tbuckley/cabot-search huggingface dataset:
Influence of hematogenous tumor cell dissemination on patterns of relapse in patients with cervical carcinoma of the uterus.
Authors: J. K. Neugebauer, C. Schindlbeck, J. K. Jueckstock, U. Andergassen, M. Guenthner-Biller, V. Engelstaedter, B. Kost, P. G. M. Hepp, H. L. Sommer, K. Friese, W. Janni, B. K. Rack
Journal: Journal of Clinical Oncology (2011)

e21148 Background: The presence of isolated tumor cells (ITC) in the bone marrow at the time of primary diagnosis has been found to indicate an increased risk for subsequent development of distant metastases in various solid tumors. In this study we evaluated the prevalence and prognostic significance of ITC in patients with primary carcinoma of the cervix uteri (Janni et al., Cancer 2003). Up-dated results are presented. Methods: Bone marrow aspirates of 133 patients with newly diagnosed carcinoma of the cervix uteri were immunocytochemically analyzed for the presence of cytokeratin(CK)-positive cells from May 1994 until July 2002. We used a quantitative immunoassay with the monoclonal anti-CK antibody A45-B/B3 and evaluated 2 x106 bone marrow cells per patient. Patients were followed prospectively for a median of 48 (range, 1-168) months. Results: ITC were found in the bone marrow of 39 patients (29%). The presence of ITC did not correlate with the FIGO tumor stage (p=0.61), or pelvic and paraaortal lymph node involvement (p=0.41), nor with invasion of peritumoral blood vessels (p=0.92). The bone marrow status at the time of primary diagnosis did not correlate with the overall survival as estimated by Kaplan-Meier-Analysis (p=0.31). Distant metastases occurred in 14.9% of the patients (n=14) with negative and in 15.4% of the patients (n=6) with positive bone marrow status (p= 1.0). The mean disease free survival was 139 months (126 – 152, 95% CI) in patients with negative, and 110 months (123 – 145) in patients with positive bone marrow status (p=0.13). Conclusions: In contrast to findings from earlier analyses with shorter follow-up time and compared to other tumor entities, the presence of ITC in the bone marrow of patients with cervical cancer does not indicate an increased risk for the development of distant metastases for these patients. Stratification for systemic treatment should not be based on the bone marrow status in this patient population.
P16.03 Efficacy and tolerability of lacosamide in patients with glioma: final results of a mono-institutional prospective study
Authors: A. Pellerino, M. Magistrello
Journal: Neuro-Oncology (2016)

AbstractBackground:Lacosamide (LCM) has been suggested in few retrospective studies to improve seizure control as an add-on treatment in brain tumor patients. We present the final results of a prospective study on a cohort of patients with low grade (LGG) and high grade gliomas (HGG) and medically intractable epilepsy who received LCM.Patients and methods:Eligibility criteria were as follows: 1) biopsy-proven grade II or III or IV gliomas according to WHO 2007; 2) persisting seizures (seizure frequency > 1 per month) despite a treatment with 1 or more antiepileptic drugs (AEDs) for at least 3 months and adequate serum concentration; 3) stable steroid dose; 4) available information on tumor response on MRI according to RANO criteria following chemotherapy or radiotherapy; 5) age > 18 years. LCM was given at 50 mg daily for one week with an increase of 50 mg twice daily every week to