tbuckley/cabot-search huggingface dataset:
Cell Cycle Biomarker Analysis from the Paloma-1/ Trio 18 Palbociclib Plus Letrozole Phase Ii Study in Er-Positive/Her2-Negative Advanced Breast Cancer (Abc)
Authors: Y. Jiang, S. Randolph, P. English, S. Kim, X. Huang, M.F. Press, D. Slamon, R.S. Finn
Journal: Annals of Oncology (2014)
Acquired C797S Mutation upon Treatment with a T790M-Specific Third-Generation EGFR Inhibitor (HM61713) in Non–Small Cell Lung Cancer
Authors: Haa-Na Song, Ki Sun Jung, Kwai Han Yoo, Jinhyun Cho, Ji Yun Lee, Sung Hee Lim, Hae Su Kim, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Yoon-La Choi, Woongyang Park, Myung-Ju Ahn
Journal: Journal of Thoracic Oncology (2015)
Morphogenesis of Minute Adenomas in Familial Polyposis Coli&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Nakamura, I Kino
Journal: JNCI Journal of the National Cancer Institute (1984)

The morphogenesis of minute colonic adenomas was investigated by complete serial sectioning of human tissues from 4 individuals with familial polyposis coli. Minute adenomas, consisting of a few atypical glands, were located in the upper part of the mucosa. Single-gland adenomas, consisting of single atypical glands, also were located in the upper to superficial part of the mucosa with endophytic growth. Twelve lesions smaller than single-gland adenomas also were detected. These lesions, buds of single-gland adenomas, consisting of epithelial clusters with mild atypia, were located in the middle part of the mucosa and had sprouted from normal crypts to the lamina propria. The conclusion was that buds of single-gland adenomas originate in the proliferative zone of normal crypts, sprout out of the lamina propria mucosae, move upward with migration of the epithelial cells of the crypts, and are identified as single-gland adenomas in the upper part of the mucosa.
Advances in targeted therapies IX
Journal: Annals of the Rheumatic Diseases (2007)

The papers brought together in this supplement of the Annals of the Rheumatic Diseases constitute summaries of presentations from the seventh International Symposium on Advances in Targeted Therapies, which was held from 18 April until 22 April 2007. As such, these presentations represent the state of the art on the biology of mechanisms of action and pathophysiology of tumour necrosis factor (TNF) as well as other important mediators of inflammation. Current knowledge on the means and consequences of blocking TNF or other molecules or cellular mechanisms is presented as well.

We are grateful to Drs Crofford, Furst, Feldmann, Klareskog, Lipsky, Maini, Moreland and Weinblatt, the members of the Advisory Board of the Symposium, for their invaluable help towards the success of the conference, the ninth of a series of similar events planned for the future. We particularly wish to thank all speakers for their excellent presentations, most of which are summarised here in writing, and all participants who have actively contributed to the discussions. Finally, we also wish to thank the sponsors of this university‐driven event who have provided unrestricted educational grants that enabled us to invite the leading scientists in the field. Moreover, a rheumatological audience and the readers of this supplement have been able to obtain back‐to‐back information on the efficacy and safety of biological agents from representatives of the major companies involved with open discussion of issues arising regarding each agent when looked at individually and compared with others. It is also thankfully acknowledged that representatives of the FDA and EMEA actively participated in this symposium. Finally, based on the presentations and as a consequence of intensive discussions, a revised consensus statement on the application of biological agents in rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis was formulated and we particularly have to thank Dr Furst for his guidance in this respect.

We hope that the readers of this supplement will enjoy the contributions as much as the participants seemed to enjoy the meeting.

The conference was organised under the sole responsibility of the departments of the Universities of Erlangen, Leiden and Vienna in collaboration with an advisory board consisting of the above‐mentioned colleagues from rheumatology departments of several US and European Universities. The following companies provided unrestricted educational grants for organising this conference: Abbott, Amgen, Bristol‐Myers Squibb, Genentech/Biogen Idec, Roche, UCB and Wyeth. The pharmaceutical industry had no part in the decisions regarding the specific programme and, with the exception of a few observers, participants were selected and solely invited by the organising committee. Several members of the advisory board and the members of the organising committee have obtained experience in the use of biological compounds in the course of their participation in clinical studies on these agents (for which the costs were defrayed by industry).
Incidence of symptomatic venous thrombosis in cervical and vulvo-vaginal carcinoma treated with concurrent chemoradiation, erythropoietin, and coumadin
Authors: A. Y. Lin, J. K. Ryu, D. Harvey, B. Sieracki, S. A. Scudder, T. Wun
Journal: Journal of Clinical Oncology (2004)

