• Title/Summary/Keyword: therapeutic factor

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Influence of Serum VEGF Levels on Therapeutic Outcome and Diagnosis/Prognostic Value in Patients with Cervical Cancer

  • Du, Ke;Gong, Hong-Ying;Gong, Zhi-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8793-8796
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    • 2014
  • Objective: To explore the influence of serum vascular endothelial growth factor (VEGF) level on therapeutic outcome and diagnosis/prognostic value in patients with cervical cancer. Materials and Methods: A total of 37 patients diagnosed with cervical cancer by biopsy were selected and treated with concurrent chemoradiotherapy. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was adopted before treatment to assess VEGF levels, and its relationships with clinicopathological features and short-term therapeutic effects were analyzed. Results: The median VEGF level in 37 patients before treatment was 647.15 (393.35~1125.16) pg/mL. Serum VEGF levels in patients aged <50 years, in International Federation of Gynecology and Obstetrics (FIGO) stage IIIa~IVa, with lymph node metastasis and tumor size >4 cm were significantly increased (P<0.05). The complete remission (CR) rate was 48.7% (18/37), partial remission (PR) rate was 35.1% (13/37), stable disease (SD) rate was 13.5% (5/37) and progressive disease (PD) rate was 2.70% (1/37), so the objective remission rate (ORR) after treatment was 83.8% (31/37). Logistic regression analysis showed that tumor size and serum VEGF level before treatment were independent risk factors affecting the therapeutic outcome, and the higher the level of serum VEGF, the worse the prognosis when tumor size>4 cm. Some 56.8% of patients manifested with myelosuppression, 37.8% with leucopenia, 24.3% with thrombocytopenia, 5.41% with diarrhea, 46.0% with nausea and vomiting, 21.6% with hair loss and 8.11% with hepatic and renal injury during the treatment. Conclusions: Serum VEGF level may reflect the degree of malignancy of cervical cancer and predict therapeutic effect, which is of great importance to cancer diagnosis and prognosis.

The Study of Tissue Dose Perturbation by Air Cavity with 6MV Photon Beam (6MV 광자선에서 공동에 의한 조직 선량변동에 관한 연구)

  • Shin, Byung-Chul;Yoo, Myung-Jin;Moon, Chang-Woo;Jeung, Tae-Sig;Yum, Ha-Yong
    • Radiation Oncology Journal
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    • v.13 no.4
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    • pp.397-402
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    • 1995
  • Purpose : To determine the perturbation effect in the tissue downstream from surface layers of lesions located in the air/tumor-tissue interface of larynx using 6MV photon beam. Materials and Methods : Thermoluminescent dosimeters(TLDs), were embedded at 3 measurement locations in slab no. 7 of a humanoid phantom and exposed to forward and backward direction using various field sizes($4{\times}4cm^2\;-\;15{\times}15cm^2$). Results : At the air/tissue interface, forward dose perturbation factor(FDPF) is about 1.085 with $4{\times}4cm^2,\;1.05\;with\;7{\times}7cm^2,\;1.048\;with\;10{\times}10cm^2$ and $1.041\;with\;15{\times}15cm^2$. Backscatter dose perturbation factor(BDPF) is about 0.99 with $4{\times}4cm^2$, 0.981 with $7{\times}7cm^2$, 0.956 with $10{\times}10cm^2$ and 0.97 with $15{\times}15cm^2$. Conclusion : FDPF is greater as field size is smaller. And FDPF is smaller as the distance is further from the air/tissue interface.

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The Effects of Alkaloid Fraction of Korean Ginseng on the Radiation-Induced DNA Strand Breaks (방사선 조사에 의한 DNA Double Strand Breaks의 생성 및 회복에 미치는 인삼 알칼로이드 분획의 효과)

