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Sample records for cancer therapies r21

  1. Polymer nanoparticles mediated codelivery of antimiR-10b and antimiR-21 for achieving triple negative breast cancer therapy.

    Science.gov (United States)

    Devulapally, Rammohan; Sekar, Narayana M; Sekar, Thillai V; Foygel, Kira; Massoud, Tarik F; Willmann, Jürgen K; Paulmurugan, Ramasamy

    2015-03-24

    The current study shows the therapeutic outcome achieved in triple negative breast cancer (TNBC) by simultaneously antagonizing miR-21-induced antiapoptosis and miR-10b-induced metastasis, using antisense-miR-21-PS and antisense-miR-10b-PS delivered by polymer nanoparticles (NPs). We synthesized the antisense-miR-21 and antisense-miR-10b loaded PLGA-b-PEG polymer NPs and evaluated their cellular uptake, serum stability, release profile, and the subsequent synchronous blocking of endogenous miR-21 and miR-10b function in TNBC cells in culture, and tumor xenografts in living animals using molecular imaging. Results show that multitarget antagonization of endogenous miRNAs could be an efficient strategy for targeting metastasis and antiapoptosis in the treatment of metastatic cancer. Targeted delivery of antisense-miR-21 and antisense-miR-10b coloaded urokinase plasminogen activator receptor (uPAR) targeted polymer NPs treated mice showed substantial reduction in tumor growth at very low dose of 0.15 mg/kg, compared to the control NPs treated mice and 40% reduction in tumor growth compared to scramble peptide conjugated NPs treated mice, thus demonstrating a potential new therapeutic option for TNBC.

  2. Epigenetic regulation of miR-21 in colorectal cancer

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    Ferraro, Angelo; Kontos, Christos K; Boni, Themis; Bantounas, Ioannis; Siakouli, Dimitra; Kosmidou, Vivian; Vlassi, Margarita; Spyridakis, Yannis; Tsipras, Iraklis; Zografos, George; Pintzas, Alexander

    2014-01-01

    Previous studies have uncovered several transcription factors that determine biological alterations in tumor cells to execute the invasion-metastasis cascade, including the epithelial-mesenchymal transition (EMT). We sought to investigate the role of miR-21 in colorectal cancer regulation. For this purpose, miR-21 expression was quantified in a panel of colorectal cancer cell lines and clinical specimens. High expression was found in cell lines with EMT properties and in the vast majority of human tumor specimens. We demonstrate in a cell-specific manner the occupancy of MIR-21 gene promoter by AP-1 and ETS1 transcription factors and, for the first time, the pattern of histone posttranslational modifications necessary for miR-21 overexpression. We also show that Integrin-β4 (ITGβ4), exclusively expressed in polarized epithelial cells, is a novel miR-21 target gene and plays a role in the regulation of EMT, since it is remarkably de-repressed after transient miR-21 silencing and downregulated after miR-21 overexpression. miR-21-dependent change of ITGβ4 expression significantly affects cell migration properties of colon cancer cells. Finally, in a subgroup of tumor specimens, ROC curve analysis performed on quantitative PCR data sets for miR-21, ITGβ4, and PDCD4 shows that the combination of high miR-21 with low ITGβ4 and PDCD4 expression is able to predict presence of metastasis. In conclusion, miR-21 is a key player in oncogenic EMT, its overexpression is controlled by the cooperation of genetic and epigenetic alterations, and its levels, along with ITGβ4 and PDCD4 expression, could be exploited as a prognostic tool for CRC metastasis. PMID:24149370

  3. miR-21 Expression in Cancer Cells may Not Predict Resistance to Adjuvant Trastuzumab in Primary Breast Cancer

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    Nielsen, Boye Schnack; Balslev, Eva; Poulsen, Tim Svenstrup

    2014-01-01

    , predominantly in cancer cells, or in both stromal and cancer cells. There was no obvious difference between the HER2-positive and HER2-negative tumors in terms of the miR-21 expression patterns and intensities. To explore the possibility that miR-21 expression levels and/or cellular localization could predict...... expression patterns and intensities revealed no association between the miR-21 scores in the cancer cell population (p = 0.69) or the stromal cells population (p = 0.13) and recurrent disease after adjuvant trastuzumab. Thus, our findings show that elevated miR-21 expression does not predict resistance......Trastuzumab is established as standard care for patients with HER2-positive breast cancer both in the adjuvant and metastatic setting. However, 50% of the patients do not respond to the trastuzumab therapy, and therefore new predictive biomarkers are highly warranted. MicroRNAs (miRs) constitute...

  4. Targeting miR-21 enhances the sensitivity of human colon cancer HT-29 cells to chemoradiotherapy in vitro

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    Deng, Jun; Lei, Wan; Fu, Jian-Chun; Zhang, Ling; Li, Jun-He; Xiong, Jian-Ping, E-mail: jpxiong@medmail.com.cn

    2014-01-17

    Highlight: •MiR-21 plays a significant role in 5-FU resistance. •This role might be attributed to targeting of hMSH2 as well as TP and DPD via miR-21 targeted hMSH2. •Indirectly targeted TP and DPD to influence 5-FU chemotherapy sensitivity. -- Abstract: 5-Fluorouracil (5-FU) is a classic chemotherapeutic drug that has been widely used for colorectal cancer treatment, but colorectal cancer cells are often resistant to primary or acquired 5-FU therapy. Several studies have shown that miR-21 is significantly elevated in colorectal cancer. This suggests that this miRNA might play a role in this resistance. In this study, we investigated this possibility and the possible mechanism underlying this role. We showed that forced expression of miR-21 significantly inhibited apoptosis, enhanced cell proliferation, invasion, and colony formation ability, promoted G1/S cell cycle transition and increased the resistance of tumor cells to 5-FU and X radiation in HT-29 colon cancer cells. Furthermore, knockdown of miR-21 reversed these effects on HT-29 cells and increased the sensitivity of HT-29/5-FU to 5-FU chemotherapy. Finally, we showed that miR-21 targeted the human mutS homolog2 (hMSH2), and indirectly regulated the expression of thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD). These results demonstrate that miR-21 may play an important role in the 5-FU resistance of colon cancer cells.

  5. Grant R21CA190028 | Division of Cancer Prevention

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    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  6. Grant R21CA182861 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  7. Grant R21CA174541 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  8. Grant R21CA174594 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  9. Grant R21CA190021 | Division of Cancer Prevention

    Science.gov (United States)

    The Division of Cancer Prevention (DCP) conducts and supports research to determine a person's risk of cancer and to find ways to reduce the risk. This knowledge is critical to making progress against cancer because risk varies over the lifespan as genetic and epigenetic changes can transform healthy tissue into invasive cancer.

  10. Plasma and saliva miR-21 expression in colorectal cancer patients.

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    Sazanov, A A; Kiselyova, E V; Zakharenko, A A; Romanov, M N; Zaraysky, M I

    2017-05-01

    MicroRNA-21 (miR-21) expression was quantified by real-time qRT-PCR in peripheral blood and saliva samples obtained from patients diagnosed with colorectal cancer (CRC) of varying degrees of malignancy and healthy volunteers. All patients had adenocarcinoma located in the distal colon at different stages. Significant differences were detected between the control group and the total experimental group of CRC patients (plasma, P = 0.0001; saliva, P = 5e-12). MiR-21 expression was also significantly different in certain subgroups of patients with CRC disease stages II-IV as compared to the control group. No correlation of miR-21 expression was found with regard to gender and age of patents. Also, there were no significant individual correlations and linear regression of miR-21 expression in the plasma and saliva. The estimated diagnostic sensitivity and specificity of miR-21 expression were respectively 65 and 85% in the plasma, and 97 and 91% in the saliva. Our data suggest that miR-21 in both the saliva and plasma could be a proper biomarker for CRC screening, although the saliva miR-21 expression test looks preferable due to its higher sensitivity, specificity, and technical simplicity.

  11. High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Jørgensen, Stine

    2011-01-01

    Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro...... RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological...... features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression...

  12. miR-21 modulates resistance of HR-HPV positive cervical cancer cells to radiation through targeting LATS1

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    Liu, Shikai; Song, Lili, E-mail: commasll@163.com; Zhang, Liang; Zeng, Saitian; Gao, Fangyuan

    2015-04-17

    Although multiple miRNAs are found involved in radioresistance development in HR-HPV positive (+) cervical cancer, only limited studies explored the regulative mechanism of the miRNAs. miR-21 is one of the miRNAs significantly upregulated in HR-HPV (+) cervical cancer is also significantly associated with radioresistance. However, the detailed regulative network of miR-21 in radioresistance is still not clear. In this study, we confirmed that miR-21 overexpression was associated with higher level of radioresistance in HR-HPV (+) cervical cancer patients and thus decided to further explore its role. Findings of this study found miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells and decrease radiation induced G2/M block and increase S phase accumulation. By using dual luciferase assay, we verified a binding site between miR-21 and 3′-UTR of large tumor suppressor kinase 1 (LATS1). Through direct binding, miR-21 can regulate LATS1 expression in cervical cancer cells. LATS1 overexpression can reverse miR-21 induced higher colony formation rate and also reduced miR-21 induced S phase accumulation and G2/M phase block reduction under radiation treatment. These results suggested that miR-21-LATS1 axis plays an important role in regulating radiosensitivity. - Highlights: • miR-21 is highly expressed in HR-HPV (+) radioresistant cervical cancer patients. • miR-21 can negatively affect radiosensitivity of HR-HPV (+) cervical cancer cells. • miR-21 can decrease radiation induced G2/M block and increase S phase accumulation. • miR-21 modulates radiosensitivity cervical cancer cell by directly targeting LATS1.

  13. Tailored Nanoparticle Codelivery of antimiR-21 and antimiR-10b Augments Glioblastoma Cell Kill by Temozolomide: Toward a "Personalized" Anti-microRNA Therapy.

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    Ananta, Jeyarama S; Paulmurugan, Ramasamy; Massoud, Tarik F

    2016-09-01

    Glioblastoma remains an aggressive brain malignancy with poor prognosis despite advances in multimodal therapy that include standard use of Temozolomide. MicroRNA-21 (miR-21) and microRNA-10b (miR-10b) are oncomiRs overexpressed in glioblastoma, promoting many aspects of cancer biology. We hypothesized that PLGA nanoparticles carrying antisense miR-21 (antimiR-21) and antisense miR-10b (antimiR-10b) might beneficially knockdown endogenous miR-21 and miR-10b function and reprogram cells prior to Temozolomide treatment. PLGA nanoparticles were effective in intracellular delivery of encapsulated oligonucleotides. Concentrations of delivered antimiR-21 and antimiR-10b were optimized and specifically tailored to copy numbers of intracellular endogenous microRNAs. Coinhibition of miR-21 and miR-10b significantly reduced the number of viable cells (by 24%; p < 0.01) and increased (2.9-fold) cell cycle arrest at G2/M phase upon Temozolomide treatment in U87 MG cells. Cell-tailored nanoparticle-assisted concurrent silencing of miR-21 and miR-10b prior to Temozolomide treatment is an effective molecular therapeutic strategy in cell culture, warranting the need for further studies prior to future in vivo "personalized" medicine applications.

  14. ERβ regulates miR-21 expression and inhibits invasion and metastasis in cancer cells

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    Tian, Junmei; Tu, Zhenzhen; Chen, Wei R.; Gu, Yueqing

    2012-03-01

    In human, estrogens play important roles in many physiological processes, and is also found to be connected with numerous cancers. In these diseases, estrogen mediates its effects through the estrogen receptor (ER), which serves as the basis for many current clinical diagnosis. Two forms of the estrogen receptor have been identified, ERα and ERβ, and show different and specific functions. The two estrogen receptors belong to a family of ligand-regulated transcription factors. Estrogen via ERα stimulates proliferation in the breast, uterus, and developing prostate, while estrogen via ERβ inhibits proliferation and promotes differentiation in the prostate, mammary gland, colon, lung, and bone marrow stem cells. MicroRNAs (miRs) are small non-coding RNA molecules that occur naturally and downregulate protein expression by translational blockade of the target mRNA or by promoting mRNA decay. MiR-21 is one of the most studied miRNAs in cancers. MiR-21 is overexpressed in the most solid tumors, promoting progression and metastasis. The miR-21 gene is located on the chromosome 17, in the 10th intron of a protein-coding gene, TMEM49. While, the function of TMEM49 is currently unknown. Our experiment is designed to identity the relationship between miR-21 and ERβ in cancer progression. The human cancer cells were transfected with ERβ. Real-time PCR analysis showed that the expression level of miR-21 was significantly inhibited down by ERβ treatment. As MTT assay showed the tumor cell survival rate was also inhibited significantly. Go/Gl phase cell cycle arrest was founded and tumor cell apoptosis was induced in ERβ group.

  15. Relationship between miR-21 and renal cancer metastasis and in-fluence of miR-21 on the invasion ability of renal cancer cell%miR-21与肾癌转移的相关性及其对肾癌细胞侵袭能力的影响*

    Institute of Scientific and Technical Information of China (English)

    张辉; 郭艳; 尚超; 宋永胜

    2013-01-01

      目的:探讨miR-21与肾癌转移的相关性,及miR-21对肾癌Caki-1细胞侵袭能力的影响。方法:实时PCR检测原发未转移肾癌和原发伴转移肾癌组织中miR-21的表达。将miR-21的前体pre-miR-21和抑制物anti-miR-21分别转染肾癌Caki-1细胞,实时PCR验证转染效果,然后检测转染后细胞的侵袭能力。结果:与原发未转移肾癌相比,原发伴转移肾癌组织中miR-21的表达显著上调;pre-miR-21和anti-miR-21转染后能够显著升高和降低Caki-1细胞miR-21的表达量;pre-miR-21组穿透滤膜的细胞数明显增加,而anti-miR-21组穿透滤膜的细胞数明显减少。结论:miR-21与肾癌的侵袭转移相关,miR-21能够促进肾癌细胞侵袭,在肾癌中具有促进转移的作用。%  Objective: The present study aims to investigate the relationship between miR-21 and renal cancer metastasis as well as the influence of miR-21 on the invasiveness ability of renal cancer Caki-1 cells. Methods: Real-time PCR was performed to detect miR-21 in primary renal cancer without and with metastasis. Pre-miR-21 and anti-miR-21 were transfected to Caki-1 cells, respectively, and real-time PCR was used to detect transfection effects. Finally, invasiveness changes in Caki-1 cells were detected after transfection. Results: miR-21 expression in primary renal cancer with metastasis was much higher than that in primary renal cancer without metasta-sis. After transfection, pre-miR-21 and anti-miR-21 significantly increased and decreased the miR-21 expression in Caki-1 cells, respec-tively. The transmembrane cells of the pre-miR-21 group increased significantly, whereas those of the anti-miR-21 group decreased sig-nificantly. Conclusion: miR-21 and renal cancer metastasis are related. miR-21 advances renal cancer cell invasion and metastasis.

  16. The prognostic importance of miR-21 in stage II colon cancer: a population-based study

    DEFF Research Database (Denmark)

    Kjaer-Frifeldt, S.; Hansen, T. F.; Nielsen, B. S.

    2012-01-01

    R-21), quantified by in situ hybridisation, in a unique, large population-based cohort. PATIENTS AND METHODS: The study included 764 patients diagnosed with stage II colon cancer in Denmark in the year 2003. One section from a representative paraffin-embedded tumour tissue specimen from each patient......-free cancer-specific survival (RF-CSS): HR = 1.26; 95% CI: 1.15-1.60; P analysis, a high level of miR-21 retained its prognostic importance and was found to be significantly related to poor RF-CSS: HR 1.41; 95% CI: 1.19-1.67; P ... was processed for analysis of miR-21 and quantitatively assessed by image analysis. RESULTS: The miR-21 signal was predominantly observed in fibroblast-like cells located in the stromal compartment of the tumours. We found that patients expressing high levels of miR-21 had significantly inferior recurrence...

  17. miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

    Science.gov (United States)

    2012-01-01

    Background Prognosis of prostate cancer (PCa) is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA) mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP) inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line. Materials and methods To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR). Results The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25) the second was characterized by miR-21 overexpression and RECK underexpression (N = 12), and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16). From men who presented the second profile (miR-21 overexpression and RECK underexpression) 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025). Conclusions Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion. PMID:22642976

  18. miR-21 may acts as an oncomir by targeting RECK, a matrix metalloproteinase regulator, in prostate cancer

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    Reis Sabrina

    2012-05-01

    Full Text Available Abstract Background Prognosis of prostate cancer (PCa is based mainly in histological aspects together with PSA serum levels that not always reflect the real aggressive potential of the neoplasia. The micro RNA (miRNA mir-21 has been shown to regulate invasiveness in cancer through translational repression of the Metaloproteinase (MMP inhibitor RECK. Our aim is to investigate the levels of expression of RECK and miR-21 in PCa comparing with classical prognostic factors and disease outcome and also test if RECK is a target of miR-21 in in vitro study using PCa cell line. Materials and methods To determine if RECK is a target of miR-21 in prostate cancer we performed an in vitro assay with PCa cell line DU-145 transfected with pre-miR-21 and anti-miR-21. To determine miR-21 and RECK expression levels in PCa samples we performed quantitative real-time polymerase chain reaction (qRT-PCR. Results The in vitro assays showed a decrease in expression levels of RECK after transfection with pre-miR-21, and an increase of MMP9 that is regulated by RECK compared to PCa cells treated with anti-miR-21. We defined three profiles to compare the prognostic factors. The first was characterized by miR-21 and RECK underexpression (N = 25 the second was characterized by miR-21 overexpression and RECK underexpression (N = 12, and the third was characterized by miR-21 underexpression and RECK overexpression (N = 16. From men who presented the second profile (miR-21 overexpression and RECK underexpression 91.7% were staged pT3. For the other two groups 48.0%, and 46.7% of patients were staged pT3 (p = 0.025. Conclusions Our results demonstrate RECK as a target of miR-21. We believe that miR-21 may be important in PCa progression through its regulation of RECK, a known regulator of tumor cell invasion.

  19. Simultaneous delivery of anti-miR21 with doxorubicin prodrug by mimetic lipoprotein nanoparticles for synergistic effect against drug resistance in cancer cells

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    Rui M

    2016-12-01

    Full Text Available Mengjie Rui, Yang Qu, Tong Gao, Yanru Ge, Chunlai Feng, Ximing Xu Department of Pharmaceutics, School of Pharmacy, Jiangsu University, Zhenjiang, People’s Republic of China Abstract: The development of drug resistance in cancer cells is one of the major obstacles to achieving effective chemotherapy. We hypothesized that the combination of a doxorubicin (Dox prodrug and microRNA (miR21 inhibitor might show synergistic antitumor effects on drug-resistant breast cancer cells. In this study, we aimed to develop new high-density lipoprotein-mimicking nanoparticles (HMNs for coencapsulation and codelivery of this potential combination. Dox was coupled with a nuclear localization signal (NLS peptide to construct a prodrug (NLS-Dox, thereby electrostatically condensing miR21 inhibitor (anti-miR21 to form cationic complexes. The HMNs were formulated by shielding these complexes with anionic lipids and Apo AI proteins. We have characterized that the coloaded HMNs had uniformly dispersed distribution, favorable negatively charged surface, and high coencapsulation efficiency. The HMN formulation effectively codelivered NLS-Dox and anti-miR21 into Dox-resistant breast cancer MCF7/ADR cells and wild-type MCF7 cells via a high-density-lipoprotein receptor-mediated pathway, which facilitated the escape of Pgp drug efflux. The coloaded HMNs consisting of NLS-Dox/anti-miR21 demonstrated greater cytotoxicity with enhanced intracellular accumulation in resistant MCF7/ADR cells compared with free Dox solution. The reversal of drug resistance by coloaded HMNs might be attributed to the suppression of miR21 expression and the related antiapoptosis network. Furthermore, the codelivery of anti-miR21 and NLS-Dox by HMNs showed synergistic antiproliferative effects in MCF7/ADR-bearing nude mice, and was more effective in tumor inhibition than other drug formulations. These data suggested that codelivery of anti-miR21 and chemotherapeutic agents by HMNs might be a

  20. miR-21 Expression in Pregnancy-Associated Breast Cancer: A Possible Marker of Poor Prognosis

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    Beatriz A. Walter, Gabriela Gómez-Macias, Vladimir A. Valera, Mark Sobel, Maria J. Merino

    2011-01-01

    Full Text Available Aims: microRNAs (miRNAs are a class of small noncoding RNAs that can act as key modulators in tumorigenesis-related genes. Specifically, it has been suggested that miR-21 overexpression plays a role in the development and progression of breast cancer. So far, the role of miRNAs in pregnancy-associated breast cancer (PABC has not been investigated.Methods and Results: We evaluated miR-21 expression by quantitative RT-PCR in 35 patients, 25 with PABC and 10 control breast cancer cases not pregnancy-associated with similar clinicopathological features. We then analyzed protein expression for PTEN, BCL2 and PDCD4 as miR-21 target genes by IHC, and finally correlated the results with patients' clinicopathological features.Significant overexpression of miR-21 in PABC tumors compared to normal adjacent tissue was found. Overexpression of miR-21 was frequently found in high grade tumors with loss of hormone receptor expression and was significantly associated with positive lymph nodes (p=0.025. In PABC patients, PTEN, BCL2 and PDCD4 target protein expression was decreased in 80%, 76% and 40% respectively.Conclusion: Our study supports the involvement of miR-21 in breast cancer progression and metastasis formation in PABC implying a role of this miRNA as a marker for poor prognosis in PABC patients.

  1. Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer.

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    Wang, Xiao-Feng; Zhang, Xiao-Wei; Hua, Rui-Xi; Du, Yi-Qun; Huang, Ming-Zhu; Liu, Yong; Cheng, Yu Fang; Guo, Wei-Jian

    2016-09-27

    Mel-18, a polycomb group protein, has been reported to act as a tumor suppressor and be down-regulated in several human cancers including gastric cancer. It was also found that Mel-18 negatively regulates self-renewal of hematopoietic stem cells and breast cancer stem cells (CSCs). This study aimed to clarify its role in gastric CSCs and explore the mechanisms. We found that low-expression of Mel-18 was correlated with poor prognosis and negatively correlated with overexpression of stem cell markers Oct4, Sox2, and Gli1 in 101 gastric cancer tissues. Mel-18 was down-regulated in cultured spheroid cells, which possess CSCs, and overexpression of Mel-18 inhibits cells sphere-forming ability and tumor growth in vivo. Besides, Mel-18 was lower-expressed in ovary metastatic lesions compared with that in primary lesions of gastric cancer, and Mel-18 overexpression inhibited the migration ability of gastric cancer cells. Interestingly, overexpression of Mel-18 resulted in down-regulation of miR-21 in gastric cancer cells and the expression of Mel-18 was negatively correlated with the expression of miR-21 in gastric cancer tissues. Furthermore, miR-21 overexpression partially restored sphere-forming ability, migration potential and chemo-resistance in Mel-18 overexpressing gastric cancer cells. These results suggests Mel-18 negatively regulates stem cell-like properties through downregulation of miR-21 in gastric cancer cells.

  2. Up/down-regulation of miR-21 changes biological function of colon can-cer cells and sensitivity to cetuximab%上/下调 miR-21对结肠癌细胞的生物学作用及对西妥昔单抗药物敏感性的影响

    Institute of Scientific and Technical Information of China (English)

    巩波; 李东风; 谢子钧; 段伊帆; 李子俊

    2014-01-01

    AIM:To explore the effects of miR-21 on biological behavior of colon cancer cells and their sensi-tivity to epidermal growth factor receptor monoclonal antibody cetuximab .METHODS:Lentiviral vectors were constructed to generate up-and down-regulations of miR-21 lentiviruses (LV-miR-21 and LV-anti-miR-21, respectively), and the cor-responding negative control viruses (LV-miR-21 NC and LV-anti-miR-21 NC, respectively) were also constructed.The vi-ruses were used to infect human colon cancer RKO cells .The changes of the miR-21 expression level , the cell prolifera-tion, the colony-forming ability, the cell apoptosis and the sensitivity of the cells to cetuximab were detected by real -time PCR, MTT assay, soft agar colony assay , flow cytometry and CCK-8 assay.RESULTS: The lentivirus titers of LV-miR-21, LV-miR-2 NC, LV-anti-miR-21 and LV-anti-miR-21 NC were 3.0 ×1012 TU/L, 6.0 ×1011 TU/L, 2.0 ×1012 TU/L and 8.0 ×1011 TU/L, respectively.The infection efficiency was over 80% by the observation of green fluorescence .The miR-21 expression level , the cell proliferation , and the colony-forming ability in LV-miR-21 group were significantly higher than those in LV-anti-miR-21 group.The early apoptotic rate and the inhibitory rate of cetuximab for the cells in LV-anti-miR-21 group were higher than those in LV-miR-21 group.CONCLUSION: miR-21 promotes the proliferation of colon cancer cells.Down-regulation of miR-21 enhances the sensitivity of the colon cancer cells to the targeted therapy drug cetuximab.%目的:探讨miR-21在结肠癌细胞中的生物学功能及对EGFR单抗西妥昔敏感性的影响。方法:通过慢病毒载体的构建及包装生成上调/下调miR-21的慢病毒LV-miR-21和LV-anti-miR-21并感染人结肠癌RKO细胞,采用qRT-PCR、MTT、非锚定依赖性细胞生长、流式细胞术、CCK-8等技术检测上调/下调miR-21后细胞的miR-21表达水平、细胞增殖、克隆形成能力、细胞凋亡能力及对西妥昔单抗

  3. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

    DEFF Research Database (Denmark)

    Winther, Mette; Alsner, Jan; Tramm, Trine

    2015-01-01

    of miR-21 and miR-375 in primary esophageal squamous cell carcinomas (ESCC) and esophagogastric adenocarcinomas (EAC). MATERIAL AND METHODS: Pre-therapeutic tumor specimens from 195 patients with loco-regional esophageal cancer treated with neoadjuvant or definitive chemoradiotherapy or perioperative...

  4. Stromal expression of MiR-21 predicts biochemical failure in prostate cancer patients with Gleason score 6.

    Directory of Open Access Journals (Sweden)

    Christian Melbø-Jørgensen

    Full Text Available microRNAs (miRNAs are involved in various neoplastic diseases, including prostate cancer (PCs. The aim of this study was to investigate the miRNA profile in PC tissue, to assess their association with clinicopathologic data, and to evaluate the potential of miRNAs as diagnostic and prognostic markers.From a cohort of 535 patients submitted to radical prostatectomy (RP, a sample of 30 patients (14 patients with rapid biochemical failure (BF and 16 patients without BF with Gleason score 7 were analyzed. A total of 1435 miRNAs were quantified by microarray hybridization, and selected miRNAs with the highest Standard deviation (n = 50 were validated by real-time quantitative PCR (qRT-PCR. In situ hybridization (ISH was used to evaluate the expression of miR-21.miR-21 was the only miR that was significantly up-regulated in the BF group (p = 0.045 miR-21 was up-regulated in patients with BF compared with non-BF group (p = 0.05. In univariate analyses, high stromal expression of miR-21 had predictive impact on biochemical failure-free survival (BFFS and clinical failure-free survival (CFFS (p = 0.006 and p = 0.04, respectively. In the multivariate analysis, high stromal expression of miR-21 expression was found to be an independent prognostic factor for BFFS in patients with Gleason score 6 (HR 2.41, CI 95% 1.06-5.49, p = 0.037.High stromal expression of miR-21 was associated with poor biochemical recurrence-free survival after RP. For patients with Gleason score 6, miR-21 may help predict the risk of future disease progression and thereby help select patients for potential adjuvant treatment or a more stringent follow-up.

  5. Programmed cell death 4 (PDCD4) is an important functional target of the microRNA miR-21 in breast cancer cells

    DEFF Research Database (Denmark)

    Frankel, Lisa; Christoffersen, Nanna R; Jacobsen, Anders

    2008-01-01

    growth. Using array expression analysis of MCF-7 cells depleted of miR-21, we have identified mRNA targets of mir-21 and have shown a link between miR-21 and the p53 tumor suppressor protein. We furthermore found that the tumor suppressor protein Programmed Cell Death 4 (PDCD4) is regulated by miR-21......MicroRNAs are emerging as important regulators of cancer-related processes. The miR-21 microRNA is overexpressed in a wide variety of cancers and has been causally linked to cellular proliferation, apoptosis, and migration. Inhibition of mir-21 in MCF-7 breast cancer cells causes reduced cell...... and demonstrated that PDCD4 is a functionally important target for miR-21 in breast cancer cells....

  6. Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells.

    Science.gov (United States)

    Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M; Yue, Junming

    2017-01-01

    CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells.

  7. Lentiviral CRISPR/Cas9 vector mediated miR-21 gene editing inhibits the epithelial to mesenchymal transition in ovarian cancer cells

    Science.gov (United States)

    Huo, Wenying; Zhao, Guannan; Yin, Jinggang; Ouyang, Xuan; Wang, Yinan; Yang, Chuanhe; Wang, Baojing; Dong, Peixin; Wang, Zhixiang; Watari, Hidemichi; Chaum, Edward; Pfeffer, Lawrence M.; Yue, Junming

    2017-01-01

    CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats) mediated genome editing is a powerful approach for loss of function studies. Here we report that lentiviral CRISPR/Cas9 vectors are highly efficient in introducing mutations in the precursor miRNA sequence, thus leading to the loss of miRNA expression and function. We constructed four different lentiviral CRISPR/Cas9 vectors that target different regions of the precursor miR-21 sequence and found that these lentiviral CRISPR/Cas9 miR-21 gRNA vectors induced mutations in the precursor sequences as shown by DNA surveyor mutation assay and Sanger sequencing. Two miR-21 lentiviral CRISPR/Cas9 gRNA vectors were selected to probe miR-21 function in ovarian cancer SKOV3 and OVCAR3 cell lines. Our data demonstrate that disruption of pre-miR-21 sequences leads to reduced cell proliferation, migration and invasion. Moreover, CRISPR/Cas9-mediated miR-21 gene editing sensitizes both SKOV3 and OVCAR3 cells to chemotherapeutic drug treatment. Disruption of miR-21 leads to the inhibition of epithelial to mesenchymal transition (EMT) in both SKOV3 and OVCAR3 cells as evidenced by the upregulation of epithelial cell marker E-cadherin and downregulation of mesenchymal marker genes, vimentin and Snai2. The miR-21 target genes PDCD4 and SPRY2 were upregulated in cells transduced with miR-21gRNAs compared to controls. Our study indicates that lentiviral CRISPR/Cas9-mediated miRNA gene editing is an effective approach to address miRNA function, and disruption of miR-21 inhibits EMT in ovarian cancer cells. PMID:28123598

  8. Radiation resistance due to high expression of miR-21 and G2/M checkpoint arrest in breast cancer cells

    Directory of Open Access Journals (Sweden)

    Anastasov Nataša

    2012-12-01

    Full Text Available Abstract Background There is evidence that the extent of the G2/M arrest following irradiation is correlated with tumour cell survival and hence therapeutic success. We studied the regulation of cellular response to radiation treatment by miR-21-mediated modulation of cell cycle progression in breast cancer cells and analysed miR-21 expression in breast cancer tissue samples with long-term follow up. Methods The miR-21 expression levels were quantified (qRT-PCR in a panel of 86 cases of invasive breast carcinomas in relation to metastasis free survival. The cellular radiosensitivity of human breast cancer cells after irradiation was determined comparing two cell lines (T47D and MDA-MB-361 by cell proliferation and colony forming assays. The influence of miR-21 overexpression or downregulation on cell cycle progression and G2/M checkpoint arrest after irradiation was assessed by flow cytometric analysis. Results The expression of miR-21 was transiently increased 8 hours after irradiation in the radioresistant T47D cells and significantly changed with lower extent in radiosensitive MDA-MB-361 cells. Anti-miR-21 treated breast cancer cells failed to exhibit the DNA damage-G2 checkpoint increase after irradiation. Apoptotic activity was significantly enhanced from 7% to 27% in T47D cells and from 18% to 30% in MDA-MB-361 cells 24 hours after 5 Gy irradiation. Additionally, we characterized expression of miR-21 in invasive breast carcinomas. In comparison to non-cancerous adjacent breast tissue, tumours samples had increased miR-21 expression that inversely correlated with the distant metastases-free survival of patients (p = 0.029. Conclusions Our data indicate that miR-21 expression in breast cancer cells contributes to radiation resistance by compromising cell cycle progression. These data point to the potential of combining radiotherapy with an anti-miR-21 as a potent G2/M check point inhibitor in overcoming radiation resistance of tumours.

  9. Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN.

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    Mingli Han

    Full Text Available BACKGROUND: Accumulating evidence suggested that epithelial-mesenchymal transition (EMT and cancer stem cell (CSC characteristics, both of which contribute to tumor invasion and metastasis, are interrelated with miR-21. MiR-21 is one of the important microRNAs associated with tumor progression and metastasis, but the molecular mechanisms underlying EMT and CSC phenotype during miR-21 contributes to migration and invasion of breast cancer cells remain to be elucidated. METHODOLOGY/PRINCIPAL FINDINGS: In this study, MDA-MB-231/anti-miR-21 cells were established by transfected hsa-miR-21 antagomir into breast cancer MDA-MB-231 cells. EMT was evaluated by the changes of mesenchymal cell markers (N-cadherin, Vimentin, and alpha-SMA, epithelial cell marker (E-cadherin, as well as capacities of cell migration and invasion; CSC phenotype was measured using the changes of CSC surface markers (ALDH1 and CD44, and the capacity of sphereforming (mammospheres. We found that antagonism of miR-21 reversed EMT and CSC phenotype, accompanied with PTEN up-regulation and AKT/ERK1/2 inactivation. Interestingly, down-regulation of PTEN by siPTEN suppressed the effects of miR-21 antagomir on EMT and CSC phenotype, confirming that PTEN is a target of miR-21 in reversing EMT and CSC phenotype. The inhibitors of PI3K-AKT and ERK1/2 pathways, LY294002 and U0126, both significantly suppressed EMT and CSC phenotype, indicating that AKT and ERK1/2 pathways are required for miR-21 mediating EMT and CSC phenotype. CONCLUSIONS/SIGNIFICANCE: In conclusion, our results demonstrated that antagonism of miR-21 reverses EMT and CSC phenotype through targeting PTEN, via inactivation of AKT and ERK1/2 pathways, and showed a novel mechanism of which might relieve the malignant biological behaviors of breast cancer.

  10. miR-21, miR-221 and miR-222 expression and prostate cancer recurrence among obese and non-obese cases

    Institute of Scientific and Technical Information of China (English)

    Ernest K Amankwah; Evelyn Anegbe; Hyun Park; Julio Pow-Sang; Ardeshir Hakam; Jong Y Park

    2013-01-01

    Recent evidence shows that certain microRNAs (miRNAs) play a role in both obesity and prostate cancer recurrence,but the association between the expression of these miRNAs and obesity in prostate cancer recurrence is unknown.In this study,we examined the effect of the interaction between obesity and miR-21,miR-221 or miR-222 expression on prostate cancer recurrence among 28 recurrent and 37 non-recurrent prostate cancer cases,miRNA expression was determined using quantitative real-time polymerase chain reaction.Cox proportional hazard models adjusting for age at diagnosis,clinical stage and Gleason score were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for recurrence free survival.A significantly (P=0.014) higher proportion of recurrent cases (78.6%) than non-recurrent cases (48.6%) had a low expression of miR-21 and the difference was more prominent in obese than non-obese patients.Multivariate analysis showed that the expression of miR-21 was an independent risk factor for recurrence in obese (HR=6.15,95% CI=1.04-36.48,P=0.045),but not in non-obese (HR=1.28,95% CI=0.30-5.49,P=0.74) cases.A significant association with recurrence was not observed for the expression of miR-221 and miR-222.In summary,our findings show that miR-21 is associated with prostate cancer recurrence after radical prostatectomy and suggest that the differential expression of miR-21 is more prominent in obese than in non-obese cases.Future larger studies are warranted to confirm these initial findings and to elucidate the mechanisms involved.

  11. The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer

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    Xiangyan Liu

    2015-01-01

    Full Text Available Upregulation of miR-21 (microRNA-21 and downregulation of miR-34b/c have been found in breast cancer (BC. However, their regulation mechanism and function roles in BC have not been fully addressed. Here, we report that miR-21 levels were inversely correlated with miR-34b/c levels in BC. MiR-21 upregulation contributes to PTEN downregulation, which is beneficial for the activation of PI3K/AKT signaling. The activation of AKT phosphorylates FOXO3a, triggering relocalization of FOXO3a proteins from the nucleus to the cytoplasm. FOXO3a is a newly identified transcription factor responsible for miR-34b/c expression. Downregulation of nuclear FOXO3a decreased the expression levels of miR-34b and miR-34c in breast cancer cells, in which p53 was mutated. We also found upregulation of circulating miR-21 and downregulation of circulating miR-34b/c in BC patients’ serum. More importantly, we showed that systemic delivery of miR-34b/c or with anti-miR-21 significantly inhibited breast tumor growth in vivo. These results suggest that high circulating levels of miR-21 and low levels of miR-34b/c may provide potential biomarkers for BC diagnosis, and systemic delivery of miR-34b/c has potential as a therapeutic option for BC treatment.

  12. Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status

    DEFF Research Database (Denmark)

    Rask, Lene; Balslev, Eva; Søkilde, Rolf;

    2014-01-01

    PURPOSE: Therapeutic decisions in breast cancer are increasingly guided by prognostic and predictive biomarkers. Non-protein-coding microRNAs (miRNAs) have recently been found to be deregulated in breast cancers and, in addition, to be correlated with several clinico-pathological features. One...... of the most consistently up-regulated miRNAs is miR-21. Here, we specifically searched for differentially expressed miRNAs in high-risk breast cancer patients as compared to low-risk breast cancer patients. In the same patients, we also compared miR-21 expression with the expression of its presumed target...... PTEN. METHODS: Both microarray and RT-qPCR techniques were used to assess miRNA expression levels in lymph node-positive and -negative human invasive ductal carcinoma tissues. Simultaneously, PTEN protein expression levels were assessed using immunohistochemistry. RESULTS: miR-486-5p and miR-139-5p...

  13. A novel panel of serum miR-21/miR-155/miR-365 as a potential diagnostic biomarker for breast cancer

    Science.gov (United States)

    Han, Ji-Guang; Jiang, Yong-Dong; Zhang, Chun-Hui; Yang, Yan-Mei; Pang, Da; Song, Yan-Ni

    2017-01-01

    Purpose Insufficient sensitivity and specificity prevent the use of most existing biomarkers for early detection of breast cancer. Recently, it was reported that serum microRNAs (miRNAs) may be potential biomarkers in many cancer diseases. In this study, we investigated whether serum levels of 5 miRNAs including miR-21, miR-125b, miR-145, miR-155, and miR-365 could discriminate breast cancer patients and healthy controls. Methods Serum levels of miRNAs were measured by using quantitative real-time polymerase chain reaction in 99 breast cancer patients and 21 healthy controls. The abundance change of serum miRNAs were also evaluated following surgical resection in 20 breast cancer patients. Receiver operating characteristic (ROC) curve analysis was performed to assess the sensitivity and specificity of miRNAs as diagnostic biomarkers. Results Serum levels of miR-21 and miR-155 was significantly higher, while miR-365 was significantly lower in breast cancer as compared with healthy controls. The serum levels of miR-21 and miR-155 significantly decreased following surgical resection. Additionally, the serum level of miR-155 at stages I and II was significantly higher compared to stage III. The serum miR-145 level was remarkably higher in progesterone receptor (PR)-positive patients than PR-negative. The positivity of miR-21, miR-155, and miR-365 was high compared to CA 153 and CEA in breast cancer. ROC curve analyses of a combination of miR-21, miR-155, and miR-365 yielded much higher area under curve and enhanced sensitivity and specificity in comparison to each miRNA alone. Conclusion The combination of serum miR-21/miR-155/miR-365 may potentially serve as a sensitive and specific biomarker that enables differentiation of breast cancer from healthy controls. PMID:28203552

  14. Role of Kallistatin Treatment in Aging and Cancer by Modulating miR-34a and miR-21 Expression

    Directory of Open Access Journals (Sweden)

    Julie Chao

    2017-01-01

    Full Text Available Kallistatin is an endogenous protein that regulates differential signaling pathways and a wide spectrum of biological activities via its two structural elements: an active site and a heparin-binding domain. Kallistatin via its heparin-binding site inhibits vascular inflammation and oxidative stress by antagonizing TNF-α-induced NADPH oxidase activity, NF-κB activation, and inflammatory gene expression in endothelial cells. Moreover, kallistatin via its active site inhibits microRNA-34a (miR-34a synthesis and stimulates eNOS and SIRT1 expression in endothelial progenitor cells, whereas its heparin-binding site is crucial for blocking TNF-α-induced miR-21 expression and oxidative stress, thus reducing cellular senescence. By downregulating miR-34a and miR-21 expression, kallistatin treatment attenuates oxidative damage and aortic senescence in streptozotocin-induced diabetic mice and extends Caenorhabditis elegans lifespan under stress conditions. Likewise, kallistatin through the heparin-binding site inhibits TGF-β-induced miR-21 synthesis and oxidative stress in endothelial cells, resulting in inhibition of endothelial-mesenchymal transition, a process contributing to fibrosis and cancer. Furthermore, kallistatin’s active site is essential for stimulating miR-34a and p53 expression and inhibiting the miR-21-Akt-Bcl-2 signaling pathway, thus inducing apoptosis in breast cancer cells. These findings reveal novel mechanisms of kallistatin in protection against senescence, aging, and cancer development by modulating miR-34a and miR-21 levels and inhibiting oxidative stress.

  15. miR-21、miR-155在乳腺癌患者血液与肿瘤组织中表达水平的相关性研究%Correlation study of the expression of miR-21 and miR-155 in the blood and tumor tissue of patients with breast cancer

    Institute of Scientific and Technical Information of China (English)

    卞国奉; 陈爱军

    2012-01-01

    目的 对健康女性血清及乳腺癌患者血清中miR-21和miR-155表达水平进行实时定量PCR检测,同肿瘤患者癌组织与对应癌旁组织的miR-21和miR-155表达水平的变化趋势相比较,以评价血清中miR-21和miR-155在乳腺癌早期诊断中的潜在价值.方法 收集健康女性血液和患者血液与患者癌组织和癌旁组织,利用实时荧光定量PCR对提取的RNA miR-21和miR-155进行相对定量检测,得到miR-21和miR-155在血清中变化趋势与在组织中变化趋势的相关性.结果 miR-21和miR-155在肿瘤组织的表达水平明显高于其在癌旁组织的表达水平,miR-21和miR-155在乳腺癌患者血清中的表达水平也要高于其在健康体检者血清中的表达水平.血清中miR-21和miR-155表达水平变化趋势与组织中miR-21和miR-155表达水平变化趋势一致.结论 血清中miR-21和miR-155能反映乳腺癌的发生,miR-21和miR-155有可能作为乳腺癌早期诊断的肿瘤标志物.%Objective To evaluate the expression levels of miR-21 and miR-155 in the serum of breast cancer patients and healthy women by real-time quantitative PCR, compared with the variation trend of the expression level of miR-21 and miR-155 in tumor tissue samples. Methods The samples were collected from the intraoperative tumor tissue, adjacent tissue, and the peripheral blood of patients and from the peripheral blood of healthy women. The miR-21 and miR-155 obtained were detected by real time quantitative PCR. Then the relationship between the trend of miR-21 and miR-155 in serum and in tumor tissues was analyzed. Results The expression levels of miR-21 and miR-155 in adjacent tissues of breast cancer patients were significantly lower than those in tumor tissues. The expression levels of miR-21 and miR-155 in the serum of breast cancer patients were significantly higher than those of healthy women. Conclusion The levels of serum miR-21 and miR-155 can be used as biomarkers for the early

  16. Value of combined detection of serum miR-21,miR-195 and miR-222 in the diagnosis of early breast cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Zhao Zhang; Ying Li; De-Xiang Wu

    2016-01-01

    Objective:To study level of miRNA in the serum of early breast carcinoma patients and to evaluate the clinical diagnostic value of combined detection of early breast carcinoma. Methods:A total of 54 cases of early breast carcinoma, 58 cases of benign breast diseases and 70 cases of healthy physical examination women were selected as the research subjects, to analysis serum miR-21, miR-195 and miR-222 levels by fluorescence quantitative PCR method and to analyze the diagnostic value of single and combined detection in early breast cancer by receiver operating characteristic curve. Results:The relative expression levels of miR-21, miR-222 and miR-195 in early breast carcinoma patients were significantly higher than those in benign breast disease and healthy controls;there was no significant difference in the relative expression of miR-21, miR-222 and miR-195 in the benign breast disease group and healthy control group;receiver operating characteristic curve analysis showed that AUC of miR-21, miR-195 and miR-222 in the diagnosis of early breast carcinoma were 0.805, 0.86 and 0.848 respectively, the sensitivity were 63.3%, 70.0%and 70.0%, and the specificity were 86.7%, 93.3%and 90.0%;AUC, sensitivity and specificity of the combined detection were 0.974, 93.3%and 96.7%respectively. Conclusion:miR-21, miR-195 and miR-222 levels in serum of patients with early breast carcinoma rise, the combined detection of the 3 indicators have a high diagnostic value for early breast carcinoma, and contribute to early breast carcinoma screening and diagnosis.

  17. Hypoxia-induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment.

    Directory of Open Access Journals (Sweden)

    Bin Bao

    Full Text Available Hypoxia is known to play critical roles in cell survival, angiogenesis, tumor invasion, and metastasis. Hypoxia mediated over-expression of hypoxia-inducible factor (HIF has been shown to be associated with therapeutic resistance, and contributes to poor prognosis of cancer patients. Emerging evidence suggest that hypoxia and HIF pathways contributes to the acquisition of epithelial-to-mesenchymal transition (EMT, maintenance of cancer stem cell (CSC functions, and also maintains the vicious cycle of inflammation-all which lead to therapeutic resistance. However, the precise molecular mechanism(s by which hypoxia/HIF drives these events are not fully understood. Here, we show, for the first time, that hypoxia leads to increased expression of VEGF, IL-6, and CSC signature genes Nanog, Oct4 and EZH2 consistent with increased cell migration/invasion and angiogenesis, and the formation of pancreatospheres, concomitant with increased expression of miR-21 and miR-210 in human pancreatic cancer (PC cells. The treatment of PC cells with CDF, a novel synthetic compound inhibited the production of VEGF and IL-6, and down-regulated the expression of Nanog, Oct4, EZH2 mRNAs, as well as miR-21 and miR-210 under hypoxia. CDF also led to decreased cell migration/invasion, angiogenesis, and formation of pancreatospheres under hypoxia. Moreover, CDF decreased gene expression of miR-21, miR-210, IL-6, HIF-1α, VEGF, and CSC signatures in vivo in a mouse orthotopic model of human PC. Collectively, these results suggest that the anti-tumor activity of CDF is in part mediated through deregulation of tumor hypoxic pathways, and thus CDF could become a novel, and effective anti-tumor agent for PC therapy.

  18. Detection of expression of miR-21 in serum of cervical cancer patients by SYBR green Ⅰ fluorescence quantitative PCR%SYBR GreenⅠ荧光定量PCR检测宫颈癌血清中miR-21的表达

    Institute of Scientific and Technical Information of China (English)

    陈文璟; 温旺荣

    2011-01-01

    Objective To establish a method of SYBR green I real-time fluorescence quantitative PCR ( FQ-PCR) for the determina tion of the expression levels of miR-21 in serum, and evaluate the significance of miR-21 in clinical monitoring of cervical diseases. Methods According to the sequence of miR-21 and U6, reverse-transcriptional primer for the stem-loop and the primers for Teal-time PCR were designed and synthesized. The expression levels of miR-21 in serum from 32 different cervical disease patients were deter mined and U6 was used as control. Results The experimental results of SYBR Green I FQ-PCR with stem-loop RT primer were highly specific. The melting curve of miR-21 in serum showed a single peak, and the product of PCR was specific. High expression levels of miR-21 were detectable in the sera of cervical cancer patients, compared with those of uterine fibroid patients. The levels of miR-21 of cervical cancer patients obviously decreased after surgical resection ( P < 0.05). The difference showed a statistical significance. Con clusion The method of SYBR Green I FQ-PCR with stem-loop RT primer is rapid, sensitive and specific to detect miR-21, which should be a promising early diagnostic approach for cervical cancer, and also its molecular staging and prognostic evaluation.%目的 建立SYBR Green Ⅰ实时荧光定量PCR法检测宫颈疾病患者血清中miR-21的表达水平,探讨miR-21在宫颈癌临床监测中的意义.方法 设计miR-21、U6茎环逆转录引物和PCR扩增引物,以U6为内参,用实时荧光定量PCR检测32例不同宫颈疾病患者血清中miR-21表达水平.结果 建立的实时荧光定量PCR法能特异地检测血清中的miR-21扩增信号,熔解曲线单一,产物特异.宫颈癌患者血清中miR-21水平明显高于子宫肌瘤、宫颈炎等其他良性宫颈疾病(P<0.05),而宫颈癌患者手术切除后血清中miR-21水平明显下降(P<0.05).结论 SYBR Green Ⅰ实时荧光定量PCR是一种快速简便、敏感

  19. Inhibition of breast cancer cell motility with a non-cyclooxygenase inhibitory derivative of sulindac by suppressing TGFβ/miR-21 signaling.

    Science.gov (United States)

    Yi, Bin; Chang, Hong; Ma, Ruixia; Feng, Xiangling; Li, Wei; Piazza, Gary A; Xi, Yaguang

    2016-02-16

    Compelling efficacy on intervention of tumorigenesis by nonsteroidal anti-inflammatory drugs (NSAIDs) has been documented intensively. However, the toxicities related to cyclooxygenase (COX) inhibition resulting in suppression of physiologically important prostaglandins limit their clinical use for human cancer chemoprevention. A novel derivative of the NSAID sulindac sulfide (SS), referred as sulindac sulfide amide (SSA), was recently developed, which lacks COX inhibitory activity, yet shows greater suppressive effect than SS on growth of various cancer cells. In this study, we focus on the inhibitory activity of SSA on breast tumor cell motility, which has not been studied previously. Our results show that SSA treatment at non-cytotoxic concentrations can specifically reduce breast tumor cell motility without influencing tumor cell growth, and the mechanism of action involves the suppression of TGFβ signaling by directly blocking Smad2/3 phosphorylation. Moreover, miR-21, a well-documented oncogenic miRNA for promoting tumor cell metastasis, was also found to be involved in inhibitory activity of SSA in breast tumor cell motility through the modulation of TGFβ pathway. In conclusion, we demonstrate that a non-COX inhibitory derivative of sulindac can inhibit breast tumor metastasis by a mechanism involving the TGFβ/miR-21 signaling axis.

  20. PIK3R1 targeting by miR-21 suppresses tumor cell migration and invasion by reducing PI3K/AKT signaling and reversing EMT, and predicts clinical outcome of breast cancer.

    Science.gov (United States)

    Yan, Li-Xu; Liu, Yan-Hui; Xiang, Jian-Wen; Wu, Qi-Nian; Xu, Lei-Bo; Luo, Xin-Lan; Zhu, Xiao-Lan; Liu, Chao; Xu, Fang-Ping; Luo, Dong-Lan; Mei, Ping; Xu, Jie; Zhang, Ke-Ping; Chen, Jie

    2016-02-01

    We have previously shown that dysregulation of miR-21 functioned as an oncomiR in breast cancer. The aim of the present study was to elucidate the mechanisms by which miR-21 regulate breast tumor migration and invasion. We applied pathway analysis on genome microarray data and target-predicting algorithms for miR-21 target screening, and used luciferase reporting assay to confirm the direct target. Thereafter, we investigated the function of the target gene phosphoinositide-3-kinase, regulatory subunit 1 (α) (PIK3R1), and detected PIK3R1 coding protein (p85α) by immunohistochemistry and miR-21 by RT-qPCR on 320 archival paraffin-embedded tissues of breast cancer to evaluate the correlation of their expression with prognosis. First, we found that PIK3R1 suppressed growth, invasiveness, and metastatic properties of breast cancer cells. Next, we identified the PIK3R1 as a direct target of miR-21 and showed that it was negatively regulated by miR-21. Furthermore, we demonstrated that p85α overexpression phenocopied the suppression effects of antimiR-21 on breast cancer cell growth, migration and invasion, indicating its tumor suppressor role in breast cancer. On the contrary, PIK3R1 knockdown abrogated antimiR‑21-induced effect on breast cancer cells. Notably, antimiR-21 induction increased p85α, accompanied by decreased p-AKT level. Besides, antimiR-21/PIK3R1-induced suppression of invasiveness in breast cancer cells was mediated by reversing epithelial-mesenchymal transition (EMT). p85α downregulation was found in 25 (7.8%) of the 320 breast cancer patients, and was associated with inferior 5-year disease-free survival (DFS) and overall survival (OS). Taken together, we provide novel evidence that miR-21 knockdown suppresses cell growth, migration and invasion partly by inhibiting PI3K/AKT activation via direct targeting PIK3R1 and reversing EMT in breast cancer. p85α downregulation defined a specific subgroup of breast cancer with shorter 5-year DFS and OS

  1. Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin.

    Directory of Open Access Journals (Sweden)

    Jingting Jiang

    Full Text Available The goal of this study is to evaluate the effectiveness of S-1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as potential prognostic biomarkers in gastric cancer patients. The expression of candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE specimens.Gastric cancer patients with KPS>70 were recruited for the trial. The control group was treated with 400 mg/twice/day Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m(2/first day/4 week cycle. The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v. with Oxaliplatin at 130 mg/m(2/first day/4 week cycle. Total RNAs were extracted from normal and gastric tumor specimens. The levels of miRNAs were quantified using real time qRT-PCR expression analysis.The overall objective response rate (CR+PR of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR vs. 17.6% (CR+PR with Doxifluridine/Oxaliplatin for advanced stage gastric cancer patients. The average overall survival for patients treated with S-1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022 and miR-21 (P = 0.0029 was significantly overexpressed in gastric tumors compared to normal gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR-21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004 and miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018 are closely associated with better patient's overall survival for both S-1 and Doxifluridine based regimens.Patients treated with S-1/Oxaliplatin had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21 and miR-181b hold great potential as prognostic biomarkers in late stage gastric cancer.

