Pulsed low-dose rate radiotherapy for recurrent bone sarcomas: case reports and brief review

Ru Xin Wong(Ru Xin Wong ),Zubin Master(Zubin Master ),Eric Pang(Eric Pang ),Valerie Yang(Valerie Yang ),Wen Shen Looi(Wen Shen Looi ) 대한방사선종양학회 2024 Radiation Oncology Journal Vol.42 No.1

Purpose: Re-irradiation for bulky recurrent sarcoma carries significant risks. Pulsed low-dose rate radiotherapy (PLDR) is an attractive option for re-irradiation due to inherent radiobiological advantages. Materials and Methods: We present two patients who underwent re-irradiation using PLDR technique, followed by a literature review. Results: The first case is that of a 76-year-old male who developed an in-field recurrence of a bulky pelvic bone high-grade chondrosarcoma after he was treated with definitive radiotherapy using helical TomoTherapy with a total dose of 66 Gy. The patient was re-irradiated using PLDR with a shrinking field technique; 50 Gy in 2 Gy fractions followed by a boost of 20 Gy in 2 Gy fractions. The patient remains disease-free without significant toxicity 60 months post-irradiation. The second case is that of an 82-year-old female who was treated with a definitive irradiation of 66 Gy in 33 fractions for a right shoulder grade II chondrosarcoma. She developed an in-field recurrence 28 months later and presented with bulky disease causing brachial plexopathy and lymphedema. The patient was re-irradiated with a palliative intent to a total dose of 50 Gy in 2 Gy fractions over 5 weeks using PLDR. Brachial plexopathy resolved shortly after re-irradiation, but local progression near the surface was evident 8 months later. She passed away from unrelated causes 11 months later. Conclusion: We present two cases highlighting our early experience with PLDR, which was effective in the re-irradiation of recurrent bony sarcoma. Our study highlights PLDR as an option for re-irradiation in recurrent unresectable tumors.

Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

Shen, Li,Choi, Inchan,Nestler, Eric J.,Won, Kyoung-Jae Korea Genome Organization 2013 Genomics & informatics Vol.11 No.2

A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE), recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

Identification of LEM-14 inhibitor of the oncoprotein NSD2

Shen, Yunpeng,Morishita, Masayo,Lee, Doohyun,Kim, Shinae,Lee, Taeho,Mevius, Damiaan E.H.F.,Roh, Yeonjeong,di Luccio, Eric Elsevier 2019 Biochemical and biophysical research communication Vol.508 No.1

<P><B>Abstract</B></P> <P>The NSD family (NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1) are histone lysine methyltransferases (HMTases) essential for chromatin regulation. The NSDs are oncoproteins, drivers of a number of tumors and are considered important drug-targets but the lack of potent and selective inhibitors hampers further therapeutic development and limits exploration of their biology. In particular, MMSET/NSD2 selective inhibition is being pursued for therapeutic interventions against multiple myeloma (MM) cases, especially in multiple myeloma t(4;14)(p16.3;q32) translocation that is associated with a significantly worse prognosis than other MM subgroups. Multiple myeloma is the second most common hematological malignancy, after non-Hodgkin lymphoma and remains an incurable malignancy.</P> <P>Here we report the discovery of LEM-14, an NSD2 specific inhibitor with an <I>in vitro</I> IC<SUB>50</SUB> of 132 μM and that is inactive against the closely related NSD1 and NSD3. LEM-14-1189, a LEM-14 derivative, differentially inhibits the NSDs with <I>in vitro</I> IC<SUB>50</SUB> of 418 μM (NSD1), IC<SUB>50</SUB> of 111 μM (NSD2) and IC<SUB>50</SUB> of 60 μM (NSD3). We propose LEM-14 and derivative LEM-14-1189 as tools for studying the biology of the NSDs and constitute meaningful steps toward potent NSDs therapeutic inhibitors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 are histone methyltransferases and oncoproteins. </LI> <LI> Inhibition of NSD2 in multiple myeloma t(4;14)(p16.3;q32) is urgently needed. </LI> <LI> We report the discovery of a NSD2 specific inhibitor and derivatives that differentially inhibits the NSDs. </LI> <LI> We investigate the molecular mechanism for NSD2 specific inhibition. </LI> <LI> We propose our inhibitors LEM-14 and LEM-14-1189 as tools for studying the biology of the NSDs and for drug-design. </LI> </UL> </P>

