tbuckley/cabot-search huggingface dataset:
Inhibition of endothelial progenitor cell differentiation from hematopoietic stem cells by vascular endothelial growth inhibitor
Authors: Tian Fang, Paulina Huang, Luyuan Li
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

279 

Bone marrow-derived endothelial progenitor cells (EPC) have been shown to play a critical role in tumor vasculogenesis. It is thought that EPC mobilize to tumors and support the formation of new blood vessels, which are essential for tumor growth and metastasis. Vascular endothelial growth inhibitor (VEGI; TNFSF15), a member of the tumor necrosis factor superfamily, is predominantly produced by endothelial cells (EC) and specifically targets EC to inhibit their proliferation and induce apoptosis. Here, we report that VEGI can inhibit the differentiation of hematopoietic stem cell (HSC) to EPC. We isolated Sca1+ cells from whole bone marrow from C57BL/6 mice and cultured them in EPC differentiating stimuli in the absence or presence of recombinant VEGI. Utilizing flow cytometry, we analyzed for occurrence of markers indicative of EPC, including CD133, c-kit, Tie-2, Flk-1, and VE-cadherin. We observed a significant inhibition of the expression of Tie-2, Flk-1 and VE-cadherin, but not that of CD133 or c-kit, on VEGI treated cells, indicating that these cells remain principally HSC. Consistently, the VEGI treated cells retained a morphology that more closely resembled the round, clustering HSC, whereas the untreated control cells gave a resemblance to EC within two weeks in culture. Functionally, HSC-derived cells cultured in the presence of VEGI exhibit a decreased capability of adhesion and migration. In addition, while the control cells were able to form tubular structures when plated on Matrigel, the VEGI treated cells lost such ability. These findings are consistent with the view that VEGI inhibits EPC differentiation from HSC under these experimental condition, suggesting that VEGI may take part in the modulation of post-natal vasculogenesis.
Breast cancer profile in patients (pts) seen at two Community Hospitals of Buenos Aires,Argentina, born between 1900 and 1970
Authors: L. Koliren, E. Soto, M. Bianconi, S. Otero, R. Zlates, P. Szabo, P. Micone, K. O′leary, G. Jankilevich, A. Etkin
Journal: Journal of Clinical Oncology (2004)

9685 Background: It is known that envirommental and life style changes may play a role in the development of breast cancer.In our country,the patients originally seen with this pathology were Spanish and Italian immigrants who came to Argentina until 1950.We analized the changes that took place with respect tothe age of breast cancer onset and menopause in this population along the last century. Methods: Two thousand and eleven female pts with breast cancer diagnosis (dx),seen at Hospital Rawson (1962–1978) and Hospital Durand (1979–2oo3), were retrospectively analyzed.All of them were born between 1900 and 1970.The following variables were taken into account: date of birth, age and menopausal status at dx.The whole population was divided into three groups based on age : Born between 1900 and 1930 Group A (GA),between 1931 and 1960 Group B (GB) and from 1961 on,Group C(GC). Results: The overall mean age was 55 +/−13 years (yrs).GA 63+/−11 yrs;GB 50+/−9 yrs; GC 35+/−4 yrs.(GA vs.GB p=0.001).As regards the menopausal status at dx,the relation between pre and postmenopausal women was GA:92/620 pts,GB:550/496 pts and GC:95/4 pts.(GA vs GB p=0.001).The age at dx for premenopausal women was GA:46+/− 6yrs,GB:44+/−6 yrs and GC 35+/− 4yrs.(GA vs. GB p=0.001) and in postmenopausal women :GA 66+/−9 yrs,GB56+/−7 yrs and GC 38 +/−3 yrs (GA vs. GB p=0.001).The time between menopause and dx was 18 yrs for GA and 10 yrs for GB.The number of women with childbearing potential under 40 years old who constituted the High Risk Premenopausal Group (HRPG) were 19,176 and 98 for Groups A,B and C respectively.This HRPG correspondedf to 13% of the total number of cases. Conclusions: In our country,the tnedency clearly shows that women are younger at the time of diagnosis (diferences between age Groups A,B and C) and that there is a predominant increase in the number of women who are premenopausal at diagnosis.The differences among Groups A,B and C are more than 10 years.This not only may reflect the early diagnosis and consultation but also other factors that need yet to be determined.The creation of a National Tumor Database could be the only means to confirm these findings. No significant financial relationships to disclose.
Initial characterization of the toxicity and efficacy of elacytarabine (CP-4055), a novel antileukemic agent, using a multidimensional exposure-response relationship model.
Authors: Murray P Ducharme, Steinar Hagen, Petter-Arnt Hals, Tove Flem Jacobsen, Francis J. Giles, Susan Mary O'Brien, Hubert Dirven, Colucci Phillipe, Corinne Seng Yue
Journal: Journal of Clinical Oncology (2012)

