Purpose: To report the treatment result of astrocytoma of the brain treated by operation combined radiotherapy. Materials and Methods: 70 patients with brain astrocytoma were treated by radiotherapy after operation from January, 1978 to January, 1989. The radiation dose ranged from 40～64Gy/5～7wks. Results: The 1-,3- and 5-year survival were 91.7%,55.8% and 45.0%,respectively. Conclusion: Radiotherapy is necessary for patients with brain astrocytoma after operation.

Objective To explore the association between the genetic polymorphism of hypoxia inducible factor 1 α (HIF-1α) G1790A and the radiosensitivity of nasopharyngeal carcinoma.Methods A total of 189 patients with nasopharyngeal carcinoma treated with radical radiotherapy were followed-up for 3 years.The patients were divided into cured group with 135 cases and recurrence group with 54 cases by clinical follow-up results.PCR-RFLP was used to determine the mononucleotide genotypes of HIF-1α G1790A.Results The observed genotype frequencies of HIF-1α gene 1790 (G→A) for GG, GA and AA were 70.04% , 20.74% , 2.22% in cured group and 59.26% , 38.89% , 1.85% in recurrence group, respectively.The allele frequencies for G and A were 87.4% , 13.9% in cured groups and 78.7% ,21.3% in recurrence group, respectively, without significant difference in distribution of allele frequencies between the two groups(x2 =6.919, P =0.077).Conclusions The genetic polymorphisms of HIF-1α G1790A might be related with the radiosensitivity of nasopharyngeal carcinoma.

Objective To determine the effects of hypoxia inducible factor-1α(HIF-1α) expression on postoperative adjuvant radiotherapy in esophageal carcinoma. Methods 95 cases with esophageal carcinoms who received radical operation were analyzed with followed-up data from 1995 to 1998.Expression of HIF-1α in 45 patients with esophageal carcinoma who received radiotherapy after radical operation were deternlined by immunohistochemical method in contrast with 50 patients with esophageal carcinoma received surgery alone.Kaplan-Meier method and COX proportional hazard model were used to analyze.Results The positive expression of HIF-1α in esophageal carcinoma was observed mainly in the nucleus of tumor cells.The positive expression rate of HIF-1α in esophageal carcinoma was 58.9%.The expression of HIF-1α had no relationship with age,sex,histologic subtype and T stage,but had positive relationship with recurrence and distant metastasis.There was significant difference between patients with positive and negative HIF-1α protein expression in surgery alone and postoperation radiotherapy group. COX model analysis showed that HIF-1α had separate and significant impacts on prognosis in surgery group and surgery plus radiotherapy group. Conclusion Over expression of HIF-1α protein suggests a poor prognosis,and has tendency to resist radiotherapy in esophageal carcinoma.

AIM: To investigate the mechanism of renal damage in chronic intermittent hypoxia (CIH) rat model.METHODS:The Sprague-Dawley rats were randomly divided into 2-week CIH group (2IH), 2-week simulated air control group (2C), 4-week CIH group (4IH) and 4-week simulated air control group (4C).HE staining, PAS staining and Masson staining were used for histological evaluation .Blood was collected for the measurement of superoxide dismutase (SOD).The mRNA expression of hypoxia-inducible factor-1α(HIF-1α), manganese superoxide dismutase (MnSOD), copper/zinc superoxide dismutase ( Cu/ZnSOD ) was detected by real-time PCR.RESULTS: ( 1 ) No significance difference of renal weight , body weight , and the ratio of renal weight to body weight was observed , while IH caused mor-phologic kidney damage , especially in 4IH group.Hypertrophy of epithelial cells in the kidney tubles and dilation in the glomeruli were observed under light microscope with HE and PAS staining , especially in 4IH group.Masson staining showed no significant fibrotic response in the kidney of the rats exposed to IH .(2) The SOD levels in the serum and kid-ney were decreased after CIH .Compared with the corresponding control groups , the levels of serum SOD were significantly lower in CIH groups, especially in 4IH group.The mRNA expression of Cu/ZnSOD and MnSOD in CIH groups decreased significantly as compared with control groups .The mRNA levels of HIF-1αwere significantly higher in CIH groups than those in the corresponding control groups .CONCLUSION: CIH induces abnormalities of glomeruli and convoluted tu-bules, while 4-week IH exposure has not led to fibrotic response .CIH participates in the process of renal oxidative stress damage by upregulating HIF-1αtranscription and downregulating Cu/ZnSOD and MnSOD transcription .