8101 Background: We had previously reported an increase in the incidence of symptomatic deep vein thrombosis (DVT) in 144 cervical and vulvo-vaginal cancer patients receiving recombinant human erythropoietin (rHuEpo) compared to patients not receiving rHuEpo in conjunction with chemoradiation therapy (Cancer 2003; 98: 1514-20). From April 2002, we instituted a policy of prophylactic low dose coumadin in an attempt to prevent DVT in this cohort receiving rHuEpo. Methods: A retrospective analysis of 56 consecutive patients with cervical or vulvo-vaginal carcinoma (FIGO Stage IB-IVA) who received chemoradiation and rHuEpo from 2001 to 2003 were performed. Subjects were divided into two groups: 32 subjects received rHuEpo alone, 24 subjects received daily coumadin (1–2 mg) in addition to rHuEpo. Primary endpoint was symptomatic DVT proven by duplex ultrasound. Results: There was no difference in baseline characteristics (e.g. age, stage, body mass index, mean and peak hemoglobin, WBC and platelet counts recorded at the time of peak hemoglobin, and number of transfusions) between these two cohorts (p ≥ 0.06, Wilcoxon rank sum test). 9 out of 24 patients (37.5%) had a symptomatic DVT while receiving coumadin compared to 10 out of 32 patients (31.3%) not on any anticoagulation. The incidence of thrombosis was not different between the two groups studied (p=0.62, Chi-square test; OR=1.32, 95% CI=(0.43,4.02)). Out of the 9 patients who had a DVT while receiving coumadin, 7 developed upper extremity (UE) DVT while 3 had lower extremity (LE) DVT (1 patient had both UE and LE thromboses). For the 10 patients who were not on coumadin and developed thromboses, 9 were UE DVT and 2 were LE DVT (1 patient had both UE and LE DVT). There was no difference between the two groups in the percentage of patients with UE DVT (p=0.83, Chi-square test; OR=1.14, 95% CI=(0.35,3.74)) or LE DVT (p=0.64, Fisher's test; OR=2.2, 95% CI=(0.33,14.79)). Conclusions: Daily low dose coumadin did not alter the incidence of symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received rHuEpo in conjunction with chemoradiation therapy. No significant financial relationships to disclose.
Novel proteasome inhibitors show potent anti-tumor efficacy
Authors: Kenichi Nomoto, Kozo Akasaka, Jiayi Wu, Erin Murphy, Yimin Jiang, Xiang-Yi Li, Karen Tendyke, Shawn Schiller, Catherine Reardon, Bruce Decosta, Christina Shaffer, Pamela McGuinness, Timothy Chamberlain, Huiming Zhang, Charles Johannes, Jean-Christophe Harmange, Mary W. Vermeulen
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

4004 

The 26S proteasome is an important contributor to cell cycle regulation. Proteasome inhibitors have recently shown potential as novel anti-tumor agents. We synthesized a series of analogs based on the natural product eponemycin, and evaluated them for their ability to inhibit proteasome activity, cancer cell growth, and growth of human tumor xenografts in nude mice. From this series of analogs, we found that ER-807446 is a potent new proteasome inihibitor with clear in vivo antitumor efficacy. The in vitro activities of ER-807446 included both potent in vitro 20S proteasome inhibition and human cancer cell growth inhibition (IC50 values in the 1-20 nM range.) Pharmacodynamic studies using murine splenocyte proteasome activity as a surrogate marker revealed that ER-807446 displays long-lasting proteasome inhibition for 72 hours. The effect was reversible, since mice treated with ER-807446 on a Q3D repeated dosing schedule did not show an accumulation of proteasome inhibition. These ex vivo pharmacodynamic results suggest that ER-807446 may generate long-lasting proteasome inhibition in patients. In monotherapy in vivo studies against MDA-MB-435 human breast cancer xenografts, ER-807446 resulted in significant tumor growth inhibition in a dose-dependent manner. Treatment with 7.0 mg/kg ER-807446 (its MTD) resulted in 84% xenograft growth inhibition. In this MDA-MB-435 model, monotherapy treatment with irinotecan (CPT-11) at its MTD resulted in tumor growth inhibition, but not tumor regression. Interestingly, treatment with the combination of ER-807446 plus CPT-11 generated tumor regression. This combination of ER-807446 and 45 mg/kg CPT-11 was tolerated well with reversible toxicity. Most interesting of all, this effect is more pronounced with larger tumors: treating mice with small tumors (∼200 μl) led to 25 % regression, while treating mice with large tumors (∼500 μl) led to ∼60% tumor regression. This finding suggests that combination therapies containing ER-807446 may be particularly effective in patients with large tumors. Further experiments will be needed to determine the cause of this enhanced effectiveness against large tumors.
Early Combination Antiretroviral Therapy Limits HIV-1 Persistence in Children
Authors: Katherine Luzuriaga
Journal: Annual Review of Medicine (2016)

