Long-Term Social Isolation-Induced Autophagy Inhibition and Cell Senescence Aggravate Cognitive Impairment in D(+)Galactose-Treated Male Mice.

Aging is associated with physiological and pathological changes and presents health complications, such as dementia. Isolation has also been associated with the experience of growing old. Both have been linked individually to the incidence of cognitive decline. In this present study, the effects of these two phenomena have been looked at in animal models where aging was induced with D(+)Galactose in mice who underwent long-term post-weaned social isolation (L-PWSI). Assessing cognitive function using Y-maze, Morris water maze (MWM), and passive avoidance tests (PATs) confirmed that cognition is impaired in either of the treatments but worsened when the D(+)Galactose mice were subjected to L-PWSI. Moreover, a synaptic protein, PSD95, and dendritic spines density were significantly reduced in the L-PWSI and D(+)Galactose-treated mice. Our previous study revealed that autophagy deficit is involved in cognitive impairment in the L-PWSI model. Here, we first report the inhibited cell cycle in L-PWSI, combined with the decreased autophagy, aggravates cognitive impairment in D(+)Galactose-treated mice. Beyond these, the autophagy and cell cycle mechanisms that link isolation and aging have been explored. The close association between isolation and aging in humans is very real and needs much research attention going forward for possible therapeutic interventions.

Salvage radiochemotherapy for lymph node recurrence after radical surgery of esophageal cancer.

To evaluate the efficacy of salvage radiochemotherapy (SRC) in patients with recurrent lymph node after radical surgery in esophageal cancer.This study enrolled 58 patients with esophageal squamous cell carcinoma who underwent SRC for lymph node recurrence after radical surgery from August 2011 to November 2015 at our hospital. Survival rates were calculated by the Kaplan-Meier method with the log-rank test. Multivariate analysis was conducted using the Cox model.The overall 1-, 3-, and 5-year survival rates after radical surgery were 94.8%, 53.0%, and 29.6%, respectively. The 1- and 3-year survival rates after SRC were 68.7% and 26.9%, respectively. The major acute toxicities were esophagitis and neutropenia, while most toxicities were grade 1 or 2. There was no unexpected increase in serious adverse events or treatment-related deaths. The results of multivariate analysis showed that time to recurrence (odds ratio [OR]: 0.25, 95% confidence interval [CI]: 0.11-0.53, P = .0004), T stage (OR: 2.75, 95%CI: 1.16-6.49, P = .021), and prophylactic radiotherapy/chemotherapy (PRC, OR: 0.39, 95%CI: 0.16-0.98, P = .045) were determinants of postoperative overall survival, and PRC was the only factor affecting the outcome of SRC (OR: 0.28, 95%CI: 0.12-0.70, P = .006).SRC is an effective treatment for recurrent lymph node after radical surgery of esophageal cancer.

Radiotherapy with or without concurrent chemotherapy for lymph node recurrence after radical surgery of thoracic esophageal squamous cell carcinoma.

PURPOSE: To retrospectively compare the outcomes of patients with lymph node recurrence after radical surgery of esophageal cancer, when given radiotherapy with or without concurrent chemotherapy. METHODS AND MATERIALS: Between January 1996 and December 2005, the data from 73 patients with lymph node recurrence after radical surgery of thoracic esophageal squamous cell carcinoma were retrospectively reviewed. The patients were separated into two groups: radiochemotherapy (RC, 31 patients) and radiotherapy alone (RA, 42 patients). Patients in the RC group received at least two cycles of 5-fluorouracil/cisplatin chemotherapy concurrently with radiotherapy. RESULTS: The median duration of follow-up was 11 months (range, 2-48). The overall survival rate for all patients was 46.7% and 4.7% at 1 and 3 years, respectively. The median overall survival time was 9 months (95% confidence interval, 6.96-11.04) and 17 months (95% confidence interval, 13.61-20.39) for RA and RC groups, respectively. The survival rate at 1 and 3 years was 62.5% and 10.5% in the RC group and 33.8% and 0% in the RA group (p = .0049, log-rank test; hazard ratio for death, 0.52; 95% confidence interval, 0.30-0.92). Acute toxicities were more frequent in the RC group than in the RA group. No significant differences were found in the late toxicity profiles between the two groups. CONCLUSION: The results of the present retrospective analysis suggest that RC should be considered an effective and well-tolerated treatment of patients with thoracic esophageal squamous cell carcinoma and postoperative lymph node recurrence.

Prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery.

