• BMB Reports
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• 제41권10호
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• pp.728-732
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• 2008

FoxO3a is a member of the forkhead box class O (FoxO) transcription factor family and an important regulator of apoptosis. This work aimed to elucidate the involvement of FoxO3a in transforming growth factor-${\beta}1$(TGF-${\beta}1$)-induced apoptosis in FaO rat hepatoma cells. TGF-${\beta}1$ caused a time-dependent activation of FoxO3a and a subsequent increase in FoxO response-element-containing luciferase reporter activity, which was Akt-sensitive. The FaO cells stably transfected with a wild type FoxO3a were more susceptible to the formation of apoptotic bodies, populations of sub-G1 apoptotic cells, and collapse of the mitochondrial-membrane potential triggered by TGF-${\beta}1$. In contrast, transfection with small-interfering RNA (siRNA) oligonucleotide specific for FoxO3a significantly inhibited caspase activation in FaO cells treated with TGF-${\beta}1$. It thus appears that FoxO3a plays a crucial mediatory role in the TGF-${\beta}1$ signaling pathway leading to apoptosis.

• Radiation Oncology Journal
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• 제32권3호
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• pp.208-212
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• 2014

Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-${\beta}1$) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-${\beta}1$ level during and after treatment. Despite maintaining stable levels of plasma TGF-${\beta}1$, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.

• Journal of Periodontal and Implant Science
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• 제31권2호
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• pp.421-436
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• 2001

Transforming growth $factor-{\beta}(TGF-{\beta})$is a polypeptide biologic mediator considered to play a role in promoting bone formation in bony defect area. The purpose of this study was to examine the effect of $TGF-{\beta}$ to the periodontal regeneration of class III furcation defect in dogs. Classs III furcation defects were surgically created on the third and the fourth premolars bilaterally in the mandibles of eight mongrel dogs. Experimental periodontitis were induced by placing small cotton pellets into the created defects for 3 weeks. Experimental sites were divided into 4 groups according to the treatment modalities: Group I-Surgical debridement only; Group II-allogenic demineralized freeze dried bone grafting; Group III-allogenic demineralized freeze dried bone soaked in $TGF-{\beta}(4ng/10{\mu}l)$grafting; Group IV-allogenic demineralized freeze dried bone soaked in $TGF-{\beta}(20ng/10{\mu}l)$ grafting. The animals were sacrificed in the 8th week after periodontal surgery and the decalcified and undecalcified specimens were for histological and histometric examination. Although no significant differences was seen in the length of epitheial growth and connective attachment, group III showed the least apical migration among treatment groups. The amount of bone repair was significantly greater in group III, IV compared to group I and group II. New attachment formation was significantly greater in group III and group IV compared to group I and group II. These results suggest the allogenic demineralized freeze dried bone with $TGF-{\beta}$ in class III furcation defect has the potentiality of promoting alveolar bone formation and periodontal regeneration.

• Clinical and Experimental Reproductive Medicine
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• 제38권4호
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• pp.210-215
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• 2011

Objective: This study was performed to identify whether growth and differentiation factor-9 (GDF-9) and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) expressions would be lower in the follicular fluid (FF) of those over age 35 who underwent IVF than under age 35. Methods: A total of 24 IVF cycles (20 patients) were included in this study. All of patients were stimulated for IVF by the GnRH short protocol and divided into two groups for analysis, according to their age: <35 group (14 cycles, 11 patients) vs. ${\geq}35$ group (10 cycles, 9 patients). The expression levels of GDF-9 and TGF-${\beta}1$ were determined by western blotting and quantitative enzyme-linked immunosorbent assay. Results: The numbers of retrieved oocytes and metaphase II oocytes were significantly lower in the ${\geq}35$ group. Lower expression of GDF-9 and TGF-${\beta}1$ by western blotting in the ${\geq}35$ group were observed as well. The mean GDF-9 and TGF-${\beta}1$ levels by enzyme-linked immunosorbent assay were lower in the ${\geq}35$ group. The values were $6,850.5{\pm}928.4$ ng/L vs. $3,333.3{\pm}1,089.2$ ng/L of GDF-9 ($p$ <0.05) and $3,844.1{\pm}571.1$ ng/L vs. $2,187.7{\pm}754.0$ ng/L of TGF-${\beta}1$ ($p$ <0.05). A negative correlation between GDF-9 and age was observed (r=-0.546, $p$=0.006). Conclusion: GDF-9 and TGF-${\beta}1$ production from stimulated ovaries during IVF appears to decrease with age.

• IMMUNE NETWORK
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• 제1권2호
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• pp.143-150
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• 2001

Background : Many investigators have found transforming growth factor-${\beta}1$ (TGF-${\beta}1$) to be elevated in tumors. Changes in responsiveness to TGF-${\beta}1$ have been linked to malignant transformation, tumor progression and tumor regression. Many malignant cell lines of epithelial or hematopoietic origin are refractory to the antiproliferative effects of TGF-${\beta}1$. However, a little is known about the association of TGF-${\beta}1$ with progression of malignant tumor. Methods : In this study, we measured the plasma level of TGF-${\beta}1$ in various cancer patients and evaluated the utility of plasma TGF-${\beta}1$ as a possible tumor marker. Plasma TGF-${\beta}1$ levels were measured using enzyme-linked immunosorbent assay in cancer patients and normal controls. Carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) as tumor marker were compared with TGF-${\beta}1$ in the aspects of sensitivity and specificity. Results : The mean of plasma TGF-${\beta}1$ levels was $1.219{\pm}0.834ng/ml$ in normal controls, $5.491{\pm}3.598ng/ml$ in breast cancer, $12.670{\pm}10.386ng/ml$ in lung cancer, $5.747{\pm}3.228ng/ml$ in hepatocellular carcinoma and $10.854{\pm}7.996ng/ml$ in cervical cancer. In comparison with CEA and AFP, TGF-${\beta}1$ is more sensitive. Conclusion : We conclude that the high levels of TGF-${\beta}1$ are common in the plasma of cancer patients. These results suggest that the plasma TGF-${\beta}1$ level can be a potent tumor marker in various cancer patients.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제26권6호
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• pp.565-580
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• 2000

