Overexpression of kinesin superfamily members as prognostic biomarkers of breast cancer.

BACKGROUND: Kinesin superfamily (KIFs) has a long-reported significant influence on the initiation, development, and progress of breast cancer. However, the prognostic value of whole family members was poorly done. Our study intends to demonstrate the value of kinesin superfamily members as prognostic biomarkers as well as a therapeutic target of breast cancer. METHODS: Comprehensive bioinformatics analyses were done using data from TCGA, GEO, METABRIC, and GTEx. LASSO regression was done to select tumor-related members. Nomogram was constructed to predict the overall survival (OS) of breast cancer patients. Expression profiles were testified by quantitative RT-PCR and immunohistochemistry. Transcription factor, GO and KEGG enrichments were done to explore regulatory mechanism and functions. RESULTS: A total of 20 differentially expressed KIFs were identified between breast cancer and normal tissue with 4 (KIF17, KIF26A, KIF7, KIFC3) downregulated and 16 (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF20B, KIF22, KIF23, KIF24, KIF26B, KIF2C, KIF3B, KIF4A, KIFC1) overexpressed. Among which, 11 overexpressed KIFs (KIF10, KIF11, KIF14, KIF15, KIF18A, KIF18B, KIF20A, KIF23, KIF2C, KIF4A, KIFC1) significantly correlated with worse OS, relapse-free survival (RFS) and distant metastasis-free survival (DMFS) of breast cancer. A 6-KIFs-based risk score (KIF10, KIF15, KIF18A, KIF18B, KIF20A, KIF4A) was generated by LASSO regression with a nomogram validated an accurate predictive efficacy. Both mRNA and protein expression of KIFs are experimentally demonstrated upregulated in breast cancer patients. Msh Homeobox 1 (MSX1) was identified as transcription factors of KIFs in breast cancer. GO and KEGG enrichments revealed functions and pathways affected in breast cancer. CONCLUSION: Overexpression of tumor-related KIFs correlate with worse outcomes of breast cancer patients and can work as potential prognostic biomarkers.

KCTD12 promotes G1/S transition of breast cancer cell through activating the AKT/FOXO1 signaling.

BACKGROUND: Sustaining proliferation is the most fundamental step for breast cancer tumor genesis. Accelerated proliferation is usually linked to the uncontrolled cell cycle. However, the internal and external factors linked to the activation of breast cancer cell cycle are still to be investigated. METHODS: quantitative PCR (qPCR) and Western blotting assay were used to detect the expression of potassium channel tetramerization domain containing 12 (KCTD12) in breast cancer. MTT and colony formation assays were performed to evaluate the effect of KCTD12 on cell proliferation of breast cancer. Anchorage-independent growth assay was used to examine the in vitro tumorigenesis of breast cancer cells. Flow cytometry assay, qPCR, and Western blotting were used to investigate the detailed mechanisms of KCTD12 on breast cancer progression. RESULTS: Herein, the result showed that the level of KCTD12 is significantly decreased in breast cancer tissues and cells, and lower level of KCTD12 predicts poorer survival for patients with breast cancer. Further cell function tests illustrated that downregulation of KCTD12 significantly promotes cell proliferation and in vitro tumor genesis. Besides, molecular biologic experiments showed that downregulation of KCTD12 can enhance the G1/S transition through activating the AKT/FOXO1 signaling. CONCLUSION: Our study inferred that downregulation of KCTD12 can be a novel factor for poor prognosis in breast cancer.

Graphene oxide-hydroxyapatite nanocomposites effectively deliver HSV-TK suicide gene to inhibit human breast cancer growth.

Gene therapy with herpes simplex virus thymidine kinase gene (HSV-TK), which is also known as "suicide" gene therapy, is effective in various tumor models. The lack of a safe and efficient gene delivery system has become a major obstacle to "suicide" gene therapy. In this study, the cytotoxicity and transfection efficiency of graphene oxide-hydroxyapatite (GO-Hap) were analyzed by MTS and flow cytometry, respectively. A series of assays were performed to evaluate the effects of GO-HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment on growth of human breast normal and cancer cells. The results showed that GO-HAp nanocomposites effectively transfected cells with minimum toxicity. GO-HAp/p-HRE/ERE-Sur-TK combined with ganciclovir treatment inhibited the proliferation and induced cell apoptosis in cancer cells, while the cytotoxic effects are tolerable in normal breast cells. We conclude that the GO-HAp nanocomposites have significant potential as a gene delivery vector for cancer therapy.