6619^ Background: Elacytarabine (CP-4055), an elaidic acid ester of ara-C, is a novel antineoplastic agent developed to treat hematologic malignancies (HM). It is metabolized to active ara-CTP and inactive ara-U. In 3 studies, diverse elacytarabine monotherapy doses and regimens were given to patients with advanced HM and solid tumours. This analysis aimed to 1) describe the pharmacokinetics (PK) of elacytarabine in these patients and 2) investigate the relationship between PK and toxicity and efficacy in HM. Methods: Population PK analyses were run with ADAPT 5 (ITS) and included 146 patients given a 2h, 4h or 120h continuous infusion (CIV) of elacytarabine. Elacytarabine, ara-C and ara-U plasma concentrations (Cp) were simultaneously modeled and explained. Standard model discrimination criteria were used to select the best model. With the model, different dosing regimens were simulated to find average exposure and % of patients with efficacious or toxic exposure. A multi-dimensional exposure-response relationship (MDERR) was developed with pre-clinical and clinical data. Results: The best model was a 2-compartment (CPT) model with linear elimination and formation rates for the metabolism of elacytarabine to ara-C. Mean PK parameters were Vc = 4.12 L/m 2 , CL= 5.27 L/h/m 2 and T 1/2 = 7.57 h. Elacytarabine PK included a peripheral CPT with a non-linear distribution process to reflect saturable binding to red blood cells, otherwise its PK was linear. Ara-C and ara-U PK were described by 2- and 1-CPT linear models, respectively. The MDERR model related efficacy and toxicity thresholds to elacytarabine dosing regimens, and indicated that a 120 h CIV dosing regimen is preferable, allowing elacytarabine to exceed efficacious Cp for longer than the other investigated regimens. A minimum dose of 1000 mg/m 2 /day is needed for most patients to receive efficacious exposure. Conclusions: Elacytarabine is a promising anti-leukemic agent for patients with advanced HM. Its PK, toxicity and efficacy were characterized in patients given diverse dosing regimens. An MDERR model, which will be further refined or confirmed in upcoming clinical trials, was proposed.
Leptomeningeal Enhancement for Multiple Sclerosis
Authors: Jagannadha Avasarala
Journal: JAMA Neurology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Junior doctor suspended for a month for falsifying temperature of nurse later found to have Ebola
Authors: Clare Dyer
Journal: BMJ (2017)

A junior doctor who helped to falsely record nurse Pauline Cafferkey’s temperature on her return to Heathrow airport from fighting Sierra Leone’s Ebola epidemic in December 2014 has been suspended from the medical register for one month for dishonesty.

Hannah Ryan, 31, a tropical diseases specialist at the Liverpool School of Tropical Medicine, had been working with Cafferkey in West Africa. The returning group of medical staff were all eager to reach their homes, …
Integrated PET based response classification for non-Hodgkin's lymphoma (NHL)
Authors: M. E. Juweid, G. Wiseman, Y. Menda, J. Wooldridge, B. K. Link, A. Stolpen, M. M. Graham, J. M. Vose
Journal: Journal of Clinical Oncology (2004)