This study was designed to evaluate the influence of cultured epidermal tissue graft and the administration of transforming growth factor(TGF)-${\beta}_3$ on maxillary growth in surgically created palatal defects. A total of 155 rats were divided into 2 groups according to surgical timing : postnatal 2 weeks(n=95), 4 weeks(n=40) and control(unoperated) group(n=20). The postnatal 2-week surgical group was subdivided into 3 groups according to repair methods: conventional surgery(Von Langenbeck technique)group(n=23); cultured tissue graft group(n=25); and full thickness skin graft group(n=25). Additionally, recombinant human TGF-${\beta}_3$ was administered(30ng or 150ng) on collagen matrix in surgically created palatal defects during surgery(9 conventional surgeries, 9 cultured tissue grafts) in 2-week-old rats. The results showed that all types of surgical treatment decreased maxillary growth compared with the control(unoperated) group(p<0.0001). On the other hand, the tissue graft group, whether cultured tissue or grafted skin, contributed to increased maxillary growth(p<0.0001).And exogenous TGF-${\beta}_3$ might play a role in connective tissue proliferation and new bone generation during wound healing on palatal defects. Our results suggest that grafting cultured epidermis with collagen matrix decreases the scar tension on maxillary growth more than conventional palatal surgery does. Therefore, exogenous TGF-${\beta}_3$ may contribute to accelerate wound healing on palatal defects.

• IMMUNE NETWORK
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• 제9권4호
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• pp.122-126
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• 2009

Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.

• IMMUNE NETWORK
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• 제14권3호
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• pp.156-163
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• 2014

Interleukin (IL) 17 is produced by T-helper (Th) 17 with a vigorous effect on cells of the immune system playing important roles in pathogenesis of immune-mediated diseases, including autoimmune disorders and cancers. Therefore, the aim of current study was to determine the serum levels of IL-6, IL-17, and transforming growth factor beta (TGF-${\beta}$) in Iranian bladder cancer patients, and to correlate them with disease status. Blood samples were collected from 40 bladder cancer patients and 38 healthy individuals with no history of malignancies or autoimmune disorders. The serum levels of IL-6, IL-17, and TGF-${\beta}$ were measured by the enzyme-linked immunosorbent assay (ELISA). The results showed that the levels of IL-17 (p<0.0001) and TGF-${\beta}$ (p<0.0001) were significantly lower in the patients compared to the controls. No significant differences in the level of serum IL-6 (p=0.16) was observed between the patients and controls. In addition, demographic characteristics between control and patients groups were not significantly different. As most of the cases studied in this investigation were in stage I and II, it is concluded that reduced Th17-related cytokines can be used as indicators for following the course and clinical stages of bladder carcinoma progress and immune response to cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• 대한의생명과학회지
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• 제5권2호
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• pp.181-190
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• 1999

한국인의 대표적인 성인 고형 종양인 위암, 간암, 유방암과 소아 백혈병 및 2종의 소아 고형 종양 환자로부터 혈장 transforming growth factor-$\beta$1 (TGF-$\beta$1) 농도를 sandwich ELISA 분석법을 이용해 측정함으로써 TGF-$\beta$1을 이 질환들에 대한 새로운 종양표지자 (tumor marker)로 사용할 수 있는지 검토하였다. 토한 연령 및 성별에 따른 혈장 TGF-$\beta$1 농도의 정상치를 조사하였다. 신생아에서 70대까지 혈장 TGF-$\beta$1 농도의 차이는 없었고 남녀간의 차이도 없었다. 위암 환자의 혈장 TGF-$\beta$1 농도는 16.0$\pm$6.8 ng/ml (평균$\pm$표준편차)로 정상 대조군의 TGF-$\beta$1 농도 (8.3$\pm$5.0 ng/ml) 보다 유의하게 높았으나 간암, 유방암 환자의 혈장 TGF-$\beta$1 농도는 대조군과 차이가 없었다. 그리고 위암 환자 16명 ,간암 환자 8명, 유방암 환자 7명 중 각각 7명 (43.7%), 1명 (12.5%), 1명 (14.3%)에서만 혈장 TGF-$\beta$1 농도가 증가되었다. 5명의 소아 백혈병 환자에서는 관해 (remission)여부와 상관없이 혈장TGF-$\beta$1농도가 모두 정상 범위에 있었으나 2명의 소아 고형암 환자에서는 종양 절제 전에는 혈장 TGF-$\beta$1농도가 높았다가 절제 후 정상으로 떨어졌다. 결론적으로 1)정상인의 혈장 TGF-$\beta$1 농도는 연령 및 성별에 따른 차이가 없다는 것을 알 수 있었고, 2)성인 고형암인 위암, 간암, 유방암에서는 낮은 민감도로 인해 TGF-$\beta$1을 진단을 위한 선별 검사로 이용하기에는 부적절한 것으로 판단되었으며, 3)정상 대조군보다 혈장 TGF-$\beta$1 농도가 높았던 위 암 환자와 종양 절제 전후로 혈장 TGF-$\beta$1 농도가 민감하게 변했던 소아 고형암 환자에 대 해서는 향후 표본 수를 늘려 부가적인 연구를 해야 할 것으로 사료된다.