  2. miR-21和miR-93联合检测在三阴性乳腺癌诊断中的价值%Significance of miR-21 and miR-93 combined detection in the diagnosis of triple negative breast cancer

    Institute of Scientific and Technical Information of China (English)

    傅少梅; 殷初阳; 宋晖

    2014-01-01

    目的:探讨miR-21和miR-93联合检测在三阴性乳腺癌( TNBC)中的表达情况及与临床病理特征的关系。方法选取行乳腺癌根治的TNBC患者33例,选取同期正常乳腺组织15例。采用RT-PCR方法检测miR-21和miR-93在TNBC组织和正常乳腺组织中的相对表达量。结果 miR-21和miR-93在TNBC组织中的相对表达量分别为0.874±0.124和0.764±0.163,而在正常乳腺组织的表达量分别为0.235±0.034和0.183±0.028,TNBC组织中的miR-21和miR-93表达量明显高于正常乳腺组织(P均<0.01)。miR-21和miR-93基因的高表达与年龄、月经状态无明显相关性,而与肿瘤直径、临床分期和淋巴结转移具有明显的相关性(P<0.05或0.01)。组织中miR-21和miR-93的高表达呈正相关(r=0.732,P<0.01)。结论 miR-21和miR-93参与了TNBC的发生、发展和转移,是重要分子标记物。%Objective It is to observe the expression of miR -21 and miR-93 in triple negative breast cancer ( TNBC) and their relationship with clinicopathological features .Methods 33 patients with TNBC treated with radical mastectomy and 15 cases with normal breast tissue were selected .The relative expression levels of miR-21 and miR-93 were detected by RT-PCR in TNBC tissue and normal breast tissue .Results The relative gene expression of miR -21 and miR-93 in TNBC tissue were 0.874 ±0.124 and 0.764 ±0.163 respectively, while were 0.235 ±0.034 and 0.183 ±0.028 respectively in normal breast tissue , the expression of miR-21 and miR-93 in TNBC were significantly higher than that in normal breast tissue ( P<0.01).The high expressions of miR -21 and miR-93 were not related to age and menstrual status , but obviously related with the tumor size, clinical stage, lymph node metastasis(P<0.05 or 0.01).The high expression of miR -21 in TNBC was positively correlated to the expression of miR -93 (r=0.732, P<0.01).Conclusion The gene of miR-21 and miR-93

  3. The role of TGF-β1–miR-21–ROS pathway in bystander responses induced by irradiated non-small-cell lung cancer cells

    Science.gov (United States)

    Jiang, Y; Chen, X; Tian, W; Yin, X; Wang, J; Yang, H

    2014-01-01

    Background: Many studies have indicated an important implication of radiation-induced bystander effects (RIBEs) in cancer radiotherapy, but the detailed signalling remains unclear. Methods: The roles of tumour growth factor-beta1 (TGF-β1) and miR-21 in medium-mediated RIBEs in H1299 non-small-cell lung cancer cells were investigated using DNA damage, changes in proliferation and levels of reactive oxygen species (ROS) as end points. SB431542, a specific inhibitor of TGF-β type 1 receptor kinases, was used to inhibit TGF-β1 pathways in irradiated and bystander cells. Exogenous miR-21 regulation was achieved through inhibitor or mimic transfection. Results: Compared with relative sham-radiation-conditioned medium, radiation-conditioned medium (RCM) from irradiated cells 1 h post radiation (1-h RCM) caused an increase in ROS levels and DNA damage in bystander cells, while 18-h RCM induced cell cycle delay and proliferation inhibition. All these effects were eliminated by TGF-βR1 inhibition. One-hour RCM upregulated miR-21 expression in bystander cells, and miR-21 inhibitor abolished bystander oxidative stress and DNA damage. Eighteen-hour RCM downregulated miR-21 of bystander cells, and miR-21 mimic eliminated bystander proliferation inhibition. Furthermore, the dysregulation of miR-21 was attenuated by TGF-βR1 inhibition. Conclusions: The TGF-β1–miR-21–ROS pathway of bystander cells has an important mediating role in RIBEs in H1299 cells. PMID:24992582

  4. Turning 21: Induction of miR-21 as a key switch in the inflammatory response

    Directory of Open Access Journals (Sweden)

    Frederick J Sheedy

    2015-01-01

    Full Text Available miR-21 is one of the most highly expressed members of the small non-coding microRNA family in many mammalian cell types. Its expression is further enhanced in many diseased states including solid tumors, cardiac injury and inflamed tissue. Whilst the induction of miR-21 by inflammatory stimuli cells has been well documented in both hematopoietic cells of the immune system (particularly monocytes/macrophages but also dendritic and T-cells and non-hematopoietic tumorigenic cells, the exact functional outcome of this elevated miR-21 is less obvious. Recent studies have confirmed a key role for miR-21 in the resolution of inflammation and in negatively regulating the proinflammatory response induced by many of the same stimuli that trigger miR-21 induction itself. In particular, miR-21 has emerged as a key mediator of the anti-inflammatory response in macrophages. This suggests that miR-21 inhibition in leukocytes will promote inflammation and may enhance current therapies for defective immune responses such as cancer, mycobacterial vaccines or Th2-associated allergic inflammation. At the same time, miR-21 has been shown to promote inflammatory mediators in non-hematopoietic cells resulting in neoplastic transformation. This review will focus on functional studies of miR-21 during inflammation which are complicated by the numerous molecular targets and processes that have emerged as miR-21 sensitive. It may be that the exact functional outcome of miR-21 is determined by multiple features including the cell type affected, the inducing signal, the transcriptomic profile of the cell, which ultimately affect the availability and ability to engage different target mRNAs and bring about its unique responses. Reviewing this data may illustrate that RNA-based oligonucleotide therapies for different diseases based upon miR-21 may have to target the unique and operative miRNA:mRNA interactions functionally active disease.

  5. Photodynamic Therapy for Cancer

    Science.gov (United States)

    ... References Dolmans DE, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003; 3(5):380–387. [PubMed Abstract] Wilson BC. Photodynamic therapy for cancer: principles. Canadian Journal of Gastroenterology 2002; ...

  6. Folate status, folate-related genes and serum miR-21 expression: Implications for miR-21 as a biomarker

    Directory of Open Access Journals (Sweden)

    Emma Louise Beckett

    2015-12-01

    General significance: This study demonstrates that serum miR-21 expression correlates with folate status and related genetic status. This may have consequences for the proposed use of miR-21 as a colorectal cancer biomarker.

  7. Photodynamic therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000906.htm Photodynamic therapy for cancer To use the sharing features on ... type of light to kill cancer cells. How Photodynamic Therapy Works First, the doctors injects a medicine that ...

  8. Laser therapy for cancer

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000905.htm Laser therapy for cancer To use the sharing features ... Lasers are also used on the skin. How Laser Therapy is Used Laser therapy can be used ...

  9. miR-21 and miR-155 in the regulation of TGF-β1/SMAD signaling pathway of the line breast cancer cells with different metastatic potential

    Directory of Open Access Journals (Sweden)

    Z. N. Nikiphorova

    2015-01-01

    Full Text Available Breast cancer (ВС is the most common form of cancer, leading to high mortality rates among women worldwide. Metastasis is the main cause of fatal outcomes in ВС. In this regard, of particular interest takes the study of molecular mechanisms of epithelial-mesenchymal transition (EMT. In the EMT processes involved in TGF-β1/SMAD-signaling pathway through the regulation of which can affect the processes of metastasis in ВС. In this study we have analyzed changes of mRNA expression of the mRNA SMADs, miR-21, and miR-155 of the tumor ВС cells with different metastatic potential MCF-7, BT-474, ZR-75-1. High expression of miR-21 was detected in all the tumor cell lines (MCF-7, ZR-75-1 and BT-474. In the ВС cell lines, the expression level of miR-155 was significantly lower than that of miR-21. Analysis of mRNA expression has clearly shown impairments of intracellular mechanisms of regulation of SMAD2, SMAD4, SMAD7 in ВС. Investigated the correlation of expression of miR-21 and miR-155 regulation of SMADs in TGF-β1/SMAD signaling pathway in three carcinomas lines of the human breast with different metastatic potential (MCF-7, ZR-75-1, BT-474. A significant inverse correlation was observed between SMAD4 and miR-155 in MCF-7 cells. Inverse correlation between the expression of SMAD2, SMAD4, SMAD7 and miR-155; miR21 was found in the BT-474 cells. The results obtained in this study showed that miR-21 and miR-155 regulate activity of several genes SMAD2, SMAD4, SMAD7 in the tumor cell ZR-75-1 and on some genes they exhibited a cumulative effect. It should be noted that the miR-155 and miR-21 in various degrees influenced the expression of SMAD2, SMAD4, SMAD7, blocking the work of these genes and, thereby exacerbating the progression and degree of malignancy of ВС cells human; in some cases their effects on individual genes were cumulative. 

  10. Biologic Therapy (Immunotherapy) for Kidney Cancer

    Science.gov (United States)

    ... Stage for Kidney Cancer Kidney Cancer Treating Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer The goal of biologic therapy ... Therapy for Kidney Cancer Targeted Therapies for Kidney Cancer Biologic Therapy (Immunotherapy) for Kidney Cancer Chemotherapy for Kidney Cancer Pain ...

  11. Radiation Therapy for Testicular Cancer

    Science.gov (United States)

    ... Testicular Cancer Treating Testicular Cancer Radiation Therapy for Testicular Cancer Radiation therapy uses a beam of high-energy ... Testicular Cancer, by Type and Stage More In Testicular Cancer About Testicular Cancer Causes, Risk Factors, and Prevention ...

  12. Targeted Knock-Down of miR21 Primary Transcripts Using snoMEN Vectors Induces Apoptosis in Human Cancer Cell Lines.

    Directory of Open Access Journals (Sweden)

    Motoharu Ono

    Full Text Available We have previously reported an antisense technology, 'snoMEN vectors', for targeted knock-down of protein coding mRNAs using human snoRNAs manipulated to contain short regions of sequence complementarity with the mRNA target. Here we characterise the use of snoMEN vectors to target the knock-down of micro RNA primary transcripts. We document the specific knock-down of miR21 in HeLa cells using plasmid vectors expressing miR21-targeted snoMEN RNAs and show this induces apoptosis. Knock-down is dependent on the presence of complementary sequences in the snoMEN vector and the induction of apoptosis can be suppressed by over-expression of miR21. Furthermore, we have also developed lentiviral vectors for delivery of snoMEN RNAs and show this increases the efficiency of vector transduction in many human cell lines that are difficult to transfect with plasmid vectors. Transduction of lentiviral vectors expressing snoMEN targeted to pri-miR21 induces apoptosis in human lung adenocarcinoma cells, which express high levels of miR21, but not in human primary cells. We show that snoMEN-mediated suppression of miRNA expression is prevented by siRNA knock-down of Ago2, but not by knock-down of Ago1 or Upf1. snoMEN RNAs colocalise with Ago2 in cell nuclei and nucleoli and can be co-immunoprecipitated from nuclear extracts by antibodies specific for Ago2.

  13. STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer.

    Science.gov (United States)

    Iliopoulos, Dimitrios; Jaeger, Savina A; Hirsch, Heather A; Bulyk, Martha L; Struhl, Kevin

    2010-08-27

    A transient inflammatory signal can initiate an epigenetic switch from nontransformed to cancer cells via a positive feedback loop involving NF-kappaB, Lin28, let-7, and IL-6. We identify differentially regulated microRNAs important for this switch and putative transcription factor binding sites in their promoters. STAT3, a transcription factor activated by IL-6, directly activates miR-21 and miR-181b-1. Remarkably, transient expression of either microRNA induces the epigenetic switch. MiR-21 and miR-181b-1, respectively, inhibit PTEN and CYLD tumor suppressors, leading to increased NF-kappaB activity required to maintain the transformed state. These STAT3-mediated regulatory circuits are required for the transformed state in diverse cell lines and tumor growth in xenografts, and their transcriptional signatures are observed in colon adenocarcinomas. Thus, STAT3 is not only a downstream target of IL-6 but, with miR-21, miR-181b-1, PTEN, and CYLD, is part of the positive feedback loop that underlies the epigenetic switch that links inflammation to cancer.

  14. PSMB4 promotes multiple myeloma cell growth by activating NF-κB-miR-21 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Peihao; Guo, Honggang [Department of Hematology, Navy General Hospital, Beijing 100048 (China); Li, Guangchao [School of Bioscience and Bioengineering, South China University of Technology, Guangzhou 510006 (China); Han, Siqi [Department of Medical Oncology, Jinling Hospital, Nanjing 210002 (China); Luo, Fei [Department of Stomatology, Jinling Hospital, Nanjing 210002 (China); Liu, Yi, E-mail: liuyi2033@163.com [Department of Hematology, Navy General Hospital, Beijing 100048 (China)

    2015-03-06

    Proteasomal subunit PSMB4, was recently identified as potential cancer driver genes in several tumors. However, the regulatory mechanism of PSMB4 on carcinogenesis process remains unclear. In this study, we investigated the expression and roles of PSMB4 in multiple myeloma (MM). We found a significant up-regulation of PSMB4 in MM plasma and cell lines. Ectopic overexpression of PSMB4 promoted cell growth and colony forming ability of MM cells, whereas inhibition of PSMB4 led to a decrease of such events. Furthermore, our results demonstrated the up-regulation of miR-21 and a positive correlation between the levels of miR-21 and PSMB4 in MM. Re-expression of miR-21 markedly rescued PSMB4 knockdown-mediated suppression of cell proliferation and clone-formation. Additionally, while enforced expression of PSMB4 profoundly increased NF-κB activity and the level of miR-21, PSMB4 knockdown or NF-κB inhibition suppressed miR-21 expression in MM cells. Taken together, our results demonstrated that PSMB4 regulated MM cell growth in part by activating NF-κB-miR-21 signaling, which may represent promising targets for novel specific therapies. - Highlights: • First reported upregulation of PSMB4 in MM plasma and cell lines. • PSMB4 promoted MM cell growth and colony forming ability. • Further found miR-21 was up-regulated by PSMB4 in MM plasma and cell lines. • PSMB4-induced miR-21 expression was modulated by NF-κB. • PSMB4-NF-κB-miR-21 axis may be potential therapeutic targets of MM.

  15. Advances in Cancer Therapy

    OpenAIRE

    Jordan BF, Sonveaux P

    2011-01-01

    The book "Advances in Cancer Therapy" is a new addition to the Intech collection of books and aims at providing scientists and clinicians with a comprehensive overview of the state of current knowledge and latest research findings in the area of cancer therapy. For this purpose research articles, clinical investigations and review papers that are thought to improve the readers' understanding of cancer therapy developments and/or to keep them up to date with the most recent advances in this fi...

  16. Differential Expression of miR-21, miR-126, miR-143, miR-373 in Normal Cervical Tissue, Cervical Cancer Tissue and Hela Cell%miR-21、miR-126、miR-143和miR-373在正常宫颈组织、宫颈癌组织及Hela细胞中的表达差异

    Institute of Scientific and Technical Information of China (English)

    刘琳; 王月玲; 王江芬

    2012-01-01

    目的 研究miR-21、miR-126、miR-143和miR-373在正常宫颈组织、宫颈癌组织及Hela细胞中的表达差异,探讨microRNAs(miRNAs)对宫颈癌发生的调控作用.方法 荧光实时定量检测20例良性肿瘤患者的正常宫颈组织,20例宫颈癌组织及Hela细胞中miR-21、miR-126、miR-143和miR-373的表达.结果 m iR-21在宫颈癌组织及Hela细胞系中高表达,在正常宫颈标本中低表达,在宫颈癌组织中相对定量为正常宫颈组织的11.3196倍(P<0.05);miR-143、miR-373在宫颈癌组织及Hela细胞中均低表达,在正常宫颈标本中高表达,miR-143、miR-373在宫颈癌组织中相对定量分别为正常宫颈组织的0.1553倍和0.4907倍(P<0.05);miR-126的表达无明显变化.结论 miRNAs与宫颈癌的发生和调控密切相关.在宫颈癌组织和Hela细胞中,miR-21表达上调,可能在宫颈癌的发生过程中发挥癌基因的作用;miR-143、miR-373表达下调可能发挥抑癌基因的作用;miR-126表达无差异,与宫颈癌无明显关系.%Objective To investigate the differential expression of miR-21 ,miR-126 ,miR-143 and miR-373 in normal cervical tissue, cervical cancer tissue and Hela cell.Methods The expressions of miR-21, miR-126, miR-143 and miR-373 were detected by real-time PCR in cervical cancer tissue,cervical tissue of benign uterine tumor and Hela cell. Results High expression of miR-21 was observed in cervical cancer and Hela cell, while low expression was observed in normal cervical tissue. The relative quantification of miR-21 in cerveical cancer was 11.3196 times that of miR-21 in normal cervical tissue (P0. 05). Conclusion miRNAs are closely related to the occurrence and regulation of cervical cancer. The high expression of miR-21 in cervical cancer and Hela cell indicate that it may play a possible role of oncogenes, while miR-143 and miR-373 with low expression may play the role of tumor suppressor genes.

  17. Nanomedicine and cancer therapies

    CERN Document Server

    Sebastian, Mathew; Elias, Eldho

    2012-01-01

    Introduction Nanotechnological-Based Systems for CancerIn vivo Spectroscopy for Detection and Treatment of GBM with NPt® ImplantationNanobiotechnology for Antibacterial Therapy and DiagnosisChitosan NanoparticlesSynthesis and Biomedical Application of Silver NanoparticlesRecent Advances in Cancer Therapy Using PhytochemicalsMitochondrial Dysfunction and Cancer: Modulation by Palladium-Lipoic Acid ComplexUnity of Mind and Body: The Concept of Life Purpose DominantThuja Occidentalis and Breast Cancer ChemopreventionAntioxidants and Com

  18. Unproven (questionable) cancer therapies.

    OpenAIRE

    Brigden, M.L.

    1995-01-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects...

  19. Gene Therapy of Cancerous Diseases

    OpenAIRE

    Valenčáková, A.; Dziaková, A.; Hatalová, E.

    2015-01-01

    Gene therapy of cancerous diseases provides new means of curing patients with oncologic illnesses. There are several approaches in treating cancer by gene therapy. Most commonly used methods are: cancer immunogene therapy, suicide gene therapy, application of tumor-suppressor genes, antiangiogenic therapy, mesenchymal stem cells used as vectors, gene directed enzyme/prodrug therapy and bacteria used as anti-cancer agents. Cancer gene immunotherapy uses several immunologic agents for the purp...

  20. Unproven (questionable) cancer therapies.

    Science.gov (United States)

    Brigden, M L

    1995-11-01

    More than half of all cancer patients use some form of alternative treatment during the course of their illness. Alternative therapies are often started early in patients' illness, and their use is frequently not acknowledged to health care professionals. Some alternative therapies are harmful, and their promoters may be fraudulent. Persons who try alternative cancer therapies may not be poorly educated but may ultimately abandon conventional treatment. Recent attention has focused on aspects of questionable therapies that make these treatments attractive to patients and that may be perceived as being deficient in the practice of conventional health care professionals. Physicians with patients with cancer should always make sure that unproven therapies are discussed early in the therapeutic relationship. They should also attempt to be aware of alternative therapies that are in vogue in their particular geographic area.

  1. Regulation of the cell cycle gene, BTG2, by miR-21 in human laryngeal carcinoma

    Institute of Scientific and Technical Information of China (English)

    Min Liu; Haidong Wu; Tao Liu; Yixuan Li; Fang Wang; Haiying Wan; Xin Li; Hua Tang

    2009-01-01

    MicroRNAs are short regulatory RNAs that negatively modulate gene expression at the post-transcriptional level, and are deeply involved in the pathogenesis of several types of cancers. To investigate whether specific miRNAs and their target genes participate in the molecular pathogenesis of laryngeal carcinoma, oligonucleotide microarrays were used to assess the differential expression profiles of microRNAs and mRNAs in laryngeal carcinoma tissues compared with normal tissues. The oncogenic miRNA, microRNA-21 (miR-21), was found to be upregulated in laryngeal carcinoma tissues. Knockdown of miR-21 by specific antisense oligonucleotides inhibited the proliferation potential of HEp-2 cells, whereas overexpression of miR-21 elevated growth activity of the cells, as detected by the colony formation assay. The cell number reduction caused by miR-21 inhibition was due to the loss of control of the GI-S phase transition, instead of a noticeable increase in apoptosis. Subsequently, a new target gene of miR-21, BTG2, was found to be downregulated in laryngeal carcinoma tissues. BTG2 is known to act as a pan-cell cycle regulator and tumor suppressor. These findings indicate that aberrant expression of miR-21 may contribute to the malignant phenotype of laryngeal carcinoma by maintaining a low level of BTG2. The identification of the oncogenic miR-21 and its target gene, BTG2, in laryngeal carcinoma is potentially valuable for cancer diagnosis and therapy.

  2. Targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Neal Rosen; Carlos Arteaga

    2011-01-01

    With unprecedented understanding of molecular events underlying human cancer in this genomic era, a large number of drugs specifically targeting hypothesized oncogenic drivers to which tumors are potentially addicted to have been developed and continue to be developed. These targeted cancer therapies are being actively tested in clinical trials with mixed successes. This editorial provides an overview on successful targeted cancer drugs on the market and those drugs that are in late clinical development stages. Importantly, the article lays out main challenges in developing molecular targeted therapies and potential path forward to overcome these challenges, as well as opportunities for China in this new era of targeted agents. The editorial serves as an introduction to the Targeted Cancer Therapies serias that will review in depth of major pathways and drugs targeting these pathways to be published in the coming issues of the Chinese Journal of Cancer.

  3. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    An essential part in cancer radiotherapy, is to direct a sufficiently high dose towards the tumour, without damaging the surrounding tissue. Different techniques such as intensity modulated radiation therapy and proton therapy have been developed, in order to reduce the dose to the normal tissue...

  4. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    An essential part in cancer radiotherapy, is to direct a sufficiently high dose towards the tumour, without damaging the surrounding tissue. Different techniques such as intensity modulated radiation therapy and proton therapy have been developed, in order to reduce the dose to the normal tissue...

  5. Radiation Therapy for Lung Cancer

    Science.gov (United States)

    ... of the lung cancer and your overall health. Radiation Therapy Radiation is a high-energy X-ray that can ... surgery, chemotherapy or both depending upon the circumstances. Radiation therapy works within cancer cells by damaging their ...

  6. Accelerators for Cancer Therapy

    Science.gov (United States)

    Lennox, Arlene J.

    2000-05-30

    The vast majority of radiation treatments for cancerous tumors are given using electron linacs that provide both electrons and photons at several energies. Design and construction of these linacs are based on mature technology that is rapidly becoming more and more standardized and sophisticated. The use of hadrons such as neutrons, protons, alphas, or carbon, oxygen and neon ions is relatively new. Accelerators for hadron therapy are far from standardized, but the use of hadron therapy as an alternative to conventional radiation has led to significant improvements and refinements in conventional treatment techniques. This paper presents the rationale for radiation therapy, describes the accelerators used in conventional and hadron therapy, and outlines the issues that must still be resolved in the emerging field of hadron therapy.

  7. Fertility and cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Maguire, L.C.

    1979-05-01

    With increased survival of increasing numbers of cancer patients as a result of therapy, the consequences, early and late, of the therapies must be realized. It is the treating physician's duty to preserve as much reproductive potential as possible for patients, consistent with adequate care. With radiotherapy this means shielding the gonads as much as possible, optimal but not excessive doses and fields, oophoropexy, or sperm collection and storage prior to irradiation. With chemotherapy it means the shortest exposure to drugs consistent with best treatment and prior to therapy the collection and storage of sperm where facilities are available. At present this is still an experimental procedure. Artificial insemination for a couple when the male has received cancer therapy is another alternative. Finally, it is the responsibility of physicians caring for patients with neoplasms to be knowledgeable about these and all other effects of therapy so that patients may be counseled appropriately and understand the implications of therapy for their life.

  8. MiR-21 expression in the tumor stroma of oral squamous cell carcinoma

    DEFF Research Database (Denmark)

    Hedbäck, Nora; Jensen, David H; Specht, Lena;

    2014-01-01

    RNA-21 (miR-21) is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ...... hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC...... samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N...

  9. Ototoxicity and cancer therapy.

    Science.gov (United States)

    Landier, Wendy

    2016-06-01

    Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health-related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration-approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss. Cancer 2016;122:1647-58. © 2016 American Cancer Society. © 2016 American Cancer Society.

  10. Drug resistance of colon cancer cells to 5-fluorouracil mediated by microRNA-21%miR-21介导的结肠癌细胞对5-氟尿嘧啶的耐药机制研究

    Institute of Scientific and Technical Information of China (English)

    吴丽媛; 李偲; 彭锐; 龚舒; 徐柳; 邹方东

    2015-01-01

    目的 通过检测microRNA-21 (miR-21)及其靶基因程序性细胞死亡因子4(programmed cell death 4,PDCD4)基因在结肠癌细胞中对下游通路的调控,研究高表达的miR-21在结肠癌细胞中对5-氟尿嘧啶(5-fuorouracil,5-FU)耐药的可能机制.方法 MTT法检测5-FU处理后miR-21敲除或PDCD4高表达对RKO细胞存活率的影响;流式细胞术检测5-FU处理后RKO-敲除型与RKO-野生型细胞凋亡;定量PCR检测miR-21敲除后以及PDCD4高表达后RKO细胞中ABCC5及CD44 mRNA水平的变化.结果 5-FU对RKO-野生型的半抑制浓度(IC50)值(52.28±0.05)μmol/L比RKO-敲除型的IC50值(32.13±0.05) μmol/L高67%,同时miR-21敲除后细胞凋亡率显著增加;PDCD4在RKO-敲除型细胞中显著高表达,并且高表达的PDCD4能够负调控转运蛋白ABCC5及干细胞表面标记CD44.结论 miR-21很可能通过抑制靶基因PDCD4调控转运蛋白ABCC5及干细胞表面标记CD44的表达,从而增强RKO细胞对5-FU的耐药性.%Objective To explore downstream regulatory pathway of microRNA-21 (miR-21) in colon cancer cells (RKO) through detecting miR-21 and its target PDCD4, and the influence of miR-21 regulation on the sensitivity of RKO cells to 5-fluorouracil (5-FU).Methods 3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay was used to determine the effect of 5-FU on the viability of RKO cells with knockout of miR-21 or high expression of PDCD4.Real-time was used to determine the expression of PDCD4, ABCC5 and CD44 in RKO cell after knockout of miR-21.Results MTT assay reveals that the IC50 of 5-FU in RKO-WT cells [(52.82±0.06) μmol/L] was~67% higher than in miR-21 knockout cells [(32.2310.05) μmol/L] (P<0.05), and the apoptosis ratio elevated after knockout of miR-21.High expression of PDCD4, a target gene of miR-21, can negatively regulate the expression of ABC transporter ABCC5 and the stem cell marker CD44.Conclusion MiR-21 can mediate the drug resistance to 5-FU by

  11. Nanotechnology Cancer Therapy and Treatment

    Science.gov (United States)

    Nanotechnology offers the means to target therapies directly and selectively to cancerous cells and neoplasms. With these tools, clinicians can safely and effectively deliver chemotherapy, radiotherapy, and the next generation of immuno- and gene therapi

  12. Gene therapy of liver cancer

    Institute of Scientific and Technical Information of China (English)

    Ruben Hernandez-Alcoceba; Bruno Sangro; Jesus Prieto

    2006-01-01

    The application of gene transfer technologies to the treatment of cancer has led to the development of new experimental approaches like gene directed enzyme/prodrug therapy (GDEPT), inhibition of oncogenes and restoration of tumor-suppressor genes. In addition,gene therapy has a big impact on other fields like cancer immunotherapy, anti-angiogenic therapy and virotherapy.These strategies are being evaluated for the treatment of primary and metastatic liver cancer and some of them have reached clinical phases. We present a review on the basis and the actual status of gene therapy approaches applied to liver cancer.

  13. Biofield therapies and cancer pain.

    Science.gov (United States)

    Anderson, Joel G; Taylor, Ann Gill

    2012-02-01

    The public and healthcare professionals have become increasingly aware and accepting of the benefit in physical, psychological, social, and spiritual support for patients with cancer. Patients with cancer often seek nonpharmacologic interventions to complement conventional care and decrease the pain associated with cancer and its treatment. Most often referred to as complementary and alternative medicine (CAM), these supportive therapies consist of a heterogeneous group of modalities used as adjuncts to allopathic health care. Biofield therapies are CAM modalities that involve the direction of healing energy through the hands to facilitate well-being by modifying the energy field of the body. This critical review of studies of biofield therapies emphasizes research using these modalities to decrease pain in patients with cancer. Although the therapies have demonstrated clinical efficacy, additional research is warranted. Oncology nurses should familiarize themselves with biofield therapies so they can offer informed recommendations to patients with cancer experiencing pain.

  14. miRNA oligonucleotide and sponge for miRNA-21 inhibition mediated by PEI-PLL in breast cancer therapy.

    Science.gov (United States)

    Gao, Shiqian; Tian, Huayu; Guo, Ye; Li, Yuce; Guo, Zhaopei; Zhu, Xiaojuan; Chen, Xuesi

    2015-10-01

    MicroRNA-21 (miR-21) inhibition is a promising biological strategy for breast cancer therapy. However its application is limited by the lack of efficient miRNA inhibitor delivery systems. As a cationic polymer transfection material for nucleic acids, the poly (l-lysine)-modified polyethylenimine (PEI-PLL) copolymer combines the high transfection efficiency of polyethylenimine (PEI) and the good biodegradability of polyllysine (PLL). In this work, PEI-PLL was successfully synthesized and confirmed to transfect plasmid and oligonucleotide more effectively than PEI in MCF-7 cells (human breast cancer cells). In this regard, two kinds of miR-21 inhibitors, miR-21 sponge plasmid DNA (Sponge) and anti-miR-21 oligonucleotide (AMO), were transported into MCF-7 cells by PEI-PLL respectively. The miR-21 expression and the cellular physiology were determined post transfection. Compared with the negative control, PEI-PLL/Sponge or PEI-PLL/AMO groups exhibited lower miR-21 expression and cell viability. The anti-tumor mechanism of PEI-PLL/miR-21 inhibitors was further studied by cell cycle and western blot analyses. The results indicated that the miR-21 inhibition could induce the cell cycle arrest in G1 phase, upregulate the expression of Programmed Cell Death Protein 4 (PDCD4) and thus active the caspase-3 apoptosis pathway. Interestingly, the PEI-PLL/Sponge and PEI-PLL/AMO also sensitized the MCF-7 cells to anti-tumor drugs, doxorubicin (DOX) and cisplatin (CDDP). These results demonstrated that PEI-PLL/Sponge and PEI-PLL/AMO complexes would be two novel and promising gene delivery systems for breast cancer gene therapy based on miR-21 inhibition. This work was a combination of the high transfection efficiency of polyethylenimine (PEI), the good biodegradability of polyllysine (PLL) and the breast cancer-killing effect of miR-21 inhibitors. The poly (l-lysine)-modified polyethylenimine (PEI-PLL) copolymer was employed as the vector of miR-21 sponge plasmid DNA (Sponge) or

  15. Adjuvant therapies for colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.

  16. Gene therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Xu Chang-tai; Guo Xue-gang; Pan Bo-rong

    2003-01-01

    @@ 1 Introduction We have reviewed the gene therapy in gastrointestinal diseases[1]. Gastric cancer is common in China[2~20] ,and its early diagnosis andtreatment are still difficult up to now[13~36]. The expression of anexogenous gene introduced by gene therapy into patients with gliomascan be monitored non- invasively by positron- emission tomography[4]. In recent years, gene study in cancer is a hotspot, and great progress hasbeen achieved[33~41].

  17. MiR-21 promoted proliferation and migration in hepatocellular carcinoma through negative regulation of Navigator-3

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhipeng, E-mail: dr_zpwang@163.com [The Digestive and Vascural Surgery Center, the First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, Xinjiang Uygur Autonomous Region (China); Yang, Huan [The Department of Liver and Biliary Pancreatic Surgery, Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi 830000, Xinjiang Uygur Autonomous Region (China); Ren, Lei [The Department of General Surgery, Branching Hospital of the First People' s Hospital of Urumqi, 830000, Xinjiang Uygur Autonomous Region (China)

    2015-09-04

    MicroRNA-21 (miR-21) has been well-established and found to be over-expressed in various human cancers and has been associated with hepatocellular carcinoma (HCC) progression. However, the underlying mechanism of miR-21 involvement in the development and progression of HCC remains to be understood. In the present study, we firstly identified that the Navigator-3 (NAV-3) gene as a novel direct target of miR-21. Knock-down of NAV-3 using shRNA can rescue the effects of anti-miR-21 inhibitor in HCC cell lines, whereas re-expression of miR-21 using transfection with miR-21 mimics phenocopied the NAV-3 knock-down model. Additionally, miR-21 levels inversely correlated with NAV-3 both in HCC cells and tissues. Knock-down of NAV-3 promoted both the proliferation and migration in HCC cells. Together, our findings suggest an important role for miR-21 in the progression of HCC, which negatively regulated Navigator-3 in the migration of HCC. - Highlights: • Navigator-3 (NAV-3) suppresses proliferation, migration and tumorigenesis of HCC cells. • NAV-3 was a novel target of miR-21. • MiR-21 negatively regulates NAV-3 in HCC.

  18. Cancer Alternative Therapies

    Science.gov (United States)

    You have many choices to make about your cancer treatment. One choice you might be thinking about ... are acupuncture, chiropractic, and herbal medicines. People with cancer may use CAM to Help cope with the ...

  19. Targeted Cancer Therapies

    Science.gov (United States)

    ... changes, hair depigmentation) Problems with blood clotting and wound healing High blood pressure Gastrointestinal perforation (a rare side effect of some targeted therapies) Certain side effects of some targeted therapies have ...

  20. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... of Medicinal Product Statistics provided individually updated exposure information. The National Cancer Register and Pathology Register provided ovarian cancer incidence data. Information on confounding factors and effect modifiers was from other national registers. Poisson regression analyses with 5-year age...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  1. Art therapy in cancer fight

    Directory of Open Access Journals (Sweden)

    Érica Rodrigues D'Alencar

    2014-01-01

    Full Text Available Art therapy is the therapeutic use of artistic activity in the context of the professional relationship with people affected by disease, injury or by seeking personal development. This study aims to report the experience of art therapy activities with a group of patients and their caregivers in a university hospital. This is an experience report, in Fortaleza - CE, during September 2010 to February 2011. In the meetings, participated 49 people, who performed activities, using the methods of art therapy, like painting, cutting, drawing, collage, creative visualization and color therapy. In the assessments, after the groups, the participants demonstrated the effects of art therapy, which described that the intervention allowed speak from the process of facing life to cancer fight. It is concluded that the techniques of art therapy provided self-knowledge, self-esteem and redemption sense of well-being with relaxation, and promote happiness and reduce stress.

  2. Sonoporation: Applications for Cancer Therapy.

    Science.gov (United States)

    Qin, Jiale; Wang, Tzu-Yin; Willmann, Jürgen K

    2016-01-01

    Therapeutic efficacy of both traditional chemotherapy and gene therapy in cancer is highly dependent on the ability to deliver drugs across natural barriers, such as the vessel wall or tumor cell membranes. In this regard, sonoporation induced by ultrasound-guided microbubble (USMB) destruction has been widely investigated in the enhancement of therapeutic drug delivery given it can help overcome these natural barriers, thereby increasing drug delivery into cancer. In this chapter we discuss challenges in current cancer therapy and how some of these challenges could be overcome using USMB-mediated drug delivery. We particularly focus on recent advances in delivery approaches that have been developed to further improve therapeutic efficiency and specificity of various cancer treatments. An example of clinical translation of USMB-mediated drug delivery is also shown.

  3. Targeted therapies for cancer

    Science.gov (United States)

    ... nih.gov/pubmed/23589545 . Kummar S, Murgo AJ, Tomaszewski JE, Doroshow JH. Therapeutic targeting of cancer cells: Era of molecularly targeted agents. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, ...

  4. Biological Therapies for Cancer

    Science.gov (United States)

    ... Gooley TA, et al. Concurrent trastuzumab and HER2/neu-specific vaccination in patients with metastatic breast cancer. ... Websites POLICIES Accessibility Comment Policy Disclaimer FOIA Privacy & Security Reuse & Copyright Syndication Services Website Linking U.S. Department ...

  5. Antiangiogenic therapies in ovarian cancer

    OpenAIRE

    Reinthaller, Alexander

    2016-01-01

    Summary Angiogenesis plays a pivotal role in normal ovarian physiology as well as in the formation and progression of ovarian cancer. Several well-designed phase II and III trials studied the efficacy of antiangiogenic agents in advanced ovarian cancer. The results of these trials demonstrated significantly prolonged progression-free survival when antiangiogenic agents were used as a maintenance therapy. To date, no effect on overall survival could be ascertained. The most widely studied anti...

  6. Targeted Therapies in Endometrial Cancer

    Directory of Open Access Journals (Sweden)

    Selen Dogan

    2014-04-01

    Full Text Available Endometrial cancer is the most common genital cancer in developed world. It is generally diagnosed in early stage and it has a favorable prognosis. However, advanced staged disease and recurrences are difficult to manage. There are some common genetic alterations related to endometrial carcinogenesis in similar fashion to other cancers. Personalized medicine, which means selection of best suited treatment for an individual, has gain attention in clinical care of patients in recent years. Targeted therapies were developed as a part of personalized or %u201Ctailored%u201D medicine and specifically acts on a target or biologic pathway. There are quite a number of molecular alteration points in endometrial cancer such as PTEN tumor suppressor genes, DNA mismatch repair genes, PI3K/AKT/mTOR pathway and p53 oncogene which all might be potential candidates for tailored targeted therapy. In recent years targeted therapies has clinical application in ovarian cancer patients and in near future with the advent of new agents these %u201Ctailored%u201D drugs will be in market for routine clinical practice in endometrial cancer patients, in primary disease and recurrences as well.

  7. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  8. Esophagus Cancer: Palliative Therapy

    Science.gov (United States)

    ... www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf on May 6, 2017. Posner MC, Minsky B, Ilson DH. Ch 45 - Cancer of the esophagus. In: DeVita VT, Hellman S, Rosenberg SA, eds. DeVita, Hellman, and ...

  9. miR-21的高表达在结直肠癌预后中的meta分析%Significance of high miR-21 expression on the prognosis of colorectal carcinoma: A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    郭仲莉; 曾照芳

    2013-01-01

    目的:评价miR-21的高表达与结直肠癌预后的相关性.方法:通过全面检索PubMed、EMBASE、Google scholar、维普、CNKI等数据库,收集关于miR-21的高表达与结直肠癌预后相关性的文献,用meta分析方法评价miR-21的高表达是否与结直肠癌的预后相关.结果:共纳入4篇文献(共783个病例),总生存率(OS)HR的合并值为1.42,95%CI:1.21至1.66,P<0.05.结论:miR-21的高表达是结直肠癌预后的一个危险因素.%Objective:To evaluate the correlation between the high expression of miR-21 and the prognosis of colorectal cancer.Methods:Eligible studies which studied the correlation between the high expression of miR-21 and the prognosis of colorectal cancer were collected through searching PubMed,EMBASE,and Google scholar,VIP,CNKI databases.A meta analysis method was used to evaluate whether the high expression of miR-21 has an association with the prognosis of colorectal cancer.Results:A total of 4 studies were involved in this meta-analysis.For overall survival (OS),the pooled hazard ratio (HR) of higher miR-21 expression in cancerous tissues was 1.42 95 % CI:1.21 ~ 1.66,P < 0.05 Conclusions:The association of high expression of miR-21and the prognosis of colorectal cancer is negative.

  10. Antiproton Cancer Therapy

    DEFF Research Database (Denmark)

    Bassler, Niels

    Antiprotons are interesting as a modality in radiation therapy for the following reasons: When fast antiprotons penetrate matter, they behave as protons. Well before the Bragg-peak, protons and antiprotons have near identical stopping powers exhibit equal radiobiology. But when the antiprotons co...

  11. Gene therapy for gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Chao Zhang; Zhan-Kui Liu

    2003-01-01

    Gastric cancer is common in China, and its early diagnosis and treatment are difficult. In recent years great progress has been achieved in gene therapy, and a wide array of gene therapy systems for gastric cancer has been investigated. The present article deals with the general principles of gene therapy and then focuses on how these principles may be applied to gastric cancer.

  12. Targeted therapy: tailoring cancer treatment

    Institute of Scientific and Technical Information of China (English)

    Min Yan; Quentin Qiang Liu

    2013-01-01

    Targeted therapies include small-molecule inhibitors and monoclonal antibodies,have made treatment more tumor-specific and less toxic,and have opened new possibilities for tailoring cancer treatment.Nevertheless,there remain several challenges to targeted therapies,including molecular identification,drug resistance,and exploring reliable biomarkers.Here,we present several selected signaling pathways and molecular targets involved in human cancers including Aurora kinases,PI3K/mTOR signaling,FOXO-FOXM1 axis,and MDM2/MDM4-p53 interaction.Understanding the molecular mechanisms for tumorigenesis and development of drug resistance will provide new insights into drug discovery and design of therapeutic strategies for targeted therapies.

  13. Noxa and cancer therapy

    OpenAIRE

    2014-01-01

    Biochemical analyses have characterized the BH3-only protein family member Noxa as a “sensitizer” with weak pro-apoptotic activity. Investigations into cancer cell responses to chemotherapeutic agents have identified Noxa as a pivotal factor mediating the cytotoxic effect of a plethora of anticancer treatments independent of its own pro-apoptotic activity. Accumulating evidence now suggests that tumor cells exert a number of strategies to counteract Noxa function by exploiting diverse cellula...

  14. Alternative cancer therapies.

    Science.gov (United States)

    Cronsberry, T

    1996-04-01

    Conventional treatments for cancer are designed to cure the disease or slow its destructive effects, but they do little to establish a feeling of control in the patient. Because of the nature of the disease, patients often consent to treatment with the frightening knowledge that a cure cannot be promised. In addition, the side effects of surgery, chemotherapy and radiotherapy can make patients very ill, both physically and psychologically.

  15. Menopausal Hormone Therapy and Cancer

    Science.gov (United States)

    ... Kidney (Renal Cell) Cancer Leukemia Liver Cancer Lung Cancer Lymphoma Pancreatic Cancer Prostate Cancer Skin Cancer Thyroid Cancer Uterine Cancer ... Myths and Misconceptions Diet Hormones Immunosuppression Infectious Agents Obesity Radiation Sunlight Tobacco Genetics NCI Cancer Genetics Services ...

  16. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard

    2010-01-01

    and optimal use of these agents for the treatment of breast cancer. Currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Small molecular inhibitors of VEGF...... tyrosine kinase activity, such as sorafenib, appear promising. While, the role of sunitinib and inhibitors of mammalian target of rapamycin (mTOR) in breast cancer has to be defined. Several unanswered questions remain, such as choice of drug(s), optimal duration of therapy and patient selection criteria......ABSTRACT: Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development...

  17. Phosphatase of regenerating liver-3-signal transducer and activators of transcription 3-miR-21 sighal pathway promotes proliferation and invasion of colon cancer cells%肝再生磷酸酶-3-信号传导和转录激活子3-微小RNA21信号通路促进结肠癌细胞增殖侵袭的研究

    Institute of Scientific and Technical Information of China (English)

    张建龙; 张育超; 孙健; 何传超; 褚忠华

    2012-01-01

    目的 观察肝再生磷酸酶-3-信号传导和转录激活子3-微小RNA21(PRL-3-STAT3miR-21)信号通路对结肠癌细胞增殖侵袭的作用.方法 构建稳定转染PRL-3基因和空白对照质粒的结肠癌细胞株LoVo-PRL-3和LoVo-VC,用荧光实时定量聚合酶链反应(RT-qPCR)检测稳转细胞株中miR-21的表达并在瞬时转染PRL-3的SW480及CaCO2细胞中进行验证.用Western blot法对PRL-3调控STAT3的表达进行检测,在LoVo-PRL-3细胞中对STAT3进行RNA干扰,检测miR-21的表达,在稳转细胞株中转染miR-21或对其进行敲除,用细胞计数试剂盒(CCK-8)、Transwell实验对细胞的增殖侵袭能力的变化进行研究.结果 LoVo-PRL-3细胞在72、96 h的增殖能力以及在Transwell实验24 h后的侵袭能力要强于对照组LoVo-VC细胞(P<0.01).在结肠癌细胞株LoVo-PRL-3中pSTAT3、miR-21的表达明显上调,干扰STAT3可以抑制miR-21的表达(P<0.05).在LoVo-VC细胞中过表达miR-21促进了细胞的增殖侵袭(P<0.01),而在LoVo-PRL-3细胞中敲除miR-21抑制了细胞的增殖侵袭(P<0.05).结论 PRL-3-STAT3-miR-21信号通路在结肠癌细胞增殖侵袭中起促进作用.%Objective To explore the effect of phosphatase of regenerating liver-3-signal transducer and activators of transcription 3-microRNA-21 (PRL-3-STAT3-miR-21) signal pathway on proliferation and invasion of colon cancer cellsMethods We stablely transfected PRL-3 expressing plasmid and empty plasmid into LoVo colon cancer cells and established two cell lines:LoVo-PRL-3 and LoVo-VC.We used quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) to detect the expression of miR-21 in LoVo cells.We also performed transient transfection of PRL-3 into SW480 and CACO2 cells to validate the expression of miR-21.Western blotting was used to detect the effect of PRL-3 on the expression of STAT3.RNA interference was used to knocked down STAT3 in LoVo-PRL-3 cells,after that miR-21 expression was

  18. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  19. Immunotoxins and Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    ZhengLi; TaoYu; PingZhao; JieMa

    2005-01-01

    In the past decade, an increased amount of clinically-oriented research involving immunotoxins has been published. Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells. These molecules composed of a targeting moiety, such as a ligand or an antibody, linked to toxin moiety, which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells. Immunotoxins can be divided into two categories: chemically conjugated immunotoxins and recombinant ones. The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors. Within the last few years, single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity. In this review, we briefly illustrate the design of the immunotoxins and their applications in clinical trials. Cellular & Molecular Immunology. 2005;2(2):106-112.

  20. Immunotoxins and Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Zheng Li; Tao Yu; Ping Zhao; Jie Ma

    2005-01-01

    In the past decade, an increased amount of clinically-oriented research involving immunotoxins has been published.Immunotoxins are a group of artificially-made cytotoxic molecules targeting cancer cells. These molecules composed of a targeting moiety, such as a ligand or an antibody, linked to toxin moiety, which is a toxin with either truncated or deleted cell-binding domain that prevents it from binding to normal cells. Immunotoxins can be divided into two categories: chemically conjugated immunotoxins and recombinant ones. The immunotoxins of the first category have shown limited efficacy in clinical trials in patients with hematologic malignancies and solid tumors. Within the last few years, single-chain immunotoxins provide enhanced therapeutic efficacy over conjugated forms and result in improved antitumor activity. In this review, we briefly illustrate the design of the immunotoxins and their applications in clinical trials. Cellular & Molecular Immunology. 2005;2(2):106-112.

  1. Neoadjuvant therapy in pancreatic cancer: review article.

    Science.gov (United States)

    Pross, Moritz; Wellner, Ulrich F; Honselmann, Kim C; Jung, Carlo; Deichmann, Steffen; Keck, Tobias; Bausch, Dirk

    2015-03-20

    Pancreatic cancer is still associated with a high mortality and morbidity for affected patients. To this date the role of neoadjuvant therapy in the standard treatment of pancreatic cancer remains elusive. The aim of our study was to review the latest results and current approaches in neoadjuvant therapy of pancreatic cancer. We performed a literature review for neoadjuvant therapy in pancreatic cancer. We divided the results into resectable disease and local advanced pancreatic cancer. Neoadjuvant therapy in pancreatic cancer is safe. But currently no standard guidelines exist in neoadjuvant approaches on pancreatic cancer. For local advanced pancreatic cancer the available data tends to show a positive effect on survival rates for neoadjuvant approaches. For resectable disease we found no benefit of neoadjuvant therapy. The negative or positive effects of neoadjuvant treatment in pancreatic cancer remain unclear for the lack of sufficient and prospective data.

  2. Sirt2 suppresses glioma cell growth through targeting NF-κB–miR-21 axis

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ya’nan; Dai, Dongwei [Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai (China); Lu, Qiong; Fei, Mingyu [Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai (China); Li, Mengmeng [Department of Rheumatology, Changzheng Hospital, Second Military Medical University, Shanghai (China); Wu, Xi, E-mail: xiwuchh@sina.com [Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai (China)

    2013-11-22

    Highlights: •Sirt2 expression is down-regulated in human glioma tissues and cell lines. •Sirt2 regresses glioma cell growth and colony formation via inducing apoptosis. •miR-21 is essential for the functions of Sirt2 in glioma cells. •Sirt2 deacetylates p65 to decrease miR-21 expression. -- Abstract: Sirtuins are NAD{sup +}-dependent deacetylases that regulate numerous cellular processes including aging, DNA repair, cell cycle, metabolism, and survival under stress conditions. The roles of sirtuin family members are widely studied in carcinogenesis. However, their roles in glioma remain unclear. Here we report that Sir2 was under expressed in human glioma tissues and cell lines. We found that Sirt2 overexpression decreased cell proliferation and colony formation capacity. In addition, Sirt2 overexpression induced cellular apoptosis via up-regulating cleaved caspase 3 and Bax, and down-regulating anti-apoptotic protein Bcl-2. Sirt2 knockdown obtained opposing results. We showed that Sirt2 overexpression inhibited miR-21 expression, and Sirt2 was not sufficient to reduce cell proliferation and colony formation as well as to induce apoptosis when miR-21 was knocked down in glioma cells. Mechanically, we demonstrated that Sirt2 deacetylated p65 at K310 and blocked p65 binding to the promoter region of miR-21, thus regressing the transcription of miR-21. In summary, Sirt2 is critical in human glioma via NF-κB–miR-21 pathway and Sirt2 activator may serve as candidate drug for glioma therapy.

  3. VEGF Inhibitors for Cancer Therapy

    OpenAIRE

    Prakash S. Sukhramani; Maulik P. Suthar

    2010-01-01

    Despite significant advances in systemic therapies, radiation oncology, and surgical techniques, many patients with cancer are still incurable. A novel therapeutic approach has been to target the vascular endothelial growth factors (VEGFs) which are often mutated and/or over-expressed in many tumors. The ligands and receptors of VEGF family are well established as key regulators of angiogenesis and vasculogenesis processes. VEGF is a homodimeric, basic, 45 kDa glycoprotein specific for vascul...

  4. Oncolytic virus therapy for cancer

    Directory of Open Access Journals (Sweden)

    Goldufsky J

    2013-09-01

    Full Text Available Joe Goldufsky,1 Shanthi Sivendran,3 Sara Harcharik,4 Michael Pan,4 Sebastian Bernardo,4 Richard H Stern,5 Philip Friedlander,4 Carl E Ruby,1,2 Yvonne Saenger,4 Howard L Kaufman1,2 Departments of 1Immunology & Microbiology and 2Surgery, Rush University Medical Center, Chicago IL, USA 3Hematology/Oncology Medical Specialists, Lancaster General Health, Lancaster, PA, USA, and Departments of 4Medical Oncology and 5Radiology, Tisch Cancer Institute, The Mount Sinai School of Medicine, New York, NY, USA Abstract: The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers. Keywords: cancer, gene therapy, oncolytic therapy, virus, treatment

  5. Targeted therapies in gastroesophageal cancer.

    Science.gov (United States)

    Kasper, Stefan; Schuler, Martin

    2014-05-01

    Gastroesophageal cancers comprising gastric cancer (GC), and cancers of the distal oesophagus and gastroesophageal junction (GEJ) are a global health threat. In Western populations the incidence of GC is declining which has been attributed to effective strategies of eradicating Helicobacter pylori infection. To the contrary, GEJ cancers are on the rise, with obesity and reflux disease being viewed as major risk factors. During the past decade perioperative chemotherapy, pre- or postoperative radio-chemotherapy, and, in Asian populations, adjuvant chemotherapy have been shown to improve the outcome of patients with advanced GC and GEJ cancers suited for surgery. Less progress has been made in the treatment of metastatic disease. The introduction of trastuzumab in combination with platinum/fluoropyrimidine-based chemotherapy for patients with HER2-positive disease has marked a turning point. Recently, several novel agents targeting growth factor receptors, angiogenic pathways, adhesion molecules and mediators of intracellular signal transduction have been clinically explored. Here we summarise the current status and future developments of molecularly targeted therapies in GC and GEJ cancer.

  6. Photodynamic therapy of gastric cancer

    Science.gov (United States)

    Kharnas, Sergey S.; Kuzin, N. M.; Zavodnov, Victor Y.; Sclyanskaya, Olga A.; Linkov, Kirill G.; Loschenov, Victor B.; Meerovich, Gennadii A.; Torshina, Nadezgda L.; Stratonnikov, Alexander A.; Steiner, Rudolf W.

    1996-01-01

    Photodynamic therapy (PDT) with the use of laser endoscopic spectrum analyzer (LESA-5), the spectral-analyzing video-imaging system, Kr laser and various types of catheters for different tumor localizations, and Phthalocyanine aluminum photosensitizers in patients with gastric cancer was discussed. PDT was carried out in fifteen patients with gastric cancer. There were the following indications for PDT: early gastric cancer (3 patients), malignant stenosis of the cardia or pyloric portion of the stomach (4 patients), cancer of gastric stump with stenosis of gastrojejunal anastomosis (1 patient), preoperative treatment of patients with large but probably resectable gastric tumor size (7 patients). Usually we used 3 - 4 seances of laser treatment 10 - 30 minutes long. Concentration of photosensitizer in normal and malignant tissue was controlled by LESA-5. Treatment was monitored by spectral-analyzing video- imaging system in fluorescent light. The results show high efficiency of PDT especially in patients with early gastric cancer (necrosis of all tumor mass, i.e. complete regression of tumor). For all other patients we obtained partial regression of gastric cancer.

  7. Magnetic nanoparticle-based cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Yu Jing; Huang Dong-Yan; Muhammad Zubair Yousaf; Hou Yang-Long; Gao Song

    2013-01-01

    Nanoparticles (NPs) with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles (MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging (MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.

  8. Targeted therapies in upper gastrointestinal cancer

    NARCIS (Netherlands)

    Kordes, S.

    2016-01-01

    Upper gastrointestinal (GI) cancers, as esophageal, gastric and pancreatic cancer, are still highly lethal diseases, in spite of advances in surgery, radiotherapy, chemotherapy and specific targeted therapy. Especially when patients are diagnosed with locally advanced or metastasized disease, upper

  9. Types of Cancer Treatment: Hormone Therapy

    Science.gov (United States)

    Describes how hormone therapy slows or stops the growth of breast and prostate cancers that use hormones to grow. Includes information about the types of hormone therapy and side effects that may happen.

  10. Cancer stem cells: therapeutic implications and perspectives in cancer therapy

    Directory of Open Access Journals (Sweden)

    Lu Han

    2013-04-01

    Full Text Available The cancer stem cell (CSC theory is gaining increasing attention from researchers and has become an important focus of cancer research. According to the theory, a minority population of cancer cells is capable of self-renewal and generation of differentiated progeny, termed cancer stem cells (CSCs. Understanding the properties and characteristics of CSCs is key to future study on cancer research, such as the isolation and identification of CSCs, the cancer diagnosis, and the cancer therapy. Standard oncology treatments, such as chemotherapy, radiotherapy and surgical resection, can only shrink the bulk tumor and the tumor tends to relapse. Thus, therapeutic strategies that focus on targeting CSCs and their microenvironmental niche address the ineffectiveness of traditional cancer therapies to eradicate the CSCs that otherwise result in therapy resistance. The combined use of traditional therapies with targeted CSC-specific agents may target the whole cancer and offer a promising strategy for lasting treatment and even cure.

  11. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)

    2004-08-21

    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  12. Emerging therapies in gastrointestinal cancers

    Institute of Scientific and Technical Information of China (English)

    Jyoti Nautiyal; Arun K Rishi; Adhip PN Majumdar

    2006-01-01

    Members of the receptor tyrosine kinase family, that include EGFR, ErbB-2/HER-2, ErbB-3/HER-3 and ErbB-4/HER-4, are frequently implicated in experimental models of epithelial cell neoplasia as well as in human cancers.Therefore, interference with the activation of these growth factor receptors represents a promising strategy for development of novel and selective anticancer therapies.Indeed, a number of inhibitors that target either EGFR or HER-2, with the exception of a few that target both;have been developed for treatment of epithelial cancers.Since most solid tumors express different ErbB receptors and/or their ligands, identification of inhibitor(s), targeting multiple EGFR family members may provide a therapeutic benefit to a broader patient population. Here we describe the significance of an ErbB family of receptors in epithelial cancers, and summarize different available therapeutics targeting these receptors. It also emphasizes the need to develop pan-ErbB inhibitors and discusses EGF-Receptor Related Protein, a recently isolated negative regulator of EGFR as a potential pan-ErbB therapeutic for a wide variety of epithelial cancers.

  13. miR-21 Is Linked to Glioma Angiogenesis

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Nielsen, Boye Schnack; Aaberg-Jessen, Charlotte

    2016-01-01

    (Sox2) and CD133. We developed an image analysis-based co-localization approach allowing global alignment and quantitation of the individual markers, and measured the miR-21 in situ hybridization signal against the immunohistochemical staining of the six different markers. miR-21 significantly co......-positive tumor cells, we systematically stained consecutive serial sections from ten astrocytomas for miR-21, hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), phosphatase and tensin homolog (PTEN), octamer-binding transcription factor 4 (Oct4), sex-determining region Y box 2......-localized with the hypoxia- and angiogenesis-associated markers HIF-1α (p=0.0020) and VEGF (p=0.0096), whereas the putative miR-21 target, PTEN, was expressed independently of miR-21. Expression of stem cell markers Oct4, Sox2 and CD133 was not associated with miR-21. In six glioblastoma cultures, miR-21 did not correlate...

  14. Stereotactic radiosurgery: a "targeted" therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Ming Zeng; Liang-Fu Han

    2012-01-01

    The developments of medicine always follow innovations in science and technology.In the past decade,such innovations have made cancer-related targeted therapies possible.In general,the term "targeted therapy" has been used in reference to cellular and molecular level oriented therapies.However,improvements in the delivery and planning of traditional radiation therapy have also provided cancer patients more options for "targeted" treatment,notably stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT).In this review,the progress and controversies of SRS and SBRT are discussed to show the role of stereotactic radiation therapy in the ever evolving multidisciplinary care of cancer patients.

