Tumor-initiating cells contribute to radiation resistance in primary human renal clear cell carcinomas by activating the DNA damage checkpoint response.

The use of radiotherapy in patients with clear cell renal carcinoma (ccRCC) is predominantly limited to palliation of metastases or control of local growth, because ccRCC cells readily develop radioresistance. The mechanisms underlying ccRCC resistance remain elusive. The present study demonstrated that ccRCC cells that survive fractionated radiation treatment display tumor-initiating cell (TIC) characteristics, such as high self-renewal and tumorigenic capacities, and overexpress stemness genes. ccRCC cells that survived fractionated radiation exhibited increased activation of the DNA damage checkpoint response and G2/M phase arrest compared with sham-irradiated cells. The results of the present study suggest that ionizing radiation destroys the bulk of tumor cells within ccRCC, but spares TICs; this subpopulation confers ccRCC radioresistance and may cause tumor recurrence or relapse following radiotherapy. Furthermore, these findings indicate that the DNA damage checkpoint response may serve as a potential therapeutic target for overcoming resistance of TICs in patients with ccRCC.

Preliminary study of brain glucose metabolism changes in patients with lung cancer of different histological types.

BACKGROUND: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. METHODS: One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. RESULTS: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). CONCLUSIONS: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

Endoplasmic reticulum stress protects human thyroid carcinoma cell lines against ionizing radiation-induced apoptosis.

Radiotherapy is one of the most effective forms of cancer treatment, used in the treatment of a number of malignant tumors. However, the resistance of tumor cells to ionizing radiation remains a major therapeutic problem and the critical mechanisms determining radiation resistance are poorly defined. In the present study, a cellular endoplasmic reticulum (ER) stress microenvironment was established through the pretreatment of cultured thyroid cancer cells with tunicamycin (TM) and thapsigargin (TG), in order to mimic the ER stress response in a tumor microenvironment. This microenviroment was confirmed through the X­box binding protein 1 splice process, glucose­regulated protein 78 kD and ER degradation­enhancing α­mannosidase­like mRNA expression. A clonogenic assay was used to measure cancer cell resistance to 60Co­Î³ following TM pretreatment; in addition, human C/EBP homologous protein (CHOP) mRNA expression was determined and apoptosis assays were performed. The results showed that TM or TG pretreatment inhibited CHOP expression and reduced the apoptotic rate of cells. Furthermore, the results demonstrated that the induced ER stress response rendered cancer cells more resistant to ionizing radiation­induced apoptosis. Therefore, the ER stress pathway may be a potential therapeutic target in order to improve the clinical efficiency of radiotherapy.

Initial study of magnetic resonance diffusion tensor imaging in brain white matter of early AIDS patients.

BACKGROUND: HIV is a neurotropic virus which can cause brain white matter demyelination, gliosis, and other pathological changes that appear as HIV encephalitis or AIDS dementia. The purpose of this study was to investigate the change of the diffused condition of water molecules in brain white matter in early acquired immune deficiency syndrome (AIDS) patients using MR diffusion tensor imaging (DTI). METHODS: DTI examinations were performed on a Siemens 3.0T MR scanner in 23 AIDS patients with normal brain appearance by conventional MRI and 20 healthy volunteers as the control group. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were measured in nine regions; corpus callosum (CC) knee, CC body, CC splenium, periventricular white matter, frontal lobe white matter, parietal lobe white matter, occipital lobe white matter, and the anterior and posterior limbs of the internal capsule. The mean FA and ADC values from each region were compared in three groups: the symptomatic, asymptomatic and the control. RESULTS: The mean FA values were significantly lower and the mean ADC values were significantly higher in all nine regions in patients in the symptomatic group than in the asymptomatic and control group patients. In the asymptomatic group, the mean FA values were significantly lower and the mean ADC values were significantly higher at the CC knee, CC body, CC splenium, periventricular white matter, frontal lobe white matter and parietal lobe white matter, than in the control group. There were no significant differences at other regions between the two groups. CONCLUSIONS: The diffused changes of water molecules in brain white matter in AIDS patients are related to brain white matter regions. DTI examination can detect the brain white matter lesions early in AIDS patients.

[A report of 4 cases about gluteal heterotopic ossification caused by injection].

OBJECTIVE: To study the pathogenesis and treatment of gluteal heterotopic ossification caused by injection. METHODS: From April 2006 to May 2011, 4 old female patients with gluteal heterotopic ossification caused by injection were treated by resection. The average age was 71 years old ranging from 67 to 76. The illness were bilateral,the clinical character was pain and hard nodules in the both hip. The X-ray, CT and pathology matched the diagnosis of heterotopic ossification. Two of them were treated by totally removing the ossified tissues, and loosing the spastic and adhesive soft tissues. The other two were treated with local resection and soft-tissue lysis. RESULTS: The wound of all patients healed well, and there were no complication. All patients were followed-up from 2 to 64 months(averaged 26 months). There were no lump and pain in the location of surgical resection. CONCLUSION: Gluteal heterotopic ossification caused by injection is the drug reaction produced by injecting benzyl alcohol or other drugs,and happens in adults. The key for the treatment is to remove part or all of the painful lump,and loose the local fascia and other soft tissues of the gluteal muscles.

Distinction between postoperative recurrent glioma and delayed radiation injury using MR perfusion weighted imaging.

