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Fardell J.E.,University of Sydney | Fardell J.E.,University of New South Wales | Thewes B.,University of Sydney | Thewes B.,Radboud University Nijmegen | And 6 more authors.
Journal of Cancer Survivorship | Year: 2016

Purpose: Fear of cancer recurrence (FCR) is prevalent among survivors. However, a comprehensive and universally accepted theoretical framework of FCR to guide intervention is lacking. This paper reviews theoretical frameworks previously used to explain FCR and describes the formulation of a novel theoretical framework for FCR. Methods: A systematic review of the literature was undertaken to identify conceptual frameworks or theories applied to FCR. MEDLINE, PubMED, CINAHL, AMED, PsycINFO and Web of Science were searched. Identified conceptual frameworks were reviewed for strength of evidence supporting their validity. Results: Of 558 papers initially identified, 16 made reference to six different conceptual frameworks relating to FCR. The most comprehensive and evidence-based theoretical approach is the Common Sense Model (CSM). Other approaches have limited evidence supporting their application to FCR. Two theoretical approaches developed in the context of emotional disorders that appear to be highly relevant to FCR: the Self-Regulatory Executive Function (S-REF) model and Relational Frame Theory were combined with the CSM to produce a novel cognitive processing account of FCR. Conclusions: Few conceptual frameworks have been used consistently to guide FCR research, and not all frameworks are empirically well supported, suggesting that further discussion regarding the conceptualisation of FCR is needed. The novel theoretical framework for FCR presented highlights the multidimensional nature of FCR and the importance of cognitive processing and metacognitions in the development and maintenance of FCR. Implications for Cancer Survivors: The novel theoretical formulation of FCR outlined here provides a much-needed comprehensive framework to further investigate and address FCR in cancer survivors. © 2016, Springer Science+Business Media New York. Source


Sun H.,Breast Cancer Institute | Lu P.,Fudan University | Chen T.,Qi Dong Liver Cancer Institute
Molecular Cancer Therapeutics | Year: 2013

Hepatocellular carcinoma is highly chemoresistant, and ATP-binding cassette subfamily G member 2 (ABCG2) is thought to play a critical role in this drug resistance. The present study aims to develop effective therapeutic strategies to decrease ABCG2 expression level and to surmount drug resistance in hepatocellular carcinoma chemotherapy. First, we verified a positive correlation between the ABCG2 protein level and the drug resistance of hepatocellular carcinoma cell lines. ABCG2 was preferentially expressed in highly chemoresistant hepatocellular carcinoma cancer stem cells (CSC) enriched with CD133. In addition, ABCG2 was N-linked glycosylated in hepatocellular carcinoma cells, and this modification was involved in sustaining its protein stability. The N-linked glycosylation (NLG) inhibitor tunicamycin dramatically reduced ABCG2 expression, altered its subcellular localization, and reversed its drug efflux effect in multiple hepatocellular carcinoma cell lines. Furthermore, tunicamycin reduced the expression levels of several CSC markers and suppressed the tumorigenicity of CD133+ CSCs. Tunicamycin combined with cisplatin (CDDP) inhibited proliferating cell nuclear antigen (PCNA) expression and increased the cleavage of PARP; this effect was partially rescued by the overexpression of ABCG2 or Akt-myr. The combination therapy more effectively suppressed tumor growth in xenograft mice than did single-agent therapy with either drug. Finally, the CDDP treatment combined with UDP-GlcNAc-dolichol- phosphate N-acetylglucosamine-1 phosphate transferase (DPAGT1) knockdown recapitulated the effect observed when CDDP was used in combination with tunicamycin. In summary, our results suggest that tunicamycin may reverse the drug resistance and improve the efficacy of combination treatments for hepatocellular carcinomas by targeting the DPAGT1/Akt/ABCG2 pathway. © 2013 AACR. Source


Xu H.,Research Division | Xu H.,University of Melbourne | Yan M.,Peter MacCallum Cancer Center | Patra J.,Research Division | And 24 more authors.
Breast Cancer Research | Year: 2011

Introduction: RAD21 is a component of the cohesin complex, which is essential for chromosome segregation and error-free DNA repair. We assessed its prognostic and predictive power in a cohort of in situ and invasive breast cancers, and its effect on chemosensitivity in vitro.Methods: RAD21 immunohistochemistry was performed on 345 invasive and 60 pure in situ carcinomas. Integrated genomic and transcriptomic analyses were performed on a further 48 grade 3 invasive cancers. Chemosensitivity was assessed in breast cancer cell lines with an engineered spectrum of RAD21 expression.Results: RAD21 expression correlated with early relapse in all patients (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.06 to 2.86, P = 0.029). This was due to the effect of grade 3 tumors (but not grade 1 or 2) in which RAD21 expression correlated with early relapse in luminal (P = 0.040), basal (P = 0.018) and HER2 (P = 0.039) groups. In patients treated with chemotherapy, RAD21 expression was associated with shorter overall survival (P = 0.020). RAD21 mRNA expression correlated with DNA copy number, with amplification present in 32% (7/22) of luminal, 31% (4/13) of basal and 22% (2/9) of HER2 grade 3 cancers. Variations in RAD21 mRNA expression in the clinical samples were reflected in the gene expression data from 36 breast cancer cell lines. Knockdown of RAD21 in the MDA-MB-231 breast cancer cell line significantly enhanced sensitivity to cyclophosphamide, 5-fluorouracil and etoposide. The findings for the former two drugs recapitulated the clinical findings.Conclusions: RAD21 expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancers. RAD21 may be a novel therapeutic target. © 2011 Xu et al.; licensee BioMed Central Ltd. Source


