Disrupting G6PD-mediated Redox homeostasis enhances chemosensitivity in colorectal cancer.

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that generates NADPH to maintain reduced glutathione (GSH), which scavenges reactive oxygen species (ROS) to protect cancer cell from oxidative damage. In this study, we mainly investigate the potential roles of G6PD in colorectal cancer (CRC) development and chemoresistance. We discover that G6PD is overexpressed in CRC cells and patient specimens. High expression of G6PD predicts poor prognosis and correlated with poor outcome of oxaliplatin-based first-line chemotherapy in patients with CRC. Suppressing G6PD decreases NADPH production, lowers GSH levels, impairs the ability to scavenge ROS levels, and enhances oxaliplatin-induced apoptosis in CRC via ROS-mediated damage in vitro. In vivo experiments further shows that silencing G6PD with lentivirus or non-viral gene delivery vector enhances oxaliplatin anti-tumor effects in cell based xenografts and PDX models. In summary, our finding indicated that disrupting G6PD-mediated NADPH homeostasis enhances oxaliplatin-induced apoptosis in CRC through redox modulation. Thus, this study indicates that G6PD is a potential prognostic biomarker and a promising target for CRC therapy.

The Correlation of Retinal Nerve Fiber Layer Thickness With Blood Pressure in a Chinese Hypertensive Population.

To investigate the association between retinal nerve fiber layer (RNFL) thickness and blood pressure (BP) in subjects with systemic hypertension. Subjects with systemic hypertension on anti-hypertensive medications were screened by fundus photography and referred for glaucoma work-up if there was enlarged vertical cup-to-disc (VCDR) ratio ≥0.6, VCDR asymmetry ≥0.2, or optic disc hemorrhage. Workup included a complete ophthalmological examination, Humphrey visual field test, and RNFL thickness measurement by optical coherence tomography. The intraocular pressure (IOP) and RNFL thicknesses (global and quadrant) were averaged from both eyes and the means were correlated with: the systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) using Pearson correlation. Among 4000 screened hypertensive subjects, 133 were referred for glaucoma workup and 110 completed the workup. Of the 4000 screened subjects, 1.3% had glaucoma (0.9% had normal tension glaucoma [NTG], 0.2% had primary open angle glaucoma, and 0.2% had primary angle closure glaucoma), whereas 0.3% were NTG suspects. The SBP was negatively correlated with the mean superior RNFL thickness (P = 0.01). The DBP was negatively correlated with the mean global (P = 0.03), superior (P = 0.02), and nasal (P = 0.003) RNFL thickness. The MAP was negatively correlated with the mean global (P = 0.01), superior (P = 0.002), and nasal (P = 0.004) RNFL thickness while positively correlated with the mean IOP (P = 0.02). In medically treated hypertensive subjects, glaucoma was present in 1.3%, with NTG being most prevalent. MAP control may help with IOP lowering and RNFL preservation, although future prospective studies will be needed.

Percutaneous manual aspiration thrombectomy followed by stenting for iliac vein compression syndrome with secondary acute isolated iliofemoral deep vein thrombosis: a prospective study of single-session endovascular protocol.

OBJECTIVE: To evaluate the feasibility, safety, and effectiveness of single-session endovascular treatment with manual aspiration thrombectomy (MAT) as the first-line method of thrombus removal for iliac vein compression syndrome (IVCS) with secondary acute isolated iliofemoral deep vein thrombosis (DVT). METHODS: This was a prospective clinical study. Twenty-six patients (19 women, 7 men, mean age 54 years) with left-sided acute iliac-common femoral DVT secondary to IVCS were enrolled. All patients presented with leg swelling or pains. Endovascular treatment, consisting of MAT, balloon angioplasty, and stent placement, was performed in the same setting. Overnight antegrade thrombolysis was performed in patients with residual thrombus after MAT. Patients were followed up by ultrasonography. The mean follow-up period was 17.8 months (12-25 months). RESULTS: Single-session endovascular procedures were performed successfully in all patients. The mean procedure time was 67 minutes (ranging from 45 to 90 minutes). Complete thrombus removal, including almost 100% of removal in 24 patients and little residual thrombus (<5%) in two, was achieved after repeated MAT. Thrombolysis was used in these two patients. Complete symptomatic relief was achieved in 25 patients (96%) and partial relief in one. The hospital stay ranged from 2 to 4 days (mean 2.7 days). Recurrent thrombosis within the stent was observed in one case and recanalized with thrombolysis. The 1-year primary and secondary patency rate was 96% and 100%, respectively. No symptomatic pulmonary embolization, bleeding, and venous reflux were observed. Five patients complained about transitory low back pains during balloon angioplasty. CONCLUSION: Single-session endovascular treatment with MAT as the first-line thrombus removal method is feasible, safe, and effective for IVCS with secondary acute isolated iliofemoral DVT. Although limited, our experience suggests that patients thought to be at high risk of bleeding may be candidates for the present single-session endovascular protocol.

