tbuckley/cabot-search huggingface dataset:
Clinical results and impact on circulating endothelial cells (CEC) of treatment with combinations of interferon-α(Iα), thalidomide (T) and celecoxib (C) in patients with solid tumors
Authors: A. Rocca, C. Noberasco, F. Bertolini, G. Curigliano, T. de Pas, A. Milani, P. Mancuso, S. Manzoni, F. de Braud
Journal: Journal of Clinical Oncology (2005)

3193 Background: Iα, T and C have antiangiogenic activity in preclinical models. CEC and apoptotic CEC are promising surrogate markers of angiogenesis. Methods: We conducted a phase II study to evaluate combinations of Iα, T and C; endpoints were long-term tolerability, activity and effect on CEC. Eligible patients (pts) had slow growing advanced solid tumors, with progressive disease (PD) at recruitment. They were randomized to: A. Iα + T (19 pts), B. Iα + C (18 pts), C. T + C (19 pts), and further to add the third drug after 2 months of therapy (28 pts) or not (28 pts). Iα was given 0.5 MU/12 hrs s.c., T 100 mg/d orally, C 200 mg/12 hrs orally. CEC and apoptotic CEC were measured by flow cytometry every 2 months. Results: Of 56 pts enrolled from 01/02 to 09/04 (hepatocellular carcinoma: 18, renal: 17, other: 21), 51 are assessable. Median time to progression was 6 months (Kaplan-Meier estimate). We observed 1 (2%) partial response (PR) and 34 (61%) stable disease (SD), with 21 pts (38%, 95%CI: 25–51%) showing clinical benefit (PR or SD ≥ 6 months). 82% of pts treated with 2 drugs had PR or SD compared with 43% of those receiving 3 drugs (p=.003, exact test). Grade III adverse events were: neutropenia 6%; anemia 2%; thrombocytopenia 2%, asthenia 4%, lethargy 8%, dermatitis 2%, hepatic 6%. On 32 assessable pts, the median CEC number decreased from 18 to 10/μL (p=.002, Wilcoxon matched pairs test) and the median apoptotic CEC from 8 to 5.5/μL (p=.053) after 2 months. The same trends were observed after 4 months, and were present both in pts with PR or SD and in those with PD. Anyway, the median percent value of CEC at 4 months relative to baseline differed between pts with PR or SD (81%) and those who had PD (63%) (p=.026, Mann-Whitney U test), as did the median percent value of apoptotic CEC (62% versus 38%, p=.004). Conclusions: We conclude that a combination of 2 drugs is feasible and fairly active, while the addition of a third drug may be detrimental. Treatment has an impact on CEC. Traditional response criteria are inadequate to evaluate effectiveness of such kind of approach. No significant financial relationships to disclose.
Early Psa Response is an Independent Prognostic Factor in Patients with Mcrpc Treated with Next-Generation Androgen Pathway Inhibitors
Authors: A.C. Fuerea, G. Baciarello, C. Massard, L. Albiges Sauvin, M. Gizzi, S.A. Terrisse, M. Di Palma, B. Escudier, K. Fizazi, Y. Loriot
Journal: Annals of Oncology (2014)
The role of PDGF-D in healthy and fibrotic kidneys
Authors: Eva M. Buhl, Sonja Djudjaj, Janka Babickova, Barbara M. Klinkhammer, Erika Folestad, Erawan Borkham-Kamphorst, Ralf Weiskirchen, Kelly Hudkins, Charles E. Alpers, Ulf Eriksson, Jürgen Floege, Peter Boor
Journal: Kidney International (2016)
Lymphatic endothelial cells are a replicative niche for Mycobacterium tuberculosis
Authors: Thomas R. Lerner, Cristiane de Souza Carvalho-Wodarz, Urska Repnik, Matthew R.G. Russell, Sophie Borel, Collin R. Diedrich, Manfred Rohde, Helen Wainwright, Lucy M. Collinson, Robert J. Wilkinson, Gareth Griffiths, Maximiliano G. Gutierrez
Journal: Journal of Clinical Investigation (2016)

