Prognostic factors for IB2-IIIB cervical cancer patients treated by radiation therapy with high-dose-rate brachytherapy in a single-institution study.

Purpose: To evaluate the efficacy of radiotherapy in locally advanced cervical cancer, and to determine the factors affecting prognosis. Material and methods: Clinical data of 211 patients with cervical cancer, treated at our institution between June 2014 and February 2017 were reviewed retrospectively. All patients were treated with definitive radiotherapy and received external irradiation of 45-50.4 Gy. High-dose-rate brachytherapy (HDR-BT) of 24-36 Gy was prescribed to a high-risk clinical target volume (HR-CTV) as a local boost. All statistical analyses were performed with SPSS version 19.0 using Kaplan-Meier survival test and Cox regression analysis. Additionally, dose parameters of patients with IIIB stage treated with combined intracavitary/interstitial (IC/IS) implants were compared with IC only. Results: With a median follow-up time of 69 months, local control (LC), overall survival (OS), disease-free survival (DFS), and nodal control (NC) at 5 years were 89%, 78%, 67%, and 88%, respectively. In multivariate analysis, the major determinant of LC was the level of pre-treatment squamous cell carcinoma antigen (SCC-Ag). The predictors of shorter OS were adenocarcinoma, pre-treatment SCC-Ag, and FIGO stage. Worse DFS was associated with adenocarcinoma, pre-treatment SCC-Ag, and involved lymph nodes. The predictors for nodal failure were positive pelvic lymph nodes. Patients with IIIB treated with IC/IS brachytherapy tended to improve DFS compared with IC alone, and obtained similar HR-CTV D90 EQD2 (n = 10) and biological effective dose (BED), 91 ±6 Gy vs. 89 ±3 Gy, and 107 ±4.5 Gy vs. 107 ±5.6 Gy, whereas decreased organs at risk (OARs) doses, including rectum and bladder D2cm3 were 7.5 Gy and 7.2 Gy lower, respectively. Late grade 3-4 bladder and bowel toxicities were observed in 1.9% of patients. Conclusions: Radiation therapy carried out in our institution results in good survival, with acceptable toxicity in locally advanced cervical cancer. Different individualized therapeutic strategies should be considered for patients with high-risk factors.

FOXA1 Leads to Aberrant Expression of SIX4 Affecting Cervical Cancer Cell Growth and Chemoresistance.

Cervical cancer (CC) is among the most prevalent cancers among female populations with high recurrence rates all over the world. Cisplatin (DDP) is the first-line treatment for multiple cancers, including CC. The main problem associated with its clinical application is drug resistance. This study is aimed at investigating the function and downstream regulation mechanism of forkhead-box A1 (FOXA1) in CC, which was verified as an oncogene in several cancers. Using GEO database and bioinformatics analysis, we identified FOXA1 as a possible oncogene in CC. Silencing of FOXA1 inhibited CC cell growth, invasion, and chemoresistance. Afterwards, the downstream gene of FOXA1 was predicted using a bioinformatics website and validated using ChIP and dual-luciferase assays. SIX4, a possible target of FOXA1, promoted CC cell malignant aggressiveness and chemoresistance. In addition, overexpression of SIX4 promoted phosphorylation of PI3K and AKT proteins and activated the PI3K/AKT signaling pathway. Further overexpression of SIX4 reversed the repressive effects of FOXA1 knockdown on CC cell growth, invasion, and chemoresistance in DDP-resistant cells. FOXA1-induced SIX4 facilitates CC progression and chemoresistance, highlighting a strong potential for FOXA1 to serve as a promising therapeutic target in CC.

Corrigendum to "Inhibition of Uncoupling Protein 2 Enhances the Radiosensitivity of Cervical Cancer Cells by Promoting the Production of Reactive Oxygen Species".

[This corrects the article DOI: 10.1155/2020/5135893.].

Inhibition of Uncoupling Protein 2 Enhances the Radiosensitivity of Cervical Cancer Cells by Promoting the Production of Reactive Oxygen Species.