Globally, 240,000 infants are newly infected with HIV-1 each year and 3.2 million children are living with the infection. Combination antiretroviral therapy (cART) has reduced HIV-1-related disease and mortality in children but is not curative owing to the early generation of a latent reservoir of long-lived memory CD4(+) T cells bearing replication-competent HIV-1 provirus integrated into cellular DNA. This review focuses on recent advances in our understanding of the establishment of HIV-1 persistence in children and how early initiation of cART in the setting of the developing infant immune system limits the formation of the long-lived latent CD4(+) cell reservoir that remains a barrier to remission or cure.
Baseline pathological and radiological assessment of tumor angiogenesis predicts survival in patients with oligodendrogliomas
Authors: B. S. Abdulkarim, A. Hasbini, J. Cougnard, L. Djafari, C. Lacroix, F. Parker, C. Haie, C. Cioloca, E. Deutsch, E. Raymond
Journal: Journal of Clinical Oncology (2004)

1545 Background. Malignant transformation of oligodendrogliomas (ODG) is associated with increased angiogenesis (endothelial hyperplasia, vascular proliferation of leaking vessels and tumor necrosis). Our aim was to evaluate the prognostic value of tumor angiogenesis assessed by pathological and radiological examinations on progression-free (PFS) and overall survival (OS) in patient (pts) with ODG. Methods.All pts with ODG consecutively treated in our Institution from 1994–2000. Pathological sections were re-evaluated to confirm the diagnosis of ODs and to assess the degree of nuclear atypia, mitosis, endothelial hyperplasia, and necrosis. CT-scan and/or MRI images were re-analyzed to assess contrast enhancement and necrosis. A multivariate analysis was performed including baseline demographic data, histological and radiological factors associated with tumor angiogenesis and treatment. Results. 134 pts with histologically confirmed low grade (WHO grade II, n=49) and anaplastic ODG (WHO grade III, n=85) were analyzed. Univariate analysis showed that prognostic factors associated with better PFS and OS were age <55 (p<0.0001), ODG revealed by seizure (p<0.0001), lack of endothelial hyperplasia (p<0.001), lack of contrast enhancement (p=0.02), and lack of histological/radiological evidence of tumor necrosis (p<0.0001). Multivariate analysis identified necrosis, endothelial hyperplasia and/or contrast enhancement, age, and seizures as independent bad-prognostic factors for OS. This enabled us to defined three pts groups (low, intermediate, and high risk ODG) according to NEVA score using the more robust parameters (necrosis, epilepsy, vessel and age). Conclusion. Endothelial hyperplasia, contrast enhancement, and necrosis that reflect a mutli-step development of tumor angiogenesis are independent factors of bad prognosis in pts with ODG. No significant financial relationships to disclose.
In vivo platforms for analysis of HIV persistence and eradication
Authors: J. Victor Garcia
Journal: Journal of Clinical Investigation (2016)

HIV persistence in patients undergoing antiretroviral therapy is a major impediment to the cure of HIV/AIDS. The molecular and cellular mechanisms underlying HIV persistence in vivo have not been fully elucidated. This lack of basic knowledge has hindered progress in this area. The in vivo analysis of HIV persistence and the implementation of curative strategies would benefit from animal models that accurately recapitulate key aspects of the human condition. This Review summarizes the contribution that humanized mouse models of HIV infection have made to the field of HIV cure research. Even though these models have been shown to be highly informative in many specific areas, their great potential to serve as excellent platforms for discovery in HIV pathogenesis and treatment has yet to be fully developed.
Immunocytochemical study of interleukin-1β in alveolar macrophages of patients with well-controlled and non-controlled asthma
Authors: Svetlana Pospelova, Vyacheslav Kravtsov, Svetlana Sobchenko, Alexander Parfionov
Journal: European Respiratory Journal (2011)