In extrapulmonary tuberculosis, the most common site of infection is within the lymphatic system, and there is growing recognition that lymphatic endothelial cells (LECs) are involved in immune function. Here, we identified LECs, which line the lymphatic vessels, as a niche for Mycobacterium tuberculosis in the lymph nodes of patients with tuberculosis. In cultured primary human LECs (hLECs), we determined that M. tuberculosis replicates both in the cytosol and within autophagosomes, but the bacteria failed to replicate when the virulence locus RD1 was deleted. Activation by IFN-γ induced a cell-autonomous response in hLECs via autophagy and NO production that restricted M. tuberculosis growth. Thus, depending on the activation status of LECs, autophagy can both promote and restrict replication. Together, these findings reveal a previously unrecognized role for hLECs and autophagy in tuberculosis pathogenesis and suggest that hLECs are a potential niche for M. tuberculosis that allows establishment of persistent infection in lymph nodes.
A decrease in preoperative to postoperative CA19–9 level is a significant predictor of survival in patients with pancreatic adenocarcinoma
Authors: C. R. Ferrone, S. P. Thayer, D. M. Finkelstein, A. Muzikansky, M. Mino-Kenudson, G. Lauwers, A. L. Warshaw
Journal: Journal of Clinical Oncology (2005)

4034 Background: Staging systems and nomograms attempt to better stratify patients with pancreatic adenocarcinoma by evaluating different prognostic factors. The purpose of this study is to determine whether a change in preoperative to post operative CA19–9 level is a significant prognostic predictor of overall survival. Methods: 424 consecutive patients with pancreatic adenocarcinoma were resected at a single US institution between 1/1/85–1/1/04. Univariate and multivariate survival analyses were performed on 172 patients with pre and postoperative CA19–9 values. Survival time was measured from the time of the first postoperative CA19–9 level (median 1 month) until death or latest follow-up. Results: Stage I disease was present in 21(12%), Stage IIA in 45(26%), Stage IIB in 104 (61%), and Stage IV in 2(1%) patients. Pancreaticoduodenectomies were performed in 143 (83%) patients, distal pancreatectomies in 21(12%) patients, and total pancreatectomies in 8 (5%) patients. Median follow-up was 1.3 years (0–12.7). Curative R0 resection was performed in 112 (69%) patients. Of the 172 patients with pre and postoperative CA19–9 levels, 141(82%) had a greater than 20% decrease in value. A decrease in CA19–9 level from pre-surgery of > 20% predicted an improved overall survival (p=0.002). Other significant univariate predictors of improved survival were lower stage, negative margins, N stage and lower T stage. In the multivariate analysis, a >20% decrease in CA19–9 level after surgery, lower stage, and negative margins were significant predictors of longer survival. The overall actuarial 3, 5, and 10 year survivals for the 172 patients are 32%, 23% and 10%. For the 41 (24%) patients with the best prognosis (CA19–9 decrease >20%, lower stage, negative margins) 3,5, and 10 year actuarial survivals are 55%, 46%, and 27% respectively. Conclusions: In patients with pancreatic adenocarcinoma a change in preoperative to postoperative CA19–9 level of greater than 20%, lower stage, and negative margins are predictors of an improved overall survival. Therefore, CA19–9 levels should be included in a patient’s perioperative evaluation, and should be considered for prognostic nomograms. No significant financial relationships to disclose.
Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination
Authors: Hongbo Hu, Hui Wang, Yichuan Xiao, Jin Jin, Jae-Hoon Chang, Qiang Zou, Xiaoping Xie, Xuhong Cheng, Shao-Cong Sun
Journal: The Journal of Experimental Medicine (2016)