OBJECTIVE: The mechanism of enhanced radiosensitivity induced by mitochondrial uncoupling protein UCP2 was investigated in HeLa cells to provide a theoretical basis as a novel target for cervical cancer treatment. METHODS: HeLa cells were irradiated with 4 Gy X-radiation at 1.0 Gy/min. The expression of UCP2 mRNA and protein was assayed by real-time quantitative polymerase chain reaction and western blotting. UCP2 siRNA and negative control siRNA fragments were constructed and transfected into HeLa cells 24 h after irradiation. The effect of UCP2 silencing and irradiation on HeLa cells was determined by colony formation, CCK-8 cell viability, γH2AX immunofluorescence assay of DNA damage, Annexin V-FITC/PI apoptosis assay, and propidium iodide cell cycle assay. The effects on mitochondrial structure and function were investigated with fluorescent probes including dichlorodihydrofluorescein diacetate (DCFH-DA) assay of reactive oxygen species (ROS), rhodamine 123, and MitoTracker Green assay of mitochondrial structure and function. RESULTS: Irradiation upregulated UCP2 expression, and UCP2 knockdown decreased the survival of irradiated HeLa cells. UCP2 silencing sensitized HeLa cells to irradiation-induced DNA damage and led to increased apoptosis, cell cycle arrest in G2/M, and increased mitochondrial ROS. Increased radiosensitivity was associated with an activation of P53, decreased Bcl-2, Bcl-xl, cyclin B, CDC2, Ku70, and Rad51 expression, and increased Apaf-1, cytochrome c, caspase-3, and caspase-9 expression. CONCLUSIONS: UCP2 inhibition augmented the radiosensitivity of cervical cancer cells, and it may be a potential target of radiotherapy of advanced cervical cancer.

The therapeutic characteristics of serial casting on congenital scoliosis: a comparison with non-congenital cases from a single-center experience.

BACKGROUND: The therapeutic efficacy of serial casting on idiopathic scoliosis has been gradually documented. However, literatures on serial casting for congenital scoliosis (CS) remain extremely rare. This paper aimed to compare the treatment outcomes of serial casting between CS and non-CS patients to comprehensively evaluate the therapeutic characteristics of serial casting on CS patients. METHODS: A total of 23 early-onset scoliosis cases were included and divided into congenital scoliosis (CS, n = 8) and non-congenital group (non-CS, n = 15). Therapeutic outcomes including the major curve Cobb angle, thoracic kyphosis angle, lumbar lodosis angle, and thoracic spine growing rate were compared between groups at precast, after the first cast, and at the latest follow-up, respectively. RESULTS: All patients received the first cast at the age of 3.25 ± 1.20 years and 5.70 ± 1.18 times of cast corrections. The average casting time was 17.17 ± 3.38 months, and the mean follow-up time was 23.91 ± 12.28 months. Both CS and non-CS groups had significant decrease in Cobb angle after the first cast and at the latest follow-up (all P < 0.05). Cobb angle was significantly lower in non-CS group than in CS group at both time points (all P < 0.01). The correction rate of Cobb angle was significantly higher in non-CS group than in CS group (around 50 vs. 20%, both P < 0.01). The mean thoracic growth rate was significantly lower in CS group than in non-CS group (0.72 ± 0.20 vs. 1.42 ± 0.22 cm/year, P < 0.001). At the latest follow-up, there are 2 cases receiving growing rod surgery, 8 cases wearing a brace, and 13 cases continuing serial casting. CONCLUSIONS: Although the therapeutic efficacy of casting on CS patients is not as good as that on non-CS patients, casting is still an efficient treatment option for CS patients to delay the need for initial surgery.

Detection of K-ras Mutations in Predicting Efficacy of Epidermal Growth Factor Receptor Tyrosine Kinase (EGFR-TK) Inhibitor in Patients with Metastatic Colorectal Cancer.

