• Biomolecules & Therapeutics
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• v.21 no.5
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• pp.323-331
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• 2013

TGF-${\beta}$ pathway is being extensively evaluated as a potential therapeutic target. The transforming growth factor-${\beta}$ (TGF-${\beta}$) signaling pathway has the dual role in both tumor suppression and tumor promotion. To design cancer therapeutics successfully, it is important to understand TGF-${\beta}$ related functional contexts. This review discusses the molecular mechanism of the TGF-${\beta}$ pathway and describes the different ways of tumor suppression and promotion by TGF-${\beta}$. In the last part of the review, the data on targeting TGF-${\beta}$ pathway for cancer treatment is assessed. The TGF-${\beta}$ inhibitors in pre-clinical studies, and Phase I and II clinical trials are updated.

• BMB Reports
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• v.50 no.12
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• pp.599-600
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• 2017

Many studies have focused on the tumor suppressive role of $TGF-{\beta}$ signaling during the early stages of tumorigenesis by activating the target genes involved in cytostasis and apoptosis. We investigated the effects of $TGF-{\beta}$ inhibition on early tumorigenesis in the liver, by employing diverse inhibitory methods. Strikingly, $TGF-{\beta}$ inhibition consistently suppressed hepatic tumorigenesis that was induced either by activated RAS plus p53 downregulation or by the co-activation of RAS and TAZ signaling; this demonstrates the requirements for canonical $TGF-{\beta}$ signaling in tumorigenesis. Moreover, we found that Snail is the target gene of the $TGF-{\beta}$ signaling pathway that promotes hepatic carcinogenesis. The knockdown of Snail suppressed the early tumorigenesis in the liver, as did the $TGF-{\beta}$ inhibition, while the ectopic expression of Snail restored tumorigenesis that was suppressed by the $TGF-{\beta}$ inhibition. Our findings establish the oncogenic $TGF-{\beta}$-Smad-Snail signaling axis during the early tumorigenesis in the liver.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.321-328
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• 2000

Purpose :NOS2 induce NO Production and NO activate TGF-${\beta}$. The TGF-${\beta}$ is a inhibitor of NOS2. If this negative feedback mechanism operating in radiation pneumonitis model, NOS2 inhibitor may play a role in TGF-${\beta}$ suppression. We planned this study to evaluate the expression patterns of NO, NOS2 and TGF-${\beta}$ in vivo radiation pneumonitis model. Materials and Methods : Sixty sprague-Dawley rat were irradiated 5 Gy or 20 Gy. They were sacrificed 3, 7, 14, 28 and 56 days after irradiation. During sacrifice, we peformed broncho-alveolar lavage (BAL). The BAL fluids were centrifuged and supernatents were used for measure NO and TGF-${\beta}$, and the cells were used for RT-PCR. Results : After 5 Gy of radiation, NO in BAL fluid increased at 28 days in both lung and TGF-${\beta}$ in left lung at 56 days. NO increased in BAL fluid at 28 days in both lung after irradiation and TGF-${\beta}$ in right lung at 28-56 days after 20 Gy of radiation. After 5 Gy of radiation, NOS2 expression was increased in right lung at 14 days, in both lung at 28 days and in left lung at 56 days. TGF-${\beta}$ expression was reduced in both lung at 28 days and increased in left lung at 56 days. Conclusions :The Proposed feedback mechanism of NO, NOS2 and TGF-${\beta}$ was operated in vivo radiation pneumonitis model. At 56 days, however, NOS2 and TGF-${\beta}$ expressed concurrently in left lung after 5 Gy and in both lung after 20 Gy of radiation.

• Korean Journal of Veterinary Service
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• v.21 no.3
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• pp.267-275
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• 1998

돼지 수정란의 체외생산은 난자의 체외성숙과 체외수정에 관한 기술의 부족으로 아직까지 만족스럽지 못한 수준이다. 특히 돼지 수정란의 체외생산에는 복잡한 세포질의 성숙과정과 높은 다정자침입율 및 전핵형성의 억제등의 문제점이 있다. 본 연구에서는 돼지 난자의 체외성숙 체계를 개선하기 위하여 transforming growth factor$\beta$(TGF$\beta$)의 첨가가 난자 및 난구세포에 미치는 효과에 대하여 검토하였다. 체외성숙용 배지에 TGF$\beta$를 1~10ng/$m\ell$의 농도로 첨가하여 미성숙 난자를 배양한 결과 성숙율이 높아졌다. TGF$\beta$의 효과는 난구세포가 제거된 난자의 성숙에도 효과적이었다. TGF$\beta$(를 첨가하지 않은 배양액 내에서는 배양 24시간 까지 metaphase-II로 성숙된 난자가 관찰되지 않았으나 TGF$\beta$를 첨가한 배양액 내에서는 관찰되었다. 한편, 난구세포가 부착된 난자의 성숙배양시 TGF$\beta$의 첨가시기에 따른 차이는 없었으나, 난구세포를 제거한 난자의 경우에는 성숙배양 전반기(59%) 또는 후반기(57%) 24시간 동안에만 TGF$\beta$를 첨가하는 것이 48시간 동안 계속하여 첨가(27%)하는 경우 또는 비첨가(38%)에 비하여 유의적으로 높은 성숙율을 나타냈다(p<0.05). 이와 같은 결과는 난구 세포가 돼지 난자의 체외성숙에 필수적이지만 TGF$\beta$는 난구세포가 제거된 난자의 체외성숙에 어 느정도 유익한 효과를 발휘하는 것으로 추측된다.