Fabrication and Characterization of Dye-sensitized Solar Cells based on Anodic Titanium Oxide Nanotube Arrays Sensitized with Heteroleptic Ruthenium Dyes

Shen, Chien-Hung,Chang, Yu-Cheng,Wu, Po-Ting,Diau, Eric Wei-Guang Korean Society of Photoscience 2014 Rapid communication in photoscience Vol.3 No.1

Anodic self-organized titania nanotube (TNT) arrays have a great potential as efficient electron-transport materials for dye-sensitized solar cells (DSSC). Herewith we report the photovoltaic and kinetic investigations for a series of heteroleptic ruthenium complexes (RD16-RD18) sensitized on TNT films for DSSC applications. We found that the RD16 device had an enhanced short-circuit current density ($J_{SC}/mAcm^{-2}=15.0$) and an efficiency of power conversion (${\eta}=7.2%$) greater than that of a N719 device (${\eta}=7.1%$) due to the increasing light-harvesting and the broadened spectral features with thiophene-based ligands. However, the device made of RD17 (adding one more hexyl chain) showed smaller $J_{SC}(14.1mAcm^{-2})$ and poorer ${\eta}(6.8%)$ compare to those of RD16 due to smaller amount of dye-loading and less efficient electron injection for the RD17 device than for the RD16 device. For the RD18 dye (adding one more thiophene unit and one more hexyl chain), we found that the device showed even lower $J_{SC}(13.2mAcm^{-2}) $ that led to a poorest device performance (${\eta}=6.2%$) for the RD18 device. These results are against to those obtained from the same dyes sensitized on $TiO_2$ nanoparticle films and they can be rationalized according to the electron transport kinetics measured using the methods of charge extraction and transient photovoltage decays.

Human Transcriptome and Chromatin Modifications: An ENCODE Perspective

Li Shen,최인찬,Eric J. Nestler,원경재 한국유전체학회 2013 Genomics & informatics Vol.11 No.2

A decade-long project, led by several international research groups, called the Encyclopedia of DNA Elements (ENCODE),recently released an unprecedented amount of data. The ambitious project covers transcriptome, cistrome, epigenome, and interactome data from more than 1,600 sets of experiments in human. To make use of this valuable resource, it is important to understand the information it represents and the techniques that were used to generate these data. In this review, we introduce the data that ENCODE generated, summarize the observations from the data analysis, and revisit a computational approach that ENCODE used to predict gene expression, with a focus on the human transcriptome and its association with chromatin modifications.

Relationships between erectile dysfunction, prostate cancer treatment type and inflatable penile prosthesis implantation

Chan Shen,Kunj Jain,Tejash Shah,Eric Schaefer,Shouhao Zhou,Dennis Fried,Drew A. Helmer,Hossein Sadeghi-Nejad 대한비뇨의학회 2022 Investigative and Clinical Urology Vol.63 No.3

Purpose: The prevalence of erectile dysfunction (ED) and the utilization of inflatable penile prosthesis (IPP) among prostate cancer patients are understudied. The aim of the study was to examine the relationships between ED, prostate cancer treatment type and IPP implantation in a national cohort. Materials and Methods: We identified a retrospective cohort of Surveillance, Epidemiology, and End Results (SEER)-Medicare patients diagnosed with locoregional prostate cancer between 2006 and 2011 and treated with surgery or radiation. Chi-square tests were used to detect significant differences in ED rates as well as use of IPP among the subset with ED. Multivariable logistic regression was used to examine factors associated with the use of IPP. Results: Among 31,233 patients in our cohort, 10,334 (33.1%) received prostatectomy and 20,899 (66.9%) received radiation. ED within 5 years was significantly more common in the prostatectomy group relative to those the radiation group (65.3% vs. 33.8%, p<0.001). In the subset of 13,812 patients with ED, the radiation group had greater median time to ED diagnosis compared to the prostatectomy group (346 vs. 133 days, p<0.001). IPP implantation was more frequent for prostatectomy patients than for radiation patients (3.6% vs. 1.4%, p<0.001). Cancer treatment type, race, and marital status were significantly associated with IPP utilization. Conclusions: ED is highly prevalent among prostate cancer patients, and IPP implantation is be underutilized. ED rates, time to ED diagnosis and utilization of IPP differed significantly by prostate cancer treatment type.