a target dose of 200–400 mg/day. The endpoints were > 50% decrease of seizure frequency and seizure freedom at 6 and 9 months.Results:Since January 2012 71 patients were evaluable. There were 26 grade II gliomas, 20 grade III and 25 glioblastomas. Eleven patients (15.5%) had generalized seizures and 32 (95.7%) partial seizures. Forty-four patients (61.8%) were or on AED monotherapy while 27 (38.2%) on polytherapy. Reasons for introduction of LCM were lack of efficacy of previous AEDs associated with (46.5%) or without (53.5%) progressive disease on MRI or unacceptable side effects of traditional AEDs in 11 patients (15.5%). Median duration of follow up was 9 months (range 3–24 months).Among LGG at 6 months from start of LCM 11/26 patients (42.3%) had a reduction of >50% of seizure frequency while seizure freedom was obtained in 11/26 (42.3%); at 9 months a reduction of >50% of seizure frequency was observed in 9/24 (37.5%) while seizure freedom was obtained in other 13 (54.2%). Moreover, 11/26 patients (42.3%) at 6 months and 10/26 (38.5%) at 9 months were seizure responders respectively, without concurrent antineoplastic therapies. As for HGG at 6 months 10/39 patients (25.6%) had a reduction of >50% of seizure frequency while seizure freedom was obtained in 18/39 (46.1%); at 9 months a reduction of >50% of seizure frequency was observed in 7/32 (21.8%) and seizure freedom in other 17 (53.1%). A resolution of an epileptic status was obtained in 6 patients of whom one receiving LCM alone. Secondary generalized seizures disappeared in 14 patients. Two responding patients were able to reduce the doses of previous AEDs. Most patients (87.3%) did not report significant toxicities: in 2 cases only LCM was withdrawn due to dizziness and fatigue and resistant epilepsy, respectively.Conclusion:At our knowledge this is the first prospective study on patients with both LGG and HGG with LCM as an add-on treatment showing a significant activity, even regardless of tumor response to antineoplastic treatment. LCM did not have interactions with AEDs.
구연 : 소간암 환자에서 고주파열치료와 수술적 절제의 치료 성적 비교
Authors: 홍성노, 최문석, 이준혁, 고광철, 백승운, 유병철, 이종철
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 소간암의 치료법으로는 수술적 절제가 가장 높은 완치의 기회를 제공하는 치료법으로 인정 받고 있으며 경피적 알콜 주입술보다 더 좋은 치료 성적을 보임이 보고 되고 있다. 최근 사용되는 고주파 열치료는 경피적 알콜 주입술보다 종양의 완전 괴사율이 높고 국소재발율이 낮아 수술적 절제에 버금가는 치료 성적이 기대되지만, 아직까지 고주파 열치료와 수술적 절제의 치료 성적를 비교한 연구는 보고 되고 있지 않다. 이에 연자 등은 소간암의 치료에 있어서 고주파 열치료와 수술적 절제의 치료 성적을 비교해 보고자 하였다. 대상과 방법: 1999년 5월부터 2002년 3월까지 간암으로 진단받고 수술적 절제 혹은 고주파열치료를 시행 받은 환자 중 간암의 크기가 3 cm 이하, 개수가 3개 이하이면서 이전에 간암에 대한 치료를 받지 않은 환자로 Child-Pugh 점수가 5점인 환자들 중 시술 또는 수술 후 1개월째 시행한 영상학적 검사에서 완전 괴사나 완전 절제가 확인된 경우만을 대상으로 하였다. 이들 환자들을 대상으로 국소 재발률, 원격 재발률 및 무병생존율과 생존율을 후향적으로 비교하였다. 고주파열치료를 시행받은 환자는 총 63명(남:여＝49:18, 평균연령＝56.5세)이었으며, 수술적 절제를 시행 받은 환자는 총 102명(남:여＝83:19, 평균연령＝51.7세)이었다. 추적 관찰기간의 중위값은 고주파열치료군이 22개월, 수술군이 24개월이었다. 결과: 1) 국소 재발률 - 고주파열치료군의 1년, 2년, 3년 국소 재발률은 각각 1.5%, 6.9%, 19.9%였으며, 수술군의 경우 각각 1.0%, 1.0%, 1.8%로 양군간에 유의한 차이를 보였다(p＝0.01). 2) 원격 재발률-고주파열치료군의 1년, 2년, 3년 원격 재발률은 각각 25.4%, 50.4%, 63.4%였으며, 수술군의 경우 각각 20.9%, 38.5%, 45.8%으로 양군 간 통계학적으로 유의한 차이를 보이지 않았다(p＝0.20). 3) 무병 생존율 - 고주파열치료군의 1년, 2년, 3년 무병 생존율은 각각 71.6%, 44.5%, 35.6%였으며, 수술군의 경우 각각 79.1%, 61.5%, 54.2%로 양군간에 유의한 차이는 보이지 않았다((p＝0.09). 4) 생존율 - 고주파열치료군의 1년, 2년, 3년 생존율은 각각 98.4%, 86.7%, 73.6%였으며, 수술군의 경우 각각 97.0%, 90.7%, 85.4%로 양군간에 통계학적 유의성이 보이지 않았다(p＝0.28). 결론: 소간암 환자의 치료에 있어서 고주파 열치료는 수술적 절제에 필적하는 효과적인 치료 방법으로 생각된다.