We have conducted dynamic immunocytochemical investigation of the level of Interleukin-1β (IL-1β) in alveolar macrophages of a group of patients (n=16) with well-controlled and non-controlled asthma. Induced sputum specimens from each of the patients were collected twice. Cytologic preparations of sputum were obtained via method of liquid cytology. Cytologic centriphugates were coloured on slides via immunocytochemical method with the use of monoclonal anti-IL-1β antibodies. The results of immunocytochemistry were evaluated using Histology Score method (HScore).  The average value of the investigated index “content of IL-1β in alveolar macrophages” in patients with non-controlled asthma was 251,5±8,3 HScore, while in patients with well controlled asthma it came to 66,4±18,0 HScore. The level of IL-1β decreased more than five times in 14 of 16 patients as a result of their treatment which included education.  Thus, the results of our study indicate that IL-1β is produced by alveolar macrophages in significant amount during non-controlled asthma and that its production decreases abruptly when asthma becomes well-controlled.
Graft-versus-tumor effect following reduced-intensity allogeneic stem cell transplantation in prostate cancer
Authors: M. Bregni, M. Bernardi, F. Ciceri, P. Rigatti, J. Peccatori
Journal: Journal of Clinical Oncology (2006)

6551 Background: Allogeneic transplantation has been utilized as adoptive immunotherapy for patients with solid tumors resistant to conventional therapy. Methods: In 2001 we started a pilot study of allogeneic hematopoietic cell transplantation after a reduced-intensity regimen in patients with metastatic, androgen-independent prostate cancer, aged 18–70, ECOG PS 0–1. Planned sample size was 10 patients. Primary endpoint was feasibility of the procedure. The conditioning regimen included thiotepa, fludarabine, and cyclophosphamide. Patients received allogeneic peripheral blood cells from an HLA-identical sibling. A median of 6.9×10e6 CD34+ cells/kg were infused (range 4.8–11.8). Graft-versus-Host Disease (GvHD) prophylaxis consisted of cyclosporine A and short-course methotrexate. All the patients were evaluable for engraftment and chimerism. Results: Six patients have been enrolled. The median age was 61 years (range 51–66). The median time to reach an absolute neutrophil count of 1.0×10e9/l and a platelet count of 20×10e9/l was 11 and 12 days respectively (range 10–14 and 11–16). All patients achieved complete lymphoid- and myeloid-chimerism at day +90 by cytogenetics or by VNTR polymorphism analysis. Median day of cyclosporine A withdrawal was +85. Three patients developed acute GvHD grade ≥2, usually soon after cyclosporine withdrawal. At a median follow-up of 401 days (range 93–682), 2 patients are alive and 4 died, 2 for disease progression (+214 and +275), one for CMV disease (+93) and one for hemorrhagic cystitis (+527). This last patient achieved an almost complete response confirmed on choline-PET scan after cyclosporine withdrawal and limited chronic GvHD. In other 4 patients we observed a PSA reduction, concurrently with cyclosporine withdrawal or development of GvHD. Conclusions: The close association between GvHD and/or cyclosporine withdrawal and tumor responses strongly suggests that tumor regression was associated with an immune-mediated reaction related to allografting. Future strategies will aim at enhancing the anti-tumor effect and at decreasing GvHD and transplant-related mortality. No significant financial relationships to disclose.
Lubrication of Articular Cartilage
Authors: Sabrina Jahn, Jasmine Seror, Jacob Klein
Journal: Annual Review of Biomedical Engineering (2016)

The major synovial joints such as hips and knees are uniquely efficient tribological systems, able to articulate over a wide range of shear rates with a friction coefficient between the sliding cartilage surfaces as low as 0.001 up to pressures of more than 100 atm. No human-made material can match this. The means by which such surfaces maintain their very low friction has been intensively studied for decades and has been attributed to fluid-film and boundary lubrication. Here, we focus especially on the latter: the reduction of friction by molecular layers at the sliding cartilage surfaces. In particular, we discuss such lubrication in the light of very recent advances in our understanding of boundary effects in aqueous media based on the paradigms of hydration lubrication and of the synergism between different molecular components of the synovial joints (namely hyaluronan, lubricin, and phospholipids) in enabling this lubrication.
Drug treatment or stem cell transplantation as primary treatment for patients with CML
Authors: R. Hehlmann, T. Lahaye, M. Pfirrmann, A. Hochhaus, M. C. Müller, J. Hasford, H. J. Kolb, H. Heimpel, D. K. Hossfeld, A. Gratwohl
Journal: Journal of Clinical Oncology (2007)