• Korean Journal of Animal Reproduction
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• v.22 no.1
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• pp.73-80
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• 1998

This study was undertaken to evaluate the interaction between cumulus cells and TGF $\beta$1 on in vitro maturation in porcine oocytes. No differ ences were found in maturation rates when follicular oocytes were cultured in medium with various concentrations of TGF $\beta$. At 24 h after maturation, the oocytes matured to metaphase-II were found in medium with TGF $\beta$ regardless of cumulus cells. On the other hand, the maturation rates were significantly(P < 0.01 higher cumulus-enclosed(70 and 52%) than cumulus-denuded oocytes(35 and 26%) in medium with or without TGF $\beta$ at 48 h after culture. In a another experiment, the same maturation rates (54-71%) were observed when cumulus-enclosed oocytes were cultured with various addition time of TGF $\beta$. However, the maturation rates in cumulus-denuded oocytes were significantly (P < 0.05) higher in medium added at 0~24 h (59%) or 24-48 h(57%) after culture than in medium with(27%) and without(38%) TGF $\beta$ for 48 h. These results indicated that cumulus cells is essential for in vitro maturation in porcine oocytes but TGF $\beta$ can promote oocytes maturation in cumulus-free oocytes.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.9
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• pp.4045-4048
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• 2014

Effects of transforming growth factor-beta (TGF-${\beta}$) were investigated in human colorectal cancer, and the influence of cantharidinate in inhibiting TGF-${\beta}1$ expression was explored. Relationships among TGF-${\beta}1$ and sex, age, tumor size, tumor location, tumor stage were also analyzed. H&E and immunohistochemistry staining were employed to assess colorectal cancer and TGF-${\beta}1$ expression, respectively. Then, HCT-116 CRC cells were randomly divided into four groups, controls, no serum-treated, chemotherapy and cantharidinate-treated. Immunohistochemistry and real-time PCR were employed to assess the expression of TGF-${\beta}1$ in CRC cells. Our data showed that the expression of TGF-${\beta}1$ might be associated with tumor size and tumor location (P<0.05). The expression of TGF-${\beta}1$ in CRC groups was higher than in adjacent groups (P<0.05). In addition, the expression of TGF-${\beta}1$ in cantharidinate-treated group was much lower than in CRC group (P<0.05). Taken together, these results suggest that TGF-${\beta}1$ plays an important role in CRC development. Cantharidinate might inhibit the expression of TGF-${\beta}1$ and control the development of colorectal cancer.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.11
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• pp.1546-1552
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• 2002

Proliferation and differentiation of ovarian cells are regulated by gonadotrophins and various intraovarian factors, with many of their actions dependent on growth factors. Transforming growth factor-$\beta$ (TGF-$\beta$) has been reportedly involved in the regulation of ovarian follicular development. The overall objectives of the present study were to examine the influence of TGF-$\beta$1 expression in ovarian follicular development or yolk formation and to investigate the association of egg weight with ovarian TGF-$\beta$1 expression at 60 wk. Egg weights of 70 Korean Native Ogol Chicken (KNOC) were recorded from 20 to 60 wk. Ovaries were taken at 60 wk, and TGF-$\beta$1 was measured with ELISA, respectively. Based on egg weight up to 60 wk and TGF-$\beta$1 expression in ovary, the chickens were divided into high and low groups. Egg weights and follicle weight in the high TGF-$\beta$1 group were higher than those in the low groups. Also, TGF-$\beta$1 expression and follicle weight in high egg weight group were higher than those in the low groups. Taken together, the results indicate that TGF-$\beta$1 is associated with egg weight in KNOC. This association of TGF-$\beta$1 with egg weight in KNOC supports the report that TGF-$\beta$ is mainly involved in the development and differentiation of follicles in the poultry. Further studies about other endocrine factors related to yolk formation are required to fully understand the endocrine mechanism of egg weight in Korean Native Ogol Chickens.

