• Title/Summary/Keyword: Tumor environment

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Cytocidal Effect of Hyperthermia on Tumor Cells in vivo (In vivo 腫瘍細胞에 미치는 溫熱處理의 細胞致死效果)

  • Kang, Man-Sik;Rhee, Jeong-Gile;Seymour H. Levitt;Chang W. Song
    • The Korean Journal of Zoology
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    • v.24 no.2
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    • pp.59-64
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    • 1981
  • The cytocidal effect of hyperthermia on subcutaneous SCK tumor cells growing in vivo was significantly greater than that on the SCK tumor cells cultured in vitro. When the tumors were left in situ after heating, the cell survival progressively decreased, and the functional intratumor vascular volume also decreased. The radiation survival curves of tumor cells heated either 30 min before or after X-irradiation in vivo were steeper than the radiation survival curves of unheated control tumors. It is concluded that the cytocidal effect of hyperthermia on tumor cells in vivo is greater than that in vitro due possibly to the intratumor environment.

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FAP Inhibitors as Novel Small Molecules for Cancer Imaging using Radionuclide

  • Anvar Mirzaei;Jung-Joon Min;Dong-Yeon Kim
    • Journal of Radiopharmaceuticals and Molecular Probes
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    • v.9 no.1
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    • pp.49-55
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    • 2023
  • Tumors are encircled by various non-cancerous cell types in the extracellular matrix, including fibroblasts, endothelial cells, immune cells, and cytokines. Fibroblasts are the most critical cells in the tumor stroma and play an important role in tumor development, which has been highlighted in some epithelial cancers. Many studies have shown a tight connection between cancerous cells and fibroblasts in the last decade. Regulatory factors secreted into the tumor environment by special fibroblast cells, cancer-associated fibroblasts (CAFs), play an important role in tumor and vessel development, metastasis, and therapy resistance. This review addresses the development of FAP inhibitors, emphasizing the first, second, and latest generations. First-generation inhibitors exhibit low selectivity and chemical stability, encouraging researchers to develop new scaffolds based on preclinical and clinical data. Second-generation enzymes such as UAMC-1110 demonstrated enhanced FAP binding and better selectivity. Targeted treatment and diagnostic imaging have become possible by further developing radionuclide-labeled fibroblast activation protein inhibitors (FAPIs). Although all three FAPIs (01, 02, and 04) showed excellent preclinical and clinical findings. The final optimization of these FAPI scaffolds resulted in FAPI-46 with the highest tumor-to-background ratio and better binding affinity.

Role of Tumor-associated Macrophage in Tumor Microenvironment (암미세환경에서 종양관련대식세포의 역할)

  • Min, Do Sik
    • Journal of Life Science
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    • v.28 no.8
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    • pp.992-998
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    • 2018
  • Cancer cells grow in an environment composed of various components that supports tumor growth. Major cell types in the tumor microenvironment are fibroblast, endothelial cells and immune cells. All of these cells communicate with cancer cells. Among infiltrating immune cells as an abundant component of solid tumors, macrophages are a major component of the tumor microenvironment and orchestrates various aspects of immunity. The complex balance between pro-tumoral and anti-tumoral effects of immune cell infiltration can create a chronic inflammatory microenvironment essential for tumor growth and progression. Macrophages express different functional programs in response to microenvironmental signals, defined as M1 and M2 polarization. Tumor-associated macrophages (TAM) secret many cytokines, chemokines and proteases, which also promote tumor angiogenesis, growth, metastasis and immunosuppression. TAM have multifaceted roles in the development of many tumor types. TAM also interact with cancer stem cells. This interaction leads to tumorigenesis, metastasis, and drug resistance. TAM obtain various immunosuppressive functions to maintain the tumor microenvironment. TAM are characterized by their heterogeneity and plasticity, as they can be functionally reprogrammed to polarized phenotypes by exposure to cancer-related factors, stromal factors, infections, or even drug interventions. Because TAMs produce tumor-specific chemokines by the stimulation of stromal factors, chemokines might serve as biomarkers that reflect disease activity. The evidence has shown that cancer tissues with high infiltration of TAM are associated with poor patient prognosis and resistance to therapies. Targeting of TAM in tumors is considered a promising therapeutic strategy for anti-cancer treatment.

