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Farrand, Lee,Kim, Ji Young,Byun, Sanguine,Im-aram, Akechai,Lee, Jihoon,Suh, Jeong-Yong,Lee, Ki-Won,Lee, Hyong Joo,Tsang, Benjamin K. American Society for Biochemistry and Molecular Bi 2014 The Journal of biological chemistry Vol.289 No.3
<▼1><P><B>Background:</B> Resistance of ovarian cancer cells to chemotherapy is a major therapeutic problem.</P><P><B>Results:</B> Hirsutenone induces cisplatin sensitivity via p53, X-linked inhibitor of apoptosis protein, and apoptosis-inducing factor.</P><P><B>Conclusion:</B> Hirsutenone sensitizes resistant ovarian cancer cells to cisplatin.</P><P><B>Significance:</B> Co-treatment with hirsutenone may have the potential to overcome chemoresistance.</P></▼1><▼2><P>Cisplatin (CDDP) and its derivatives are considered first-line treatments for ovarian cancer (OVCA). However, despite initial results that often appear promising, in most cases patients will return with recurrent disease that fails to respond to further chemotherapy. We assayed a number of food phytochemicals with reported PI3K inhibitory ability to identify candidates that can influence CDDP treatment outcomes in chemoresistant OVCA cell lines. A direct comparison revealed that the diarylheptanoid hirsutenone from the tree bark of <I>Alnus hirsuta</I> var. sibirica was superior at inducing CDDP sensitivity in a number of chemoresistant cancer cell lines. Whereas hirsutenone treatment activated p53, its modest efficacy in <I>p53</I>-mutant and -null cell lines suggested the existence of a p53-independent mode of action. Further investigation revealed that hirsutenone causes CDDP-dependent apoptosis in chemoresistant cells by ubiquitin-proteasome-dependent X-linked inhibitor of apoptosis degradation and by enhancing the translocation of apoptosis-inducing factor from the mitochondria to the nucleus. This was found to be, at least in part, under the influence of upstream Akt activity, linking hirsutenone-dependent PI3K inhibition with downstream effects on apoptosis-inducing factor, X-linked inhibitor of apoptosis, and apoptosis. Our findings provide rationale for further investigation of the effects of hirsutenone on chemoresistant OVCA in clinical studies.</P></▼2>
Molecular determinants of ovarian cancer chemoresistance: new insights into an old conundrum
Ali, Ahmed Y.,Farrand, Lee,Kim, Ji Young,Byun, Sanguine,Suh, Jeong‐,Yong,Lee, Hyong Joo,Tsang, Benjamin K. Blackwell Publishing Inc 2012 Annals of the New York Academy of Sciences Vol.1271 No.1
<P>Ovarian cancer is the most lethal gynecological malignancy. Cisplatin and its derivatives are first-line chemotherapeutics, and their resistance is a major hurdle in successful ovarian cancer treatment. Understanding the molecular dysregulation underlying chemoresistance is important for enhancing therapeutic outcome. Here, we review two established pathways in cancer chemoresistance. p53 is a major tumor suppressor regulating proliferation and apoptosis, and its mutation is a frequent event in human malignancies. The PI3K/Akt axis is a key oncogenic pathway regulating survival and tumorigenesis by controlling several tumor suppressors, including p53. The interplay between these pathways is well established, although the oncogenic phosphatase PPM1D adds a new layer to this intricate relationship and provides new insights into the processes determining cell fate. Inhibition of the PI3K/Akt pathway by functional food compounds as an adjunct to chemotherapeutics may tip the balance in favor of apoptosis rather than survival, enhancing therapeutic efficacy, and reducing side effects.</P>
ADVANCED MEASUREMENTS OF FIBER DIMENSIONS : NEW KAJAANI FIBERLAB
Tiikkaja,Esa,Kauppinen,Marko,Sopenlehto,Taina,Farrand,Nigel 강원대학교 부설 창강제지 기술연구소 1998 제지기술 Vol.- No.12
Valmet Automation has over 15 years experience in fiber analysis. The first true fiber length analyzer, KAJAANI FS-100, was introduced to the market in 1982. Later in 1987, the fully automatic KAJAANI FS-200 was launched and soon became the standard for fiber length measurement. The on-line KAJAANI FSA analyzer, based on FS-200 technology, arrived in mills during 1993. The unique KAJAANI FiberLab analyzer is now set to write the next chapter in the story of fiber characteristic analysis. The KAJAANI FiberLab combines the standardized fiber length measurement with new fiber width and cell wall thickness measurements. The unique accuracy of the KAJAANI FiberLab makes it equally suitable for research and as a standard production laboratory tool. Connected to the mill information system FiberLab can provide rapid fiber characteristics for faster process control decisions and valuable data for efficient fiber utilization.