INTRODUCTION: Distinction between postoperative recurrent glioma and radiation injury remains a tough diagnostic problem for routine imaging methods. The purpose of this study is to evaluate the differentiated effectiveness of perfusion weighted imaging (PWI) for the two entities. METHODS: PWI was performed using Siemens 3.0-T MR system for 35 patients with new contrast-enhancing lesions at the site of treated glioma. Regions of interest (ROIs) were manually drawn at the contrast-enhancing lesion and peri-lesion edema areas. For calculation of standardised relative cerebral blood volume (rCBV) ratios, the same size ROIs were drawn at the area of contralateral hemisphere normal white matter on rCBV maps. At least five ROIs were selected at each lesion. The rCBV values were measured and the rCBV ratios were calculated. The maximum rCBV (rCBV(max)) ratio at each region was chosen for analysis. The patients were divided into two groups: tumour recurrence and radiation injury. The mean rCBV(max) ratios were compared between the two groups. RESULTS: The mean rCBV(max) ratio in the contrast-enhancing lesion was significantly higher in the tumour recurrence (4.36 ± 1.98) compared with that (1.28 ± 0.64) in the radiation injury (P < 0.01). The mean rCBV(max) ratio in the peri-lesion edema was also significantly higher in the tumour recurrence (1.79 ± 0.51) compared with that (0.85 ± 0.28) in the radiation injury (P < 0.05). A recurrent tumour was suggested when the rCBV(max) ratio >2.15 based on the receiver operating characteristic curve. Four patients with recurrent tumour and three with radiation injury were misclassified. CONCLUSION: PWI is a useful method to distinguish tumour recurrence and radiation injury.

Non-enhanced MR angiography of renal artery using inflow-sensitive inversion recovery pulse sequence: a prospective comparison with enhanced CT angiography.

PURPOSE: To prospectively evaluate the diagnostic value of non-enhanced inflow-sensitive inversion recovery (IFIR) MR angiography for the detection of renal artery stenosis (RAS), with enhanced CT angiography performed as the reference standard. MATERIALS AND METHODS: Sixty consecutive patients suspected of RAS underwent both of IFIR MR and enhanced CT angiography. Subjective image quality, renal artery depiction and renal artery grading were all evaluated on artery-by-artery basis. Spearman rank correlation analysis was used to assess agreement between the two techniques. The diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for RAS detection at IFIR MR angiography were calculated. RESULTS: One hundred twenty-six main renal arteries were visualized on enhanced CT and non-enhanced MR angiographic images, respectively. The Spearman rank correlation was 0.773 (P<.001) for renal artery depiction, 0.998 (P<.001) for renal arteries grading and 0.833 (P<.001) for RAS detection between the two modalities. The sensitivity, specificity, PPV and NPV of IFIR MR angiography for RAS detection demonstrated 100%, 99.0%, 92.0% and 100%, respectively. CONCLUSION: Non-enhanced IFIR MR angiography had high sensitivity, specificity, PPV and NPV for RAS detection. It could be the first choice of renal artery imaging methods to avoid ionizing irradiation and renal toxicity from contrast media.

Minimally invasive plate internal fixation for calcaneal fractures.

OBJECTIVE: To assess the clinical efficacy of minimally invasive plate internal fixation for the treatment of calcaneal fractures. METHODS: Manual reduction, rectification of deformity, and cold compress with traditional Chinese medicine were used preoperatively to relieve swelling and pain. A small incision was made to expose the articular facet and to perform anatomic reduction and plate fixation. Self-made traditional Chinese pharmaceutics were applied postoperatively on the surface of the wound to accelerate bony union. RESULTS: All the 40 patients were followed up for at least 1 year postoperatively. According to the Maryland scoring system, the excellent and good rate was 87.5%. CONCLUSION: Minimally invasive plate internal fixation has the advantages of relatively mild injury, reliable fixation, good recovery, and rare complications in the treatment of intraarticular fractures.

Distinction between postoperative recurrent glioma and radiation injury using MR diffusion tensor imaging.

INTRODUCTION: This study aims to evaluate the differentiated effectiveness of MR diffusion tensor imaging (DTI) to postoperative recurrent glioma and radiation injury. METHODS: Conventional MRI and DTI examination were performed using Siemens 3.0 T MR System for patients with new contrast-enhancing lesions at the site of treated tumor with postoperative radiotherapy. The region of interest was manually drawn on ADC and FA maps at contrast-enhancing lesion area, peri-lesion edema, and the contra-lateral normal white matter. Then ADC and FA values were measured and, the ADC ratio and FA ratio were calculated. Twenty patients with recurrent tumor and 15 with radiation injury were confirmed by histopathologic examination (23 patients) and clinical imaging follow-up (12 patients), respectively. The mean ADC ratio and FA ratio were compared between the two lesion types. RESULTS: The mean ADC ratio at contrast-enhancing lesion area was significantly lower in patients with recurrent tumor (1.34 ± 0.15) compared to that with radiation injury (1.62 ± 0.17; P < 0.01). The mean FA ratio at contrast-enhancing lesion area was significantly higher in patients with recurrent tumor (0.45 ± 0.03) compared to that with radiation injury (0.32 ± 0.03; P < 0.01). Neither mean ADC ratio nor FA ratio in edema areas had statistical difference between the two groups. A recurrent tumor was suggested when either ADC ratio <1.65 or/and FA ratio >0.36 at contrast-enhancing lesion area according to the receiver operating characteristics curve analysis. Three patients with recurrent tumor and two with radiation injury were misclassified. CONCLUSION: DTI is a valuable method to distinguish postoperative recurrent glioma and radiation injury.