Signal transduction from the T cell receptor (TCR) is crucial for T cell–mediated immune responses and, when deregulated, also contributes to the development of autoimmunity. How TCR signaling is regulated is incompletely understood. In this study, we demonstrate a ubiquitin-dependent mechanism in which the deubiquitinase Otud7b has a crucial role in facilitating TCR signaling. Upon TCR ligation, Otud7b is rapidly recruited to the tyrosine kinase Zap70, a central mediator of TCR-proximal signaling. Otud7b deficiency attenuates the activation of Zap70 and its downstream pathways and impairs T cell activation and differentiation, rendering mice refractory to T cell–mediated autoimmune and inflammatory responses. Otud7b facilitated Zap70 activation by deubiquitinating Zap70, thus preventing the association of Zap70 with the negative-regulatory phosphatases Sts1 and Sts2. These findings establish Otud7b as a positive regulator of TCR-proximal signaling and T cell activation, highlighting the importance of deubiquitination in regulating Zap70 function.
Adjuvant trastuzumab (T) in early stage breast cancer (EBC): Is cardiac dysfunction (CD) clinically significant?
Authors: S. F. Dent, L. A. Vandermeer, J. N. Spaans, J. L. Verreault, J. S. Azzi, S. Hopkins, S. Verma
Journal: Journal of Clinical Oncology (2007)

11072 Background: T was funded for women with EBC in Ontario in Aug 05. Clinicians remain concerned about the potential cardiotoxicity of T in women with EBC. The purpose of this retrospective study is to evaluate CD in women with EBC prescribed adjuvant T therapy. Methods: Women with HER2-overexpressing EBC who were initiated on T and chemotherapy (CT) at TOHRCC between Aug 05 and Nov 06 were included in this analysis. A retrospective chart review collected: demographics, CT regimen, T treatment (dose delays, termination of T), CD (defined by the New York Heart Association functional classification, 2002), and management. Results: Outcomes reflect the preliminary results of 108 patients (pts) initiated on adjuvant T therapy. Median age was 52 years (range 30–79). 107 pts (95%) received T and CT; 1 pt received T alone. Pts received an average of 6 cycles of CT (range 1–12), including anthracycline (A; 99%) (A alone 55%; A-taxane 44%) and non-A (1%) regimens. 18 pts (28%) were treated with concurrent T and taxol. Therapy with T has been completed (median 46.7 weeks) in 28 pts (26%) while 72 pts (67%) remain on T. 85% of pts underwent at least 3 MUGA scans during T treatment. CD was observed in 18 pts (17%): congestive heart failure (2 pts), decrease in left ventricular ejection fraction (LVEF) of =10% to less than 55% (14 pts) or decrease in LVEF &gt;20% (2pts). Of 18 pts with CD, 7 underwent a treatment delay (median 8 weeks) 3 permanently stopped T (median 45 weeks) and 8 pts continued T. 31 pts experiencing any decrease in LVEF were managed successfully through: delay, (16 pts), referral to a cardiologist (14 pts) and medical treatment with: ACE-inhibitors (5 pts), beta blockers (1 pt), or combination (2 pts). Discussion: The results of this first analysis indicate that outside of a clinical trial setting, the majority of women receive adjuvant T according to treatment guidelines, do not experience significant CD and are able to complete therapy uninterrupted. The long term consequences of CD in these pts are unknown. No significant financial relationships to disclose.
Role of trabectedin (T) in the management of advanced uterine leiomyosarcoma (U-LM)
Authors: F. Grosso, R. Sanfilippo, R. L. Jones, P. Collini, C. Morosi, F. Raspagliesi, J. C. Tercero, M. D'Incalci, I. R. Judson, P. G. Casali
Journal: Journal of Clinical Oncology (2009)