Protein‐Modified CuS Nanotriangles: A Potential Multimodal Nanoplatform for In Vivo Tumor Photoacoustic/Magnetic Resonance Dual‐Modal Imaging
Authors: Duyang Gao, Zonghai Sheng, Yubin Liu, Dehong Hu, Jian Zhang, Xuanjun Zhang, Hairong Zheng, Zhen Yuan
Journal: Advanced Healthcare Materials (2016)

Controllable preparation of water-soluble multifunctional nanoprobes is of great significance for cancer early diagnosis. In this study, protein-modified hydrophilic copper sufide (CuS) nanotriangles with tunable absorption in the second near-infrared region are developed in the presence of halide ions. Further, gadolinium ions chelated diethylenetriaminepentaacetic acid is conjugated on it by using the unique characteristics of the protein-protected nanotriangles. Specifically, the as-obtained nanostructures are investigated as contrast agents for enhanced in vivo photoacoustic/magnetic resonance dual-modal tumor imaging. More importantly, in vitro and in vivo toxicity analysis are also performed, which show that the dual-modal nanoprobes are biocompatible for most of the cases. It is demonstrated that the novel as-prepared protein-modified nanotriangles are able to work as a nanoplatform to construct dual-modal nanoprobes, which paves a new avenue for improving the photoacoustic/magnetic resonance imaging contrast in cancer detection. It should be pointed out that other functional blocks may also be linked on it, which makes it a general method to design multifunctional nanoprobes.
709. Characterization of Nanoparticles in Lentiviral Vector Preparations
Authors: Erik Hansen, Kristen Lee, Suzanna Melotti, Jesse Milling, Maya Miatkowski, James Warren, Mercedes Segura
Journal: Molecular Therapy (2016)

The potential of lentivirus-based gene therapy vectors for the treatment of severe genetic diseases using genetically modified CD34+ cells and hematological malignancies using chimeric antigen receptor T-cells (CAR-T) is supported by recent positive data in clinical trials showing promising therapeutic benefits and safety. The progress from early-to-late stage clinical development requires enhanced characterization of the purified lentivirus vector product. Lentiviral vector preparations are complex in nature and contain a heterogeneous mixture of transduction-competent as well as transduction-deficient virus particles. In addition, lentiviral vector production utilizes host cells that can produce not only the viral particles of interest, but a variety of closely-related impurities that include exosomes and microvesicles. These cell-derived impurities can overlap key biophysical and biochemical attributes of the lentiviral vector, including size, net charge and composition, making them challenging to analyze. We used a variety of analytical tools to further characterize lentiviral vector preparations in terms of size distribution, particle counts and to determine the total particle (viral or non-viral) to infectious particle ratio. These tools included Nanoparticle Tracking Analysis (Nanosight), Field-Flow Fractionation coupled to Multi-Angle Light Scattering (FFF-MALS), and p24-ELISA. Particle protein composition was evaluated by several standard orthogonal protein quantitation assays. Characterization of nanoparticle subpopulations is important as it can support the refinement of manufacturing processes. The impact of variation of these parameters on lentivirus vector performance still remains largely unknown, so interpretations of the results must be carefully assessed and further study is warranted.