7028 Background: Early allogeneic stem cell transplantation (SCT) has been proposed as primary treatment modality for patients (pts) with chronic myeloid leukemia (CML). This concept has been challenged by persisting transplantation mortality and improved drug therapy. Methods: A randomized controlled trial was designed to compare primary SCT and best available drug treatment in 621 newly diagnosed CML pts in chronic phase (CP). Assignment to treatment strategy was by eligibility for SCT and genetic randomization according to availability of a matched related donor (MRD). 354 pts (62% male; median age 40 (11–59) years) were eligible and randomized. 135 pts (38%) had a MRD of which 123 (91%) received a transplant within a median of 10 (2–106) months from diagnosis. 4 pts died before scheduled SCT, 8 pts withdrew consent. 219 pts (62%) had no MRD and received drug therapy. Of these, 97 pts (44%) received a matched unrelated donor (MUD) transplant in 1st CP and were censored at the time of SCT. As 1st line drug treatment pts received interferon alpha based therapy. During the study 197 pts were switched to imatinib. Results: With an observation time up to 11.2 (median 8.9) years median survival of all 621 pts was 8.1 years. During the first 8 years after diagnosis survival curves of drug treated patients were superior to those of transplanted patients reflecting transplant-related mortality. Beyond 8 years survival curves were no longer distinct. 5 (10) year survival was 62% (53%) for transplanted and 73% (52%) for drug treated pts. Survival was superior for drug treated pts up to the cutpoint of survival curves at year 8 (p&lt;0.041) and during the study period up to 11 years from diagnosis (p&lt;0.049). Significantly higher proportions of complete cytogenetic remissions (91% vs 48%, p=0.002) and of major molecular responses (ratio BCR-ABL/ABL &lt;0.1%; 81% vs 45%, p=0.001) were found in the transplant group. These results will be compared to those of a more recent randomized trial of the group (CML-study IIIA). Conclusions: The general recommendation of SCT as 1st line treatment option in CP CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first. Exceptions may be patients’ preference, very low transplantation risk and economic reasons. No significant financial relationships to disclose.
Assessment of clinical trials knowledge and beliefs in cancer patients treated in an urban public hospital serving predominantly African American patients.
Authors: J. A. Potter, J. Liu, R. Hull, S. D. Bright, S. Higgins, L. Bost, A. Thaker, R. Matthews, R. O'Regan, S. Gabram-Mendola
Journal: Journal of Clinical Oncology (2010)

e16511 Background: The Georgia Cancer Center for Excellence (GCCE) at Grady Hospital is committed to reducing health disparities by improving access to cancer clinical trials. We conducted an assessment to better understand our patients' (pts) knowledge and beliefs about clinical trials, as well as perceived barriers to participation. Methods: From 817newly diagnosed cancer pts in 2008, a random sample of 277 pts were identified for a 10 min telephone survey of 27 multiple choice and open-ended questions. Results: 35 pts agreed to participate; 16 (5.8%) pts declined. The low response rate was due to 105 (37.9%) wrong/disconnected phone numbers. 27 (77.1%) were no longer in active treatment. 21 (60%) pts were female; 14 (40%) were male. Ages ranged from 24-79 (mean = 56.6) years. 9 (25.7%) pts previously participated in clinical trials. A clinical trials knowledge score was calculated from 5 knowledge-based questions; 0 = least and 5 = most knowledge. The mean knowledge score was 2.6 (1.8 sd). Pts who previously participated in a clinical trial had higher scores than those who had not (p < 0.001). Knowledge scores were not correlated with pts' perceptions of clinical trials importance (r = 0.15, p = 0.42) or safety (r = 0.01, p = 0.95). All respondents said their physician's advice influenced their health care decisions and they preferred to learn about clinical trials directly from an MD or RN. There was a significant association between being asked to participate in a clinical trial and actually enrolling (p < 0.0001). 24 (68.6%) pts believed clinical trials were “very important;” only 6 (17.1%) considered trials “very safe.” Perceived safety was a significant predictor of willingness to participate in trials (p = 0.03). Conclusions: GCCE pts need clinical trials education with an emphasis on patient safety measures. Pts are willing to participate in clinical trials if they are provided with sufficient information from their health care provider. We are creating a comprehensive, culturally appropriate clinical trials education plan to increase awareness of clinical trials, involve health care providers and past clinical trial participants, and focus on perceptions of safety. No significant financial relationships to disclose.