10530 Background: To explore the clinical impact of T in U-LM. T has been approved in Europe for second line treatment of advanced soft tissue sarcomas (STS). Efficacy is well established in liposarcoma and leiomyosarcoma. U-LMs display peculiar clinical and genetic features compared to other STS. These differences may be responsible for the sensitivity of this subtype to therapy, thus justifying an evaluation of the activity of T in a relatively homogeneous series of U-LM patients. Methods: From April 2000, 56 patients (pts) with advanced disease, previously exposed to a median of 3 chemotherapy lines (range 1–5), received T within an expanded access programme at two European referral institutions for sarcoma. The clinical records were reviewed focusing on response and treatment outcome. Two pts were excluded from the analysis having received only 1 course of T. Median age was 56 yrs (range 29–73), median number of metastatic sites was 2 (range 1–4), the most frequent metastatic site was lung (88%), 24 patients had a local relapse. Results: A total of 252 courses were delivered (median 3, IQR2–6) and 36% of patients received more than 5 courses of T. Fifty-two patients were evaluable for response. A partial response was observed in 11 patients and stable disease in 15, for a PR rate of 21% and a tumor control rate of 50%. The median progression-free survival was 3.6 months (CI95% 2.6–6.7), with 41% of patients free from progression at 6 months. Conclusions: These results compare favourably with other systemic treatments in advanced U-LMS and support their sensitivity to T. This should prompt further studies to prospectively evaluate the efficacy of T in U-LMS and elucidate possible biological predictive factors (e.g. DNA repair protein expression). [Table: see text]
Cetuximab in combination with intensity modulated radiotherapy (IMRT) and gemcitabine for patients with locally advanced pancreatic cancer: A prospective phase II trial [PARC-Study ISRCTN56652283]
Authors: R. Krempien, M. W. Munter, C. Timke, H. Friess, G. Hartung, K. K. Herfarth, A. Abdollahi, M. W. Buchler, P. E. Huber, J. Debus
Journal: Journal of Clinical Oncology (2007)

4573 Background: The induction of EGFR targeting with cetuximab in radiation based therapy of solid tumors has yielded promising results. Thus, we initiated a prospective phase II trial designed to analyze the feasibility and effectivity of trimodal therapy with gemcitabine-based chemoradiation and cetuximab in locally advanced inoperable pancreatic cancer. Methods: In this phase 2 study, pts with locally advanced pancreatic cancer without prior cytotoxic therapy were treated with radiotherapy (RT), gemcitabine weekly (300mg/m 2 ), and cetuximab weekly (loading dose 400mg/m 2 day 1, and concomitant with radiation day 8,15,22,29,36 250mg/m 2 ). RT was delivered by using an integrated IMRT boost concept (54 Gy GTV, 45 Gy CTV) over 5 weeks. RT was followed by gemcitabine (1,000mg/m 2 ) weekly x 3 in 4 weeks. Response evaluation using CT followed at week 12. All pts were intended for surgical treatment between week 12–15. Pts were followed for adverse events and response. Results: 55 pts were enrolled. Preliminary results are presented on 36 pts with the following characteristics: pancreatic adenocarcinoma c2 T4 N1 36/36, median age = 61.5 (range 48–79); M/F = 24/12; ECOG PS 0/1/2 = 6/26/4; median days on treatment: 90 (range 70–100). Treatment-related toxicities were observed in 22 pts. Grade 3 toxicities included diarrhea (n=5), fatigue (n=4), nausea (n=6), neutropenia (n=10), thrombocytopenia (n=4), and vomiting (n=4). 34/36 pts developed some acneiforme rush during therapy. No omittance of cetuximab was necessary in any of the pts. 1 patient died during treatment due to tumor bleeding. Median follow-up at present is 13 month, 1-year survival was 57%, median survival has not been reached. Partial remissions 12/36, stable disease 20/36, progressive disease 4/36 (RECIST). 21/36 pts were amenable for secondary potentially curative resection. 9 pts could be resected, while 8 pts were found to have abdominal metastatic spread. Conclusions: Early data from trimodal therapy in pancreatic adenocarcinoma with chemoradiation (IMRT), gemcitabine, and cetuximab indicate feasibility without increased toxicity profile. The local response appears to be very promising in pancreatic cancer. [Table: see text]
Risk Factors For Relapse In Children Undergoing Preemptive Immunomodulatory Therapy After Allogeneic Hematopoietic Stem Cell (HSCT) For Acute Leukemia
Authors: Marie Ouachee-Chardin, Christopher C. Dvorak, Justin Wahlstrom, Morton Jerome Cowan, Janelle Facchino, Biljana N. Horn
Journal: Blood (2013)
Uropod-Bearing Lymphocytes (Hand Mirror Cells) in a Virus-Induced Murine Lymphoma&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: H R Schumacher, S A Stass, W J Creegan, O S Weislow
Journal: JNCI Journal of the National Cancer Institute (1979)