Genome-Wide Association Study Identifies a Novel Susceptibility Locus At 10p12.31-12.2 for Childhood Acute Lymphoblastic Leukemia in Ethinically Diverse Populations
Authors: Jun J. Yang, Heng Xu, Wenjian Yang, Virginia Perez-Andreu, Meenakshi Devidas, Yiping Fan, Cheng Cheng, Deqing Pei, Paul Scheet, Esteban Gonzalez Burchard, Celeste Eng, Scott Huntsman, Dara G Torgerson, Michael Dean, Naomi Winick, Paul L. Martin, Bruce Camitta, W. Paul Bowman, Cheryl L Willman, William L. Carroll, Charles G Mullighan, Deepa Bhojwani, Stephen P. Hunger, Ching-Hon Pui, William E. Evans, Mary V. Relling, Mignon L. Loh
Journal: Blood (2012)
Spatial signalling mediated by the transforming growth factor-β signalling pathway during tooth formation
Authors: Xin-Yu He, Ke Sun, Ruo-Shi Xu, Jia-Li Tan, Cai-Xia Pi, Mian Wan, Yi-Ran Peng, Ling Ye, Li-Wei Zheng, Xue-Dong Zhou
Journal: International Journal of Oral Science (2016)

Tooth development relies on sequential and reciprocal interactions between the epithelial and mesenchymal tissues, and it is continuously regulated by a variety of conserved and specific temporal-spatial signalling pathways. It is well known that suspensions of tooth germ cells can form tooth-like structures after losing the positional information provided by the epithelial and mesenchymal tissues. However, the particular stage in which the tooth germ cells start to form tooth-like structures after losing their positional information remains unclear. In this study, we investigated the reassociation of tooth germ cells suspension from different morphological stages during tooth development and the phosphorylation of Smad2/3 in this process. Four tooth morphological stages were designed in this study. The results showed that tooth germ cells formed odontogenic tissue at embryonic day (E) 14.5, which is referred to as the cap stage, and they formed tooth-like structures at E16.5, which is referred to as the early bell stage, and E18.5, which is referred to as the late bell stage. Moreover, the transforming growth factor-β signalling pathway might play a role in this process. The stage at which tooth precursor cells in suspension form tooth-like structures has been determined in rat cells. Xue-Dong Zhou of Sichuan University, China, and colleagues created single-cell preparations from tooth precursor cells at different stages of development, and assessed their ability to form tooth structures when removed from the normal surroundings of tooth development. The results showed that cells 16.5 days old or more formed distinct tooth-like structures including pulp and dentin, while younger cells formed disordered tissue. Cells aged 18.5 days before isolation went on to exhibit partially formed enamel. The researchers suggest the TGF-beta signaling pathway, identified in previous studies as a mediator of tooth formation, may play a role in this setting. The findings warrant further investigation into tooth bioengineering, which may ultimately yield therapies to replace defective teeth in humans.
Rate of hemoglobin (Hb) decline from less than 10 g/dl to less than 9 g/dl by electronic medical-record (EMR) evaluation in community oncology patients (pts) receiving chemotherapy in the absence of erythropoiesis-stimulating agents (ESAs).
