Screening and identification of hub-gene associated with brain metastasis in breast cancer.

BACKGROUND: The presence of breast cancer in the brain, also known as brain metastasis (BMS), is the primary reason for a bad prognosis in cases of breast cancer. Breast cancer is the most prevalent malignant tumor seen in women in developing nations. At present, there is no effective method to inhibit brain metastasis of breast cancer. Therefore, it is necessary to conduct a systematic study on BMS of breast cancer, which will not provide ideas and sites for follow-up studies on the treatment and inhibition of BMS. METHODS: In this study, data set GSE43837 was screened from gene expression omnibus database, and then R language tool was used for differential analysis of its expression spectrum, The gene ontology functional enrichment and Kyoto encyclopedia of genes and genomes signal pathway enrichment analyses, as well as the interactive gene retrieval tool for hub-gene analysis, were performed. RESULTS: According to the findings, the primary genes linked to breast cancer brain metastases are those that involve interactions between cytokines and their respective receptors and between neuroactive ligands and their respective receptors. The majority of the gene ontology enrichment took place in the extracellular structural tissues, the extracellular matrix tissues, and the second message-mediated signaling. We were able to identify 8 genes that are linked to breast cancer spreading to the brain. The gene score for matrix metallopeptidase1 (MMP-1) was the highest among them, and the genes MMP10, tumor necrosis factor alpha-inducible protein 8, collagen type I alpha 2 chain, vascular cell adhesion molecule 1, and TNF superfamily member 11 were all connected to 1 another in an interaction way. CONCLUSIONS: There is a possibility that the 8 key genes that were identified in this research are connected to the progression of BMS in breast cancer. Among them, MMP1 is 1 that has the potential to have a role in the diagnosis and treatment of BMS in breast cancer.

Potent immunosuppressive and anti-inflammatory bisindole alkaloids from Melodinus fusiformis.

Phytochemical investigation of Melodinus fusiformis led to a new aspidosperma-aspidosperma bisindole alkaloid (BIA), bis-19ß-hydroxyvenalstonidine (1), together with three known BIAs (2-4). The structures were established by extensive analysis of their HRESIMS, NMR data, and comparing with the reported data. BIA 1 is an almost symmetrical structure, linked by C3-C14' bond, while BIAs 2-4 are reported for the first time from the plant. The cytotoxic, immunosuppressive and anti-inflammatory activities of BIAs 1-4 were evaluated in vitro. BIAs 1, 3 and 4 showed good toxicity against MOLT-4 cell lines with IC50 values in the range of 1.5-17.5 -M. BIA 2 exhibited the strongest inhibitory effect against MCF-7 cell lines with an IC50 value of 7.1 µM. BIA 1 significantly inhibited Con A-stimulated mice splenocytes proliferation equal to that of the positive control (DXM) in a concentration-dependent manner. BIAs 1 and 2 were able to decrease the NO production in LPS-induced RAW 264.7 cells at 30 µM concentration. BIA 2 showed similar inhibition of nitric oxide release, compared to that of DXM. Furthermore, BIA 2 remarkably inhibited the levels of IL-6 and TNF-α compared to the LPS induced group. Interestingly, BIA 2 displayed an inhibitory effect on TNF-α production similar to that of dexamethasone at a concentration of 20 µM.

Effect of brachytherapy on NF-κB and VEGF in gastric carcinoma xenografts.

Iodine-125 (125I) seed irradiation can be used as an important supplementary treatment for unresectable advanced gastric cancer. However, the radiobiological mechanism underlying brachytherapy remains unclear. Therefore, we investigated the influence of continuous and low-energy 125I irradiation on the cell cycle distribution, apoptosis, expression of NF-κB and VEGF and tumor growth in a human gastric cancer xenograft model. To create an animal model of gastric cancer, SGC-7901 cells were surgically implanted into mice. The 60 mice bearing SGC-7901 gastric cancer xenografts were randomly separated into 2 groups. Sham seeds (0 mCi) were implanted into the control group (n=30); 125I seeds (0.6 mCi) were implanted into the treatment group (n=30). At 28 days after irradiation, apoptosis was detected by flow cytometry. fluorescence micrograph detected intense VEGF and NF-κB immunofluorescence in the tumor samples, and changes in NF-κB and VEGF mRNA and protein expression were assessed by real-time PCR and western blot analysis, respectively. The tumor volume and weight were measured 0-28 days after 125I seed implantation. 125I seed irradiation induced significant apoptosis and G2/M phase arrest. Reduction in the intensities of VEGF and NF-κB immunofluorescence in tumor vessels was observed after treatment. NF-κB and VEGF mRNA and protein expression levels were substantially lower in the implantation treatment group than in the control group. Consequently, 125I seed implantation inhibited cancer growth and reduced cancer volume. The present study revealed that 125I seed irradiation significantly induced apoptosis and cell cycle arrest in the human gastric cancer xenografts. 125I-induced changes in NF-κB and VEGF expression are suggested as potential mechanisms underlying effective brachytherapy.