A Moloney murine leukemia virus-induced T-cell preleukemic thymic lymphoma tissue culture from an inbred C3H/HeJ mouse contained numerous hand mirror cells (HMC). The cells were studied by light and phase-contrast microscopy, special stains, indirect immunofluorescence for terminal deoxynucleotidyl transferase, and scanning and transmission electron microscopy. The uropods of the mouse and human HMC were similar. In contrast, viruses were noted on the tip of the mouse HMC uropod by transmission electron microscopy. These observations, reported for the first time in an animal model, will enable investigators to study the HMC under controlled conditions.
Long-term survival patterns of a large nationwide cohort of elderly veterans with colorectal cancer
Authors: K. S. Virgo, M. P. Valentine, L. C. Dauz, L. H. Marietta, B. S. Adams, S. Devarajan, W. E. Longo, F. E. Johnson
Journal: Journal of Clinical Oncology (2004)

3708 Background: Administrative databases have generally not been designed to permit cancer researchers to readily follow patients forward from the period pre-diagnosis through initial curative intent treatment, adjuvant therapy, post-treatment follow-up, to the final endpoint of either death or loss to follow-up. One major hurdle to cancer research using such databases has been the lack of data such as stage at diagnosis, and histopathologic type and grade. A second major hurdle is that many patients use more than one system of care, in this instance, Department of Veterans Affairs (VA) and Medicare-reimbursed care. These dual users would be inaccurately represented in the analysis if only one source of data were analyzed. Methods: A retrospective analysis of 13 years of nationwide Medicare and VA inpatient and institutional outpatient data beginning with the three years pre-diagnosis (1986–1990) through a minimum of five years post-diagnosis (1994–1998) was conducted. Death data were available through December 2003. Data were also extracted from tumor registry files, Computerized Patient Record System Files, and paper medical records at each VA. The population studied included all VA patients diagnosed with colorectal cancer and surgically treated for cure during the five-year period 1989–1993, who were Medicare-eligible at diagnosis, and survived the index admission. Results: Of the 6612 patients treated with curative intent during the five-year period, 4902 (74%) could be staged. Of these, 4535 (93%) were deemed eligible for the study. Of the eligible patients, 77% were diagnosed with colon cancer and 23 percent with rectal cancer. The majority (88%) had adenocarcinoma. The histopathologic grade was moderately differentiated for 54% and well differentiated for 19%. As of December 2003, 74% had died. Including all stages (0- IV), the average survival in months after treatment was 75 (median=61). Conclusions: This rich database provides a wealth of data for subgroup analyses of survival, recurrence patterns, and particularly, of health services utilization patterns within and across systems of care. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Heartland Division, Department of Veteran's Affairs Medical Center
Risk of venous thromboembolism (VTE) in Danish cancer patients: A population-based cohort study from 1997 to 2005
Authors: K. Cetin, D. P. Cronin-Fenton, F. Søndergaard, L. Pedersen, J. P. Fryzek, J. F. Acquavella, J. A. Baron, H. T. Sørensen
Journal: Journal of Clinical Oncology (2008)