Epidermal growth factor receptor tyrosine kinase (EGFR-TK) inhibitors are useful in treating different advanced human cancers; however, their clinical efficacy varies. This study detected K-ras mutations to predict the efficacy of EGFR-TK inhibitor cetuximab treatment on Chinese patients with metastatic colorectal cancer (mCRC). A total of 87 patients with metastatic colorectal cancer were treated with cetuximab for 2-16 months, in combination with chemotherapy between August 2008 and July 2012, and tissue samples were used to detect K-ras mutations. The data showed that K-ras mutation occurred in 27/87 (31%). The objective response rates and disease control rate in K-ras wild type and mutant patients were 42% (25/60) versus 11% (3/27) (p<0.05) and 60% (36/60) versus 26% (7/27) (p<0.05), respectively. Patients with the wild-type K-ras had significantly higher median survival times and progression-free survival, than patients with mutated K-ras (21 months versus 17 months, p=0.017; 10 months versus 6 months, p=0.6). These findings suggest that a high frequency of K-ras mutations occurs in Chinese mCRC patients and that K-ras mutation is required to select patients for eligibility for cetuximab therapy. Further prospective studies using a large sample size are needed to confirm these preliminary findings.

Utilization of brewery wastewater for culturing yeast cells for use in river water remediation.

Successful in situ bio-augmentation of contaminated river water involves reducing the cost of the bio-agent. In this study, brewery wastewater was used to culture yeast cells for degrading the COD(Cr) from a contaminated river. The results showed that 15 g/L of yeast cells could be achieved after being cultured in the autoclaved brewery wastewater with 5 mL/L of saccharified starch and 9 g/L of corn steep liquor. The COD(Cr) removal efficiency was increased from 22% to 33% when the cells were cultured using the mentioned method. Based on the market price of materials used in this method, the cost of the medium for remediating 1 m3 of river water was 0.0076 US dollars. If the additional cost of field implementation is included, the total cost is less than 0.016 US dollars for treating 1 m3 of river water. The final cost was dependent on the size of remediation: the larger the scale, the lower the cost. By this method, the nutrient in the brewery wastewater was reused, the cost of brewery wastewater treatment was saved and the cost of the remediation using bio-augmentation was reduced. Hence, it is suggested that using brewery wastewater to culture a bio-agent for bio-augmentation is a cost-effective method.

[Diagnosis and treatment of bone lymphangioma associated with spinal deformity in children].

OBJECTIVE: To investigate the diagnosis, treatment and outcomes of bone lymphangioma associated with spinal deformity in children. METHODS: Eight cases of children with bone lymphangioma associated with spinal deformity at our hospital from 1983 to 2010 were reviewed and analyzed with the following criteria: clinical manifestations, imaging features, histopathological characteristics and therapeutic options. The outcomes of early intervention treatment were assessed. The key diagnostic points and therapeutic principles were summarized on the basis of our own as well as international and domestic experiences. RESULTS: Paraplegia developed in 2 cases because of delayed treatment. The remaining 6 cases were followed up for 10 months to 2 years with satisfactory effects. By curettage lesions, bone grafts, intralesional injection of bleomycin and pedicle screw-stick system maintaining the spinal stability, bone lymphangioma became smaller or disappeared and spinal deformity was effectively controlled. The mean scoliosis and kyphosis correction rates were 57.0% and 58.4% respectively. CONCLUSIONS: Bone lymphangioma in children is rare. If costa and vertebrae are involved, spinal deformity will progressively develop and lead eventually to paraplegia. With an early diagnosis and the administration of proper drugs, bone lymphangioma can be effectively controlled. Surgery for the stability of spinal deformity will effectively prevent the occurrence of paraplegia.

[EPS, SMP and microbial biodiversity under the oligotrophic environment].

