[Radiosensitivity and/or radioresistance of head and neck cancers: Biological angle].

[Radiosensitivity and/or radioresistance of head and neck cancers: Biological angle].

Bull Cancer. 2015 Dec 15;

Authors: Guy JB, Rancoule C, Méry B, Espenel S, Wozny AS, Simonet S, Vallard A, Alphonse G, Ardail D, Rodriguez-Lafrasse C, Magné N

Abstract
Radiation therapy is a cornerstone of head and neck cancer management. Technological improvements in recent years in radiation therapy, with intensity-modulated techniques, reinforce even more its role. However, both local and locoregional relapses are still observed. Understanding biological mechanisms of treatment resistance is a topic of major interest. From the cancer cell itself, its ability to repair and proliferate, its microenvironment and oxygenation conditions, migratory and invasive capacity, to biological parameters related to the patient, there are many mechanisms involving radiosensitivity and/or radioresistance of head and neck cancer. The present study explores the main biological mechanisms involved in radiation resistance of head and neck cancer, and describes promising therapeutic approaches.

PMID: 26702507 [PubMed - as supplied by publisher]

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[Cancer stem cells: Radiotherapeutic features and therapeutic targets].

[Cancer stem cells: Radiotherapeutic features and therapeutic targets].

Bull Cancer. 2015 Dec 15;

Authors: Méry B, Rancoule C, Guy JB, Espenel S, Wozny AS, Simonet S, Vallard A, Alphonse G, Ardail D, Rodriguez-Lafrasse C, Magné N

Abstract
Recent evidences suggest that many types of cancers contain a cell population presenting stem cell properties. While the great majority of tumor cells are destined to differentiate, and eventually stop dividing, only a minority population of cells, termed cancer stem cells (CSCs), possesses extensive self-renewal capability and can recapitulate tumor pathophysiology in an immune-compromised animal model. Tumor initiating cells have been identified and isolated in many tumor types including brain, colon and prostate. They are virtually resistant to radiation and may contribute to treatment resistance and recurrence. Therefore, therapies specifically targeting CSCs will likely be needed for complete tumor eradication. The present study reviews published reports identifying the mechanisms of radioresistance of CSCs and potential targets based on the pathways of self-renewal. Further elucidation of pathways that regulate CSCs may provide insights into the development of novel innovative therapies.

PMID: 26702506 [PubMed - as supplied by publisher]

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Clinical significance of OCT4 and SOX2 protein expression in cervical cancer

Abstracts

Background

Cancer stem cell markers have become a major research focus because of their relationship with radiation or chemotherapy resistance in cancer therapy. Cancer stem cell markers including OCT4 and SOX2 have been found in various solid tumors. Here, we investigate the expression and clinical significance of OCT4 and SOX2 in cervical cancer.

Methods

To define the clinical significance of OCT4 and SOX2 expression, we performed immunohistochemistry for OCT4 and SOX2 on 305 normal cervical epithelium samples, 289 cervical intraepithelial neoplasia samples, and 161 cervical cancer cases and compared the data with clinicopathologic factors, including survival rates of patients with cervical cancer.

Results

OCT4 and SOX2 expression was higher in cervical cancer than normal cervix (both p < 0.001). OCT4 overexpression was associated with lymphovascular space invasion (p = 0.045), whereas loss of SOX2 expression was correlated with large tumor size (p = 0.015). Notably, OCT4 and SOX2 were significantly co-expressed in premalignant cervical lesions, but not in malignant cervical tumor. OCT4 overexpression showed worse 5-year disease-free and overall survival rates (p = 0.012 and p = 0.021, respectively) when compared to the low-expression group, while SOX2 expression showed favorable overall survival (p = 0.025). Cox regression analysis showed that OCT4 was an independent risk factor (hazard ratio = 11.23, 95 % CI, 1.31 - 95.6; p = 0.027) for overall survival while SOX2 overexpression showed low hazard ratio for death (hazard ratio = 0.220, 95 % CI, 0.06–0.72; p = 0.013).

Conclusions

These results suggest that OCT4 overexpression and loss of SOX2 expression are strongly associated with poor prognosis in patients with cervical cancer.

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Low-power photodynamic therapy induces survival signaling in perihilar cholangiocarcinoma cells

Abstract

Background

Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways).

Methods

To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm²). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo.

Results

PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic.

Conclusions

PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.

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Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

Pomegranate exerts chemoprevention of experimentally induced mammary tumorigenesis by suppression of cell proliferation and induction of apoptosis.