9604 Background: Although venous thromboembolism (VTE) is recognized as a serious complication of malignancy, population-based data on the incidence of VTE in cancer, particularly by site and stage, are limited. Methods: Using population-based health care databases in Northern Denmark, we identified patients with primary cancer diagnosed from 1997 to 2005 (n=58,151) and assembled a general population cohort (n=290,755) matched (5:1, general population members to cancer patients) on the county, age and sex distribution of the cancer cohort. We estimated the incidence of VTE among members of both cohorts from the index date (date of cancer diagnosis for cancer patients and their matched general population members) through December 31, 2006. Using Cox Proportional Hazards regression, we estimated the incidence rate ratio (IRR) to compare the incidence of VTE in cancer patients to members of the general population cohort, adjusting for gender, age, and other co-morbid conditions. Results: Overall, the incidence of VTE among cancer patients was 6.1 per 1,000 person- years (py) (95% Confidence Interval (CI) 5.7–6.5) compared to an incidence of 1.6 per 1,000 py (95% CI 1.6–1.7) in the general population cohort. Among cancer patients, the incidence of VTE increased with age, varied by cancer site, and was highest in patients with advanced cancer and during the first year following cancer diagnosis. VTE rates were highest in pancreatic cancer, liver cancer and multiple myeloma (24.7, 16.9 and 12.8 per 1,000 py, respectively) and among patients who received chemotherapy or no/symptomatic treatment (12.7 and 11.4 per 1,000 py, respectively). Compared to the general population, IRRs were greatest for liver tumors (IRR=24.9, 95% CI 4.3–145.6), pancreatic tumors (IRR=11.9, 95% CI 6.3–22.3), malignant brain tumors (IRR=24.7, 95% CI 7.7–79.8) and multiple myeloma (IRR=8.3, 95% CI 3.7–18.3) and increased with advancing disease stage and post-chemotherapy. Conclusions: The rate of VTE is markedly higher in patients with cancer compared to that in the general population. Increased age, advanced stage cancer, receipt of anti-cancer treatment, time since diagnosis, and cancer site are all predictors of VTE occurrence among cancer patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Inc. Amgen Inc.
Outcome After First Relapse Or Refractory Acute Lymphoblastic Leukemia In Children From 1996 To 2011 – Comparison Of Two Different Treatment Strategies
Authors: Francesco Ceppi, Michel Duval, Caroline Laverdiere, Jean-Marie Leclerc, Yveline Delvas, Sonia Cellot, Pierre Teira, Henrique Bittencourt
Journal: Blood (2013)
Efficacy of the endoscopic rendez-vous technique for the reconstruction of complete esophageal disruptions
Authors: Jean-Michel Gonzalez, Geoffroy Vanbiervliet, Mohamed Gasmi, Jean-Charles Grimaud, Marc Barthet
Journal: Endoscopy (2015)

<b>Background and study aims:</b> The rendezvous endoscopic approach, already described, might be an interesting technique in complete esophageal obstructions (CEO). <b>Patients and methods:</b> This retrospective report on nine patients referred because of CEO classified patients into two groups based on length of their esophageal disruption: the long (> 5 cm) group were three patients (esophageal stripping at stent removal [n = 2] and caustic ingestion [n = 1]; two patients having superior esophageal sphincter [SES] destruction); the short (< 5 cm) group were six patients (anastomotic or post-radiotherapy). The procedures were performed under radiographic guidance. <b>Results:</b> All the reconstructions were successful. In four patients, a neo-SES was created, by transillumination (n = 2) or surgery (n = 2). The first dilation was performed by hydrostatic balloon, with additional metal stents (n = 4) and nasogastric tubes (n = 2) used. All the patients were able to eat after the procedure. Two delayed bleeds occurred, which were managed endoscopically. The patients underwent a median of seven dilations (range 3 – 55) over 8 months (2 – 32 months), with dilations ongoing in five patients, but all able to eat normally. <b>Conclusion:</b> Endoscopic rendezvous for CEO is safe and effective, even in patients with long disruptions and complete loss of SES.