The depletion of interleukin-8 causes cell cycle arrest and increases the efficacy of docetaxel in breast cancer cells.

IL-8 is a multi-functional pro-inflammatory chemokine, which is highly expressed in cancers, such as ER-negative breast cancer. The present study demonstrates the pervasive role of IL-8 in the malignant progression of ER-negative breast cancer. IL-8 siRNA inhibited proliferation and delayed the G1 to S cell cycle progression in MDA-MB-231 and BT549 cells. IL-8 silencing resulted in the upregulation of the CDK inhibitor p27, the downregulation of cyclin D1, and the reduction of phosphorylated-Akt and NF-κB activities. IL-8 depletion also increased the chemosensitivity to docetaxel. These results indicate a role for IL-8 in promoting tumor cell survival and resistance to docetaxel and highlight the potential therapeutic significance of IL-8 depletion in ER-negative breast cancer patients.

Clinical analysis of vascular anomalies: a hospital-based retrospective study of 592 patients in southeast China.

BACKGROUND: Vascular anomalies are common and multidisciplinary involved diseases. The greatest impediment to their treatment in the past was their confusing terminology and clinical heterogeneities. This hospital-based retrospective study assessed some clinical characteristics, diagnosis, therapies and outcomes of patients with vascular anomalies in southeast China. METHODS: A total of 592 vascular anomalies patients (patients with intracranial tissues or viscera involved were excluded), admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2006 to September 2009, were enrolled in the study. Data for clinical characteristics, diagnosis, therapies and outcomes were collected and analyzed. RESULTS: Of the 592 patients, the male:female ratios in the vascular tumor group (n = 187) and the vascular malformation group (n = 405) were 1:1.49 and 1:1.06 respectively, with no significant difference between them. The mean onset age of the vascular tumor group was significantly younger than that of the vascular malformation group (p < 0.001). The head and neck were the most commonly (31.4%) involved areas in vascular anomalies. A total of 23.8% of the patients with vascular anomalies had definite symptoms caused by the vascular lesions. In the vascular tumor group, 94.1% of them were infantile hemangiomas. Venous malformation was the most common (41.0%) subtype of vascular malformations. Surgical therapy was undertaken in 94.2% of the patients with vascular anomalies. Of the 519 patients available for the 16 - 58 month follow-up, 322 patients (62.0%) were cured, 108 patients (20.8%) were markedly improved, 57 patients (11.0%) were partially improved, and 32 patients (6.2%) were uncured. CONCLUSIONS: Vascular anomalies are clinically heterogeneous. While the outcome is generally favorable, further effort should be made to determine the appropriate terminology and management.

[Potential causes and optimal treatment strategy of recurrent venous ulceration in lower limb].

OBJECTIVE: To explore the potential causes and the optimal treatments of recurrent venous ulceration of lower limbs after initial operation. METHODS: Data of patients admitted between January 2000 and June 2010 for recurrent ulceration in lower limbs after previous operation were retrospectively analyzed. Altogether 81 limbs in 73 patients were recruited. There were 55 male patients (60 limbs) and 18 female patients (21 limbs). The average age was 52.6 years (ranging from 31 to 73 years). All the patients had received at least one surgery procedures before recurrence. The average time between ulceration recurrence and the last operation was 10.6 months (ranging from 5 to 37 months). Average diameter of ulcers was 3.7 cm (ranging from 1.3 to 6.5 cm). Color duplex sonography before re-treatment revealed incompetent calf perforators in 57 limbs (70.4%), primary deep vein insufficiency in 38 limbs (46.9%), post-DVT syndrome in 16 limbs (19.8%), reflux of accessory saphenous veins in 11 limbs (13.6%) and residual/re-opened great saphenous vein in 8 limbs (9.9%). Managements including stripping of great saphenous vein, ligation around the ulcer, percutanous ligation of varicose veins, valvoplasty, and adjuvant compressive therapy were adopted according to different venous abnormality. RESULTS: All the patients were followed. All the ulcers healed and hemodynamic indexes were greatly improved 6 months after re-operation. Only 3 limbs (3.7%) suffered again from recurrence 1 year after re-operation. CONCLUSIONS: Incompetent perforators in calf, primary or secondary deep vein insufficiency and incorrectly treated saphenous veins are main causes for recurrent venous ulceration in our series. Management of residual vein abnormalities can still achieve satisfying clinical outcome.