Clinical studies of apoptosis and proliferation in breast cancer.

Dowsett, Mitch; Archer, Caroline; Assersohn, L.; Gregory, R. K.; Ellis, Patricia; Salter, Janine; Chang, Jenny C.; Mainwaring, Paul N.; Boeddinghaus, Irene; Johnston, Stephen; Powles, T. J.; Smith, Ian

doi:10.1677/erc.0.0060025

Cited by 46 publications

(30 citation statements)

References 9 publications

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“…Inducing apoptosis is an important strategy to overcome cancer [36,37,38]. Previous studies proved that activations of caspase-9 and caspase-3 lead to apoptosis in FaDu cells [39,40].…”

Section: Discussionmentioning

confidence: 99%

Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell

Xie¹,

Fan²,

Jiang³

et al. 2015

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For decades, despite the advancement of medical science, the prognosis of head and neck squamous cell carcinoma (HNSCC), has not improved. Deltonin is one of the major active components of Dioscorea Zingiberensis Wright that has been used for anthrax, rheumatic heart disease, rheumatoid arthritis etc. By employing HNSCC FaDu cell and normal human epidermal keratinocyte, we investigate deltonin efficacy and associated mechanism in both cell culture and nude mice xenografts. Deltonin treatment selectively prevents proliferation of FaDu cells by cell-cycle arrest and induction of apoptosis, via activating checkpoint kinase Chk1and Chk2 as well as caspases 8, 9 and 3. Meanwhile, we found that treatment with deltonin induced autophagy, which played a protective role against deltonin-induced apoptosis. Further studies revealed that deltonin activated autophagy by Akt-mTOR signaling. Additionally, xenograft model showed that administration of deltonin significantly inhibited tumor growth and prolonged survival of tumor bearing mice. Our studies suggested that deltonin might be a potential chemotherapeutic agent against HNSCC, which might contribute to clinical application and pharmacological study of deltonin in future anti-cancer research.

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“…Inducing apoptosis is an important strategy to overcome cancer [36,37,38]. Previous studies proved that activations of caspase-9 and caspase-3 lead to apoptosis in FaDu cells [39,40].…”

Section: Discussionmentioning

confidence: 99%

Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell

Xie¹,

Fan²,

Jiang³

et al. 2015

neo

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“…Induction of apoptosis and decreased proliferation are factors in the biological response of breast cancer to chemotherapy and endocrine therapy (Dowsett et al, 1999) and, therefore, defects in their regulatory machinery could relate to poor Survivin as a marker of poor prognosis in breast cancer AR Hinnis et al response. As well as examining proteins more extensively studied, such as p53, bcl-2, bax and p21, the phosphorylation status of p53, Chk2 and the IAP family members survivin and XIAP were considered.…”

Section: Discussionmentioning

confidence: 99%

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

2007

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Established clinico -pathological factors can place patients with breast cancer into good and poor prognostic categories, but even within these groups behaviour and response to treatment can differ. This study examined the value of cell cycle and apoptotic regulatory proteins in predicting behaviour in a poor prognostic group. A total of 165 patients, all of whom had died of breast cancer with duration of survival 12 -127 months, median 38 months, were examined using immunohistochemistry for proliferation, apoptosis, p53, phosphorylated p53, p21, checkpoint kinase 2 (Chk2), bcl-2, bax, survivin and XIAP. All had received chemotherapy and/or hormonal therapy and were predominantly T2, node positive, grade III with only half oestrogen-receptor (ER) positive. High proliferation, phosphorylated p53, Chk2 and survivin expression correlated with grade III and lack of ER, whereas low proliferation, p21 and bcl-2 related to better grade and presence of ER. On univariate analysis grade, proliferation, phosphorylated p53, bcl-2, ER and survivin related to duration of survival. In multivariate analysis, grade (P ¼ 0.001) and survivin (P ¼ 0.005) were independent prognostic factors, grade III and presence of survivin relating to shorter survival. The latter was particularly for those patients receiving neoadjuvant therapy and adjuvant chemo-and hormonal therapy. The presence of the inhibitor of apoptosis protein survivin is a highly significant independent predictor of shorter duration of survival of patients with poor prognostic features, and merits investigation as a marker in other prognostic groups.

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“…43,44 A series of studies on animal models and clinical cancer specimens have demonstrated that apoptosis plays an important role in the genesis and development of malignancies and appears to be a critical approach through which endocrine therapy, radiotherapy, chemotherapy and molecular targeting therapy with trastuzumab exert their biological effects. [12][13][14][15][16][17][18][19][43][44][45][46][47][48] It was reported that cyclophosphamide treatment of mice bearing the murine mammary adenocarcinoma MCa-4 increased the apoptotic index from 2.5% at baseline to more than 20% after treatment. 13 Similar results were also found after treatment with cisplatin, doxorubicin and ionizing radiation.…”

Section: Discussionmentioning

confidence: 99%

Correlation between hybrid 18F-FDG PET/CT and apoptosis induced by neoadjuvant chemotherapy in breast cancer

Yao²,

Liu³

et al. 2007

Cancer Biology & Therapy

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Quantitative or semi-quantitative analysis of fluorine-18 fluorodeoxyglucose positron emission tomography ( 18 F-FDG PET) has been reported to correlate with the clinical and pathological response of tumors to preoperative treatment. This study was conceived to evaluate the correlation between hybrid 18 F-FDG PET/CT and apoptosis in breast cancer after neoadjuvant chemotherapy. Three cycles of neoadjuvant chemotherapy were given to forty-five patients with primary breast cancer proven by core needle biopsy. Hybrid PET/CT was performed before and after treatment and tumor to non-tumor radioactivity ratio (T/N) was calculated. The apoptotic index (AI) in core-cut and surgically resected samples was determined using TUNEL techniques. The mean T/N pre-and postchemotherapy was 3.23 ± 0.63 and 2.31 ± 0.49, respectively (p = 0.006), with the mean reduction rate below baseline of 31.18 ± 13.18% (range, 6.4-50.8%). The mean AI pre-and post-chemotherapy was 2.81 ± 0.76% and 17.31 ± 6.85%, respectively (p < 0.0001). The mean AI change was 14.34 ± 5.36% (range, 1.9-41.3%). A positive correlation was detected between the T/N reduction rate and AI change (r s = 0.850, p < 0.0001). At a threshold of 20% decrease from baseline in T/N, the mean AI change in the tumors with a reduction of 20% or more in T/N was 20.86 ± 4.29%, while that in the tumors with a reduction of less than 20% in T/N was 8.59 ± 2.87% (p < 0.0001). The sensitivity, specificity, positive and negative predictive values, and the accuracy of PET/CT for the prediction of clinical response were 90.9%, 83.3%, 93.8%, 76.9% and 92%, respectively. These data suggested that neoadjuvant chemotherapy may effectively induce apoptosis in breast tumors and decrease their glucose uptake. Hybrid PET/CT imaging appeared to be positively related to apoptosis level and therefore to be of value in predicting the response of breast cancer to neoadjuvant chemotherapy.

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Clinical studies of apoptosis and proliferation in breast cancer.

Cited by 46 publications

References 9 publications

Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell

Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell

Survivin is an independent predictor of short-term survival in poor prognostic breast cancer patients

Correlation between hybrid 18F-FDG PET/CT and apoptosis induced by neoadjuvant chemotherapy in breast cancer

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