Recombinant Protein Expression and Purification of the Human HMTase MMSET/NSD2

Morishita, Masayo,Mevius, Damiaan,Shen, Yunpeng,Di Luccio, Eric Institute of Agricultural Science and Technology 2013 慶北大農學誌 Vol.31 No.3

Chromatin remodelers that include histone methyl transferases (HMTases) are becoming a focal point in cancer drug development. The NSD family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L are bona fide oncogenes found aberrantly expressed in several cancers, suggesting their potential role for novel therapeutic strategies. Several histone modifiers including HMTase have clear roles in human carcinogenesis but the extent of their functions and regulations are not well understood, especially in pathological conditions. The extents of the NSDs biological roles in normal and pathological conditions remain unclear. In particular, the substrate specificity of the NSDs remains unsettled and discrepant data has been reported. NSD2/MMSET is a focal point for therapeutic interventions against multiple myeloma and especially for t(4;14) myeloma, which is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma. Herein, as a first step before entering a pipeline for protein x-ray crystallography, we cloned, recombinantly expressed and purified the catalytic SET domain of NSD2. Next, we demonstrated the catalytic activities, in vitro, of the recombinantly expressed NSD2-SET on H3K36 and H4K20, its biological targets at the chromatin.

Be Prepared: Preoperative Coronal Malalignment Often Leads to More Extensive Surgery Than Sagittal Malalignment During Adult Spinal Deformity Surgery

Scott L. Zuckerman,Christopher S. Lai,Yong Shen,Mena G. Kerolus,Alex S. Ha,Ian A. Buchanan,Nathan J. Lee,Eric Leung,Meghan Cerpa,Ronald A. Lehman,Lawrence G. Lenke 대한척추신경외과학회 2021 Neurospine Vol.18 No.3

Objective: To evaluate the effect of coronal alignment on: (1) surgical invasiveness and operative complexity and (2) postoperative complications. Methods: A retrospective, cohort study of adult spinal deformity patients was conducted. Alignment groups were: (1) neutral alignment (NA): coronal vertical axis (CVA)≤3 cm and sagittal vertical axis (SVA)≤5 cm; (2) coronal malalignment (CM) only: CVA>3 cm; (3) Sagittal malalignment (SM) only: SVA>5 cm; and (4) coronal and sagittal malalignment (CCSM): CVA>3 cm and SVA>5 cm. Results: Of 243 patients, alignment groups were: NA 115 (47.3%), CM 48 (19.8%), SM 38 (15.6%), and CCSM 42 (17.3%). Total instrumented levels (TILs) were highest in CM (14.5±3.7) and CCSM groups (14±4.0) (p<0.001). More 3-column osteotomies (3COs) were performed in SM (21.1%) and CCSM (28.9%) groups than CM (10.4%) (p=0.003). CM patients had more levels instrumented (p=0.029), posterior column osteotomies (PCOs) (p<0.001), and TLIFs (p=0.002) than SM patients. CCSM patients had more TLIFs (p=0.012) and higher estimated blood loss (EBL) (p=0.003) than SM patients. CVA displayed a stronger relationship with TIL (p=0.002), EBL (p<0.001), and operative time (p<0.001) than SVA, which had only one significant association with EBL (p=0.010). Both SM/CCSM patients had higher readmissions (p=0.003) and reoperations (p<0.001) than CM patients. Conclusion: Amount of preoperative CM was a better predictor of surgical invasiveness than the amount of SM, despite 3COs more commonly performed in SM patients. CM patients had more instrumented levels, PCOs, and TLIFs than SM patients.

Recombinant Protein Expression and Purification of the Human HMTase MMSET/NSD2

Masayo Morishita,Damiaan Mevius,Yunpeng Shen,Eric di Luccio 경북대학교 농업생명과학대학 2013 Current Research on Agriculture and Life Sciences Vol.31 No.3

Chromatin remodelers that include histone methyl transferases (HMTases) are becoming a focal point in cancer drug development. The NSD family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L are bona fide oncogenes found aberrantly expressed in several cancers, suggesting their potential role for novel therapeutic strategies. Several histone modifiers including HMTase have clear roles in human carcinogenesis but the extent of their functions and regulations are not well understood, especially in pathological conditions. The extents of the NSDs biological roles in normal and pathological conditions remain unclear. In particular, the substrate specificity of the NSDs remains unsettled and discrepant data has been reported. NSD2/MMSET is a focal point for therapeutic interventions against multiple myeloma and especially for t(4;14) myeloma, which is associated with a significantly worse prognosis than other biological subgroups. Multiple myeloma is the second most common hematological malignancy in the United States, after non-Hodgkin lymphoma. Herein, as a first step before entering a pipeline for protein x-ray crystallography, we cloned, recombinantly expressed and purified the catalytic SET domain of NSD2. Next, we demonstrated the catalytic activities, in vitro, of the recombinantly expressed NSD2-SET on H3K36 and H4K20, its biological targets at the chromatin.