In order to investigate the extracellular polymeric substances (EPS), soluble microbial product (SMP) and microbial biodiversity of the sludge lacking of nutrition, to provide evidence for optimizing MBR's operation and lessening membrane fouling, a series of experiments were undertaken under the oligotrophic environment using the sludge from the MBR of Tianjin University. The contents of EPS and SMP were determined, and microbial biodiversity was analyzed by PCR-DGGE technology and cloning-sequencing. Furthermore, the sequences were used for homology analysis and then the phylogenetic tree was constructed. In the initial stage, the EPS and SMP contents raised from 15.04 mg/g and 0 mg/g to 17.99 mg/g and 3.29 mg/g, respectively. Along with the experiment progress, the EPS content dropped to 2.40 mg/g; but the SMP content varied around 3.5 mg/g. This indicates that the EPS and SMP possess the buffer action towards the variation of the environment, and the microorganism can utilize the EPS and SMP under the condition of oligotrophic. Because of the utilization of the EPS and SMP, the Shannon index of the sludge raised from 0.81 to 1.09. Then, it began to decline and stabilized at 0.95 finally. The clone and sequence results reflect that the microbial structure is very rich, and most of the dominant species are uncultured bacterium. Some of the bacterium, which are mostly belong to Bacteroidetes, Flavobacterium, Saprospiraceae and Firmicutes, can degrade the EPS and SMP by secreting protein and polysaccharide hydrolyzing enzymes.

Combined IFN-gamma-endostatin gene therapy and radiotherapy attenuates primary breast tumor growth and lung metastases via enhanced CTL and NK cell activation and attenuated tumor angiogenesis in a murine model.

BACKGROUND: Gene-radiotherapy, a combination of gene therapy and radiotherapy, is a new paradigm for cancer treatment, with the potential to simultaneously improve local and systemic breast cancer control. The aim of this study was to evaluate antitumor effect of interferon (IFN)-gamma-endostatin-based gene-radiotherapy in a murine metastatic breast tumor model, and to elucidate possible mechanisms involved. METHODS: Murine mammary adenocarcinoma 4T1 cells transfected with pEgr-IFN-gamma and pEgr-endostatin plasmids were irradiated (2-20 Gy). IFN-gamma and endostatin levels in the culture supernatants were measured. In vivo female BALB/c mice were inoculated with 1 x 10(5) 4T1 cells by mammary fat pad injection and divided into control, empty vector, gene therapy (pEgr-IFN-gamma and pEgr-endostatin), radiotherapy, and combined gene-radiotherapy groups. Tumor growth, tumor/body weight ratio, lung metastases, and survival of the tumor-bearing mice were observed. Splenic cytotoxic T-lymphocyte (CTL) and natural killer (NK) cell activity and intratumor microvessel density were also assessed. RESULTS: Irradiation significantly enhanced IFN-gamma and endostatin secretion from the transfected 4T1 cells. In vivo mice that received combined gene-radiotherapy showed maximal attenuation in tumor growth rate and lung metastases with increased survival compared with mice that received gene therapy or radiotherapy alone. This was associated with significantly enhanced CTL and NK cell activity and reduced intratumor microvessel density. CONCLUSION: These results demonstrate that IFN-gamma-endostatin-based gene-radiotherapy provide a potent antitumor effect in a murine metastatic breast tumor model, which may relate to IFN-gamma-stimulated CTL and NK cell activation, and endostatin-induced antiangiogenic activity. Thus, gene-radiotherapy may represent a useful addition to neoadjuvant management of locally advanced breast cancer.

[Effects of soluble microbial product on the performance of submerged membrane bioreactor].

The behaviors of soluble microbial products (SMP) and SMP effects on an operational process of submerged membrane bioreactor (SMBR) were studied. Within 90 days performance period, total organic carbon (TOC), molecular weight distributions (MWDs), specific oxygen uptake rate (SOUR)were periodically monitored. The dead-end filtration tests were used to indicate the SMP effect on membrane fouling. Experiment results showed that the concentration of SMP in SMBR supernatant obviously accumulated. As the operation time was prolonged, the concentrations of SMP with MW > 10,000 remarkably increased in SMBR supernatant. Compared with the SMP of MW < 1,000, the SMP with MW > 10,000 obviously affected sludge activity and membrane fouling, but did not significantly influence the SMBR effluent.

[Effect of aeration intensity on the filterability of mixed liquor in membrane bioreactor].

