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Moon, Kyeong Hwan,Kim, Hyoung-Tai,Lee, Dahye,Rao, Mahesh B.,Levine, Edward M.,Lim, Dae-Sik,Kim, Jin Woo Elsevier 2018 DEVELOPMENTAL CELL Vol.44 No.1
<P><B>Summary</B></P> <P>The optic neuroepithelial continuum of vertebrate eye develops into three differentially growing compartments: the retina, the ciliary margin (CM), and the retinal pigment epithelium (RPE). Neurofibromin 2 (Nf2) is strongly expressed in slowly expanding RPE and CM compartments, and the loss of mouse <I>Nf2</I> causes hyperplasia in these compartments, replicating the ocular abnormalities seen in human <I>NF2</I> patients. The hyperplastic ocular phenotypes were largely suppressed by heterozygous deletion of <I>Yap</I> and <I>Taz</I>, key targets of the Nf2-Hippo signaling pathway. We also found that, in addition to feedback transcriptional regulation of <I>Nf2</I> by Yap/Taz in the CM, activation of <I>Nf2</I> expression by Mitf in the RPE and suppression by Sox2 in retinal progenitor cells are necessary for the differential growth of the corresponding cell populations. Together, our findings reveal that Nf2 is a key player that orchestrates the differential growth of optic neuroepithelial compartments during vertebrate eye development.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Different parts of the eye neuroepithelium vary in proliferation rates </LI> <LI> Nf2 is enriched in slowly proliferating optic neuroepithelial compartments </LI> <LI> <I>Nf2</I> expression is regulated differentially in each optic compartment </LI> <LI> Nf2 mediates Hippo pathway to inhibit hyperproliferation of optic neuroepithelium </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>
Potjana Jitawatanarat,Tracey L. O’Connor,Ellen B. Kossoff,Ellis G. Levine,Kaweesak Chittawatanarat,Nuttapong Ngamphaiboon 한국유방암학회 2014 Journal of breast cancer Vol.17 No.4
Purpose: We evaluated the tolerability and cardiac safety ofdocetaxel, cyclophosphamide, and trastuzumab (TCyH) for thetreatment of early-stage human epidermal growth factor receptor2 (HER2)-positive breast cancer and compared to the standardtrastuzumab-based chemotherapy regimens doxorubicin withcyclophosphamide followed by paclitaxel and trastuzumab (ACTH)and docetaxel, carboplatin, and trastuzumab (TCaH). Methods:We retrospectively reviewed early-stage, resectable, HER2-positive breast cancer patients treated with trastuzumab-basedchemotherapy at a single comprehensive cancer center between2004 and 2011. Patient characteristics, comorbidities, relativedose intensity (RDI) of each regimen, tolerability, and cardiac toxicitywere evaluated. Results: One hundred seventy-seven patientswere included in the study (AC-TH, n=114; TCaH, n=39;TCyH, n=24). TCyH was solely administered in the adjuvant setting,whereas two-thirds of the AC-TH and TCaH groups wereadministered postoperatively. Patients treated with TCyH tendedto have a more significant underlying cardiac history, higherCharlson comorbidity index, and were of an earlier stage. All patientstreated with TCyH received granulocyte colony stimulatingfactor primary prophylaxis. No febrile neutropenia or grade ≥3hematologic toxicity was observed in the TCyH group as comparedto the AC-TH and TCaH groups. There were no significantdifferences in the rates of early termination, hospitalization, dosereduction, or RDI between the regimens. The symptomatic congestiveheart failure rate between AC-TH, TCaH, and TCyHgroups was not significantly different (4.4% vs. 2.6% vs. 8.3%,respectively, p=0.57). There was also no significant difference inthe rate of early trastuzumab termination between patients treatedwith each regimen. Conclusion: TCyH is well tolerated andshould be investigated as an alternative adjuvant chemotherapyoption for patients who are not candidates for standard trastuzumab-containing regimens. Larger clinical trials are necessary tosupport the wider use of TCyH as an adjuvant regimen.
