The aim of this study was to highlight the significance of IL-6 in esophageal squamous cell carcinoma (SCC). METHODS: We retrospectively analyzed the clinical outcomes of 173 patients with esophageal SCC, and examined the correlation between IL-6 levels and clinical outcomes in esophageal cancer patients. Furthermore, the human esophageal SCC cell line CE81T was selected for cellular and animal experiments to investigate changes in tumor behavior and treatment response after manipulation of IL-6 expression. RESULTS: In clinical outcome analysis, positive IL-6 staining and poor treatment response was significantly associated with shorter survival. Furthermore, the frequency of IL-6 immunoreactivity was significantly higher in esophageal cancer specimens than in non-malignant epithelium, and this staining was positively linked to the development of distant metastasis (p = 0.0003) and lower treatment response rates (p = 0.0001).By ELISA analysis, IL-6 serum levels were significantly elevated in patients developing disease failure.When IL-6 expression was inhibited, aggressive tumor behavior and radiation resistance could be overcome in vitro and in vivo. The underlying changes included increased cell death, less epithelial-mesenchymal transition and attenuated STAT3 activation. IL-6 inhibition was also associated with attenuated angiogenesis in tumor-bearing mice. CONCLUSIONS: IL-6 was significantly associated with poor prognosis in patients with esophageal cancer. Targeting this cytokine could be a promising strategy for treatment of esophageal cancer, as evidenced by inhibition of aggressive tumor behavior and treatment resistance.

Outcome of patients with esophageal cancer: a nationwide analysis.

BACKGROUND: Esophageal cancer is 1 of the 10 most common cancers and is a particular devastating form of cancer worldwide. More than 90% patients with esophageal cancer in Taiwan have squamous cell carcinoma (SCC). In the present study, we assessed the factors affecting survival of patients with esophageal cancer using data from Taiwan, a high-incidence area for esophageal SCC. METHODS: We performed a retrospective review of 12,482 patients who were newly diagnosed with esophageal cancer from 1998 to 2007. The data were obtained from the National Health Insurance Research Database in Taiwan. Study participants were followed-up until the end of 2008. RESULTS: Of the 12,482 patients, 11,490 (92.1%) were male with a median age of 60 years, and 992 (7.9%) were female with a median age of 71 years at the time of diagnosis. The overall 1-, 2-, 5-, and 10-year survival rates after diagnosis were 40.3, 22.9, 12.8, and 7.6%, respectively. Among parametric models for esophageal cancer prognosis, male sex, no curative treatment (surgery and/or radiotherapy), old age, and low socioeconomic status were significantly associated with shorter survival. Furthermore, curative treatment with surgery improved the survival of esophageal cancer patients more significantly compared with patients who undergo definite radiotherapy. CONCLUSIONS: Our data indicated that age, sex, and curative treatment were significant predictors of lifetime survival in patients with esophageal cancer. The overall survival rates of patients with esophageal cancer are relatively low, while survival of patients who undergo surgery is improved significantly.

Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model.

Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 µg + 0 µg, B: 0.1 µg + 0.1 µg, C: 1 µg + 1 µg, and D: 10 µg + 10 µg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 µgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.