Co-Expression of a Chimeric Protease Inhibitor Secreted by a Tumor-Targeted Salmonella Protects Therapeutic Proteins from Proteolytic Degradation

  • Quintero, David;Carrafa, Jamie;Vincent, Lena;Kim, Hee Jong;Wohlschlegel, James;Bermudes, David
    • Journal of Microbiology and Biotechnology
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    • v.28 no.12
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    • pp.2079-2094
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    • 2018
  • Sunflower trypsin inhibitor (SFTI) is a 14-amino-acid bicyclic peptide that contains a single internal disulfide bond. We initially constructed chimeras of SFTI with N-terminal secretion signals from the Escherichia coli OmpA and Pseudomonas aeruginosa ToxA, but only detected small amounts of protease inhibition resulting from these constructs. A substantially higher degree of protease inhibition was detected from a C-terminal SFTI fusion with E. coli YebF, which radiated more than a centimeter from an individual colony of E. coli using a culture-based inhibitor assay. Inhibitory activity was further improved in YebF-SFTI fusions by the addition of a trypsin cleavage signal immediately upstream of SFTI, and resulted in production of a 14-amino-acid, disulfide-bonded SFTI free in the culture supernatant. To assess the potential of the secreted SFTI to protect the ability of a cytotoxic protein to kill tumor cells, we utilized a tumor-selective form of the Pseudomonas ToxA (OTG-PE38K) alone and expressed as a polycistronic construct with YebF-SFTI in the tumor-targeted Salmonella VNP20009. When we assessed the ability of toxin-containing culture supernatants to kill MDA-MB-468 breast cancer cells, the untreated OTG-PE38K was able to eliminate all detectable tumor cells, while pretreatment with trypsin resulted in the complete loss of anticancer cytotoxicity. However, when OTG-PE38K was co-expressed with YebF-SFTI, cytotoxicity was completely retained in the presence of trypsin. These data demonstrate SFTI chimeras are secreted in a functional form and that co-expression of protease inhibitors with therapeutic proteins by tumor-targeted bacteria has the potential to enhance the activity of therapeutic proteins by suppressing their degradation within a proteolytic environment.

Extracellular acidity enhances tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis via DR5 in gastric cancer cells

  • Hong, Ran;Han, Song Iy
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.5
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    • pp.513-523
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    • 2018
  • The tumor microenvironment greatly influences cancer cell characteristics, and acidic extracellular pH has been implicated as an essential factor in tumor malignancy and the induction of drug resistance. Here, we examined the characteristics of gastric carcinoma (GC) cells under conditions of extracellular acidity and attempted to identify a means of enhancing treatment efficacy. Acidic conditions caused several changes in GC cells adversely affecting chemotherapeutic treatment. Extracellular acidity did inhibit GC cell growth by inducing cell cycle arrest, but did not induce cell death at pH values down to 6.2, which was consistent with down-regulated cyclin D1 and up-regulated p21 mRNA expression. Additionally, an acidic environment altered the expression of atg5, HSPA1B, collagen XIII, collagen XXAI, slug, snail, and zeb1 genes which are related to regulation of cell resistance to cytotoxicity and malignancy, and as expected, resulted in increased resistance of cells to multiple chemotherapeutic drugs including etoposide, doxorubicin, daunorubicin, cisplatin, oxaliplatin and 5-FU. Interestingly, however, acidic environment dramatically sensitized GC cells to apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Consistently, the acidity at pH 6.5 increased mRNA levels of DR4 and DR5 genes, and also elevated protein expression of both death receptors as detected by immunoblotting. Gene silencing analysis showed that of these two receptors, the major role in this effect was played by DR5. Therefore, these results suggest that extracellular acidity can sensitize TRAIL-mediated apoptosis at least partially via DR5 in GCs while it confers resistance to various type of chemotherapeutic drugs.

Historical research of the Chi Jong Cheong, - korean ancient tumor medical center (치종청(治腫廳)에 대한 의사학적 고찰)

  • Seo, Ji Youn;Kim, Nam Il;Ahn, Sang Woo
    • The Journal of Korean Medical History
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    • v.20 no.1
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    • pp.13-21
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    • 2007
  • In Korea tumors occurred frequently, and the tumor medicine used to treat them developed. Because tumors due to Koreans' physical constitution and environment and there has always been an impeding need for a cure, traces of such efforts can be found throughout Korean medical history. During the mid-Chosun dynasty, the government founded a government office that specialized in curing tumors. This study observes the establishment and operation of this institution.

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A Study of Yangseng-method in Tumor (종양(腫瘍)의 양생법(養生法)에 관한 소고(小考))

  • Shin, Yong-Cheol
    • Journal of Society of Preventive Korean Medicine
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    • v.12 no.3
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    • pp.213-222
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    • 2008
  • Objective : The Purpose of this study was to investigate the Yangseng-method in Tumor, to know how to help the patients from the disease. Method : In order to know the relations between Yangseng and disease, various books and reports are investigated. And the results as follows. Conclusions : According to the traditonal medical theory, Oriental medicine focused on Yangseng(養生). And it is able to resist the disease and adapt to the environment and assist the healing of the body. And it is in harmony with Qi-circulation, so smoothing the circulation of meridians, strengthened Essentialmaterial, Qi, Sprit. Yangseng can be effective for cancer patients to control mind and improve self-confidence and is helpful of preventation of disease and mental health. Especially Mind-control of Yangseng is more important of all.

