• Title/Summary/Keyword: Novel cancer therapy

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Cervical Cancer Gene Therapy by Gene Loaded PEG-PLA Nanomedicine

  • Liu, Bo;Han, Shu-Mei;Tang, Xiao-Yong;Han, Li;Li, Chang-Zhong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4915-4918
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    • 2014
  • Background and Aims: Advances in the treatment of cervical cancer over the last decade have predominantly involved the development of genes directed at molecular targets. Gene therapy is recognized to be a novel method for the treatment of cervical cancer. Genes can be administered into target cells via nanocarriers. This study aimed to develop systemically administrable nano-vectors. Floate (Fa) containing gene loaded nanoparticles (NPs) could target HeLa human cervical cancer cells through combination with receptors on the cells to increase the nuclear uptake of genetic materials. Methods: Fa was linked onto Poly (ethylene glycol)-b-poly (D, L-lactide) (PEG-PLA) to form Fa-PEG-PLA, and the resulting material was used to load plasmids of enhanced green fluorescence protein (pEGFP) to obtain gene loaded nanoparticles (Fa-NPs/DNA). Physical-chemical characteristics, in vitro release and cytotoxicity of Fa-NPs/DNA were evaluated. The in vitro transfection efficiency of Fa-NPs/DNA was evaluated in HeLa cells and human umbilical vein endothelial cells (HUVEC). PEG-PLA without Fa was used to load pEGFP from NPs/DNA as a control. Results: Fa-NPs/DNA has a particle size of 183 nm and a gene loading quantity of 92%. After 72h of transfection, Fa-NPs/DNA displayed over 20% higher transfection efficiency than NPs/DNA and 40% higher than naked DNA in HeLa cells. However, in HUVECs, no significant difference appeared between Fa-NPs/DNA and NPs/DNA. Conclusions: Fa-PEG-PLA NPs could function as excellent materials for gene loading. This nano-approach could be used as tumor cell targeted medicine for the treatment of cervical cancer.

Genomic Profiling of Liver Cancer

  • Lee, Ju-Seog
    • Genomics & Informatics
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    • v.11 no.4
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    • pp.180-185
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    • 2013
  • Development of liver cancers is driven largely by genomic alterations that deregulate signaling pathways, influencing growth and survival of cancer cells. Because of the hundreds or thousands of genomic/epigenomic alterations that have accumulated in the cancer genome, it is very challenging to find and test candidate genes driving tumor development and progression. Systematic studies of the liver cancer genome have become available in recent years. These studies have uncovered new potential driver genes, including those not previously known to be involved in the development of liver cancer. Novel approaches combining multiple datasets from patient tissues have created an unparalleled opportunity to uncover potential new therapeutic targets and prognostic/predictive biomarkers for personalized therapy that can improve clinical outcomes of the patients with liver cancer.

Inhibitory Effects of Harmine on Migration and Invasion of Human Breast Cancer Cells by Regulating Notch Signaling (Harmine의 Notch 신호전달 조절에 의한 유방암세포주 이동 및 침윤 억제 효과)

  • Yun, Jieun
    • Korean Journal of Pharmacognosy
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    • v.49 no.4
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    • pp.285-290
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    • 2018
  • Harmine, a beta-carboline alkaloid isolated from the seeds of Peganum harmala has been reported as a promising drug candidate for cancer therapy. However, the effect of harmine on breast cancer remains still unclear. In this study, the effect of harmine on the cell proliferation, migration, and invasion of breast cancer MDA-MB231 cells and the underlying mechanism were investigated. The results indicated that harmine inhibited the proliferation MDA-MB231 cells in a dose-dependent manner and markedly suppressed migration and invasion of MDA-MB231 cells. The mechanism involved in part through Notch signaling. The Notch activity was significantly inhibited by harmine treatment and harmine suppressed the expression of Jagged1 which is a key ligand to activate Notch signaling. These findings suggest a novel mechanism of harmine on anti-cancer activity and harmine may act as a potential therapeutic drug for breast cancer treatment.