  15. MiR-21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway.

    Science.gov (United States)

    Gui, Fu; Hong, Zhengdong; You, Zhipeng; Wu, Hongxi; Zhang, Yulan

    2016-12-01

    MicroRNA-21 (miR-21) was reported to act as an oncogene during the development of many human tumors. However, little was revealed about the function of miR-21 in retinoblastoma (RB). In this study, we examined the expression of miR-21 in RB tissues and explored the relationship between miR-21 and phosphatase and tensin homolog (PTEN)/phosphatidylinositol-3-OH kinase (PI3K)/AKT signal. Quantitative real-time PCR (qRT-PCR) results showed that the level of miR-21 in RB tissues was higher than that in retinal normal tissues. In Weri-Rb-1 cells, miR-21 inhibitor suppressed the expression of miR-21 and cell viability, but improved cell apoptotic rates by modulating the levels of PDCD4, Bax, and Bcl-2. Meanwhile, miR-21 inhibitor suppressed cell migration and invasion via inhibiting the protein levels of MMP2 and MMP9 and significantly affected the expression of PTEN, PI3K, and p-AKT. Taken together, miR-21 inhibitor suppressed cell proliferation, migration, and invasion via the PTEN/PI3K/AKT signal. These findings revealed the molecular basis of miR-21 functioning in the progression of RB and provided a new means for cell therapy in RB.

  16. Bacterial proteins and peptides in cancer therapy

    Science.gov (United States)

    Chakrabarty, Ananda M; Bernardes, Nuno; Fialho, Arsenio M

    2014-01-01

    Cancer is one of the most deadly diseases worldwide. In the last three decades many efforts have been made focused on understanding how cancer grows and responds to drugs. The dominant drug-development paradigm has been the “one drug, one target.” Based on that, the two main targeted therapies developed to combat cancer include the use of tyrosine kinase inhibitors and monoclonal antibodies. Development of drug resistance and side effects represent the major limiting factors for their use in cancer treatment. Nowadays, a new paradigm for cancer drug discovery is emerging wherein multi-targeted approaches gain ground in cancer therapy. Therefore, to overcome resistance to therapy, it is clear that a new generation of drugs is urgently needed. Here, regarding the concept of multi-targeted therapy, we discuss the challenges of using bacterial proteins and peptides as a new generation of effective anti-cancer drugs. PMID:24875003

  17. Peptide Vaccine Therapy in Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Shi-Yu Yang

    2012-08-01

    Full Text Available Colorectal cancer is the third most common cause of cancer-related deaths and the second most prevalent (after breast cancer in the western world. High metastatic relapse rates and severe side effects associated with the adjuvant treatment have urged oncologists and clinicians to find a novel, less toxic therapeutic strategy. Considering the limited success of the past clinical trials involving peptide vaccine therapy to treat colorectal cancer, it is necessary to revise our knowledge of the immune system and its potential use in tackling cancer. This review presents the efforts of the scientific community in the development of peptide vaccine therapy for colorectal cancer. We review recent clinical trials and the strategies for immunologic monitoring of responses to peptide vaccine therapy. We also discuss the mechanisms underlying the therapy and potential molecular targets in colon cancer.

  18. Metronomic therapy for gynecologic cancers

    Directory of Open Access Journals (Sweden)

    Wen-Hsiang Su

    2012-06-01

    Full Text Available Systemic administration of cytotoxic drugs is the primary treatment strategy for patients with advanced cancer. The effect of cytotoxic drugs is to disrupt the DNA of the cells, rendering them unable to replicate and finally killing them; therefore, the fundamental role of a wide range of treatment regimens is typically to induce lethal toxicity in the largest possible number of cancer cells. However, these cytotoxic drugs also damage the normal cells of the host, which limits the dose of the cytotoxic drug. Thus, cancer patients are usually treated at or near the maximum tolerated dose with the implicit intent of eradicating (curing the tumor after balancing between efficacy in tumor killing and toxicity to the host. With significantly improving patient care, most efforts are focused on the corollary, “The higher the dose, the better.” However, the concept that cancer could be considered as a chronic disease and might be treated like other chronic diseases to achieve a status called tumor dormancy is gaining popularity. In addition, there has been increasing interest in putting more effort into administering cytotoxic drugs on a more continuous basis, with a much shorter break period, or none at all, and generally lower doses of various cytotoxic drugs or combinations with other newer, targeted therapies, like anti-angiogenesis agents. This practice has come to be known as metronomic chemotherapy. There is still much to be learned in this field, especially with regard to optimization of the proper drugs, dose, schedule, and tumor type applications. This review will explore recent studies that have addressed the mechanism of metronomic chemotherapy in the management of various tumors, especially gynecologic cancers.

  19. Nanoshells for photothermal cancer therapy.

    Science.gov (United States)

    Morton, Jennifer G; Day, Emily S; Halas, Naomi J; West, Jennifer L

    2010-01-01

    Cancer is a leading cause of death in the United States and contributes to yearly rising health care costs. Current methods of treating cancer involve surgical removal of easily accessible tumors, radiation therapy, and chemotherapy. These methods do not always result in full treatment of the cancer and can in many cases damage healthy cells both surrounding the tissue area and systemically. Nanoshells are optically tunable core/shell nanoparticles that can be fabricated to strongly absorb in the near-infrared (NIR) region where light transmits deeply into tissue. When injected systemically, these particles have been shown to accumulate in the tumor due to the enhanced permeability and retention (EPR) effect and induce photothermal ablation of the tumor when irradiated with an NIR laser. Tumor specificity can be increased via functionalizing the nanoshell surface with tumor-targeting moieties. Nanoshells can also be made to strongly scatter light and therefore can be used in various imaging modalities such as dark-field microscopy and optical coherence tomography (OCT).

  20. Oncolytic virus therapy for cancer

    Science.gov (United States)

    Goldufsky, Joe; Sivendran, Shanthi; Harcharik, Sara; Pan, Michael; Bernardo, Sebastian; Stern, Richard H; Friedlander, Philip; Ruby, Carl E; Saenger, Yvonne; Kaufman, Howard L

    2013-01-01

    The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers. PMID:27512656

  1. Oncolytic virus therapy for cancer.

    Science.gov (United States)

    Goldufsky, Joe; Sivendran, Shanthi; Harcharik, Sara; Pan, Michael; Bernardo, Sebastian; Stern, Richard H; Friedlander, Philip; Ruby, Carl E; Saenger, Yvonne; Kaufman, Howard L

    2013-01-01

    The use of oncolytic viruses to treat cancer is based on the selection of tropic tumor viruses or the generation of replication selective vectors that can either directly kill infected tumor cells or increase their susceptibility to cell death and apoptosis through additional exposure to radiation or chemotherapy. In addition, viral vectors can be modified to promote more potent tumor cell death, improve the toxicity profile, and/or generate host antitumor immunity. A variety of viruses have been developed as oncolytic therapeutics, including adenovirus, vaccinia virus, herpesvirus, coxsackie A virus, Newcastle disease virus, and reovirus. The clinical development of oncolytic viral therapy has accelerated in the last few years, with several vectors entering clinical trials for a variety of cancers. In this review, current strategies to optimize the therapeutic effectiveness and safety of the major oncolytic viruses are discussed, and a summary of current clinical trials is provided. Further investigation is needed to characterize better the clinical impact of oncolytic viruses, but there are increasing data demonstrating the potential promise of this approach for the treatment of human and animal cancers.

  2. Gene Therapy In Oral Cancer : An Overview

    OpenAIRE

    2010-01-01

    The treatment and prevention of oral cancer is one of the major hurdles in the field ofcancer. Gene therapy is one of the recent advances in this field to tackle this hurdle with promisingprospects. This overview introduces the reader into the basic idea of gene therapy, types of genetherapy and the various modes of introduction of therapeutic gene into the cancer affected cell.

  3. Boron neutron capture therapy: Moving toward targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Hamid Reza Mirzaei

    2016-01-01

    Full Text Available Boron neutron capture therapy (BNCT occurs when a stable isotope, boton-10, is irradiated with low-energy thermal neutrons to yield stripped down helium-4 nuclei and lithium-7 nuclei. It is a binary therapy in the treatment of cancer in which a cytotoxic event is triggered when an atom placed in a cancer cell. Here, we provide an overview on the application of BNCT in cancer therapy as well as current preclinical and clinical evidence on the efficacy of BNCT in the treatment of melanoma, brain tumors, head and neck cancer, and thyroid cancer. Several studies have shown that BNCT is effective in patients who had been treated with a full dose of conventional radiotherapy, because of its selectivity. In addition, BNCT is dependent on the normal/tumor tissue ratio of boron distribution. Increasing evidence has shown that BNCT can be combined with different drug delivery systems to enhance the delivery of boron to cancer cells. The flexibility of BNCT to be used in combination with different tumor-targeting approaches has made this strategy a promising option for cancer therapy. This review aims to provide a state-of-the-art overview of the recent advances in the use of BNCT for targeted therapy of cancer.

  4. Antiangiogenic Steroids in Human Cancer Therapy

    OpenAIRE

    2005-01-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of ...

  5. Nanomaterials in Targeting Cancer Stem Cells for Cancer Therapy

    Science.gov (United States)

    Qin, Weiwei; Huang, Guan; Chen, Zuanguang; Zhang, Yuanqing

    2017-01-01

    Cancer stem cells (CSCs) have been identified in almost all cancers and give rise to metastases and can also act as a reservoir of cancer cells that may cause a relapse after surgery, radiation, or chemotherapy. Thus they are obvious targets in therapeutic approaches and also a great challenge in cancer treatment. The threat presented by CSCs lies in their unlimited proliferative ability and multidrug resistance. These findings have necessitated an effective novel strategy to target CSCs for cancer treatment. Nanomaterials are on the route to providing novel methods in cancer therapies. Although, there have been a large number of excellent work in the field of targeted cancer therapy, it remains an open question how nanomaterials can meet future demands for targeting and eradicating of CSCs. In this review, we summarized recent and highlighted future prospects for targeting CSCs for cancer therapies by using a variety of nanomaterials.

  6. Proton therapy for pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Romaine; C; Nichols; Soon; Huh; Zuofeng; Li; Michael; Rutenberg

    2015-01-01

    Radiotherapy is commonly offered to patients with pancreatic malignancies although its ultimate utility is compromised since the pancreas is surrounded by exquisitely radiosensitive normal tissues, such as the duodenum, stomach, jejunum, liver, and kidneys. Proton radiotherapy can be used to create dose distributions that conform to tumor targets with significant normal tissue sparing. Because of this, protons appear to represent a superior modality for radiotherapy delivery to patients with unresectable tumors and those receiving postoperative radiotherapy. A particularly exciting opportunity for protons also exists for patients with resectable and marginally resectable disease. In this paper, we review the current literature on proton therapy for pancreatic cancer and discuss scenarios wherein the improvement in the therapeutic index with protons may have the potential to change the management paradigm for this malignancy.

  7. Proteasome inhibitors in cancer therapy

    Directory of Open Access Journals (Sweden)

    Wioletta Romaniuk

    2015-12-01

    Full Text Available Proteasomes are multisubunit enzyme complexes. They contain three enzymatic active sites which are termed chymotrypsin-like, trypsin-like, and caspase-like. The elementary function of the proteasomes is degradation of damaged proteins. Proteasome inhibition leads to accumulation of damaged protein, which leads to caspase activation and cell death. This relationship is used in cancer therapy. Bortezomib is the first proteasome inhibitor approved by the US Food and Drug Administration for the treatment of relapsed/refractory multiple myeloma. Carfilzomib belongs to the second generation of drugs, which was approved by the US FDA in 2012. Currently in the study phase there are four new inhibitors: ixazomib (MLN9780/MLN2238, delanzomib (CEP-18770, oprozomib (ONX0912/PR-047 and marizomib (NPI-0052.

  8. Adjuvant therapy in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos

    2001-01-01

    The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.

  9. miR -21的高表达与乳腺癌预后关系的meta分析%Significance of high miR-21 expression on the prognosis of breast carcinoma:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    郭仲莉; 王箭

    2013-01-01

    提目的:评价miR-21的高表达与乳腺癌预后的相关性。方法:检索PubMed ,MEDLINE ,EMBASE ,Web of science ,维普,CNKI数据库,收集从建库至2013年9月期间关于miR-21的高表达与乳腺癌预后相关性的文献,用meta分析方法评价miR-21的高表达是否与乳腺癌的预后相关。结果:共纳入4篇文献(总计548个病例),总生存率(OS )HR的合并值为1.61(95% CI :1.09至2.37,P<0.05)。结论:miR -21的高表达是乳腺癌预后的一个危险因素。%Objective :To evaluate the correlation between the high expression of miR -21 and the prognosis of breast cancer .Methods :Eligible studies which studied the correlation between the high expression of miR -21 and the prognosis of breast cancer were collected through searching PubMed ,MEDLINE , EMBASE ,and Wed of science ,VIP ,CNKI databases .A meta analysis method was used to evaluate whether the high expression of miR -21 has an association with the prognosis of breast cancer .Results :A total of 4 studies (548 cases ) were involved in this meta -analysis .For overall survival (OS ) ,the pooled hazard ratio (HR) of higher miR -21 expression in cancerous tissues was 1 .61(95% CI :1 .09~2 .37 ,P<0 .05) .Conclusions :High expression of miR -21 is a risk factor of breast cancer .

  10. Cancer stem cells, cancer cell plasticity and radiation therapy.

    Science.gov (United States)

    Vlashi, Erina; Pajonk, Frank

    2015-04-01

    Since the first prospective identification of cancer stem cells in solid cancers the cancer stem cell hypothesis has reemerged as a research topic of increasing interest. It postulates that solid cancers are organized hierarchically with a small number of cancer stem cells driving tumor growth, repopulation after injury and metastasis. They give rise to differentiated progeny, which lack these features. The model predicts that for any therapy to provide cure, all cancer stem cells have to be eliminated while the survival of differentiated progeny is less critical. In this review we discuss recent reports challenging the idea of a unidirectional differentiation of cancer cells. These reports provide evidence supporting the idea that non-stem cancer cells exhibit a remarkable degree of plasticity that allows them to re-acquire cancer stem cell traits, especially in the context of radiation therapy. We summarize conditions under which differentiation is reversed and discuss the current knowledge of the underlying mechanisms.

  11. Silicon nanostructures for cancer diagnosis and therapy.

    Science.gov (United States)

    Peng, Fei; Cao, Zhaohui; Ji, Xiaoyuan; Chu, Binbin; Su, Yuanyuan; He, Yao

    2015-01-01

    The emergence of nanotechnology suggests new and exciting opportunities for early diagnosis and therapy of cancer. During the recent years, silicon-based nanomaterials featuring unique properties have received great attention, showing high promise for myriad biological and biomedical applications. In this review, we will particularly summarize latest representative achievements on the development of silicon nanostructures as a powerful platform for cancer early diagnosis and therapy. First, we introduce the silicon nanomaterial-based biosensors for detecting cancer markers (e.g., proteins, tumor-suppressor genes and telomerase activity, among others) with high sensitivity and selectivity under molecular level. Then, we summarize in vitro and in vivo applications of silicon nanostructures as efficient nanoagents for cancer therapy. Finally, we discuss the future perspective of silicon nanostructures for cancer diagnosis and therapy.

  12. Music therapy in supportive cancer care.

    Science.gov (United States)

    Stanczyk, Malgorzata Monika

    2011-06-08

    The purpose of this paper is to show some aspects of music therapy application in cancer care and to present the integration of music therapy program into a continuous supportive cancer care for inpatients. A cancer diagnosis is one of the most feared and serious life events that causes stress in individuals and families. Cancer disrupts social, physical and emotional well-being and results in a range of emotions, including anger, fear, sadness, guilt, embarrassment and shame. Music therapy is a part of a complementary medicine program in supportive cancer care which accompanies medical treatment. There are many benefits of music therapy for cancer patients-interactive music therapy techniques (instrumental improvisation, singing) as well as receptive music therapy techniques (listening to recorded or live music, music and imaginary) can be used to improve mood, decrease stress, pain, anxiety level and enhance relaxation. Music therapy is an effective form of supporting cancer care for patients during the treatment process. It may be also basic for planning effective programs of rehabilitation to promote wellness, improve physical and emotional well-being and the quality of life.

  13. AC1MMYR2 impairs high dose paclitaxel-induced tumor metastasis by targeting miR-21/CDK5 axis.

    Science.gov (United States)

    Ren, Yu; Zhou, Xuan; Yang, Juan-Juan; Liu, Xia; Zhao, Xiao-hui; Wang, Qi-xue; Han, Lei; Song, Xin; Zhu, Zhi-yan; Tian, Wei-ping; Zhang, Lun; Mei, Mei; Kang, Chun-sheng

    2015-07-01

    Paclitaxel (taxol) is a widely used chemo-drug for many solid tumors, while continual taxol treatment is revealed to stimulate tumor dissemination. We previously found that a small molecule inhibitor of miR-21, termed AC1MMYR2, had the potential to impair tumorigenesis and metastasis. The aim of this study was to investigate whether combining AC1MMYR2 with taxol could be explored as a means to limit tumor metastasis. Here we showed that abnormal activation of miR-21/CDK5 axis was associated with breast cancer lymph node metastasis, which was also contribute to high dose taxol-induced invasion and epithelial mesenchymal transition (EMT) in both breast cancer cell line MDA-MB-231 and glioblastoma cell line U87VIII. AC1MMYR2 attenuated CDK5 activity by functional targeting CDK5RAP1, CDK5 activator p39 and target p-FAK(ser732). A series of in vitro assays indicated that treatment of AC1MMYR2 combined with taxol suppressed tumor migration and invasion ability in both MDA-MB-231 and U87VIII cell. More importantly, combination therapy impaired high-dose taxol induced invadopodia, and EMT markers including β-catenin, E-cadherin and vimentin. Strikingly, a significant reduction of lung metastasis in mice was observed in the AC1MMYR2 plus taxol treatment. Taken together, our work demonstrated that AC1MMYR2 appeared to be a promising strategy in combating taxol induced cancer metastasis by targeting miR-21/CDK5 axis, which highlighted the potential for development of therapeutic modalities for better clinic taxol application.

  14. Microtubule-Targeting Therapy for Prostate Cancer

    Science.gov (United States)

    2007-02-01

    Cancer1828 Mol Cancer Ther 2005;4(12). December 2005 22. Sambrook J, Fritsch EF, Maniatis T. Molecular cloning : a laboratory manual. 2nd ed. Cold Spring...Harbor (NY): Cold Spring Harbor Laboratory; 1989. 23. Zhu XX, Kozarsky K, Strahler JR, et al. Molecular cloning of a novel human leukemia-associated...of Cancer Research, Abstract #4940, 2005. 3. Mistry, SJ, Atweh, GF. Microtubule targeting therapy: Anti-stathmin based molecular cancer

  15. CERN launches new cancer therapy initiative

    CERN Multimedia

    2002-01-01

    "The first meeting of a new European network for research in cancer therapy was held at CERN, in February 2002. ENLIGHT, the European Network for Research in Light Ion Therapy aims to coordinate the development of a variety of projects at European facilities for "light ion therapy" - a form of radiation therapy that uses beams of the nuclei of lightweight atoms" (1/2 page).

  16. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    , including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women......Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers...

  17. Targeting the EGFR pathway for cancer therapy

    DEFF Research Database (Denmark)

    Johnston, JB; Navaratnam, S; Pitz, MW

    2006-01-01

    provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side......Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally...... effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, ZD1839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e...

  18. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...

  19. Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

    Science.gov (United States)

    2014-04-21

    Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity

  20. Liposomal cancer therapy: exploiting tumor characteristics

    DEFF Research Database (Denmark)

    Kaasgaard, Thomas; Andresen, Thomas Lars

    2010-01-01

    of cancer treatments. In the search for more effective cancer treatments, nanoparticle- based drug delivery systems, such as liposomes, that are capable of delivering their drug payload selectively to cancer cells are among the most promising approaches. Areas covered in this review: This review provides...... of new liposomal drug delivery systems that better exploit tumor characteristic features is likely to result in more efficacious cancer treatments....... an overview of current strategies for improving the different stages of liposomal cancer therapy, which involve transporting drug-loaded liposomes through the bloodstream, increasing tumor accumulation, and improving drug release and cancer cell uptake after accumulation at the tumor target site. What...

  1. Radiation Therapy for Lung Cancer

    Science.gov (United States)

    ... are available to help. HELPFUL WEB SITES ON LUNG CANCER American Lung Association www.lung.org Lungcancer.org www.lungcancer.org Lung Cancer Alliance www.lungcanceralliance.org Lung Cancer Online www. ...

  2. Neoadjuvant breast cancer therapy and drug development.

    Science.gov (United States)

    Cortazar, Patricia; Kluetz, Paul G

    2015-11-01

    Neoadjuvant treatment of breast cancer initially was limited to patients with locally advanced breast cancer in which downstaging was necessary. Now, neoadjuvant trials have become an increasingly common way to facilitate the rapid assessment of new cancer therapies. The appeal of neoadjuvant trials is that they provide the opportunity to study translational science, tumor biomarkers, and intermediate endpoints in response to systemic therapy within a shortened period. This review summarizes the data that contribute to our understanding of the association between pathological complete response and long-term outcomes, describes the implications of drug development and accelerated approval in neoadjuvant treatment of breast cancer, and provides a perspective on future neoadjuvant drug development.

  3. Building immunity to cancer with radiation therapy.

    Science.gov (United States)

    Haikerwal, Suresh J; Hagekyriakou, Jim; MacManus, Michael; Martin, Olga A; Haynes, Nicole M

    2015-11-28

    Over the last decade there has been a dramatic shift in the focus of cancer research toward understanding how the body's immune defenses can be harnessed to promote the effectiveness of cytotoxic anti-cancer therapies. The ability of ionizing radiation to elicit anti-cancer immune responses capable of controlling tumor growth has led to the emergence of promising combination-based radio-immunotherapeutic strategies for the treatment of cancer. Herein we review the immunoadjuvant properties of localized radiation therapy and discuss how technological advances in radio-oncology and developments in the field of tumor-immunotherapy have started to revolutionize the therapeutic application of radiotherapy.

  4. Targeting tumor suppressor genes for cancer therapy.

    Science.gov (United States)

    Liu, Yunhua; Hu, Xiaoxiao; Han, Cecil; Wang, Liana; Zhang, Xinna; He, Xiaoming; Lu, Xiongbin

    2015-12-01

    Cancer drugs are broadly classified into two categories: cytotoxic chemotherapies and targeted therapies that specifically modulate the activity of one or more proteins involved in cancer. Major advances have been achieved in targeted cancer therapies in the past few decades, which is ascribed to the increasing understanding of molecular mechanisms for cancer initiation and progression. Consequently, monoclonal antibodies and small molecules have been developed to interfere with a specific molecular oncogenic target. Targeting gain-of-function mutations, in general, has been productive. However, it has been a major challenge to use standard pharmacologic approaches to target loss-of-function mutations of tumor suppressor genes. Novel approaches, including synthetic lethality and collateral vulnerability screens, are now being developed to target gene defects in p53, PTEN, and BRCA1/2. Here, we review and summarize the recent findings in cancer genomics, drug development, and molecular cancer biology, which show promise in targeting tumor suppressors in cancer therapeutics.

  5. Anaplastic thyroid cancer, tumorigenesis and therapy.

    LENUS (Irish Health Repository)

    O'Neill, J P

    2010-03-01

    Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

  6. Gene Therapy In Oral Cancer : An Overview

    Directory of Open Access Journals (Sweden)

    Kanaram Choudhary

    2010-07-01

    Full Text Available The treatment and prevention of oral cancer is one of the major hurdles in the field ofcancer. Gene therapy is one of the recent advances in this field to tackle this hurdle with promisingprospects. This overview introduces the reader into the basic idea of gene therapy, types of genetherapy and the various modes of introduction of therapeutic gene into the cancer affected cell.

  7. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  8. Radiation Therapy for Early Stage Lung Cancer

    OpenAIRE

    Parashar, Bhupesh; Arora, Shruthi; Wernicke, A. Gabriella

    2013-01-01

    Radiation therapy for early stage lung cancer is a promising modality. It has been traditionally used in patients not considered candidates for standard surgical resection. However, its role has been changing rapidly since the introduction of new and advanced technology, especially in tumor tracking, image guidance, and radiation delivery. Stereotactic radiation therapy is one such advancement that has shown excellent local control rates and promising survival in early stage lung cancer. In a...

  9. Systemic therapy of cancer: facts and expectations

    Directory of Open Access Journals (Sweden)

    Tanja Čufer

    2007-12-01

    Full Text Available Background: Systemic therapy of cancer had its first major expansion in the second half of the 20th century with the development of chemotherapy and hormonal therapy. Some cancers, like leukemias, lymphomas, osteosarcoma and testicular cancer became highly curable irrespective of anatomic size – stage of the disease. Other more common cancers, such as breast cancer, colon cancer, ovarian cancer, lung cancer and prostate cancer became on a larger scale curable in the early stages of the disease while in the advanced stages of the disease long term remissions could be achieved by chemotherapy and/or hormonal therapy.Conclusions: Cancer patients nowadays live longer and with a better quality of life. With mapping of the human genom, possibilities for determining and identifying the cancer genom became available at the turn of the last century. The era of molecular oncology which enables personalized treatment tailored to each patient and his tumor is now upon us. Molecular oncology makes it possible to identify the molecular targets and to develop therapy which targets them. In addition it gives us more knowledge about the prognostic as well as predictive markers. Good examples of effective targeted cancer therapy are treatment of GIST with imatinib and treatment of HER2+ breast cancer with trastuzumab. In both cases the target as well as the patients were precisely selected. Experience from various trastuzumab trials teach us that targeted therapy will also be the most effective in the early stages of cancer, when the burden of the disease is quite limited. Treatment of advanced cancer with targeted treatment so far mostly results in remissions but not cure. Numerous additional new targeted therapies are currently under development and by no doubt they will very soon allow us to facilitate the selection of proper treatment at proper time for proper patients. In contrast to empirical treatment approaches, a personalized one enables the best

  10. miR-21的高表达与肺癌预后关系的meta分析%Significance of high miR-21 expression on the prognosis of lung carcinoma:A meta-analysis

    Institute of Scientific and Technical Information of China (English)

    郭仲莉; 曾照芳

    2014-01-01

    Objective To evaluate the correlation between the high expression of miR-21 and the prognosis of lung cancer. Methods:Eligible studies which studied the correlation between the high expression of miR-21 and the prognosis of lung cancer were collected through searching PubMed,EMBASE, and Google scholar , VIP , CNKI databases, etc. A meta analysis method was used to use stata v12.0 software to evaluate whether the high expression of miR-21 has an association with the prognosis of lung cancer. Results:A total of 7 studies (369 cases) were involved in this meta-analysis. For overall survival (OS),the pooled hazard ratio (HR) of higher miR-21 expression in cancerous tissues was 1.34(95%CI: 1.19~1.50 , P<0.05). Conclusions: High expression of miR-21 is a risk factor of lung cancer.%目的:评价miR-21的高表达与肺癌预后的相关性。方法:检索PubMed,EMBASE,Google scholar ,维普,CNKI等数据库,收集已公开发表的关于miR-21的高表达与肺癌预后相关性的文献,按meta分析的要求对原始文献的质量进行评估,采用STATA V12.0软件对各研究的效应量进行统计分析。结果:共纳入7篇文献(共369个病例),总生存率(OS)HR的合并值为1.34(95%CI:1.19至1.50,P <0.05)。结论:miR-21的高表达是肺癌预后的一个危险因素。

  11. Biologic therapies for advanced pancreatic cancer.

    Science.gov (United States)

    He, Aiwu Ruth; Lindenberg, Andreas Peter; Marshall, John Lindsay

    2008-08-01

    Patients with metastatic pancreatic cancer have poor prognosis and short survival due to lack of effective therapy and aggressiveness of the disease. Pancreatic cancer has widespread chromosomal instability, including a high rate of translocations and deletions. Upregulated EGF signaling and mutation of K-RAS are found in most pancreatic cancers. Therefore, inhibitors that target EGF receptor, K-RAS, RAF, MEK, mTOR, VEGF and PDGF, for example, have been evaluated in patients with pancreatic cancer. Although significant activities of these inhibitors have not been observed in the majority of pancreatic cancer patients, an enormous amount of experience and knowledge has been obtained from recent clinical trials. With a better inhibitor or combination of inhibitors, and improvement in the selection of patients for available inhibitors, better therapy for pancreatic cancer is on the horizon.

  12. Therapy for bone metastasis from different cancers

    Institute of Scientific and Technical Information of China (English)

    Zheng Zhang; Peng Tan; Baoguo Mi; Chao Song; Yi Deng; Hanfeng Guan

    2016-01-01

    The bone is the most common target organ of cancer metastasis. Bone metastasis leads to considerable morbidity due to skeletal-related events (SREs). These include bone pain, hypercalcemia, pathologic frac-tures, and compression of the spinal cord. Cancers such as those of the lung, breast, prostate, and kidney are more likely to cause SREs than other cancer types. Additionaly, some blood cancers, including multiple myeloma and lymphoma, frequently cause SREs. In this article, we review the conventional therapies for metastatic bone disease, including drug therapy, radiotherapy, and surgery. Among osteoclast-targeting agents, bisphosphonates and nuclear factor kappa-B ligand inhibitors are the most widely used agents to prevent cancer-related bone loss. Unsealed radioisotopes are also considered promising in cancer therapy. Currently, iodine-131, strontium-89, and radium-223 are available for the treatment of bone metastasis. However, the treatments for blood cancers with SREs are diferent from those of other cancers. In those cases, new classes of agents including proteasome inhibitors, immunomodulatory drugs, monoclonal anti-bodies, and histone deacetylase inhibitors have shown remarkable eficacy. We also discuss the potential development of new therapies for these diseases.

  13. Palliative Endoscopic Therapy of Esophageal Cancer

    Institute of Scientific and Technical Information of China (English)

    H.Schaefer; A.H.Hoelscher

    2004-01-01

    Patients with locally unresectable esophageal cancer or distant metastasis are usually treated with definite radiotherapy or radiochemotherapy. Dysphagia of these patients should further be treated by endoscopic therapy in order to maintain swallowing and oral food intake as long as possible. The same situation is present in patients with local recurrence of esophageal cancer after surgery or radiochemotherapy.

  14. Network systems biology for targeted cancer therapies

    Institute of Scientific and Technical Information of China (English)

    Ting-Ting Zhou

    2012-01-01

    The era of targeted cancer therapies has arrived.However,due to the complexity of biological systems,the current progress is far from enough.From biological network modeling to structural/dynamic network analysis,network systems biology provides unique insight into the potential mechanisms underlying the growth and progression of cancer cells.It has also introduced great changes into the research paradigm of cancer-associated drug discovery and drug resistance.

  15. Future Directions in Pancreatic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    David Orchard-Webb

    2015-05-01

    Full Text Available Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics.

  16. Targeted Radiation Therapy for Cancer Initiative

    Science.gov (United States)

    2015-09-01

    and whether this difference changed the outcome for palliative patients, 6) use of the Calypso system, and other advanced radiation therapy equipment...use of advanced technology radiation therapy techniques, such as IMRT and VMAT, in treating palliative patients. The main obstacle to overcome in...treating low-to-intermediate risk prostate cancer with intensity modulated radiation therapy (IMRT) using an electromagnetic localization system. IMRT

  17. Antiangiogenic therapy for breast cancer

    DEFF Research Database (Denmark)

    Nielsen, D.L.; Andersson, M.; Andersen, Jon Alexander Lykkegaard

    2010-01-01

    ABSTRACT: Angiogenesis is an important component of cancer growth, invasion and metastasis. Therefore, inhibition of angiogenesis is an attractive strategy for treatment of cancer. We describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development...

  18. Hormone Therapy for Prostate Cancer

    Science.gov (United States)

    ... Galvão DA, Taaffe DR, Spry N, Newton RU. Exercise can prevent and even reverse adverse effects of androgen suppression treatment in men with prostate cancer. Prostate Cancer and Prostatic Diseases 2007; 10(4): ...

  19. Dance as a therapy for cancer prevention.

    Science.gov (United States)

    Aktas, Gurbuz; Ogce, Filiz

    2005-01-01

    Even though the field of medicine has developed tremendously, the wide variety of cancer is still among chronic and life threatening disease today. Therefore, the specialists constantly research and try every possible way to find cure or preventive ways to stop its further development. For this reason, studies concerning the chronic disease such as cancer have been spread to many different fields. In this regard, many other alternative ways besides medicine, are used in prevention of cancer. Nutritional therapy, herbal therapy, sportive activities, art therapy, music therapy, dance therapy, imagery, yoga and acupuncture can be given as examples. Among these, dance/movement therapy which deals with individuals physical, emotional, cognitive as well as social integration is widely used as a popular form of physical activity. The physical benefits of dance therapy as exercise are well documented. Studies have shown that physical activity is known to increase special neurotransmitter substances in the brain (endorphins), which create a state of well-being. And total body movement such as dance enhances the functions of other body systems, such as circulatory, respiratory, skeletal, and muscular systems. Regarding its unique connection to the field of medicine, many researches have been undertaken on the effects of dance/movement therapy in special settings with physical problems such as amputations, traumatic brain injury, and stroke, chronic illnesses such as anorexia, bulimia, cancer, Alzheimer's disease, cystic fibrosis, heart disease, diabetes, asthma, AIDS, and arthritis. Today dance/movement therapy is a well recognized form of complementary therapy used in hospitals as well as at the comprehensive clinical cancer centres.

  20. Functionalized nanobodies for cancer therapy

    NARCIS (Netherlands)

    van Vught, R.W.M.

    2014-01-01

    Cancer treatment is complicated by the high similarity between cancerous and healthy tissue. New anti-cancer drugs, the monoclonal antibodies, act on one specific molecule/process and thereby minimize side effects. Despite that these monoclonal antibodies are highly specific and harbor multiple mode

  1. Photodynamic therapy for skin field cancerization

    DEFF Research Database (Denmark)

    Braathen, L R; Morton, C A; Basset-Seguin, N

    2012-01-01

    in this area. With respect to the skin, this term is used to define the presence of multiple non-melanoma skin cancer, its precursors, actinic keratoses and dysplastic keratinocytes in sun exposed areas. The multiplicity of the lesions and the extent of the area influence the treatment decision. Providing...... at least equivalent efficacy and tolerability, field directed therapies are therefore often more worthwhile than lesion targeted approaches. Photodynamic therapy (PDT) with its selective sensitization and destruction of diseased tissue is one ideal form of therapy for this indication. In the following...... paper the use of PDT for the treatment of field cancerized skin is reviewed and recommendations are given for its use....

  2. NFkappaB activation is essential for miR-21 induction by TGFβ1 in high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Madhyastha, Radha, E-mail: radharao@med.miyazaki-u.ac.jp; Madhyastha, HarishKumar; Pengjam, Yutthana; Nakajima, Yuichi; Omura, Sayuri; Maruyama, Masugi

    2014-09-05

    Highlights: • Transforming growth factor beta 1 (TGFβ1) induces miR-21 in high glucose conditions. • NFkappaB activation and subsequent ROS generation are necessary for TGFβ1’s effect. • TGFβ1 facilitates binding of NFkB p65 to miR-21 promoter. • SMAD proteins bind to R-SBE sites on primary miR-21, in NFkB dependent manner. - Abstract: Transforming growth factor beta1 (TGFβ1) is a pleiotropic growth factor with a very broad spectrum of effects on wound healing. Chronic non-healing wounds such as diabetic foot ulcers express reduced levels of TGFβ1. On the other hand, our previous studies have shown that the microRNA miR-21 is differentially regulated in diabetic wounds and that it promotes migration of fibroblast cells. Although interplay between TGFβ1 and miR-21 are studied in relation to cancer, their interaction in the context of chronic wounds has not yet been investigated. In this study, we examined if TGFβ1 could stimulate miR-21 in fibroblasts that are subjected to high glucose environment. MiR-21 was, in fact, induced by TGFβ1 in high glucose conditions. The induction by TGFβ1 was dependent on NFκB activation and subsequent ROS generation. TGFβ1 was instrumental in degrading the NFκB inhibitor IκBα and facilitating the nuclear translocation of NFκB p65 subunit. EMSA studies showed enhanced DNA binding activity of NFκB in the presence of TGFβ1. ChIP assay revealed binding of p65 to miR-21 promoter. NFκB activation was also required for the nuclear translocation of Smad 4 protein and subsequent direct interaction of Smad proteins with primary miR-21 as revealed by RNA-IP studies. Our results show that manipulation of TGFβ1–NFκB–miR-21 pathway could serve as an innovative approach towards therapeutics to heal diabetic ulcers.

  3. Cancer therapy-related oral mucositis.

    Science.gov (United States)

    Redding, Spencer W

    2005-08-01

    Oral mucositis is a common side effect of cancer therapies, particularly radiation therapy for head and neck cancer and various forms of chemotherapy. It commonly results in severe oral pain that can compromise the duration and success of cancer management. Hospitalizations are common because patients lose the ability to take anything by mouth due to severe pain and must have alimentation supported during this period. Pain management usually requires potent narcotic analgesia. Cancer therapy-related oral mucositis is commonly described as the most significant and debilitating acute complication associated with radiation therapy and chemotherapy. Until recently, cancer therapy-induced oral mucositis was thought to be a process involving the epithelium only. Evidence is building that the process of oral mucositis involves far more than just the epithelium, but includes multiple cellular processes of the submucosa as well. Many strategies have been evaluated to prevent oral mucositis, but the data is confusing since it is often conflicting. Therapy with the growth factor, KGF1, appears promising, as it is the only medication currently approved by the FDA. A multifaceted approach that targets the entire mucositis process will probably be needed to optimize overall prevention.

  4. Cancer and electromagnetic radiation therapy: Quo Vadis?

    CERN Document Server

    Makropoulou, Mersini

    2016-01-01

    In oncology, treating cancer with a beam of photons is a well established therapeutic technique, developed over 100 years, and today over 50% of cancer patients will undergo traditional X-ray radiotherapy. However, ionizing radiation therapy is not the only option, as the high-energy photons delivering their cell-killing radiation energy into cancerous tumor can lead to significant damage to healthy tissues surrounding the tumor, located throughout the beam's path. Therefore, in nowadays, advances in ionizing radiation therapy are competitive to non-ionizing ones, as for example the laser light based therapy, resulting in a synergism that has revolutionized medicine. The use of non-invasive or minimally invasive (e.g. through flexible endoscopes) therapeutic procedures in the management of patients represents a very interesting treatment option. Moreover, as the major breakthrough in cancer management is the individualized patient treatment, new biophotonic techniques, e.g. photo-activated drug carriers, help...

  5. Cognitive Behavioral Therapy in Cancer Patients

    Directory of Open Access Journals (Sweden)

    Cem Soylu

    2014-09-01

    Full Text Available Cognitive behavioral therapy is one of the structured but flexible psychosocial interventions that could be applied to patients with cancer. In many studies the positive effects of cognitive behavioral therapy in reducing psychological morbidity and improving the quality of life of cancer patients have been shown. In this article, the contents and techniques of adapted cognitive behavioral therapy for patients with cancer and its effectiveness in commonly seen psychiatric disorders have been reviewed. The aim of this article is to contribute positively to physicians and nurses in Turkey for early detection of psychological distress and referral to the therapist that would clearly increase the quality of life of cancer patients. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 257-270

  6. Exercise therapy across the lung cancer continuum.

    Science.gov (United States)

    Jones, Lee W; Eves, Neil D; Waner, Emily; Joy, Anil A

    2009-07-01

    A lung cancer diagnosis and associated therapeutic management are associated with unique and varying degrees of adverse physical/functional impairments that dramatically reduce patients' ability to tolerate exercise. Poor exercise capacity predisposes to increased susceptibility to other common age-related diseases, poor quality of life, and likely premature death. This article reviews the literature investigating the role of exercise as an adjunct therapy across the lung cancer continuum (ie, prevention to palliation). The current evidence suggests that exercise training is a safe and feasible adjunct therapy for patients with operable lung cancer both before and after pulmonary resection. Among patients with inoperable disease, feasibility and safety studies of carefully prescribed exercise training are warranted. Preliminary evidence in this area suggests that exercise therapy may be an important consideration in multidisciplinary management of patients diagnosed with lung cancer.

  7. Optimizing systemic therapy for bladder cancer.

    Science.gov (United States)

    Pal, Sumanta K; Milowsky, Matthew I; Plimack, Elizabeth R

    2013-07-01

    Over the past several decades, few new systemic agents have been incorporated into the treatment paradigm for bladder cancer. Platinum-based therapy remains the cornerstone of treatment in the perioperative and metastatic settings. Despite level one evidence, use of cisplatin-based therapy in the neoadjuvant setting has been dismal. Second-line therapy for metastatic disease has only modest activity with no survival benefit. However, the elucidation and investigation of novel molecular targets, new therapeutics, and associated biomarkers with strong biologic rationale are actively changing the landscape in bladder cancer. Although the field is moving rapidly, no new drug approvals are currently pending and a need remains to continue to educate the medical oncology and urology communities on the optimal use of currently available treatments. This article outlines the evidence, including that from prospective studies and meta-analyses, providing the basis for the current recommendations from NCCN, and details previous and ongoing studies of targeted therapy for bladder cancer.

  8. miR-21 Reduces Hydrogen Peroxide-Induced Apoptosis in c-kit+ Cardiac Stem Cells In Vitro through PTEN/PI3K/Akt Signaling

    Science.gov (United States)

    Wang, Yan; Long, Xianping; Zhao, Ranzun; Wang, Zhenglong; Liu, Zhijiang

    2016-01-01

    The low survival rate of cardiac stem cells (CSCs) in the infarcted myocardium hampers cell therapy for ischemic cardiomyopathy. MicroRNA-21 (miR-21) and one of its target proteins, PTEN, contribute to the survival and proliferation of many cell types, but their prosurvival effects in c-kit+ CSC remain unclear. Thus, we hypothesized that miR-21 reduces hydrogen peroxide- (H2O2-) induced apoptosis in c-kit+ CSC and estimated the contribution of PTEN/PI3K/Akt signaling to this oxidative circumstance. miR-21 mimics efficiently reduced H2O2-induced apoptosis in c-kit+ CSC, as evidenced by the downregulation of the proapoptosis proteins caspase-3 and Bax and upregulation of the antiapoptotic Bcl-2. In addition, the gain of function of miR-21 in c-kit+ CSC downregulated the protein level of PTEN although its mRNA level changed slightly; in the meantime, miR-21 overexpression also increased phospho-Akt (p-Akt). The antiapoptotic effects of miR-21 were comparable with Phen (bpV), the selective inhibitor of PTEN, while miR-21 inhibitor or PI3K's inhibitor LY294002 efficiently attenuated the antiapoptotic effect of miR-21. Taken together, these results indicate that the anti-H2O2-induced apoptosis effect of miR-21 in c-kit+ CSC is contributed by PTEN/PI3K/Akt signaling. miR-21 could be a potential molecule to facilitate the c-kit+ CSC therapy in ischemic myocardium. PMID:27803763

  9. DNA origami applications in cancer therapy.

    Science.gov (United States)

    Udomprasert, Anuttara; Kangsamaksin, Thaned

    2017-08-01

    Due to the complexity and heterogeneity of cancer, the development of cancer diagnosis and therapy is still progressing, and a complete understanding of cancer biology remains elusive. Recently, cancer nanomedicine has gained much interest as a promising diagnostic and therapeutic strategy, as a wide range of nanomaterials possess unique physical properties that can render drug delivery systems safer and more effective. Also, targeted drug delivery and precision medicine have now become a new paradigm in cancer therapy. With nanocarriers, chemotherapeutic drugs could be directly delivered into target cancer cells, resulting in enhanced efficiency with fewer side-effects. DNA, a biomolecule with molecular self-assembly properties, has emerged as a versatile nanomaterial to construct multifunctional platforms; DNA nanostructures can be modified with functional groups to improve their utilities as biosensors or drug carriers. Such applications have become possible with the advent of the scaffolded DNA origami method. This breakthrough technique in structural DNA nanotechnology provides an easier and faster way to construct DNA nanostructures with various shapes. Several experiments proved that DNA origami nanostructures possess abilities to enhance efficacies of chemotherapy, reduce adverse side-effects, and even circumvent drug resistance. Here, we highlight the principles of the DNA origami technique and its applications in cancer therapeutics and discuss current challenges and opportunities to improve cancer detection and targeted drug delivery. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  10. The marriage of conventional cancer treatments and alternative cancer therapies.

    Science.gov (United States)

    Decker, Georgia M

    2008-06-01

    The terms "alternative" or "unconventional" have been used to describe any therapy used instead of conventional approaches. Conventional approaches, known as "standard" or "traditional" or "biomedical" approaches, have had broad application in Western medicine. Complementary and alternative medicine has been referred to as "integrative," "integrated," or "complementary" when therapies are combined with conventional approaches, such as those for cancer.

  11. Combination antiretroviral therapy and cancer risk

    DEFF Research Database (Denmark)

    Borges, Álvaro H

    2017-01-01

    PURPOSE OF REVIEW: To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. RECENT FINDINGS: HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies...... initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection....... into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk...

  12. The therapy of gefitinib towards breast cancer partially through ...

    African Journals Online (AJOL)

    The therapy of gefitinib towards breast cancer partially through reversing breast cancer biomarker arginine. ... Background: Breast cancer remains the leading reason of cancer death among women worldwide, and gefitinib is ... Article Metrics.

  13. Ganetespib radiosensitization for liver cancer therapy

    Science.gov (United States)

    Chettiar, Sivarajan T.; Malek, Reem; Annadanam, Anvesh; Nugent, Katriana M.; Kato, Yoshinori; Wang, Hailun; Cades, Jessica A.; Taparra, Kekoa; Belcaid, Zineb; Ballew, Matthew; Manmiller, Sarah; Proia, David; Lim, Michael; Anders, Robert A.; Herman, Joseph M.; Tran, Phuoc T.

    2016-01-01

    ABSTRACT Therapies for liver cancer particularly those including radiation are still inadequate. Inhibiting the stress response machinery is an appealing anti-cancer and radiosensitizing therapeutic strategy. Heat-shock-protein-90 (HSP90) is a molecular chaperone that is a prominent effector of the stress response machinery and is overexpressed in liver cancer cells. HSP90 client proteins include critical components of pathways implicated in liver cancer cell survival and radioresistance. The effects of a novel non-geldanamycin HSP90 inhibitor, ganetespib, combined with radiation were examined on 3 liver cancer cell lines, Hep3b, HepG2 and HUH7, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γH2AX foci kinetics and client protein expression in pathways important for liver cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined ganetespib-radiation treatment on tumor cell proliferation in a HepG2 hind-flank tumor graft model. Nanomolar levels of ganetespib alone exhibited liver cancer cell anti-cancer activity in vitro as shown by decreased clonogenic survival that was associated with increased apoptotic cell death, prominent G2-M arrest and marked changes in PI3K/AKT/mTOR and RAS/MAPK client protein activity. Ganetespib caused a supra-additive radiosensitization in all liver cancer cell lines at low nanomolar doses with enhancement ratios between 1.33–1.78. These results were confirmed in vivo, where the ganetespib-radiation combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in HepG2 tumor grafts. Our data suggest that combined ganetespib-radiation therapy exhibits promising activity against liver cancer cells, which should be investigated in clinical studies. PMID:26980196

  14. Complementary therapies for cancer pain.

    Science.gov (United States)

    Cassileth, Barrie; Trevisan, Carrie; Gubili, Jyothirmai

    2007-08-01

    Pharmacologic treatment of pain does not always meet patients' needs and may produce difficult side effects. Complementary therapies, which are safe, noninvasive, and generally considered to be relatively free of toxicity, may be used adjunctively with standard pain management techniques to improve outcome and reduce the need for prescription medication. Approaches such as acupuncture, massage therapy, mind-body interventions, and music therapy effectively reduce pain, enhance quality of life, and provide patients with the opportunity to participate in their own care. Such therapies have an important role in modern pain management.

  15. MiR-21 expression in the tumor stroma of oral squamous cell carcinoma: an independent biomarker of disease free survival.

    Directory of Open Access Journals (Sweden)

    Nora Hedbäck

    Full Text Available Oral squamous cell carcinoma (OSCC patients have a high mortality rate; thus, new clinical biomarkers and therapeutic options are needed. MicroRNAs (miRNAs are short noncoding RNAs that regulate posttranscriptional gene expression and are commonly deregulated in OSCC and other cancers. MicroRNA-21 (miR-21 is the most consistently overexpressed miRNA in several types of cancer, and it might be a useful clinical biomarker and therapeutic target. To better understand the role of miR-21 in OSCC, paraffin-embedded tumor tissue samples from 86 patients with primary OSCC were analyzed by in situ hybridization. We found that miR-21 was primarily expressed in the tumor stroma and in some tumor-associated blood vessels with no expression in the adjacent normal epithelia or stroma. Using image analysis, we quantitatively estimated miR-21 expression levels specifically in the stroma of a cohort of OSCC samples. These miR-21 levels significantly correlated with disease free survival with the highest levels being located in the stroma. Stromal miR-21 expression was independently associated with a poorer prognosis, even after adjusting for clinical parameters (perineural invasion and N-stage in a multivariate analysis. In summary, we have shown that miR-21 is located in the carcinoma cells, stroma and blood vessels of tumors, and its expression specifically in the stromal compartment has a negative prognostic value in OSCC.

  16. Epigenetic Therapy in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Stephen V Liu

    2013-05-01

    Full Text Available Epigenetic dysregulation of gene function has been strongly implicated in carcinogenesis and is one of the mechanisms contributing to the development of lung cancer. The inherent reversibility of epigenetic alterations makes them viable therapeutic targets. Here, we review the therapeutic implications of epigenetic changes in lung cancer, and recent advances in therapeutic strategies targeting DNA methylation and histone acetylation.

  17. Radiation Therapy for Skin Cancer

    Science.gov (United States)

    ... complete chart of side effects. Side effects of Skin Cancer Treatment OrganSystem General Body • cTo ( i D rme ... scrilineesnr/ desbuaoocrnfettedhh) e( ersatkrrieena) tment HELPFUL WEBSITES ON SKIN CANCER TARG E T I NG C A NC ...

  18. New possibilities for cancer therapy with advances in cancer immunology.

    Science.gov (United States)

    MacLean, G D; Longenecker, B M

    1994-04-01

    There has been progress over the last decade in addressing three questions: Are there cancer-associated antigens that could be targets for immunotherapy? Can the human immune system recognize cancer-associated antigens? Can an anti-cancer immune response affect cancer cells and lead to increased survival? Results from animal model studies have been interpreted by optimists as encouraging, and by pessimists as being irrelevant to human cancer. Earlier studies on "cancer vaccines" utilized heterogeneous cell extracts of cell components. Monoclonal antibodies have enabled identification of relevant cancer-associated antigens or epitopes, such as the ganglioside GM2, the carbohydrates TF and STn, and the peptide sequences of MUC-1. In parallel with research on immune adjuvants and measures designed to inhibit suppressor activity, these epitopes are being tested for their potential in the immunotherapy of solid tumors. It is clear that some of these cancer-associated epitopes are immunogenic in humans. Mixed responses may relate to cancer heterogeneity and may indicate the importance of multi-epitopic vaccines. Responses are encouraging, but are they relevant? Prolonged disease stability challenges us to re-think the goals of cancer therapy. Recent advances in the knowledge of the effect of cytokines on tumor antigen expression and the regulation of the immune response, coupled with advances in active specific immunotherapy, provide hope that biomodulation may become an important part of the therapy of solid tumors in the next century.

  19. MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer.

    Science.gov (United States)

    Bertoli, Gloria; Cava, Claudia; Castiglioni, Isabella

    2015-01-01

    Dysregulation of microRNAs (miRNAs) is involved in the initiation and progression of several human cancers, including breast cancer (BC), as strong evidence has been found that miRNAs can act as oncogenes or tumor suppressor genes. This review presents the state of the art on the role of miRNAs in the diagnosis, prognosis, and therapy of BC. Based on the results obtained in the last decade, some miRNAs are emerging as biomarkers of BC for diagnosis (i.e., miR-9, miR-10b, and miR-17-5p), prognosis (i.e., miR-148a and miR-335), and prediction of therapeutic outcomes (i.e., miR-30c, miR-187, and miR-339-5p) and have important roles in the control of BC hallmark functions such as invasion, metastasis, proliferation, resting death, apoptosis, and genomic instability. Other miRNAs are of interest as new, easily accessible, affordable, non-invasive tools for the personalized management of patients with BC because they are circulating in body fluids (e.g., miR-155 and miR-210). In particular, circulating multiple miRNA profiles are showing better diagnostic and prognostic performance as well as better sensitivity than individual miRNAs in BC. New miRNA-based drugs are also promising therapy for BC (e.g., miR-9, miR-21, miR34a, miR145, and miR150), and other miRNAs are showing a fundamental role in modulation of the response to other non-miRNA treatments, being able to increase their efficacy (e.g., miR-21, miR34a, miR195, miR200c, and miR203 in combination with chemotherapy).

  20. Future of Bacterial Therapy of Cancer.

    Science.gov (United States)

    Hoffman, Robert M

    2016-01-01

    Bacterial therapy of cancer has a centuries-long history and was first-line therapy at the hospital in New York City that would become Memorial Sloan-Kettering Cancer Center, under Dr. William B. Coley. However, after Coley's death in 1936, bacterial therapy of cancer ceased in the clinic until the present century. Clinical trials have been recently carried out for strains of the obligate anaerobe Clostridium novyi with the toxin gene deleted, and on an attenuated strain of Salmonella typhimurium (S. typhimurium), which is a facultative anaerobe that can grow in viable, as well as necrotic, areas of tumors, unlike Clostridium, which can only grow in the hypoxic areas. Our laboratory has developed the novel strain S. typhimurium A1-R that is effective against all tumor types in clinically-relevant mouse models, including patient-derived orthotopic xenograft (PDOX) mouse models. This chapter suggests future clinical applications for S. typhimurium A1-R.

  1. IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia.

    Directory of Open Access Journals (Sweden)

    Natalia Ruiz-Lafuente

    Full Text Available Interleukin 4 (IL-4 induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL cells. MicroRNAs (miRNAs regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC, and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p, miR-500a (3p, miR-502 (3p, and miR-532 (3p and 5p genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL.

  2. Immunotoxin: A new tool for cancer therapy.

    Science.gov (United States)

    Allahyari, Hossein; Heidari, Sahar; Ghamgosha, Mehdi; Saffarian, Parvaneh; Amani, Jafar

    2017-02-01

    Cancer is one of the main reasons of death in the most countries and in Iran. Immunotherapy quickly became one of the best methods of cancer treatment, along with chemotherapy and radiation. "Immunotoxin Therapy" is a promising way of cancer therapy that is mentioned in this field. Immunotoxins are made from a toxin attaching to an antibody target proteins present on cancer cells. The first-generation immunotoxins were made of a full-length toxin attached to whole monoclonal antibodies. But, these immunotoxins could bind to normal cells. DAB389IL2 was the first immunotoxin approved by the Food and Drug Administration. Current trends and researches are ongoing on finding proteins that in combination with immunotoxins have minimal immunogenicity and the most potency for target cell killing.

  3. Immune-Mediated Therapies for Liver Cancer

    Science.gov (United States)

    Aravalli, Rajagopal N.; Steer, Clifford J.

    2017-01-01

    In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma. PMID:28218682

  4. Combination antiretroviral therapy and cancer risk.

    Science.gov (United States)

    Borges, Álvaro H

    2017-01-01

    To review the newest research about the effects of combination antiretroviral therapy (cART) on cancer risk. HIV+ persons are at increased risk of cancer. As this risk is higher for malignancies driven by viral and bacterial coinfections, classifying malignancies into infection-related and infection-unrelated has been an emerging trend. Cohorts have detected major reductions in the incidence of Kaposi sarcoma and non-Hodgkin lymphoma (NHL) following cART initiation among immunosuppressed HIV+ persons. However, recent randomized data indicate that cART reduces risk of Kaposi sarcoma and NHL also during early HIV infection before overt immunosuppression occurs. Long-term effects of cART exposure on cancer risk are not well defined; according to basic and epidemiological research, there might be specific associations of each cART class with distinct patterns of cancer risk. The relationship between cART exposure and cancer risk is complex and nuanced. It is an intriguing fact that, whether initiated during severe immunosuppression or not, cART reduces risk of Kaposi sarcoma and NHL. Further research should identify mediators of the benefit of immediate cART initiation in reducing cancer risk, understand the relationship between long-term cART exposure and cancer incidence and assess whether adjuvant anti-inflammatory therapies can reduce cancer risk during treated HIV infection.