6533 Background: FDG-PET is increasingly being utilized for response assessment of NHL. The purpose of this study was to determine whether FDG-PET+CT result in a more accurate response classification compared with CT alone in patients with NHL. Methods: FDG-PET and CT were performed in 54 aggressive NHL patients 1–3 months following 4–8 cycles of CHOP-based chemotherapy. 18-month progression-free survival (18-mo PFS) was compared between CT- and PET+CT-assigned response designations, such as complete response (CR), unconfirmed CR (CRu), partial response (PR), stable disease (SD) and progressive disease (PD). Response designations by CT were based on the International Workshop Criteria. PET+CT-based were derived from CT-based designations by integrating the PET findings into those of CT (e.g., patients with CR by CT alone who were positive by PET were classified as PR by PET+CT; those with CRu, PR, or SD by CT who were negative by PET were classified as CR by PET+CT). Results: CT-based response designations were 18CR, 6CRu, 17PR, 12SD and 1PD. PET+CT-based designations were 39CR, 9PR, 5SD, and 1PD. Similar 18-mo PFS was found in patients with CR by PET+CT or CT alone (92% vs. 89%), while there was a statistically significant difference in 18-mo PFS between patients with PR by PET+CT vs. by CT alone (22% vs.70%, P=0.05). Difference in 18-mo PFS between patients with CR and PR by CT was not significant (P=0.3), while difference between CR and PR using PET+CT was highly significant (P<0.0005). Conclusions: Compared with CT-, PET+CT-based response designations more accurately reflect expected outcome in aggressive NHL. These results challenge the current paradigm in response assessment of patients with NHL and suggest that PET/CT-based response classification may become the new standard for NHL. No significant financial relationships to disclose.
Intraoperative sentinel lymph node identification using novel receptor binding agent (technetium-99m neomannosyl human serum albumin, <sup>99m</sup>Tc-MSA) in stage I non-small cell lung cancer
Authors: H. Kim, S. Kim, D. Kang, H. Yong, S. Lee, J. Jeong, Y. Choi
Journal: Journal of Clinical Oncology (2009)

7588 Background: In order to simplify synthesis and labelling procedures and to improve the biological properties, we developed a novel mannose receptor-binding agent, Technetium-99m neomannosyl human serum albumin ( 99m Tc-MSA). This study was designed to test the reliability and feasibility of sentinel nodes identification using this new radioactive agent in stage I non-small cell lung cancer. Methods: A total dose of 1mCi of 99m Tc- MSA in 0.2ml was administered in one shot at the peri-tumoral region under the chest CT or bronchoscope guidance 3 hours before surgery in the CT room. Dynamic whole-body SPECT lymphoscintigraphic image was obtained at 30 min after injection and static thoracic SPECT lymphoscintigraphy images were acquired at 1 and 2 hour after injection. During operation, the radioactivity of the lymph nodes was counted with a handheld gamma probe before (in vivo) and after (ex vivo) dissection. Lymph nodes with an ex vivo radioactive count more than 5 times the radioactivity count of the resected lung tissue were identified as sentinel nodes. The correlation between the in vivo and ex vivo results was examined. All harvested lymph nodes were examined histologically. Results: Thirty patients (20 men, 10 women; mean age, 62.6±9.40 years) who were candidates for lobectomy with mediastinal lymph node dissection for stage I non-small cell lung cancer were enrolled consecutively. Sentinel nodes could be detected from 30 minutes to 5 hours after the injection of 99m Tc-MSA on lymphoscintigraphy. The mean number of dissected lymph nodes per patients was 20.7±1.30 (8∼41). Among 30 patients, sentinel lymph nodes could be identified in all patients (100%). The mean number of sentinel lymph nodes identified was 2.4±1.04 stations (range, 1∼5) per patient. No false-negative sentinel lymph nodes were detected in any of the 8 patients with N1 or N2 disease (0%). The relationship between in vivo and ex vivo results for mediastinal sentinel lymph nodes showed concurrence in 25 of 30 patients (83.3%). Conclusions: The results of this clinical trial showed that 99m Tc-MSA had promising properties for sentinel nodes identification in non-small cell lung cancer. No significant financial relationships to disclose.
Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related-protein 1
Authors: Teng-Jian Zhou, Shi-Li Zhang, Cheng-Yong He, Qun-Ying Zhuang, Pei-Yu Han, Sheng-Wei Jiang, Huan Yao, Yi-Jun Huang, Wen-Hua Ling, Yu-Chun Lin, Zhong-Ning Lin
Journal: Theranostics (2017)