Radioimmunotherapy in Head and Neck Cancer (두경부암에서 방사면역치료의 역할)

  • Choi, Ik Joon
    • Korean Journal of Otorhinolaryngology-Head and Neck Surgery
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    • v.61 no.12
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    • pp.637-643
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    • 2018
  • Radioimmunotherapy (RIT) is a therapy that takes advantage of the "cross-fire" effect of emitted radiation by radionuclides conjugated to tumor-directed monoclonal antibodies (mAb) (including those fragments) or peptides. While RIT has been successfully employed for the treatment of lymphoma, mostly with radiolabeled antibodies against CD20 [$^{90}yttrium$ ($^{90}Y$)-ibritumomab tiuxetan; $Zevalin^{(R)}$ and $^{131}iodine$ ($^{131}I)-tositumomab$; $Bexxar^{(R)}$], its use in solid tumors is more challenging, so far. Immuno-PET, a tool for tracking and quantification of mAbs with PET in vivo, is an exciting novel option to improve diagnostic imaging and guide mAb-based therapy. RIT in solid tumors including head and neck cancer may be an alternative treatment with advances in various biological, chemical, and treatment procedures, and it may help to reduce unnecessary exposure and enhance the therapeutic efficacy. Also, immuno-PET based on RIT might play an important role in cancer staging, in patients or targets selection of targeted therapeutics and in monitoring the response of targeted therapeutics as precision medicine. In this review, fundamentals of RIT/immune-PET and current knowledge of the preclinical/clinical trials in RIT for solid tumor including head and neck cancer are reviewed.

35-Year Research History of Cytotoxicity and Cancer: a Quantitative and Qualitative Analysis

  • Farghadani, Reyhaneh;Haerian, Batoul Sadat;Ebrahim, Nader Ale;Muniandy, Sekaran
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.7
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    • pp.3139-3145
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    • 2016
  • Cancer is the leading cause of morbidity and mortality worldwide, characterized by irregular cell growth. Cytotoxicity or killing tumor cells that divide rapidly is the basic function of chemotherapeutic drugs. However, these agents can damage normal dividing cells, leading to adverse effects in the body. In view of great advances in cancer therapy, which are increasingly reported each year, we quantitatively and qualitatively evaluated the papers published between 1981 and December 2015, with a closer look at the highly cited papers (HCPs), for a better understanding of literature related to cytotoxicity in cancer therapy. Online documents in the Web of Science (WOS) database were analyzed based on the publication year, the number of times they were cited, research area, source, language, document type, countries, organization-enhanced and funding agencies. A total of 3,473 publications relevant to the target key words were found in the WOS database over 35 years and 86% of them (n=2,993) were published between 2000-2015. These papers had been cited 54,330 times without self-citation from 1981 to 2015. Of the 3,473 publications, 17 (3,557citations) were the most frequently cited ones between 2005 and 2015. The topmost HCP was about generating a comprehensive preclinical database (CCLE) with 825 (23.2%) citations. One third of the remaining HCPs had focused on drug discovery through improving conventional therapeutic agents such as metformin and ginseng. Another 33% of the HCPs concerned engineered nanoparticles (NPs) such as polyamidoamine (PAMAM) dendritic polymers, PTX/SPIO-loaded PLGAs and cell-derived NPs to increase drug effectiveness and decrease drug toxicity in cancer therapy. The remaining HCPs reported novel factors such as miR-205, Nrf2 and p27 suggesting their interference with development of cancer in targeted cancer therapy. In conclusion, analysis of 35-year publications and HCPs on cytotoxicity in cancer in the present report provides opportunities for a better understanding the extent of topics published and may help future research in this area.

Current Status of Systemic Therapy in Hepatocellular Carcinoma (진행성 간세포암종의 전신치료제)

  • Lee, Han Ah;Seo, Yeon Seok
    • Journal of Digestive Cancer Research
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    • v.8 no.1
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    • pp.65-70
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    • 2020
  • Although being one of the major causes of malignancy related death globally, hepatocellular carcinoma (HCC) has not received much attention in respect of novel drug development. Fortunately, several new drugs were found to be effective and tolerable in patients with advanced HCC from a number of phase 3 studies during the recent several years. Novel multi-targeted kinase inhibitors and immune checkpoint inhibitors were approved for clinical use, and combination strategies to maximize the potent of drugs demonstrated promising antitumor activity and safety with high response rate and improved safety profile. The increased number of available agents for HCC will contribute to change of treatment strategies and prognosis of patients with advanced HCC. Still, there is a many critical questions remain unanswered. Currently ongoing trials and future studies will provide better understanding of tumor biology and optimized criteria for patient selection and combination therapies.