  5. Clinical adenoviral gene therapy for prostate cancer.

    Science.gov (United States)

    Schenk, Ellen; Essand, Magnus; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Danielsson, Angelika; Dautzenberg, Iris J C; Dzojic, Helena; Erbacher, Patrick; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Hoeben, Rob; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Lindholm, Leif; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nilsson, Berith; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schooten, Erik; Seymour, Len; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; Veldhoven-Zweistra, Joke L M; de Vrij, Jeroen; van Weerden, Wytske; Wagner, Ernst; Willemsen, Ralph

    2010-07-01

    Prostate cancer is at present the most common malignancy in men in the Western world. When localized to the prostate, this disease can be treated by curative therapy such as surgery and radiotherapy. However, a substantial number of patients experience a recurrence, resulting in spreading of tumor cells to other parts of the body. In this advanced stage of the disease only palliative treatment is available. Therefore, there is a clear clinical need for new treatment modalities that can, on the one hand, enhance the cure rate of primary therapy for localized prostate cancer and, on the other hand, improve the treatment of metastasized disease. Gene therapy is now being explored in the clinic as a treatment option for the various stages of prostate cancer. Current clinical experiences are based predominantly on trials with adenoviral vectors. As the first of a trilogy of reviews on the state of the art and future prospects of gene therapy in prostate cancer, this review focuses on the clinical experiences and progress of adenovirus-mediated gene therapy for this disease.

  6. [Cancer therapy by PARP inhibitors].

    Science.gov (United States)

    Seimiya, Hiroyuki

    2015-08-01

    Poly(ADP-ribose) polymerases(PARP) synthesize the ADP-ribose polymers onto proteins and play a role in DNA repair. PARP inhibitors block the repair of single-strand breaks, which in turn gives rise to double-strand breaks during DNA replication. Thus, PARP inhibitors elicit synthetic lethality in cancer with BRCA1/2 loss-of-function mutations that hamper homologous recombination repair of double-strand breaks. Olaparib, the first-in-class PARP inhibitor, was approved for treatment of BRCA-mutated ovarian cancer in Europe and the United States in 2014. Other PARP inhibitors under clinical trials include rucaparib, niraparib, veliparib, and the "PARP-trapping" BMN-673. BRCA1/2 sequencing is an FDA-approved companion diagnostics, which predicts the cancer vulnerability to PARP inhibition. Together, synthetic lethal PARP inhibition is a novel promising strategy for cancer intervention even in cases without prominent driver oncogenes.

  7. Testosterone Replacement Therapy and Prostate Cancer Incidence

    OpenAIRE

    Eisenberg, Michael Louis

    2015-01-01

    While early studies demonstrated a positive association between testosterone and prostate cancer, evidence on the nature of the relationship has evolved with time and newer data. Studies examining links between baseline testosterone levels as well as testosterone therapy and incident prostate cancer, reveal a more complex relationship. Moreover, investigators have reported their initial experiences with supplementing testosterone in men with a history of both treated and untreated prostate ca...

  8. Cardiovascular disease after cancer therapy

    Directory of Open Access Journals (Sweden)

    Berthe M.P. Aleman

    2014-06-01

    Better knowledge of these cardiac effects will contribute to both primary and secondary prevention of late complications where exposure to cardiotoxic treatment is unavoidable. Also surrogate markers would help to identify patients at increased risk of cardiotoxicity. Evidence-based screening guidelines for CVD following cancer are also needed. Finally, risk prediction models should be developed to guide primary treatment choice and appropriate follow up after cancer treatment.

  9. PARP Inhibitors for Cancer Therapy.

    Science.gov (United States)

    Lin, Ken Y; Kraus, W Lee

    2017-04-06

    Rucaparib is an inhibitor of nuclear poly (ADP-ribose) polymerases (inhibition of PARP-1 > PARP-2 > PARP-3), following a similar drug, Olaparib. It disrupts DNA repair and replication pathways (and possibly transcription), leading to selective killing of cancer cells with BRCA1/2 mutations. Rucaparib is approved for recurrent ovarian cancers with germline or somatic mutations in BRCA1/2. Copyright © 2017. Published by Elsevier Inc.

  10. Cardiovascular disease after cancer therapy

    Science.gov (United States)

    Aleman, Berthe M.P.; Moser, Elizabeth C.; Nuver, Janine; Suter, Thomas M.; Maraldo, Maja V.; Specht, Lena; Vrieling, Conny; Darby, Sarah C.

    2014-01-01

    Improvements in treatment and earlier diagnosis have both contributed to increased survival for many cancer patients. Unfortunately, many treatments carry a risk of late effects including cardiovascular diseases (CVDs), possibly leading to significant morbidity and mortality. In this paper we describe current knowledge of the cardiotoxicity arising from cancer treatments, outline gaps in knowledge, and indicate directions for future research and guideline development, as discussed during the 2014 Cancer Survivorship Summit organised by the European Organisation for Research and Treatment of Cancer (EORTC). Better knowledge is needed of the late effects of modern systemic treatments and of radiotherapy to critical structures of the heart, including the effect of both radiation dose and volume of the heart exposed. Research elucidating the extent to which treatments interact in causing CVD, and the mechanisms involved, as well as the extent to which treatments may increase CVD indirectly by increasing cardiovascular risk factors is also important. Systematic collection of data relating treatment details to late effects is needed, and great care is needed to obtain valid and generalisable results. Better knowledge of these cardiac effects will contribute to both primary and secondary prevention of late complications where exposure to cardiotoxic treatment is unavoidable. Also surrogate markers would help to identify patients at increased risk of cardiotoxicity. Evidence-based screening guidelines for CVD following cancer are also needed. Finally, risk prediction models should be developed to guide primary treatment choice and appropriate follow up after cancer treatment. PMID:26217163

  11. Targeting the TGFβ pathway for cancer therapy.

    Science.gov (United States)

    Neuzillet, Cindy; Tijeras-Raballand, Annemilaï; Cohen, Romain; Cros, Jérôme; Faivre, Sandrine; Raymond, Eric; de Gramont, Armand

    2015-03-01

    The TGFβ signaling pathway has pleiotropic functions regulating cell growth, differentiation, apoptosis, motility and invasion, extracellular matrix production, angiogenesis, and immune response. TGFβ signaling deregulation is frequent in tumors and has crucial roles in tumor initiation, development and metastasis. TGFβ signaling inhibition is an emerging strategy for cancer therapy. The role of the TGFβ pathway as a tumor-promoter or suppressor at the cancer cell level is still a matter of debate, due to its differential effects at the early and late stages of carcinogenesis. In contrast, at the microenvironment level, the TGFβ pathway contributes to generate a favorable microenvironment for tumor growth and metastasis throughout all the steps of carcinogenesis. Then, targeting the TGFβ pathway in cancer may be considered primarily as a microenvironment-targeted strategy. In this review, we focus on the TGFβ pathway as a target for cancer therapy. In the first part, we provide a comprehensive overview of the roles played by this pathway and its deregulation in cancer, at the cancer cell and microenvironment levels. We go on to describe the preclinical and clinical results of pharmacological strategies to target the TGFβ pathway, with a highlight on the effects on tumor microenvironment. We then explore the perspectives to optimize TGFβ inhibition therapy in different tumor settings.

  12. The autophagic paradox in cancer therapy.

    Science.gov (United States)

    Wu, W K K; Coffelt, S B; Cho, C H; Wang, X J; Lee, C W; Chan, F K L; Yu, J; Sung, J J Y

    2012-02-23

    Autophagy, hallmarked by the formation of double-membrane bound organelles known as autophagosomes, is a lysosome-dependent pathway for protein degradation. The role of autophagy in carcinogenesis is context dependent. As a tumor-suppressing mechanism in early-stage carcinogenesis, autophagy inhibits inflammation and promotes genomic stability. Moreover, disruption of autophagy-related genes accelerates tumorigenesis in animals. However, autophagy may also act as a pro-survival mechanism to protect cancer cells from various forms of cellular stress. In cancer therapy, adaptive autophagy in cancer cells sustains tumor growth and survival in face of the toxicity of cancer therapy. To this end, inhibition of autophagy may sensitize cancer cells to chemotherapeutic agents and ionizing radiation. Nevertheless, in certain circumstances, autophagy mediates the therapeutic effects of some anticancer agents. Data from recent studies are beginning to unveil the apparently paradoxical nature of autophagy as a cell-fate decision machinery. Taken together, modulation of autophagy is a novel approach for enhancing the efficacy of existing cancer therapy, but its Janus-faced nature may complicate the clinical development of autophagy modulators as anticancer therapeutics.

  13. Targets for molecular therapy of skin cancer.

    Science.gov (United States)

    Green, Cheryl L; Khavari, Paul A

    2004-02-01

    Cancers of the skin encompass the first and second most common neoplasms in the United States, epidermal basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), respectively, as well as the melanocytic malignancy, malignant melanoma (MM). Recently identified alterations in the function of specific genes in these cancers provide new potential therapeutic targets. These alterations affect conserved regulators of cellular proliferation and viability, including the Sonic Hedgehog, Ras/Raf, ARF/p53, p16(INK4A)/CDK4/Rb and NF-kappaB pathways. New modalities designed to target these specific proteins may represent promising approaches to therapy of human skin cancers.

  14. [Photodynamic therapy for gastric cancer].

    Science.gov (United States)

    Mimura, S; Narahara, H; Uehara, H; Otani, T; Okuda, S

    1996-01-01

    In this article, we first present our clinical data on PDT for the treatment of gastric cancer and make a comparison between a continuous wave laser and a pulsed laser. The reasons for PDT failure in certain cases are also discussed. In the fifteen years from 1981 to 1995, we have treated a total of 76 gastric cancer lesions (73 cases), which was consist of 69 early gastric cancer lesions (66 cases) and seven advanced gastric cancer lesions (seven cases) by PDT. From 1981 to 1990, we used an argon dye laser (ADL, Models 171-08 and 375-03, Spectra-Physics, Mountain View, Calif., US) as an excitation light source for PDT with HpD (Photofrin I), DHE (Photofrin II) or PHE (freeze-dried Photofrin II). From analysis of the results in terms of the depth of cancer invasion in these 44 lesions (41 cases), the rate of cure for mucosal carcinomas was 57% (13/23), that of submucosal carcinomas was 53% (10/19), and that of carcinomas invading more than the muscularis propria was 0% (0/2). These data can be interpreted to indicate that the ADL laser beam could not penetrate and supply sufficient energy to activate HpD not only in the submoucosal layer but also in the mucosal layer. In 1990, therefore, we investigated an excimer dye laser (EDL, Hamamatsu Photonics, Hamamatsu, Japan), because its pulsed beam with extremely high peak power was expected to be more efficient at exciting HpD than continuous wave lasers such as ADL and high frequency pulsed lasers such as cooper vapor dye laser (Cu VDL). From 1990 to 1995, twenty-seven early gastric cancer lesions (27 cases) and five advanced gastric cancer lesions (five cases) were treated by PDT with EDL and PHE. Of these 32 lesions, the rate of cure for mucosal carcinomas was 100% (15/15), that of submucosal carcinomas was 75% (9/12), and that of carcinomas invading more than the muscularis propria was 20% (1/5). For the purpose of determining how much energy was required for a complete cure in early gastric cancer, and to compare

  15. Occupational therapy use by older adults with cancer.

    Science.gov (United States)

    Pergolotti, Mackenzi; Cutchin, Malcolm P; Weinberger, Morris; Meyer, Anne-Marie

    2014-01-01

    Occupational therapy may significantly improve cancer survivors' ability to participate in activities, thereby improving quality of life. Little is known, however, about the use of occupational therapy services by adults with cancer. The objective of this study was to understand what shapes patterns of occupational therapy use to help improve service delivery. We examined older (age >65 yr) adults diagnosed with breast, prostate, lung, or melanoma (skin) cancer between 2004 and 2007 (N = 27,131) using North Carolina Central Cancer Registry data linked to Medicare billing claims. Survivors who used occupational therapy within 1 yr before their cancer diagnosis were more likely to use occupational therapy after diagnosis but also experienced the highest levels of comorbidities. Survivors with Stage 4 cancers or lung cancer were less likely to use occupational therapy. These findings suggest possible disparities in utilization of occupational therapy by older adults with cancer. Copyright © 2014 by the American Occupational Therapy Association, Inc.

  16. Drug therapy for hereditary cancers

    Directory of Open Access Journals (Sweden)

    Imyanitov Evgeny N

    2011-08-01

    Full Text Available Abstract Tumors arising in patients with hereditary cancer syndromes may have distinct drug sensitivity as compared to their sporadic counterparts. Breast and ovarian neoplasms from BRCA1 or BRCA2 mutation carriers are characterized by deficient homologous recombination (HR of DNA, that makes them particularly sensitive to platinum compounds or inhibitors of poly (ADP-ribose polymerase (PARP. Outstandingly durable complete responses to high dose chemotherapy have been observed in several cases of BRCA-related metastatic breast cancer (BC. Multiple lines of evidence indicate that women with BRCA1-related BC may derive less benefit from taxane-based treatment than other categories of BC patients. There is virtually no reports directly assessing drug response in hereditary colorectal cancer (CRC patients; studies involving non-selected (i.e., both sporadic and hereditary CRC with high-level microsatellite instability (MSI-H suggest therapeutic advantage of irinotecan. Celecoxib has been approved for the treatment of familial adenomatous polyposis (FAP. Hereditary medullary thyroid cancers (MTC have been shown to be highly responsive to a multitargeted tyrosine kinase inhibitor vandetanib, which exerts specific activity towards mutated RET receptor. Given the rapidly improving accessibility of DNA analysis, it is foreseen that the potential predictive value of cancer-associated germ-line mutations will be increasingly considered in the future studies.

  17. [Therapy of recurrent cervical cancer].

    Science.gov (United States)

    Sekiba, K; Hayase, R

    1990-09-01

    1,122 uterine cancer patients above FIGO stage I a were treated at our hospital in the decade from 1980 to 1989. Total 69 patients diagnosed as recurrent cervical cancer had 82 lesions in 11 sites. The most frequent recurrent sites were uterus, vaginal stump and vaginal wall; the second sites were parametrium and pelvic wall. Radiotherapy and hyperthermia were done to patients with these lesions. Chemotherapy and radiotherapy were used to patients with distant metastatic lesions to left supraclavicular lymph nodes and lung. But there has been no good results.

  18. Breast cancer stem-like cells and breast cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Niansong Qian; Nobuko Kawaguchi-Sakita; Masakazu Toi

    2010-01-01

    @@ Until the early 1990s, human cancers were considered a morphologically heterogeneous population of cells. In 1997, Bonnet et al[1] demonstrated that a small population of leukemia cells was able to differentiate in vivo into leukemic blasts, indicating that the leukemic clone was organized as a hierarchy; this was subsequently denoted as cancer stem like cells (CSCs). CSCs are cancer cells that possess characteristics associated with normal stem cells and have the specific ability to give rise to all cell types found in a particular cancer. One reason for the failure of traditional anti tumor therapies might be their inability to eradicate CSCs. Therefore, therapies must identify and destroy CSCs in both primary and metastatic tumors.

  19. Diabetes, pancreatic cancer, and metformin therapy

    Directory of Open Access Journals (Sweden)

    Jun eGong

    2014-11-01

    Full Text Available Pancreatic cancer carries a poor prognosis as most patients present with advanced disease and preferred chemotherapy regimens offer only modest effects on survival. Risk factors include smoking, obesity, heavy alcohol, and chronic pancreatitis. Pancreatic cancer has a complex relationship with diabetes, as diabetes can be both a risk factor for pancreatic cancer and a result of pancreatic cancer. Insulin, insulin-like growth factor-1 (IGF-1, and certain hormones play an important role in promoting neoplasia in diabetics. Metformin appears to reduce risk for pancreatic cancer and improve survival in diabetics with pancreatic cancer primarily by decreasing insulin/IGF signaling, disrupting mitochondrial respiration, and inhibiting the mammalian target of rapamycin (mTOR pathway. Other potential anti-tumorigenic effects of metformin include the ability to downregulate specificity protein transcription factors and associated genes, alter microRNAs, decrease cancer stem cell proliferation, and reduce DNA damage and inflammation. Here, we review the most recent knowledge on risk factors and treatment of pancreatic cancer and the relationship between diabetes, pancreatic cancer, and metformin as a potential therapy.

  20. [Photodynamic therapy for head and neck cancer

    DEFF Research Database (Denmark)

    Lajer, C.B.; Specht, Lena; Kirkegaard, J.

    2006-01-01

    Photodynamic therapy (PDT) is a new treatment for head and neck cancer. The principle of the treatment is a photochemical reaction initiated by light activation of a photosensitizer, which causes the death of the exposed tissue. This article presents the modes of action of PDT and the techniques...

  1. Enhancing photodynamic therapy of refractory solid cancers

    NARCIS (Netherlands)

    Weijer, R.

    2017-01-01

    Photodynamic therapy (PDT) is based on the activation of a photosensitizer by (laser) light to locally produce highly destructive reactive oxygen species. When employed for cancer treatment, PDT is able to induce tumor cell death, microvascular damage, and an anti-tumor immune response. All these

  2. Apoptosis : Target of cancer therapy

    NARCIS (Netherlands)

    Ferreira, CG; Epping, M; Kruyt, FAE; Giaccone, G

    2002-01-01

    Recent knowledge on apoptosis has made it possible to devise novel approaches, which exploit this process to treat cancer. In this review, we discuss in detail approaches to induce tumor cell apoptosis, their mechanism of action, stage of development, and possible drawbacks. Finally, the obstacles y

  3. Apoptosis : Target of cancer therapy

    NARCIS (Netherlands)

    Ferreira, CG; Epping, M; Kruyt, FAE; Giaccone, G

    2002-01-01

    Recent knowledge on apoptosis has made it possible to devise novel approaches, which exploit this process to treat cancer. In this review, we discuss in detail approaches to induce tumor cell apoptosis, their mechanism of action, stage of development, and possible drawbacks. Finally, the obstacles y

  4. [Systemic therapy for colorectal cancer].

    Science.gov (United States)

    Pestalozzi, B C; Jäger, D; Knuth, A

    2005-06-01

    Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.

  5. Cardiovascular disease after cancer therapy

    DEFF Research Database (Denmark)

    Aleman, Berthe M P; Moser, Elizabeth C; Nuver, Janine

    2014-01-01

    Improvements in treatment and earlier diagnosis have both contributed to increased survival for many cancer patients. Unfortunately, many treatments carry a risk of late effects including cardiovascular diseases (CVDs), possibly leading to significant morbidity and mortality. In this paper we des...

  6. Targeted Therapies for Kidney Cancer

    Science.gov (United States)

    ... The most common side effects seen with this drug include fatigue, rash, diarrhea, increases in blood pressure, and redness, pain, swelling, ... other targets that help cancer cells grow. This drug is taken as a ... effects are nausea, diarrhea, changes in skin or hair color, mouth sores, ...

  7. Heterogeneity of liver cancer and personalized therapy.

    Science.gov (United States)

    Li, Liang; Wang, Hongyang

    2016-09-01

    Liver cancer is an extraordinarily heterogeneous malignant disease among the tumors that have so far been identified. Hepatocellular carcinoma (HCC) arises most frequently in the setting of chronic liver inflammation and fibrosis, and takes a variety of course in individual patients to process to tumor. The risk factors such as HBV and/or HCV infections, aflatoxin infection, abuse alcohol intake, metabolic syndrome, obesity and diabetes are closely related to the environmental and genetic susceptibilities to HCC. The consequent resulting genomic instability, molecular and signal transduction network disorders and microenvironmental discrepancies are characterized by the extraordinary heterogeneity of liver cancer. The histology-based definition of the morphological heterogeneity of liver cancer has been modified and refined to treat patients with targeted therapies, but this still cannot solve all the problems. Lack of consistent outcome for anticancer agents and conventional therapies in liver cancer treatment calls for assessing the benefits of new molecularly targeted drugs and combined therapy, under the heterogeneity condition of tumor. The present review article will provide the complex mechanism and phenotype of liver cancer heterogeneity, and help us to execute precision medicine in a really personalized manner.

  8. An overview of gene therapy in head and neck cancer

    OpenAIRE

    2013-01-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction...

  9. Enhancing Immune Responses for Cancer Therapy

    Institute of Scientific and Technical Information of China (English)

    Shao-An Xue; Hans J Stauss

    2007-01-01

    Although the immune system possesses the means to respond to cancer, it often fails to control the spread of malignancy. Nonetheless, equipping endogenous immunity to release a strong antitumor response has significant advantages over conventional therapies. This review explores some of the options available to accomplish this,focusing first on vaccinations with tumor antigens to stimulate the immune system and empower stronger antitumor responses. We then compare and contrast the so-far limited clinical success of vaccination with the well-documented curative potential of adoptive therapy using T lymphocytes transfer. Finally, we highlight novel approaches using T cell receptor (TCR) gene transfer strategy to exploit allogeneic T cell repertoires in conjunction with receptors selected in vitro for defined MHC/peptide combinations, as a basis for antigen-specific gene therapy of cancers.

  10. Selected Secondary Plant Metabolites for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Simone Fulda

    2015-01-01

    Full Text Available Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human diseases. As the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics, either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in oncology. Two major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid, artesunate, dicentrine and camptothecin derivatives.

  11. Endocrine Therapy of Breast Cancer

    Science.gov (United States)

    2009-06-01

    inhibitor of both the src and abl kinases, selectively inhibits growth of basal -type/“triple-negative” breast cancer cell lines growing in vitro. Breast...Welch JN, Lu J, Liu A, Zhu Y, Davis N, Leonessa F, Brunner N, Wang Y, Clarke R. Association of interferon regulatory factor-1, nucleo - phosmin...nmol/L 4HT (within the range of clinically relevant concentrations; ref. 10) was designated SUM44/LCCTam (hereafter called LCCTam). The basal growth

  12. Quantifying and reducing uncertainties in cancer therapy

    Science.gov (United States)

    Barrett, Harrison H.; Alberts, David S.; Woolfenden, James M.; Liu, Zhonglin; Caucci, Luca; Hoppin, John W.

    2015-03-01

    There are two basic sources of uncertainty in cancer chemotherapy: how much of the therapeutic agent reaches the cancer cells, and how effective it is in reducing or controlling the tumor when it gets there. There is also a concern about adverse effects of the therapy drug. Similarly in external-beam radiation therapy or radionuclide therapy, there are two sources of uncertainty: delivery and efficacy of the radiation absorbed dose, and again there is a concern about radiation damage to normal tissues. The therapy operating characteristic (TOC) curve, developed in the context of radiation therapy, is a plot of the probability of tumor control vs. the probability of normal-tissue complications as the overall radiation dose level is varied, e.g. by varying the beam current in external-beam radiotherapy or the total injected activity in radionuclide therapy. The TOC can be applied to chemotherapy with the administered drug dosage as the variable. The area under a TOC curve (AUTOC) can be used as a figure of merit for therapeutic efficacy, analogous to the area under an ROC curve (AUROC), which is a figure of merit for diagnostic efficacy. In radiation therapy AUTOC can be computed for a single patient by using image data along with radiobiological models for tumor response and adverse side effects. In this paper we discuss the potential of using mathematical models of drug delivery and tumor response with imaging data to estimate AUTOC for chemotherapy, again for a single patient. This approach provides a basis for truly personalized therapy and for rigorously assessing and optimizing the therapy regimen for the particular patient. A key role is played by Emission Computed Tomography (PET or SPECT) of radiolabeled chemotherapy drugs.

  13. Cancer therapy with particle accelerators

    CERN Document Server

    Amaldi, Ugo

    1999-01-01

    This review paper is devoted to conventional radiotherapy and to hadron therapy. In this therapeutical modality, proposed by R. R. Wilson in 1946, the physical selectivity of proton and light ion beams is used to irradiate tissues very close to organs at risk, which cannot be irradiated (the brain and the spinal cord for instance). Also fast neutrons are employed, but they are not suitable for a truly conformal irradiation. Carbon ions have the added advantage, with respect to protons, of the high density of ionization at the end of the range in matter. This property is very valuable for the control of tumours which are radioresistant to both X-rays and protons. After clarifying the general principles, a review is presented of the world hadron therapy centres which are running or are in the design and construction stage. (33 refs).

  14. Kundalini yoga as a support therapy for cancer patients

    OpenAIRE

    Kröneck, Mia

    2016-01-01

    This study was designed to describe cancer patient’s experience of kundalini yoga and its effect on their internal coping resources. The intention of this study is to put forward kundalini yoga as a support therapy for cancer patients for improving their wellbeing during active cancer treatment. This is a descriptive study. An academic literature review was conducted for cancer, cancer treatment, internal coping resources and yoga as therapy topics. Four voluntary female cancer patients (...

  15. Cancer therapies in HIV cure research

    DEFF Research Database (Denmark)

    Rasmussen, Thomas A; Anderson, Jenny L; Wightman, Fiona;

    2016-01-01

    PURPOSE OF REVIEW: This article provides an overview of anticancer therapies in various stages of clinical development as potential interventions to target HIV persistence. RECENT FINDINGS: Epigenetic drugs developed for cancer have been investigated in vitro, ex vivo and in clinical trials...... as interventions aimed at reversing HIV latency and depleting the amount of virus that persists on antiretroviral therapy. Treatment with histone deacetylase inhibitors induced HIV expression in patients on antiretroviral therapy but did not reduce the frequency of infected cells. Other interventions that may...... accelerate the decay of latently infected cells, in the presence or absence of latency-reversing therapy, are now being explored. These include apoptosis-promoting agents, nonhistone deacetylase inhibitor compounds to reverse HIV latency and immunotherapy interventions to enhance antiviral immunity...

  16. [Modern therapy concepts for endometrial cancer].

    Science.gov (United States)

    Emons, G; Hellriegel, M; Hawighorst, T

    2009-07-01

    Most cases of endometrial cancer (EC) become symptomatic at an early stage and have a good prognosis. EC has been traditionally treated with total abdominal hysterectomy plus bilateral salpingo-oophorectomy. For early stage, low grade cases (endometrioid, pT1a, pT1b; G1, G2) this is adequate therapy. For higher stages and grades, especially for type II EC (serous, clear cell) this therapy is insufficient. The efficacy of systematic pelvic and paraaortic lymphadenectomy for high risk EC, however, remains to be evaluated. External pelvic radiotherapy has been shown to improve local control in stage I and II EC, but has no positive effect on survival. A comparable improvement of local control can be achieved by vaginal brachytherapy with significantly less toxicity. Adjuvant chemotherapy is probably efficacious in EC. Its usefulness as exclusive adjuvant therapy or in combination with brachytherapy and/or external beam therapy remains to be evaluated by prospective trials.

  17. Targeted Therapy in Nonmelanoma Skin Cancers

    Energy Technology Data Exchange (ETDEWEB)

    Spallone, Giulia; Botti, Elisabetta; Costanzo, Antonio, E-mail: antonio.costanzo@uniroma2.it [Department of Dermatology, University of Rome “Tor Vergata”, Via Montpellier 1, 00199, Rome (Italy)

    2011-05-03

    Nonmelanoma skin cancer (NMSC) is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC), representing around 75% of NMSC and Squamous Cell Carcinomas (SCC). The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  18. Death receptors: Targets for cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Mahmood, Zafar [Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001 (India); Shukla, Yogeshwer, E-mail: yogeshwer_shukla@hotmail.com [Proteomics Laboratory, Indian Institute of Toxicology Research, Mahatma Gandhi Marg, Lucknow 226001 (India)

    2010-04-01

    Apoptosis is the cell's intrinsic program to death, which plays an important role in physiologic growth control and homeostasis. Apoptosis can be triggered by death receptors (DRs), without any adverse effects. DRs are the members of tumor necrosis factor (TNF) receptor superfamily, known to be involved in apoptosis signaling, independent of p53 tumor-supressor gene. Selective triggering of DR-mediated apoptosis in cancer cells is a novel approach in cancer therapy. So far, the best characterized DRs are CD95 (Fas/Apo1), TNF-related apoptosis-inducing ligand receptor (TRAILR) and tumor necrosis factor receptor (TNFR). Among these, TRAILR is emerging as most promising agent for cancer therapy, because it induces apoptosis in a variety of tumor and transformed cells without any toxicity to normal cells. TRAIL treatment in combination with chemotherapy or radiotherapy enhances TRAIL sensitivity or reverses TRAIL resistance by regulating downstream effectors. This review covers the current knowledge about the DRs, summarizes main signaling in DRs and also summarizes the preclinical approaches of these DRs in cancer therapy.

  19. Targeted Therapy in Nonmelanoma Skin Cancers

    Directory of Open Access Journals (Sweden)

    Giulia Spallone

    2011-05-01

    Full Text Available Nonmelanoma skin cancer (NMSC is the most prevalent cancer in light-skinned populations, and includes mainly Basal Cell Carcinomas (BCC, representing around 75% of NMSC and Squamous Cell Carcinomas (SCC. The incidence of these tumors is continuously growing. It was found that the overall number of procedures for NMSC in US rose by 76%, from 1,158,298 in 1992 to 2,048,517 in 2006. Although mortality from NMSC tends to be very low, clearly the morbidity related to these skin cancers is very high. Treatment options for NMSC include both surgical and nonsurgical interventions. Surgery was considered the gold standard therapy, however, advancements in the knowledge of pathogenic mechanisms of NMSCs led to the identification of key targets for drug intervention and to the consequent development of several targeted therapies. These represent the future in treatment of these common forms of cancer ensuring a high cure rate, preservation of the maximal amount of normal surrounding tissue and optimal cosmetic outcome. Here, we will review recent advancements in NMSC targeted therapies focusing on BCC and SCC.

  20. An overview of gene therapy in head and neck cancer.

    Science.gov (United States)

    Bali, Amit; Bali, Deepika; Sharma, Ashutosh

    2013-07-01

    Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA) and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

  1. Cancer stem cell targeted therapy: progress amid controversies

    Science.gov (United States)

    Wang, Tao; Shigdar, Sarah; Gantier, Michael P.; Hou, Yingchun; Wang, Li; Li, Yong; Shamaileh, Hadi Al; Yin, Wang; Zhou, Shu-Feng; Zhao, Xinhan; Duan, Wei

    2015-01-01

    Although cancer stem cells have been well characterized in numerous malignancies, the fundamental characteristics of this group of cells, however, have been challenged by some recent observations: cancer stem cells may not necessary to be rare within tumors; cancer stem cells and non-cancer stem cells may undergo reversible phenotypic changes; and the cancer stem cells phenotype can vary substantially between patients. Here the current status and progresses of cancer stem cells theory is illustrated and via providing a panoramic view of cancer therapy, we addressed the recent controversies regarding the feasibility of cancer stem cells targeted anti-cancer therapy. PMID:26496035

  2. Antiangiogenic Steroids in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Richard J. Pietras

    2005-01-01

    Full Text Available Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na+/H+ exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell–cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies

  3. Antiangiogenic Steroids in Human Cancer Therapy.

    Science.gov (United States)

    Pietras, Richard J; Weinberg, Olga K

    2005-03-01

    Despite advances in the early detection of tumors and in the use of chemotherapy, radiotherapy and surgery for disease management, the worldwide mortality from human cancer remains unacceptably high. The treatment of cancer may benefit from the introduction of novel therapies derived from natural products. Natural products have served to provide a basis for many of the pharmaceutical agents in current use in cancer therapy. Emerging research indicates that progressive growth and spread of many solid tumors depends, in part, on the formation of an adequate blood supply, and this process of tumor-associated angiogenesis is reported to have prognostic significance in several human cancers. This review focuses on the potential application in antitumor therapy of naturally-occurring steroids that target tumor-associated angiogenesis. Squalamine, a 7,24 dihydroxylated 24-sulfated cholestane steroid conjugated to a spermidine at position C-3, is known to have strong antiangiogenic activity in vitro, and it significantly disrupts tumor proliferation and progression in laboratory studies. Work on the interactions of squalamine with vascular endothelial cells indicate that it binds with cell membranes, inhibits the membrane Na(+)/H(+) exchanger and may further function as a calmodulin chaperone. These primary actions appear to promote inhibition of several vital steps in angiogenesis, such as blockade of mitogen-induced actin polymerization, cell-cell adhesion and cell migration, leading to suppression of endothelial cell proliferation. Preclinical studies with squalamine have shown additive benefits in tumor growth delay when squalamine is combined with cisplatin, paclitaxel, cyclophosphamide, genistein or radiation therapy. This compound has also been assessed in early phase clinical trials in cancer; squalamine was found to exhibit little systemic toxicity and was generally well tolerated by treated patients with various solid tumor malignancies, including ovarian, non

  4. Prodrug applications for targeted cancer therapy.

    Science.gov (United States)

    Giang, Irene; Boland, Erin L; Poon, Gregory M K

    2014-09-01

    Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy. In this review, we explore a unified view of cancer-targeted prodrugs and highlight several examples from recombinant technology that exemplify the prodrug concept but are not identified as such. Recombinant "prodrugs" such as engineered anthrax toxin show promise in biological specificity through the conditionally targeting of multiple cellular markers. Conditional targeting is achieved by structural complementation, the spontaneous assembly of engineered inactive subunits or fragments to reconstitute functional activity. These complementing systems can be readily adapted to achieve conditionally bispecific targeting of enzymes that are used to activate low-molecular weight prodrugs. By leveraging strengths from medicinal chemistry, polymer science, and recombinant technology, prodrugs are poised to remain a core component of highly focused and tailored strategies aimed at conditionally attacking complex molecular phenotypes in clinically relevant cancer.

  5. New targeted therapies in pancreatic cancer.

    Science.gov (United States)

    Seicean, Andrada; Petrusel, Livia; Seicean, Radu

    2015-05-28

    Patients with pancreatic cancer have a poor prognosis with a median survival of 4-6 mo and a 5-year survival of less than 5%. Despite therapy with gemcitabine, patient survival does not exceed 6 mo, likely due to natural resistance to gemcitabine. Therefore, it is hoped that more favorable results can be obtained by using guided immunotherapy against molecular targets. This review summarizes the new leading targeted therapies in pancreatic cancers, focusing on passive and specific immunotherapies. Passive immunotherapy may have a role for treatment in combination with radiochemotherapy, which otherwise destroys the immune system along with tumor cells. It includes mainly therapies targeting against kinases, including epidermal growth factor receptor, Ras/Raf/mitogen-activated protein kinase cascade, human epidermal growth factor receptor 2, insulin growth factor-1 receptor, phosphoinositide 3-kinase/Akt/mTOR and hepatocyte growth factor receptor. Therapies against DNA repair genes, histone deacetylases, microRNA, and pancreatic tumor tissue stromal elements (stromal extracellular matric and stromal pathways) are also discussed. Specific immunotherapies, such as vaccines (whole cell recombinant, peptide, and dendritic cell vaccines), adoptive cell therapy and immunotherapy targeting tumor stem cells, have the role of activating antitumor immune responses. In the future, treatments will likely include personalized medicine, tailored for numerous molecular therapeutic targets of multiple pathogenetic pathways.

  6. Progress of Photodynamic Therapy in Gastric Cancer

    OpenAIRE

    Seishiro Mimura; Hiroyuki Narahara; Toru Otani; Shigeru Okuda

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm2 for an argon dye laser and 60 J/cm2 for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm2 in...

  7. Porphyrins for photodynamic therapy of cancer

    Science.gov (United States)

    Ion, Rodica-Mariana; Pascu, Mihail-Lucian

    2001-06-01

    Photodynamic therapy (PDT) of cancer is based on the dye- sensitized photooxidation of different biological targets in the tumoral tissue yielding to a photochemically induced cell's death. The effectiveness of this treatment method depends on the photophysical and photochemical properties of the used photosensitizer-drug during the irradiation with visible light (laser beam) and/or the ionizing radiation. The purpose of this paper is to summarize the photodynamic therapy applications: substitution effects, ionization and aggregation processes effects, photodegradation reaction implications, the correlation with some medical applications on human brain cells.

  8. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy

    Directory of Open Access Journals (Sweden)

    Jaleh Barar

    2013-02-01

    Full Text Available It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

  9. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy.

    Science.gov (United States)

    Barar, Jaleh; Omidi, Yadollah

    2013-01-01

    It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called "tumor microenvironment (TME)", in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

  10. Hadrontherapy - macrobenefit in cancer therapy?

    Science.gov (United States)

    Habrand, J. L.; Baron, E.; Bourhis, J.; Datchary, J.; Mazal, A.; Meflah, K.

    2012-07-01

    Hadrontherapy is one of the most promising radiotherapeutical innovations that deal with accelerated heavy charged particles, mainly proton and carbon ions. Their salient features include an original dose-distribution, based on the Bragg curve, and in some of them an increased RBE at the range-end. Approximately 100 000 patients have been treated so far in approximately 40 centers worldwide. Outstanding outcomes have been substantiated in rare neoplasms using protons, such as ocular melanomas, skull base sarcomas, and pediatric malignancies, while only promising evidences have emerged using carbons. Assessing their place in more common tumor-sites, such as lung, pancreas, prostate, esophagus remains to be determined, and justifies the expansion of future particle therapy programs.

  11. The use of biofield therapies in cancer care.

    Science.gov (United States)

    Pierce, Beverly

    2007-04-01

    Biofield therapies form a subcategory of the domain of energy therapies, as defined by the National Center for Complementary and Alternative Medicine. Specific biofield therapies addressed in this article include Therapeutic Touch, Healing Touch, Polarity Therapy, Reiki, and Qigong. This article will identify core concepts in biofield therapies, review controlled trials of the use of biofield therapies with patients with cancer, describe the process of biofield therapies implementation in one cancer center, and suggest research to benefit not only patients with cancer but also family members and oncology professionals.

  12. Novel Therapies in Development for Metastatic Colorectal Cancer

    OpenAIRE

    Lee, Michael S.; Kopetz, Scott

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer mortality in the United States. Despite advances in therapy, metastatic CRC remains lethal, and further improvements in therapy are needed. Growing understanding of cancer biology, particularly in growth factor signaling, angiogenesis, and cancer immunology, has translated into many novel therapies under investigation. Patients are increasingly selected for clinical trials rationally on the basis of integral biomarkers. This re...

  13. Radiation therapy for stage IVA cervical cancer.

    Science.gov (United States)

    Murakami, Naoya; Kasamatsu, Takahiro; Morota, Madoka; Sumi, Minako; Inaba, Koji; Ito, Yoshinori; Itami, Jun

    2013-11-01

    To evaluate the outcome and discover predictive factors for patients with stage IVA cervical cancer treated with definitive radiation therapy. We retrospectively reviewed 34 patients with stage IVA cervical cancer who received definitive radiation therapy between 1992 and 2009. On univariate analysis, statistically significant prognostic factors for improved local control rate (LCR) were absence of pyometra (p=0.037) and equivalent dose in 2 Gy fractions (EQD2) at point A greater than 60 Gy (p=0.023). Prognostic factors for improved progression-free survival (PFS) were absence of pelvic lymph node metastasis at initial presentation (p=0.014), and EQD2 at point A greater than 60 Gy (p=0.023). Patients with stage IVA disease had poor median survival. However adequate radiation dose to point A produced favorable LCR and PFS, therefore efforts should be made to increase the point A dose.

  14. Immune-Mediated Therapies for Liver Cancer

    OpenAIRE

    Aravalli, Rajagopal N; Steer, Clifford J.

    2017-01-01

    In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion ...

  15. Adenoviral gene therapy in gastric cancer: A review

    Institute of Scientific and Technical Information of China (English)

    Nima Khalighinejad; Hesammodin Hariri; Omid Behnamfar; Arash Yousefi; Amir Momeni

    2008-01-01

    Gastric cancer is one of the most common malignancies worldwide. With current therapeutic approaches the prognosis of gastric cancer is very poor, as gastric cancer accounts for the second most common cause of death in cancer related deaths. Gastric cancer like almost all other cancers has a molecular genetic basis which relies on disruption in normal cellular regulatory mechanisms regarding cell growth, apoptosis and cell division. Thus novel therapeutic approaches such as gene therapy promise to become the alternative choice of treatment in gastric cancer. In gene therapy, suicide genes, tumor suppressor genes and anti-angiogenesis genes among many others are introduced to cancer cells via vectors.Some of the vectors widely used in gene therapy are Adenoviral vectors. This review provides an update of the new developments in adenoviral cancer gene therapy including strategies for inducing apoptosis, inhibiting metastasis and targeting the cancer cells.

  16. Silencing of MicroRNA-21 confers the sensitivity to tamoxifen and fulvestrant by enhancing autophagic cell death through inhibition of the PI3K-AKT-mTOR pathway in breast cancer cells.

    Science.gov (United States)

    Yu, Xinfeng; Li, Ruilian; Shi, Wenna; Jiang, Tao; Wang, Yufei; Li, Cong; Qu, Xianjun

    2016-02-01

    Tamoxifen (TAM) and fulvestrant (FUL) represent the major adjuvant therapy to estrogen receptor-alpha positive (ER(+)) breast cancer patients. However, endocrine resistance to TAM and FUL is a great impediment for successful treatment. We hypothesized that miR-21 might alter the sensitivity of breast cancer cells to TAM or FUL by regulating cell autophagy. Using the ER(+) breast cancer cells, we knockdown miR-21.by transfection with miR-21 inhibitor, then the cells were exposed to TAM or FUL and the percentages of apoptosis and autophagy were determined. Knockdown of miR-21 significantly increased the TAM or FUL-induced apoptosis in ER(+) breast cancer cells. Further, silencing of miR-21 in MCF-7 cells enhanced cell autophagy at both basal and TAM or FUL-induced level. The increase of autophagy in miR-21-knockdown MCF-7 cells was also indicated by increase of beclin-1, LC3-II and increased GFP-LC3 dots. Importantly, knockdown of miR-21 contributed to autophagic cell death, which is responsible for part of TAM induced cell death in miR-21 inhibitor-transfected cells. Further analysis suggested that miR-21 inhibitor enhance autophagic cell death through inhibition of PI3K-AKT-mTOR pathway. MiR-21 coordinated the function of autophagy and apoptosis by targeting Phosphatase and tensin homolog (PTEN) through inhibition of PI3K-AKT-mTOR pathway. In conclusion, silencing of miR-21 increased the sensitivity of ER(+) breast cancer cells to TAM or FUL by increasing autophagic cell death. Targeting autophagy-related miRNAs is a potential strategy for overcoming endocrine resistance to TAM and FUL.

  17. Bacterial Toxins for Cancer Therapy.

    Science.gov (United States)

    Zahaf, Nour-Imene; Schmidt, Gudula

    2017-07-28

    Several pathogenic bacteria secrete toxins to inhibit the immune system of the infected organism. Frequently, they catalyze a covalent modification of specific proteins. Thereby, they block production and/or secretion of antibodies or cytokines. Moreover, they disable migration of macrophages and disturb the barrier function of epithelia. In most cases, these toxins are extremely effective enzymes with high specificity towards their cellular substrates, which are often central signaling molecules. Moreover, they encompass the capacity to enter mammalian cells and to modify their substrates in the cytosol. A few molecules, at least of some toxins, are sufficient to change the cellular morphology and function of a cell or even kill a cell. Since many of those toxins are well studied concerning molecular mechanisms, cellular receptors, uptake routes, and structures, they are now widely used to analyze or to influence specific signaling pathways of mammalian cells. Here, we review the development of immunotoxins and targeted toxins for the treatment of a disease that is still hard to treat: cancer.

  18. Employment of Salmonella in Cancer Gene Therapy.

    Science.gov (United States)

    Lee, Che-Hsin

    2016-01-01

    One of the primary limitations of cancer gene therapy is lack of selectivity of the therapeutic gene to tumor cells. Current efforts are focused on discovering and developing tumor-targeting vectors that selectively target only cancer cells but spare normal cells to improve the therapeutic index. The use of preferentially tumor-targeting bacteria as vectors is one of the innovative approaches for the treatment of cancer. This is based on the observation that some obligate or facultative-anaerobic bacteria are capable of multiplying selectively in tumors and inhibiting their growth. In this study, we exploited attenuated Salmonella as a tumoricidal agent and a vector to deliver genes for tumor-targeted gene therapy. Attenuated Salmonella, carrying a eukaryotic expression plasmid encoding an anti-angiogenic gene, was used to evaluate its' ability for tumor targeting and gene delivery in murine tumor models. We also investigated the use of a polymer to modify or shield Salmonella from the pre-existing immune response in the host in order to improve gene delivery to the tumor. These results suggest that tumor-targeted gene therapy using Salmonella carrying a therapeutic gene, which exerts tumoricidal and anti-angiogenic activities, represents a promising strategy for the treatment of tumors.

  19. Personalized Targeted Therapy for Lung Cancer

    Directory of Open Access Journals (Sweden)

    William C.S. Cho

    2012-09-01

    Full Text Available Lung cancer has long been recognized as an extremely heterogeneous disease, since its development is unique in every patient in terms of clinical characterizations, prognosis, response and tolerance to treatment. Personalized medicine refers to the use of markers to predict which patient will most likely benefit from a treatment. In lung cancer, the well-developed epidermal growth factor receptor (EGFR and the newly emerging EML4-anaplastic lymphoma kinase (ALK are important therapeutic targets. This review covers the basic mechanism of EGFR and EML4-ALK activation, the predictive biomarkers, the mechanism of resistance, and the current targeted tyrosine kinase inhibitors. The efficacy of EGFR and ALK targeted therapies will be discussed in this review by summarizing the prospective clinical trials, which were performed in biomarker-based selected patients. In addition, the revolutionary sequencing and systems strategies will also be included in this review since these technologies will provide a comprehensive understanding in the molecular characterization of cancer, allow better stratification of patients for the most appropriate targeted therapies, eventually resulting in a more promising personalized treatment. The relatively low incidence of EGFR and ALK in non-Asian patients and the lack of response in mutant patients limit the application of the therapies targeting EGFR or ALK. Nevertheless, it is foreseeable that the sequencing and systems strategies may offer a solution for those patients.

  20. Epigallocatechin Gallate Nanodelivery Systems for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Andreia Granja

    2016-05-01

    Full Text Available Cancer is one of the leading causes of morbidity and mortality all over the world. Conventional treatments, such as chemotherapy, are generally expensive, highly toxic and lack efficiency. Cancer chemoprevention using phytochemicals is emerging as a promising approach for the treatment of early carcinogenic processes. (−-Epigallocatechin-3-gallate (EGCG is the major bioactive constituent in green tea with numerous health benefits including anti-cancer activity, which has been intensively studied. Besides its potential for chemoprevention, EGCG has also been shown to synergize with common anti-cancer agents, which makes it a suitable adjuvant in chemotherapy. However, limitations in terms of stability and bioavailability have hampered its application in clinical settings. Nanotechnology may have an important role in improving the pharmacokinetic and pharmacodynamics of EGCG. Indeed, several studies have already reported the use of nanoparticles as delivery vehicles of EGCG for cancer therapy. The aim of this article is to discuss the EGCG molecule and its associated health benefits, particularly its anti-cancer activity and provide an overview of the studies that have employed nanotechnology strategies to enhance EGCG’s properties and potentiate its anti-tumoral activity.

  1. Minimally invasive local therapies for liver cancer

    Institute of Scientific and Technical Information of China (English)

    David Li; Josephine Kang; Benjamin J Golas; Vincent W Yeung; David C Madoff

    2014-01-01

    Primary and metastatic liver tumors are an increasing global health problem, with hepatocellular carcinoma (HCC) now being the third leading cause of cancer-related mortality worldwide. Systemic treatment options for HCC remain limited, with Sorafenib as the only prospectively validated agent shown to increase overall survival. Surgical resection and/or transplantation, locally ablative therapies and regional or locoregional therapies have iflled the gap in liver tumor treatments, providing improved survival outcomes for both primary and metastatic tumors. Minimally invasive local therapies have an increasing role in the treatment of both primary and metastatic liver tumors. For patients with low volume disease, these therapies have now been established into consensus practice guidelines. This review highlights technical aspects and outcomes of commonly utilized, minimally invasive local therapies including laparoscopic liver resection (LLR), radiofrequency ablation (RFA), microwave ablation (MWA), high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), and stereotactic body radiation therapy (SBRT). In addition, the role of combination treatment strategies utilizing these minimally invasive techniques is reviewed.

  2. Targeting hypoxic response for cancer therapy

    Science.gov (United States)

    Paolicchi, Elisa; Gemignani, Federica; Krstic-Demonacos, Marija; Dedhar, Shoukat; Mutti, Luciano; Landi, Stefano

    2016-01-01

    Hypoxic tumor microenvironment (HTM) is considered to promote metabolic changes, oncogene activation and epithelial mesenchymal transition, and resistance to chemo- and radio-therapy, all of which are hallmarks of aggressive tumor behavior. Cancer cells within the HTM acquire phenotypic properties that allow them to overcome the lack of energy and nutrients supply within this niche. These phenotypic properties include activation of genes regulating glycolysis, glucose transport, acidosis regulators, angiogenesis, all of which are orchestrated through the activation of the transcription factor, HIF1A, which is an independent marker of poor prognosis. Moreover, during the adaptation to a HTM cancer cells undergo deep changes in mitochondrial functions such as “Warburg effect” and the “reverse Warburg effect”. This review aims to provide an overview of the characteristics of the HTM, with particular focus on novel therapeutic strategies currently in clinical trials, targeting the adaptive response to hypoxia of cancer cells. PMID:26859576

  3. “Smart”nanomaterials for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    LE; GUYADER; Laurent

    2010-01-01

    Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics.Because of their small size,nanoscale devices readily interact with biomolecules both on the cell surface and inside the cell.Nanomaterials,such as fullerenes and their derivatives,are effective in terms of interactions with the immune system and have great potential as anticancer drugs.Comparatively,other nanomaterials are able to load active drugs to cancer cells by selectively using the unique tumor environment,such as their enhanced permeability,retention effect and the specific acidic microenvironment.Multifunctional and multiplexed nanoparticles,as the next generation of nanoparticles,are now being extensively investigated and are promising tools to achieve personalized and tailored cancer treatments.

  4. Modulating autophagy: a strategy for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jun-Lin Li; Shao-Liang Han; Xia Fan

    2011-01-01

    Autophagy is a process in which long-lived proteins,damaged cell organelles,and other cellular particles are sequestered and degraded.This process is important for maintaining the cellular microenvironment when the cell is under stress.Many studies have shown that autophagy plays a complex role in human diseases,especially in cancer,where it is known to have paradoxical effects.Namely,autophagy provides the energy for metabolism and tumor growth and leads to cell death that promotes tumor suppression.The link between autophagy and cancer is also evident in that some of the genes that regulate carcinogenesis,oncogenes and tumor suppressor genes,participate in or impact the autophagy process.Therefore,modulating autophagy will be a valuable topic for cancer therapy.Many studies have shown that autophagy can inhibit the tumor growth when autophagy modulators are combined with radiotherapy and/or chemotherapy.These findings suggest that autophagy may be a potent target for cancer therapy.

  5. Digital pathology in personalized cancer therapy

    Directory of Open Access Journals (Sweden)

    Marcial Garcia Rojo

    2012-01-01

    Full Text Available The development of small molecule inhibitors of growth factor receptors, and the discovery of somatic mutations of the thyrosine kinase domain, have resulted in new paradigms for cancer therapy. Digital microscopy is an important tool for surgical pathologists. The achievements in the digital pathology field have modified the workflow of pathomorphology labs, enhanced the pathologist’s role in diagnostics, and increased their contribution to personalized targeted medicine. Digital image analysis is now available in a variety of platforms to improve quantification performance of diagnostic pathology. We here describe the state of digital microscopy as it applies to the field of quantitative immunohistochemistry of biomarkers related to the clinical personalized targeted therapy of breast cancer, non-small lung cancer and colorectal cancer: HER-2, EGFR, KRAS and BRAF genes. The information is derived from the experience of the authors and a review of the literature. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 570–578

  6. Small RNA combination therapy for lung cancer

    Science.gov (United States)

    Xue, Wen; Dahlman, James E.; Tammela, Tuomas; Khan, Omar F.; Sood, Sabina; Dave, Apeksha; Cai, Wenxin; Chirino, Leilani M.; Yang, Gillian R.; Bronson, Roderick; Crowley, Denise G.; Sahay, Gaurav; Schroeder, Avi; Langer, Robert; Anderson, Daniel G.; Jacks, Tyler

    2014-01-01

    MicroRNAs (miRNAs) and siRNAs have enormous potential as cancer therapeutics, but their effective delivery to most solid tumors has been difficult. Here, we show that a new lung-targeting nanoparticle is capable of delivering miRNA mimics and siRNAs to lung adenocarcinoma cells in vitro and to tumors in a genetically engineered mouse model of lung cancer based on activation of oncogenic Kirsten rat sarcoma viral oncogene homolog (Kras) and loss of p53 function. Therapeutic delivery of miR-34a, a p53-regulated tumor suppressor miRNA, restored miR-34a levels in lung tumors, specifically down-regulated miR-34a target genes, and slowed tumor growth. The delivery of siRNAs targeting Kras reduced Kras gene expression and MAPK signaling, increased apoptosis, and inhibited tumor growth. The combination of miR-34a and siRNA targeting Kras improved therapeutic responses over those observed with either small RNA alone, leading to tumor regression. Furthermore, nanoparticle-mediated small RNA delivery plus conventional, cisplatin-based chemotherapy prolonged survival in this model compared with chemotherapy alone. These findings demonstrate that RNA combination therapy is possible in an autochthonous model of lung cancer and provide preclinical support for the use of small RNA therapies in patients who have cancer. PMID:25114235

  7. Bladder cancer: molecular determinants of personalized therapy.

    Science.gov (United States)

    Lopez-Beltran, Antonio; Santoni, Matteo; Massari, Francesco; Ciccarese, Chiara; Tortora, Giampaolo; Cheng, Liang; Moch, Holger; Scarpelli, Marina; Reymundo, Carlos; Montironi, Rodolfo

    2015-01-01

    Several molecular and genetic studies have provided new perspectives on the histologic classification of bladder tumors. Recent developments in the field of molecular mutational pathway analyses based on next generation sequencing technology together with classic data derived from the description of mutations in the FGFR3 (fibroblast growth factor receptor 3) gene, mutations on TP53 gene, and cDNA technology profiling data gives support to a differentiated taxonomy of bladder cancer. All these changes are behind the use of non-traditional approach to therapy of bladder cancer patients and are ready to change our daily practice of uro-oncology. The observed correlation of some molecular alterations with tumor behavior and the identification of their targets at cellular level might support the use of molecular changes together with morphological data to develop new clinical and biological strategies to manage patients with urothelial cancer. The current review provides comprehensive data to support personalized therapy for bladder cancer based on an integrated approach including pathologic and clinical features and molecular biology.

  8. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    Science.gov (United States)

    Le, Valerie H.; Camille, Nadia; Miles, Brett A.; Teng, Marita S.; Genden, Eric M.; Misiukiewicz, Krzysztof J.

    2016-01-01

    Objectives. Invasion of differentiated thyroid cancer (DTC) into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs) hold promise for use in the neoadjuvant setting in DTC.

  9. Neoadjuvant Therapy in Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Rajan P. Dang

    2016-01-01

    Full Text Available Objectives. Invasion of differentiated thyroid cancer (DTC into surrounding structures can lead to morbid procedures such as laryngectomy and tracheal resection. In these patients, there is a potential role for neoadjuvant therapy. Methods. We identified three studies involving the treatment of DTC with neoadjuvant chemotherapy: two from Slovenia and one from Japan. Results. These studies demonstrate that in selected situations, neoadjuvant chemotherapy can have a good response and allow for a more complete surgical resection, the treatment of DTC. Additionally, the SELECT trial shows that the targeted therapy lenvatinib is effective in the treatment of DTC and could be useful as neoadjuvant therapy for this disease due to its short time to response. Pazopanib has also demonstrated promise in phase II data. Conclusions. Thus, chemotherapy in the neoadjuvant setting could possibly be useful for managing advanced DTC. Additionally, some of the new tyrosine kinase inhibitors (TKIs hold promise for use in the neoadjuvant setting in DTC.