Nutr Cancer. 2015 Dec 23;:1-11

Authors: Bishayee A, Mandal A, Bhattacharyya P, Bhatia D

Abstract
Breast cancer is the second leading cause of cancer-related death in women in the United States and discovery and development of safe chemopreventive drugs is urgently needed. The fruit pomegranate (Punica granatum) is gaining importance because of its various health benefits. This study was initiated to investigate chemopreventive potential of a pomegranate emulsion (PE) against 7,12-dimethylbenz(a)anthracene (DMBA) rat mammary carcinogenesis. The animals were orally administered with PE (0.2-5.0 g/kg), starting 2 wk before and 16 wk following DMBA treatment. PE exhibited a striking reduction of DMBA-induced mammary tumor incidence, total tumor burden, and reversed histopathological changes. PE dose-dependently suppressed cell proliferation and induced apoptosis in mammary tumors. Immunohistochemical studies showed that PE increased intratumor Bax, decreased Bcl2 and manifested a proapoptotic shift in Bax/Bcl2 ratio. In addition, our gene expression study showed PE-mediated upregulation of Bad, caspase-3, caspase-7, caspase-9, poly (ADP ribose) polymerase and cytochrome c in mammary tumors. Thus, PE exerts chemoprevention of mammary carcinogenesis by suppressing cell proliferation and inducing apoptosis mediated through upregulation of Bax and downregulation of Bcl2 in concert with caspase cascades. Pomegranate bioactive phytoconstituents could be developed as a chemopreventive drug to reduce the risk of breast cancer.

PMID: 26699876 [PubMed - as supplied by publisher]

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Rubus occidentalis: The black raspberry-its potential in the prevention of cancer.

Rubus occidentalis: The black raspberry-its potential in the prevention of cancer.

Nutr Cancer. 2015 Dec 23;:1-11

Authors: Kula M, Krauze-Baranowska M

Abstract
Rubus occidentalis is a black-fruited raspberry originating from North America. Its popularity and demand has been growing over the years, as studies outline its high anthocyanin and ellagitannin content and significance for human health. Interaction between chemical composition and pharmacological activity, mechanisms of action at cellular and molecular levels are all active areas of study. The vast majority of research concerning black raspberries is focused on chemoprevention and anticancer effects. This review summarizes the data on chemical composition and anticancer activity of black raspberry fruits throughout the years.

PMID: 26699735 [PubMed - as supplied by publisher]

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Suggestive evidence for the induction of colonic aberrant crypts in mice fed sodium nitrite.

Suggestive evidence for the induction of colonic aberrant crypts in mice fed sodium nitrite.

Nutr Cancer. 2015 Dec 23;:1-8

Authors: Zhou L, Zahid M, Anwar MM, Pennington KL, Cohen SM, Wisecarver JL, Shostrom V, Mirvish SS

Abstract
A reported linkage between processed (nitrite-treated) meat products and the incidence of colon cancer could be due to sodium nitrite (NaNO2) itself or to N-nitroso compounds produced from the nitrite. Exposure to nitrite occurs due to residual nitrite in processed meat and to salivary nitrite arising by reduction of nitrate in vegetables and drinking water. Here we tested whether NaNO2 could induce colonic aberrant crypts (ABC) or ABC foci (ACF), which are putative precursors of colon cancer. We fed NaNO2 in drinking water for 20-25 wk to groups of 8-20 adult female mice. After sacrifice, ABC and ACF were counted in 2-cm distal colonic segments. In Experiment 1, no significant differences in ABC/ACF induction were seen between groups of 13-14 A/J mice fed 0, 0.5, or 1.0 g NaNO2/l drinking water. NaNO2 also did not affect fasting blood glucose levels. In Experiment 2, we fed 0, 1.0, 1.25, or 1.5 g NaNO2/l water to groups of 15 CF-1 mice. Five of the mice fed 1.5 g NaNO2/l showed ABC, whereas all other groups showed only 0-2 ABC/group, including 0 ABC for the group fed 1.25 g NaNO2/l. Overall statistical analysis indicated a dose-response p trends of 0.04. Pairwise comparison of ABC between groups fed 1.25 and 1.5 g NaNO2/l showed p 0.02 for both ABC and ACF, but a similar comparison between the untreated and 1.5 g/l groups showed no significant effects. In Experiment 3, hot dogs (18% of diet), which were fed to CF-1 mice previously treated with azoxymethane, inhibited ABC and ACF induction, but this effect was not significant (P = 0.10-0.12). In conclusion, these results support the view that NaNO2 may be a risk factor for colon carcinogenesis.

PMID: 26699517 [PubMed - as supplied by publisher]

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