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Kamarajugadda S.,University of Florida | Cai Q.,University of Florida | Chen H.,University of Florida | Nayak S.,Florida College | And 8 more authors.
Cell Death and Disease | Year: 2013

Normal cells require adhesion to extracellular matrix for survival. Cell detachment causes a drastic increase in reactive oxygen species (ROS) that promotes anoikis. In the present study, we observed that upon detachment from matrix, human mammary epithelial cells strongly upregulate manganese superoxide dismutase (MnSOD, or SOD2), a principal mitochondrial antioxidant enzyme that detoxifies ROS through dismutation of superoxide. Induction of MnSOD by cell detachment is dependent on the NFκB transcription factor. Detachment of mammary epithelial cells potently increases mitochondrial superoxide levels, which are further elevated by depletion of MnSOD in suspended cells. Consequently, cells depleted of MnSOD are hypersensitive to matrix detachment and exhibit increased anoikis. These results suggest that detachment-induced MnSOD counters mitochondrial superoxide accumulation and confers anoikis resistance. Taken together with our previous finding that detached cells evade excessive ROS production by attenuating oxidative metabolism of glucose, we conclude that mammary epithelial cells coordinate their responses to detachment through increasing MnSOD and decreasing ROS generation from mitochondrial glucose oxidation, thereby mitigating anoikis. Anoikis is a barrier to tumor metastasis. Indeed, MnSOD expression is elevated in human breast cancer metastases compared with primary tumors. Expression of MnSOD correlates with histologic tumor grades in human cancer and contributes to cancer cell's resistance to anoikis. Our study suggests that inhibition of ROS detoxification coupled with stimulation of glucose oxidative metabolism may be an efficient strategy to enhance anoikis and block metastasis. © 2013 Macmillan Publishers Limited All rights reserved.

Shi H.-P.,Lanzhou University | Zhang Q.-N.,Gansu Provincial Tumor Hospital | Liu G.-Q.,Lanzhou University | Wang X.-H.,Lanzhou University
Journal of Practical Oncology | Year: 2014

Objective: To evaluate the clinical efficacy and safety of hyperthermia (HT) combined with pleural infusion chemotherapy(observation group) vs pleural infusion chemotherapy alone(control group) for malignant pleural effusion. Methods: Randomized controlled trials (RCTs) on HT plus pleural infusion chemotherapy vs pleural infusion chemotherapy alone for malignant pleural effusion were searched in PubMed, Cochrane Library, EMBASE, VIP, Wanfang, CNKI, CBM, Chinese Journal Full-text Database and other electronic databases. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and assessed quality of the included studies independently, based on the cochrane system evaluation method. Then meta-analyses were performed using RevMan 5.1. Results: A total of 19 RCTs involving 1 134 cases were included. Meta-analysis results showed that the efficacy rate(OR=3.82, 95%CI: 2.89~5.06;P<0.00001) and life quality improvement rate (OR=3.34, 95%CI: 2.39~4.68;P<0.00001) of observation group were higher than those of control group. In the safety aspect, there were no significant differences in the incidence of gastrointestinal reaction, myelosuppression and chest pain between the two groups; but the incidence rates of skin burn(OR=4.88, 95%CI: 1.38~17.22, P=0.01) and subcutaneous scleroma(OR=5.41, 95%CI: 1.36~21.47, P=0.02) in observation group were higher than those in control group. Conclusion: Compared with pleural infusion chemotherapy alone, hyperthermia combined with pleural infusion chemotherapy can significantly improve the efficacy and life quality of patients with malignant pleural effusion, and its side effects are acceptable.

Cai H.-Y.,Gansu Provincial Peoples Hospital | Wang X.-H.,Gansu Provincial Tumor Hospital | Gao L.-Y.,Gansu Provincial Tumor Hospital | Zhang H.,CAS Lanzhou Institute of Modern Physics | And 3 more authors.
Chinese Journal of Cancer Prevention and Treatment | Year: 2010