The aim of this study was to retrospectively analyze and assess the outcomes and prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. One hundred twenty-six patients with node-positive thoracic esophageal squamous cell carcinoma who had undergone adjuvant therapy (postoperative radiotherapy alone or postoperative sequential chemoradiotherapy without receiving postoperative concurrent chemoradiotherapy) after radical surgery, were retrospectively reviewed from January 1996 to December 2003. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazard models, and survival curves were estimated using the Kaplan-Meier method. The 1-, 3- and 5-year overall survival rates of all 126 patients were 71.4, 39.1, and 22.0%, and disease-free survival rates were 64.3, 36.4, and 21.5%, respectively. Lymph node ratio (the ratio of the number of metastatic lymph nodes to the number of lymph nodes removed, LNR) > or = 0.2 (P= 0.006), pT3 + pT4 (P= 0.06) and sequential chemoradiotherapy (P= 0.08) were associated with a poorer survival by univariate analysis. In multivariate analysis, LNR (P= 0.01, hazard ratio = 0.57, 95% confidence interval, 0.37-0.87) and tumor depth of invasion (P= 0.03, hazard ratio = 0.62, 95% confidence interval, 0.41-0.96) were the independent predictors of survival. Sequential chemoradiotherapy receded survival tendency without significant difference (P= 0.09, hazard ratio = 0.64, 95% confidence interval, 0.37-1.08). Therefore, LNR and tumor depth of invasion were the independent prognostic factors of radiotherapy in patients with node-positive thoracic esophageal squamous cell carcinoma after radical surgery. The addition of chemotherapy does not seem to confer a survival benefit.

Staging of nasopharyngeal carcinoma investigated by magnetic resonance imaging.

BACKGROUND AND PURPOSE: To investigate the American Joint Commission on Cancer (AJCC) sixth edition staging system of nasopharyngeal carcinoma (NPC) by Magnetic Resonance Imaging (MRI). PATIENTS AND METHODS: One hundred and fifty-nine non-disseminated biopsy-proven NPC patients were studied with MRI before treatment. Retrieval of MRI information enabled us to restage all patients accurately according to the sixth edition of the AJCC staging system. Splitting the respective T and N stages by the significant defining factors identified, the cancer death hazard ratios were modeled by the Cox model in SPSS 10.0 for windows (SPSS Inc, Chicago, IL). RESULTS: Single site of skull base abnormality (HR = 3.91, 95% CI: 0.74-20.56) has a superior result to others involved in T3 (HR = 5.83, 95% CI: 1.24-27.29). Involvement of either anterior or posterior cranial nerves solely (HR = 6.02, 95% CI: 1.55-35.60) was not found to be as a poor prognostic indicator as others involved in T4 (HR = 7.81, 95% CI: 1.81-33.63). Less than or equal to 3 cm of N1 (HR = 4.01, 95% CI: 0.48-33.83) and N2 (HR = 4.72, 95% CI: 0.62-35.78) have a better result than >3 cm of N1 (HR = 8.09, 95% CI: 0.95-68.97) and N2 (HR = 10.58, 95% CI: 1.32-84.62), respectively. CONCLUSIONS: Perhaps, it is better to down-stage single site of skull base abnormality from T3 to T2, and involvement of either anterior or posterior cranial nerves solely from T4 to T3, meanwhile, < or =3 cm of N2 down-stage to N1, >3 cm of N1 up-stage to N2.

Influence of MRI abnormality in skull base bone on prognosis of nasopharyngeal carcinoma.

PURPOSE: To evaluate the influence of skull base bone (SBB) abnormality showed by MRI on prognosis of nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: From March 1993 to December 1998, 122 NPC patients received prime radiotherapy treatment. All of them were proved pathologically and checked by magnetic resonance imaging (MRI). Every patient received radiation through conjoint facio-cervical field and conventional dose-fractionation schedules. The total dose to the primary tumor was 60-75 Gy (median, 70 Gy). The Kaplan-Meier method, the Log-rank test and the Cox regression model were used to evaluate the significance of prognostic factors on NPC patient survival. RESULTS: The overall median survival period was 50 (6-92) months, and the 1, 3 and 5 year-survival rates were, respectively, 99.2%, 87.9%, and 73.3%. The 1, 3, and 5 year-survival rates of abnormality and normality of the SBB on MRI were 98.9%, 87.2%, 71.9%, and 100.0%, 89.8%, 77.0%, respectively (P = 0.4233). Gender, age, head pain, SBB abnormality, cranial nerve palsy, cervical lymphadenopathy and primary tumor extent were analyzed with the Cox regression model and SBB abnormality on MRI did not prove to have statistical significance (P = 0.6934). According to the analysis of regrouping, patients with SBB abnormalities > or =2 sites have a worse prognosis (P = 0.0427). Then, the above seven factors are analyzed by Cox regression model and the result had statistical significance (P = 0.0385). CONCLUSION: The SBB abnormality on MRI is of no obvious influence on prognosis of NPC. However, when SBB abnormality sites were > or =2, there is obvious statistical significance on the prognosis.