• Journal of Veterinary Clinics
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• v.11 no.1
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• pp.389-392
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• 1994

To purify transforming growth factor type beta(TGF-$\beta$) in canine platelets, Sephadex G-75 gel filtration and semipreparative HPLC were carried out. The column of $2.0 {\times}120cm$ was used for gel filtration and one inch semipreparative column filled with SP-Toyopeal for HPLC. Electrophoresis and bioassay using African green monkey kidney cell were used for identification of TGF-$\beta$ Crude TGF-$\beta$ of 2.75mg was extracted from 5.2g of the platelets by the treatment of acid/ethanol. In gel filtration of crude TGF-$\beta$, 4 peaks were observed at the detection of spectrophotometer at 280nm. Electrophoresis and bioassay identified the 3rd peak TGF-$\beta$. Linear gradient elution from 0 to 3M NaCl in sornipreparative HPLC showed TGF-$\beta$ at 1.5M NaCl. Gel filtration was less expensive and useful method for the purification of TGF-$\beta$.

• Biomedical Science Letters
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• v.24 no.4
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• pp.305-310
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• 2018

Microglia are emerging as critical regulators of innate immune responses in AD and other neurodegenerative disorders, highlighting the importance of understanding their molecular and cellular mechanisms. We attempted to determine the role of crosstalk signaling between $IFN-{\gamma}$ and $TGF-{\beta}$ in $A{\beta}$ clearance by microglia cells. We used in vitro and in vivo mouse models that recapitulated acute and chronic aspects of microglial responses to $A{\beta}$ peptides. We showed that crosstalk signaling between $TGF-{\beta}$ and Smad2 was an important mediator of neuro-inflammation. These findings suggest that microglial $TGF-{\beta}$ activity enhances the pathological progression to AD. As $TGF-{\beta}$ displays broad regulatory effects on beneficial microglial functions, the activation of inflammatory crosstalk signaling between $TGF-{\beta}$ and Smad2 may be a promising strategy to restore microglial functions, halt the progression of $A{\beta}$-driven pathology, and prevent AD development.

• Proceedings of the Korean Society for Food Science of Animal Resources Conference
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• 2001.11a
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• pp.43-56
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• 2001

Colostrum contains various kinds of cytokines including TGF-${\beta}$ which is known to be multifunctional in immune response and act as an anti-inflammatory agent. First, we measured the amount of TGF-${\beta}$ in bovine and human colostrum. Expression pattern of TGF-${\beta}$ isotypes was dramatically different between human and bovine colostrial samples. Bovine colostrum collected on day 1 post-delivery retained $41.79{\pm}16.96ng/ml$ of TGF-${\beta}$ 1 and $108.4{\pm}78.65ng/ml$ of TGF-${\beta}$ 2 while in human, $284{\pm}124.75ng/ml$ of TGF-${\beta}$ 1 and $29.75{\pm}6.73ng/ml$ of TGF-${\beta}$ 2. Thus, TGF-${\beta}$ is the predominant TGF-${\beta}$ isotype in bovine colostrum and vice versa in human colostrum. Both TGF-${\beta}$ isotypes diminished significantly in human and bovine colostrum with time. Next, biological activity of colostrial samples was examined in vitro. Both human and bovine colostrum increased IgA synthesis by LPS-activated mouse spleen B cells, which is a typical effect of TGF-${\beta}$ on the mouse B cell differentiation. Futhermore, we found that anti-proliferative activity in MV1LU cells by colostrum samples disappeared by addition of anti-TGF-${\beta}$ 1 and anti-TGF-${\beta}$ 2 antibody. In conclusion, there are substantial amounts of biologically active TGF-${\beta}$ 1 and TGF-${\beta}$ 2 in bovine and human colostrum. The results that the colostrum can increase IgA expression has important implications since IgA is the major Ig class produced in the gastrointestinal tract. We have previously shown that the stimulatory effect of Bifidobacteria bifidum on spllen B cells was quite similar to that of LPS which is a well-known polyclonal activator for murine B cells. In the present study, we further asked whether B. bifidum regulate the synthesis of IgA by mucosal lymphoid cells present in Peyers patches (PP) and mesenteric lymph nodes (MLN). B. bifidum alone, but not C. perfringens, significantly induced overall IgA and IgM synthesis by both MLN and PP cells. This observation indicates that B. bifidum possesses a modulatory effect on the mucosal antibody production in vivo. We, therefore, investigated the mucosal antibody prodduction following peroral administration of B. bifidum to mice. Ingested B. bifidum significantly increased the numbers of Ig (IgM, IgG, and IgA) secreting cells in the culture of both MLN and spleen cells, indicating that peroally introduced B. bifidum enhances mucosal and systemic antibody response. Importantly, however, B. bifidum itself does not induce the own specific antibody responses, implying that B. bifidum do not incite any unwanted immune reaction. Subsequently, it was found that excapsulation of B. bifidum further augments the total IgA production by increasing the number of IgA-secreting cells in the culture of both MLN and spleen cells. Finally, we found that the immuno-stimulating activity of B. bifidum is due to its cell wall components but not due to any actively secreting component(s) from bacteria. Thus our data reveal that peroral administration of B. bifidum can enhance intestinal IgA production and that encapsulation of B. bifidum further reinforces the IgA production.