Authors: M. Pirolli, H. Collins, S. A. Hulnick, J. Quigley
Journal: Journal of Clinical Oncology (2011)

e19625 Background: Cancer pts often develop chemotherapy-induced anemia (CIA), which can be treated with transfusions and/or ESAs. Restrictions on ESA use in CIA were recently added to the ESA labels (ie, ESA initiation now occurs in the US at Hb < 10 g/dL). Since pts with low Hb (< 9 g/dL) at ESA initiation may be at higher risk for transfusion, understanding how quickly CIA pts transition from Hb < 10 to < 9 g/dL may help optimize ESA use. Methods: Clinic-based EMR data were used in a retrospective observational assessment to estimate the proportion of chemotherapy episodes with pts whose Hb declined from < 10 to < 9 g/dL by 3, 6 and 9 weeks (wks). Chemotherapy episodes containing gemcitabine, platinum, anthracycline, or taxane doublets were indentified at the time of 10 ≤ Hb < 11 g/dL and at the time when Hb subsequently declined to < 10 g/dL at least once in a 9-wk period. Chemotherapy episodes were re-indexed at the time of Hb < 10 g/dL to estimate the proportion that further declined to Hb < 9 g/dL by 3, 6 and 9 wks without ESAs. Results: Between 8/1/08 and 6/24/10, 8057 episodes with 10 ≤ Hb < 11 g/dL were identified in 7766 pts from 44 US community oncology practices. Episodes evaluated included 72% women; 61% of the sample was < 65 years old, 41% had breast cancer, and 30% lung cancer. 4035 episodes (50%) declined from baseline 10 ≤ Hb < 11 g/dL to Hb < 10 g/dL by 9 wks. An estimate of the proportion of these episodes that declined from Hb < 10 to < 9 g/dL was 36% by 3 wks, 43% by 6 wks and 46% by 9 wks (Table). Gemcitabine and platinum containing doublets were more often associated with a Hb decline from < 10 to < 9 g/dL by 9 wks. Conclusions: These results suggest that cancer pts receiving common chemotherapy regimens transition quickly from Hb < 10 to < 9 g/dL without ESAs. As initiating ESAs may take time, assessing the appropriateness of ESA therapy early may mitigate some risk of pts falling to low Hb levels. Proportion of 4,035 episodes with Hb decline < 10 g/dL to < 9 g/dL. 3 wks 6 wks 9 wks Total 36% 43% 46% By chemotherapy doublet* Gemcitabine 42% 51% 55% Platinum 40% 48% 51% Anthracycline 32% 38% 41% Taxane 31% 38% 42% * Categories are not mutually exclusive.
20. A Novel Approach in the Treatment of Dystrophic Cardiomyopathy
Authors: Mona El Refaey, Li Xu, Jing Xu, Lixia Zhao, Yandi Gao, Renzhi Han
Journal: Molecular Therapy (2016)

Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy with a worldwide incidence of one in 3500 live male births. It is caused by the lack of dystrophin, a critical muscle protein that connects the cytoskeleton and the extracellular matrix (ECM). Cardiomyopathy develops in at least 90% of patients and alone can shorten the life expectancy of DMD patients by at least 2 years and up to 40% of DMD patients eventually die from heart failure. Recently, RNA-guided, nuclease-mediated genome editing based on type II CRISPR (clustered regularly interspaced short palindromic repeat)/Cas (CRISPR-associated) system, has been emerged to alter the genome. In this study, we hypothesize that CRISPR-mediated genome editing could offer a novel therapy for DMD-associated cardiomyopathy in live mice. Two gRNA target sites were chosen from intron 20 and 23 of mouse Dmd. Co- transfection of the two gRNA with cas9 plasmids into mouse C2C12 cells resulted in the detection of a small PCR product as predicted, indicating successful CRISPR-mediated genome editing. DNA sequencing confirmed that the transcripts from C2C12 cells treated with gRNA/cas9 were formed due to successful deletion of exons 21-23 of mouse Dmd. Moreover, we injected the adenoviral vectors carrying GFP-2A-cas9 and gRNAs systemically and locally into the newborn pups. Four weeks after adenovirus transduction, dystrophin expression was restored in the heart muscles positive for GFP. Our PCR and western blotting data demonstrated that in-frame deletion of the genomic DNA covering exon 23 restored functional dystrophin expression in the hearts of mdx mice. Immunofluorescence staining also demonstrated that β-dystroglycan, which is normally located to the sarcolemma in healthy heart muscles via interaction with dystrophin-glycoprotein complex, was also restored at the sarcolemma of GFP-positive heart muscle fibers. These data provide the proof evidence of systemic restoration of dystrophin in the hearts of live mice.
A Cell-Death-Defying Factor, Anamorsin, Contributes Cell Growth through Binding with PICOT and Inactivation of PKCs and p38MAPK.
