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| 1 | Effects of insulin and pathway inhibitors on the PI3K-Akt- mTOR phosphorylation profile in acute myeloid leukemia cells显示文摘The phosphatidylinositol 3-kinase(PI3K)-Akt-mechanistic target of rapamycin(mTOR)pathway is constitutively activated in human acute myeloid leukemia(AML)cells and is regarded as a possible therapeutic target.Insulin is an agonist of this pathway and a growth factor for AML cells.We characterized the effect of insulin on the phosphorylation of 10 mediators in the main track of the PI3K-Akt-mTOR pathway in AML cells from 76 consecutive patients.The overall results showed that insulin significantly increased the phosphorylation of all investigated mediators.However,insulin effects on the pathway activation profile varied among patients,and increased phosphorylation in all mediators was observed only in a minority of patients;in other patients,insulin had divergent effects.Global gene expression profiling and proteomic/phosphoproteomic comparisons suggested that AML cells from these two patient subsets differed with regard to AML cell differentiation,transcriptional regulation,RNA metabolism,and cellular metabolism.Strong insulin-induced phosphorylation was associated with weakened antiproliferative effects of metabolic inhibitors.PI3K,Akt,and mTOR inhibitors also caused divergent effects on the overall pathway phosphorylation profile in the presence of insulin,although PI3K and Akt inhibition caused a general reduction in Akt pT308 and 4EBP1 pT36/pT45 phosphorylation.For Akt inhibition,the phosphorylation of upstream mediators was generally increased or unaltered.In contrast,mTOR inhibition reduced mTOR pS2448 and S6 pS244 phosphorylation but increased Akt pT308 phosphorylation.In conclusion,the effects of both insulin and PI3K-Akt-mTOR inhibitors differ between AML patient subsets,and differences in insulin responsiveness are associated with differential susceptibility to metabolic targeting. | Ina Nepstad Kimberley Joanne Hatfield Ida Sofie Grønningsæter Elise Aasebø Maria Hernandez-Valladares Karen Marie Hagen Kristin Paulsen Rye Frode SBerven Frode Selheim Håkon Reikvam Øystein Bruserud | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 4 |
| 2 | Significance of postoperative follow-up of patients with metastatic colorectal cancer using circulating tumor DNA显示文摘BACKGROUND One of the most notable applications for circulating tumor DNA(ctDNA)detection in peripheral blood of patients with metastatic colorectal cancer(mCRC)is a long-term postoperative follow-up.Sometimes referred to as a“liquid(re)biopsy”it is a minimally invasive procedure and can be performed repeatedly at relatively short intervals(months or even weeks).The presence of the disease and the actual extent of the tumor burden(tumor mass)within the patient’s body can be monitored.This is of particular importance,especially when evaluating radicality of surgical treatment as well as for early detection of disease progression or recurrence.AIM To confirm the radicality of surgery using ctDNA and compare available methods for detection of recurrence in metastatic colorectal cancer.METHODSA total of 47 patients with detected ctDNA and indications for resection of mCRC were enrolled in the multicenter study involving three surgical centers.Standard postoperative follow-ups using imaging techniques and the determination of tumor markers were supplemented by ctDNA sampling.In addition to the baseline ctDNA testing prior to surgery,a postoperative observation was conducted by evaluating ctDNA presence up to a week after surgery and subsequently at approximately three-month intervals.The presence of ctDNA was correlated with radicality of surgical treatment and the actual clinical status of the patient.RESULTS Among the monitored patients,the R0(curative)resection correlated with postoperative ctDNA negativity in 26 out of 28 cases of surgical procedures(26/28,93%).In the remaining cases of R0 surgeries that displayed ctDNA,both patients were diagnosed with a recurrence of the disease after 6 months.In 7 patients who underwent an R1 resection,4 ctDNA positivities(4/7,57%)were detected after surgery and associated with the confirmation of early disease recurrence(after 3 to 7 months).All 15 patients(15/15,100%)undergoing R2 resection remained constantly ctDNA positive during the entire follow-up period.In 22 cases of recurrence,ctDNA positivity was detected 22 times(22/22,100%)compared to 16 positives(16/22,73%)by imaging methods and 15 cases(15/22,68%)of elevated tumor markers.CONCLUSION ctDNA detection in patients with mCRC is a viable tool for early detection of disease recurrence as well as for confirmation of the radicality of surgical treatment. | Lucie Benešová Tereza Hálková Renata Ptáčková Anastasiya Semyakina Kateřina Menclová JiříPudil Miroslav Ryska Miroslav Levý JaromírŠimša Filip Pazdírek JiříHoch Milan Blaha Marek Minárik | 2019 | World Journal of Gastroenterology2019，25，48： | 3 |
