• Title/Summary/Keyword: cancer tissue engineering

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p53 Nuclear Accumulation as a Possible Biomarker for Biological Radio-dosimetry in Oral Mucosal Epithelial Cells

  • Kim, Youn-Young;Kim, Jong-il;Kim, Jin;Yook, Jong-In;Kim, The-Hwan;Son, Young-Sook
    • BMB Reports
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    • v.34 no.2
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    • pp.123-129
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    • 2001
  • Cellular response to ionizing radiation is affected by cell types, radiation doses, and post-irradiation time. Based on the trypan blue dye exclusion assay in normal oral mucosal cells (OM cells), a 48 h post-irradiation was sufffcient and an adequate time point for the evaluation of radiation sensitivity Its $LD_{50}$ was approximately 1.83 Gy To investigate possible biomarkers useful for the biological radiodosimetry of normal epithelial cells (p53, c-fos, cyclin D1, cdc-2, pRb) EGF receptor phosphorylation and Erk activation were evaluated at different radiation doses and different post-irradiation times. From 0.5 Gy, p53 was accumulated in the nucleus of basal cells of the OM raft culture at 4 h post-irradiation and sustained up to 24 h post-irradiation, which suggests that radiation-induced apoptosis or damage repair was not yet completed. The number of p53 positive cells and biosynthesis of p53 were correlated with radiation doses. Both cyclin D1 and c-fos were only transiently induced within 1 h post-irradiation. Cyclin D1 was induced at all radiation doses. However, cfos induction was highest at 0.1 Gy, approximately 7.3 fold more induction than the control, whose induction was reduced in a reverse correlation with radiation dose. The phosphorylation pattern of cdc-2 and pRb were unaffected by radiation. In contrast to A431 tails overexpressing the EGF receptor approximately 8.5 fold higher than normal epithelial, the OM cells reduced the basal level of the EGF receptor phosphorylation in a radiation dose dependent fashion. In conclusion, among radiation-induced biomolecules, the p53 nuclear accumulation may be considered for the future development of a useful marker far biological radiodosimetry in normal epithelial tissue since it was sustained for a longer period and showed a dose response relationship. Specific c-fos induction at a low dose may also be an important finding in this study It needs to be studied further for the elucidation of its possible connection with the low dose radio-adaptive response.

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MicroRNA controls of cellular senescence

  • Suh, Nayoung
    • BMB Reports
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    • v.51 no.10
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    • pp.493-499
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    • 2018
  • Cellular senescence is a state of permanent cell-cycle arrest triggered by different internal and external stimuli. This phenomenon is considered to be both beneficial and detrimental depending on the cell types and biological contexts. During normal embryonic development and after tissue injury, cellular senescence is critical for tissue remodeling. In addition, this process is useful for arresting growth of tumor cells, particularly during early onset of tumorigenesis. However, accumulation of senescent cells decreases tissue regenerative capabilities and induces inflammation, which is responsible for cancer and organismal aging. Therefore cellular senescence has to be tightly regulated, and dysregulation might lead to the aging and human diseases. Among many regulators of cellular senescence, in this review, I will focus on microRNAs, small non-coding RNAs playing critical roles in diverse biological events including cellular senescence.

Microwave Cavity with Controllable Temperature for In Vitro Hyperthermia Investigations

  • Kiourti, Asimina;Sun, Mingrui;He, Xiaoming;Volakis, John L.
    • Journal of electromagnetic engineering and science
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    • v.14 no.3
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    • pp.267-272
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    • 2014
  • Hyperthermia is a form of cancer treatment in which affected human tissue is exposed to $>40^{\circ}C$ temperature. In this paper, our goal is to assess the efficacy of fullerene agents to reduce heating time for cancer treatment. Such agents can accelerate heating of cancer cells and improve hyperthermia treatment efficacy. Typically, in vitro testing involves cancer cell culturing, heating cell cultures in accordance to specifications, and recording cancer cell viability after hyperthermia. To heat cell cultures, we design and evaluate a 2.4-GHz microwave cavity with controllable temperature. The cavity is comprised of a polystyrene cell culture dish (diameter = 54 mm, height = 13.5 mm) and a printed monopole antenna placed within the cavity for microwave heating. The culture temperature can be controlled through the intensity and duration of the antenna's microwave radiation. Heating experiments were carried out to validate the cavity's performance for F-12K culture medium (Kaighn's F-12K medium, ATCC). Importantly, fullerene agents were shown to reduce heating time and improve hyperthermia treatment efficacy. The culture medium temperature increased, on average, from $24.0^{\circ}C$ to $50.9^{\circ}C$ (without fullerene) and from $24.0^{\circ}C$ to $56.8^{\circ}C$ (with 3 mg/mL fullerene) within 15 minutes.