Pham T.T.,Breast Cancer Institute | Gebski V.,University of New South Wales | Ahern V.,University of New South Wales | Tiver K.,Breast Cancer Institute | And 2 more authors.
Journal of Medical Imaging and Radiation Oncology | Year: 2016

Introduction: Left-sided breast cancer radiotherapy has been associated with an increase in cardiac mortality. This study investigated the potential heart-sparing effect of volumetric-modulated arc radiotherapy (VMAT). We compared VMAT to tangential intensity-modulated radiotherapy (t-IMRT) in the loco-regional treatment of left-sided breast cancer, including internal mammary nodal irradiation, based on deep inspiration breath-hold (DIBH) and free-breathing (FB). Methods: Radiotherapy for 15 patients was re-planned. Four plans were compared: t-IMRT-DIBH; VMAT-DIBH; t-IMRT-FB; VMAT-FB. Prescribed dose was 50 Gy in 25 fractions. T-IMRT plans were generated using tangentially orientated fields. VMAT plans were generated using two partial arcs (average arc 190°). Results: Mean heart dose (MHD) was 5 ± 2.4 Gy, 5.7 ± 1.4 Gy, 9.7 ± 3.3 Gy and 8.1 ± 2.0 Gy for t-IMRT-DIBH, VMAT-DIBH, IMRT-FB and VMAT-FB respectively. The difference in MHD between IMRT-DIBH and VMAT-DIBH was not significant (P = 0.14). VMAT-DIBH significantly spared the volume of heart irradiated to doses of 20 Gy and above (p < 0.05), however, resulted in a significantly higher V5 Gy (P < 0.001), compared to t-IMRT-DIBH. VMAT-DIBH resulted in higher combined lung mean (11 ± 0.8 Gy vs. 8.8 ± 1.1 Gy, P < 0.001) and higher contralateral breast mean dose (5 ± 1 Gy vs. 1.6 ± 1.2 Gy, P < 0.001) compared with t-IMRT-DIBH. Conclusions: On average, there was no significant difference in MHD between VMAT-DIBH and t-IMRT-DIBH. However, VMAT-DIBH was found to benefit a select group of patients. For patients in whom the MHD was >6.3 Gy with t-IMRT-DIBH, the use of VMAT-DIBH resulted in a benefit in reducing the MHD. © 2016 The Royal Australian and New Zealand College of Radiologists. Source


Chi Y.,Breast Cancer Institute | Huang S.,Breast Cancer Institute | Wang L.,Fudan University | Zhou R.,Fudan University | And 5 more authors.
BMC Cancer | Year: 2014

Background: CDK11p58, a Ser/Thr kinase that belongs to the cell division cycle 2-like 1 (CDC2L1) subfamily, is associated with cell cycle progression, tumorigenesis and apoptotic signaling. CDK11p58 is also involved in the regulation of steroid receptors, such as androgen and estrogen receptors. We previously found that CDK11p58 was abnormally expressed in prostate cancer. However, its role in breast cancer remains unclear.Methods: CDK11p58 expression was evaluated by immunohistochemical staining in a tissue array. A Transwell assay was used to detect invasion and metastasis in breast cancer cells. The TaqMan® Metastasis Gene Expression Assay was used to search for potential downstream factors in the CDK11p58 signaling pathway. qRT-PCR was used to evaluate mRNA levels, and the dual luciferase array was used to analyze promoter activity. Western blotting was used to detect the protein level.Results: CDK11p58 expression was negatively correlated with node status (P = 0.012), relapse status (P = 0.002) and metastasis status (P = 0.023). Kaplan-Meier survival curves indicated that the disease-free survival (DFS) was significantly poor in breast cancer patients with low CDK11 expression. Interestingly, using the breast cancer cell lines ZR-75-30 and MDA-MB-231, we found that CDK11p58 was capable of repressing the migration and invasion of ERα-positive breast cancer cells, but not ERα-negative breast cancer cells, in a kinase-dependent manner. Gene expression assays demonstrated that integrin β3 mRNA was dramatically repressed by CDK11p58, and luciferase results confirmed that the integrin β3 promoter was inhibited by CDK11p58 through ERα repression. The expression of integrin β3 was highly related to ERα signaling; ERα overexpression stimulated integrin β3 expression, whereas siRNA-mediated knockdown of ERα attenuated integrin β3 expression.Conclusions: These data indicate that CDK11p58 is an anti-metastatic gene in ERα-positive breast cancer and that the regulation of integrin β3 by CDK11p58 via the repression of ERα signaling may constitute part of a signaling pathway underlying breast cancer invasion. © 2014 Chi et al.; licensee BioMed Central Ltd. Source

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