| 3 | Hepatic pseudolesion in the left lobe around the falciform ligament at helical CT显示文摘 | Ohashi I Ina H Gomi N | 1995 | Radiology1995，196，1： | 2 |
| 4 | Suppression of thymic lymphoma induction by life-long low-dose-rate irradiation accompanied by immune activation in C57BL/6 mice显示文摘 | Ina Y Tanooka H Yamada T | 2005 | Radiat Res2005，163，2： | 1 |
| 5 | Isolation and identification of xanthatin as an anti-attaching repellent against Blue mussel 显示文摘 | Harada A Sakata K Ina H | 1985 | Agricultural and Biological Chemistry1985，49，6： | 1 |
| 6 | Intestinal SGLT1- mediated absorption and metabolism of benzyl b-glucoside contained in Prunus mume: cartier-mediated transport increases intestinal availability 显示文摘 | Mizuma T Nakamura M Ina H | 2005 | Biochim Biophys Acta2005，1722，： | 1 |
| 7 | Fourier-transform mcthod of fringepattern analysis for computer-based topography and interferometry显示文摘 | Takcda M Ina H Kobayashi S | 1982 | Optical Society of America1982，72，： | 1 |
| 8 | Fourier - transform method of fringe- pattern analysis for computer- based topography and interferometry 显示文摘 | TAKEDA M INA H KOBAYASHI S | 1982 | Journal of the Optical Society of America1982，72，1： | 1 |
| 9 | Isoform-specific alanine aminotransferase measurement can distinguishhepatic from extrahepatic injury in humans显示文摘 | Ingalill Rafter Truls Gr?berg Anna Kotronen Lovisa Str?mmer C. Mattson Ray Kim Ewa Ehrenborg H?kan Andersson Hannele Yki-J?rvinen Ina Schuppe-Koistinen Bj?rn Ekblom Ian Cotgreave Bj?rn Glinghammar | 2012 | International Journal of Molecular Medicine2012，，5： | 1 |
| 10 | New technique for the neurolytic celiac plexus block:the transintervertebral disc approach显示文摘 | Ina H Kitoh T Kobayashi M | 1996 | Anesthesiology1996，85，： | 1 |
| 11 | Control of Nanoparticle Size,Crystal Structure and Growth of Layered Double Hydroxide by Hydrothermal Treatment显示文摘 | Mohamed R B Inas H H Keiji M | 2012 | International Journal of Modern Physics:Conference Series2012，6，： | 1 |
| 12 | Ultrastructural study of capillary and myocytic changes in the masseter and heart of KK-AY mice显示文摘 | Takeshita M Ina K Kitamura H | 1997 | Electron Microsc1997，46，： | 1 |
| 13 | Procalcitonin-guided interven- tions against infections to increase early appropriate antibiotics and im- prove survival in the intensive care unit:A randomized trial 显示文摘 | JENS U J LARS H BETI'INA L | 2011 | Crit Care Med2011，39，9： | 1 |
| 14 | Left atrium thrombus in an extremely low-birth weight infant with late-onset circulato- ry dysfunction显示文摘 | Ina S Futatani T Higashiyama H | 2012 | Pediatr Int2012，54，4： | 1 |
| 15 | Annexin A2 in amniotic fluid: correlation with histological chorioamnionitis, preterm premature rup- ture of membranes, and subsequent preterm delivery 显示文摘 | Namba F Ina S Kitajima H | 2012 | J Obstet Gynaecol Res2012，38，1： | 1 |
| 16 | Fourier-transform method of fringe-pattern analysis for computer-based topography and interferometry显示文摘 | TAKEDA M INA H KOBAYASHI S | 1982 | Journal of the Optical Society of America A1982，72，1： | 1 |
| 17 | Vasscular cell adhesion molecule-1 exprssion in the renal interstitium of diabetic KKAy mice Diabetes显示文摘 | Ina K Kitamura H Okedam T | 1999 | Research and Clinical Practice1999，44，： | 1 |
| 18 | Isolation and identification of xanthatin as an antiattaching repellent against Blue mussel显示文摘 | Harada A Sakata K Ina H | 1985 | Agric Biolchem1985，49，6： | 1 |
| 19 | Transformation of intersti- tial fibroblasts and tubulointerstitial fibrosis in diabetic nephropathy 显示文摘 | Ina K Kitamura H Tatsukawa S | 2002 | Med Electron Microsc2002，35，2： | 1 |
| 20 | New technique for the neurolytic celiac plexus block:the transintervertebral between disc approach 显示文摘 | Ina H Kitoh T Kobayashi M | 1996 | Anesthesiology1996，85，1： | 1 |
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