Overnight heart rate variability in patients with obstructive sleep apnoea: a time and frequency domain study.

Heightened sympathetic activity plays a role in the cardiovascular sequelae of obstructive sleep apnoea (OSA). Cardiac autonomic function may be assessed non-invasively by studying heart rate variability (HRV). The aim of the present study was to compare overnight HRV between a control group and a group of subjects with severe OSA. The potential confounding effects of age, sex, baseline autonomic status and sleep stage distribution were taken into account. Our prospective Holter study compared overnight (0030-0530 hours) HRV in 23 controls (apnoea hypopnoea index (AHI) = 5 ± 3 /h) and 23 subjects with severe OSA (AHI = 65 ± 23 /h), matched for age and sex and with a similar percentage of rapid eye movement sleep. The mean normal-to-normal RR interval (NN) was shorter in the OSA compared with control group (903 vs 1039 ms, respectively), whereas the other time-domain indices of HRV, as well as the classic frequency-domain indices, were similar. Essentially similar results were obtained hourly and when only subjects with high mean values of the standard deviation of all NN (≥ 90 ms) were evaluated. In the 0.01-0.06 Hz range corresponding to the typical OSA pattern of bradycardia-tachycardia termed cyclic variation of heart rate (CVHR), higher power was documented hourly in OSA, with a significant correlation between overnight power and both AHI and mean oxyhaemoglobin saturation. The percentage of NN > x ms different from the previous one (pNNx family) had no diagnostic value. The results of the present study suggest that NN may be the best index to quantify the overnight sympathovagal balance in OSA and that a spectral band overlapping the apnoea-related pattern of CVHR slightly improved the characterization of the apnoea-related HRV patterns.

[125I seed implantation in sphincter preservation for treatment of low rectal cancer].

OBJECTIVE: To evaluate the effects of (125)I seed implantation in sphincter preservation for treatment of low rectal cancer. METHODS: Seventy-six patients with low rectal cancer were randomly divided into 2 group: group A, 17 males and 13 females, aged 48.5 +/- 2.4, receiving rectostomy and anal sphincter preservation and group B, 24 males and 22 females, aged 49.4 +/- 2.6, receiving modified TME and anal sphincter preservation combined with brachytherapy by (125)I seed implantation. Two to four weeks after operation chemotherapy with 5-FU/CF were performed. Follow-up was carried out 6, 12, 24, and 36 months after operation. RESULTS: The local recurrence rates 6, 12, 24, and 36 months after operation were 0%, 11.1%, 14.3%, and 23% respectively in the group A, and all 0% in the group B (P < 0.05 for the rate 36 months later). The survival rates 6, 12, 24, and 36 months after operation were 100%, 100%, 85.7%, and 76.7% respectively in the group A, and were 100%, 100%, 97.1%, and 93% respectively in the group B (P < 0.05 for the rate 36 months later). The functions of defecation and erection were better in the group B and the symptom of pain was improved better in the group A too (all P < 0.05). CONCLUSIONS: Safe, simple, and effective, surgery with sphincter preservation combined with brachytherapy in low rectal cancer is one of the ideal methods for treatment of low rectal cancer.

[Iodine-125 interstitial brachytherapy for malignant tumor].

OBJECTIVE: To assess the clinical effects of (125)I interstitial brachytherapy for malignant tumors. METHODS: One hundred and twelve patients with malignant tumors of stage II stage and III under went radical resection combined with (125)I intraoperative implantation. Seven days and three month after operation WBC count and immune markers were observed. Blood biochemistry ultrasonography and X-ray were performed to observe recurrence and metastasis of tumors per three months. RESULTS: In the 112 patients, 3 died of tumor recurrence in six months, and others survived with the longest time of 35 months. CONCLUSION: (125)I interstitial brachytherapy for malignant tumor is simple, safe and effective.