• Title/Summary/Keyword: Targeted agents

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Release Properties of BSA from Pectin Heads for Colonic Drug Delivery (Colonic Delivery를 위한 펙틴 비드로부터 BSA의 방출 특성)

  • 최춘순;박상무;송원현;이창문;이기영;김동운;김진철
    • KSBB Journal
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    • v.18 no.2
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    • pp.161-164
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    • 2003
  • Oral drug delivery system using pectin gel was developed for colon-targeting of peptide drug. BSA(bovine serum albumin)-loaded pectin and pectin-alginate beads were prepared for drug release properties in vitro. Morphological studies by electron microscopy indicated that pectin and pectin-alginate beads were spherical in shape and approximately 1.0 mm. In order to find the suitable beads, effects of cross-linking agents (calcium chloride or zinc acetate) and drying temperature of beads were investigated. Drug release decreased with concentration of cross-linking agents and drying temperature. For colonic drug delivery from pectin and pectin-alginate beads, pectin degradable enzymes were added at 5 hrs from the beginning of drug release. After addition of enzymes, drug release was suddenly increased against free enzymes. Therefore, pectin and pectin-alginate beads can be promised as useful drug release carriers for colon-targeted delivery.

Application of Stimuli-responsive Chitosan Micelles for Improved Therapeutic Efficiency of Anticancer Agents (항암제의 치료 효율성을 높이기 위한 다양한 자극 응답성 물질이 개질된 키토산 마이셀의 응용성 고찰)

  • Jeong, Gyeong-Won;Park, Jun-Kyu;Nah, Jae-Woon
    • Applied Chemistry for Engineering
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    • v.29 no.2
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    • pp.147-154
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    • 2018
  • Currently, to overcome low therapeutic efficiencies and side effects of anticancer agents, the study of drug carrier based on polymers have been consistently investigated. Although the traditional drug carrier based on polymers displayed an excellent result and significant progress, there has been a problem with the side effect and low therapeutic efficiency because of the premature drug release before reached to the targeted region by the low stability in blood stream and sustained drug release. In this review article, to improve the problem of inefficient drug release, methods were suggested, which can maximize the therapeutic efficiency by increasing the stability in the blood stream and triggering drug release at the target site by introducing a stimuli-responsive substance to the non-toxic and biocompatible natural polymer chitosan.

Investigation of Antitumor Effects of Sorafenib and Lapatinib Alone and in Combination on MCF-7 Breast Cancer Cells

  • Kacan, Turgut;Altun, Ahmet;Altun, Gulsah Gultekin;Kacan, Selen Baloglu;Sarac, Bulent;Seker, Mehmet Metin;Bahceci, Aykut;Babacan, Nalan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3185-3189
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    • 2014
  • Background: Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and $6.25{\mu}M$ concentrations of sorafenib and 200, 100, 50 and $25{\mu}M$ concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and $IC_{50}$ values are calculated according to the absorbance data Results: Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an $IC_{50}$ value of $32.0{\mu}M$; in contrast with lapatinib the $IC_{50}$ was $136.6{\mu}M$. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells. Conclusions: Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.

Prognostic Factors for Overall Survival in Patients With Metastatic Colorectal Carcinoma Treated With Vascular Endothelial Growth Factor-Targeting Agents

  • Cetin, Bulent;Kaplan, Mehmet Ali;Berk, Veli;Ozturk, Selcuk Cemil;Benekli, Mustafa;Isikdogan, Abdurrahman;Ozkan, Metin;Coskun, Ugur;Buyukberber, Suleyman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.3
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    • pp.1059-1063
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    • 2012
  • Objective: Angiogenesis represents a key element in the pathogenesis of malignancy. There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic colorectal cancer treated with vascular endothelial growth factor (VEGF)-targeted therapy. The present study was conducted to establish a prognostic model for patients using an oxaliplatin-based or irinotecan-based chemotherapy plus bevacizumab in metastatic colorectal cancer. Methods: Baseline characteristics and outcomes on 170 patients treated with FOLFIRI or XELOX plus anti-VEGF therapy-naive metastatic colorectal cancer were collected from three Turkey cancer centers. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median OS for the whole cohort was 19 months (95% CI, 14.3 to 23.6 months). Three of the seven adverse prognostic factors according to the Anatolian Society of Medical Oncology (ASMO) were independent predictors of short survival: serum lactate dehydrogenase (LDH) greater than the upper limit of normal (ULN; p<0.001); neutrophils greater than the ULN (p<0.0014); and progression free survival (PFS) less than 6 months (p =0.001). Conclusion: Serum LDH and neutrophil levels were the main prognostic factors in predicting survival, followed by PFS. This model validates incorporation of components of the ASMO model into patient care and clinical trials that use VEGF-targeting agents.