OBJECTIVE: To evaluate the toxicity and efficacy of carbon ion radiotherapy for malignant neoplasm of skin. METHODS: Twenty-nine patients with superficial carcinoma, which including mucosal malignant melanoma(n= 13), squamous-celled carcinoma(n = 6), Bowen's disease(n = 6), basal cell carcinoma(n = 2), vulvar cancer(n = 1) and mebiomian adenocarcinoma(n = 1). The range of total dose was 50 to 70 GyE, 6-12 fractions within 6-12 days. The single dose was 5.5-11.67 GyE, 1 f/d. The toxicity on organs such as the skin and blood was assessed according to the Radiation Therapy Oncology Group (RTOG), and the efficacy was evaluated with WHO criteria. RESULTS: The median follow-up period was 13.5 months (range, 1-25 months) and the follow-up rate was 100%. Of the 29 patients, 24 (82.8%) achieved complete remission (CR), 5 (17.2%) achieved partial remission (PR); The overall response rate (RR) was 100%, and the median survival time was 22.8 mouths (95% CI: 20.6-24.9). The skin reaction occurred grade 0, 1, 2, 3 and 4 was 11 (37.9%), 9, (31.0%), 6 (20.7%), 2 (6.9%) and 1(3.4%), respectively. The changes of blood had not a significant difference before and after radiotherapy. CONCLSIONS: Carbon ion radiotherapy is a safe and effective treatment for malignant neoplasm of skin in terms of high local control and acceptable toxicities. Additional clinical studies using a larger subject group are required to confirm the therapeutic efficacy.

Wan Q.,Gansu Provincial Tumor Hospital | Xi A.,Gansu Academy of Medical science | Zhang C.,Gansu Provincial Tumor Hospital | Liu X.,Gansu Provincial Tumor Hospital
Zhongguo Zhongyao Zazhi | Year: 2011

Objective: To assess the efficacy and toxicity of the kangai injection combination of fludarabine(Flud), cytosine arabinoside (Ara-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) in refractory/relapsed acute leukemia (AL) patients. Method: From 2004 to 2010 in our hospital, the 49 cases of refractory/relapsed acute luekemia were randomly divided into treatment group(28 cases) and control group(21 cases). The control group were treated by kangai injection plus FLAG regimen,and the control group were treated by FLAG regimen. Result: The remission rate of treatment and total effective rate treatment group were 57.1%(16/28) and 71.4% (21/28), the control group were 52.3% (11/21) and 61.9% (13/21), there were no significant differences in the two groups. Duration of neutrophils less than 0.5 × 10 9/L in treatment group was (14±6) day, control group was (23 ± 3) day, Duration of platelet less than 25 ± 10 9/L in treatment group was (17 ± 6) day, control group was (31 ± 2) day, treatment group of III-IV degree of infection was 6.9% (1/28) and control group was 23.8% (5/21) between the two groups were significantly different (P < 0.05). treatment group of III-IV degree of gastrointestinal toxicity was 10.7% (3/28) arid control group was 28.5% (6/21). Conclusion: Kangai injection plus FLAG regimen could increase the remission rate, shorten the period of bone marrow suppression, significantly reduced the incidence and degree of infection, play a important role in attenuated efficiency.

Luo H.-T.,Gansu Provincial Tumor Hospital | Wang X.-H.,Gansu Provincial Tumor Hospital | Wei S.-H.,Gansu Provincial Tumor Hospital | Tian J.-H.,Lanzhou University | Yang K.-H.,Lanzhou University
Chinese Journal of Cancer Prevention and Treatment | Year: 2010

OBJECTIVE: To evaluate the efficiency and safety of external beam radiotherapy plus brachytherapy ( EBR + B) compared with external beam radiotherapy alone in the treatment of esophageal cancer. METHODS: CBMdisc, VIP, CNKI, Cochrane Library, Pubmed, Embeas etc. were searched by computer and eight major Chinese journals of oncology were searched by manual. Randomized and quasi-randomized controlled trials compared external beam radiotherapy plus brachytherapy with external beam radiotherapy alone in the treatment of esophageal cancer were included. The statistical software RevMan 4. 2. 10 was used. RESULTS: Fourteen published articals were included (1400 patients), and all trails methodological quality were grade C. The results of Meta-analysis showed that: 1,3-year survival rates of EBR+B was significantly higher than that in EBR alone, while the tumor regrowth rates reduced, and the difference was significant (P values were 0. 03, <0. 000 01, 0. 005 and 0. 02 respectively), but the 5-year survival rates and tumor metastasis rates in the two groups were not significant different (P values were 0. 29 and 0. 43 respectively). As for the occurrence rates of radiation esophagitis, bleeding, benign esophageal stenosis in EBR+ B were higher than those to EBR, and there were significant difierent (P value were 0. 04, 0. 002 and 0. 03 respectively), while esophageal perforation and esophageal ulcer were not significantly different between the two groups (P values were 0. 77 and 0. 20 respectively). Radiation pneumonitis in EBR was higher than that in EBR+B with a significant difference (P = O. 000 5). CONCLUSIONS: Compared with EBR alone, EBR+B can improve shortterm survival rates and reduce the toumor regrowth, but not improve longterm survival rates and reduce metastasis rates. There are more incidences of adverse reactions in EBR+B.

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