Calcium Sensing Receptor Modulation for Cancer Therapy

  • Sarkar, Puja;Kumar, Sudhir
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3561-3568
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    • 2012
  • The calcium sensing receptor (CaSR) is a member of the largest family of cell surface receptors, the G protein-coupled receptors involved in calcium homeostasis. The role of the CaSR in neoplasia appears to be homeostatic; loss of normal CaSR-induced response to extracellular calcium is observed in cancers of the colon and ovary, while increased release of PTHrP is observed in cancers of the breast, prostate and Leydig cells. Currently CaSR can be considered as a molecule that can either promote or prevent tumor growth depending on the type of cancer. Therefore, recognition of the multifaceted role of CaSR in gliomas and other malignant tumors in general is fundamental to elucidating the mechanisms of tumor progression and the development of novel therapeutic agents. Emphasis should be placed on development of drug-targeting methods to modulate CaSR activity in cancer cells.

A novel HDAC1 inhibitor, CBUD-1001, exerts anticancer effects by modulating the apoptosis and EMT of colorectal cancer cells

  • Se Lim Kim;Minh Thanh La;Min Woo Shin;Sang-Wook Kim;Hee-Kwon Kim
    • International Journal of Oncology
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    • v.57 no.4
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    • pp.1027-1038
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    • 2020
  • Colorectal cancer (CRC) is one of the most commonly diagnosed malignancies and is a leading cause of cancer-related mortality worldwide. Histone deacetylases (HDACs) are a class of enzymes responsible for the epigenetic regulation of gene expression. Some HDAC inhibitors have been shown to be efficient agents for cancer treatment. The aim of the present study was to discover a novel, potent HDAC inhibitor and demonstrate its anticancer effect and molecular mechanisms in CRC cells. A novel fluorinated aminophenyl-benzamide-based compound, CBUD-1001, was designed to specifically target HDAC1, and it was then synthesized and evaluated. CBUD-1001 exerted a potent inhibitory effect on HDAC enzyme activity and exhibited anticancer potency against CRC cell lines. Molecular docking analysis rationalized the high potency of CBUD-1001 by validating its conformation in the HDAC active site. Further investigation using CRC cells demonstrated that CBUD-1001 inhibited HDAC activity by hyper-acetylating histones H3 and H4, and it exerted an apoptotic effect by activating a mitochondrial-dependent pathway. Of note, it was found that CBUD-1001 attenuates the cell motility of CRC cells by downregulating the EMT signaling pathway. Thus, CBUD-1001 may prove to be a promising novel drug candidate for CRC therapy.

Self-organized Nanogels of Polysaccharide Derivatives in Anti-Cancer Drug Delivery

  • Park, Sin-Jung;Na, Kun
    • Journal of Pharmaceutical Investigation
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    • v.40 no.4
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    • pp.201-212
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    • 2010
  • Self-organized nanogels from polysaccharide derivatives offer a promising approach in treatment of cancer due to their flexibility in chemistry and their ability to improve the therapeutic index of a drug by modifying biodistribution by their preferential localization at target sites and lower distribution in normal healthy tissues. These properties have promoted studies of active cancer targeting by self-organized nanogels for even better accumulation in solid tumors. However although many researchers have reported their potential by using cell culture systems and small animal tumor models in cancer therapy, these nanogels need more decoration such as conjugation with targeting moiety and endowment of stimuli-sensitivity for precise targeting of the cancer site. In this review, we summarize the recent efforts in developing novel targeting approaches via active endocytosis and stimuli-sensitive systems responding to hyperthermic or acidic tumor pH conditions.

Precision Medicine in Head and Neck Cancer (두경부암에서 정밀의료)

  • Hye-sung Park;Jin-Hyoung Kang
    • Korean Journal of Head & Neck Oncology
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    • v.39 no.1
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    • pp.1-9
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    • 2023
  • Technological advancement in human genome analysis and ICT (information & communication technologies) brought 'precision medicine' into our clinical practice. Precision medicine is a novel medical approach that provides personalized treatments tailored to each individual by precisely segmenting patient populations, based on robust data including a person's genetic information, disease information, lifestyle information, etc. Precision medicine has a potential to be applied to treating a range of tumors, in addition to non-small cell lung cancer, in which precision oncology has been actively practiced. In this article, we are reviewing precision medicine in head and neck cancer (HNC) with focus on tumor agnostic biomarkers and treatments such as NTRK, MSI-H/dMMR, TMB-H and BRAF V600E, all of which were recently approved by U.S. Food and Drug Administration (FDA).