  • Cho Chul Koo;Kim Tae Hwan;Yoo Seong Yul;Koh Kyoung Hwan;Kim Mi Sook;Kim Jeong Hee;Kim Seong Ho;Yoon Hyung Keun;Ji Young Hoon
    • Radiation Oncology Journal
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    • v.13 no.2
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    • pp.113-120
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    • 1995
  • Purpose : To investigate the effect of alkaloid fraction from Korean ginseng on radiation-induced DNA double strand breaks (dsb) formation and repair in murine lymphocytes Materials and Methods : We used the neutral filter elution technique to assay $^{60}Co\;{\gamma}$ ray-induced DNA double strand breaks formation and repair in C57BL/6 mouse spleen lymphocytes for evaluating the dose-response relationship in the presence of alkaloid fraction as a radioprotective agent. The lymphocytes were stimulated with Phytohemagglutinin (PHA, 2 u g/ml) to label $^3[H]-thymidine.$ Isotope-labelled lymphocytes in suspension were exposed to 100 Gy at $0^{\cdot}C$ in the alkaloid fraction-treated group and elution procedure was performed at PH 9.6. The extents of formation of radiation-induced DNA double strand breaks and repair were compared respectively via strand scission factor (SSF) and relative strand scission factor (RSSF). Results: Alkaloid fraction reduced the formation of double strand breaks with dose modification factor of 2 15, compared to control group Rejoining of DNA dsb appeared to take place via two components. The first fast component was completed within 20.4 minutes, but the second slow component was not completed until 220.2 minutes after irradiation. About $30\%$ of dsb formed by irradiation was ultimately unrejoined despite the administration of alkaloid fraction. The administration of alkaloid fraction had a great effect on the second slow component of repair; the half-time of fast component repair was not changed, but that of slow component was 621.8 minutes. Conclusion: Neutral filter elution assay Proved to be a very effective method to quantitate the extents of DNA dsb formation and its repair. By using this technique, we were able to evaluate the efficiency of alkaloid fraction from Korean ginseng as a valuable radioprotector. Alkaloid fraction can be used prophylactically to prevent or ameliorate the severe radiation damages in workers and neighbors around the atomic power plants. For more refined study, however, more advanced purification of alkaloid fraction wil be needed in the near future.

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The Effect of EGF, T3 and HB-EGF on Human Periodontal Fibroblasts (EGF, T3, HB-EGF 가 치주인대섬유모세포에 미치는 영향)

  • Hong, Eun-Kyoung;Cha, Jeong-Heon;Kim, Yun-Tae;Choi, Byung-Jai;Kim, Seong-Oh
    • Journal of the korean academy of Pediatric Dentistry
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    • v.34 no.3
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    • pp.438-446
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    • 2007
  • Viable cells of periodontal ligament would be an important factor for the successful replantation of an avulsed tooth. Therefore, it is critical to choose the storage medium for the preservation of traumatically avulsed teeth. Growth factors and hormones could be considered for the therapeutic application of the maintenance of viable periodontal ligament fibroblasts (PDLFs). Epidermal growth factor (EGF) has been suggested as an important player for the regeneration and wound healing process on other tissues. Therefore, EGF was evaluated for the therapeutic application on avulsed teeth. In addition, the synergic effect of EGF with tri-iodothyronine (T3) and heparin-binding epidermal growth factor-like growth factor (HB-EGF). The cell proliferation of PDLFs was determined by MTT assay and increased dose-dependently up to 10 ng/ml in the presence of EGF. Maximum cellular growth was shown at the concentration of 10 ng/ml EGF. Also, EGF promoted the wound healing of PDLFs examined by in vitro wound healing assay. Combined effects of EGF with T3 or HB-EGF on the proliferation of PDLFs were also studied. Interestingly, EGF showed the synergic effect on the proliferation of PDLFs with T3 and HB-EGF. To find out the mechanism of the synergic effect of EGF and T3, the effect of T3 on the expression of endogenous EGF receptor was determined by RT-PCR. The result was that T3 enhanced the expression of EGF receptor in PDLFs. It suggested that EGF might be a good choice for a therapeutic application, which can be used as combination with T3 and HB-EGF.