Authors: Hirohiko Shibayama, Yuri Saito, Akira Tanimura, Hirokazu Tanaka, Itaru Matsumura, Yuzuru Kanakura
Journal: Blood (2010)
Generic Versions of Low Molecular Weight Heparin May Not Have the Same Safety-Efficacy Profile as the Branded Low Molecular Weight Heparins In Acute Coronary Syndrome.
Authors: Debra Hoppensteadt, Walter Jeske, Evangelos Litinas, Omer Iqbal, Jeanine M. Walenga, Bruce E Lewis, Hussein Kahn, Jawed Fareed
Journal: Blood (2010)
Validation of a Non-Invasive Hemoglobin Estimation in Patients with Sickle Cell Disease
Authors: Murtadha K. Al-Khabori, Abdulhakeem Al-Hashim, Zeba Jabeen, Khalil Al Farsi, Mohammed Al-Huneini, Arwa Z. Al-Riyami, Nasser Al-Kemyani, Shahina Daar
Journal: Blood (2012)
Abstract 3442: Ganetespib sensitizes colorectal cancer <i>in vitro</i> and <i>in vivo</i> to a clinically relevant regimen of radiation and chemotherapy
Authors: Ganji Purnachandra Nagaraju, Kirtesh Patel, Jing Wen, Roberto Diaz, El-Rayes F. Bassel
Journal: Cancer Research (2015)

Abstract Purpose: We describe the efficacy of the second generation HSP90 inhibitor ganetespib in combination with radiation and chemotherapy against colorectal adenocarcinoma in vitro and in vivo. Methods and Materials: Ganetespib's effects on colorectal adenocarcinoma proliferation and ability to sensitize to radiation and/or chemotherapy were analyzed in the colorectal cell lines HCT-116 and HT-29. Ganetespib's ability to modulate apoptosis when combined with radiation and chemotherapy was characterized, and its effects on the AKT, ERK and PI3K pathways were investigated. Tumor growth delay of colorectal adenocarcinoma with ganetespib alone and in combination with radiation and chemotherapy was analyzed in xenografts. Lastly, immunohistochemical analyses of HSP90 and p-AKT levels where performed in paired normal and tumor colorectal tissue samples from 10 patients. Results: At the clinically achievable dose of 50 nM, ganetespib inhibited colorectal cancer cells proliferation (p&amp;lt;0.014), potentiated 5-FU chemotherapy and 2Gy of ionizing radiation (p&amp;lt;0.0001), increased pro-apoptotic signaling proteins, and decreased levels of p-AKT, PI3K, and p-ERK in vitro. Combinations of ganetespib, 5-FU, and radiation therapy exhibited synergistic efficacy in human xenograft models in vivo (p&amp;lt;0.0001). Finally, HSP90 and p-AKT were both co-overexpressed in human colorectal cancer tissue samples relative to normal colon tissue. Conclusion: Altogether, these data show the clinically relevant combination of ganetespib with chemotherapy and radiation is effective in colorectal adenocarcinoma in vitro and in vivo. We are currently evaluating ganetespib's safety with chemotherapy and radiation therapy in a phase I study of patients with localized colorectal adenocarcinoma. Citation Format: Ganji Purnachandra Nagaraju, Kirtesh Patel, Jing Wen, Roberto Diaz, El-Rayes F. Bassel. Ganetespib sensitizes colorectal cancer in vitro and in vivo to a clinically relevant regimen of radiation and chemotherapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3442. doi:10.1158/1538-7445.AM2015-3442
Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits
Authors: Jacqueline M Lane, Jingjing Liang, Irma Vlasac, Simon G Anderson, David A Bechtold, Jack Bowden, Richard Emsley, Shubhroz Gill, Max A Little, Annemarie I Luik, Andrew Loudon, Frank A J L Scheer, Shaun M Purcell, Simon D Kyle, Deborah A Lawlor, Xiaofeng Zhu, Susan Redline, David W Ray, Martin K Rutter, Richa Saxena
Journal: Nature Genetics (2016)