Iron Oxide Nanoparticle-incorporated Alginate Capsules as Magnetic Field-assisted Potential Delivery Platforms for Agriculture Pesticides and Biocontrol Agents

  • Lee, Dohyeon;Choi, Kyoung Soon;Kim, Daun;Park, Sunho;Kim, Woochan;Jang, Kyoung-Je;Lim, Ki-Taek;Chung, Jong Hoon;Seonwoo, Hoon;Kim, Jangho
    • Journal of Biosystems Engineering
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    • v.42 no.4
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    • pp.323-329
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    • 2017
  • Purpose: Biocompatible capsules have recently been highlighted as a novel platform for delivering various components, such as drug, food, and agriculture pesticides, to overcome the current limitations of living systems, such as those in agriculture, biology, the environment, and foods. However, few active targeting systems using biocompatible capsules and physical forces simultaneously have been developed in the agricultural engineering field. Methods: Here, we developed an active targeting delivery platform that uses biocompatible alginate capsules and controls movements by magnetic forces for agricultural and biological engineering applications. We designed and fabricated large-scale biocompatible capsules, using custom-made nozzles ejecting alginate solutions for encapsulation. Results: To develop the active target delivery platforms, we incorporated iron oxide nanoparticles in the large-scale alginate capsules. The sizes of alginate capsules were controlled by regulating the working conditions, such as concentrations of alginate solutions and iron oxide nanoparticles. Conclusions: We confirmed that the iron oxide particle-incorporated large-scale alginate capsules moved actively in response to magnetic fields, which will be a good strategy for active targeted delivery platforms for agriculture and biological engineering applications, such as for the controlled delivery of agriculture pesticides and biocontrol agents.

Novel Biomarkers for Prediction of Response to Preoperative Systemic Therapies in Gastric Cancer

  • Cavaliere, Alessandro;Merz, Valeria;Casalino, Simona;Zecchetto, Camilla;Simionato, Francesca;Salt, Hayley Louise;Contarelli, Serena;Santoro, Raffaela;Melisi, Davide
    • Journal of Gastric Cancer
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    • v.19 no.4
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    • pp.375-392
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    • 2019
  • Preoperative chemo- and radiotherapeutic strategies followed by surgery are currently a standard approach for treating locally advanced gastric and esophagogastric junction cancer in Western countries. However, in a large number of cases, the tumor is extremely resistant to these treatments and the patients are exposed to unnecessary toxicity and delayed surgical therapy. The current clinical trials evaluating the combination of preoperative systemic therapies with modern targeted and immunotherapeutic agents represent a unique opportunity for identifying predictive biomarkers of response to select patients that would benefit the most from these treatments. However, it is of utmost importance that these potential biomarkers are corroborated by extensive preclinical and translational research. The aim of this review article is to present the most promising biomarkers of response to classic chemotherapeutic, anti-HER2, antiangiogenic, and immunotherapeutic agents that can be potentially useful for personalized preoperative systemic therapies in gastric cancer patients.

Immunotherapy for Advanced/Metastatic Esophageal Squamous Cell Carcinoma (진행성/전이성 식도 편평상피세포암의 면역치료)

  • Sung Eun Kim;Kyoungwon Jung;Moo In Park
    • Journal of Digestive Cancer Research
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    • v.12 no.2
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    • pp.72-81
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    • 2024
  • Esophageal squamous cell carcinomas constitute a major proportion of esophageal cancers in Korea. Conventional chemotherapy and radiation therapy are the options for treating advanced/metastatic esophageal cancer, but the prognosis remains poor. Immunotherapy has significantly improved the prognosis of several advanced/metastatic cancers including esophageal squamous cell carcinoma. In Korea, immunotherapy is used to treat advanced/metastatic esophageal squamous cell carcinoma, and treatment results are expected to further improve. Immunotherapy is a term used to describe a treatment modality involving a biological/targeted agent that aims to enhance and restore the ability of the immune system to detect and destroy cancer cells by modifying or blocking co-stimulating signals. Immune checkpoint inhibitors have revolutionized cancer treatment with the administration of a single agent (monotherapy) or combinations of multiple agents, with the three approved agents being anti-PD-1 (programmed death 1), anti-PD-L1 (programmed cell death ligand 1), and anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) monoclonal antibodies. Anti-PD-1 drugs including nivolumab and pembrolizumab have been mainly investigated for treating advanced/metastatic esophageal squamous cell cancer. Studies on their effectiveness in a neoadjuvant setting, a curative adjuvant setting, or as the first-line treatment for advanced or metastatic setting are ongoing. This review describes the principle of action, summary of existing clinical studies, and prospects for immune checkpoint inhibitors used in the treatment of advanced/metastatic esophageal squamous cell cancer.