[ ABSTRACT] AIM: To investigate the effect of chronic intermittent hypoxia on AMP-activated protein kinase ( AMPK) pathway in the brain of young rats.METHODS:Part one:SD mice (3~4 weeks old) were randomly divided into 4 groups (n=8): simulated air control group for 2 weeks (2AC), chronic intermittent hypoxia group for 2 weeks (2IH), simulated air control group for 4 weeks (4AC) and chronic intermittent hypoxia group for 4 weeks (4IH).Part two:SD mice (3~4 weeks old) were randomly divided into 2 groups (n=8): chronic intermittent hypoxia group for 4 weeks (4IH) and chronic intermittent hypoxia group treated with AMPK inhibitor for 4 weeks (4IHI).After modeling, the eight-arm maze test was performed.TUNEL method was used to detect the neuronal apoptosis in the hippocampal and pre-frontal cortical tissues.The mRNA expression of adenosine A2a receptor was examined by RT-qPCR, and the protein levels of phosphorylated AMPK (p-AMPK) and mammalian target of rapamycin (p-mTOR) were determined by Western blot.
RESULTS:Compared with control group, the numbers of reference memory error ( RME) , working memory error ( WME) and total error (TE) in 2IH group and 4IH group significantly increased (P<0.01).Compared with 2IH group, the num-bers of errors in 4IH group also increased significantly (P<0.01).Compared with 4IH group, the values in 4IHI group significantly decreased.Compared with control group, the neuronal apoptosis of hippocampus and prefrontal cortex in 2IH group and 4IH group increased, and that in 4IH group was more evident (P<0.05).In 4IHI group, the neuronal apopto-sis decreased.The mRNA expression of adenosine A2a receptor in the hippocampal and cortical tissues in 2IH group and 4IH group was higher than that in control group.The protein level of p-AMPK was higher, and p-mTOR was lower in 2IH group and 4IH group, and those in 4IH group were more evident (P<0.05).Compared with 4IH group, the protein level of p-AMPK was lower, and p-mTOR was higher in 4IHI group.CONCLUSION: Chronic intermittent hypoxia induces neuronal apoptosis, resulting in impairment of learning and memory in a time-dependent manner by upregulating adenosine A2a receptor, activating AMPK activity, and inhibiting mTOR phosphorylation in rats.

Objective To evaluate long-term changes in health-related quality of life (QOL) of patients with local advanced prostate cancer after intensity modulated radiotherapy (IMRT) combined with androgen deprivation therapy.Methods The patients who met the criteria for this study were enrolled and were treated with IMRT combined with androgen deprivation.The total dose of radiation was 68.2Gy(2.2Gy per fraction).QOL was evaluated before and 3,12,36,48 and 60 months after treatment using the Expanded Prostate Cancer Index Composite(EPIC),a validated tool that assesses four primary domains (urinary,bowel,sexual and hormonal).Results From 2002 to 2007,87 patients were enrolled.At each follow-up time point,the number of cases was 87,87,86,81,75,65,56 and 47,respectively.The median follow-up time was 76.8 months.Compared with baseline assessment,all of four domain scores were declined in follow-up assessments.The mean score of urinary,bowel and hormonal domains were significantly reduced.At 3 months after treatment,the scores of bowel domain were lowest,in which the total,function and symptom scores were 75.7,78.4 and 72.8,respectively.However,there was no statistically significant difference in the mean sexual domain score.The mean change scores in urinary incontinence and obstructive were-13.0±8.3 and-6.12±3.9,respectively.Conclusions IMRT combined with androgen deprivation therapy was well tolerated in patients with local advanced prostate cancer.QOL was decreased in urinary,bowel and hormonal toxicity,most of which could be tolerated in five years.

Lenvatinib, a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer, facing limitations due to drug resistance. Here, we applied a multidimensional, high-throughput screening platform comprising patient-derived resistant liver tumor cells (PDCs), organoids (PDOs), and xenografts (PDXs) to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings. Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment, expediting drug repurposing screens. Pharmacological screening identified romidepsin, YM155, apitolisib, NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models. Notably, romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway. A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models. Collectively, our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer, providing a feasible multidimensional platform for personalized medicine.