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Influence of Upper extremity function, Activities of Daily Living, Therapeutic Flow and Quality of Life in Stroke patients (뇌졸중 환자의 상지기능, 일상생활활동, 치료적 몰입이 삶의 질에 미치는 영향)

  • Kim, Ji-Hoon
    • Journal of Digital Convergence
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    • v.16 no.12
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    • pp.417-425
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    • 2018
  • The purpose of this study was to analyzed the correlation between upper extremity function, activities of daily living, quality of life and therapeutic flow in stroke clients and identify the factors influencing therapeutic flow. Total 249 stroke patients from 13 hospitals were measure at therapist and researcher for upper extremity function, activities of daily living, therapeutic flow and quality of life. Factors that affect the quality of life correlation as s result of positively correlated with upper extremity function(r=.312, p<.001), activities of daily living(r=.605, p<.001), therapeutic flow(r=.525, p<.001). And the effect on quality of life in stroke clients variables affecting therapeutic flow(${\beta}=.344$, p<.001), activities of daily living(${\beta}=.293$, p<.05) and Time since of onset(${\beta}=.145$, p<.05) were the order of analysis. The regression model explained 35.9% of variances(F=35.736, p<.001). Therefore, it was found that therapeutic flow in stroke clients is an important factor for quality of life, future therapeutic flow study will continue to be needed.

Enhancement of Neural Death by Nerve Growth Factor

  • Chung, Jun-Mo;Hong, Jin-Hee
    • BMB Reports
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    • v.29 no.3
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    • pp.200-204
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    • 1996
  • Nerve growth factor (NGF) is literally known to promote neural differentiation and survival in several peripheral and central neurons. Thus, it is Widely believed that NGF may serve as a therapeutic agent for many types of neuronal diseases. One of the mechanisms suggested to explain the protective role of NGF is that the trophic factor can prevent the increase of intracellular calcium ions which might be responsible for neural death. To examine whether or not the calcium hypothesis works even under pathological conditions, we applied NGF to cultures deprived of glucose. Surprisingly, what was observed here is that NGF rather promoted cell death under a glucose-deprived condition. What we call the NGF paradox phenomenon occurred in a calcium concentration-dependent manner, indirectly suggesting that NGF might increase intracellular calcium ions in cells deprived of glucose. This suggestion is further supported by the fact that nifedipine, a well-known L-type calcium channel blocker, could block the cell death potentiated by NGF. Here it is still premature to propose the complete mechanism underlying the NGF paradox phenomenon. However, this study certainly indicates that NGF as a therapeutic agent for neuronal diseases should be carefully considered before use.

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Regulation of Wound Healing and Fibrosis by Hypoxia and Hypoxia-Inducible Factor-1

  • Ruthenborg, Robin J.;Ban, Jae-Jun;Wazir, Anum;Takeda, Norihiko;Kim, Jung-Whan
    • Molecules and Cells
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    • v.37 no.9
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    • pp.637-643
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    • 2014
  • Wound healing is a complex multi-step process that requires spatial and temporal orchestration of cellular and non-cellular components. Hypoxia is one of the prominent microenvironmental factors in tissue injury and wound healing. Hypoxic responses, mainly mediated by a master transcription factor of oxygen homeostasis, hypoxia-inducible factor-1 (HIF-1), have been shown to be critically involved in virtually all processes of wound healing and remodeling. Yet, mechanisms underlying hypoxic regulation of wound healing are still poorly understood. Better understanding of how the wound healing process is regulated by the hypoxic microenvironment and HIF-1 signaling pathway will provide insight into the development of a novel therapeutic strategy for impaired wound healing conditions such as diabetic wound and fibrosis. In this review, we will discuss recent studies illuminating the roles of HIF-1 in physiologic and pathologic wound repair and further, the therapeutic potentials of HIF-1 stabilization or inhibition.

Therapeutic potential of targeting kinase inhibition in patients with idiopathic pulmonary fibrosis