Optical Monitoring of Tumors in BALB/c Nude Mice Using Optical Coherence Tomography

  • Song, Hyun-Woo;Lee, Sang-Won;Jung, Myung-Hwan;Kim, Kye Ryung;Yang, Seungkyoung;Park, Jeong Won;Jeong, Min-Sook;Jung, Moon Youn;Kim, Seunghwan
    • Journal of the Optical Society of Korea
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    • v.17 no.1
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    • pp.91-96
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    • 2013
  • We report a method for optical monitoring of tumors in an animal model using optical coherence tomography (OCT). In a spectral domain OCT system, a superluminescent diode light source with a full width of 66 nm at half maximum and peak wavelength of 950 nm was used to take images having an axial resolution of 6.8 ${\mu}m$. Cancer cells of PC-3 were cultured and inoculated into the hypodermis of auricle tissues in BALB/c nude mice. We observed tumor formation and growth at the injection region of cancer cells in vivo and obtained the images of tumor mass center and sparse circumferences. On the $5^{th}$ day from an inoculation of cancer cells, histological images of the tumor region using cross-sectional slicing and dye staining of specimens were taken in order to confirm the correlation with the high resolution OCT images. The OCT image of tumor mass compared with normal tissues was analyzed using its A-scan data so as to obtain a tissue attenuation rate which increases according to tumor growth.

Mechanosensitive ion channels in apoptosis and ferroptosis: focusing on the role of Piezo1

  • Yong-Jae Kim;Jeongeun Hyun
    • BMB Reports
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    • v.56 no.3
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    • pp.145-152
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    • 2023
  • Mechanosensitive ion channels sense mechanical stimuli applied directly to the cellular membranes or indirectly through their tethered components, provoking cellular mechanoresponses. Among others, Piezo1 mechanosensitive ion channel is a relatively novel Ca2+-permeable channel that is primarily present in non-sensory tissues. Recent studies have demonstrated that Piezo1 plays an important role in Ca2+-dependent cell death, including apoptosis and ferroptosis, in the presence of mechanical stimuli. It has also been proven that cancer cells are sensitive to mechanical stresses due to higher expression levels of Piezo1 compared to normal cells. In this review, we discuss Piezo1-mediated cell death mechanisms and therapeutic strategies to inhibit or induce cell death by modulating the activity of Piezo1 with pharmacological drugs or mechanical perturbations induced by stretch and ultrasound.

Effect of Trichostatin A on Anti HepG2 Liver Carcinoma Cells: Inhibition of HDAC Activity and Activation of Wnt/β-Catenin Signaling

  • Shi, Qing-Qiang;Zuo, Guo-Wei;Feng, Zi-Qiang;Zhao, Lv-Cui;Luo, Lian;You, Zhi-Mei;Li, Dang-Yang;Xia, Jing;Li, Jing;Chen, Di-Long
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.18
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    • pp.7849-7855
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    • 2014
  • Purpose: To investigate the effect of deacetylase inhibitory trichostatin A (TSA) on anti HepG2 liver carcinoma cells and explore the underlying mechanisms. Materials and Methods: HepG2 cells exposed to different concentrations of TSA for 24, 48, or 72h were examined for cell growth inhibition using CCK8, changes in cell cycle distribution with flow cytometry, cell apoptosis with annexin V-FTIC/PI double staining, and cell morphology changes under an inverted microscope. Expression of ${\beta}$-catenin, HDAC1, HDAC3, H3K9, CyclinD1 and Bax proteins was tested by Western blotting. Gene expression for ${\beta}$-catenin, HDAC1and HDAC3 was tested by q-PCR. ${\beta}$-catenin and H3K9 proteins were also tested by immunofluorescence. Activity of Renilla luciferase (pTCF/LEF-luc) was assessed using the Luciferase Reporter Assay system reagent. The activity of total HDACs was detected with a HDACs colorimetric kit. Results: Exposure to TSA caused significant dose-and time-dependent inhibition of HepG2 cell proliferation (p<0.05) and resulted in increased cell percentages in G0/G1 and G2/M phases and decrease in the S phase. The apoptotic index in the control group was $6.22{\pm}0.25%$, which increased to $7.17{\pm}0.20%$ and $18.1{\pm}0.42%$ in the treatment group. Exposure to 250 and 500nmol/L TSA also caused cell morphology changes with numerous floating cells. Expression of ${\beta}$-catenin, H3K9and Bax proteins was significantly increased, expression levels of CyclinD1, HDAC1, HDAC3 were decreased. Expression of ${\beta}$-catenin at the genetic level was significantly increased, with no significant difference in HDAC1and HDAC3 genes. In the cytoplasm, expression of ${\beta}$-catenin fluorescence protein was not obvious changed and in the nucleus, small amounts of green fluorescence were observed. H3K9 fluorescence protein were increased. Expression levels of the transcription factor TCF werealso increased in HepG2 cells following induction by TSA, whikle the activity of total HDACs was decreased. Conclusions: TSA inhibits HDAC activity, promotes histone acetylation, and activates Wnt/${\beta}$-catenin signaling to inhibit proliferation of HepG2 cell, arrest cell cycling and induce apoptosis.

