• Title/Summary/Keyword: Radiobiology

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Ethanolic Extract from Derris scandens Benth Mediates Radiosensitzation via Two Distinct Modes of Cell Death in Human Colon Cancer HT-29 Cells

  • Hematulin, Arunee;Ingkaninan, Kornkanok;Limpeanchob, Nanteetip;Sagan, Daniel
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1871-1877
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    • 2014
  • Enhancing of radioresponsiveness of tumors by using radiosensitizers is a promising approach to increase the efficacy of radiation therapy. Recently, the ethanolic extract of the medicinal plant, Derris scandens Benth has been identified as a potent radiosensitizer of human colon cancer HT29 cells. However, cell death mechanisms underlying radiosensitization activity of D scandens extract have not been identified. Here, we show that treatment of HT-29 cells with D scandens extract in combination with gamma irradiation synergistically sensitizes HT-29 cells to cell lethality by apoptosis and mitotic catastrophe. Furthermore, the extract was found to decrease Erk1/2 activation. These findings suggest that D scandens extract mediates radiosensitization via at least two distinct modes of cell death and silences pro-survival signaling in HT-29 cells.

ATM-induced Radiosensitization in vitro and in vivo

  • Choi, E.K.;Ahn, S.D.;Rhee, Y.H.;Chung, H.S.;Ha, S.W.;Song, C.W.;Griffin, R.J.;Park, H.J.
    • Proceedings of the Korean Biophysical Society Conference
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    • 2002.06b
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    • pp.52-52
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    • 2002
  • It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorecta1 cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. (omitted)

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Novel biological strategies to enhance the radiation therapeutic ratio

  • Kim, Jae Ho;Jenrow, Kenneth A.;Brown, Stephen L.
    • Radiation Oncology Journal
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    • v.36 no.3
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    • pp.172-181
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    • 2018
  • Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.

ATM-induced Radiosensitization in Vitro and in Vivo

  • Choi, E.K.;Ahn, S.D.;Rhee, Y.H.;Chung, H.S.;Ha, S.W.;Song, C.W.;Griffin, R.J.;Park, H.J.
    • Journal of Radiation Protection and Research
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    • v.28 no.3
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    • pp.233-237
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    • 2003
  • It has been known that ATM plays a central role in response of cells to ionizing radiation by enhancing DNA repair. We have investigated the feasibility of increasing radiosensitivity of tumor cells with the use of ATM inhibitors such as caffeine, pentoxifylline and wortmannin. Human colorectal cancer RKO.C cells and RKO-ATM cells (RKO cells overexpressing ATM) were used in the present study. The clonogenic cell survival in vitro indicated that RKO-ATM cells were markdely radioresistant than RKO.C cells. Treatment with 3 mM of caffeine significantly increased the radiosensitivity of cells, particulary the RKO-ATM cells, so that the radiosensitivity of RKO.C cells and RKO-ATM cells were almost similar. The radiation induced G2/M arrest in RKO-ATM cells was noticeably longer than that in RKO.C cells and caffeine treatment significantly reduced the length of the radiation induced G2/M arrest in both RKO.C and RKO-ATM cells. Pentoxifylline and wortmannin were also less effective than caffeine to radiosensitize RKO.C or RKO-ATM cells. However, wortmannin was more effective than caffeine against human lung adenocarcinoma A549 cells indicating the efficacy of ATM inhibitor to increase radiosensitivity is cell line dependent. For in vivo study, RKO.C cells were injected s.c. into the hind-leg of BALB/C-nuslc nude mice, and allowed to grow to 130mm3 tumor. The mice were i.p. injected with caffeine solution or saline and the tumors irradiated with 10 Gy of X-rays. The radiation induced growth delay was markedly increased by 1-2 mg/g of caffeine. It was concluded that caffeine increases radiosensitivity of tumor cells by inhibiting ATM kinase function, thereby inhibiting DNA repair, that occurs during the G2/M arrest after radiation.

Triple Negative Breast Cancer

  • Cetin, Idil;Topcul, Mehmet
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2427-2431
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    • 2014
  • Triple-negative breast cancers (TNBC), characterized by absence of the estrogen receptor (ER) and progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), have a poor prognosis. To overcome therapy limitations of TNBC, various new approaches are needed. This mini-review focuses on discovery of new targets and drugs which might offer new hope for TNBC patients.

Prevalence and Genotype Distribution of Human Papillomavirus Infections in Women Attending Hospitals in Chaozhou of Guangdong Province

  • Chen, Qiang;Luo, Zhao-Yun;Lin, Min;Lin, Qi-Li;Chen, Chan-Yu;Yang, Chun;Xie, Long-Xu;Li, Hui;Zheng, Jia-Kun;Yang, Li-Ye;Ju, Gui-Zhi
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.4
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    • pp.1519-1524
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    • 2012
  • Background: Human papillomavirus (HPV) infection is the main cause of cervical cancer. Limited epidemiologic data of HPV prevalence are available for women attending hospitals in southern China. This study aimed to evaluate the profiles of HPV infection and cytology status in gynecological outpatients in Chaozhou City. Methods: A total of 2833 eligible women were enrolled. The HPV GenoArray test was used for HPV detection and genotyping. Nearly one half of the HPV positive women received liquid-based cytology test. Logistic regression analysis was performed to assess the predictable effects of age and genotype for categories of abnormal cytology. Results: The prevalence of overall, high-risk, and low-risk HPV infection were 24.5%, 19.5% and 8.4%, respectively. A U-shaped age-specific prevalence curve was observed in overall HPV and high-risk HPV, but not in low-risk HPV, which declined with age increasing. The 6 most common high-risk HPV type in descending order, were types 52, 16, 58, 18, 68, and 33. Age and HPV genotype were both important determinants of abnormal cytology incidence, the older women (>45 years) and those infected with HPV type 16 and/or 18 having the highest risk for abnormal cytology. Conclusion: Our findings support the hypothesis that second-generation HPV prophylactic vaccines including HPV-52 and -58 may offer higher protection for women residing in Chaozhou and neighboring cities in Guangdong.

Endpoint of Cancer Treatment: Targeted Therapies

  • Topcul, Mehmet;Cetin, Idil
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4395-4403
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    • 2014
  • Nowadays there are several limitations in cancer treatment. One of these is the use of conventional medicines which not only target cancer cells and thus also cause high toxicity precluding effective treatment. Recent elucidation of mechanisms that cause cancer has led to discovery of novel key molecules and pathways which have have become successful targets for the treatments that eliminate only cancer cells. These so-called targeted therapies offer new hope for millions of cancer patients, as briefly reveiwed here focusing on different types of agents, like PARP, CDK, tyrosine kinase, farnysyl transferase and proteasome inhibitors, monoclonal antibodies and antiangiogenic agents.