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Mobi-kids: A Case-control Study Protocol on Electromagnetic Field Radiation Exposure from Telecommunication and Brain Tumors in Children and Adolescents (모비키즈: 통신전자파 노출과 어린이청소년의 뇌종양에 관한 환자 -대조군 연구 프로토콜)

  • Choi, Kyung-Hwa;Kim, Dong-Seok;Lee, Jung-il;Ra, Young-Shin;Phi, Ji Hoon;Ahn, Young Hwan;Kwon, Jong Hwa;Lee, Ae-Kyoung;Choi, Hyung-Do;Ha, Mina
    • Journal of Environmental Health Sciences
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    • v.41 no.3
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    • pp.182-190
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    • 2015
  • Objectives: To introduce a protocol of Mobi-kids study which was aimed to examine an association between radiofrequency (RF) radiation exposure by mobile phone use and brain tumor risk in children and adolescents. Methods: The Mobi-kids study was a multinational matched case control study using a standardized protocol with the number of subjects targeted about 1,000 cases and 2,000 controls aged 10 to 24. In Mobi-Kids Korea, the source population was restricted to Seoul, Incheon, and Gyeonggi-do province. Eligible cases of primary brain tumor (glioma, meningioma, and others) were diagnosed from January 2012 to June 2015. Eligible controls were appendicitis patients operated during the study period. Two controls were matched on age, gender, and study region for 1 case. Information about pattern and history of mobile phone use and other covariates were obtained by face to face interview by trained interviewer. The Mobi-kids study has been involved in Mobi-expo as a validation study about mobile phone use, XGridmaster to localize tumor in the brain for RF energy calculation, and histological review for validation of diagnosis. Results: The Mobi-kids was the first and largest study in children and adolescents to estimate risk of brain tumor in association with the RF energy absorption in the brain estimated by mobile phone use. Forty-six-cases and 54 controls were collected as of September 2014 in Korea. Conclusions: The meaningful results of the study were expected because of the largest sample size, high validity of EMF exposure assessment as well as the susceptible study populationof children and adolescents.

Antitumor and Apoptosis Induction Effects of Paeonol on Mice Bearing EMT6 Breast Carcinoma

  • Ou, Yetao;Li, Qingwang;Wang, Jianjie;Li, Kun;Zhou, Shaobo
    • Biomolecules & Therapeutics
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    • v.22 no.4
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    • pp.341-346
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    • 2014
  • Paeonol is a major phenolic micromolecular component of Moutan cortex Radicis, a traditional Chinese Medicine. It has shown antitumor effects in previous studies; however, the underlying mechanisms remain unknown. This study investigated the mechanism by giving treatments of placebo, cyclophosphamide, paeonol of 150 and 300 mg/kg to 4 groups of mice bearing EMT6 breast cancer. Apoptosis in tumor cells were confirmed by morphology analysis, including hematoxylin, eosin staining and TUNEL staining. The results showed that the weight of EMT6 breast tumor was significantly reduced in the groups treated with both 150 and 300 mg/kg of paeonol. Immunohistochemical and Western blot results showed that the expression of Bcl-2 was down-regulated while the expression of Bax, caspase 8 and caspase 3 was up-regulated respectively. These results suggest that paeonol exhibits antitumor effects and the mechanism of the inhibition is via induction of apoptosis, regulation of Bcl-2 and Bax expression, and activation of caspase 8 and caspase 3.

The Comparative of Inhibitory Effect of Various Solvent Extracts from Aloe arborescens and Aloe vera on Tumor Cell Lines Using Clonoginic Assay (Clonogenic Assay를 이용한 Aloe arborescens와 Aloe vera 용매 추출물의 종양세포 억제효과의 비교)

  • Hong, Hee-Sun;Lee, Keyong-Ho;Kim, Jeong-Hwan;Kang, Hee-Gon;Cho, Choa-Hyoung;Kim, Chang-Han
    • Korean Journal of Pharmacognosy
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    • v.30 no.3
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    • pp.275-279
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    • 1999
  • The solvent extracts from Aloe arborescens and Aloe vera were randomly screened for inhibitory effects on the growth of tumor cell lines. In case of Aloe vera extracts, butyl alcohol extract and ethyl alcohol extract showed antitumor activity at $100\;{\mu}g/ml$ on lung cell lines(A427, Sk-mes-1, Calu-3 and 3LL). In Aloe arborescens extracts, butyl alcohol extract and ethyl alcohol extract exerted high activity at $100\;{\mu}g/ml$ on breast cell line(Hs-578T) and lung cell line(Sk-mes-1), respectively. The solvent extracts from Aloe vera exerted antitumor activity broadly on various tumor cell lines. In contract, the solvent extracts from Aloe arborescens exerted specific antitumoricity on a few tumor cell lines.

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