Cancer stem cells (CSCs) are a small subset of malignant cells, possessing stemness, with strong tumorigenic capability, conferring resistance to therapy and leading to the relapse of nasopharyngeal carcinoma (NPC). Our previous study suggested that cyclooxygenase-2 (COX-2) would be a novel target for the CSCs-like side population (SP) cells in NPC. In the present study, we further found that COX-2 maintained the stemness of NPC by enhancing the activity of mitochondrial dynamin-related protein 1 (Drp1), a mitochondrial fission mediator, by studying both sorted SP cells from NPC cell lines and gene expression analyses in NPC tissues. Using both overexpression and knockdown of COX-2, we demonstrated that the localization of COX-2 at mitochondria promotes the stemness of NPC by recruiting the mitochondrial translocation of p53, increasing the activity of Drp1 and inducing mitochondrial fisson. Inhibition of the expression or the activity of Drp1 by siRNA or Mdivi-1 downregulates the stemness of NPC. The present study also found that inhibition of mitochondrial COX-2 with resveratrol (RSV), a natural phytochemical, increased the sensitivity of NPC to 5-fluorouracil (5-FU), a classical chemotherapy drug for NPC. The underlying mechanism is that RSV suppresses mitochondrial COX-2, thereby reducing NPC stemness by inhibiting Drp1 activity as demonstrated in both the in vitro and the in vivo studies. Taken together, the results of this study suggest that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC.
춘계학술대회 발표 : 포스터 발표 ; 급성 간질환 : 급성 A형간염 환자들에서 비전형적인 임상양상의 분석
Authors: 송기섭, 김주현, 김영생, 김민주, 장욱순, 장창수, 정혁상, 유상균, 권광안, 박동균, 권오상, 김연석, 김선숙, 구양서, 김유경, 김연수, 최덕주
Journal: Clinical and Molecular Hepatology (2006)
Epoetin alfa 40,000 U QW vs darbepoetin alfa 200 mcg Q2W in anemic cancer patients receiving chemotherapy: Preliminary results of a comparative trial
Authors: R. J. Waltzman, M. Fesen, G. R. Justice, C. Croot, D. Williams
Journal: Journal of Clinical Oncology (2004)

8153 Background: Epoetin alfa (EPO) and darbepoetin alfa (DARB) both decrease transfusion requirements and increase hemoglobin (Hb) in anemic cancer patients (pts) receiving chemotherapy (CT). Methods: This ongoing comparative, open-label, multicenter trial will assess Hb response, transfusions, quality of life, and safety in at least 300 anemic cancer pts undergoing CT randomized to EPO or DARB. Eligible pts ≥18 y with solid tumors, baseline (BL) Hb ≤11 g/dL, and scheduled to receive CT for ≥12 wks. Pts randomized 1:1 to EPO 40,000 U SC QW or DARB 200 μg SC Q2Wfor ≤ 16 wks, with dose increases for nonresponders after 4 wks (EPO) or 6 wks (DARB), per NCCN guidelines. Dose reductions required for Hb rise (>1.3 [EPO] or >1.0 g/dL [DARB]) in a 2-wk period or Hb >13 g/dL. End points include proportion of pts achieving ≥1-g/dL Hb increase after 4 wks, Hb change over time for pts with Hb data at 4, 8, and 12 wks, and transfusion rates for all pts. Mean Hb changes exclude values obtained within 28 days after transfusion. Pts are stratified by study center and CT (+/− platinum) and are withdrawn if CT is stopped. Results: 123 pts (EPO, 59; DARB, 64) receiving ≥1 dose of study drug are included in this analysis. BL demographics (mean age 63 y, 59% women, 82% ECOG PS 0–1, 65% nonplatinum CT) were similar in each arm. Most common tumor types were breast and lung. Mean BL Hb was 10.1 g/dL for EPO (n = 56) and 9.9 g/dL for DARB (n = 61). The table shows Hb results. 10/59 (17%) EPO and 11/64 (17%) DARB pts were transfused. Most frequent AEs (EPO %, DARB %): diarrhea (17, 13), nausea (14, 13), vomiting (17, 6), fatigue (10, 16). 8 EPO and 9 DARB pts had serious AEs. 11 (19%) EPO and 14 (22%) DARB pts discontinued treatment, none as a result of drug-related AEs. 1 death unrelated to study drug occurred in each arm. Conclusions: These data suggest a greater Hb increase at each time point with EPO 40,000 U QW vs DARB 200 mcg Q2W. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho Biotech Products, L.P. Amgen; Johnson & Johnson Amgen; Johnson & Johnson Johnson & Johnson; Ortho Biotech Amgen; Bristol-Myers Squibb; Eli Lilly; AstraZeneca; Novartis; Aventis; Ortho Biotech Products, LP; Merck Pacific Coast Hematology/ Oncology Medical Group Pacific Coast Hematology/ Oncology Medical Group
Morphological, molecular and genetic study of MMR-deficient colorectal cancer: Contribution of somatic tools in diagnosis of Lynch syndrome.
Authors: Anne-Pascale Laurenty, Janick Selves, Delphine Bonnet, Anne Staub, Camille Herve, Marie Danjoux, Edith Chipoulet, Christine Toulas, Bastien Cabarrou, Thomas Filleron, Rosine Guimbaud
Journal: Journal of Clinical Oncology (2015)