  • Kim, Suji;Lim, Jae Hyang;Woo, Chang-Hoon
    • Journal of Yeungnam Medical Science
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    • v.37 no.4
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    • pp.269-276
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    • 2020
  • Fibrosis is characterized by excessive accumulation of extracellular matrix components. The fibrotic process ultimately leads to organ dysfunction and failure in chronic inflammatory and metabolic diseases such as pulmonary fibrosis, advanced kidney disease, and liver cirrhosis. Idiopathic pulmonary fibrosis (IPF) is a common form of progressive and chronic interstitial lung disease of unknown etiology. Pathophysiologically, the parenchyma of the lung alveoli, interstitium, and capillary endothelium becomes scarred and stiff, which makes breathing difficult because the lungs have to work harder to transfer oxygen and carbon dioxide between the alveolar space and bloodstream. The transforming growth factor beta (TGF-β) signaling pathway plays an important role in the pathogenesis of pulmonary fibrosis and scarring of the lung tissue. Recent clinical trials focused on the development of pharmacological agents that either directly or indirectly target kinases for the treatment of IPF. Therefore, to develop therapeutic targets for pulmonary fibrosis, it is essential to understand the key factors involved in the pathogenesis of pulmonary fibrosis and the underlying signaling pathway. The objective of this review is to discuss the role of kinase signaling cascades in the regulation of either TGF-β-dependent or other signaling pathways, including Rho-associated coiled-coil kinase, c-jun N-terminal kinase, extracellular signal-regulated kinase 5, and p90 ribosomal S6 kinase pathways, and potential therapeutic targets in IPF.

Identification of MFGE8 in mesenchymal stem cell secretome as an anti-fibrotic factor in liver fibrosis

  • Jang, Yu Jin;An, Su Yeon;Kim, Jong-Hoon
    • BMB Reports
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    • v.50 no.2
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    • pp.58-59
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    • 2017
  • The beneficial paracrine roles of mesenchymal stem cells (MSCs) in tissue repair have potential in therapeutic strategies against various diseases. However, the key therapeutic factors secreted from MSCs and their exact molecular mechanisms of action remain unclear. In this study, the cell-free secretome of umbilical cord-derived MSCs showed significant anti-fibrotic activity in the mouse models of liver fibrosis. The involved action mechanism was the regulation of hepatic stellate cell activation by direct inhibition of the $TGF{\beta}$/Smad-signaling. Antagonizing the milk fat globule-EGF factor 8 (MFGE8) activity blocked the anti-fibrotic effects of the MSC secretome in vitro and in vivo. Moreover, MFGE8 was secreted by MSCs from the umbilical cord as well as other tissues, including teeth and bone marrow. Administration of recombinant MFGE8 protein alone had a significant anti-fibrotic effect in two different models of liver fibrosis. Additionally, MFGE8 downregulated $TGF{\beta}$ type I receptor expression by binding to ${\alpha}v{\beta}3$ integrin on HSCs. These findings revealed the potential role of MFGE8 in modulating $TGF{\beta}$-signaling. Thus, MFGE8 could serve as a novel therapeutic agent for liver fibrosis.

Global Proteomic Analysis of Mesenchymal Stem Cells Derived from Human Embryonic Stem Cells via Connective Tissue Growth Factor Treatment under Chemically Defined Feeder-Free Culture Conditions

  • Seo, Ji-Hye;Jeon, Young-Joo
    • Journal of Microbiology and Biotechnology
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    • v.32 no.1
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    • pp.126-140
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    • 2022
  • Stem cells can be applied usefully in basic research and clinical field due to their differentiation and self-renewal capacity. The aim of this study was to establish an effective novel therapeutic cellular source and create its molecular expression profile map to elucidate the possible therapeutic mechanism and signaling pathway. We successfully obtained a mesenchymal stem cell population from human embryonic stem cells (hESCs) cultured on chemically defined feeder-free conditions and treated with connective tissue growth factor (CTGF) and performed the expressive proteomic approach to elucidate the molecular basis. We further selected 12 differentially expressed proteins in CTGF-induced hESC-derived mesenchymal stem cells (C-hESC-MSCs), which were found to be involved in the metabolic process, immune response, cell signaling, and cell proliferation, as compared to bone marrow derived-MSCs(BM-MSCs). Moreover, these up-regulated proteins were potentially related to the Wnt/β-catenin pathway. These results suggest that C-hESC-MSCs are a highly proliferative cell population, which can interact with the Wnt/β-catenin signaling pathway; thus, due to the upregulated cell survival ability or downregulated apoptosis effects of C-hESC-MSCs, these can be used as an unlimited cellular source in the cell therapy field for a higher therapeutic potential. Overall, the study provided valuable insights into the molecular functioning of hESC derivatives as a valuable cellular source.