Radiotracer Methods for Targeted Imaging of the Epidermal Growth Factor Receptor (Epidermal Growth factor 수용체 영상을 위한 방사성추적자 기술)

  • Jung, Kyung-Ho;Lee, Kyung-Han
    • Nuclear Medicine and Molecular Imaging
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    • v.42 no.3
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    • pp.185-191
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    • 2008
  • While indirect targeting strategies using reporter-genes are taking center stage in current molecular imaging research, another vital strategy has long involved direct imaging of specific receptors using radiolabeled ligands. Recently, there is renewal of immense interest in this area with particular attention to the epidermal growth factor receptor (EGFR), a transmembrane glycoprotein critically involved in the regulation of many cellular functions and malignancies. Recently, two novel classes of EGFR-targeting anticancer drugs have entered clinical trials with great expectations. These are monoclonal antibodies such as cetuximab that target the extracellular domain, and small molecule tyrosine kinase inhibitors such as gefitinib (lressa) and erlotinib (Tarceva) that target the catalytic domain of the receptor. However, early results have showed disappointing survival benefits, disclosing a major challenge for this therapeutic strategy; namely, the need to identify tumors that are most likely to respond to the agents. To address this important clinical issue, several noninvasive imaging techniques are under investigation including radiolabeled probes based on small molecule tyrosine kinase inhibitors, anti-EGFR antibodies, and EGF peptides. This review describes the current status, limitations, and future prospects in the development of radiotracer methods for EGFR imaging.

Medulloblastoma in the Molecular Era

  • Kuzan-Fischer, Claudia Miranda;Juraschka, Kyle;Taylor, Michael D.
    • Journal of Korean Neurosurgical Society
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    • v.61 no.3
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    • pp.292-301
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    • 2018
  • Medulloblastoma is the most common malignant brain tumor of childhood and remains a major cause of cancer related mortality in children. Significant scientific advancements have transformed the understanding of medulloblastoma, leading to the recognition of four distinct clinical and molecular subgroups, namely wingless (WNT), sonic hedgehog, group 3, and group 4. Subgroup classification combined with the recognition of subgroup specific molecular alterations has also led to major changes in risk stratification of medulloblastoma patients and these changes have begun to alter clinical trial design, in which the newly recognized subgroups are being incorporated as individualized treatment arms. Despite these recent advancements, identification of effective targeted therapies remains a challenge for several reasons. First, significant molecular heterogeneity exists within the four subgroups, meaning this classification system alone may not be sufficient to predict response to a particular therapy. Second, the majority of novel agents are currently tested at the time of recurrence, after which significant selective pressures have been exerted by radiation and chemotherapy. Recent studies demonstrate selection of tumor sub-clones that exhibit genetic divergence from the primary tumor, exist within metastatic and recurrent tumor populations. Therefore, tumor resampling at the time of recurrence may become necessary to accurately select patients for personalized therapy.

Citrus Fruits and their Bioactive Ingredients: Leading Four Horsemen from Front

  • Farooqi, Ammad Ahmad;Wang, Zhiqiang;Hasnain, Sidra;Attar, Rukset;Aslam, Ayesha;Mansoor, Qaisar;Ismail, Muhammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.6
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    • pp.2575-2580
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    • 2015
  • Cancer is a multifaceted and genomically complex disease and rapidly accumulating high impact research is deepening our understanding related to the mechanisms underlying cancer development, progression and resistance to therapeutics. Increasingly it is being realized that genetic/epigenetic mutations, inactivation of tumor suppressor genes, overexpression of oncogenes, deregulation of intracellular signaling cascades and loss of apoptosis are some of the extensively studied aspects. Confluence of information suggested that rapidly developing resistance to therapeutics is adding another layer of complexity and overwhelmingly increasing preclinical studies are identifying different natural agents with efficacy and minimal off-target effects. We partition this multi-component review into citrus fruits and their bioactive ingredients mediating rebalancing of pro- and anti-apoptotic proteins to induce apoptosis in resistant cancer cells. We also discuss how oncogenic protein networks are targeted in cancer cells and how these findings may be verified in preclinical studies.