Kim, H. Stanley,Yi, Hyojeong,Myung, Jaehee,Piper, Kevin R.,Farrand, Stephen K. American Society for Microbiology 2008 Journal of Bacteriology Vol.190 No.10
<B>ABSTRACT</B><P><I>Agrobacterium tumefaciens</I> strain C58 can transform plant cells to produce and secrete the sugar-phosphate conjugate opines agrocinopines A and B. The bacterium then moves in response to the opines and utilizes them as exclusive sources of carbon, energy, and phosphate via the functions encoded by the <I>acc</I> operon. These privileged opine-involved activities contribute to the formation of agrobacterial niches in the environment. We found that the expression of the <I>acc</I> operon is induced by agrocinopines and also by limitation of phosphate. The main promoter is present in front of the first gene, <I>accR</I>, which codes for a repressor. This operon structure enables efficient repression when opine levels are low. The promoter contains two putative operators, one overlapping the −10 sequence and the other in the further upstream from it; two partly overlapped putative <I>pho</I> boxes between the two operators; and two consecutive transcription start sites. DNA fragments containing either of the operators bound purified repressor AccR in the absence of agrocinopines but not in the presence of the opines, demonstrating the on-off switch of the promoter. Induction of the <I>acc</I> operon can occur under low-phosphate conditions in the absence of agrocinopines and further increases when the opines also are present. Such opine-phosphate dual regulatory system of the operon may ensure maximum utilization of agrocinopines when available and thereby increase the chances of agrobacterial survival in the highly competitive environment with limited general food sources.</P>
Byun, Sanguine,Lim, Semi,Mun, Ji Young,Kim, Ki Hyun,Ramadhar, Timothy R.,Farrand, Lee,Shin, Seung Ho,Thimmegowda, N. R.,Lee, Hyong Joo,Frank, David A.,Clardy, Jon,Lee, Sam W.,Lee, Ki Won American Society for Biochemistry and Molecular Bi 2015 The Journal of biological chemistry Vol.290 No.39
<P>Bioactive phytochemicals can suppress the growth of malignant cells, and investigation of the mechanisms responsible can assist in the identification of novel therapeutic strategies for cancer therapy. Ginger has been reported to exhibit potent anti-cancer effects, although previous reports have often focused on a narrow range of specific compounds. Through a direct comparison of various ginger compounds, we determined that gingerenone A selectively kills cancer cells while exhibiting minimal toxicity toward normal cells. Kinase array screening revealed JAK2 and S6K1 as the molecular targets primarily responsible for gingerenone A-induced cancer cell death. The effect of gingerenone A was strongly associated with relative phosphorylation levels of JAK2 and S6K1, and administration of gingerenone A significantly suppressed tumor growth <I>in vivo</I>. More importantly, the combined inhibition of JAK2 and S6K1 by commercial inhibitors selectively induced apoptosis in cancer cells, whereas treatment with either agent alone did not. These findings provide rationale for dual targeting of JAK2 and S6K1 in cancer for a combinatorial therapeutic approach.</P>
Cho, Tae-Min,Kim, Ji Young,Kim, Yoon-Jae,Sung, Daeil,Oh, Eunhye,Jang, Seojin,Farrand, Lee,Hoang, Van-Hai,Nguyen, Cong-Truong,Ann, Jihyae,Lee, Jeewoo,Seo, Jae Hong Elsevier 2019 Cancer letters Vol.447 No.-
<P><B>Abstract</B></P> <P>Triple-negative breast cancer (TNBC) is an aggressive heterogeneous disease with a divergent profile. It has an earlier tendency to form metastases and is associated with poor clinical outcomes due to the limited treatment options available. Heat-shock protein (HSP90) represents a potential treatment target as it promotes tumor progression and metastasis by modulating the maturation and stabilization of signal transduction proteins. We sought to investigate the efficacy of the C-terminal HSP90 inhibitor L80 on cell proliferation, breast cancer stem cell (BCSC)-like properties, tumor growth and metastasis. L80 suppressed cell viability and concomitantly inhibited AKT/MEK/ERK/JAK2/STAT3 signaling in TNBC cells but did not induce cytotoxicity in normal cells. L80 effectively targeted BCSC-like traits, together with significant reductions in the CD44high/CD24low-population, ALDH1 activity and mammosphere forming-ability. In support of the <I>in vitro</I> observations, L80 administration caused significant impairment in tumor growth, angiogenesis and distant metastases in an orthotopic allograft model with BCSC-enriched cells <I>in vivo</I>. These phenomena were associated with the suppression of BCSC-like characteristics and STAT3 dysfunction. Our findings highlight properties of the L80 compound that may be useful in suppressing metastatic TNBC.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The C-terminal HSP90 inhibitor L80 targets cancer stem-like properties. </LI> <LI> L80 inhibits HSP90 client protein kinases including AKT, MEK, JAK and STAT3. </LI> <LI> L80 suppresses tumor growth and distant TNBC metastases <I>in vivo.</I> </LI> <LI> Antitumor activity of L80 is associated with dysregulation of STAT3 activation. </LI> </UL> </P>