  10. Transcriptional Selectivity of Epigenetic Therapy in Cancer.

    Science.gov (United States)

    Sato, Takahiro; Cesaroni, Matteo; Chung, Woonbok; Panjarian, Shoghag; Tran, Anthony; Madzo, Jozef; Okamoto, Yasuyuki; Zhang, Hanghang; Chen, Xiaowei; Jelinek, Jaroslav; Issa, Jean-Pierre J

    2017-01-15

    A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation, and ChIP-seq analyses the epigenetic response of a set of colon, breast, and leukemia cancer cell lines to small-molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343). We also characterized the effects of DAC as combined with the other compounds. Averaged over the cancer cell models used, we found that DAC affected 8.6% of the transcriptome and that 95.4% of the genes affected were upregulated. DAC preferentially regulated genes that were silenced in cancer and that were methylated at their promoters. In contrast, Depsi affected the expression of 30.4% of the transcriptome but showed little selectivity for gene upregulation or silenced genes. S2101, UNC0638, and GSK343 affected only 2% of the transcriptome, with UNC0638 and GSK343 preferentially targeting genes marked with H3K9me2 or H3K27me3, respectively. When combined with histone methylase inhibitors, the extent of gene upregulation by DAC was extended while still maintaining selectivity for DNA-methylated genes and silenced genes. However, the genes upregulated by combination treatment exhibited limited overlap, indicating the possibility of targeting distinct sets of genes based on different epigenetic therapy combinations. Overall, our results demonstrated that DNA methyltransferase inhibitors preferentially target cancer-relevant genes and can be combined with inhibitors targeting histone methylation for synergistic effects while still maintaining selectivity. Cancer Res; 77(2); 470-81. ©2016 AACR.

  11. Targeted Therapy for Biliary Tract Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Furuse, Junji, E-mail: jfuruse@ks.kyorin-u.ac.jp [Department of Internal Medicine, Medical Oncology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo, 181-8611 (Japan); Okusaka, Takuji [Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

    2011-05-03

    It is necessary to establish effective chemotherapy to improve the survival of patients with biliary tract cancer, because most of these patients are unsuitable candidates for surgery, and even patients undergoing curative surgery often have recurrence. Recently, the combination of cisplatin plus gemcitabine was reported to show survival benefits over gemcitabine alone in randomized clinical trials conducted in the United Kingdom and Japan. Thus, the combination of cisplatin plus gemcitabine is now recognized as the standard therapy for unresectable biliary tract cancer. One of the next issues that need to be addressed is whether molecular targeted agents might also be effective against biliary tract cancer. Although some targeted agents have been investigated as monotherapy for first-line chemotherapy, none were found to exert satisfactory efficacy. On the other hand, monoclonal antibodies such as bevacizumab and cetuximab have also been investigated in combination with a gemcitabine-based regimen and have been demonstrated to show promising activity. Furthermore, clinical trials using new targeted agents for biliary tract cancer are also proposed. This cancer is a relatively rare and heterogeneous tumor consisting of cholangiocarcinoma and gallbladder carcinoma. Therefore, a large randomized clinical trial is necessary to confirm the efficacy of chemotherapy, and international collaboration is important.

  12. Cancer Epigenetics: New Therapies and New Challenges

    Directory of Open Access Journals (Sweden)

    Eleftheria Hatzimichael

    2013-01-01

    Full Text Available Cancer is nowadays considered to be both a genetic and an epigenetic disease. The most well studied epigenetic modification in humans is DNA methylation; however it becomes increasingly acknowledged that DNA methylation does not work alone, but rather is linked to other modifications, such as histone modifications. Epigenetic abnormalities are reversible and as a result novel therapies that work by reversing epigenetic effects are being increasingly explored. The biggest clinical impact of epigenetic modifying agents in neoplastic disorders thus far has been in haematological malignancies, and the efficacy of DNMT inhibitors and HDAC inhibitors in blood cancers clearly attests to the principle that therapeutic modification of the cancer cell epigenome can produce clinical benefit. This paper will discuss the most well studied epigenetic modifications and how these are linked to cancer, will give a brief overview of the clinical use of epigenetics as biomarkers, and will focus in more detail on epigenetic drugs and their use in solid and blood cancers.

  13. Particle therapy and treatment of cancer.

    Science.gov (United States)

    Halperin, Edward C

    2006-08-01

    The desire of radiation oncologists and medical physicists to maximise the radiation dose to the tumour while minimising that to healthy tissues has led to attempts to improve the dose distributions and biological effects achievable with photons and electrons. Protons, neutrons, pions, boron-neutron capture therapy, and charged-nuclei therapy (with argon, carbon, helium [alpha particles], neon, nitrogen, and silicon) have been assessed for their physical, biological, and clinical effects. In the 90 years since protons and neutrons were discovered, investigations of particle therapy for cancer have helped to elucidate many fundamental radiobiological ideas, such as linear energy transfer, relative biological effectiveness, oxygen effect, and oxygen enhancement. Particle therapy has contributed to our understanding of medical ethics when neutron therapy became intertwined with the debate over standards of informed consent in radiation experiments in humans during the cold war era. Particle teletherapy and brachytherapy continue to show promise in some clinical situations. In the future, the insights of molecular biology might clarify the ideal particles for clinical situations.

  14. Cancer immunology - development of novel anti-cancer therapies.

    Science.gov (United States)

    Rothschild, Sacha I; Thommen, Daniela S; Moersig, Wolfgang; Müller, Philipp; Zippelius, Alfred

    2015-01-01

    The vast majority of tumours are characterised by high frequencies of genetic and epigenetic alterations resulting in tumour-specific antigens, which may, in principle, be recognised by cytotoxic T cells. Though early clinical immunotherapy trials have yielded mixed results with ambiguous clinical benefit, cancer immunotherapy is now attracting increasing attention as a viable therapeutic option, mainly in melanoma and lung cancer, but increasingly also in other malignancies. In particular, recent therapeutic efforts targeting inhibitory receptors on T cells to overcome tumour-induced immune dysfunction have the potential to reshape current treatment standards in oncology. The clinical development has been pioneered by the antibody ipilimumab, which blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and has demonstrated survival benefit in two randomised landmark trials in melanoma. Capitalising on this success, the research on the clinical implication of T cell checkpoint inhibition has been boosted. Early clinical trials have demonstrated meaningful response rates, sustained clinical benefits with encouraging survival rates and good tolerability of next-generation checkpoint inhibitors, including programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, across multiple cancer types. Attractive perspectives include the concurrent blockade of immunological (non-redundant) checkpoints, which has recently been demonstrated using combinations of immune checkpoint modulators themselves or with other therapies, such as chemotherapy, targeted therapy or radiotherapy. This article summarises the mechanism of action and subsequent clinical studies of immune checkpoint antibodies in oncology with a particular focus on melanoma and lung cancer.

  15. Systemic cancer multistep therapy; Systemische Krebs-Mehrschritt-Therapie

    Energy Technology Data Exchange (ETDEWEB)

    Weigang-Koehler, K. [Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Staedtisches Klinikum Nuernberg (Germany); Kaiser, G. [Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Staedtisches Klinikum Nuernberg (Germany); Gallmeier, W.M. [Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Staedtisches Klinikum Nuernberg (Germany)

    1997-04-11

    To get an insight into the claimed efficacy of `systemic cancer multistep therapy` (sKMT) with hyperglycemia, whole-body hyperthermia and hyperoxemia, we conducted a best case analysis with 20 patients who had received sKMT alone (9 patients) or in combination with chemo- or radiotherapy (11 patients). There was no complete remission or an unquestionable partial remission when sKMT was used alone. When sKMT was combined with classical effective therapies like chemo- and radiotherapy, 1 patient had questionable complete remission and 3 patients had partial remission. In these three patients sKMT had been combined with a newly applied chemotherapy: Therefore, it remains unclear which method was effective in causing the remission. (orig.) [Deutsch] Um eine Ueberblick ueber die behauptete Wirksamkeit der systemischen Krebs-Mehrschritt-Therapie (sKMT) nach von Ardenne zu erlangen, fuehrten wir eine Best-case-Analyse bei 20 Patienten durch, die die sKMT ohne Chemotherapie (9 Patienten) und in Kombination mit Chemo- bzw. Strahlentherapie (11 Patienten) erhalten hatten. sKMT allein hatte zu keiner kompletten Remission oder sicheren partiellen Remission gefuehrt. Bei der Kombination von sKMT mit klassischen Therapieverfahren wie Chemotherapie und Bestrahlung trat bei einem Patienten eine fragliche komplette Remission ein sowie bei 3 Patienten eine partielle Remission. Im letzteren Fall war jeweils eine fuer den Patienten neue Chemotherapie mit der sKMT kombiniert worden, so dass unklar bleibt, was die Verbesserung herbeifuehrte. (orig.)

  16. Targeted Cancer Therapy Using Engineered Salmonella typhimurium

    Science.gov (United States)

    Zheng, Jin Hai

    2016-01-01

    Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy. PMID:27689027

  17. Targeted Cancer Therapy Using Engineered Salmonella typhimurium.

    Science.gov (United States)

    Zheng, Jin Hai; Min, Jung-Joon

    2016-09-01

    Obligate or facultative anaerobic bacteria such as Bifidobacterium, Clostridium, Salmonella, or Escherichia coli specifically colonize and proliferate inside tumor tissues and inhibit tumor growth. Among them, attenuated Salmonella typhimurium (S. typhimurium) has been widely studied in animal cancer models and Phase I clinical trials in human patients. S. typhimurium genes are easily manipulated; thus diverse attenuated strains of S. typhimurium have been designed and engineered as tumor-targeting therapeutics or drug delivery vehicles that show both an excellent safety profile and therapeutic efficacy in mouse models. An attenuated strain of S. typhimurium, VNP20009, successfully targeted human metastatic melanoma and squamous cell carcinoma in Phase I clinical trials; however, the efficacy requires further refinement. Along with the characteristics of self-targeting, proliferation, and deep tissue penetration, the ease of genetic manipulation allows for the production of more attenuated strains with greater safety profiles and vector systems that deliver designable cargo molecules for cancer diagnosis and/or therapy. Here, we discuss recent progress in the field of Salmonellae-mediated cancer therapy.

  18. Lipid Metabolism, Apoptosis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Chunfa Huang

    2015-01-01

    Full Text Available Lipid metabolism is regulated by multiple signaling pathways, and generates a variety of bioactive lipid molecules. These bioactive lipid molecules known as signaling molecules, such as fatty acid, eicosanoids, diacylglycerol, phosphatidic acid, lysophophatidic acid, ceramide, sphingosine, sphingosine-1-phosphate, phosphatidylinositol-3 phosphate, and cholesterol, are involved in the activation or regulation of different signaling pathways. Lipid metabolism participates in the regulation of many cellular processes such as cell growth, proliferation, differentiation, survival, apoptosis, inflammation, motility, membrane homeostasis, chemotherapy response, and drug resistance. Bioactive lipid molecules promote apoptosis via the intrinsic pathway by modulating mitochondrial membrane permeability and activating different enzymes including caspases. In this review, we discuss recent data in the fields of lipid metabolism, lipid-mediated apoptosis, and cancer therapy. In conclusion, understanding the underlying molecular mechanism of lipid metabolism and the function of different lipid molecules could provide the basis for cancer cell death rationale, discover novel and potential targets, and develop new anticancer drugs for cancer therapy.

  19. Personalized Radiation Therapy (PRT) for Lung Cancer.

    Science.gov (United States)

    Jin, Jian-Yue; Kong, Feng-Ming Spring

    2016-01-01

    This chapter reviews and discusses approaches and strategies of personalized radiation therapy (PRT) for lung cancers at four different levels: (1) clinically established PRT based on a patient's histology, stage, tumor volume and tumor locations; (2) personalized adaptive radiation therapy (RT) based on image response during treatment; (3) PRT based on biomarkers; (4) personalized fractionation schedule. The current RT practice for lung cancer is partially individualized according to tumor histology, stage, size/location, and combination with use of systemic therapy. During-RT PET-CT image guided adaptive treatment is being tested in a multicenter trial. Treatment response detected by the during-RT images may also provide a strategy to further personalize the remaining treatment. Research on biomarker-guided PRT is ongoing. The biomarkers include genomics, proteomics, microRNA, cytokines, metabolomics from tumor and blood samples, and radiomics from PET, CT, SPECT images. Finally, RT fractionation schedule may also be personalized to each individual patient to maximize therapeutic gain. Future PRT should be based on comprehensive considerations of knowledge acquired from all these levels, as well as consideration of the societal value such as cost and effectiveness.

  20. Harnessing Endogenous Systems for Cancer Therapy

    DEFF Research Database (Denmark)

    Klauber, Thomas Christopher Bogh

    In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect on the dis......In the recent decade, two strategies in particular have attracted attention due to the prospect of significantly improving cancer treatment: Gene silencing therapy and immunotherapy. Both strategies work by manipulating endogenous mechanisms and theoretically promise very strong effect...... immunotherapy (Project II). Transfer into the clinic of therapies based on gene silencing by siRNA delivered by synthetic vectors has yet to happen. A major reason is the lack of efficiency in the delivery process, partly due to insufficient understanding of cellular uptake and processing of the si......RNA-containing particles. Project I aims to provide new mechanistic understanding of intracellular processing and vector interaction with target cells by investigating siRNA delivery using branched polyethyleneimine (bPEI), which is a well-known synthetic vector for DNA delivery, and comparing the properties of b...

  1. Immunotherapy and gene therapy of thyroid cancer.

    Science.gov (United States)

    Schott, M; Scherbaum, W A

    2004-12-01

    Most forms of thyroid cancer have a good prognosis. Some tumours, however, dedifferentiate and may finally develop into highly malignant anaplastic thyroid carcinomas with a low survival time. Due to their dedifferentiation these tumours are inaccessible to classical therapeutic options as radioiodide treatment or thyrotropin-suppression. Radical surgical revision of the tumour masses is the therapy of choice of patients with limited disease stages including patients with medullary thyroid carcinomas. Despite progress in radiation and chemotherapy regimes, many metastatic forms remain, however, incurable by conventional therapies. During the past few years new developments in immunology have revealed increasing information about the molecular basis of tumour-host interactions. The multitude of information resulting from basic science in cellular immunology, together with the availability of biologic reagents in pharmacological amounts, has opened new venues for the development of immunotherapy approaches for patients with different kind of cancers including thyroid malignancies. This review describes some most important developments in cellular immunotherapies e.g. dendritic cells-based protocols and gene therapy. It also provides a brief overview on the role of cytokines and antibodies in the treatment of advanced thyroid malignancies.

  2. Novel therapy for advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Yue; Zhang; Shenhong; Wu

    2015-01-01

    Gastric cancer(GC) is a common lethal malignancy.Gastroesophageal junction and gastric cardia tumors are the fastest rising malignancies due to increasing prevalence of obesity and acid reflex in the United States.Traditional chemotherapy remains the main treatment with trastuzumab targeting human epidermal growth factor receptor 2 positive disease.The median overall survival(OS) is less than one year for advanced GC patients; thus,there is an urgent unmet need to develop novel therapy for GC.Although multiple targeted agents were studied,only the vascular endothelial growth factor receptor inhibitor ramucirumab was approved recently by the United States Food and Drug Administration because of its 1.4 mo OS benefit(5.2 mo vs 3.8 mo,P = 0.047) as a single agent; 2.2 mo improvement of survival(9.6 mo vs 7.4 mo,P = 0.017) when combined with paclitaxel in previously treated advanced GC patients.It is the first single agent approved for previously treated GC and the second biologic agent after trastuzumab.Even with limited success,targeted therapy may be improved by developing new biomarkers.Immune therapy is changing the paradigm of cancer treatment and is presently under active investigation for GC in clinical trials.More evidence supports GC stem cells existence and early stage studies are looking for its potential therapeutic possibilities.

  3. Transcriptionally regulated, prostate-targeted gene therapy for prostate cancer.

    Science.gov (United States)

    Lu, Yi

    2009-07-02

    Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer deaths in American males today. Novel and effective treatment such as gene therapy is greatly desired. The early viral based gene therapy uses tissue-nonspecific promoters, which causes unintended toxicity to other normal tissues. In this chapter, we will review the transcriptionally regulated gene therapy strategy for prostate cancer treatment. We will describe the development of transcriptionally regulated prostate cancer gene therapy in the following areas: (1) Comparison of different routes for best viral delivery to the prostate; (2) Study of transcriptionally regulated, prostate-targeted viral vectors: specificity and activity of the transgene under several different prostate-specific promoters were compared in vitro and in vivo; (3) Selection of therapeutic transgenes and strategies for prostate cancer gene therapy (4) Oncolytic virotherapy for prostate cancer. In addition, the current challenges and future directions in this field are also discussed.

  4. Hyaluronan-Based Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-07-01

    interplay between the extrinsic and intrinsic apoptotic pathways would be an effective rationale for cancer therapy . In reality , however, dulanermin...AWARD NUMBER: W81XWH-14-1-0184 TITLE: Hyaluronan-Based Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Dr. Magdelena...5a. CONTRACT NUMBER W81XWH-14-1-0184 Hyaluronan-Based Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0184 5c. PROGRAM

  5. Nanomaterial-based drug delivery carriers for cancer therapy

    CERN Document Server

    Feng, Tao

    2017-01-01

    This brief summarizes different types of organic and inorganic nanomaterials for drug delivery in cancer therapy. It highlights that precisely designed nanomaterials will be the next-generation therapeutic agents for cancer treatment.

  6. Radiation Therapy and You: Support for People with Cancer

    Science.gov (United States)

    ... Terms Blogs and Newsletters Health Communications Publications Reports Radiation Therapy and You: Support for People With Cancer ... Copy This booklet covers: Questions and Answers About Radiation Therapy. Answers common questions, such as what radiation ...

  7. Risk-optimized proton therapy to minimize radiogenic second cancers

    DEFF Research Database (Denmark)

    Rechner, Laura A; Eley, John G; Howell, Rebecca M

    2015-01-01

    Proton therapy confers substantially lower predicted risk of second cancer compared with photon therapy. However, no previous studies have used an algorithmic approach to optimize beam angle or fluence-modulation for proton therapy to minimize those risks. The objectives of this study were...... to demonstrate the feasibility of risk-optimized proton therapy and to determine the combination of beam angles and fluence weights that minimizes the risk of second cancer in the bladder and rectum for a prostate cancer patient. We used 6 risk models to predict excess relative risk of second cancer. Treatment...

  8. Chlorambucil gemcitabine conjugate nanomedicine for cancer therapy.

    Science.gov (United States)

    Fan, Mingliang; Liang, Xiaofei; Li, Zonghai; Wang, Hongyang; Yang, Danbo; Shi, Bizhi

    2015-11-15

    Self-assembly of anticancer small molecules into nanostructures may represent an attractive approach to improve the treatment of experimental solid tumors. As a proof of concept, we designed and synthesized the conjugate prodrug of hydrophilic gemcitabine by its covalent coupling to hydrophobic chlorambucil via a hydrolyzable ester linkage. The resulting amphiphilic conjugates self-assembled into nanoparticles in water and exhibited significant anticancer activity in vitro against a variety of human cancer cells. In vivo anticancer activity of these nanoparticles has been tested on subcutaneous grafted SMMC-7721 hepatocellular carcinoma model. Such chlorambucil gemcitabine conjugate nanomedicine should have potential applications in cancer therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. PHOTODYNAMIC THERAPY OF CANCER: AN UPDATE

    Science.gov (United States)

    Agostinis, Patrizia; Berg, Kristian; Cengel, Keith A.; Foster, Thomas H.; Girotti, Albert W.; Gollnick, Sandra O.; Hahn, Stephen M.; Hamblin, Michael R.; Juzeniene, Asta; Kessel, David; Korbelik, Mladen; Moan, Johan; Mroz, Pawel; Nowis, Dominika; Piette, Jacques; Wilson, Brian C.; Golab, Jakub

    2011-01-01

    Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative particularly in early-stage tumors. It can prolong survival in inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment. PMID:21617154

  10. Carbon materials for drug delivery & cancer therapy

    Directory of Open Access Journals (Sweden)

    Zhuang Liu

    2011-07-01

    Full Text Available Carbon nanotubes and graphene are both low-dimensional sp2 carbon nanomaterials exhibiting many unique physical and chemical properties that are interesting in a wide range of areas including nanomedicine. Since 2004, carbon nanotubes have been extensively explored as drug delivery carriers for the intracellular transport of chemotherapy drugs, proteins, and genes. In vivo cancer treatment with carbon nanotubes has been demonstrated in animal experiments by several different groups. Recently, graphene, another allotrope of carbon, has also shown promise in various biomedical applications. In this article, we will highlight recent research on these two categories of closely related carbon nanomaterials for applications in drug delivery and cancer therapy, and discuss the opportunities and challenges in this rapidly growing field.

  11. Thermohydrogel Containing Melanin for Photothermal Cancer Therapy.

    Science.gov (United States)

    Kim, Miri; Kim, Hyun Soo; Kim, Min Ah; Ryu, Hyanghwa; Jeong, Hwan-Jeong; Lee, Chang-Moon

    2016-12-01

    Melanin is an effective absorber of light and can extend to near infrared (NIR) regions. In this study, a natural melanin is presented as a photothermal therapeutic agent (PTA) because it provides a good photothermal conversion efficiency, shows biodegradability, and does not induce long-term toxicity during retention in vivo. Poloxamer solution containing melanin (Pol-Mel) does not show any precipitation and shows sol-gel transition at body temperature. After irradiation from 808 nm NIR laser at 1.5 W cm(-2) for 3 min, the photothermal conversion efficiency of Pol-Mel is enough to kill cancer cells in vitro and in vivo. The tumor growth of mice bearing CT26 tumors treated with Pol-Mel injection and laser irradiation is suppressed completely without recurrence postirradiation. All these results indicate that Pol-Mel can become an attractive PTA for photothermal cancer therapy.

  12. Advanced strategies in liposomal cancer therapy

    DEFF Research Database (Denmark)

    Andresen, Thomas Lars; Jensen, Simon Skøde; Jørgensen, Kent

    2005-01-01

    , none of them have yet led to marketed drugs and are still far from achieving this goal. The most advanced and prospective technologies are probably the prodrug strategies where nontoxic drugs are carried and activated specifically in the malignant tissue by overexpressed enzymes. In the second part......Tumor specific drug delivery has become increasingly interesting in cancer therapy, as the use of chemotherapeutics is often limited due to severe side effects. Conventional drug delivery systems have shown low efficiency and a continuous search for more advanced drug delivery principles...... is therefore of great importance. In the first part of this review, we present current strategies in the drug delivery field, focusing on site-specific triggered drug release from liposomes in cancerous tissue. Currently marketed drug delivery systems lack the ability to actively release the carried drug...

  13. COMBINATION THERAPY FOR PROSTATE CANCER: CLINICAL OBSERVATIONS

    Directory of Open Access Journals (Sweden)

    B. Ya. Alekseev

    2014-08-01

    Full Text Available Prostate cancer (PC is one of the urgent problems of modern urological oncology. The incidence of this pathology is steadily growing worldwide. Despite the fact that PSA diagnosis is extensively used and programs for the early detection of this disease are introduced, the rate of dia gnosis of advanced PC forms remains high. Furthermore, a number of aspects of therapy for this disease remain controversial so far. The 7 th Congress of the Russian Society of Urological Oncologists, which dealt with some issues of combination therapy for locally advanced PC, was held in Moscow in October 3 to 5, 2012. The paper covers a number of controversial issues in the management of patients with PC in different clinical situations.

  14. Alphavirus vectors for cancer gene therapy (review).

    Science.gov (United States)

    Yamanaka, Ryuya

    2004-04-01

    Alphaviruses have several characteristics that make them attractive as gene therapy vectors such as transient and high-level expression of a heterologous gene. Alphavirus vectors, Semliki Forest virus (SFV), Sindbis virus (SIN) and Venezuelan equine encephalitis virus (VEE) have been developed as gene expression vectors. Alphaviruses are positive-strand RNA viruses that can mediate efficient cytoplasmic gene expression in mammalian cells. The alphavirus RNA replication machinery has been engineered for high level heterologous gene expression. Since an RNA virus vector cannot integrate into chromosomal DNA, concerns about cell transformation are reduced. Alphavirus vectors demonstrate promise for the safe tumor-killing and tumor-specific immune responses. Recombinant alphavirus RNA replicons may facilitate gene therapy of cancer.

  15. Targeting DNA Replication Stress for Cancer Therapy

    Science.gov (United States)

    Zhang, Jun; Dai, Qun; Park, Dongkyoo; Deng, Xingming

    2016-01-01

    The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR) mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress. PMID:27548226

  16. Targeting DNA Replication Stress for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2016-08-01

    Full Text Available The human cellular genome is under constant stress from extrinsic and intrinsic factors, which can lead to DNA damage and defective replication. In normal cells, DNA damage response (DDR mediated by various checkpoints will either activate the DNA repair system or induce cellular apoptosis/senescence, therefore maintaining overall genomic integrity. Cancer cells, however, due to constitutive growth signaling and defective DDR, may exhibit “replication stress” —a phenomenon unique to cancer cells that is described as the perturbation of error-free DNA replication and slow-down of DNA synthesis. Although replication stress has been proven to induce genomic instability and tumorigenesis, recent studies have counterintuitively shown that enhancing replicative stress through further loosening of the remaining checkpoints in cancer cells to induce their catastrophic failure of proliferation may provide an alternative therapeutic approach. In this review, we discuss the rationale to enhance replicative stress in cancer cells, past approaches using traditional radiation and chemotherapy, and emerging approaches targeting the signaling cascades induced by DNA damage. We also summarize current clinical trials exploring these strategies and propose future research directions including the use of combination therapies, and the identification of potential new targets and biomarkers to track and predict treatment responses to targeting DNA replication stress.

  17. Potential role of tetrandrine in cancer therapy

    Institute of Scientific and Technical Information of China (English)

    CHEN Yu-Jen

    2002-01-01

    Tetrandrine, a bisbenylisoquinoline alkaloid isolated from the dried root of Stephenia tetrandra S Moore, exhibits very broad pharmacological actions, including anti-tumor activity. The beneficial effects of tetrandrine on tumor cell cytotoxicity and radiosensitization, multidrug resistance, normal tissue radioprotection, and angiogenesis are most promising and deserve great attention. Tetrandrine has potential either as a tumoricidal agent or as an adjunct to chemotherapy and radiotherapy. To evaluate the potential clinical efficacy of tetrandrine for cancer therapy,more mechanism-based pharmacological, pharmacokinetic, and pharmacodynamic studies are required.

  18. Novel therapies in genitourinary cancer: an update

    Directory of Open Access Journals (Sweden)

    Wu Shenhong

    2008-08-01

    Full Text Available Abstract In recent years, new treatment for renal cell carcinoma (RCC has been a spotlight in the field of cancer therapeutics. With several emerging agents branded as 'targeted therapy' now available, both medical oncologists and urologists are progressively more hopeful for better outcomes. The new remedies may provide patients with improved survival and at the same time less toxicity when compared to traditional cytotoxic agents. This article will center on current and emerging treatment strategies for advanced RCC and other GU malignancies with updates from 2008 annual ASCO meeting.

  19. Application of gold nanoparticles in cancer therapy.

    Science.gov (United States)

    Zhao, Chuan-tong; Liu, Zhen-bao

    2014-06-01

    With their unique physicochemical properties including excellent stability and biocompatibility, large specific surface area, and easy surface modification, gold nanoparticles (AuNPs) can be used as delivery vectors for drugs, genes, proteins, etc. In addition, AuNPs have excellent photothermal effects and radiosensitization characteristics, and therefore can be widely applied in the photothermal therapy and radiotherapy of cancers. This article reviews the construction, cellular uptake, and drug release of AuNPs drug-delivery systems and their applications in the treatment of tumors.

  20. Radiation Therapy in Elderly Skin Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jin Hee [Keimyung University College of Medicine, Daegu (Korea, Republic of)

    2008-06-15

    To evaluate the long term results (local control, survival, failure, and complications) after radiation therapy for skin cancer in elderly patients. The study spanned from January 1990 to October 2002. Fifteen elderly patients with skin cancer were treated by radiotherapy at the Keimyung University Dongsan Medical Center. The age distribution of the patients surveyed was 72 to 95 years, with a median age of 78.8 years. The pathologic classification of the 15 patients included squamous cell carcinoma (10 patients), basal cell carcinoma (3 patients), verrucous carcinoma (1 patient) and skin adnexal origin carcinoma (1 patient). The most common tumor location was the head (13 patients). The mean tumor diameter was 4.9 cm (range 2 to 9 cm). The radiation dose was delivered via an electron beam of 6 to 15 MeV. The dose range was adjusted to the tumor diameter and depth of tumor invasion. The total radiation dose ranged from 50{approx}80 Gy (mean: 66 Gy) with a 2 Gy fractional dose prescribed to the 80% isodose line once a day and 5 times a week. One patient with lymph node metastasis was treated with six MV photon beams boosted with electron beams. The length of the follow-up periods ranged from 10 to 120 months with a median follow-up period of 48 months. The local control rates were 100% (15/15). In addition, the five year disease free survival rate (5YDFS) was 80% and twelve patients (80%) had no recurrence and skin cancer recurrence occurred in 3 patients (20%). Three patients have lived an average of 90 months (68{approx}120 months) without recurrence or metastasis. A total of 9 patients who died as a result of other causes had a mean survival time of 55.8 months after radiation therapy. No severe acute or chronic complications were observed after radiation therapy. Only minor complications including radiation dermatitis was treated with supportive care. The results suggest that radiation therapy is an effective and safe treatment method for the treatment of skin

  1. Neutron therapy for salivary and thyroid gland cancer

    Science.gov (United States)

    Gribova, O. V.; Musabaeva, L. I.; Choynzonov, E. L.; Lisin, V. A.; Novikov, V. A.

    2016-08-01

    The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

  2. Neutron therapy for salivary and thyroid gland cancer

    Energy Technology Data Exchange (ETDEWEB)

    Gribova, O. V., E-mail: gribova79@mail.ru; Choynzonov, E. L., E-mail: nii@oncology.tomsk.ru [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation); National Research Tomsk Polytechnic University, Lenina Avenue 30, Tomsk, 634050 (Russian Federation); Musabaeva, L. I., E-mail: musabaevaLI@oncology.tomsk.ru; Lisin, V. A., E-mail: Lisin@oncology.tomsk.ru; Novikov, V. A., E-mail: dr.vanovikov@gmail.com [Tomsk Cancer Research Institute, Kooperativny Street 5, Tomsk, 634050 (Russian Federation)

    2016-08-02

    The purpose of this study was to analyze the results of the combined modality treatment and radiation therapy using 6.3 MeV fast neutrons for salivary gland cancer and prognostically unfavorable thyroid gland cancer. The study group comprised 127 patients with salivary gland cancer and 46 patients with thyroid gland cancer, who received neutron therapy alone and in combination with surgery. The results obtained demonstrated that the combined modality treatment including fast neutron therapy led to encouraging local control in patients with salivary and thyroid gland cancers.

  3. Gene-modified bone marrow cell therapy for prostate cancer.

    Science.gov (United States)

    Wang, H; Thompson, T C

    2008-05-01

    There is a critical need to develop new and effective cancer therapies that target bone, the primary metastatic site for prostate cancer and other malignancies. Among the various therapeutic approaches being considered for this application, gene-modified cell-based therapies may have specific advantages. Gene-modified cell therapy uses gene transfer and cell-based technologies in a complementary fashion to chaperone appropriate gene expression cassettes to active sites of tumor growth. In this paper, we briefly review potential cell vehicles for this approach and discuss relevant gene therapy strategies for prostate cancer. We further discuss selected studies that led to the conceptual development and preclinical testing of IL-12 gene-modified bone marrow cell therapy for prostate cancer. Finally, we discuss future directions in the development of gene-modified cell therapy for metastatic prostate cancer, including the need to identify and test novel therapeutic genes such as GLIPR1.

  4. [Genetic basis of head and neck cancers and gene therapy].

    Science.gov (United States)

    Özel, Halil Erdem; Özkırış, Mahmut; Gencer, Zeliha Kapusuz; Saydam, Levent

    2013-01-01

    Surgery and combinations of traditional treatments are not successful enough particularly for advanced stage head and neck cancer. The major disadvantages of chemotherapy and radiation therapy are the lack of specificity for the target tissue and toxicity to the patient. As a result, gene therapy may offer a more specific approach. The aim of gene therapy is to present therapeutic genes into cancer cells which selectively eliminate malignant cells with no systemic toxicity to the patient. This article reviews the genetic basis of head and neck cancers and important concepts in cancer gene therapy: (i) inhibition of oncogenes; (ii) tumor suppressor gene replacement; (iii) regulation of immune response against malignant cells; (iv) genetic prodrug activation; and (v) antiangiogenic gene therapy. Currently, gene therapy is not sufficient to replace the traditional treatments of head and neck cancers, however there is no doubt that it will have an important role in the near future.

  5. Drug targeting systems for cancer therapy: nanotechnological approach.

    Science.gov (United States)

    Tigli Aydin, R Seda

    2015-01-01

    Progress in cancer treatment remains challenging because of the great nature of tumor cells to be drug resistant. However, advances in the field of nanotechnology have enabled the delivery of drugs for cancer treatment by passively and actively targeting to tumor cells with nanoparticles. Dramatic improvements in nanotherapeutics, as applied to cancer, have rapidly accelerated clinical investigations. In this review, drug-targeting systems using nanotechnology and approved and clinically investigated nanoparticles for cancer therapy are discussed. In addition, the rationale for a nanotechnological approach to cancer therapy is emphasized because of its promising advances in the treatment of cancer patients.

  6. FDG-PET in monitoring therapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Biersack, H.J.; Bender, H.; Palmedo, H. [Department of Nuclear Medicine, University Hospital Bonn, Sigmund-Freud-Strasse 25, 53127, Bonn (Germany)

    2004-06-01

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been used successfully for the staging and re-staging of breast cancer. Another significant indication is the evaluation of therapy response. Only limited data are available on the use of FDG-PET in breast cancer after radiation therapy. The same holds true for chemotherapy. Only the therapy response in locally advanced breast cancer after chemotherapy has been investigated thoroughly. Histopathological response could be predicted with an accuracy of 88-91% after the first and second courses of therapy. A quantitative evaluation is, of course, a prerequisite when FDG-PET is used for therapy monitoring. Only a small number of studies have focussed on hormone therapy. In this context, a flare phenomenon with increasing standardised uptake values after initiation of tamoxifen therapy has been observed. More prospective multicentre trials will be needed to make FDG-PET a powerful tool in monitoring chemotherapy in breast cancer. (orig.)

  7. Fullerenols in therapy and diagnosis of cancer

    Directory of Open Access Journals (Sweden)

    Anna Lichota

    2016-12-01

    Full Text Available Malignant tumors are one of the main causes of death in Poland. One of the objectives of contemporary biomedical research is to maximize the effects of therapeutic strategies. The actions undertaken to improve therapeutic agents are aimed at reducing the side effects of cancer treatments. Another direction of investigations is the search for protective substances that reduce the toxicity of the drug to normal cells. Carbon-based nanomaterials (fullerenes and their derivatives, graphene, carbon nanotubes, nanodiamonds are a broad class of nanoparticles that have potential biomedical applications in both therapy and diagnostics. The aim of this paper is to review biological properties of fullerenols in the context of their use in various strategies of cancer treatments. The authors also discuss the possibility of simultaneous use of nanoparticles in therapy and diagnosis, that is, in theranostics. Current knowledge indicates that fullerenes and their hydrophilic derivatives, especially fullerenols, show low or no toxicity. They may contribute to the inhibition of tumor growth and protection of normal cells through their antioxidant properties, as well as to the regulation of expression of genes involved in apoptosis and angiogenesis, and stimulation of the immune response. Gadoliniumcontaining endohedral fullerenes are less toxic as a contrast agents in magnetic resonance imaging, and they may also inhibit tumor growth, which is a promising result for theranostics. Med Pr 2016;67(6:817–831

  8. Photodynamic therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Kamil H Nelke

    2014-02-01

    Full Text Available Photodynamic therapy (PDT is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells in different areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC, and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers, their use, and therapeutic advantages and disadvantages.

  9. Drug Carrier for Photodynamic Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Tilahun Ayane Debele

    2015-09-01

    Full Text Available Photodynamic therapy (PDT is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS, and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0 to an excited singlet state (S1–Sn, followed by intersystem crossing to an excited triplet state (T1. The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*, which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer.

  10. Combination immunotherapy and photodynamic therapy for cancer

    Science.gov (United States)

    Hamblin, Michael R.; Castano, Ana P.; Mroz, Pawel

    2006-02-01

    Cancer is a leading cause of death among modern people largely due to metastatic disease. The ideal cancer treatment should target both the primary tumor and the metastases with minimal toxicity towards normal tissue. This is best accomplished by priming the body's immune system to recognize the tumor antigens so that after the primary tumor is destroyed, distant metastases will also be eradicated. Photodynamic therapy (PDT) involves the IV administration of photosensitizers followed by illumination of the tumor with red light producing reactive oxygen species leading to vascular shutdown and tumor cell death. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, generation of tumor-specific antigens, and induction of heat-shock proteins. Combination regimens using PDT and immunostimulating treatments are likely to even further enhance post-PDT immunity. These immunostimulants are likely to include products derived from pathogenic microorganisms that are effectively recognized by Toll-like receptors and lead to upregulation of transcription factors for cytokines and inflammatory mediators. The following cascade of events causes activation of macrophages, dendritic and natural killer cells. Exogenous cytokine administration can be another way to increase PDT-induced immunity as well as treatment with a low dose of cyclophosphamide that selectively reduces T-regulatory cells. Although so far these combination therapies have only been used in animal models, their use in clinical trials should receive careful consideration.

  11. Photodynamic therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Kamil H Nelke

    2014-02-01

    Full Text Available Photodynamic therapy (PDT is a special type of treatment involving the use of a photosensitizer or a photosensitizing agent along with a special type of light, which, combined together, induces production of a form of oxygen that is used to kill surrounding cells in different areas of the human body. Specification of the head and neck region requires different approaches due to the surrounding of vital structures. PDT can also be used to treat cells invaded with infections such as fungi, bacteria and viruses. The light beam placed in tumor sites activates locally applied drugs and kills the cancer cells. Many studies are taking place in order to invent better photosensitizers, working on a larger scale and to treat deeply placed and larger tumors. It seems that PDT could be used as an alternative surgical treatment in some tumor types; however, all clinicians should be aware that the surgical approach is still the treatment of choice. PDT is a very accurate and effective therapy, especially in early stages of head and neck squamous cell carcinomas (HNSCC, and can greatly affect surgical outcomes in cancerous patients. We present a detailed review about photosensitizers, their use, and therapeutic advantages and disadvantages.

  12. Drug Carrier for Photodynamic Cancer Therapy

    Science.gov (United States)

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

  13. Targeting angiogenesis with integrative cancer therapies.

    Science.gov (United States)

    Yance, Donald R; Sagar, Stephen M

    2006-03-01

    An integrative approach for managing a patient with cancer should target the multiple biochemical and physiological pathways that support tumor development while minimizing normal tissue toxicity. Angiogenesis is a key process in the promotion of cancer. Many natural health products that inhibit angiogenesis also manifest other anticancer activities. The authors will focus on natural health products (NHPs) that have a high degree of antiangiogenic activity but also describe some of their many other interactions that can inhibit tumor progression and reduce the risk of metastasis. NHPs target various molecular pathways besides angiogenesis, including epidermal growth factor receptor (EGFR), the HER-2/neu gene, the cyclooxygenase-2 enzyme, the NF-kB transcription factor, the protein kinases, Bcl-2 protein, and coagulation pathways. The herbalist has access to hundreds of years of observational data on the anticancer activity of many herbs. Laboratory studies are confirming the knowledge that is already documented in traditional texts. The following herbs are traditionally used for anticancer treatment and are antiangiogenic through multiple interdependent processes that include effects on gene expression, signal processing, and enzyme activities: Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (turmeric), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinale (ginger), Panax ginseng, Rabdosia rubescens (rabdosia), and Chinese destagnation herbs. Quality assurance of appropriate extracts is essential prior to embarking on clinical trials. More data are required on dose response, appropriate combinations, and potential toxicities. Given the multiple effects of these agents, their future use for cancer therapy probably lies in synergistic combinations

  14. STAT5 induces miR-21 expression in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lindahl, Lise M; Fredholm, Simon; Joseph, Claudine;

    2016-01-01

    In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression...... in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR-21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression was inhibited...... by Tofacitinib (CP-690550), a clinical-grade JAK3 inhibitor. Chromatin immunoprecipitation (ChIP) analysis showed direct binding of STAT5 to the miR-21 promoter. Cytokine starvation ex vivo triggered a decrease in miR-21 expression, whereas IL-2 induced an increased miR-21 expression in primary SS T cells...

  15. Pancreatic cancer vaccine: a unique potential therapy

    Directory of Open Access Journals (Sweden)

    Cappello P

    2015-12-01

    Full Text Available Paola Cappello, Moitza Principe, Francesco Novelli Department of Molecular Biotechnologies and Health Sciences, Center for Experimental Research and Medical Studies, AOU Città della Salute e della Scienza di Torino, University of Turin, Turin, Italy Abstract: Pancreatic ductal adenocarcinoma (PDA is a lethal disease and is one of the cancers that is most resistant to traditional therapies. Historically, neither chemotherapy nor radiotherapy has provided any significant increase in the survival of patients with PDA. Despite intensive efforts, any attempts to improve the survival in the past 15 years have failed. This holds true even after the introduction of molecularly targeted agents, chosen on the basis of their involvement in pathways that are considered to be important in PDA development and progression. Recently, however, FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin treatment has provided a limited survival advantage in patients with advanced PDA. Therefore, effective therapeutic strategies are urgently needed to improve the survival rate of patients with PDA. Results from the last 10 years of research in the field of PDA have helped to identify new immunological targets and develop new vaccines that are capable of stimulating an immune response. In addition, the information obtained about the role of the tumor microenvironment in suppressing the immune response and the possibility of targeting PDA microenvironment to limit immune suppression and enhance the response of effector T-cells has opened new avenues for treating this incurable disease. The time is ripe for developing new therapeutic approaches that are able to effectively counteract the progression and spreading of PDA. This review discusses the potential prospects in the care of patients with pancreatic cancer through vaccination and its combination therapy with surgery, chemotherapy, targeting of the tumor microenvironment, and inhibition of immunological

  16. Auger Emitting Radiopharmaceuticals for Cancer Therapy

    Science.gov (United States)

    Falzone, Nadia; Cornelissen, Bart; Vallis, Katherine A.

    Radionuclides that emit Auger electrons have been of particular interest as therapeutic agents. This is primarily due to the short range in tissue, controlled linear paths and high linear energy transfer of these particles. Taking into consideration that ionizations are clustered within several cubic nanometers around the point of decay the possibility of incorporating an Auger emitter in close proximity to the cancer cell DNA has immense therapeutic potential thus making nuclear targeted Auger-electron emitters ideal for precise targeting of cancer cells. Furthermore, many Auger-electron emitters also emit γ-radiation, this property makes Auger emitting radionuclides a very attractive option as therapeutic and diagnostic agents in the molecular imaging and management of tumors. The first requirement for the delivery of Auger emitting nuclides is the definition of suitable tumor-selective delivery vehicles to avoid normal tissue toxicity. One of the main challenges of targeted radionuclide therapy remains in matching the physical and chemical characteristics of the radionuclide and targeting moiety with the clinical character of the tumor. Molecules and molecular targets that have been used in the past can be classified according to the carrier molecule used to deliver the Auger-electron-emitting radionuclide. These include (1) antibodies, (2) peptides, (3) small molecules, (4) oligonucleotides and peptide nucleic acids (PNAs), (5) proteins, and (6) nanoparticles. The efficacy of targeted radionuclide therapy depends greatly on the ability to increase intranuclear incorporation of the radiopharmaceutical without compromising toxicity. Several strategies to achieve this goal have been proposed in literature. The possibility of transferring tumor therapy based on the emission of Auger electrons from experimental models to patients has vast therapeutic potential, and remains a field of intense research.

  17. Adherence to adjuvant endocrine therapy in women with breast cancer.

    Science.gov (United States)

    Danilak, Melanie; Chambers, Carole R

    2013-06-01

    To determine how many breast cancer patients who initiated adjuvant endocrine therapy discontinued early and to evaluate adherence in patients who persisted with therapy. Secondary objectives were to explore possible trends to see if certain factors may correlate to early discontinuation of therapy. A retrospective review of charts and pharmacy dispensing records was conducted, including patients who initiated adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute from 1 January to 31 December, 2006. Out of 346 patients, 81 (22%) discontinued therapy within 2 years. Adherence rates calculated for the 265 patients who remained on therapy beyond 2 years showed that 247 (93%) of these patients had 80% or better adherence. Patients who did not undergo chemotherapy and patients with Cross Cancer Institute follow-up times of less than 1 year were significantly more likely to discontinue therapy early. The majority of patients who were prescribed adjuvant endocrine therapy for breast cancer at the Cross Cancer Institute remained on therapy for at least 2 years and were adherent. Longer follow-up by Cross Cancer Institute practitioners may help decrease discontinuation rates.

  18. Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBERS: W81XWH-14-1-0554 TITLE: Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer PRINCIPAL INVESTIGATOR...Dr. Nora M. Navone (Initiating PI) RECIPIENT: The University of Texas MD Anderson Cancer Center Houston, TX 77030 REPORT DATE: TYPE OF...21Sep2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER N/A Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer 5b. GRANT

  19. Hormone Replacement Therapy After Breast Cancer

    Directory of Open Access Journals (Sweden)

    Mueck AO

    2008-01-01

    Full Text Available So far, patient samples in all studies investigating hormone replacement therapy (HRT after breast cancer have been small.Therefore, HRT should only be used if alternatives such as specifically not contraindicated phytopreparations or selective sero-tonin reuptake inhibitors (SSRIs are not effective. This is primarily due to forensic reasons since clinical data on the risk ofalternatives (based on present evidence are even more sparse. Regarding HRT, four prospective randomized studies and at least15 observational studies after breast cancer are available. Only the HABITS study shows an increased risk of relapse. The authorssuggest that this is probably associated with the relatively high number of patients with HRT treatment after ER-positive cancersas well as due to the preferred use of estrogen/progestin-combined preparations. Based on the results of the randomized pla-cebo-controlled study Women’s Health Initiative (WHI as well as of at least 12 observational studies, the progestin componentseems to be mainly responsible for the probability of increased diagnosis frequency of primary breast cancer. However, no dataare available on the impact of progestin on the use of combined HRT after breast cancer. However, also with estrogen only anincreased risk of relapse must be expected and patients should be informed about it. This has to be concluded due to biologicalplausibility and observational studies although the estrogen-only arm in WHI did not show any increased primary risk. Thus, anyform of HRT should only be performed in exceptional cases, and treatment duration should be as short as possible with thelowest effective dose.

  20. Targeting copper in cancer therapy: 'Copper That Cancer'.

    Science.gov (United States)

    Denoyer, Delphine; Masaldan, Shashank; La Fontaine, Sharon; Cater, Michael A

    2015-11-01

    Copper is an essential micronutrient involved in fundamental life processes that are conserved throughout all forms of life. The ability of copper to catalyze oxidation-reduction (redox) reactions, which can inadvertently lead to the production of reactive oxygen species (ROS), necessitates the tight homeostatic regulation of copper within the body. Many cancer types exhibit increased intratumoral copper and/or altered systemic copper distribution. The realization that copper serves as a limiting factor for multiple aspects of tumor progression, including growth, angiogenesis and metastasis, has prompted the development of copper-specific chelators as therapies to inhibit these processes. Another therapeutic approach utilizes specific ionophores that deliver copper to cells to increase intracellular copper levels. The therapeutic window between normal and cancerous cells when intracellular copper is forcibly increased, is the premise for the development of copper-ionophores endowed with anticancer properties. Also under investigation is the use of copper to replace platinum in coordination complexes currently used as mainstream chemotherapies. In comparison to platinum-based drugs, these promising copper coordination complexes may be more potent anticancer agents, with reduced toxicity toward normal cells and they may potentially circumvent the chemoresistance associated with recurrent platinum treatment. In addition, cancerous cells can adapt their copper homeostatic mechanisms to acquire resistance to conventional platinum-based drugs and certain copper coordination complexes can re-sensitize cancer cells to these drugs. This review will outline the biological importance of copper and copper homeostasis in mammalian cells, followed by a discussion of our current understanding of copper dysregulation in cancer, and the recent therapeutic advances using copper coordination complexes as anticancer agents.

  1. Gene Therapy of Cancer: Induction of Anti-Tumor Immunity

    Institute of Scientific and Technical Information of China (English)

    Cheng Qian; Jesus Prieto

    2004-01-01

    Many malignancies lack satisfactory treatment and new therapeutic options are urgently needed. Gene therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the tissues. Different gene therapy strategies against cancers have been developed. A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene therapy. Among these strategies,induction of anti-tumorimmunity is the most promising approach. Gene therapy with cytokines has reached unprecedented success in preclinical models of cancer. Synergistic rather than additive effects have beendemonstrated by combination of gene transfer of cytokines/chemokines, costimulatory molecules or adoptive cell therapy. Recent progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy, a procedure which may have a notorious impact in the management of cancers lacking effective treatment.

  2. An overview of gene therapy in head and neck cancer

    Directory of Open Access Journals (Sweden)

    Amit Bali

    2013-01-01

    Full Text Available Gene therapy is a new treatment modality in which new gene is introduced or existing gene is manipulated to cause cancer cell death or slow the growth of the tumor. In this review, we have discussed the different treatment approaches for cancer gene therapy; gene addition therapy, immunotherapy, gene therapy using oncolytic viruses, antisense ribonucleic acid (RNA and RNA interference-based gene therapy. Clinical trials to date in head and neck cancer have shown evidence of gene transduction and expression, mediation of apoptosis and clinical response including pathological complete responses. The objective of this article is to provide an overview of the current available gene therapies for head and neck cancer.

  3. Oral complications of cancer and cancer therapy: from cancer treatment to survivorship.

    Science.gov (United States)

    Epstein, Joel B; Thariat, Juliette; Bensadoun, Rene-Jean; Barasch, Andrei; Murphy, Barbara A; Kolnick, Leanne; Popplewell, Leslie; Maghami, Ellie

    2012-01-01

    Answer questions and earn CME/CNE Oral complications resulting from cancer and cancer therapies cause acute and late toxicities that may be underreported, underrecognized, and undertreated. Recent advances in cancer treatment have led to changes in the incidence, nature, and severity of oral complications. As the number of survivors increases, it is becoming increasingly recognized that the aggressive management of oral toxicities is needed to ensure optimal long-term oral health and general well-being. Advances in care have had an impact on previously recognized oral complications and are leading to newly recognized adverse effects. Here, the authors briefly review advances in cancer therapy, including recent advances in surgery, oral care, radiation therapy, hematopoietic cell transplantation, and medical oncology; describe how these advances affect oral health; and discuss the frequent and/or severe oral health complications associated with cancer and cancer treatment and their effect upon long-term health. Although some of the acute oral toxicities of cancer therapies may be reduced, they remain essentially unavoidable. The significant impact of long-term complications requires increased awareness and recognition to promote prevention and appropriate intervention. It is therefore important for the primary oncologist to be aware of these complications so that appropriate measures can be implemented in a timely manner. Prevention and management is best provided via multidisciplinary health care teams, which must be integrated and communicate effectively in order to provide the best patient care in a coordinated manner at the appropriate time.

  4. Systemic cancer therapy: achievements and challenges that lie ahead.

    Science.gov (United States)

    Palumbo, Michael O; Kavan, Petr; Miller, Wilson H; Panasci, Lawrence; Assouline, Sarit; Johnson, Nathalie; Cohen, Victor; Patenaude, Francois; Pollak, Michael; Jagoe, R Thomas; Batist, Gerald

    2013-01-01

    In the last half of the century, advances in the systemic therapy of cancer, including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy have been responsible for improvements in cancer related mortality in developed countries even as the population continues to age. Although such advancements have yet to benefit all cancer types, systemic therapies have led to an improvement in overall survival in both the adjuvant and metastatic setting for many cancers. With the pressure to make therapies available as soon as possible, the side-effects of systemic therapies, in particular long-term side-effects are not very well characterized and understood. Increasingly, a number of cancer types are requiring long-term and even lifelong systemic therapy. This is true for both younger and older patients with cancer and has important implications for each subset. Younger patients have an overall greater expected life-span, and as a result may suffer a greater variety of treatment related complications in the long-term, whereas older patients may develop earlier side-effects as a result of their frailty. Because the incidence of cancer in the world will increase over the next several decades and there will be more people living with cancer, it is important to have an understanding of the potential side-effects of new systemic therapies. As an introductory article, in this review series, we begin by describing some of the major advances made in systemic cancer therapy along with some of their known side-effects and we also make an attempt to describe the future of systemic cancer therapy.

  5. [Gastrointestinal surgeons should master the adjuvant therapy of colorectal cancer].

    Science.gov (United States)

    Gu, Jin; Chen, Pengju

    2015-10-01

    The diagnosis and treatment of colorectal cancer is one of the main diseases of gastrointestinal surgeons. It is very important to master the adjuvant chemotherapy of colorectal cancer for gastrointestinal surgeons. In recent years, with the development of a number of clinical trials and the appearance of new drugs, fluorouracil combined with oxaliplatin had been established as the standard regimen of adjuvant chemotherapy for colorectal cancer. In the current guidelines, stage III( colon cancer is the indication for adjuvant chemotherapy, while stage II( colon cancer should receive adjuvant chemotherapy is uncertain. Unlike colon cancer, adjuvant therapy of rectal cancer is not evidence-based. Especially, the indication and duration of adjuvant chemotherapy for rectal cancer after neoadjuvant chemoradiotherapy remain controversial. Adjuvant therapy of colorectal cancer still needs further investigation.

  6. Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy

    Science.gov (United States)

    2016-12-01

    AD_________________ Award Number: W81XWH-14-1-0350 TITLE: Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy PRINCIPAL...30 Sep 2014 - 29 Sep 2016 4. TITLE AND SUBTILE Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy 5a. CONTRACT NUMBER... cancer . To eradicate chemoresistant tumor cells, it is important to identify the subset of tumor cells that can survive from chemotherapy and

  7. X-Ray Psoralen Activated Cancer Therapy (X-PACT)

    OpenAIRE

    Oldham, Mark; Yoon, Paul; Fathi, Zak; Wayne F Beyer; Adamson, Justus; Liu, Leihua; Alcorta, David; Xia, Wenle; Osada, Takuya; Liu, Congxiao; Yang, Xiao Y.; Dodd, Rebecca D.; Herndon, James E.; Meng, Boyu; Kirsch, David G.

    2016-01-01

    This work investigates X-PACT (X-ray Psoralen Activated Cancer Therapy): a new approach for the treatment of solid cancer. X-PACT utilizes psoralen, a potent anti-cancer therapeutic with current application to proliferative disease and extracorporeal photopheresis (ECP) of cutaneous T Cell Lymphoma. An immunogenic role for light-activated psoralen has been reported, contributing to long-term clinical responses. Psoralen therapies have to-date been limited to superficial or extracorporeal scen...

  8. Targeting the hedgehog pathway for gallbladder cancer therapy?

    Science.gov (United States)

    Mittal, Balraj; Yadav, Saurabh

    2016-02-01

    Gallbladder carcinoma is a fatal malignancy of hepatobiliary tract that is generally diagnosed at advanced stages of cancer because of its asymptomatic nature. Advanced GBC tumors are unresectable with poor prognosis. Improvement in GBC patient care requires better understanding of the biological signaling pathways and application of newly discovered drugs for cancer therapy. Herein, we discuss the possibilities and challenges in targeting the hedgehog pathway in gallbladder cancer therapy based on recent developments in the area.

  9. Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0551 TITLE: Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer PRINCIPAL INVESTIGATOR: Ze’ev Ronai...4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Targeting Siah2 as Novel Therapy for Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-14-1-0551 5c...project is to develop a novel means to inhibit prostate cancer development and progression. The development of Siah1/2 inhibitors to the ubiquitin

  10. P52 Activation and Enzalutamide Therapy in Prostate Cancer

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-14-1-0437 TITLE: p52 Activation and Enzalutamide Therapy in Prostate Cancer PRINCIPAL INVESTIGATOR: Allen C Gao, MD, PhD...Enzalutamide Therapy in Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-14-1-0437 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Allen C...that provide temporary respite, almost all patients will go on to die from progressive and resistant prostate cancer . Therefore, there is an urgent

  11. Stereotactic Body Radiotherapy and Ablative Therapies for Lung Cancer.

    Science.gov (United States)

    Abbas, Ghulam; Danish, Adnan; Krasna, Mark J

    2016-07-01

    The treatment paradigm for early stage lung cancer and oligometastatic disease to the lung is rapidly changing. Ablative therapies, especially stereotactic body radiation therapy, are challenging the surgical gold standard and have the potential to be the standard for operable patients with early stage lung cancer who are high risk due to co- morbidities. The most commonly used ablative modalities include stereotactic body radiation therapy, microwave ablation, and radiofrequency ablation.