Is the 1997 AJCC staging system for nasopharyngeal carcinoma prognostically useful for Chinese patient populations?

PURPOSE: The 5th edition of the American Joint Committee on Cancer (AJCC) staging manual defines new rules for classifying nasopharyngeal carcinoma (NPC). The study was conducted to assess its effectiveness in predicting the prognosis for Chinese patient populations. METHODS AND MATERIALS: Between June 1993 and June 1994, 621 consecutively admitted patients with nondisseminated NPC were treated with definitive-intent radiation therapy alone. All had computed tomography of the nasopharynx, skull base, and the upper neck. A computer database containing all information for staging was formed on presentation. The extent of disease of each patient was restaged according to the 1997 AJCC system. RESULTS: Of the 621 patients, The 5-year overall survival (OS) rate was 60%. The 1997 AJCC system creates subgroups (Stages I to IV) that are assigned to 38 (6.1%), 270 (43.5%), 157 (25.3%), and 156 (25.1%) patients, respectively. The incidence of parapharyngeal extension was 74.1% (460/621). Of these patients (460) with parapharyngeal extension, 310 (67.4%) patients were classified as T2b disease. The 1997 AJCC system showed highly significant differences between the overall stages for both OS and relapse-free survival (RFS). The 1997 AJCC T classifications showed significant correlation with local failure, and N classification was accurate in predicting FDM. Multivariate analysis showed that paraoropharyngeal involvement was an independently significant prognostic factor for OS, freedom from local recurrence (FLR), and freedom form distant metastasis (FDM). CONCLUSION: The 1997 AJCC staging system for NPC is prognostically useful for Chinese patient populations. We proposed that subdivision of parapharyngeal extension should be included in future revisions of the staging system.

Results of a prospective randomized trial comparing neoadjuvant chemotherapy plus radiotherapy with radiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma.

PURPOSE: A prospective randomized trial was performed to evaluate the contribution of neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. PATIENTS AND METHODS: Patients with locoregionally advanced nasopharyngeal carcinoma were treated either with radiotherapy alone (RT group) or neoadjuvant chemotherapy plus radiotherapy (CT/RT group). Neoadjuvant chemotherapy consisting of two to three cycles of cisplatin (100 mg/m(2), day 1), bleomycin (10 mg/m(2), days 1 and 5), and fluorouracil (5-FU; 800 mg/m(2), days 1 through 5, continuous infusion) followed by radiotherapy was given to the CT/RT group. All patients were treated in a uniform fashion by definitive-intent radiation therapy in both groups. RESULTS: Between July 1993 and July 1994, 456 patients were entered onto the study, with 228 patients randomized to each treatment arm, and 449 patients (225 in the RT group and 224 in the CT/RT group) were assessable. All 456 patients were included in survival analysis according to the intent-to-treat principle. The 5-year overall survival (OS) rates were 63% for the CT/RT group and 56% for the RT group (P =.11). The median relapse-free survival (RFS) time was 50 months for the RT group and not reached for the CT/RT group. The 5-year RFS rate was 49% for the RT group versus 59% for the CT/RT group (P =.05). The 5-year freedom from local recurrence rate was 82% for the CT/RT group and 74% for the RT group (P =.04). There was no significant difference in freedom from distant metastasis between the two treatment groups (CT/RT group, 79%; RT group, 75%; P =.40). CONCLUSION: This randomized study failed to demonstrate any significant survival benefit with the addition of neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma. Therefore, neoadjuvant chemotherapy for nasopharyngeal carcinoma should not be used outside of the context of a clinical trial.

Delayed cutaneous hypersensitivity reactions in Qigong (chun do sun bup) trainees by multitest cell mediated immunity.

To determine the difference of cellular immunity between a Qigong trainee group and a normal healthy group, skin tests for delayed cutaneous hypersensitivity (DCH) were carried out with ubiquitous seven antigens. The maximal antigen response time was faster in Qigong trainee group (24 hr) and the response antigen number was also higher in the Qigong trainee group (6 antigens) than in normal healthy person (48 hr and 4 antigens). Qigong trainee also had a larger induration diameter (5.14 mm) than normal healthy person (3.79 mm) at 24 hr. Our results represent the difference in cell mediated immunity (CMI) between Qigong trainees and normal healthy subjects.

Effect of heterospecific DNA on the development of Rana nigromaculata.

Both the DNA of a balancer-bearing species (Cynops orientalis) and that of a non-balancer-bearing species (Rana nigromaculata), when injected into the fertilized eggs of R. nigromaculata, cause some tadpoles derived from the injected eggs to bear a single balancer-like process on the left operculum. Based upon these results, it may be so concluded that the occurrence of the balancer-like process in the tadpole is neither due to genetic transformation, nor due to balancer induction, but rather due to a non-specific developmental effect of DNA.