Amy D. Dobberfuhl,Sara Spettel,Catherine Schuler,Robert M. Levin,Andrew H. Dubin,Elise J.B. De 대한비뇨의학회 2015 Investigative and Clinical Urology Vol.56 No.12
Purpose: Existing data supports a relationship between pelvic floor dysfunction and lower urinary tract symptoms. We developed a survival model of pelvic floor dysfunction in the rabbit and evaluated cystometric (CMG), electromyographic (EMG) and ambulatory voiding behavior. Materials and Methods: Twelve female adult virgin rabbits were housed in metabolic cages to record voiding and defecation. Anesthetized CMG/EMG was performed before and after treatment animals (n=9) received bilateral tetanizing needle stimulation to the pubococcygeous (PC) muscle and controls (n=3) sham needle placement. After 7 days all animals were subjected to tetanizing transvaginal stimulation and CMG/EMG. After 5 days a final CMG/EMG was performed. Results: Of rabbits that underwent needle stimulation 7 of 9 (78%) demonstrated dysfunctional CMG micturition contractions versus 6 of 12 (50%) after transvaginal stimulation. Needle stimulation of the PC musculature resulted in significant changes in: basal CMG pressure, precontraction pressure change, contraction pressure, interval between contractions and postvoid residual; with time to 3rd contraction increased from 38 to 53 minutes (p=0.008 vs. prestimulation). Vaginal noxious stimulation resulted in significant changes in: basal CMG pressure and interval between contractions; with time to 3rd contraction increased from 37 to 46 minutes (p=0.008 vs. prestimulation). Changes in cage parameters were primarily seen after direct needle stimulation. Conclusions: In a majority of animals, tetanizing electrical stimulation of the rabbit pelvic floor resulted in voiding changes suggestive of pelvic floor dysfunction as characterized by a larger bladder capacity, longer interval between contractions and prolonged contraction duration.
Amy D. Dobberfuhl,Catherine Schuler,Robert E. Leggett,Elise J.B. De,Robert M. Levin 대한비뇨의학회 2020 Investigative and Clinical Urology Vol.61 No.4
Purpose: To explore the effect of estrogen replacement on pelvic floor and bladder contractile response to electrical field stimulation, following in vitro hypoxia in an animal model of surgical menopause. Materials and Methods: Twelve female adult rabbits were divided into three groups: control, ovariectomy, and ovariectomy with estradiol replacement. At 4 weeks animals were euthanized. Bladder, coccygeus, and pubococcygeus were isolated. Tissues were equilibrated with oxygenated Tyrodes containing glucose and stimulated with electrical field stimulation. Tissues were then stimulated under hypoxic conditions for 1 hour using nitrogenated Tyrodes without glucose. Tissues were then re-oxygenated for 2 hours and stimulated. Results: Pelvic floor required 10 times the stimulation duration (power) to achieve maximum contraction at 2 g baseline tension (10 ms duration) when compared to bladder (1 ms duration). Maximal tension generated was significantly greater for bladder than pelvic floor. Coccygeus and pubococcygeus were significantly less sensitive to the effects of hypoxia and had stable contractile response to field stimulation throughout the hour of hypoxia. Hypoxia resulted in progressive and rapid decline of bladder contractile strength. Following hypoxia, pelvic floor contractile recovery was superior to bladder. Improvement in the contractile response of both bladder and pelvic floor, during the period of post-hypoxia re-oxygenation, was significantly greater in ovariectomy animals treated with estradiol replacement. Conclusions: Replacement of estradiol at time of ovariectomy reduced oxidative stress on tissue and was protective to the effects of hypoxia on pelvic floor and bladder contractile function.
Exploring the Ecology of Deep-Sea Hydrothermal Vents in a Metacommunity Framework
Mullineaux, Lauren S.,Metaxas, Anna,Beaulieu, Stace E.,Bright, Monika,Gollner, Sabine,Grupe, Benjamin M.,Herrera, Santiago,Kellner, Julie B.,Levin, Lisa A.,Mitarai, Satoshi,Neubert, Michael G.,Thurnhe Frontiers Media SA 2018 Frontiers in marine science Vol.5 No.-
( Dennis S. Chi ),( Nadeem R. Abu-Rustum ),( Yukio Sonoda ),( Joseph Ivy ),( Eunice Rhee B. A. ),( Kathleen Moore ),( Douglas A. Levine ),( Richard R. Barakat ) 대한산부인과학회 2007 서울심포지움 Vol.12 No.-
Objective: To compare the safety and efficacy of laparoscopic (LSC) staging of ovarian or fallopian tube cancers to staging via laparotomy (LAP) for epithelial ovarian carcinoma (EOC). Study Design: We performed a case-control study of all patients (pts) with apparent stage I adnexal cancers who had LSC staging from 10/00-3/03. The control group consisted of all pts with apparent stage I EOC who had staging via LAP during the same time period. Results: Staging was LSC in 20 pts and via LAP in 30.There were no differences in mean age and body mass index. There were also no differences in omental specimen size and number of lymph nodes removed. Estimated blood loss and hospital stay were lower for LSC, while operating time was longer. There were no conversions to LAP or complications in the LSC group compared with 3 minor complications in the LAP group. Conclusion: In this preliminary analysis, it appears that pts with apparent stage I ovarian or fallopian tube cancer can safely and adequately undergo LSC surgical staging.