종자발아율, 수량, 그리고 화분발아율 비교를 통한 내서성 고추 자원 선발

서태철,양은영,조명철,Marteen Van Zonneveld,Roland Schafleitner,Derek Barchenger,Sanjeet Kumar,Susan Lin,Eric Shen,강석범 한국국제농업개발학회 2020 韓國國際農業開發學會誌 Vol.32 No.3

본 연구는 농촌진흥청 국립원예특작과학원 채소과에서 육성 중인 고추 34계통과 세계채소센터 육성 계통과 자원 12점 등 총 46점의 고추를 공시하여, 종자의 발아율, 수량 및 상품과율, 그리고 화분발아율을 조사하여 내서성이 강한 고추 자원을 선발하기 위하여 수행되었다. 1. 종자발아율 비교에서 여름종자는 가을종자 대비 상대적인 피해율은 4.3~100% 범위였고, H42(1.6%), H16(5.0%), H14(6.3%), H02(12.4%), H44(13.7%), H12(15.9%), H03 (17.6%), H17(23.4%) 순으로 대조 계통인 H37(26.2%)에 비해 피해율이 낮았다. 2. 고추 과실의 수량은 34.4~446.5g, 총 과실수는 2.0~134.3 개를 나타냈다. 상품과 비율에 있어서 75% 이상은 H22(95.0%), H16(89.1%), H37(88.4%), H40(86.4%), H6 (86.0), H27(83.7%), H04(83.6%), H03(82.6%), H08(81.1%), H44(81.4%), H02(80.0%), H45(79.1%), H17(78.7%), H19 (77.7%), H34(77.0%), H15(76.9%), H42(76.3%) 순으로 나타 났다. 3. 고온 처리에 의한 화분발아율의 피해율은 H06(59.5%), H14(74.4%), H44(85.3%), H03(90.2%)가 대조구인 H37 (94.7%)과 나머지 다른 고추에 비해 상대적으로 낮았다. 이상의 결과, 가을종자 대비 여름종자 종자발아율의 피해율, 수량 및 상품과율, 그리고 고온 처리에 의한 화분발아율 등을 고려하여, H03, H04, H06, H14, H17, H22, H44, H45 계 통을 내서성이 높은 자원으로 선발하였다. This study was conducted to select heat tolerant pepper accessions in tropical regions. Fruit yield and pollen germination rate between heat stress and normal condition as well as germination rate between seeds harvested in summer and fall were compared using 46 pepper accessions including 34 from Rural Development Administration and 12 from World Vegetable Center. For seed germination rate, the relative injury rate of summer seed ranged between 4.3 to 100%. Among accessions, H42 (1.6%), H16 (5.0%), H14 (6.3%), H02 (12.4%), H44 (13.7%), H12 (15.9%), H03 (17.6%) and H17 (23.4%) showed lower injury rate in seed germination than H37 (26.2%) which is known for its heat tolerance. Fruit yield and number per plant were in the range of between 34.4 to 446.5g and 2.0 to 134.3 fruits, respectively. The marketable fruit ratio ranged between 41.0 to 95.0% and accessions producing marketable fruits more than 75% were H22 (95.0%), H16 (89.1%), H37 (88.4%), H40 (86.4%), H6 (86.0), H27 (83.7%), H04 (83.6%), H03 (82.6%), H08 (81.1%), H44 (81.4%), H02 (80.0%), H45 (79.1%), H17 (78.7%), H19 (77.7%), H34 (77.0%), H15 (76.9%), and H42 (76.3%). The relative injury rate of pollen germination in heat stress condition was low in H06 (59.5%), H14 (74.4%), H44 (85.3%) and H03 (90.2%) compared to a control, H37 (94.9%). Based on the results of seed germination, marketable fruit yield and pollen germination, H03, H04, H06, H14, H17, H22, H44, H45 were selected for heat tolerance in tropical climate.