Gut Microbiota-Derived Short-Chain Fatty Acids, T Cells, and Inflammation

  • Kim, Chang H.;Park, Jeongho;Kim, Myunghoo
    • IMMUNE NETWORK
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    • v.14 no.6
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    • pp.277-288
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    • 2014
  • T cells are central players in the regulation of adaptive immunity and immune tolerance. In the periphery, T cell differentiation for maturation and effector function is regulated by a number of factors. Various factors such as antigens, co-stimulation signals, and cytokines regulate T cell differentiation into functionally specialized effector and regulatory T cells. Other factors such as nutrients, micronutrients, nuclear hormones and microbial products provide important environmental cues for T cell differentiation. A mounting body of evidence indicates that the microbial metabolites short-chain fatty acids (SCFAs) have profound effects on T cells and directly and indirectly regulate their differentiation. We review the current status of our understanding of SCFA functions in regulation of peripheral T cell activity and discuss their impact on tissue inflammation.

Peripheral Blood Immune Cell-based Biomarkers in Anti-PD-1/PD-L1 Therapy

  • Kyung Hwan Kim;Chang Gon Kim;Eui-Cheol Shin
    • IMMUNE NETWORK
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    • v.20 no.1
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    • pp.8.1-8.15
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    • 2020
  • Immune checkpoint blockade targeting PD-1 and PD-L1 has resulted in unprecedented clinical benefit for cancer patients. Anti-PD-1/PD-L1 therapy has become the standard treatment for diverse cancer types as monotherapy or in combination with other anticancer therapies, and its indications are expanding. However, many patients do not benefit from anti-PD-1/PD-L1 therapy due to primary and/or acquired resistance, which is a major obstacle to broadening the clinical applicability of anti-PD-1/PD-L1 therapy. In addition, hyperprogressive disease, an acceleration of tumor growth following anti-PD-1/PD-L1 therapy, has been proposed as a new response pattern associated with deleterious prognosis. Anti-PD-1/PD-L1 therapy can also cause a unique pattern of adverse events termed immune-related adverse events, sometimes leading to treatment discontinuation and fatal outcomes. Investigations have been carried out to predict and monitor treatment outcomes using peripheral blood as an alternative to tissue biopsy. This review summarizes recent studies utilizing peripheral blood immune cells to predict various outcomes in cancer patients treated with anti-PD-1/PD-L1 therapy.

High Intensity Focused Ultrasound for Cancer Treatment: Current Agenda and the Latest Technology Trends (HIFU: 현황 및 기술적 동향)

  • Seo, Jong-Bum
    • The Journal of the Acoustical Society of Korea
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    • v.29 no.2E
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    • pp.55-63
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    • 2010
  • High Intensity Focused Ultrasound (HIFU) is a noninvasive surgical method mainly targeting deeply located cancer tissue. Ultrasound is generated from an extemally located transducer and the beam is focused at the target volume, so that selective damage can be achieved without harm to overlying or surrounding tissues. The mechanism for cell killing can be combination of thermal and cavitational damage. Although cavitation can be an effective means of tissue destruction, the possibility of massive hemorrhage and the unpredictable nature of cavitational events prevent clinical application of cavitation. Hence, thermal damage has been a main focus related to HIFU research. 2D phased array transducer systems allow electronic scanning of focus, multi-foci, and anti-focus with multi-foci, so that HIFU becomes more applicable in clinical use. Currently, lack of noninvasive monitoring means of HIFU is the main factor to limit clinical applications, but development in MRI and Ultrasound Imaging techniques may be able to provide solutions to overcome this problem. With the development of advanced focusing algorithm and monitoring means, complete noninvasive surgery is expected to be implemented in the near future.

Detection of Mammographic Microcalcifications by Pattern Matching (Pattern Matching을 이용한 유방영상의 미세 석회화 검출)

  • Yang, Y.S.;Kim, E.K.;Kim, D.W.
    • Proceedings of the KOSOMBE Conference
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    • v.1997 no.05
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    • pp.68-71
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    • 1997
  • The early detection of brest cancer is clearly a key ingredient for any strategy designed to reduce breast cancer mortality. Microcalcification(MCC) is one of the primary signatures to discriminate between normal and cancerous tissue. The detection and locating procedures can be automated by digital image processing, however, MCCs have various sizes, shapes, and intensity levels in film images, so it is difficult to find accurate locations and sizes. Firstly, we made quantitative analysis for many characteristic features of mammograms that can be used to segment MCCs from normal tissues. Secondly, we developed algorithms proper to segmentation like pattern matching. The performance was evaluated with TP and FP rates.

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