  12. Cancer and Radiation Therapy: Current Advances and Future Directions

    Directory of Open Access Journals (Sweden)

    Rajamanickam Baskar, Kuo Ann Lee, Richard Yeo, Kheng-Wei Yeoh

    2012-01-01

    Full Text Available In recent years remarkable progress has been made towards the understanding of proposed hallmarks of cancer development and treatment. However with its increasing incidence, the clinical management of cancer continues to be a challenge for the 21st century. Treatment modalities comprise of radiation therapy, surgery, chemotherapy, immunotherapy and hormonal therapy. Radiation therapy remains an important component of cancer treatment with approximately 50% of all cancer patients receiving radiation therapy during their course of illness; it contributes towards 40% of curative treatment for cancer. The main goal of radiation therapy is to deprive cancer cells of their multiplication (cell division potential. Celebrating a century of advances since Marie Curie won her second Nobel Prize for her research into radium, 2011 has been designated the Year of Radiation therapy in the UK. Over the last 100 years, ongoing advances in the techniques of radiation treatment and progress made in understanding the biology of cancer cell responses to radiation will endeavor to increase the survival and reduce treatment side effects for cancer patients. In this review, principles, application and advances in radiation therapy with their biological end points are discussed.

  13. Current role of surgical therapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ryan Swan; Thomas J Miner

    2006-01-01

    Surgery is currently the only potentially curative treatment for gastric cancer. Since the inception of the gastrectomy for cancer of the stomach, there has been debate over the bounds of surgical therapy, balancing potential long-term survival with perioperative morbidity and mortality. This review delineates the current role of surgery in preoperative staging, curative resection, and palliative treatment for gastric cancer.

  14. Development of novel radiosensitizers for cancer therapy

    CERN Document Server

    Akamatsu, K

    2002-01-01

    The novel radiosensitizers for cancer therapy, which have some atoms with large X-ray absorption cross sections, were synthesized. The chemical and radiation (X-rays, W target, 100kVp) toxicities and the radiosensitivities to LS-180 human colon adenocarcinoma cells were also evaluated. 2,3,4,5,6-pentabromobenzylalcohol (PBBA) derivatives were not radiosensitive even around the maximum concentration. On the other hand, the hydrophilic sodium 2,4,6-triiodobenzoate (STIB) indicated meaningful radiosensitivity to the cells. Moreover, the membrane-specific radiosensitizers, cetyl fluorescein isthiocyanate (cetyl FITC), cetyl eosin isothiocyanate (cetyl br-FITC), cetyl erythrosin isothiocyanate (cetyl I-FITC), which aim for the membrane damage by X-ray photoabsorption on the target atoms, were localized in the plasma membrane. As the results of the colony formation assay, it was found that both cetyl FITC are similarly radiosensitive. In this report, we demonstrate the synthetic methods of the radiosensitizers, the...

  15. Advances in target therapy in lung cancer

    Directory of Open Access Journals (Sweden)

    Jean-Paul Sculier

    2015-03-01

    Full Text Available Herein, we have reviewed and analysed recent literature, published in 2013 and early 2014, in the context of pre-existing data. Considered target therapies were tyrosine kinase inhibitors of active epidermal growth factor receptor mutations (e.g. erlotinib, gefinitib and afatinib, anaplastic lymphoma kinase rearrangements (e.g. crizotinib or angiogenesis (drugs under development, or monoclonal antibodies against vascular endothelial growth factor (e.g. bevacizumab or epidermal growth factor receptors (e.g. cetuximab. The therapeutic project has to consider tyrosine kinase inhibitors in the case of nonsmall cell lung cancer with active epidermal growth factor receptor mutations or anaplastic lymphoma kinase rearrangement. However, these drugs should not be used in the absence of the targeted genetic abnormalities.

  16. Inorganic nanoparticles for cancer imaging and therapy.

    Science.gov (United States)

    Huang, Huang-Chiao; Barua, Sutapa; Sharma, Gaurav; Dey, Sandwip K; Rege, Kaushal

    2011-11-07

    Inorganic nanoparticles have received increased attention in the recent past as potential diagnostic and therapeutic systems in the field of oncology. Inorganic nanoparticles have demonstrated successes in imaging and treatment of tumors both ex vivo and in vivo, with some promise towards clinical trials. This review primarily discusses progress in applications of inorganic nanoparticles for cancer imaging and treatment, with an emphasis on in vivo studies. Advances in the use of semiconductor fluorescent quantum dots, carbon nanotubes, gold nanoparticles (spheres, shells, rods, cages), iron oxide magnetic nanoparticles and ceramic nanoparticles in tumor targeting, imaging, photothermal therapy and drug delivery applications are discussed. Limitations and toxicity issues associated with inorganic nanoparticles in living organisms are also discussed.

  17. Nanomedicine-mediated cancer stem cell therapy.

    Science.gov (United States)

    Shen, Song; Xia, Jin-Xing; Wang, Jun

    2016-01-01

    Circumstantial evidence suggests that most tumours are heterogeneous and contain a small population of cancer stem cells (CSCs) that exhibit distinctive self-renewal, proliferation and differentiation capabilities, which are believed to play a crucial role in tumour progression, drug resistance, recurrence and metastasis in multiple malignancies. Given that the existence of CSCs is a primary obstacle to cancer therapy, a tremendous amount of effort has been put into the development of anti-CSC strategies, and several potential approaches to kill therapeutically-resistant CSCs have been explored, including inhibiting ATP-binding cassette transporters, blocking essential signalling pathways involved in self-renewal and survival of CSCs, targeting CSCs surface markers and destroying the tumour microenvironment. Meanwhile, an increasing number of therapeutic agents (e.g. small molecule drugs, nucleic acids and antibodies) to selectively target CSCs have been screened or proposed in recent years. Drug delivery technology-based approaches hold great potential for tackling the limitations impeding clinical applications of CSC-specific agents, such as poor water solubility, short circulation time and inconsistent stability. Properly designed nanocarrier-based therapeutic agents (or nanomedicines) offer new possibilities of penetrating CSC niches and significantly increasing therapeutic drug accumulation in CSCs, which are difficult for free drug counterparts. In addition, intelligent nanomedicine holds great promise to overcome pump-mediated multidrug resistance which is driven by ATP and to decrease detrimental effects on normal somatic stem cells. In this review, we summarise the distinctive biological processes related to CSCs to highlight strategies against inherently drug-resistant CSCs. We then focus on some representative examples that give a glimpse into state-of-the-art nanomedicine approaches developed for CSCs elimination. A perspective on innovative therapeutic

  18. STAT5 induces miR-21 expression in cutaneous T cell lymphoma

    DEFF Research Database (Denmark)

    Lindahl, Lise M; Fredholm, Simon; Joseph, Claudine

    2016-01-01

    In cutaneous T cell lymphomas (CTCL), miR-21 is aberrantly expressed in skin and peripheral blood and displays anti-apoptotic properties in malignant T cells. It is, however, unclear exactly which cells express miR-21 and what mechanisms regulate miR-21. Here, we demonstrate miR-21 expression...... in situ in both malignant and reactive lymphocytes as well as stromal cells. qRT-PCR analysis of 47 patients with mycosis fungoides (MF) and Sezary Syndrome (SS) confirmed an increased miR- 21 expression that correlated with progressive disease. In cultured malignant T cells miR-21 expression...... T cells and cultured cytokine-dependent SS cells (SeAx). siRNA-mediated depletion of STAT5 inhibited constitutive- and IL-2- induced miR-21 expression in cytokine- independent and dependent T cell lines, respectively. IL-15 and IL-2 were more potent than IL-21 in inducing miR-21 expression...

  19. Therapeutic miR-21 Silencing Ameliorates Diabetic Kidney Disease in Mice.

    Science.gov (United States)

    Kölling, Malte; Kaucsar, Tamas; Schauerte, Celina; Hübner, Anika; Dettling, Angela; Park, Joon-Keun; Busch, Martin; Wulff, Xaver; Meier, Matthias; Scherf, Kristian; Bukosza, Nóra; Szénási, Gábor; Godó, Mária; Sharma, Amit; Heuser, Michael; Hamar, Peter; Bang, Claudia; Haller, Hermann; Thum, Thomas; Lorenzen, Johan M

    2017-01-04

    Diabetic nephropathy is the main cause of end-stage renal disease. MicroRNAs are powerful regulators of the genome, and global expression profiling revealed miR-21 to be among the most highly regulated microRNAs in kidneys of mice with diabetic nephropathy. In kidney biopsies of diabetic patients, miR-21 correlated with tubulointerstitial injury. In situ PCR analysis showed a specific enrichment of miR-21 in glomerular cells. We identified cell division cycle 25a (Cdc25a) and cyclin-dependent kinase 6 (Cdk6) as novel miR-21 targets in mesangial cells. miR-21-mediated repression of Cdc25a and Cdk6 resulted in impaired cell cycle progression and subsequent mesangial cell hypertrophy. miR-21 increased podocyte motility by regulating phosphatase and tensin homolog (Pten). miR-21 antagonism in vitro and in vivo in streptozotocin-induced diabetic mice decreased mesangial expansion, interstitial fibrosis, macrophage infiltration, podocyte loss, albuminuria, and fibrotic- and inflammatory gene expression. In conclusion, miR-21 antagonism rescued various functional and structural parameters in mice with diabetic nephropathy and, thus, might be a viable option in the treatment of patients with diabetic kidney disease.

  20. Sequential co-delivery of miR-21 inhibitor followed by burst release doxorubicin using NIR-responsive hollow gold nanoparticle to enhance anticancer efficacy.

    Science.gov (United States)

    Ren, Yu; Wang, Ruirui; Gao, Lizhang; Li, Ke; Zhou, Xuan; Guo, Hua; Liu, Chaoyong; Han, Donglin; Tian, Jianguo; Ye, Qing; Hu, Ye Tony; Sun, Duxin; Yuan, Xubo; Zhang, Ning

    2016-04-28

    Previous literature and our study showed the delivery sequence of microRNA inhibitor and chemotherapeutic compounds achieve distinct therapeutic anticancer efficacy. Yet, it is challenging to use nanoparticle to achieve sequential drug delivery. In the current study, we designed sequential co-delivery system using a near-infrared-radiation (NIR) responsive hollow gold nanoparticle (HGNPs) to achieve sequential release of microRNA inhibitor (miR-21i)/doxirubicin(Dox) in order to achieve synergistic efficacy. PAMAM modified HGNPs was used to encapsulate miR-21i and Dox. Upon entering tumor cells, miRNA-21i was released first to sensitize the cancer cells, the subsequent burst release of Dox was achieved by NIR triggered collapse of HGNPs. This sequential delivery of miRNA-21i and Dox produced a synergistic apoptotic response, thereby enhancing anticancer efficacy by 8-fold and increasing anti-cancer stem cell activity by 50-fold. The sequential delivery of miR-21i and Dox using HGNPs under NIR after intravenous administration showed high tumor accumulation and significantly improved efficacy, which was 4-fold compared to free Dox group. These data suggested that the sequential co-delivery of miR-21i followed by burst release Dox using NIR-responsive HGNPs sensitized cancer cells to chemotherapeutic compound, which provided a novel concept for co-delivery miRNA inhibitors and chemotherapeutic compounds to enhance their efficacy.

  1. Optimization of adaptive radiation therapy in cervical cancer: Solutions for photon and proton therapy

    NARCIS (Netherlands)

    van de Schoot, A.J.A.J.

    2016-01-01

    In cervical cancer radiation therapy, an adaptive strategy is required to compensate for interfraction anatomical variations in order to achieve adequate dose delivery. In this thesis, we have aimed at optimizing adaptive radiation therapy in cervical cancer to improve treatment efficiency and

  2. Optimization of adaptive radiation therapy in cervical cancer: Solutions for photon and proton therapy

    NARCIS (Netherlands)

    van de Schoot, A.J.A.J.

    2016-01-01

    In cervical cancer radiation therapy, an adaptive strategy is required to compensate for interfraction anatomical variations in order to achieve adequate dose delivery. In this thesis, we have aimed at optimizing adaptive radiation therapy in cervical cancer to improve treatment efficiency and reduc

  3. Music therapy as part of the alternative-complementary therapy in cancer patients in hospital

    Directory of Open Access Journals (Sweden)

    Efstratios Athanassakis

    2012-01-01

    Full Text Available Cancer is one of the modern health problems of people living in developed countries. Furthermore, therapeutic approaches to cancer patients is constantly updated with new data. Aim: The aim of the present study was to review the international literature referred to the application of music therapy in the treatment for pediatric and adult patients with cancer. Method and materials: The method of this study included bibliography research from both the review and the research literature on MEDLINE (2000-2010 database and using as key words music, music therapy, alternative-complementary therapy, cancer, children. Results: Music therapy, the last few years, seems to be one of the forms of alternative-complementary therapy for patients treated for cancer. Music therapy is applied as part of complementary therapy in pediatric and adult patients with cancer. Complementary-alternative methods are non-invasive, non-toxic, cheap, safe and can be easily used by the patients themselves. Primarily, the music therapy aimed to the reduction of the emotional trauma and the feeling of the pain during the process of the treatment (radiotherapy, chemotherapy, other painful procedures but also in the whole patients life. Conclusions: Scientific bibliographic databases research concerning the music therapy in patients with cancer seem encouraging, especially in children. Nevertheless, the further study of the role of the music during hospitalization in the outcome of the treatment is essential

  4. Senescence induction; a possible cancer therapy

    Directory of Open Access Journals (Sweden)

    Kondoh Hiroshi

    2009-01-01

    Full Text Available Abstract Cellular immortalization is a crucial step during the development of human cancer. Primary mammalian cells reach replicative exhaustion after several passages in vitro, a process called replicative senescence. During such a state of permanent growth arrest, senescent cells are refractory to physiological proliferation stimuli: they have altered cell morphology and gene expression patterns, although they remain viable with preserved metabolic activity. Interestingly, senescent cells have also been detected in vivo in human tumors, particularly in benign lesions. Senescence is a mechanism that limits cellular lifespan and constitutes a barrier against cellular immortalization. During immortalization, cells acquire genetic alterations that override senescence. Tumor suppressor genes and oncogenes are closely involved in senescence, as their knockdown and ectopic expression confer immortality and senescence induction, respectively. By using high throughput genetic screening to search for genes involved in senescence, several candidate oncogenes and putative tumor suppressor genes have been recently isolated, including subtypes of micro-RNAs. These findings offer new perspectives in the modulation of senescence and open new approaches for cancer therapy.

  5. Emerging HIFU applications in cancer therapy.

    Science.gov (United States)

    Maloney, Ezekiel; Hwang, Joo Ha

    2015-05-01

    High intensity focused ultrasound (HIFU), is a promising, non-invasive modality for treatment of tumours in conjunction with magnetic resonance imaging or diagnostic ultrasound guidance. HIFU is being used increasingly for treatment of prostate cancer and uterine fibroids. Over the last 10 years a growing number of clinical trials have examined HIFU treatment of both benign and malignant tumours of the liver, breast, pancreas, bone, connective tissue, thyroid, parathyroid, kidney and brain. For some of these emerging indications, HIFU is poised to become a serious alternative or adjunct to current standard treatments--including surgery, radiation, gene therapy, immunotherapy, and chemotherapy. Current commercially available HIFU devices are marketed for their thermal ablation applications. In the future, lower energy treatments may play a significant role in mediating targeted drug and gene delivery for cancer treatment. In this article we introduce currently available HIFU systems, provide an overview of clinical trials in emerging oncological targets, and briefly discuss selected pre-clinical research that is relevant to future oncological HIFU applications.

  6. [Pharmacological therapy of cancer anorexia-cachexia].

    Science.gov (United States)

    Cardona, D

    2006-05-01

    Anorexia is one of the most common symptoms of patients with advanced cancer and it presents as loss of appetite due to satiety. On the other hand, cachexia is described in those patients with unwanted weight loss. Cancerous processes produce an energy unbalance by decreased food intake and increased catabolism, resulting in a clearly negative balance. Several factors determining cachexia are observed, from metabolic unbalances produced by tumoral products and endocrine impairments or the inflammatory response produced by cytokines, all of them leading to higher lipolysis, loss of muscle protein, and anorexia. Besides, causes of anorexia are multiple, from chemotherapy agents, radiotherapy, or immunotherapy, which may produce different degrees of nausea, vomiting, diarrhea, and also leading to impairments of taste and smell, to obstruction of the digestive tract, pain, depression, constipation, etc. From the knowledge of the different mechanisms producing the anorexia-cachexia syndrome, hypercaloric diets for artificial nutrition have been studied with varying success, and different drugs with a positive effect on appetite gain such as progestogens, steroids, and with lesser clinical evidence cannabinoids, cyproheptadine, mirtazapine (antidepressant), and olanzapine (antipsychotic). Other drugs have been studied because of their anti-inflammatory properties, anti-cytokine, such as melatonin, polyunsaturated omega-3 fatty acids, pentoxifylline, and thalidomide; with the exception of the latter, clinical data are still scant for daily usage. Similarly happens with testosterone-derived anabolic drugs or with metabolism inhibitors such as hydrazine sulfate. With no doubt, progestogens, especially megestrol, and corticosteroids will be first-line therapies for anorexia-cachexia syndrome to stimulate the appetite and increase weight (megestrol), and have an effect on quality of life improvement and comfort in patients with advanced cancer.

  7. Progress of photodynamic therapy in gastric cancer.

    Science.gov (United States)

    Mimura, S; Narahara, H; Otani, T; Okuda, S

    1999-01-01

    Progress of photodynamic therapy (PDT) in gastric cancer and the clinical outcome are described in this paper. (1) We included the whole lesion and a 5 mm margin in the field for irradiation. Marking by injection of India-ink showing the irradiation field was performed beforehand. (2) We established the standard light dose to be 90 J/cm(2) for an argon dye laser and 60 J/cm(2) for a pulse wave laser. (3) The size of cancerous lesion curable by PDT was expanded from 3 cm in diameter, i.e. 7 cm(2) in area to 4 cm in diameter, i.e. 13 cm(2) by employing a new excimer dye laser model, which could emit 4mJ/pulse with 80 Hz pulse frequency. (4) The depth of cancer invasion which could be treated by PDT was increased from about 4 mm, i.e. the superficial part of the submucosal layer (SM-1) to more than 10 mm in depth, i.e. the proper muscular layer. These improvements owe much to the pulse laser, the photodynamic action induced by which permits deeper penetration than that of a continuous wave laser. (5) We employed a side-viewing fiberscope for gastric PDT to irradiate the lesion from an angle of 90 degrees . (6) We designed a simple cut quartz fiber for photoradiation with a spiral spring thickened toward the end. (7) We developed an endoscopic device for photoradiation in PDT which achieves accurate and efficient irradiation. As a result of these improvements a higher cure rate was obtained even with a lower light dose of irradiation.

  8. A New Era for Cancer Target Therapies: Applying Systems Biology and Computer-Aided Drug Design to Cancer Therapies.

    Science.gov (United States)

    Wong, Yung-Hao; Chiu, Chia-Chiun; Lin, Chih-Lung; Chen, Ting-Shou; Jheng, Bo-Ren; Lee, Yu-Ching; Chen, Jeremy; Chen, Bor-Sen

    In recent years, many systems biology approaches have been used with various cancers. The materials described here can be used to build bases to discover novel cancer therapy targets in connection with computer-aided drug design (CADD). A deeper understanding of the mechanisms of cancer will provide more choices and correct strategies in the development of multiple target drug therapies, which is quite different from the traditional cancer single target therapy. Targeted therapy is one of the most powerful strategies against cancer and can also be applied to other diseases. Due to the large amount of progress in computer hardware and the theories of computational chemistry and physics, CADD has been the main strategy for developing novel drugs for cancer therapy. In contrast to traditional single target therapies, in this review we will emphasize the future direction of the field, i.e., multiple target therapies. Structure-based and ligand-based drug designs are the two main topics of CADD. The former needs both 3D protein structures and ligand structures, while the latter only needs ligand structures. Ordinarily it is estimated to take more than 14 years and 800 million dollars to develop a new drug. Many new CADD software programs and techniques have been developed in recent decades. We conclude with an example where we combined and applied systems biology and CADD to the core networks of four cancers and successfully developed a novel cocktail for drug therapy that treats multiple targets.

  9. Complementary and alternative (CAM) dietary therapies for cancer.

    Science.gov (United States)

    Weitzman, Sheila

    2008-02-01

    Complementary and alternative (CAM) therapies include a wide spectrum of dietary practices, some of which are claimed to cure cancer. Observational studies have shown consistently that predominantly plant-based diets reduce the risk for some adult type cancers such as breast cancer and prostate cancer. These studies form the basis of the American Cancer Society (ACS) nutritional guidelines. Many CAM diets prescribe a similar low fat, high fiber, high fruit and vegetable type diet, but also add detoxification and many different supplements to the basic diet which is then claimed to cure cancer. The potential advantages and disadvantages of CAM diets are discussed. Many aspects can be potentially harmful, particularly to the child with cancer. Advantages include involvement of the child and family in decision-making and care. There is no evidence to support the claims that CAM dietary therapies cure cancer.

  10. Nanoscale insights into ion-beam cancer therapy

    CERN Document Server

    2017-01-01

    This book provides a unique and comprehensive overview of state-of-the-art understanding of the molecular and nano-scale processes that play significant roles in ion-beam cancer therapy. It covers experimental design and methodology, and reviews the theoretical understanding of the processes involved. It offers the reader an opportunity to learn from a coherent approach about the physics, chemistry and biology relevant to ion-beam cancer therapy, a growing field of important medical application worldwide. The book describes phenomena occurring on different time and energy scales relevant to the radiation damage of biological targets and ion-beam cancer therapy from the molecular (nano) scale up to the macroscopic level. It illustrates how ion-beam therapy offers the possibility of excellent dose localization for treatment of malignant tumours, minimizing radiation damage in normal tissue whilst maximizing cell-killing within the tumour, offering a significant development in cancer therapy. The full potential ...

  11. Gene therapy for gastric cancer: Is it promising?

    Institute of Scientific and Technical Information of China (English)

    Andreas P Sutter; Henry Fechner

    2006-01-01

    Gastric cancer is one of the most common tumors worldwide. The therapeutic outcome of conventional therapies is inefficient. Thus, new therapeutic strategies are urgently needed. Gene therapy is a promising molecular alternative in the treatment of gastric cancer,including the replacement of defective tumor suppressor genes, the inactivation of oncogenes, the introduction of suicide genes, genetic immunotherapy, anti-angiogenetic gene therapy, and virotherapy. Improved molecular biological techniques and a better understanding of gastric carcinogenesis have allowed us to validate a variety of genes as molecular targets for gene therapy.This review provides an update of the new developments in cancer gene therapy, new principles, techniques,strategies and vector systems, and shows how they may be applied in the treatment of gastric cancer.

  12. Autophagy Therapeutic Potential of Garlic in Human Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yung-Lin Chu

    2013-07-01

    Full Text Available Cancer is one of the deadliest diseases against humans. To tackle this menace, humans have developed several high-technology therapies, such as chemotherapy, tomotherapy, targeted therapy, and antibody therapy. However, all these therapies have their own adverse side effects. Therefore, recent years have seen increased attention being given to the natural food for complementary therapy, which have less side effects. Garlic 大 蒜 Dà Suàn; Allium sativum, is one of most powerful food used in many of the civilizations for both culinary and medicinal purpose. In general, these foods induce cancer cell death by apoptosis, autophagy, or necrosis. Studies have discussed how natural food factors regulate cell survival or death by autophagy in cancer cells. From many literature reviews, garlic could not only induce apoptosis but also autophagy in cancer cells. Autophagy, which is called type-II programmed cell death, provides new strategy in cancer therapy. In conclusion, we wish that garlic could be the pioneer food of complementary therapy in clinical cancer treatment and increase the life quality of cancer patients.

  13. [Radiation therapy for prostate cancer in modern era].

    Science.gov (United States)

    Nishimura, Takuya

    2016-01-01

    The purpose of this paper is to provide overview of the latest research trend on technique of radiation therapy of prostate cancer. Three-dimensional conformal radiation therapy(3D -CRT) has achieved better outcome of treatment for prostate cancer than 2-dimensional radiation therapy. Intensity-modulated radiation therapy(IMRT) is considered to be superior to 3D-CRT at certain points. Image-guided (IG) radiation therapy (IGRT), mainly IG-IMRT, is investigated what kind of influence it has on an outcome, both tumor control rate and adverse events. Particle therapy is a most ideal therapy theoretically. There is, however, few evidence which revealed that the therapy is superior to any other modalities.

  14. The impact of cancer therapy on cognition in the elderly

    Directory of Open Access Journals (Sweden)

    Victoria eMandilaras

    2013-04-01

    Full Text Available Cancer and cancer therapy-related cognitive impairment (formerly known as chemobrain or chemo-fog are often described in the literature. In the past, studies have failed to prove the existence of cancer therapy-related cognitive dysfunction. However, more recently, prospective trials have shown that patients undergoing chemotherapy do display impairment in specific cognitive domains.Aging confers an increased risk of developing cancer, as well as cognitive impairment. The Geriatric Oncology clinic of the Segal Cancer Centre, Jewish General Hospital in Montreal was founded in 2006 to address the unique needs of older cancer patients. We will describe two cases of cancer therapy-related cognitive impairment from our Geriatric Oncology clinic. The first case is that of a 75 year old male diagnosed with stage III non-small cell lung carcinoma who complained of forgetfulness since starting carboplatin-paclitaxel. The second case is that of a 65 year old female diagnosed with stage I, ER positive breast cancer who had undergone lumpectomy followed by adjuvant CMF chemotherapy, radiation therapy and was on exemestane when she was evaluated.We will also briefly review the literature of cancer therapy-related cognitive impairment.

  15. The influence of hormone therapies on colon and rectal cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Lidegaard, Øjvind; Keiding, Niels;

    2016-01-01

    followed 1995-2009. Information on HT exposures was from the National Prescription Register and updated daily, while information on colon (n = 8377) and rectal cancers (n = 4742) were from the National Cancer Registry. Potential confounders were obtained from other national registers. Poisson regression...... analyses with 5-year age bands included hormone exposures as time-dependent covariates. Use of estrogen-only therapy and combined therapy were associated with decreased risks of colon cancer (adjusted incidence rate ratio 0.77, 95 % confidence interval 0.68-0.86 and 0.88, 0.80-0.96) and rectal cancer (0......Exogenous sex hormones seem to play a role in colorectal carcinogenesis. Little is known about the influence of different types or durations of postmenopausal hormone therapy (HT) on colorectal cancer risk. A nationwide cohort of women 50-79 years old without previous cancer (n = 1,006,219) were...

  16. Photodynamic therapy for cutaneous metastases of breast cancer

    Directory of Open Access Journals (Sweden)

    E. V. Goranskaya

    2011-01-01

    Full Text Available Breast cancer is the most common cancer and the leading cause of cancer death in w omen. Cutaneous metastases are observed in 20 % pa- tients with breast cancer. 36 breast cancer patients with cutaneous metastases were treated with photodynamic therapy in the de partment of laser and photodynamic therapy MRRC. Complete regression was obtained in 33.9 %, partial — in 39 % of cases, the stabilization achieved in 25.4 %, progression noted in 1.7 %. The objective response was obtained in 72.9 % of cases, treatment effect — in 97.4 %. Photodynamic therapy has good treatment results of cutaneous metastases of breast cancer with a small number of side effects.

  17. Adenovirus-derived vectors for prostate cancer gene therapy.

    Science.gov (United States)

    de Vrij, Jeroen; Willemsen, Ralph A; Lindholm, Leif; Hoeben, Rob C; Bangma, Chris H; Barber, Chris; Behr, Jean-Paul; Briggs, Simon; Carlisle, Robert; Cheng, Wing-Shing; Dautzenberg, Iris J C; de Ridder, Corrina; Dzojic, Helena; Erbacher, Patrick; Essand, Magnus; Fisher, Kerry; Frazier, April; Georgopoulos, Lindsay J; Jennings, Ian; Kochanek, Stefan; Koppers-Lalic, Daniela; Kraaij, Robert; Kreppel, Florian; Magnusson, Maria; Maitland, Norman; Neuberg, Patrick; Nugent, Regina; Ogris, Manfred; Remy, Jean-Serge; Scaife, Michelle; Schenk-Braat, Ellen; Schooten, Erik; Seymour, Len; Slade, Michael; Szyjanowicz, Pio; Totterman, Thomas; Uil, Taco G; Ulbrich, Karel; van der Weel, Laura; van Weerden, Wytske; Wagner, Ernst; Zuber, Guy

    2010-07-01

    Prostate cancer is a leading cause of death among men in Western countries. Whereas the survival rate approaches 100% for patients with localized cancer, the results of treatment in patients with metastasized prostate cancer at diagnosis are much less successful. The patients are usually presented with a variety of treatment options, but therapeutic interventions in prostate cancer are associated with frequent adverse side effects. Gene therapy and oncolytic virus therapy may constitute new strategies. Already a wide variety of preclinical studies has demonstrated the therapeutic potential of such approaches, with oncolytic prostate-specific adenoviruses as the most prominent vector. The state of the art and future prospects of gene therapy in prostate cancer are reviewed, with a focus on adenoviral vectors. We summarize advances in adenovirus technology for prostate cancer treatment and highlight areas where further developments are necessary.

  18. Occupational Therapy for Adults With Cancer: Why It Matters.

    Science.gov (United States)

    Pergolotti, Mackenzi; Williams, Grant R; Campbell, Claudine; Munoz, Lauro A; Muss, Hyman B

    2016-03-01

    Adults with cancer may be at risk for limitations in functional status and quality of life (QOL). Occupational therapy is a supportive service with the specific mission to help people functionally engage in life as safely and independently as possible with the primary goal of improving QOL. Unfortunately, for people with cancer, occupational therapy remains underused. The overall purpose of this review is to provide an understanding of what occupational therapy is and its relevance to patients with cancer, highlight the reasons to refer, and, last, provide general advice on how to access services. ©AlphaMed Press.

  19. Arginine Metabolism in Bacterial Pathogenesis and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Lifeng Xiong

    2016-03-01

    Full Text Available Antibacterial resistance to infectious diseases is a significant global concern for health care organizations; along with aging populations and increasing cancer rates, it represents a great burden for government healthcare systems. Therefore, the development of therapies against bacterial infection and cancer is an important strategy for healthcare research. Pathogenic bacteria and cancer have developed a broad range of sophisticated strategies to survive or propagate inside a host and cause infection or spread disease. Bacteria can employ their own metabolism pathways to obtain nutrients from the host cells in order to survive. Similarly, cancer cells can dysregulate normal human cell metabolic pathways so that they can grow and spread. One common feature of the adaption and disruption of metabolic pathways observed in bacterial and cancer cell growth is amino acid pathways; these have recently been targeted as a novel approach to manage bacterial infections and cancer therapy. In particular, arginine metabolism has been illustrated to be important not only for bacterial pathogenesis but also for cancer therapy. Therefore, greater insights into arginine metabolism of pathogenic bacteria and cancer cells would provide possible targets for controlling of bacterial infection and cancer treatment. This review will summarize the recent progress on the relationship of arginine metabolism with bacterial pathogenesis and cancer therapy, with a particular focus on arginase and arginine deiminase pathways of arginine catabolism.

  20. Cancer incidence and novel therapies developed in Japan.

    Science.gov (United States)

    Iwasaki, M

    2012-01-01

    According to the ministry of Health, Labour and welfare of Japan, Cancer has been the leading cause of death in Japan since 1981. ([1]) As per the data in 2010, in Japan, one in every three deaths was due to cancer. ([2]) The Japanese Government has introduced so far, three terms of 10 years strategies for Cancer control since 1984 till date. The budget allocated for cancer control in 2009 was 52.5 billion yen in Japan. ([3]) Lung is the leading site for cancer in both males and females in Japan. In males, following the lung, stomach, liver, colon and pancreas are other leading sites while in the females, stomach, colon, pancreas and breast are the other leading sites. ([1]) In 2006, the cancer incidence was 694,000 and the male cancer incidence was 1.4 times as large as that of females. The peak age for cancer deaths in males is their fifties while in the females it is the sixties among Japanese. In addition to the conventional treatments such as surgery, radiotherapy and chemotherapy, some of other therapies in practice in Japan are the Hyperthermia ([4]) that uses high temperatures to kill or damage the cancer cells, the Ion Beam therapy using proton beams ([5]) to damage the DNA of the cells as cancer cells have high rate of cell divisions and lesser ability to repair DNA damage, the molecular targeted therapies that interfere with a specific molecular target involved in tumour growth and progression([6]) and most importantly the autologous cell based Immunotherapies. Modern Cancer Immunotherapy started in the 1970s in Japan. The immunopotentiators using compounds from Bacteria, Beta Glucans from fungi were the first forms of modern Immunotherapy. Then was the era of direct injection of cytokines such as Interleukins, Interferons etc. The adverse effects associated with the injection of cytokines led to development of cell based Immunotherapies in the 1980s. ([7]) Immuno-cell therapies involve isolation of immune cells which are then processed and re

  1. The Fluid Mechanics of Cancer and Its Therapy

    Science.gov (United States)

    Koumoutsakos, Petros; Pivkin, Igor; Milde, Florian

    2013-01-01

    Fluid mechanics is involved in the growth, progression, metastasis, and therapy of cancer. Blood vessels transport oxygen and nutrients to cancerous tissues, provide a route for metastasizing cancer cells to distant organs, and deliver drugs to tumors. The irregular and leaky tumor vasculature is responsible for increased interstitial pressure in the tumor microenvironment, whereas multiscale flow-structure interaction processes control tumor growth, metastasis, and nanoparticle-mediated drug delivery. We outline these flow-mediated processes, along with related experimental and computational methods for the diagnosis, predictive modeling, and therapy of cancer.

  2. Head and Neck Cancer Treatment with Particle Beam Therapy

    Directory of Open Access Journals (Sweden)

    Mehrzad Zargarzadeh

    2013-01-01

    Full Text Available In this century, cancer incidence has become one of the most significant problems concerning human. Conventional radiotherapy damage healthy tissue and in some cases may cause new primary cancers. This problem can be partially solved by hadron therapy which would be more effective and less harmful compared to other forms of radiotherapies used to treat some cancers. Although carbon ion and proton therapy both are effective treatments, they have serious differences which are mentioned in this paper and compared between the two methods. Furthermore, various treatments have been performed on head and neck cancer with hadrons so far will be discussed.

  3. Role of miR-21 in alkalinity stress tolerance in tilapia.

    Science.gov (United States)

    Zhao, Yan; Wu, Jun-Wei; Wang, Yan; Zhao, Jin-Liang

    2016-02-26

    MicroRNAs (miRNAs) are a class of short, evolutionary conserved non-coding RNA molecules, which are shown as the key regulators of many biological functions. External stress can alter miRNA expression levels, thereby changing the expression of mRNA target genes. Here, we show that miR-21 is involved in the regulation of alkalinity tolerance in Nile tilapia. Alkalinity stress results in a marked reduction in miR-21 levels. miR-21 loss of function could affect ion balance regulation, ROS production, and antioxidant enzyme activity in vivo. Moreover, miR-21 knockdown protects cell against alkalinity stress-induced injury in vitro. miR-21 directly regulates VEGFB and VEGFC expression by targeting the 3'-untranslated regions (UTRs) of their mRNAs, and inhibition of miR-21 significantly increases the levels of VEGFB and VEGFC expression in vivo. Taken together, our study reveals that miR-21 knockdown plays a protective role in alkalinity tolerance in tilapia.

  4. Functional Genomics for Personalized Cancer Therapy

    Science.gov (United States)

    Tyner, Jeffrey W.

    2017-01-01

    Integration of functional and genomic screening strategies reveals clinically actionable genetic events that impact the effectiveness of cancer treatment regimens and the outcomes of cancer patients. PMID:24990879

  5. On dendritic cell-based therapy for cancers

    Institute of Scientific and Technical Information of China (English)

    Morikazu Onji; Sk. Md. Fazle Akbar

    2005-01-01

    Dendritic cells (DCs), the most prevalent antigen-presenting cell in vivo, had been widely characterized in the last three decades. DCs are present in almost all tissues of the body and play cardinal roles in recognition of microbial agents,autoantigens, allergens and alloantigen. DCs process the microbial agents or their antigens and migrate to lymphoid tissues to present the antigenic peptide to lymphocytes. This leads to activation of antigen-specific lymphocytes. Initially, it was assumed that DCs are principally involved in the induction and maintenance of adaptive immune responses, but now it is evident that DCs also have important roles in innate immunity. These features make DCs very good candidates for therapy against various pathological conditions including malignancies. Initially, DC-based therapy was used in animal models of cancers. Data from these studies inspired considerable optimism and DC-based therapies was started in human cancers 8 years ago. In general,DC-based therapy has been found to be safe in patients with cancers, although few controlled trials have been conducted in this regard. Because the fundamentals principles of human cancers and animal models of cancers are different, the therapeutic efficacy of the ongoing regime of DC-based therapy in cancer patients is not satisfactory. In this review, we covered the various aspects that should be considered for developing better regime of DC-based therapy for human cancers.

  6. Research advances in molecular targeted therapy for pancreatic cancer

    Directory of Open Access Journals (Sweden)

    XU Ying

    2016-10-01

    Full Text Available Pancreatic cancer remains one of the malignant tumors with the worst prognosis, and its incidence is associated with Western diet, smoking, drinking, obesity, chronic pancreatitis, and a family history of pancreatic cancer. Currently, the treatment of pancreatic cancer focuses on surgery and chemotherapy, but no ideal therapeutic effect has been achieved. An understanding of the specific molecular mechanism of the development of pancreatic cancer helps to better prevent and treat pancreatic cancer. This article introduces the latest advances in the specific molecular mechanism of the development of pancreatic cancer and its targeted therapy and points out that molecular-targeted therapy in addition to traditional treatment helps to improve the prognosis of patients with pancreatic cancer.

  7. Targeted and shielded adenovectors for cancer therapy.

    Science.gov (United States)

    Hedley, Susan J; Chen, Jian; Mountz, John D; Li, Jing; Curiel, David T; Korokhov, Nikolay; Kovesdi, Imre

    2006-11-01

    Conditionally replicative adenovirus (CRAd) vectors are novel vectors with utility as virotherapy agents for alternative cancer therapies. These vectors have already established a broad safety record in humans and overcome some of the limitations of non-replicative adenovirus (Ad) vectors. In addition, one potential problem with these vectors, attainment of tumor or tissue selectivity has widely been addressed. However, two confounding problems limiting efficacy of these drug candidates remains. The paucity of the native Ad receptor on tumor tissues, and host humoral response due to pre-existing titers of neutralizing antibodies against the vector itself in humans have been highlighted in the clinical context. The well-characterized CRAd, AdDelta24-RGD, is infectivity enhanced, thus overcoming the lack of coxsackievirus and adenovirus receptor (CAR), and this agent is already rapidly progressing towards clinical translation. However, the perceived host humoral response potentially will limit gains seen from the infectivity enhancement and therefore a strategy to blunt immunity against the vector is required. On the basis of this caveat a novel strategy, termed shielding, has been developed in which the genetic modification of a virion capsid protein would provide uniformly shielded Ad vectors. The identification of the pIX capsid protein as an ideal locale for genetic incorporation of shielding ligands to conceal the Ad vector from pre-existing neutralizing antibodies is a major progression in the development of shielded CRAds. Preliminary data utilizing an Ad vector with HSV-TK fused to the pIX protein indicates that a shield against neutralizing antibodies can be achieved. The utility of various proteins as shielding molecules is currently being addressed. The creation of AdDelta24S-RGD, an infectivity enhanced and shielded Ad vector will provide the next step in the development of clinically and commercially feasible CRAds that can be dosed multiple times for

  8. Stem cells’ guided gene therapy of cancer: New frontier in personalized and targeted therapy

    Directory of Open Access Journals (Sweden)

    Mavroudi M

    2014-01-01

    Full Text Available Diagnosis and therapy of cancer remain to be the greatest challenges for all physicians working in clinical oncology and molecular medicine. The grim statistics speak for themselves with reports of 1,638,910 men and women diagnosed with cancer and nearly 577,190 patients passed away due to cancer in the USA in 2012. For practicing clinicians, who treat patients suffering from advanced cancers with contemporary systemic therapies, the main challenge is to attain therapeutic efficacy, while minimizing side effects. Unfortunately, all contemporary systemic therapies cause side effects. In treated patients, these side effects may range from nausea to damaged tissues. In cancer survivors, the iatrogenic outcomes of systemic therapies may include genomic mutations and their consequences. Therefore, there is an urgent need for personalized and targeted therapies. Recently, we reviewed the current status of suicide gene therapy for cancer. Herein, we discuss the novel strategy: genetically engineered stem guided gene therapy. Stem cells have the unique potential for self-renewal and differentiation. This potential is the primary reason for introducing them into medicine to regenerate injured or degenerated organs, as well as to rejuvenate aging tissues. Recent advances in genetic engineering and stem cell research have created the foundations for genetic engineering of stem cells as the vectors for delivery of therapeutic transgenes. Specifically in oncology, the stem cells are genetically engineered to deliver the cell suicide inducing genes selectively to the cancer cells. Expression of the transgenes kills the cancer cells, while leaving healthy cells unaffected. Herein, we present various strategies to bioengineer suicide inducing genes and stem cell vectors. Moreover, we review results of the main preclinical studies and clinical trials. However, the main risk for therapeutic use of stem cells is their cancerous transformation. Therefore, we

  9. Therapeutic Cancer Vaccines in Combination with Conventional Therapy

    DEFF Research Database (Denmark)

    Andersen, Mads Hald; Junker, N.; Ellebaek, E.

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  10. Therapeutic cancer vaccines in combination with conventional therapy

    DEFF Research Database (Denmark)

    Junker, Niels; Ellebaek, Eva; Svane, Inge Marie

    2010-01-01

    The clinical efficacy of most therapeutic vaccines against cancer has not yet met its promise. Data are emerging that strongly support the notion that combining immunotherapy with conventional therapies, for example, radiation and chemotherapy may improve efficacy. In particular combination...

  11. MRI-guided focal therapy of prostate cancer.

    Science.gov (United States)

    Mathew, Melvy Sarah; Oto, Aytekin

    2017-03-01

    With the advent of focal therapy as a recognized treatment option for men with prostate cancer, there are a host of emerging interventions that take advantage of MRI for image guidance. Focal therapy affords a middleground option for patients with low- to intermediate-grade prostate cancer by providing a means of keeping their cancer at bay while avoiding the negative consequences of radical therapies. However, the practice of focal treatment is far from straightforward, with some believing focal treatment errs on the side of overtreatment among patients with low-grade cancer; others worry it is undertreatment in potentially significant multifocal disease. Further research is necessary, both relating to focal therapy in general and to the utility of each MRI-guided focal treatment discussed.

  12. Nanoparticles for cancer gene therapy: Recent advances, challenges, and strategies.

    Science.gov (United States)

    Wang, Kui; Kievit, Forrest M; Zhang, Miqin

    2016-12-01

    Compared to conventional treatments, gene therapy offers a variety of advantages for cancer treatment including high potency and specificity, low off-target toxicity, and delivery of multiple genes that concurrently target cancer tumorigenesis, recurrence, and drug resistance. In the past decades, gene therapy has undergone remarkable progress, and is now poised to become a first line therapy for cancer. Among various gene delivery systems, nanoparticles have attracted much attention because of their desirable characteristics including low toxicity profiles, well-controlled and high gene delivery efficiency, and multi-functionalities. This review provides an overview on gene therapeutics and gene delivery technologies, and highlight recent advances, challenges and insights into the design and the utility of nanoparticles in gene therapy for cancer treatment.

  13. Herbal therapy for advanced breast cancer. Personal experience ...

    African Journals Online (AJOL)

    Box 2234, Eldoret-KENYA. Key words: ... Results: Herbal therapy given in advanced breast cancer was found to produce remarkable ... in females in Rift valley region of Kenya next to ... metastases in bone, liver and lungs were destroyed.

  14. The therapy of gefitinib towards breast cancer partially through ...

    African Journals Online (AJOL)

    The therapy of gefitinib towards breast cancer partially through reversing ... Department of Medical Oncology, Affiliated Yuhuangding Hospital, Medical College of Qingdao University, ... solution containing isotope labeled amino acid internal.

  15. Combination Therapy Shows Promise for Treating Advanced Breast Cancer

    Science.gov (United States)

    Adding the drug everolimus (Afinitor®) to exemestane helped postmenopausal women whose advanced breast cancer had stopped responding to hormonal therapy live about 4 months longer without the disease progressing than women who received exemestane alone.

  16. Cancer incidence and novel therapies developed in Japan

    Directory of Open Access Journals (Sweden)

    Masaru Iwasaki

    2012-01-01

    Full Text Available According to the ministry of Health, Labour and welfare of Japan, Cancer has been the leading cause of death in Japan since 1981. [1] As per the data in 2010, in Japan, one in every three deaths was due to cancer. [2] The Japanese Government has introduced so far, three terms of 10 years strategies for Cancer control since 1984 till date. The budget allocated for cancer control in 2009 was 52.5 billion yen in Japan. [3] Lung is the leading site for cancer in both males and females in Japan. In males, following the lung, stomach, liver, colon and pancreas are other leading sites while in the females, stomach, colon, pancreas and breast are the other leading sites.[1] In 2006, the cancer incidence was 694,000 and the male cancer incidence was 1.4 times as large as that of females. The peak age for cancer deaths in males is their fifties while in the females it is the sixties among Japanese. In addition to the conventional treatments such as surgery, radiotherapy and chemotherapy, some of other therapies in practice in Japan are the Hyperthermia [4] that uses high temperatures to kill or damage the cancer cells, the Ion Beam therapy using proton beams [5] to damage the DNA of the cells as cancer cells have high rate of cell divisions and lesser ability to repair DNA damage, the molecular targeted therapies that interfere with a specific molecular target involved in tumour growth and progression [6] and most importantly the autologous cell based Immunotherapies. Modern Cancer Immunotherapy started in the 1970s in Japan. The immunopotentiators using compounds from Bacteria, Beta Glucans from fungi were the first forms of modern Immunotherapy. Then was the era of direct injection of cytokines such as Interleukins, Interferons etc. The adverse effects associated with the injection of cytokines led to development of cell based Immunotherapies in the 1980s. [7] Immuno-cell therapies involve isolation of immune cells which are then processed and re

  17. Cancer-targeted BikDD gene therapy elicits protective antitumor immunity against lung cancer.

    Science.gov (United States)

    Sher, Yuh-Pyng; Liu, Shih-Jen; Chang, Chun-Mien; Lien, Shu-Pei; Chen, Chien-Hua; Han, Zhenbo; Li, Long-Yuan; Chen, Jin-Shing; Wu, Cheng-Wen; Hung, Mien-Chie

    2011-04-01

    Targeted cancer-specific gene therapy is a promising strategy for treating metastatic lung cancer, which is a leading cause of lung cancer-related deaths. Previously, we developed a cancer-targeted gene therapy expression system with high tumor specificity and strong activity that selectively induced lung cancer cell killing without affecting normal cells in immunocompromised mice. Here, we found this cancer-targeted gene therapy, SV-BikDD, composed of the survivin promoter in the VP16-GAL4-WPRE integrated systemic amplifier system to drive the apoptotic gene BikDD, not only caused cytotoxic effects in cancer cells but also elicited a cancer-specific cytotoxic T lymphocyte response to synergistically increase the therapeutic effect and further develop an effective systemic antitumoral immunity against rechallenges of tumorigenic dose of parental tumor cells inoculated at distant sites in immunocompetent mice. In addition, this cancer-targeted gene therapy does not elicit an immune response against normal tissues, but CMV-BikDD treatment does. The therapeutic vector could also induce proinflammatory cytokines to activate innate immunity and provide some benefits in antitumor gene therapy. Thus, this study provides a promising strategy with benefit of antitumoral immune response worthy of further development in clinical trials for treating lung cancer via cancer-targeted gene therapy.

  18. Adjuvant systemic therapy in older women with breast cancer

    Science.gov (United States)

    Leone, Julieta; Leone, Bernardo Amadeo; Leone, José Pablo

    2016-01-01

    Breast cancer in the elderly is an increasing clinical problem. In addition, ~60% of deaths from breast cancer occur in women aged 65 years and older. Despite this, older women with breast cancer have been underrepresented in clinical trials, and this has led to less than optimal evidence to guide their therapy. The management of elderly women with early breast cancer is a complex process that requires careful evaluation of life expectancy, comorbidities, patient values, and risks and benefits of available treatment options. This review will focus on current adjuvant systemic therapy options for older women with breast cancer, discuss the principles in the decision-making process, and define the role of endocrine therapy, chemotherapy, and targeted agents. PMID:27524919

  19. EGFR targeted therapy in lung cancer; an evolving story

    Directory of Open Access Journals (Sweden)

    C. Bartholomew

    2017-01-01

    Full Text Available Specific oncogenes with driver mutations, such as the Epidermal Growth Factor Receptor (EGFR 1 gene can lead to non-small-cell lung cancer formation. Identification of these oncogenes, their driver mutations and downstream effects allow the targeting of these pathways by drugs. Such personalised therapy has become an important strategy in combating lung cancer and highlights the need to test for these mutations. Tyrosine Kinase Inhibitors (TKIs against EGFR, such as Erlotinib, are able to halt these tumour promoting properties in non-small-cell lung cancers. Third generation EGFR TKIs, such as Osimertinib, are focussing on resulting acquired TKI resistance. Here we report the clinical course of a patient with metastatic non-small-cell lung cancer who has undergone EGFR targeted therapy and been further challenged by TKI acquired resistance. Her extended survival and maintained quality of life are a consequence of these modern, genotype-targeted, personalised metastatic non-small-cell lung cancer therapies.

  20. Precision Therapy for Lung Cancer: Tyrosine Kinase Inhibitors and Beyond.

    Science.gov (United States)

    Rajan, Arun; Schrump, David S

    2015-01-01

    For patients with advanced cancers there has been a concerted effort to transition from a generic treatment paradigm to one based on tumor-specific biologic, and patient-specific clinical characteristics. This approach, known as precision therapy has been made possible owing to widespread availability and a reduction in the cost of cutting-edge technologies that are used to study the genomic, proteomic, and metabolic attributes of individual tumors. This review traces the evolution of precision therapy for lung cancer from the identification of molecular subsets of the disease to the development and approval of tyrosine kinase, as well as immune checkpoint inhibitors for lung cancer therapy. Challenges of the precision therapy era including the emergence of acquired resistance, identification of untargetable mutations, and the effect on clinical trial design are discussed. We conclude by highlighting newer applications for the concept of precision therapy.

  1. Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy.

    Science.gov (United States)

    Babu, Anish; Ramesh, Rajagopal

    2017-03-27

    Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.

  2. Multifaceted Applications of Chitosan in Cancer Drug Delivery and Therapy

    Directory of Open Access Journals (Sweden)

    Anish Babu

    2017-03-01

    Full Text Available Chitosan is a versatile polysaccharide of biological origin. Due to the biocompatible and biodegradable nature of chitosan, it is intensively utilized in biomedical applications in scaffold engineering as an absorption enhancer, and for bioactive and controlled drug release. In cancer therapy, chitosan has multifaceted applications, such as assisting in gene delivery and chemotherapeutic delivery, and as an immunoadjuvant for vaccines. The present review highlights the recent applications of chitosan and chitosan derivatives in cancer therapy.

  3. Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

    OpenAIRE

    Md Zahidul Islam Pranjol; Amin Hajitou

    2015-01-01

    Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent dev...

  4. Translational Approaches towards Cancer Gene Therapy: Hurdles and Hopes

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2012-09-01

    Full Text Available Introduction: Of the cancer gene therapy approaches, gene silencing, suicide/apoptosis inducing gene therapy, immunogene therapy and targeted gene therapy are deemed to sub­stantially control the biological consequences of genomic changes in cancerous cells. Thus, a large number of clinical trials have been conducted against various malignancies. In this review, we will discuss recent translational progresses of gene and cell therapy of cancer. Methods: Essential information on gene therapy of cancer were reviewed and discussed towards their clinical translations. Results: Gene transfer has been rigorously studied in vitro and in vivo, in which some of these gene therapy endeavours have been carried on towards translational investigations and clinical applications. About 65% of gene therapy trials are related to cancer therapy. Some of these trials have been combined with cell therapy to produce personalized medicines such as Sipuleucel-T (Provenge®, marketed by Dendreon, USA for the treatment of asymptomatic/minimally symptomatic metastatic hormone-refractory prostate cancer. Conclusion: Translational approach links two diverse boundaries of basic and clinical researches. For successful translation of geno­medicines into clinical applications, it is essential 1 to have the guidelines and standard operating procedures for development and application of the genomedicines specific to clinically relevant biomarker(s; 2 to conduct necessary animal experimental studies to show the “proof of concept” for the proposed genomedicines; 3 to perform an initial clinical investigation; and 4 to initiate extensive clinical trials to address all necessary requirements. In short, translational researches need to be refined to accelerate the geno­medicine development and clinical applications.

  5. Vector-mediated cancer gene therapy: an overview.

    Science.gov (United States)

    Seth, Prem

    2005-05-01

    In recent years there has been a dramatic increase in developing gene therapy approaches for the treatment of cancer. The two events that have permitted the formulation of concept of cancer gene therapy are the new understanding of the molecular mechanisms underlying oncogenesis, and the development of the DNA-delivery vehicles or vectors. Many approaches to cancer gene therapy have been proposed, and several viral and non-viral vectors have been utilized. The purpose of this review article is to describe the various strategies of cancer gene therapy (transfer of tumor suppressor genes, suicide genes-enzyme/pro-drug approach, inhibition of dominant oncogenes, immunomodulation approaches, expression of molecules that affect angiogenesis, tumor invasion and metastasis, chemosensitization and radiosensitization approaches, and chemoprotection of stem cells). The chapter also reviews the commonly used vectors (retroviral vectors, adenoviral vectors, adeno-associated viral vectors, pox viruses, herpes simplex viruses, HIV- vectors, non-viral vectors and targetable vectors) for cancer gene therapy. Some of the important issues in cancer gene therapy, and the potential future directions are also being discussed.

  6. Functional nanomaterials for near-infrared-triggered cancer therapy.

    Science.gov (United States)

    Liu, Bei; Li, Chunxia; Cheng, Ziyong; Hou, Zhiyao; Huang, Shanshan; Lin, Jun

    2016-06-24

    The near-infrared (NIR) region (700-1100 nm) is the so-called transparency "therapeutic window" for biological applications owing to its deeper tissue penetration and minimal damage to healthy tissues. In recent years, various NIR-based therapeutic and interventional strategies, such as NIR-triggered drug delivery, photothermal therapy (PTT) and photodynamic therapy (PDT), are under research in intensive preclinical and clinical investigations for cancer treatment. The NIR control in these cancer therapy systems is considered crucial to boost local effective tumor suppression while minimizing side effects, resulting in improved therapeutic efficacy. Some researchers even predict the NIR-triggered cancer therapy to be a new and exciting possibility for clinical nanomedicine applications. In this review, the rapid development of NIR light-responsive cancer therapy based on various smartly designed nanocomposites for deep tumor treatments is introduced. In detail, the use of NIR-sensitive materials for chemotherapy, PTT as well as PDT is highlighted, and the associated challenges and potential solutions are discussed. The applications of NIR-sensitive cancer therapy modalities summarized here can highlight their potential use as promising nanoagents for deep tumor therapy.

  7. A systematic review of trismus induced by cancer therapies in head and neck cancer patients

    NARCIS (Netherlands)

    Bensadoun, Rene-Jean; Riesenbeck, Dorothea; Lockhart, Peter B.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Mike T.

    2010-01-01

    This systematic review represents a thorough evaluation of the literature to clarify the impact of cancer therapies on the prevalence, quality of life and economic impact, and management strategies for cancer-therapy-induced trismus. A systematic literature search was conducted with assistance from

  8. A systematic review of trismus induced by cancer therapies in head and neck cancer patients

    NARCIS (Netherlands)

    Bensadoun, Rene-Jean; Riesenbeck, Dorothea; Lockhart, Peter B.; Elting, Linda S.; Spijkervet, Fred K. L.; Brennan, Mike T.