The influence of aeration intensity on membrane fouling in membrane bioreactors (MBR) was to investigate. Two lab-scale MBR with aeration intensity of 500 and 100 L/h were operated for 60 days at a constant permeate flux. The dead-end filtration tests were conducted to confirm the mixed sludge filterability under each condition. The effect of aeration intensity on relative molecular mass distributions of SMP, the particle size distributions (PSD) of flocs and the quantity of extracellular polymeric substances (EPS) in MBRs were also tested. The results show that large aeration intensity has a negative influence on the filterability of mixed sludge in MBR. Further research finds that the large aeration intensity results in the increase of soluble microbial products (SMP) with a relative molecular mass (M(r)) > 10 000 in supernatant, which obviously affects the filtration of mixed sludge. It is also found that small particles in the range of 1-10 microm and the concentration of EPS in flocs remarkably increase under high aeration intensity of 500 L/h.

[Comparison of microbial community structure in MBRs treating different wastewater].

In order to investigate the microbial community structures in different membrane bioreactors, total bacterial genomic DNA was extracted from biomass in four MBRs treating different wastewater. The microbial community structures were studied by polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and cloning-sequencing. Furthermore, and the sequences were used for homology analysis and then two phylogenetic trees were constructed. Results indicate that each MBR owns its specific ecological community after a long-term of operation. Influent wastewater composition has a significant impact on total bacterial community structures. Population diversity, which is in the bioreactor fed with more complex components wastewater, is higher than those of other MBRs. The Shannon Index are 0.77 and 0.78. Proteobacteria and Bacillus, which contain 8 OUTs and 2 OUTs, are the climax communities in the investigable MBRs. The profiles of ammonia-oxidizing bacterial community in the four reactors are very similar. There may exist several modes of nitrification and denitrification in MBR because sequences revealed that there exist multitude nitrifying organisms, in which Nitrosomonas are the most predominant, and two denitrifying bacterium (uncultured Achromobacter sp. and uncultured denitrifying bacterium)in reactors.

Taurolidine induces apoptosis of murine melanoma cells in vitro and in vivo by modulation of the Bcl-2 family proteins.

BACKGROUND: This study evaluates whether taurolidine, a novel antibiotic agent, induces murine melanoma cell apoptosis in vitro and in vivo. METHODS: Murine melanoma cells (B16 4A5 and B16 F10) were treated with taurolidine (0-100 microM) for 12 and 24 hr. Cell viability and apoptosis were assessed by MTT assay and FACScan analysis. Expression of the Bcl-2 family proteins was detected by Western blot analysis. In vivo, taurolidine-induced anti-tumor cytotoxicity was assessed in C57BL/6 mice. Therapeutic effectiveness, by intraperitoneal injection of taurolidine (15 mg/mouse) on alternate days for 2 weeks, was evaluated in mice bearing B16 4A5 tumor xenografts. Primary and metastatic tumor growth and intra-tumor apoptotic index were measured. RESULTS: Taurolidine induced cell apoptosis and reduced cell viability in murine melanoma cells. The pro-apoptotic protein Bax was enhanced, whereas the anti-apoptotic protein Bcl-2 was inhibited by taurolidine treatment. In vivo, systemic injection of 15-mg taurolidine was identified as the maximally tolerated dose. Administration of taurolidine at 15 mg/mouse significantly inhibited primary and metastatic tumor growth, which was mirrored by a significantly increased intra-tumor apoptotic index. CONCLUSIONS: These results demonstrate that taurolidine significantly attenuated melanoma tumor growth, which may result from taurolidine-induced apoptosis by modulation of the Bcl-2 family proteins.

[Comparison of sludge filtration characteristics between a membrane bioreactor and a conventional activated sludge process].

According to the filtration characteristics of sludge, a comparison between a membrane bioreactor (MBR) and a conventional activated sludge process(CAS) was carried out under similar conditions. Experiment results show that the filtration resistance in MBR was 2 to approximately 3 times of that in CAS. The contribution of supernatant resistance to filtration resistance was about 90% both in CAS and in MBR. The test on resistance distribution showed the cake resistance made up 87.30% and 94.18% of total resistance in CAS and MBR, respectively.