e14629 Background: Lynch syndrome (LS) is the most frequent inherited colorectal cancer (CRC) syndrome, due to germline mutations in one of the mismatch repair (MMR) genes. Out of the 15% of CRCs associated with deficient DNA mismatch repair system (dMMR) that are characterized by high levels of microsatellite instability (MSI-H), only 3% are attributable to Lynch syndrome. The other 12% are sporadic, with acquired dMMR phenotype caused in tumors by hypermethylation of the promoter of gene hMLH1, often associated with BRAF V600E mutation. A probably underestimated group does not respond to any of these definitions and is called Lynch-like syndrome (LLS). The aim of the study was to compare the pathological and clinical features of the LS, LLS, and sporadic CRCs and to evaluate the contribution of somatic tools to the screening of potential LS patients. Methods: Two hundred and twelve patients with a dMMR CRC were included. The clinical, surgical, pathological and genetic data were retrieved. A complete MMR phenotype analysis of the tumor was realized, including MSI, expression of the MMR proteins, hypermethylation of the promoter of hMLH1 gene, and BRAF V600E mutation. Results: The only differentiating features between Sporadic (45.5% of the CRC), LLS (20.4%) and LS CRCs (34.1%) are the age of onset (68.5 vs 46 vs 47 years of age; p < 0.001) and the existence of cancers in the family (42.4% vs 42.4% vs 81.5%; p < 0.001). Detection of BRAF V600E is a sensitive (63%) and specific (100%) test in identifying sporadic tumors. The status of hypermethylation is also essential for sporadic diagnosis but can be traced in LS (3.5%). It turns out that the systematic use of these somatic tools in addition to basic clinical information (age of onset, location of the CRC, personal history of CRC or endometrial cancer) could save 25.5% of useless, expensive and time-consuming oncogenetic research, with a risk of error of 1.2%. Conclusions: No isolated clinical or pathological feature seems adequate to differentiate dMMR CRCs. In addition to MSI, a new algorithm including systematic BRAF V600E, hypermethylation of the promoter of the hMLH1 gene and clinical information may help to identify Lynch syndrome patients.
Radiation therapist (RT) perceptions and practices related to safety culture (SC) and error reporting in radiation oncology.
Authors: David Hashemi, Kristina Demas Woodhouse, Brian Monzon, Seth A. Rosenthal, Neha Vapiwala
Journal: Journal of Clinical Oncology (2017)

42 Background: The delivery of radiotherapy is complex and demands careful management, high vigilance, and precise coordination of clinical personnel. RTs are at the frontline and are often first to discover or report an error. However, few studies have examined RT patient safety practices. We conducted a national survey to explore the attitudes, training, and experiences of RTs related to safety in radiation oncology. Methods: In 2016, an electronic survey was sent in June and July to a random sample of 1,500 RTs (~10% of licensed RTs in the US). The survey assessed department SC, error reporting, knowledge, and practices. Questions were multiple choice or recorded on a 5-point Likert scale. Results were summarized using descriptive statistics and analyzed using multivariate logistic regression. Results: A total of 702 RTs from 48 states (47% response rate) completed the survey. Respondents represented a broad distribution across practice and geographic settings with varying levels of work experience (see table). Most RTs gave their department a “Patient Safety Grade” of Excellent (61%) or Very Good (32%), especially if they had an Incident Learning System (ILS) (OR: 2.0). Most departments (58%) had an ILS; however 59% of RTs had not reported an event in the previous year. When an error occurred but did not result in patient harm, 39% of RTs said they would report it and 37% said they would not. Bullying was reported among 17% of respondents; 40% reported that burnout, stress, and anxiety negatively impacted their ability to effectively treat patients. RTs reported errors were more likely to occur with longer work days (&gt;8hrs) and poor multidisciplinary communication during handoffs and transitions. Most (62%) reported they could benefit from additional patient safety education and training, indicating significant interest in this topic. Conclusions: The majority of RTs reported excellent SC practices within their treatment facilities. Most facilities had systems in place to report errors. The obstacles identified, the results of this study may inform future educational efforts and safety initiatives directed towards RTs and should help increase awareness of patient SC in radiation oncology.