    This systematic review represents a thorough evaluation of the literature to clarify the impact of cancer therapies on the prevalence, quality of life and economic impact, and management strategies for cancer-therapy-induced trismus. A systematic literature search was conducted with assistance from

  9. Oncolytic adenovirus-mediated therapy for prostate cancer

    Directory of Open Access Journals (Sweden)

    Sweeney K

    2016-07-01

    Full Text Available Katrina Sweeney, Gunnel Halldén Centre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK Abstract: Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting localized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support

  10. FGFR Signaling as a Target for Lung Cancer Therapy.

    Science.gov (United States)

    Desai, Arpita; Adjei, Alex A

    2016-01-01

    Lung cancer is the leading cause of cancer-related death in developed countries. Recently, molecular targeted therapies have shown promising results in the management of lung cancer. These therapies require a clear understanding of the relevant pathways that drive carcinogenesis and maintenance of the malignant phenotype. The fibroblast growth factor receptor (FGFR) signaling axis is one such pathway that plays a central role in normal cellular function. Alterations in this pathway have been found in many cancers. In this review article, we focus on the role of this pathway in lung cancer. We present the molecular structure of FGFR, the interaction of the receptor with its ligands (the fibroblast growth factors), its downstream signaling, and aberrations in the FGFR pathway. We also discuss clinical trials involving selective and multikinase FGFR inhibitors in lung cancer treatment.

  11. Targeted therapy in non-small cell lung cancer

    Institute of Scientific and Technical Information of China (English)

    Shou-Ching Tang

    2004-01-01

    @@ 1 Introduction Recent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

  12. [Hormonal therapy for prostatic cancer--state of the art].

    Science.gov (United States)

    Miyakita, Hideshi

    2005-02-01

    Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

  13. Exercise therapy for trismus in head and neck cancer

    NARCIS (Netherlands)

    Dijkstra, P.U.; Sterken, M.W.; Spijkervet, F.K.L.; Roodenburg, J.L.N.; Pater, R.

    2007-01-01

    The aim of this study was to analyze retrospectively effects of exercise therapy on trismus related to head and neck cancer or as a consequence of its treatment, and to compare these effects with trismus not related to head and neck cancer. Medical records of patients referred to the department of p

  14. Exercise therapy for trismus in head and neck cancer

    NARCIS (Netherlands)

    Dijkstra, P.U.; Sterken, M.W.; Spijkervet, F.K.L.; Roodenburg, J.L.N.; Pater, R.

    The aim of this study was to analyze retrospectively effects of exercise therapy on trismus related to head and neck cancer or as a consequence of its treatment, and to compare these effects with trismus not related to head and neck cancer. Medical records of patients referred to the department of

  15. Exercise therapy for trismus in head and neck cancer

    NARCIS (Netherlands)

    Dijkstra, P.U.; Sterken, M.W.; Spijkervet, F.K.L.; Roodenburg, J.L.N.; Pater, R.

    2007-01-01

    The aim of this study was to analyze retrospectively effects of exercise therapy on trismus related to head and neck cancer or as a consequence of its treatment, and to compare these effects with trismus not related to head and neck cancer. Medical records of patients referred to the department of p

  16. Starting Hormone Therapy at Menopause Increases Breast Cancer Risk

    Science.gov (United States)

    According to a January 28, 2011 article in the Journal of the National Cancer Institute, women who start taking menopausal hormone therapy around the time of menopause have a higher risk of breast cancer than women who begin taking hormones a few years later.

  17. Morbidity of the neck after head and neck cancer therapy

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; van der Laan, B.F.; Plukker, J.T.; Roodenburg, J.L.

    2004-01-01

    Background. Studies on morbidity of the neck after head and neck cancer therapy are scarcely described. Methods. Patients who underwent surgery, including neck dissection, with and without radiation therapy at least 1 year before the study were asked to participate. We assessed neck pain, loss of se

  18. Morbidity of the neck after head and neck cancer therapy

    NARCIS (Netherlands)

    van Wilgen, C.P.; Dijkstra, P.U.; van der Laan, B.F.; Plukker, J.T.; Roodenburg, J.L.

    Background. Studies on morbidity of the neck after head and neck cancer therapy are scarcely described. Methods. Patients who underwent surgery, including neck dissection, with and without radiation therapy at least 1 year before the study were asked to participate. We assessed neck pain, loss of

  19. Oral care of the cancer patient receiving radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Holtzhausen, T. (Medical Univ. of Southern Africa, Pretoria (South Africa). Dept. of Community Dentistry)

    1982-07-01

    Radiation therapy is frequently being used for the patient with oral cancer. The survival rate is increasing, due to more effective treatment technique. The question of whether any teeth should be extracted, the mode of therapy and the side effects of radiation like Xerostomia, caries, stomatitis, trismus and osteo-radionecrosis and also post radiation care are discussed.

  20. ORAL-THERAPY FOR SMALL-CELL LUNG-CANCER

    NARCIS (Netherlands)

    POSTMUS, PE; SMIT, EF

    After a remarkable improvement of the very poor prognosis of small cell lung cancer with very simple therapy such as iv and oral cyclophosphamide the role of oral therapy has become minimal. However, since more than a decade results of combination chemotherapy are at a plateau and it is necessary to

  1. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mecha

  2. VAV3 mediates resistance to breast cancer endocrine therapy

    NARCIS (Netherlands)

    H. Aguilar (Helena); A. Urruticoechea (Ander); P. Halonen (Pasi); K. Kiyotani (Kazuma); T. Mushiroda (Taisei); X. Barril (Xavier); J. Serra-Musach (Jordi); A.B.M.M.K. Islam (Abul); L. Caizzi (Livia); L. Di Croce (Luciano); E. Nevedomskaya (Ekaterina); W. Zwart (Wilbert); J. Bostner (Josefine); E. Karlsson (Elin); G. Pérez Tenorio (Gizeh); T. Fornander (Tommy); D.C. Sgroi (Dennis); R. Garcia-Mata (Rafael); M.P.H.M. Jansen (Maurice); N. García (Nadia); N. Bonifaci (Núria); F. Climent (Fina); E. Soler (Eric); A. Rodríguez-Vida (Alejo); M. Gil (Miguel); J. Brunet (Joan); G. Martrat (Griselda); L. Gómez-Baldó (Laia); A.I. Extremera (Ana); J. Figueras; J. Balart (Josep); R. Clarke (Robert); K.L. Burnstein (Kerry); K.E. Carlson (Kathryn); J.A. Katzenellenbogen (John); M. Vizoso (Miguel); M. Esteller (Manel); A. Villanueva (Alberto); A.B. Rodríguez-Peña (Ana); X.R. Bustelo (Xosé); Y. Nakamura (Yusuke); H. Zembutsu (Hitoshi); O. Stål (Olle); R.L. Beijersbergen (Roderick); M.A. Pujana (Miguel)

    2014-01-01

    textabstractIntroduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mecha

  3. MiR-21 expression in the tumor cell compartment holds unfavorable prognostic value in gliomas

    DEFF Research Database (Denmark)

    Hermansen, Simon Kjær; Dahlrot, Rikke Hedegaard; Nielsen, Boye Schnack

    2013-01-01

    miR-21 was associated with poor prognosis when adjusting for known clinical parameters (age, grade, and sex) in a multivariate analysis [p = 0.049, hazard ratio (HR) = 1.545, 95 % CI, 1.002-2.381]. In conclusion, we have shown that miR-21 is located in both tumor cells and tumor blood vessels...... and that its level in the tumor cell compartment holds unfavorable prognostic value in gliomas....

  4. Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy

    Science.gov (United States)

    2015-10-01

    AD_________________ (Leave blank) Award Number: W81XWH-14-1-0350 TITLE: Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After...30 Sep 2014 - 29 Sep 2015 4. TITLE AND SUBTILE Targeting Quiescent Cancer Cells to Eliminate Tumor Recurrence After Therapy 5a. CONTRACT NUMBER...Innovative reporter gene systems are designed to mark quiescent or proliferating lung cancer cells (Aim 1) and then used to track and trace the dynamics of

  5. Applicability of RNA interference in cancer therapy: Current status

    Directory of Open Access Journals (Sweden)

    S Maduri

    2015-01-01

    Full Text Available Cancer is a manifestation of dysregulated gene function arising from a complex interplay of oncogenes and tumor suppressor genes present in our body. Cancer has been constantly chased using various therapies but all in vain as most of them are highly effective only in the early stages of cancer. Recently, RNA interference (RNAi therapy, a comparatively new entrant is evolving as a promising player in the battle against cancer due to its post-transcriptional gene silencing ability. The most alluring feature of this non-invasive technology lies in its utility in the cancer detection and the cancer treatment at any stage. Once this technology is fully exploited it can bring a whole new era of therapeutics capable of curing cancer at any stage mainly due to its ability to target the vital processes required for cell proliferation such as response to growth factors, nutrient uptake/synthesis, and energy generation. This therapy can also be used to treat stage IV cancer, the most difficult to treat till date, by virtue of its metastasis inhibiting capability. Recent research has also proved that cancer can even be prevented by proper modulation of physiological RNAi pathways and researchers have found that many nutrients, which are a part of routine diet, can effectively modulate these pathways and prevent cancer. Even after having all these advantages the potential of RNAi therapy could not be fully tapped earlier, due to many limitations associated with the administration of RNAi based therapeutics. However, recent advancements in this direction, such as the development of small interfering RNA (siRNA tolerant to nucleases and the development of non-viral vectors such as cationic liposomes and nanoparticles, can overcome this obstacle and facilitate the clinical use of RNAi based therapeutics in the treatment of cancer. The present review focuses on the current status of RNAi therapeutics and explores their potential as future diagnostics and

  6. NOTCH INHIBITION AS A PROMISING NEW APPROACH TO CANCER THERAPY

    OpenAIRE

    Purow, Benjamin

    2012-01-01

    The Notch pathway powerfully influences stem cell maintenance, development and cell fate and is increasingly recognized for the key roles it plays in cancer. Notch promotes cell survival, angiogenesis and treatment resistance in numerous cancers, making it a promising target for cancer therapy. It also crosstalks with other critical oncogenes, providing a means to affect numerous signaling pathways with one intervention. While the gamma-secretaase inhibitors are the only form of Notch inhibit...

  7. Targeted cancer gene therapy : the flexibility of adenoviral gene therapy vectors

    NARCIS (Netherlands)

    Rots, MG; Curiel, DT; Gerritsen, WR; Haisma, HJ

    2003-01-01

    Recombinant adenoviral vectors are promising reagents for therapeutic interventions in humans, including gene therapy for biologically complex diseases like cancer and cardiovascular diseases. In this regard, the major advantage of adenoviral vectors is their superior in vivo gene transfer efficienc

  8. Hormone Therapy for Breast Cancer in Men

    Science.gov (United States)

    ... of testosterone and other androgens (male hormones). Most male breast cancers have androgen receptors that may cause the cells ... into estrogens in the body. Orchiectomy shrinks most male breast cancers, and may help make other treatments like tamoxifen ...

  9. Exercise therapy for trismus in head and neck cancer

    OpenAIRE

    Dijkstra, P.U.; Sterken, M.W.; Spijkervet, F K L; Roodenburg, J.L.N.; Pater, R.

    2007-01-01

    The aim of this study was to analyze retrospectively effects of exercise therapy on trismus related to head and neck cancer or as a consequence of its treatment, and to compare these effects with trismus not related to head and neck cancer. Medical records of patients referred to the department of physical therapy with the diagnosis trismus were retrieved and analyzed. Data of 27 patients with trismus related to head and neck cancer and data of eight patients with trismus not related to cance...

  10. Bacteriophage-Derived Vectors for Targeted Cancer Gene Therapy

    Directory of Open Access Journals (Sweden)

    Md Zahidul Islam Pranjol

    2015-01-01

    Full Text Available Cancer gene therapy expanded and reached its pinnacle in research in the last decade. Both viral and non-viral vectors have entered clinical trials, and significant successes have been achieved. However, a systemic administration of a vector, illustrating safe, efficient, and targeted gene delivery to solid tumors has proven to be a major challenge. In this review, we summarize the current progress and challenges in the targeted gene therapy of cancer. Moreover, we highlight the recent developments of bacteriophage-derived vectors and their contributions in targeting cancer with therapeutic genes following systemic administration.

  11. Antisense Oligonucleotide Therapy for Patients with Advanced Cancer | Center for Cancer Research

    Science.gov (United States)

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the U.S. Improvements in therapy have increased the survival of patients with CRC from 10 months to two years, but for patients who stop responding to treatments, such as irinotecan, options for additional therapy are limited. Antisense oligonucleotides (ASOs) may offer advantages over traditional therapies if an appropriate target can be identified.

  12. PET Imaging to Monitor Cancer Therapy

    NARCIS (Netherlands)

    Malviya, Gaurav; Nayak, Tapan K.

    2013-01-01

    Improved knowledge and understanding of key aspects of cancer has led to the development of novel cancer therapeutics acting through complex pathways and mode of actions. The success of these novel cancer therapeutics is often difficult to predict using standard response criteria based on anatomic c

  13. PET Imaging to Monitor Cancer Therapy

    NARCIS (Netherlands)

    Malviya, Gaurav; Nayak, Tapan K.

    2013-01-01

    Improved knowledge and understanding of key aspects of cancer has led to the development of novel cancer therapeutics acting through complex pathways and mode of actions. The success of these novel cancer therapeutics is often difficult to predict using standard response criteria based on anatomic

  14. Nanomedicines for image-guided cancer therapy (Conference Presentation)

    Science.gov (United States)

    Zheng, Jinzi

    2016-09-01

    Imaging technologies are being increasingly employed to guide the delivery of cancer therapies with the intent to increase their performance and efficacy. To date, many patients have benefited from image-guided treatments through prolonged survival and improvements in quality of life. Advances in nanomedicine have enabled the development of multifunctional imaging agents that can further increase the performance of image-guided cancer therapy. Specifically, this talk will focus on examples that demonstrate the benefits and application of nanomedicine in the context of image-guide surgery, personalized drug delivery, tracking of cell therapies and high precision radiotherapy delivery.

  15. Adoptive T cell therapy: Addressing challenges in cancer immunotherapy

    Directory of Open Access Journals (Sweden)

    Yee Cassian

    2005-04-01

    Full Text Available Abstract Adoptive T cell therapy involves the ex vivo selection and expansion of effector cells for the treatment of patients with cancer. In this review, the advantages and limitations of using antigen-specific T cells are discussed in counterpoint to vaccine strategies. Although vaccination strategies represent more readily available reagents, adoptive T cell therapy provides highly selected T cells of defined phenotype, specificity and function that may influence their biological behavior in vivo. Adoptive T cell therapy offers not only translational opportunities but also a means to address fundamental issues in the evolving field of cancer immunotherapy.

  16. Natural health products and cancer chemotherapy and radiation therapy

    Directory of Open Access Journals (Sweden)

    Doreen Oneschuk

    2011-12-01

    Full Text Available Complementary therapies, notably natural health products such as herbs and vitamins, are frequently used by cancer patients receiving chemotherapy and radiation therapy. There is much controversy as to whether these natural health products should be taken during conventional cancer treatments. Supporters of this practice cite beneficial effects of the antioxidant properties, while opponents are concerned about the potential for natural health product-chemotherapy/radiation related negative interactions. This involves understanding the role and effect on metabolizing enzymes. This review will highlight the present evidence for both the beneficial and negative consequences of the use of natural health products during chemotherapy and radiation therapy.

  17. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    Science.gov (United States)

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  18. Stem Cell Based Gene Therapy in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jae Heon Kim

    2014-01-01

    Full Text Available Current prostate cancer treatment, especially hormone refractory cancer, may create profound iatrogenic outcomes because of the adverse effects of cytotoxic agents. Suicide gene therapy has been investigated for the substitute modality for current chemotherapy because it enables the treatment targeting the cancer cells. However the classic suicide gene therapy has several profound side effects, including immune-compromised due to viral vector. Recently, stem cells have been regarded as a new upgraded cellular vehicle or vector because of its homing effects. Suicide gene therapy using genetically engineered mesenchymal stem cells or neural stem cells has the advantage of being safe, because prodrug administration not only eliminates tumor cells but consequently kills the more resistant therapeutic stem cells as well. The attractiveness of prodrug cancer gene therapy by stem cells targeted to tumors lies in activating the prodrug directly within the tumor mass, thus avoiding systemic toxicity. Therapeutic achievements using stem cells in prostate cancer include the cytosine deaminase/5-fluorocytosine prodrug system, herpes simplex virus thymidine kinase/ganciclovir, carboxyl esterase/CPT11, and interferon-beta. The aim of this study is to review the stem cell therapy in prostate cancer including its proven mechanisms and also limitations.

  19. Biomedical nanomaterials for imaging-guided cancer therapy

    Science.gov (United States)

    Huang, Yuran; He, Sha; Cao, Weipeng; Cai, Kaiyong; Liang, Xing-Jie

    2012-09-01

    To date, even though various kinds of nanomaterials have been evaluated over the years in order to develop effective cancer therapy, there is still significant challenges in the improvement of the capabilities of nano-carriers. Developing a new theranostic nanomedicine platform for imaging-guided, visualized cancer therapy is currently a promising way to enhance therapeutic efficiency and reduce side effects. Firstly, conventional imaging technologies are reviewed with their advantages and disadvantages, respectively. Then, advanced biomedical materials for multimodal imaging are illustrated in detail, including representative examples for various dual-modalities and triple-modalities. Besides conventional cancer treatment (chemotherapy, radiotherapy), current biomaterials are also summarized for novel cancer therapy based on hyperthermia, photothermal, photodynamic effects, and clinical imaging-guided surgery. In conclusion, biomedical materials for imaging-guided therapy are becoming one of the mainstream treatments for cancer in the future. It is hoped that this review might provide new impetus to understand nanotechnology and nanomaterials employed for imaging-guided cancer therapy.

  20. 5-Aminolevulinic acid-mediated photodynamic therapy for bladder cancer.

    Science.gov (United States)

    Inoue, Keiji

    2017-02-01

    Photodynamic therapy using 5-aminolevulinic acid is a treatment method in which the fluorescent substance of protoporphyrin IX excessively accumulated specifically in cancer cells is excited by visible red or green light irradiation, and reactive oxygen is produced and injures cancer cells. Photodynamic therapy using 5-aminolevulinic acid less markedly influences the surrounding normal cells and tissue as a result of no accumulation of protoporphyrin IX, being a low-invasive, less harmful treatment localized to cancer. Furthermore, photodynamic therapy using 5-aminolevulinic acid is painless, requiring no anesthesia because localized lesions are treated at a low-energy level, and repeatedly applicable, unlike radiotherapy, and so is expected to be a new low-invasive treatment based on a concept completely different from existing treatments. In fact, photodynamic therapy using 5-aminolevulinic acid for bladder cancer was clinically demonstrated mainly for treatment-resistant bladder carcinoma in situ, and favorable outcomes have been obtained. Photodynamic therapy using 5-aminolevulinic acid are photodynamic technologies based on the common biological characteristic of cancers, and are expected as novel therapeutic strategies for many types of cancer. © 2017 The Japanese Urological Association.

  1. Xenogeneic homologous genes, molecular evolution and cancer therapy

    Institute of Scientific and Technical Information of China (English)

    田聆; 魏于全

    2001-01-01

    Cancer is one of the main causes for death of human beings to date, and cancer biotherapy (mainlyimmunotherapy and gene therapy) has become the most promising approach after surgical therapy, radiotherapy andchemotherapy. However, there are still many limitations on cancer immunotherapy and gene therapy; therefore great ef-fort is being made to develop new strategies. It has been known that, in the process of evolution, a number of genes, theso-called xenogeneic homologous genes, are well-conserved and show the structural and/or functional similarity betweenvarious species to some degree. The nucleotide changes between various xenogeneic homologous genes are derived frommutation, and most of them are neutral mutations. Considering that the subtle differences in xenogeneic homologousgenes can break immune tolerance, enhance the immunogenicity and induce autologous immune response so as to elimi-nate tumor cells, we expect that a strategy of inducing autoimmune response using the property of xenogeneic homologousgenes will become a new therapy for cancer. Moreover, this therapy can also be used in the treatment of other diseases,such as autoimmune diseases and AIDS. This article will discuss the xenogeneic homologous genes, molecular evolutionand cancer therapy.

  2. New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2012-03-01

    Full Text Available Abstract A summit on cellular therapy for cancer discussed and presented advances related to the use of adoptive cellular therapy for melanoma and other cancers. The summit revealed that this field is advancing rapidly. Conventional cellular therapies, such as tumor infiltrating lymphocytes (TIL, are becoming more effective and more available. Gene therapy is becoming an important tool in adoptive cell therapy. Lymphocytes are being engineered to express high affinity T cell receptors (TCRs, chimeric antibody-T cell receptors (CARs and cytokines. T cell subsets with more naïve and stem cell-like characteristics have been shown in pre-clinical models to be more effective than unselected populations and it is now possible to reprogram T cells and to produce T cells with stem cell characteristics. In the future, combinations of adoptive transfer of T cells and specific vaccination against the cognate antigen can be envisaged to further enhance the effectiveness of these therapies.

  3. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies.

    Science.gov (United States)

    Jin, Xun; Zhang, Peilan; Luo, Li; Cheng, Hao; Li, Yunzu; Du, Ting; Zou, Bingwen; Gou, Maling

    Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol) (DPP) nanoparticles to deliver doxorubicin (Dox) for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer.

  4. Personalized therapy in endometrial cancer: Challenges and opportunities

    Science.gov (United States)

    Westin, Shannon N

    2012-01-01

    Early stage endometrial cancer is generally curable. However, progress in the treatment of advanced and recurrent endometrial cancer has been limited. This has led to a shift from the use of traditional chemotherapeutic agents and radiotherapy regimens to the promising area of targeted therapy, given the large number of druggable molecular alterations found in endometrial cancer. To maximize the effects of directed targeted therapy, careful molecular characterization of the endometrial tumor is necessary. This represents an important difference in the use of targeted therapy vs. traditional chemotherapy or radiation treatment. This review will discuss relevant pathways to target in endometrial cancer as well as the challenges that arise during development of a personalized oncology approach. PMID:22198566

  5. Manipulation of Innate Immunity for Cancer Therapy in Dogs

    Directory of Open Access Journals (Sweden)

    Daniel Regan

    2015-12-01

    Full Text Available Over the last one to two decades, the field of cancer immunotherapy has rapidly progressed from early preclinical studies to a successful clinical reality and fourth major pillar of human cancer therapy. While current excitement in the field of immunotherapy is being driven by several major breakthroughs including immune checkpoint inhibitors and adoptive cell therapies, these advances stem from a foundation of pivotal studies demonstrating the immune systems role in tumor control and eradication. The following will be a succinct review on veterinary cancer immunotherapy as it pertains to manipulation of the innate immune system to control tumor growth and metastasis. In addition, we will provide an update on recent progress in our understanding of the innate immune system in veterinary tumor immunology, and how these gains may lead to novel therapies for the treatment of cancer in companion animals.

  6. Targeted Gene Therapy of Cancer: Second Amendment toward Holistic Therapy

    OpenAIRE

    Jaleh Barar; Yadollah Omidi

    2013-01-01

    It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME)”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrie...

  7. Bacteria as vectors for gene therapy of cancer.

    LENUS (Irish Health Repository)

    Baban, Chwanrow K

    2012-01-31

    Anti-cancer therapy faces major challenges, particularly in terms of specificity of treatment. The ideal therapy would eradicate tumor cells selectively with minimum side effects on normal tissue. Gene or cell therapies have emerged as realistic prospects for the treatment of cancer, and involve the delivery of genetic information to a tumor to facilitate the production of therapeutic proteins. However, there is still much to be done before an efficient and safe gene medicine is achieved, primarily developing the means of targeting genes to tumors safely and efficiently. An emerging family of vectors involves bacteria of various genera. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally. Furthermore, invasive species can deliver heterologous genes intra-cellularly for tumor cell expression. Here, we review the use of bacteria as vehicles for gene therapy of cancer, detailing the mechanisms of action and successes at preclinical and clinical levels.

  8. Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells

    Directory of Open Access Journals (Sweden)

    Mauricio P. Pinto

    2016-09-01

    Full Text Available Tumor angiogenesis is widely recognized as one of the “hallmarks of cancer”. Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic therapy escape: (1 upregulation of compensatory/alternative pathways for angiogenesis; (2 vasculogenic mimicry; and (3 vessel co-option. We suggest that an understanding of how a cancer cell adapts to antiangiogenic therapy may also parallel the mechanisms employed in the bourgeoning tumor and isolated metastatic cells delivering responsible for residual disease. Finally, we speculate on strategies to adapt antiangiogenic therapy for future clinical uses.

  9. Molecular therapy of colorectal cancer: progress and future directions.

    Science.gov (United States)

    Weng, Wenhao; Feng, Junlan; Qin, Huanlong; Ma, Yanlei

    2015-02-01

    Colorectal cancer (CRC) remains one of the most common types of cancer and leading causes of cancer death worldwide. Although the introduction of cytotoxic drugs such as oxaliplatin, irinotecan and fluorouracil has improved the treatment of advanced CRC, the individual response to chemoradiotherapy varies tremendously from one patient to another. However, recent progress in CRC molecular therapies may provide new insight into the treatment of this disease. Currently, components of the EGFR, VEGF, Wnt and NF-kB pathways are the most important targets for CRC therapy. This review chronicles the development of molecular CRC therapies over the past few decades. We also provide an update on the current progress of research concerning the molecular pathways leading to CRC and discuss the possible implications for CRC therapy.

  10. Epigenetic therapy in gastrointestinal cancer: the right combination

    Science.gov (United States)

    Abdelfatah, Eihab; Kerner, Zachary; Nanda, Nainika; Ahuja, Nita

    2016-01-01

    Epigenetics is a relatively recent field of molecular biology that has arisen over the past 25 years. Cancer is now understood to be a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. The development of drugs targeting these processes has rapidly progressed; with several drugs already FDA approved as first-line therapy in hematological malignancies. Gastrointestinal (GI) cancers possess high degrees of epigenetic dysregulation, exemplified by subtypes such as CpG island methylator phenotype (CIMP), and the potential benefit of epigenetic therapy in these cancers is evident. The application of epigenetic drugs in solid tumors, including GI cancers, is just emerging, with increased understanding of the cancer epigenome. In this review, we provide a brief overview of cancer epigenetics and the epigenetic targets of therapy including deoxyribonucleic acid (DNA) methylation, histone modifications, and chromatin remodeling. We discuss the epigenetic drugs currently in use, with a focus on DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors, and explain the pharmacokinetic and mechanistic challenges in their application. We present the strategies employed in incorporating these drugs into the treatment of GI cancers, and explain the concept of the cancer stem cell in epigenetic reprogramming and reversal of chemo resistance. We discuss the most promising combination strategies in GI cancers including: (1) epigenetic sensitization to radiotherapy, (2) epigenetic sensitization to cytotoxic chemotherapy, and (3) epigenetic immune modulation and priming for immune therapy. Finally, we present preclinical and clinical trial data employing these strategies thus far in various GI cancers including colorectal, esophageal, gastric, and pancreatic cancer. PMID:27366224

  11. Efficient intravesical therapy of bladder cancer with cationic doxorubicin nanoassemblies

    Directory of Open Access Journals (Sweden)

    Jin X

    2016-09-01

    Full Text Available Xun Jin,1 Peilan Zhang,1 Li Luo,1 Hao Cheng,1 Yunzu Li,1 Ting Du,1 Bingwen Zou,2 Maling Gou1 1State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, People’s Republic of China; 2Department of Thoracic Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, People’s Republic of China Abstract: Nanoparticles have promising applications in drug delivery for cancer therapy. Herein, we prepared cationic 1,2-dioleoyl-3-trimethylammonium propane/methoxypoly (ethyleneglycol (DPP nanoparticles to deliver doxorubicin (Dox for intravesical therapy of bladder cancer. The DPP micelles have a mean dynamic diameter of 18.65 nm and a mean zeta potential of +19.6 mV. The DPP micelles could prolong the residence of Dox in the bladder, enhance the penetration of Dox into the bladder wall, and improve cellular uptake of Dox. The encapsulation by DPP micelles significantly improved the anticancer effect of Dox against orthotopic bladder cancer in vivo. This work described a Dox-loaded DPP nanoparticle with potential applications in intravesical therapy of bladder cancer. Keywords: bladder cancer, drug delivery, nanoparticles, intravesical therapy

  12. Targeted endometrial cancer therapy as a future prospect.

    Science.gov (United States)

    Thanapprapasr, Duangmani; Cheewakriangkrai, Chalong; Likittanasombut, Puchong; Thanapprapasr, Kamolrat; Mutch, David G

    2013-03-01

    Among female-specific cancers worldwide, endometrial cancer is the third most common after breast cancer and cervical cancer. In addition, it is the most common gynecological cancer in the USA and Europe. The incidence of this disease appears to be increasing. The cause of this increase is multifactorial, but a few possible factors involved are increasing obesity, an aging population leading to more postmenopausal women and greater tamoxifen use. Surgery is generally the primary treatment of this disease and postoperative radiation therapy in some patients with high or intermediate risk may prevent locoregional recurrences. Adjuvant chemotherapy improves progression-free survival in advanced or recurrent cancer. However, overall survival in patients with advanced disease is poor. Hence, better therapy is needed and targeted molecular therapies are emerging as possible treatment candidates. These include molecules that target VEGF, mTOR, tyrosine kinases, human EGF receptors and FGF receptors. Therapies targeting specific molecular features should be evaluated in future strategies in the treatment of endometrial cancer.

  13. Increased circulating miR-21 levels are associated with kidney fibrosis.

    Directory of Open Access Journals (Sweden)

    François Glowacki

    Full Text Available MicroRNAs (miRNAs are a class of noncoding RNA acting at a post-transcriptional level to control the expression of large sets of target mRNAs. While there is evidence that miRNAs deregulation plays a causative role in various complex disorders, their role in fibrotic kidney diseases is largely unexplored. Here, we found a strong up-regulation of miR-21 in the kidneys of mice with unilateral ureteral obstruction and also in the kidneys of patients with severe kidney fibrosis. In addition, mouse primary fibroblasts derived from fibrotic kidneys exhibited higher miR-21 expression level compared to those derived from normal kidneys. Expression of miR-21 in normal primary kidney fibroblasts was induced upon TGFβ exposure, a key growth factor involved in fibrogenesis. Finally, ectopic expression of miR-21 in primary kidney fibroblasts was sufficient to promote myofibroblast differentiation. As circulating miRNAs have been suggested as promising non-invasive biomarkers, we further assess whether circulating miR-21 levels are associated with renal fibrosis using sera from 42 renal transplant recipients, categorized according to their renal fibrosis severity, evaluated on allograft biopsies (Interstitial Fibrosis/Tubular Atrophy (IF/TA. Circulating miR-21 levels are significantly increased in patients with severe IF/TA grade (IF/TA grade 3: 3.0±1.0 vs lower grade of fibrosis: 1.5±1.2; p = 0.001. By contrast, circulating miR-21 levels were not correlated with other renal histological lesions. In a multivariate linear regression model including IF/TA grade and estimated GFR, independent associations were found between circulating miR-21 levels and IF/TA score (ß = 0.307, p = 0.03, and between miR-21 levels and aMDRD (ß = -0.398, p = 0.006. Altogether, these data suggest miR-21 has a key pathogenic role in kidney fibrosis and may represent a novel, predictive and reliable blood marker of kidney fibrosis.

  14. Precision medicine and personalized breast cancer: combination pertuzumab therapy

    Directory of Open Access Journals (Sweden)

    Reynolds K

    2014-03-01

    Full Text Available Kerry Reynolds, Sasmit Sarangi, Aditya Bardia, Don S Dizon Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA, USA Abstract: Trastuzumab (Herceptin, a monoclonal antibody directed against the human epidermal growth-factor receptor 2 (HER2, is the poster child for antibody-based targeted therapy in breast cancer. Pertuzumab, another humanized monoclonal antibody, binds to a different domain of HER2 and prevents the formation of HER2:HER3 dimers, which is the most potent heterodimer in the HER family. The combination of trastuzumab and pertuzumab has synergistic activity, and is associated with improved clinical outcomes. The US Food and Drug Administration (FDA approved pertuzumab in combination with trastuzumab-based chemotherapy originally as first-line therapy for metastatic HER2-positive breast cancer in 2012, and more recently as neoadjuvant therapy for localized disease in 2013. Pertuzumab is the first neoadjuvant drug to receive accelerated approval by the FDA based on pathological complete response as the primary end point. In this article, we review the mechanism of action, pharmacokinetics, clinical efficacy, safety, and current role of pertuzumab in the management of breast cancer, as well as ongoing clinical trials and future directions regarding the utility of pertuzumab as a personalized therapeutic option for HER2-positive breast cancer. In the coming years, we anticipate increased utilization of neoadjuvant trials for drug development, biomarker discovery, and validation, and envision conduct of personalized breast cancer clinics in which therapies will be routinely selected based on genetic alterations in the tumor. Regardless of the targeted therapy combinations employed based on tumor genomic profile, trastuzumab and pertuzumab will likely continue to form the backbone of the personalized regimen for HER2-positive breast cancer. Keywords: pertuzumab, HER2 breast cancer, personalized therapy

  15. Navigating cancer network attractors for tumor-specific therapy

    DEFF Research Database (Denmark)

    Creixell, Pau; Schoof, Erwin; Erler, Janine Terra

    2012-01-01

    Cells employ highly dynamic signaling networks to drive biological decision processes. Perturbations to these signaling networks may attract cells to new malignant signaling and phenotypic states, termed cancer network attractors, that result in cancer development. As different cancer cells reach...... these malignant states by accumulating different molecular alterations, uncovering these mechanisms represents a grand challenge in cancer biology. Addressing this challenge will require new systems-based strategies that capture the intrinsic properties of cancer signaling networks and provide deeper...... understanding of the processes by which genetic lesions perturb these networks and lead to disease phenotypes. Network biology will help circumvent fundamental obstacles in cancer treatment, such as drug resistance and metastasis, empowering personalized and tumor-specific cancer therapies....

  16. Nutrients and cancer: an introduction to cesium therapy.

    Science.gov (United States)

    Sartori, H E

    1984-01-01

    A brief overview on the relevance in dietary factors in both development and prevention of cancer is presented. The pharmacologic properties of various food ingredients are discussed. Establishing of a special diet for the cancer patient is suggested. In addition, avoidance of certain foods is recommended to counteract mucus production of cancer cells. Evaluation of the nutrient content of certain diets in regions with low incidence of cancer has advanced the use of certain alkali metals, i.e., rubidium and cesium, as chemotherapeutic agents. The rationale for this approach termed the "high pH" therapy resides in changing the acidic pH range of the cancer cell by cesium towards weak alkalinity in which the survival of the cancer cell is endangered, and the formation of acidic and toxic materials, normally formed in cancer cells, is neutralized and eliminated.

  17. Hormone therapy for patients with advanced or recurrent endometrial cancer.

    Science.gov (United States)

    Lee, Wen-Ling; Yen, Ming-Shyen; Chao, Kuan-Chong; Yuan, Chiou-Chung; Ng, Heung-Tat; Chao, Hsiang-Tai; Lee, Fa-Kung; Wang, Peng-Hui

    2014-05-01

    The "gold standard" treatment for endometrial cancer is completely staged surgery, followed by radiation or chemotherapy, based on the final pathological surgical stage and requirements. In the primary treatment of endometrial cancers, hormones are rarely taken into consideration after primary surgery. Primary treatment with hormones to preserve fertility in younger women with endometrial cancer is an attractive option, and many successful cases have been reported, although the majority of them finally received definite therapy, including total hysterectomy. The role of hormone therapy is often delayed in recurrent disease; response rates to progestins and tamoxifen or aromatase inhibitors in advanced/recurrent endometrial cancers are approximately 15-20% and nearly ≤ 10%, respectively. This review is focused on updated information and recent knowledge on the use of hormones in the management of women with advanced or recurrent endometrial cancers.

  18. [An overview of antibody-based cancer therapy].

    Science.gov (United States)

    Miao, Qing-fang; Shao, Rong-guang; Zhen, Yong-su

    2012-10-01

    The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Approximate 17 monoclonal antibodies have been approved as cancer therapeutics since 1997. Antibody-drug conjugates (ADC) are powerful new treatment options for cancer, and naked antibodies have recently achieved remarkable success. The safety and effectiveness of therapeutic mAbs in oncology vary depending on the nature of the target antigen and the mechanisms of tumor cell killing. This review provides a summary of the current state of antibody-based cancer therapy, including the mechanisms of tumor cell killing by antibodies, tumor antigens as antibody targets, clinical effectiveness of antibodies in cancer patients and nanoparticles-based ADCs.

  19. Smart Multifunctional Theranostics: Simultaneous Diagnosis and Therapy of Cancer

    Directory of Open Access Journals (Sweden)

    Yadollah Omidi

    2011-09-01

    Full Text Available Clinical applications of advanced nanomedicines such as PEGylated liposomal doxorubicin and paclitaxel-albumin bioconjugates have significantly improved the cancer treatment strategies. However, these pharmaceuticals lack early detection and single cell tracking capabilities. Thus, engineering of smart multifunctional theranostics appear to be our next stepfor simultaneous diagnosis and therapy of cancer. Clinical translation of multifunctional theranostics appears to be dependent upon specificity of cancer biomarkers, biocompatibility of components used for formulation, and advancement of bioconjugation techniques. While many cancer biomarker candidates often fail to be used for clinical diagnosis/therapy because of their nonspecific functional expression in normal tissues, biocompatibility of materials used for bioconjugationalso needs to be approved. All these issues need to be fully addressed prior to the translation of smart multifunctional cancer theranostics.

  20. Phytochemicals for breast cancer therapy: current status and future implications.

    Science.gov (United States)

    Siddiqui, Jawed Akhtar; Singh, Aru; Chagtoo, Megha; Singh, Nidhi; Godbole, Madan Madhav; Chakravarti, Bandana

    2015-01-01

    Breast cancer is one of the most common malignancies among women, representing nearly 30% of newly diagnosed cancers every year. Till date, various therapeutic interventions, including surgery, chemotherapy, hormonal therapy, and radiotherapy are available and are known to cause a significant decline in the overall mortality rate. However, therapeutic resistance, recurrence and lack of treatment in metastasis are the major challenges that need to be addressed. Increasing evidence suggests the presence of cancer stem cells (CSCs) in heterogeneous population of breast tumors capable of selfrenewal and differentiation and is considered to be responsible for drug resistance and recurrence. Therefore, compound that can target both differentiated cancer cells, as well as CSCs, may provide a better treatment strategy. Due to safe nature of dietary agents and health products, investigators are introducing them into clinical trials in place of chemotherapeutic agents.This current review focuses on phytochemicals, mainly flavonoids that are in use for breast cancer therapy in preclinical phase. As phytochemicals have several advantages in breast cancer and cancer stem cells, new synthetic series for breast cancer therapy from analogues of most potent natural molecule can be developed via rational drug design approach.

  1. Nanomedicine for cancer therapy from chemotherapeutic to hyperthermia-based therapy

    CERN Document Server

    Kumar, Piyush

    2017-01-01

    This Brief focuses on the cancer therapy available till date, from conventional drug delivery to nanomedicine in clinical trial. In addition, it reports on future generation based nanotherapeutics and cancer theranostic agent for effective therapeutic diagnosis and treatment. Breast cancer was chosen as the model system in this review. The authors give emphasis to multiple drug resistance (MDR) and its mechanism and how to overcome it using the nanoparticle approach. .

  2. Evaluating localized prostate cancer and identifying candidates for focal therapy.

    Science.gov (United States)

    Sartor, A Oliver; Hricak, Hedvig; Wheeler, Thomas M; Coleman, Jonathan; Penson, David F; Carroll, Peter R; Rubin, Mark A; Scardino, Peter T

    2008-12-01

    Can focal therapy successfully control prostate cancer? Also, if so, which patients should be considered eligible? With limited data available from relatively few patients, these questions are difficult to answer. At this writing, the most likely candidates for focal therapy are patients with low-risk, small-volume tumors, located in 1 region or sector of the prostate, who would benefit from early intervention. The difficulty lies in reliably identifying these men. The larger number of cores obtained in each needle biopsy session has increased both the detection of prostate cancer and the potential risk of overtreating many patients whose cancers pose very little risk to life or health. Urologists typically perform at least a 12-core template biopsy. Although the debate continues about the optimal template, laterally and peripherally directed biopsies have been shown to improve the diagnostic yield. However, as many as 25% of tumors arise anteriorly and can be missed with peripherally directed techniques. Prostate cancer tends to be multifocal, even in its earliest stages. However, the secondary cancers are usually smaller and less aggressive than the index cancer. They appear similar to the incidental cancers found in cystoprostatectomy specimens and appear to have little effect on prognosis in surgical series. When a single focus of cancer is found in 1 core, physicians rightly suspect that more foci of cancer are present in the prostate. Assessing the risk in these patients is challenging when determined by the biopsy data alone. To predict the presence of a very low-risk or "indolent" cancer, nomograms have been developed to incorporate clinical stage, Gleason grade, prostate-specific antigen levels, and prostate volume, along with the quantitative analysis of the biopsy results. Transperineal "mapping" or "saturation" biopsies have been advocated to detect cancers missed or underestimated by previous transrectal biopsies. This approach could provide the

  3. Oncolytic adenovirus-mediated therapy for prostate cancer

    Science.gov (United States)

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  4. Meta-Analysis of Massage Therapy on Cancer Pain.

    Science.gov (United States)

    Lee, Sook-Hyun; Kim, Jong-Yeop; Yeo, Sujung; Kim, Sung-Hoon; Lim, Sabina

    2015-07-01

    Cancer pain is the most common complaint among patients with cancer. Conventional treatment does not always relieve cancer pain satisfactorily. Therefore, many patients with cancer have turned to complementary therapies to help them with their physical, emotional, and spiritual well-being. Massage therapy is increasingly used for symptom relief in patients with cancer. The current study aimed to investigate by meta-analysis the effects of massage therapy for cancer patients experiencing pain. Nine electronic databases were systematically searched for studies published through August 2013 in English, Chinese, and Korean. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) and Cochrane risk-of-bias scales. Twelve studies, including 559 participants, were used in the meta-analysis. In 9 high-quality studies based on the PEDro scale (standardized mean difference, -1.24; 95% confidence interval, -1.72 to -0.75), we observed reduction in cancer pain after massage. Massage therapy significantly reduced cancer pain compared with no massage treatment or conventional care (standardized mean difference, -1.25; 95% confidence interval, -1.63 to -0.87). Our results indicate that massage is effective for the relief of cancer pain, especially for surgery-related pain. Among the various types of massage, foot reflexology appeared to be more effective than body or aroma massage. Our meta-analysis indicated a beneficial effect of massage for relief of cancer pain. Further well-designed, large studies with longer follow-up periods are needed to be able to draw firmer conclusions regarding the effectiveness.

  5. Trimodality therapy in bladder cancer: who, what, and when?

    Science.gov (United States)

    Premo, Christopher; Apolo, Andrea B; Agarwal, Piyush K; Citrin, Deborah E

    2015-05-01

    Radical cystectomy is a standard treatment of nonmetastatic, muscle-invasive bladder cancer. Treatment with trimodality therapy consisting of maximal transurethral resection of the bladder tumor followed by concurrent chemotherapy and radiation has emerged as a method to preserve the native bladder in highly motivated patients. Several factors can affect the likelihood of long-term bladder preservation after trimodality therapy and therefore should be taken into account when selecting patients. New radiation techniques such as intensity modulated radiation therapy and image-guided radiation therapy may decrease the toxicity of radiotherapy in this setting. Novel chemotherapy regimens may improve response rates and minimize toxicity.

  6. Reactive Oxygen Species and Targeted Therapy for Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Lun Zhang

    2016-01-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer-related death in the United States. Reactive oxygen species (ROS are generally increased in pancreatic cancer cells compared with normal cells. ROS plays a vital role in various cellular biological activities including proliferation, growth, apoptosis, and invasion. Besides, ROS participates in tumor microenvironment orchestration. The role of ROS is a doubled-edged sword in pancreatic cancer. The dual roles of ROS depend on the concentration. ROS facilitates carcinogenesis and cancer progression with mild-to-moderate elevated levels, while excessive ROS damages cancer cells dramatically and leads to cell death. Based on the recent knowledge, either promoting ROS generation to increase the concentration of ROS with extremely high levels or enhancing ROS scavenging ability to decrease ROS levels may benefit the treatment of pancreatic cancer. However, when faced with oxidative stress, the antioxidant programs of cancer cells have been activated to help cancer cells to survive in the adverse condition. Furthermore, ROS signaling and antioxidant programs play the vital roles in the progression of pancreatic cancer and in the response to cancer treatment. Eventually, it may be the novel target for various strategies and drugs to modulate ROS levels in pancreatic cancer therapy.

  7. Cancer research and therapy: Where are we today?

    Directory of Open Access Journals (Sweden)

    Sampada Sawant

    2014-12-01

    Full Text Available Till date scientists are struggling to understand the complete mechanism of carcinogenesis. In future, the real time detection of cancer may help scientists to identify some of the complicated biological mechanisms. Certain special features of cancer cells enable researchers to deliver the drug or to develop the right drug therapy. These cell properties include over expression or over activity in uptake of certain nutrients e.g. folic acid and increased permeability. Listed properties might vary depending upon the type of cancer and can be fully exploited by using nanoparticles either to detect the site of cancer or to direct the drug at the affected site. Product approach like drug conjugates, complexes serves as a good platform to solve issues like solubility, toxicity, poor penetration and stability related to cancer drugs. Beside this, several drug delivery platforms are under development by researchers in academia as well as in industry to deliver therapeutic molecules and new chemical entities to the targeted site in body. Amongst them, nanotechnology both at molecular and supramolecular level is a leading platform and can help to image, detect and treat cancer. Surface modification of nanoparticles by coating or anchoring their surface with special markers, materials, peptide, proteins, antibodies or antigens add extra feature and thereby can enhance the effectiveness. These treatments can be used individually or in combined form. In this review, advances on nanotechnological platform are discussed together with some assisting techniques like magnetic field, photo or light field, sonic rays are touched upon. New biological therapies that are advancing in this direction include the antisense therapy, cell therapy, gene therapy, radiation therapy and SiRNA interfaces which are discussed in brief in this article. This article gives short overview on use of complementary and alternative medicine for treatment of cancer such as traditional

  8. Radiation-Induced Second Cancer Risk Estimates From Radionuclide Therapy

    Science.gov (United States)

    Bednarz, Bryan; Besemer, Abigail

    2017-09-01

    The use of radionuclide therapy in the clinical setting is expected to increase significantly over the next decade. There is an important need to understand the radiation-induced second cancer risk associated with these procedures. In this study the radiation-induced cancer risk in five radionuclide therapy patients was investigated. These patients underwent serial SPECT imaging scans following injection as part of a clinical trial testing the efficacy of a 131Iodine-labeled radiopharmaceutical. Using these datasets the committed absorbed doses to multiple sensitive structures were calculated using RAPID, which is a novel Monte Carlo-based 3D dosimetry platform developed for personalized dosimetry. The excess relative risk (ERR) for radiation-induced cancer in these structures was then derived from these dose estimates following the recommendations set forth in the BEIR VII report. The radiation-induced leukemia ERR was highest among all sites considered reaching a maximum value of approximately 4.5. The radiation-induced cancer risk in the kidneys, liver and spleen ranged between 0.3 and 1.3. The lifetime attributable risks (LARs) were also calculated, which ranged from 30 to 1700 cancers per 100,000 persons and were highest for leukemia and the liver for both males and females followed by radiation-induced spleen and kidney cancer. The risks associated with radionuclide therapy are similar to the risk associated with external beam radiation therapy.

  9. BACTERIA IN CANCER THERAPY: AN EMERGING ROBUST STRATEGY

    Directory of Open Access Journals (Sweden)

    Preenu P Sen

    2013-06-01

    Full Text Available Cancer is one of the leading causes of death in the world. Solid tumors account for 90% of all cancers. Despite rapid developments in the conventional modalities of cancer treatment (chemotherapy and radiotherapy there is still no definitive “cure” for cancer. The present observation aims to an eye on alternative cancer therapies. The search for alternative therapies dates back to early 1800’s when a patient was observed to recover spontaneously following an infection. This resulted in the birth of Coley’s toxin for the treatment of sarcomas and use of live Bacillus Calmette – Guerin (BCG for bladder cancer. The same provoked for a series of researches in this field, but was heralded due to lack of specificity, lack of complete tumor lyses and ineffectiveness against small tumors. However with the advent of recombinant DNA technology and its developments, it has paved the way for a new era for a tumor- targeted bacterial vector system for gene therapy of solid tumors. In this review we will discuss the potential of genetically manipulated bacteria that will usher in the new era of bacterial therapy for solid tumors.

  10. Aptamers: active targeting ligands for cancer diagnosis and therapy.

    Science.gov (United States)

    Wu, Xu; Chen, Jiao; Wu, Min; Zhao, Julia Xiaojun

    2015-01-01

    Aptamers, including DNA, RNA and peptide aptamers, are a group of promising recognition units that can specifically bind to target molecules and cells. Due to their excellent specificity and high affinity to targets, aptamers have attracted great attention in various fields in which selective recognition units are required. They have been used in biosensing, drug delivery, disease diagnosis and therapy (especially for cancer treatment). In this review, we summarized recent applications of DNA and RNA aptamers in cancer theranostics. The specific binding ability of aptamers to cancer-related markers and cancer cells ensured their high performance for early diagnosis of cancer. Meanwhile, the efficient targeting ability of aptamers to cancer cells and tissues provided a promising way to deliver imaging agents and drugs for cancer imaging and therapy. Furthermore, with the development of nanoscience and nanotechnology, the conjugation of aptamers with functional nanomaterials paved an exciting way for the fabrication of theranostic agents for different types of cancers, which might be a powerful tool for cancer treatment.

  11. Combined Radiation Therapy and Immune Checkpoint Blockade Therapy for Breast Cancer.

    Science.gov (United States)

    Hu, Zishuo I; Ho, Alice Y; McArthur, Heather L

    2017-09-01

    Treatment with checkpoint inhibitors has shown durable responses in a number of solid tumors, including melanoma, lung, and renal cell carcinoma. However, most breast cancers are resistant to monotherapy with checkpoint inhibitors. Radiation therapy (RT) has been shown to have a number of immunostimulatory effects, including priming the immune system, recruiting immune cells to the tumor environment, and altering the immunosuppressive effects of the tumor microenvironment. RT therefore represents a promising adjuvant therapy to checkpoint blockade in breast cancer. We review the data from the checkpoint blockade studies on breast cancer reported to date, the mechanisms by which RT potentiates immune responses, the preclinical and clinical data of checkpoint blockade and RT combinations, and the landscape of current clinical trials of RT and immune checkpoint inhibitor combinations in breast cancer. Clinical trials with checkpoint blockade therapy have demonstrated response rates of up to 19% in breast cancer, and many of the responses are durable. Preclinical data indicate that RT combined with checkpoint inhibition synergizes not only to enhance antitumor efficacy but also to induce responses outside of the radiation field. Thus multiple clinical trials are currently investigating the combination of checkpoint inhibition with RT. The use of combination strategies that incorporate chemotherapy and/or local strategies such as RT may be needed to augment responses to immune therapy in breast cancer. Preclinical and clinical results show that RT in combination with checkpoint blockade may be a promising therapeutic option in breast cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Targeted Gene Therapy for Breast Cancer

    Science.gov (United States)

    2005-06-01

    vein endothelial cells (HUVEC) cortisone , human FGF-fl, VEGF, ascorbic acid, heparin, were obtained from Dr Francoise Booyse (The University human EGF...cell mice resulted in a decrease in proliferative and metastatic lung cancer. Cancer Res. 2002;62:7124-7129. indices, further suggesting the feasibility

  13. New Approaches for Prostate Cancer Combination Therapy

    Science.gov (United States)

    2009-04-01

    In prostate cancer PDEF is involved in regulating NFkB -promoter 0 1 2 3 4 5 pCI PDEF fo ld in d u ct io n PC-3 LNCaP Figure 4. PDEF...Although current studies indicate that members of the GADD45 family appear infrequently mutated in cancer, reduced GADD45 expression due to gene and or

  14. MiR-21 is involved in radiation-induced bystander effects

    Science.gov (United States)

    Xu, Shuai; Ding, Nan; Pei, Hailong; Hu, Wentao; Wei, Wenjun; Zhang, Xurui; Zhou, Guangming; Wang, Jufang

    2014-01-01

    Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication. PMID:25483031

  15. Therapies targeting cancer stem cells: Current trends and future challenges

    Institute of Scientific and Technical Information of China (English)

    Denisa; L; Dragu; Laura; G; Necula; Coralia; Bleotu; Carmen; C; Diaconu; Mihaela; Chivu-Economescu

    2015-01-01

    Traditional therapies against cancer, chemo- and radiotherapy, have multiple limitations that lead to treatment failure and cancer recurrence. These limitations are related to systemic and local toxicity, while treatment failure and cancer relapse are due to drug resistance and self-renewal, properties of a small population of tumor cells called cancer stem cells(CSCs). These cells are involved in cancer initiation, maintenance, metastasis and recurrence. Therefore, in order to develop efficient treatments that can induce a longlasting clinical response preventing tumor relapse it is important to develop drugs that can specifically target and eliminate CSCs. Recent identification of surface markers and understanding of molecular feature associated with CSC phenotype helped with the design of effective treatments. In this review we discuss targeting surface biomarkers, signaling pathways that regulate CSCs self-renewal and differentiation, drug-efflux pumps involved in apoptosis resistance, microenvironmental signals that sustain CSCs growth, manipulation of mi RNA expression, and induction of CSCs apoptosis and differentiation, with specific aim to hamper CSCs regeneration and cancer relapse. Some of these agents are under evaluation in preclinical and clinical studies, most of them for using in combination with traditional therapies. The combined therapy using conventional anticancer drugs with CSCs-targeting agents, may offer a promising strategy for management and eradication of different types of cancers.

  16. Photodynamic therapy for chest wall recurrence from breast cancer.

    Science.gov (United States)

    Allison, R R; Sibata, C; Mang, T S; Bagnato, V S; Downie, G H; Hu, X H; Cuenca, R

    2004-09-01

    Breast cancer is common with over 230,000 new cases diagnosed each year in North America alone. While great strides have been made to achieve excellent cancer control and survival, a significant minority of patients fail locally. While initial salvage to regain disease control is of the utmost importance, it is not universally successful. This leads to a therapeutic quagmire. Additional surgery, radiation and chemo-hormonal therapy are possible, but they are usually highly morbid with low success rates. Photodynamic therapy appears to be an underutilized salvage modality for this unfortunate patient population. This report analyzes and reviews the role of photodynamic therapy for patients with chest wall re-recurrence from breast cancer.

  17. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Science.gov (United States)

    Liu, Yang; Yuan, Hsiangkuo; Fales, Andrew; Register, Janna; Vo-Dinh, Tuan

    2015-08-01

    Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS) exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET), as well as nanoprobes for photoacoustic tomography (PAT), two-photon photoluminescence (TPL) and surface-enhanced Raman spectroscopy (SERS). Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  18. Multifunctional Gold Nanostars for Molecular Imaging and Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yang eLiu

    2015-08-01

    Full Text Available Plasmonics-active gold nanoparticles offer excellent potential in molecular imaging and cancer therapy. Among them, gold nanostars (AuNS exhibit cross-platform flexibility as multimodal contrast agents for macroscopic X-ray computer tomography (CT, magnetic resonance imaging (MRI, positron emission tomography (PET, as well as nanoprobes for photoacoustic tomography (PAT, two-photon photoluminescence (TPL and surface-enhanced Raman spectroscopy (SERS. Their surfactant-free surface enables versatile functionalization to enhance cancer targeting, and allow triggered drug release. AuNS can also be used as an efficient platform for drug carrying, photothermal therapy, and photodynamic therapy. This review paper presents the latest progress regarding AuNS as a promising nanoplatform for cancer nanotheranostics. Future research directions with AuNS for biomedical applications will also be discussed.

  19. Nanoparticulate carriers: an emerging tool for breast cancer therapy.

    Science.gov (United States)

    Tharkar, Priyanka; Madani, Asad Ullah; Lasham, Annette; Shelling, Andrew N; Al-Kassas, Raida

    2015-02-01

    Breast cancer is a leading cause of death for women in the world. Cancer has the potential to spread to different organs around the body, and form metastases that can even develop after surgical removal of the primary tumour. Nanotechnology offers new promising strategies for the treatment of breast cancer, and has emerged as a powerful tool for fighting cancer. Nanoparticles can be fabricated to perform more than one task simultaneously, and can have a number of roles, such as acting as a therapeutic agent, drug delivery vehicle and/or tumour imaging agent. This review will focus on various forms of nanoparticles serving as potential agents for cancer therapeutics, illustrating their use in breast cancer therapies. This article also highlights the properties, current progress in the design and engineering of nanoparticles.

  20. Targeting SR-BI for cancer diagnostics, imaging and therapy

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    Maneesha Amrita Rajora

    2016-09-01

    Full Text Available Scavenger receptor class B type I (SR-BI plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumours and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents.

  1. MiR-21 simultaneously regulates ERK1 signaling in HSC activation and hepatocyte EMT in hepatic fibrosis.

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    Juan Zhao

    Full Text Available BACKGROUND: MicroRNA-21 (miR-21 plays an important role in the pathogenesis and progression of liver fibrosis. Here, we determined the serum and hepatic content of miR-21 in patients with liver cirrhosis and rats with dimethylnitrosamine-induced hepatic cirrhosis and examined the effects of miR-21 on SPRY2 and HNF4α in modulating ERK1 signaling in hepatic stellate cells (HSCs and epithelial-mesenchymal transition (EMT of hepatocytes. METHODS: Quantitative RT-PCR was used to determine miR-21 and the expression of SPRY2, HNF4α and other genes. Immunoblotting assay was carried out to examine the expression of relevant proteins. Luciferase reporter assay was performed to assess the effects of miR-21 on its predicted target genes SPRY2 and HNF4α. Primary HSCs and hepatocytes were treated with miR-21 mimics/inhibitors or appropriate adenoviral vectors to examine the relation between miR-21 and SPRY2 or HNF4α. RESULTS: The serum and hepatic content of miR-21 was significantly higher in cirrhotic patients and rats. SPRY2 and HNF4α mRNA levels were markedly lower in the cirrhotic liver. MiR-21 overexpression was associated with enhanced ERK1 signaling and EMT in liver fibrosis. Luciferase assay revealed suppressed SPRY2 and HNF4α expression by miR-21. Ectopic miR-21 stimulated ERK1 signaling in HSCs and induced hepatocyte EMT by targeting SPRY2 or HNF4α. Downregulating miR-21 suppressed ERK1 signaling, inhibited HSC activation, and blocked EMT in TGFβ1-treated hepatocytes. CONCLUSIONS: MiR-21 modulates ERK1 signaling and EMT in liver fibrosis by regulating SPRY2 and HNF4α expression. MiR-21 may serve as a potentially biomarker as well as intervention target for hepatic cirrhosis.

  2. Individualized therapies in colorectal cancer: KRAS as a marker for response to EGFR-targeted therapy

    Directory of Open Access Journals (Sweden)

    Li Kuiyuan

    2009-04-01

    Full Text Available Abstract Individualized therapies that are tailored to a patient's genetic composition will be of tremendous value for treatment of cancer. Recently, Kirsten ras (KRAS status has emerged as a predictor of response to epidermal growth factor receptor (EGFR targeted therapies. In this article, we will discuss targeted therapies for colorectal cancers (CRC based on EGFR signaling pathway and review published data about the potential usefulness of KRAS as a biological marker for response to these therapies. Results from relevant studies published since 2005 and unpublished results presented at national meetings were retrieved and summarized. These studies reflected response (or lack of response to EGFR-targeted therapies in patients with metastatic CRC as a function of KRAS status. It has become clear that patients with colorectal cancer whose tumor has an activating mutation in KRAS do not respond to monoclonal antibody therapies targeting EGFR. It should now become a standard practice that any patients being considered for EGFR targeted therapies have their tumors tested for KRAS status and only those with wild-type KRAS being offered such therapies.

  3. From cell signaling to cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Jin DING; Yun FENG; Hong-yang WANG

    2007-01-01

    Cancer has been seriously threatening the health and life of humans for a long period. Despite the intensive effort put into revealing the underlying mechanisms of cancer, the detailled machinery of carcinogenesis is still far from fully understood.Numerous studies have illustrated that cell signaling is extensively involved in tumor initiation, promotion and progression. Therefore, targeting the key mol-ecules in the oncogenic signaling pathway might be one of the most promising ways to conquer cancer. Some targeted drugs, such as imatinib mesylate (Gleevec),herceptin, gefitinib (Iressa), sorafenib (Nexavar) and sunitinib (Sutent), which evolve from monotarget drug into multitarget ones, have been developed with encouraging effects.

  4. Genitourinary cancers: molecular determinants for personalized therapies.

    Science.gov (United States)

    Mazzucchelli, Roberta; Gasparrini, Silvia; Galosi, Andrea B; Massari, Francesco; Raspollini, Maria Rosaria; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2016-09-26

    Recent insights and emerging strategies for individualized therapeutic approaches in patients with genitourinary (GU) cancers are based on patient's genomic and cancer's molecular profiles. This depends on the significant advances made in molecular biology technologies, such as next-generation sequencing and whole-exome sequencing. The rise of such novel techniques has grayly increased our knowledge on cancer cell biology and development, thus allowing to identify complex abnormalities at the genomic level. These findings have paved the way toward what is called precision medicine, thus providing healthcare from an individual perspective in patients with GU tumors.

  5. Anti-cancer effects of oncolytic viral therapy combined with photodynamic therapy in human pancreatic cancer cell lines.

    Science.gov (United States)

    Khaled, Yazan S; Wright, Kathleen; Melcher, Alan; Jayne, David

    2015-02-26

    Oncolytic viral therapy and photodynamic therapy are potential therapies for inoperable or advanced pancreatic cancer. Our aim was to investigate the anti-cancer killing effects of reovirus therapy combined with protoporphyrin IX (PpIX)-mediated photodynamic therapy on a variety of human pancreatic cancer cell lines. Pancreatic cancer cell lines (PsPC-1 and BXPC-3) and a non-cancer control cell line (HEK293) were infected with reovirus serotype 3 strain Dearing (T3D) at 0, 0·1, 1, and 10 plaque-forming units (PFU) per cell for 48 h. Cells were incubated with PpIX pro-drug 5-aminolevulinic acid (5-ALA) at 0, 1, 2, 3, and 4 mM for 4 h. Then, cells were photo-irradiated for 15 min with visible red light-emitting diodes with a light-fluence of 0·54 J/cm(2) of 653 nm (PpIX optimal excitation wavelength). The killing effects of reovirus combined with PpIX-mediated photodynamic therapy were analysed in methylthiazoltetrazolium (MTT) and trypan blue assays. The effect of adding reovirus after photodynamic therapy was also assessed. The statistical significance of the difference between groups was assessed with the two-tailed Student's t test. pphotodynamic therapy resulted in a significantly increased cytotoxic effect compared with reovirus monotherapy and photodynamic therapy (p=0·042) with 100% cell death observed across pancreatic cell lines with 10 PFU per cell combined with 1 and 2 mM 5-ALA. There was no difference in cytotoxicity observed between added reovirus before or after photodynamic therapy. To our knowledge, this is the first in-vitro study to combine reovirus oncolytic viral therapy with PpIX-mediated photodynamic therapy to treat pancreatic cancer. These results show a significant additive effect in cell killing and they provide initial evidence for a novel combined therapeutic intervention. National Institute for Health Research. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. FOREWORD: Conference on Advanced Metrology for Cancer Therapy 2011 Conference on Advanced Metrology for Cancer Therapy 2011

    Science.gov (United States)

    Ankerhold, Ulrike

    2012-10-01

    Although physical treatments play a central role in cancer therapy, SI-traceable metrology has only been established for some of them. Several forms of treatment currently used (particularly intensity-modulated radiation therapy (IMRT), hadron therapy, high-intensity therapeutic ultrasound (HITU) and brachytherapy) suffer from the limited metrological support, which restricts the success of these techniques. Recognizing this deficit, the European Union identified metrology for health as one of the first four Targeted Programmes in the framework of the European Metrology Research Programme (EMRP) running from 2008 to 2011. This programme included two EMRP projects addressing metrology for cancer therapy: project T2.J06 dealing with brachytherapy project T2.J07 dealing with external beam cancer therapy using ionizing radiation and high-intensity therapeutic ultrasound. Primary measurement standards applicable to modern treatment conditions were developed under both projects, together with measurement techniques which are meant as a basis for future protocols for dosimetry, treatment planning and monitoring. In order to provide a platform for the presentation of current developments in clinical measurement techniques for cancer therapy, together with the achievements of both projects, an international Conference on Advanced Metrology for Cancer Therapy (CAMCT) was held from 29 November to 1 December 2011 at the Physikalisch-Technische Bundesanstalt (PTB) in Braunschweig, Germany. The main sessions of the conference: Primary and secondary standards of absorbed dose to water for IMRT and brachytherapy, 3D dose distributions and treatment planning for IMRT and brachytherapy, Hadron therapy (protons and carbon ions), High-intensity therapeutic ultrasound (HITU), were geared to the main foci of the projects. Metrologists and medical physicists from countries all over the world attended the conference and made it into a forum for the exchange of information and expertise

  7. Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy.

    Science.gov (United States)

    Sharma, Aman; Khatun, Zamila; Shiras, Anjali

    2016-02-01

    Nanosized (30-150 nm) extracellular vesicles 'exosomes' are secreted by cells for intercellular communication during normal and pathological conditions. Exosomes carry biomacromolecules from cell-of-origin and, therefore, represent molecular bioprint of the cell. Tumor-derived exosomes or TDEx modulate tumor microenvironment by transfer of macromolecules locally as well as at distant metastatic sites. Due to their biological stability, TDEx are rich source of biomarkers in cancer patients. TDEx focused cancer diagnosis allows liquid biopsy-based tumor typing and may facilitate therapy response monitoring by developing novel exosomes diagnostics. Therefore, efficient and specific capturing of exosomes for subsequent amplification of the biomessages; for example, DNA, RNA, miRNA can reinvent cancer diagnosis. Here, in this review, we discuss advancements in exosomes isolation strategies, presence of exosomes biomarkers and importance of TDEx in gauging tumor heterogeneity for their potential use in cancer diagnosis, therapy.

  8. Photodynamic therapy of cancer — Challenges of multidrug resistance

    Directory of Open Access Journals (Sweden)

    Zheng Huang

    2015-01-01

    Full Text Available Photodynamic therapy (PDT of cancer is a two-step drug-device combination modality, which involves the topical or systemic administration of a photosensitizer followed by light illumination of cancer site. In the presence of oxygen molecules, the light illumination of photosensitizer (PS can lead to the generation of cytotoxic reactive oxygen species (ROS and consequently destroy cancer. Similar to many other anticancer therapies, PDT is also subject to intrinsic cancer resistance mediated by multidrug resistance (MDR mechanisms. This paper will review the recent progress in understanding the interaction between MDR transporters and PS uptake. The strategies that can be used in a clinical setting to overcome or bypass MDR will also be discussed.

  9. Baculoviruses as Vectors for Gene Therapy against Human Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Lindsay J. Stanbridge

    2003-01-01

    Full Text Available Current curative strategies for prostate cancer are restricted to the primary tumour, and the effect of treatments to control metastatic disease is not sustained. Therefore, the application of gene therapy to prostate cancer is an attractive alternative. Baculoviruses are highly restricted insect viruses, which can enter, but not replicate in mammalian cells. Baculoviruses can incorporate large amounts of extra genetic material, and will express transgenes in mammalian cells when under the control of a mammalian or strong viral promoter. Successful gene delivery has been achieved both in vitro and in vivo and into both dividing and nondividing cells, which is important since prostate cancers divide relatively slowly. In addition, the envelope protein gp64 is sufficiently mutable to allow targeted transduction of particular cell types. In this review, the advantages of using baculoviruses for prostate cancer gene therapy are explored, and the mechanisms of viral entry and transgene expression are described.

  10. Nanoshell bioconjugates for integrated imaging and therapy of cancer

    Science.gov (United States)

    Loo, Christopher H.; Lee, Min-Ho; Hirsch, Leon R.; West, Jennifer L.; Halas, Naomi J.; Drezek, Rebekah A.

    2004-06-01

    Currently, separate diagnostic and therapeutic modalities are required for the diagnosis and treatment of cancer. In many cases, the present standard of care requires invasive surgical procedures and/or other treatments associated with significant side effect profiles, high cost, and poor clinical outcome. A single technology with dual diagnostic/therapeutic capabilities would potentially yield significant savings in the time and cost associated with diagnosing and treating many cancers. In this paper, we discuss gold nanoshell bioconjugates and their role in the development of an integrated cancer imaging and therapy application. Nanoshells are a novel class of nanomaterials that have unique properties including continuous and broad wavelength tunability, far greater scattering and absorption coefficients, increased chemical stability, and improved biocompatibility. Here, we describe the development of an integrated cancer imaging and therapy application using near-infrared (NIR) gold nanoshell bioconjugates.

  11. Cancer patients' interest and preferences for music therapy.

    Science.gov (United States)

    Burns, Debra S; Sledge, Renata B; Fuller, Leigh Ann; Daggy, Joanne K; Monahan, Patrick O

    2005-01-01

    The reason for lack of routine integration of music therapy into healthcare may be that patients are not comfortable being involved in a music therapy intervention. Therefore, the goal of this study was to examine cancer patients' interest in and preferences for using 2 types of music therapy interventions, music-making and music listening. Sixty-five patients completed the Music Interest Survey in addition to standardized measures of coping, affect, anxiety, and fatigue. Results suggest adult cancer patients are interested in music therapy, especially music listening. Patient interest and preference were associated with negative affect, anxiety, age, perceived intervention-specific benefits, barriers, and self-efficacy. Findings highlight the need for a comprehensive assessment of patient needs and preferences prior to intervention.

  12. Effect of physical therapy on breast cancer related lymphedema

    DEFF Research Database (Denmark)

    Tambour, Mette; Tange, Berit; Christensen, Robin Daniel Kjersgaard

    2014-01-01

    BACKGROUND: Physical therapy treatment of patients with lymphedema includes treatment based on the principles of 'Complete Decongestive Therapy' (CDT). CDT consists of the following components; skin care, manual lymphatic drainage, bandaging and exercises. The scientific evidence regarding what...... type of treatment is most effective is sparse. The objective of this study is to investigate whether CDT is equally effective if it includes manual lymphatic drainage or not in the treatment of arm lymphedema among patients with breast cancer. METHODS/DESIGN: A randomized, single-blind, equivalence...... trial. A total of 160 breast cancer patients with arm lymphedema will be recruited from 3 hospitals and randomized into one of two treatment groups A: Complete Decongestive Therapy including manual drainage or B: Complete Decongestive Therapy without manual lymphatic drainage. The intervention period...

  13. Significance of Cancer Stem Cells in Anti-Cancer Therapies

    Science.gov (United States)

    Botelho, Mónica; Alves, Helena

    2017-01-01

    Stem cells are the focus of cutting edge research interest because of their competence both to self-renew and proliferate, and to differentiate into a variety of tissues, offering enticing prospects of growing replacement organs in vitro, among other possible therapeutic implications. It is conceivable that cancer stem cells share a number of biological hallmarks that are different from their normal-tissue counterparts and that these might be taken advantage of for therapeutic benefits. In this review we discuss the significance of cancer stem cells in diagnosis and prognosis of cancer as well as in the development of new strategies for anti-cancer drug design.

  14. Pharmacogenomics: Biomarker-Directed Therapy for Bladder Cancer.

    Science.gov (United States)

    Jones, Robert T; Felsenstein, Kenneth M; Theodorescu, Dan

    2016-02-01

    The clinical management of bladder cancer has seen little change over the last three decades and there is pressing need to identify more effective treatments for advanced disease. Low clinical use of neoadjuvant therapies stems from historical limitations in the ability to predict patients most likely to respond to combination chemotherapies. This article focuses on recent molecular and genetic studies, highlighting promising clinical trials and retrospective studies, and discusses emerging trials that use predictive biomarkers to match patients with therapies to which they are most likely to respond. The implementation of predictive genomic and molecular biomarkers will revolutionize urologic oncology and the clinical management of bladder cancer.

  15. Cancer gene therapy targeting angiogenesis: An updated review

    Institute of Scientific and Technical Information of China (English)

    Ching-Chiu Liu; Zan Shen; Hsiang-Fu Kung; Marie CM Lin

    2006-01-01

    Since the relationship between angiogenesis and tumor growth was established by Folkman in 1971,scientists have made efforts exploring the possibilities in treating cancer by targeting angiogenesis. Inhibition of angiogenesis growth factors and administration of angiogenesis inhibitors are the basics of antiangiogenesis therapy. Transfer of anti-angiogenesis genes has Received attention recently not only because of the advancement of recombinant vectors, but also because of the localized and sustained expression of therapeutic gene product inside the tumor after gene transfer. This review provides the up-to-date information about the strategies and the vectors studied in the field of anti-angiogenesis cancer gene therapy.

  16. Nucleic acid aptamers: an emerging frontier in cancer therapy.

    Science.gov (United States)

    Zhu, Guizhi; Ye, Mao; Donovan, Michael J; Song, Erqun; Zhao, Zilong; Tan, Weihong

    2012-11-04

    The last two decades have witnessed the development and application of nucleic acid aptamers in a variety of fields, including target analysis, disease therapy, and molecular and cellular engineering. The efficient and widely applicable aptamer selection, reproducible chemical synthesis and modification, generally impressive target binding selectivity and affinity, relatively rapid tissue penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal recognition elements for use as therapeutics or for in vivo delivery of therapeutics. In this feature article, we discuss the development and biomedical application of nucleic acid aptamers, with emphasis on cancer cell aptamer isolation, targeted cancer therapy, oncology biomarker identification and drug discovery.

  17. Third-line therapy for metastatic colorectal cancer

    DEFF Research Database (Denmark)

    Gundgaard, M.G.; Ehrnrooth, E.; Sørensen, Jens Benn

    2008-01-01

    , panitumumab. As a result, third-line treatment is now a necessary step in the optimal treatment of patients with metastatic colorectal cancer (MCRC). MATERIALS AND METHODS: We conducted a literature review of English language publications on third-line therapy for MCRC from January 2000 to April 2007. Data......OS of 16 months. With irinotecan and 5-FU, mOS around 8 months were reported and with cetuximab combined with irinotecan, the highest mOS was 9.8 months. CONCLUSION: Third-line therapy in advanced colorectal cancer may improve mOS for patients with MCRC. Therefore, randomized studies should be conducted...

  18. Anticopper therapy against cancer and diseases of inflammation and fibrosis.

    Science.gov (United States)

    Brewer, George J

    2005-08-15

    Anticopper drugs that have been developed to treat Wilson's disease, a disease of copper toxicity, include tetrathiomolybdate, zinc, penicillamine, and trientine. Lowering copper levels by a modest amount in non-Wilson's patients with tetrathiomolybdate inhibits angiogenesis, fibrosis and inflammation while avoiding clinical copper deficiency. Through this mechanism tetrathiomolybdate has proven effective in numerous animal models of cancer, retinopathy, fibrosis, and inflammation. Penicillamine has efficacy in rheumatoid arthritis and trientine has efficacy in diabetic neuropathy and diabetic heart disease. If clinical studies support the animal work, anticopper therapy holds promise for therapy of cancer, fibrotic disease and inflammatory and autoimmune diseases.

  19. Grand challenges in bioengineered nanorobotics for cancer therapy.

    Science.gov (United States)

    Lenaghan, Scott C; Wang, Yongzhong; Xi, Ning; Fukuda, Toshio; Tarn, Tzyhjong; Hamel, William R; Zhang, Mingjun

    2013-03-01

    One of the grand challenges currently facing engineering, life sciences, and medicine is the development of fully functional nanorobots capable of sensing, decision making, and actuation. These nanorobots may aid in cancer therapy, site-specific drug delivery, circulating diagnostics, advanced surgery, and tissue repair. In this paper, we will discuss, from a bioinspired perspective, the challenges currently facing nanorobotics, including core design, propulsion and power generation, sensing, actuation, control, decision making, and system integration. Using strategies inspired from microorganisms, we will discuss a potential bioengineered nanorobot for cancer therapy.

  20. Tyrosine kinase blockers: new hope for successful cancer therapy.

    Science.gov (United States)

    Pytel, Dariusz; Sliwinski, Tomasz; Poplawski, Tomasz; Ferriola, Deborah; Majsterek, Ireneusz

    2009-01-01

    Tyrosine kinases (TKs) are attractive targets for cancer therapy, as quite often their abnormal signaling has been linked with tumor development and growth. Constitutive activated TKs stimulate multiple signaling pathways responsible for DNA repair, apoptosis, and cell proliferation. During the last few years, thorough analysis of the mechanism underlying tyrosine kinase's activity led to novel cancer therapy using TKs blockers. These drugs are remarkably effective in the treatment of various human tumors including head and neck, gastric, prostate and breast cancer and leukemias. The most successful example of kinase blockers is Imatinib (Imatinib mesylate, Gleevec, STI571), the inhibitor of Bcr/Abl oncoprotein, which has become a first-line therapy for chronic myelogenous leukemia. The introduction of STI571 for the treatment of leukemia in clinical oncology has had a dramatic impact on how this disease is currently managed. Others kinase inhibitors used recently in cancer therapy include Dasatinib (BMS-354825) specific for ABL non-receptor cytoplasmic kinase, Gefitinib (Iressa), Erlotinib (OSI-774, Tarceva) and Sunitinib (SU 11248, Sutent) specific for VEGF receptor kinase, AMN107 (Nilotinib) and INNO-406 (NS-187) specific for c-KIT kinase. The following TK blockers for treatment of various human tumors are in clinical development: Lapatinib (Lapatinib ditosylate, Tykerb, GW-572016), Canertinib (CI-1033), Zactima (ZD6474), Vatalanib (PTK787/ZK 222584), Sorafenib (Bay 43-9006, Nexavar), and Leflunomide (SU101, Arava). Herein, we discuss the chemistry, biological activity and clinical potential of new drugs with tyrosine kinase blockers for cancer treatment.

  1. Bacteria in cancer therapy: a novel experimental strategy.

    Science.gov (United States)

    Patyar, S; Joshi, R; Byrav, D S Prasad; Prakash, A; Medhi, B; Das, B K

    2010-03-23

    Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment.

  2. Bacteria in cancer therapy: a novel experimental strategy

    Directory of Open Access Journals (Sweden)

    Medhi B

    2010-03-01

    Full Text Available Abstract Resistance to conventional anticancer therapies in patients with advanced solid tumors has prompted the need of alternative cancer therapies. Moreover, the success of novel cancer therapies depends on their selectivity for cancer cells with limited toxicity to normal tissues. Several decades after Coley's work a variety of natural and genetically modified non-pathogenic bacterial species are being explored as potential antitumor agents, either to provide direct tumoricidal effects or to deliver tumoricidal molecules. Live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumors and inhibiting their growth. Due to their selectivity for tumor tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins too have emerged as promising cancer treatment strategy. The most potential and promising strategy is bacteria based gene-directed enzyme prodrug therapy. Although it has shown successful results in vivo yet further investigation about the targeting mechanisms of the bacteria are required to make it a complete therapeutic approach in cancer treatment.

  3. Potentials of interferon therapy in the treatment of pancreatic cancer.

    Science.gov (United States)

    Booy, Stephanie; Hofland, Leo; van Eijck, Casper

    2015-05-01

    Pancreatic cancer is a highly aggressive malignancy with limited treatment options. To improve survival for patients with pancreatic cancer, research has focused on other treatment modalities like adding biological modulators such as type-I interferons (IFNs). Type I IFNs (ie, IFN-α/IFN-β) have antiproliferative, antiviral, and immunoregulatory activities. Furthermore, they are able to induce apoptosis, exert cell cycle blocking, and sensitize tumor cells for chemo- and radiotherapy. A few years ago in vitro, in vivo, and several clinical trials have been described regarding adjuvant IFN-α therapy in the treatment of pancreatic cancer. Some studies reported a remarkable increase in the 2- and 5-year survival. Unfortunately, the only randomized clinical trial did not show a significant increase in overall survival, although the increased median survival implicated that some patients in the experimental group benefited from the adjuvant IFN-α therapy. Furthermore, encouraging in vitro and in vivo data points to a possible role for adjuvant IFN therapy. However, up till now, the use of IFNs in the treatment of pancreatic cancer remains controversial. This review, therefore, aims to describe, based on the available data, whether there is a distinct role for IFN therapy in the treatment of pancreatic cancer.

  4. Gene Therapy For Oral Cancer - Journey To A New Horizon

    Directory of Open Access Journals (Sweden)

    Arpita Kabiraj

    2012-01-01

    Full Text Available The past two decades have been golden years for the genetics of cancer. It has become clear through the work of countless laboratory groups that both inherited and sporadic cancers arise through defects or misregulations of their genomes. Despite advances in surgery, radiotherapy, and chemotherapy, the survival of patients with oral squamous cell carcinoma have not significantly improved over the past several decades. Thus, an entirely new approach to its treatment utilizing genetic aids has evolved. The majority of the head and neck cancers comprise of Oral squamous cell carcinoma (OSCC. The traditional therapies for the management of cancer and their various modifications including surgery, radiotherapy and chemotherapy have not refined the survival rates yet. Gene therapy represents a fundamentally new mode for the effective treatment of a disease. It essentially consists of the introduction of the genetic material into the target cells of an individual without producing toxic effects on surrounding tissues. The essence of gene therapy is attributed to the replacement of the defective gene with a normal gene, thus restoring the lost function in the patient’s body. The aim of this review is to analyze the different modalities of gene therapy currently used to manage precancerous and cancerous lesions of the oral cavity.

  5. Salmonella-mediated cancer therapy: Roles and potential

    Energy Technology Data Exchange (ETDEWEB)

    Nguyen, Vu Hong [Dept. of Experimental TherapeuticsBeckman Research Institute of City of Hope, Duarte (United States); Min, Jung Joon [Dept. of Nuclear MedicineChonnam National University Medical School, Gwangju (Korea, Republic of)

    2017-06-15

    The use of bacteria for cancer therapy, which was proposed many years ago, was not recognized as a potential therapeutic strategy until recently. Technological advances and updated knowledge have enabled the genetic engineering of bacteria for their safe and effective application in the treatment of cancer. The efficacy of radiotherapy depends mainly on tissue oxygen levels, and low oxygen concentrations in necrotic and hypoxic regions are a common cause of treatment failure. In addition, the distribution of a drug is important for the therapeutic effect of chemotherapy, and the poor vasculature in tumors impairs drug delivery, limiting the efficacy of a drug, especially in necrotic and hypoxic regions. Bacteria-mediated cancer therapy (BMCT) relies on facultative anaerobes that can survive in well or poorly oxygenated regions, and it therefore improves the therapeutic efficacy drug distribution throughout the tumor mass. Since the mid-1990s, the number of published bacterial therapy papers has increased rapidly, with a doubling time of 2.5 years in which the use of Salmonella increased significantly. BMCT is being reevaluated to overcome some of the drawbacks of conventional therapies. This review focuses on Salmonella-mediated cancer therapy as the most widely used type of BMCT.{sub 2}.

  6. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  7. Redefining Adjuvant Therapy for Colon Cancer

    Science.gov (United States)

    In this trial, patients with resected stage III colon cancer are being randomly assigned to receive FOLFOX chemotherapy for either 3 or 6 months and to take either a pill called celecoxib or a matching placebo pill for 3 years.

  8. Intrahepatic therapy for liver-dominant metastatic colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Kerlijne; De; Groote; Hans; Prenen

    2015-01-01

    In patients with metastatic colorectal cancer, the liver is the most common site of metastatic disease. In patients with liver-dominant disease, consideration needs to be given to locoregional treatments such as hepatic arterial infusion chemotherapy, transarterial chemoembolisation and selective internal radiation therapy because hepatic metastases are a major cause of liver failure especially in chemorefractory disease. In this review we provide insights on the published literature for locoregional treatment of liver metastases in metastatic colorectal cancer.

  9. Mesenchymal Stem Cell Based Therapy for Prostate Cancer

    Science.gov (United States)

    2015-11-01

    Prostate: From Birth to Death and Potential Applications in Between. Prostate Cancer Foundation Tumor Microenvironment/ Immunology Working Group...Award Number: W81XWH-13-1-0304 TITLE: Mesenchymal Stem Cell-Based Therapy for Prostate Cancer PRINCIPAL INVESTIGATOR: John Isaacs CONTRACTING...Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

  10. Mobile genetic elements and cancer. From mutations to gene therapy.

    Science.gov (United States)

    Kozeretska, I A; Demydov, S V; Ostapchenko, L I

    2011-12-01

    In the present review, an association between cancer and the activity of the non-LTR retroelements L1, Alu, and SVA, as well as endogenous retroviruses, in the human genome, is analyzed. Data suggesting that transposons have been involved in embryogenesis and malignization processes, are presented. Events that lead to the activation of mobile elements in mammalian somatic cells, as well as the use of mobile elements in genetic screening and cancer gene therapy, are reviewed.

  11. Aberrant upregulation of miR-21 in placental tissues of macrosomia.

    Science.gov (United States)

    Jiang, H; Wu, W; Zhang, M; Li, J; Peng, Y; Miao, T-T; Zhu, H; Xu, G

    2014-09-01

    With China's rapid economic growth in the past 3 decades, an increase in rate of macrosomia has been reported in China. Fetal growth is a result of multiple factors including genetic potential for growth, maternal nutrition, maternal metabolism, endocrine factors and placental perfusion and function. However, the detailed mechanism of how macrosomia happened remains poorly known. Recent studies showed that the expression of a number of microRNAs (miRNAs) in placentas is involved in fetal growth. We hypothesized that aberrant expression of microRNA-21 (miR-21) and microRNA-16 (miR-16) in placenta is associated with macrosomia. Using quantitative real time PCR, we analyzed the expression level of miR-21 and miR-16 in terminal placentas of macrosomia pregnancies (n=35) and normal controls (n=35). Potential target genes of miRNA were predicted using TargetScan, miRanda and PicTar. Target genes were mapped to KEGG pathways using KEGG Mapper with an in-house Perl script with KEGG Gene IDs. MiR-21 showed significant up-regulation in macrosomia (P=0.037). After controlling the potential confounders, multivariable logistic regression analysis suggested the risk of macrosomia increased, multivariable adjusted ORs of macrosomia for those in the highest tertile was 3.931 (95%CI: 1.049-14.736) compared with those in the lowest tertile in terms of miR-21 level. The target genes of miR-21 were involved in eight possible signaling pathways. They were pathways in P53 signaling pathway, MAPK signaling pathway, HIF-1 signaling pathway, TGF-beta signaling pathway and PI3K-Akt signaling pathway (Pmacrosomia. Our results indicate that the expression level of miR-21 in placental tissue may be involved in the development of macrosomia.

  12. Lymphedema following cancer therapy in Slovenia: a frequently overlooked condition?

    OpenAIRE

    Rucigaj, Tanja Planinsek; Leskovec, Nada Kecelj; Zunter*, Vesna Tlaker

    2010-01-01

    Introduction Secondary lymphedema following cancer therapy is a frequent, often painful, quality of life disturbing condition, reducing the patients’ mobility and predisposing them to complications, e.g. infections and malignancies. The critical aspect of lymphedema therapy is to start as soon as possible to prevent the irreversible tissue damage. Patients and methods We performed a retrospective study of patients with lymphedema, treated at the Department of Dermatovenereology, University Me...

  13. Ultrasound for molecular imaging and therapy in cancer

    OpenAIRE

    Kaneko, Osamu F; Willmann, Jürgen K.

    2012-01-01

    Over the past decade, molecularly-targeted contrast enhanced ultrasound (ultrasound molecular imaging) has attracted significant attention in preclinical research of cancer diagnostic and therapy. Potential applications for ultrasound molecular imaging run the gamut from early detection and characterization of malignancies to monitoring treatment responses and guiding therapies. There may also be a role for ultrasound contrast agents for improved delivery of chemotherapeutic drugs and gene th...

  14. Lymphedema following cancer therapy in Slovenia: a frequently overlooked condition?:

    OpenAIRE

    Rucigaj, Tanja Planinsek; Leskovec, Nada Kecelj; Zunter*, Vesna Tlaker

    2010-01-01

    Introduction Secondary lymphedema following cancer therapy is a frequent, often painful, quality of life disturbing condition, reducing the patients’ mobility and predisposing them to complications, e.g. infections and malignancies. The critical aspect of lymphedema therapy is to start as soon as possible to prevent the irreversible tissue damage. Patients and methods We performed a retrospective study of patients with lymphedema, treated at the Department of Dermatovenereology, University Me...

  15. Advances in biodegradable nanomaterials for photothermal therapy of cancer

    OpenAIRE

    He, Chao-Feng; Wang, Shun-Hao; Yu, Ying-Jie; Shen, He-Yun; Zhao, Yan; Gao, Hui-Ling; Wang, Hai; Li, Lin-Lin; Liu, Hui-Yu

    2016-01-01

    Photothermal cancer therapy is an alternative to chemotherapy, radiotherapy, and surgery. With the development of nanophotothermal agents, this therapy holds immense potential in clinical translation. However, the toxicity issues derived from the fact that nanomaterials are trapped and retained in the reticuloendothelial systems limit their biomedical application. Developing biodegradable photothermal agents is the most practical route to address these concerns. In addition to the physicochem...

  16. Targeted Radiation Therapy for Cancer Initiative

    Science.gov (United States)

    2012-09-01

    technique for treating left-sided breast cancer, which allows sparing of the heart. The Calypso system provides a previously unavailable level of...from both centers. Task 6. Post-prostatectomy Daily Target Guided Radiotherapy Using Real-Time, State-of-the-Art Motion Tracking with the Calypso...the skin surface to track breathing motion during a breath-hold technique for left-sided breast cancer treatment. Analysis would reveal the

  17. Breast cancer and possible mechanisms of therapy resistance

    Directory of Open Access Journals (Sweden)

    Ana-Maria Florea

    2013-03-01

    Full Text Available Breast cancer represents one of the most common cancers in women and is a major life threatening illness found all over the world. Therapy approaches include irradiation and surgery, with chemotherapy considered an important strategy to treat breast cancer. Platinum based anticancer drugs, such as cisplatin (cis-di-amino-dichloride-platin, CDDP, carboplatin, orthoplatin, etc., have been successfully used in breast cancer therapy because they activate multiple mechanisms to induce apoptosis in tumor cells. Nevertheless, during chemotherapy, drug resistance frequently develops; this impairs the successful treatment of breast cancer and often leads to patients’ decease. While combinations of anticancer drugs used in chemotherapy regimens reduced the occurrence of drug resistance (e.g. doxorubicin + docetaxel, doxorubicin + cyclophosphamide, docetaxel + herceptin + carboplatin the molecular mechanism of those effects are not completely understood. Here we review possible mechanisms related to breast cancer treatment and resistance to current therapies as well as possible new therapeutic targets (e.g. calcium signaling which could be used in the future.

  18. Improvement of different vaccine delivery systems for cancer therapy

    Directory of Open Access Journals (Sweden)

    Safaiyan Shima

    2011-01-01

    Full Text Available Abstract Cancer vaccines are the promising tools in the hands of the clinical oncologist. Many tumor-associated antigens are excellent targets for immune therapy and vaccine design. Optimally designed cancer vaccines should combine the best tumor antigens with the most effective immunotherapy agents and/or delivery strategies to achieve positive clinical results. Various vaccine delivery systems such as different routes of immunization and physical/chemical delivery methods have been used in cancer therapy with the goal to induce immunity against tumor-associated antigens. Two basic delivery approaches including physical delivery to achieve higher levels of antigen production and formulation with microparticles to target antigen-presenting cells (APCs have demonstrated to be effective in animal models. New developments in vaccine delivery systems will improve the efficiency of clinical trials in the near future. Among them, nanoparticles (NPs such as dendrimers, polymeric NPs, metallic NPs, magnetic NPs and quantum dots have emerged as effective vaccine adjuvants for infectious diseases and cancer therapy. Furthermore, cell-penetrating peptides (CPP have been known as attractive carrier having applications in drug delivery, gene transfer and DNA vaccination. This review will focus on the utilization of different vaccine delivery systems for prevention or treatment of cancer. We will discuss their clinical applications and the future prospects for cancer vaccine development.

  19. Kaempferol inhibits vascular smooth muscle cell migration by modulating BMP-mediated miR-21 expression.

    Science.gov (United States)

    Kim, Kwangho; Kim, Sunghwan; Moh, Sang Hyun; Kang, Hara

    2015-09-01

    Bioflavonoids are known to induce cardioprotective effects by inhibiting vascular smooth muscle cell (VSMC) proliferation and migration. Kaempferol has been shown to inhibit VSMC proliferation. However, little is known about the effect of kaempferol on VSMC migration and the underlying molecular mechanisms. Our studies provide the first evidence that kaempferol inhibits VSMC migration by modulating the BMP4 signaling pathway and microRNA expression levels. Kaempferol activates the BMP signaling pathway, induces miR-21 expression and downregulates DOCK4, 5, and 7, leading to inhibition of cell migration. Moreover, kaempferol antagonizes the PDGF-mediated pro-migratory effect. Therefore, our study uncovers a novel regulatory mechanism of VSMC migration by kaempferol and suggests that miRNA modulation by kaempferol is a potential therapy for cardiovascular diseases.

  20. Bacterial Toxins for Oncoleaking Suicidal Cancer Gene Therapy.

    Science.gov (United States)

    Pahle, Jessica; Walther, Wolfgang

    For suicide gene therapy, initially prodrug-converting enzymes (gene-directed enzyme-producing therapy, GDEPT) were employed to intracellularly metabolize non-toxic prodrugs into toxic compounds, leading to the effective suicidal killing of the transfected tumor cells. In this regard, the suicide gene therapy has demonstrated its potential for efficient tumor eradication. Numerous suicide genes of viral or bacterial origin were isolated, characterized, and extensively tested in vitro and in vivo, demonstrating their therapeutic potential even in clinical trials to treat cancers of different entities. Apart from this, growing efforts are made to generate more targeted and more effective suicide gene systems for cancer gene therapy. In this regard, bacterial toxins are an alternative to the classical GDEPT strategy, which add to the broad spectrum of different suicide approaches. In this context, lytic bacterial toxins, such as streptolysin O (SLO) or the claudin-targeted Clostridium perfringens enterotoxin (CPE) represent attractive new types of suicide oncoleaking genes. They permit as pore-forming proteins rapid and also selective toxicity toward a broad range of cancers. In this chapter, we describe the generation and use of SLO as well as of CPE-based gene therapies for the effective tumor cell eradication as promising, novel suicide gene approach particularly for treatment of therapy refractory tumors.

  1. Cancer-Associated Fibroblasts: Perspectives in Cancer Therapy

    NARCIS (Netherlands)

    Prakash, Jai

    2016-01-01

    The interplay between cancer cells and stromal cells is increasingly recognized as a main driver of tumor progression and metastasis. This Forum article highlights the role of cancer-associated stromal fibroblasts (CAFs) in tumorigenesis and discusses the potential for developing specific stromal ca

  2. Cancer-Associated Fibroblasts: Perspectives in Cancer Therapy

    NARCIS (Netherlands)

    Prakash, Jai

    2016-01-01

    The interplay between cancer cells and stromal cells is increasingly recognized as a main driver of tumor progression and metastasis. This Forum article highlights the role of cancer-associated stromal fibroblasts (CAFs) in tumorigenesis and discusses the potential for developing specific stromal ca

  3. Cancer-Associated Fibroblasts: Perspectives in Cancer Therapy

    NARCIS (Netherlands)

    Prakash, Jai

    2016-01-01

    The interplay between cancer cells and stromal cells is increasingly recognized as a main driver of tumor progression and metastasis. This Forum article highlights the role of cancer-associated stromal fibroblasts (CAFs) in tumorigenesis and discusses the potential for developing specific stromal

  4. Successful treatment of accessory breast cancer with endocrine therapy().

    Science.gov (United States)

    Wang, Chun-Xi; Guo, Shu-Li; Han, Li-Na

    Accessory breast cancers in males are extremely rare, and only a few cases have been reported in the literature. In this paper, an 87-year-old male patient was diagnosed with an accessory breast cancer by means of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography-computed tomography (PET-CT), and immunohistochemistry based on needle biopsy, and has undergone successful resection and postoperative adjuvant endocrine therapy. He was the oldest male patient with an accessory breast cancer reported in the Chinese Hospital Knowledge Database and PubMed literature from 1975 to 2015.

  5. To Your Health: NLM update transcript - First gene therapy cancer treatment

    Science.gov (United States)

    ... Your Health: NLM update Transcript First gene therapy cancer treatment : 09/11/2017 To use the sharing features ... up on weekly topics. The first gene therapy treatment for cancer recently was approved by the U.S. Food and ...

  6. The cancer journey: bridging art therapy and museum education.

    Science.gov (United States)

    Deane, K; Carman, M; Fitch, M

    2000-01-01

    This paper describes the application of art therapy in assisting cancer patients to visually express their cancer experience on several levels--physically, psychosocially, and spiritually. The art therapy/museum education program was developed in 1996 at the McMichael Canadian Art Collection in partnership with Toronto-Sunnybrook Regional Cancer Centre-Bayview Support Network. To date, the program has run for three rounds with 16 sessions in each round. The facilitator for all three rounds was a trained art therapist. The program provided an unique opportunity for an arts institution to serve the community at large by offering an artistic outlet in a peaceful, rural setting in contrast to a sterile hospital environment. The specific goals of the program and the general therapeutic benefits of art therapy are described. In addition, the effectiveness of an existential/phenomenological approach in not only serving the cancer population, but also bridging the two diverse disciplines--art therapy and museum education--is explored. It is suggested that an existential therapeutic approach promotes the confrontation and acceptance of death that is necessary in order to lead a more meaningful life. Moreover, a phenomenological approach promotes the act of "seeing" as an essential ingredient in gaining objectivity and bringing unconscious thoughts into consciousness. The importance of social and emotional support in the way of art therapy in addition to medical care is emphasized. Through art therapy, cancer patients are encouraged to discover ways to face pain and misfortune and be creative in their "art of living."

  7. Advanced Treatment Planning in Cancer Thermal Therapies

    Institute of Scientific and Technical Information of China (English)

    Theodoros SAMARAS; Esra NEUFELD; Niels KUSTER

    2016-01-01

    CEM43 thermal dose is a very common concept in thermal oncology. Thermal dose is the maximum amount of energy that can be transmitted during hyperthermia therapy conducted on temperature-sensitive tissue. Thermal dose is also the maximum value of local energy accumulation in human bodies, which can lead to tissue injury and pain. Thermal dose can also decrease the ifnishing temperature and reduce the energy to the tolerable range. There are two functions of the individualized hyperthermia treatment plan: it determines the setting and location that can realize the best tumor hyperthermia therapy; at the same time, it can decrease the effect of hyperthermia therapy on healthy tissues. There are four steps in the treatment plan of hyperthermia therapy for tumors: the ifrst step is to establish a three dimensional human body model and its corresponding an atomical structure that can be used in numerical algorithmvia medical imaging resources; the second step is to determine the volume of the electromagnetic energy accumulation. Based on the peculiarity of frequency and materials, even full-wave electromagnetic wave or quasi-static technique can be used to determine the tissue distribution. Evaluation of the therapy can be conducted based on thermal dose and the corresponding tissue damage model; the third step is to use Arrhenius model to provide direct evaluation of tissues in the thermal ablation zone, solidiifcation zone, as well as the necrotic area; the last step is the optimization of the treatment plan.

  8. Mitochondrial Peroxiredoxin III is a Potential Target for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Byoung Doo Rhee

    2011-10-01

    Full Text Available Mitochondria are involved either directly or indirectly in oncogenesis and the alteration of metabolism in cancer cells. Cancer cells contain large numbers of abnormal mitochondria and produce large amounts of reactive oxygen species (ROS. Oxidative stress is caused by an imbalance between the production of ROS and the antioxidant capacity of the cell. Several cancer therapies, such as chemotherapeutic drugs and radiation, disrupt mitochondrial homeostasis and release cytochrome c, leading to apoptosome formation, which activates the intrinsic pathway. This is modulated by the extent of mitochondrial oxidative stress. The peroxiredoxin (Prx system is a cellular defense system against oxidative stress, and mitochondria in cancer cells are known to contain high levels of Prx III. Here, we review accumulating evidence suggesting that mitochondrial oxidative stress is involved in cancer, and discuss the role of the mitochondrial Prx III antioxidant system as a potential target for cancer therapy. We hope that this review will provide the basis for new strategic approaches in the development of effective cancer treatments.

  9. Castration-resistant prostate cancer: systemic therapy in 2012

    Directory of Open Access Journals (Sweden)

    Fernando C. Maluf

    2012-01-01

    Full Text Available Prostate cancer is the most common non-cutaneous neoplasm in the male population worldwide. It is typically diagnosed in its early stages, and the disease exhibits a relatively indolent course in most patients. Despite the curability of localized disease with prostatectomy and radiation therapy, some patients develop metastatic disease and die. Although androgen deprivation is present in the majority of patients with metastatic prostate cancer, a state of androgen resistance eventually develops. Castration-resistant prostate cancer, defined when there is progression of disease despite low levels of testosterone, requires specialized care, and improved communication between medical and urologic oncologists has been identified as a key component in delivering effective therapy. Despite being considered a chemoresistant tumor in the past, the use of a prostate-specific antigen has paved the way for a new generation of trials for castration-resistant prostate cancer. Docetaxel is a life-prolonging chemotherapy that has been established as the standard first-line agent in two phase III clinical trials. Cabazitaxel, a novel taxane with activity in cancer models resistant to paclitaxel and docetaxel, is the only agent that has been compared to a chemotherapy control in a phase III clinical trial as a second-line therapy; it was found to prolong the overall survival of patients with castration-resistant prostate cancer previously treated with docetaxel when compared to mitoxantrone. Other agents used in this setting include abiraterone and sipuleucel-T, and novel therapies are continually being investigated in an attempt to improve the outcome for patients with castration-resistant prostate cancer.

  10. Cancer Therapy Due to Apoptosis: Galectin-9

    Directory of Open Access Journals (Sweden)

    Koji Fujita

    2017-01-01

    Full Text Available Dysregulation of apoptosis is a major hallmark in cancer biology that might equip tumors with a higher malignant potential and chemoresistance. The anti-cancer activities of lectin, defined as a carbohydrate-binding protein that is not an enzyme or antibody, have been investigated for over a century. Recently, galectin-9, which has two distinct carbohydrate recognition domains connected by a linker peptide, was noted to induce apoptosis in thymocytes and immune cells. The apoptosis of these cells contributes to the development and regulation of acquired immunity. Furthermore, human recombinant galectin-9, hG9NC (null, which lacks an entire region of the linker peptide, was designed to resist proteolysis. The hG9NC (null has demonstrated anti-cancer activities, including inducing apoptosis in hematological, dermatological and gastrointestinal malignancies. In this review, the molecular characteristics, history and apoptosis-inducing potential of galectin-9 are described.

  11. Cancer therapy and cardiotoxicity: The need of serial Doppler echocardiography

    Directory of Open Access Journals (Sweden)

    Pardo Moira

    2007-01-01

    Full Text Available Abstract Cancer therapy has shown terrific progress leading to important reduction of morbidity and mortality of several kinds of cancer. The therapeutic management of oncologic patients includes combinations of drugs, radiation therapy and surgery. Many of these therapies produce adverse cardiovascular complications which may negatively affect both the quality of life and the prognosis. For several years the most common noninvasive method of monitoring cardiotoxicity has been represented by radionuclide ventriculography while other tests as effort EKG and stress myocardial perfusion imaging may detect ischemic complications, and 24-hour Holter monitoring unmask suspected arrhythmias. Also biomarkers such as troponine I and T and B-type natriuretic peptide may be useful for early detection of cardiotoxicity. Today, the widely used non-invasive method of monitoring cardiotoxicity of cancer therapy is, however, represented by Doppler-echocardiography which allows to identify the main forms of cardiac complications of cancer therapy: left ventricular (systolic and diastolic dysfunction, valve heart disease, pericarditis and pericardial effusion, carotid artery lesions. Advanced ultrasound tools, as Integrated Backscatter and Tissue Doppler, but also simple ultrasound detection of "lung comet" on the anterior and lateral chest can be helpful for early, subclinical diagnosis of cardiac involvement. Serial Doppler echocardiographic evaluation has to be encouraged in the oncologic patients, before, during and even late after therapy completion. This is crucial when using anthracyclines, which have early but, most importantly, late, cumulative cardiac toxicity. The echocardiographic monitoring appears even indispensable after radiation therapy, whose detrimental effects may appear several years after the end of irradiation.

  12. Testosterone replacement therapy and the risk of prostate cancer.

    Science.gov (United States)

    Warburton, Daniel; Hobaugh, Christopher; Wang, Grace; Lin, Haocheng; Wang, Run

    2015-01-01

    Understanding the role of testosterone replacement therapy (TRT) in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN), in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

  13. Testosterone replacement therapy and the risk of prostate cancer

    Directory of Open Access Journals (Sweden)

    Daniel Warburton

    2015-01-01

    Full Text Available Understanding the role of testosterone replacement therapy (TRT in the development and progression of prostate cancer is an important concept in treating patients with symptoms of hypogonadism. This article revealed a small number of mostly retrospective, observational studies describing the use of TRT in the general population, in men with prostatic intraepithelial neoplasia (PIN, in men with a history of treated prostate cancer, and in men on active surveillance for prostate cancer. The current literature does not report a statistically significant increase in the development or progression of prostate cancer in men receiving testosterone replacement for symptomatic hypogonadism, and the prostate saturation theory provides a model explaining the basis for these results. The use of TRT in men with a history of prostate cancer is considered experimental, but future results from randomized controlled trials could lead to a change in our current treatment approach.

  14. Direct Activation of Bax Protein for Cancer Therapy

    Science.gov (United States)

    Liu, Zhiqing; Ding, Ye; Ye, Na; Wild, Christopher; Chen, Haiying; Zhou, Jia

    2015-01-01

    Bax, a central cell death regulator, is an indispensable gateway to mitochondrial dysfunction and a major pro-apoptotic member of the Bcl-2 family proteins that control apoptosis in normal and cancer cells. Dysfunction of apoptosis renders the cancer cell resistant to treatment as well as promotes tumorigenesis. Bax activation induces mitochondrial membrane permeabilization, thereby leading to the release of apoptotic factor cytochrome c and consequently cancer cell death. A number of drugs in clinical use are known to indirectly activate Bax. Intriguingly, recent efforts demonstrate that Bax can serve as a promising direct target for small-molecule drug discovery. Several direct Bax activators have been identified to hold promise for cancer therapy with the advantages of specificity and the potential of overcoming chemo- and radioresistance. Further investigation of this new class of drug candidates will be needed to advance them into the clinic as a novel means to treat cancer. PMID:26395559

  15. The T61 human breast cancer xenograft: an experimental model of estrogen therapy of breast cancer

    DEFF Research Database (Denmark)

    Brunner, N; Spang-Thomsen, M; Cullen, K

    1996-01-01

    Endocrine therapy is one of the principal treatment modalities of breast cancer, both in an adjuvant setting and in advanced disease. The T61 breast cancer xenograft described here provides an experimental model of the effects of estrogen treatment at a molecular level. T61 is an estrogen recepto...

  16. Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer.

    NARCIS (Netherlands)

    Hamakawa, H.; Nakashiro, K.; Sumida, T.; Shintani, S.; Myers, J.N.; Takes, R.P.; Rinaldo, A.; Ferlito, A.

    2008-01-01

    BACKGROUND: Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The a

  17. Assessment of the Evolution of Cancer Treatment Therapies

    Directory of Open Access Journals (Sweden)

    Mónica Valladares

    2011-08-01

    Full Text Available Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.. In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine. We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

  18. Assessment of the Evolution of Cancer Treatment Therapies

    Energy Technology Data Exchange (ETDEWEB)

    Arruebo, Manuel [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Vilaboa, Nuria [CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Zaragoza 50018 (Spain); Hospital Universitario La Paz-IdiPAZ, Paseo de la Castellana 261, Madrid 28046 (Spain); Sáez-Gutierrez, Berta; Lambea, Julio; Tres, Alejandro [Instituto de Nanociencia de Aragón (INA), Mariano Esquillor, Edif. I+D, University of Zaragoza, Zaragoza 50018 (Spain); Servicio de Oncología Médica, Hospital Clínico Universitario Lozano Blesa, Avda. San Juan Bosco 50009, Zaragoza (Spain); Instituto Aragonés de Ciencias de la Salud (I-CS), Avda. Gómez Laguna, 25, Zaragoza 50009 (Spain); Valladares, Mónica [Lonza Biologics Porriño, A relva s/n, Porriño (Pontevedra) 36410 (Spain); González-Fernández, África, E-mail: africa@uvigo.es [Immunology Department, Biomedical Research Center (CINBIO), University of Vigo, Campus Lagoas Marcosende, Vigo (Pontevedra) 36310 (Spain)

    2011-08-12

    Cancer therapy has been characterized throughout history by ups and downs, not only due to the ineffectiveness of treatments and side effects, but also by hope and the reality of complete remission and cure in many cases. Within the therapeutic arsenal, alongside surgery in the case of solid tumors, are the antitumor drugs and radiation that have been the treatment of choice in some instances. In recent years, immunotherapy has become an important therapeutic alternative, and is now the first choice in many cases. Nanotechnology has recently arrived on the scene, offering nanostructures as new therapeutic alternatives for controlled drug delivery, for combining imaging and treatment, applying hyperthermia, and providing directed target therapy, among others. These therapies can be applied either alone or in combination with other components (antibodies, peptides, folic acid, etc.). In addition, gene therapy is also offering promising new methods for treatment. Here, we present a review of the evolution of cancer treatments, starting with chemotherapy, surgery, radiation and immunotherapy, and moving on to the most promising cutting-edge therapies (gene therapy and nanomedicine). We offer an historical point of view that covers the arrival of these therapies to clinical practice and the market, and the promises and challenges they present.

  19. Enhancing Cold Atmospheric Plasma Treatment Efficiency for Cancer Therapy

    Science.gov (United States)

    Cheng, Xiaoqian

    To improve efficiency and safety of anti-cancer therapies the researchers and clinicians alike are prompted to develop targeted combined therapies that especially minimize damage to healthy tissues while eradicating the body of cancerous tissues. Previous research in cold atmospheric plasma (CAP) and cancer cell interaction has repeatedly proven that cold plasma induced cell death. In this study, we seek to integrate the medical application of CAP. We proposed and implemented 3 novel ideas to enhance efficacy and selectivity of cancer therapy. It is postulated that the reactive oxygen species (ROS) and reactive nitrogen species (RNS) play a major role in the CAP cancer therapy. We determined a mechanism of CAP therapy on glioblastoma cells (U87) through an understanding of the composition of CAP, including output voltage, treatment time, and gas flow-rate. We varied the characteristics of the cold plasma in order to obtain different major species (such as O, OH, N2+, and N2 lines). "plasma dosage" D ~ Q * V * t. is defined, where D is the entire "plasma dosage"; Q is the flow rate of feeding gas; V is output voltage; t is treatment time. The proper CAP dosage caused 3-fold cell death in the U87 cells compared to the normal human astrocytes E6/E7 cells. We demonstrated there is a synergy between AuNPS and CAP in cancer therapy. Specifically, the concentration of AuNPs plays an important role on plasma therapy. At an optimal concentration, gold nanoparticles can significantly induce U87 cell death up to a 30% overall increase compared to the control group with the same plasma dosage but no AuNPs applied. The ROS intensity of the corresponding conditions has a reversed trend compared to cell viability. This matches with the theory that intracellular ROS accumulation results in oxidative stress, which further changes the intracellular pathways, causing damage to the proteins, lipids and DNA. Our results show that this synergy has great potential in improving the

  20. Future options ofanti-angiogenic cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Yihai Cao

    2016-01-01

    In human patients, drugs that block tumor vessel growth are widely used to treat a variety of cancer types. Many rigorous phase 3 clinical trials have demonstrated signiifcant survival beneifts; however, the addition of an anti-angio-genic component to conventional therapeutic modalities has generally produced modest survival beneifts for cancer patients. Currently, it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients. In this article, we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.