tbuckley/cabot-search huggingface dataset:
Correlation of serum urokinase plasminogen activator (uPA) to progression of recurrent malignant glioma during bevacizumab treatment: A marker of invasive phenotype and a candidate to monitor therapy
Authors: O. L. Chinot, F. Boudouresque, C. Bequet, M. Barrie, A. Thiebaut, M. Matta, D. Autran, L. Ouafik
Journal: Journal of Clinical Oncology (2009)

2059 Background: Identification of circulating markers that predict tumor response or reflect progression is of crucial importance when using antiangiogenic agents. However, to date, no such parameters have been identified particularly for bevacizumab, for which, recently, increasing data have supported a role in patient with recurrent malignant glioma. Methods: Serial serum levels of VEGF, VEGFR2, FGF, SDFα, urokinase plasminogen activator (uPA), plasminogen activator inhibitor type I (PAI-1), and metalloprotesase type 9 (MMP9) were determined in a cohort of 32 patients treated with bevacizumab and irinotecan for recurrent malignant glioma. Samples were collected at the start of treatment and then at 4 weeks intervals until progression. Serum levels were measured using an enzyme-linked immunosorbent assay. Progression was defined by MacDonald's criteria, modified by integrating increase of infiltration as measured on MRI by Flair sequence. All subjects were followed for PFS and OS. Cox model analysis is used for correlation between markers and clinical outcome. Results: This preliminary analysis is restricted to pre-treatment (D0; n = 32), day 30 (D30; n = 27), and at progression time (DP; n = 15). None of the pretreatment serum level (n = 32) significantly affect PFS or OS although uPA and MMP9 tend to influence OS. Decrease of median level of all serum markers except PAI1 and VEGFR2 is observed from D0 to D30 under bevacizumab therapy, but only uPA and FGF variations tend to impact clinical outcome. From D30 to DP, increase of uPA is correlated to PFS (p = 0.028) while the observed increased of FGF and SDFα fail to reach significant correlation to PFS and OS. Conclusions: Increase of uPA serum level appear to be correlated to disease progression for patients with recurrent malignant glioma treated with bevacizumab and may reflect the invasive phenotype of glioma progression. Serum uPA may help in assessing treatment response under bevacizumab and warrant further studies. No significant financial relationships to disclose.
SAT0044 Class ii mhc molecules in patients with sporadic ankylosing spondylitis in the southern european population
Authors: VC Perez-Guijo, E Muñoz-Gomariz, A Escudero, M Romero, MA Aguirre, J Gonzalez, FG Martinez, MC Muñoz-Villanueva, C Castro, R Solana, J Peña, E Collantes
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> To evaluate the relationship between the presence of HLA-DRB1 genes and predisposition to AS in a demographically well-defined population. <h3>Objectives</h3> 113 individuals with sporadic (non-familial) Ankylosing Spondylitis (AS) from six different cities and 747 bone marrow donors (BMD) as control group. <h3>Methods</h3> All individuals were typed for HLA-B27 by either flow cytometry with monoclonal antibodies or PCR-SSP, as well as for HLA-DRB using the Dynal ELITM SSO HLA-DRB Test (Dynal AS, Oslo, Norway). The Inno-Lipa DRB key and DRB Decoder (Innogenetics NV Zwijndrecht, Belgium), which is based on PCR-SSO technology, was used for high-resolution HLA -DRB typing. <h3>Results</h3> Table 1 shows the results. <h3>Conclusion</h3> The incidence of the DRB1*01 antigen in the studied population is significantly higher in B27(+) healthy individuals (BMD) than in B27(+) AS patients. Also the incidence of this antigen is significantly higher in B27(-) AS patients than B27(-) healthy individuals. This could implicate that in the absence of B27, the DRB1*01 antigen could take part in the development of the disease.
Abstract 16559: Acute Psychological Stress, Autonomic Function, And Arterial Stiffness Among Women
Authors: Xiaoyue Liu, Soojung Ahn, Jeongok G Logan
Journal: Circulation (2019)

Objective: Previous studies have identified chronic psychological stress as a significant predictor of arterial stiffness in non-hypertensive people, independent of age and blood pressure (BP). Sti...
Daratumumab Mitigates B-Cell Receptor Signaling and Enhances Antitumor Activity of Ibrutinib in Chronic Lymphocytic Leukemia (CLL) Cells
Authors: Alak Manna, Sharoon Akhtar, Zahara Meghji, Kirtipal Bhatia, Paul Yi, Sameer A. Parikh, Wei Ding, Jose F. Leis, Taimur Sher, Fabio Malavasi, Victoria R. Alegria, Sikander Ailawadhi, Asher A. Chanan-Khan, Aneel Paulus
Journal: Blood (2017)
Initial phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration-resistant prostate cancer (mCRPC)
Authors: S. F. Slovin, T. M. Beer, C. S. Higano, S. Tejwani, O. Hamid, J. Picus, A. Harzstark, H. I. Scher, Z. Lan, I. Lowy
Journal: Journal of Clinical Oncology (2009)

5138 Background: IPI is a fully human, monoclonal anti-CTLA-4 antibody capable of enhancing anti-tumor immunity. In preclinical models, XRT releases tumor antigens and enhances anti-tumor activity of CTLA-4 blockade. In the dose escalation part of this Phase I/II trial 10 mg/kg dosing of IPI with or without prior priming by single fraction XRT was feasible. We now report initial phase II results. Methods: 45 patients (pts) with mCRPC and ECOG PS of 0–1 received 10 mg/kg q3 weeks (wks) X 4 of IPI in 3 groups: (1) IPI alone n=16, (2) IPI + XRT n=15 chemotherapy naïve (NoCHEMO), and (3) IPI + XRT n=14 chemotherapy experienced (CHEMO) pts. XRT (800 cGy) was given to up to 3 involved bony sites (GI tract sparing) just prior to starting IPI. PSA was monitored monthly, with scans q 3 months. Endpoints were to confirm safety and an initial assessment of activity. Results: 17 pts (38%) experienced 26 immune-related adverse events (irAEs) including diarrhea/colitis (12), rash/pruritus (6), hepatitis (4), endocrinopathy (4). 11 pts (24%) experienced 13 ≥ Grade 3 irAEs: GI (9; 20%) and hepatitis (4; 9%); all resolved with immunosuppression. 10 of 45 pts (22%; 95% CI 10–34%) had confirmed PSA declines ≥ 50% as follows in the table below. Median time to PSA decline was 5.7 wks (r 3 to 21 wks); median duration 23 wks (r 3 to 84+ wks). In one pt dosed with IPI alone, PSA ≤ 0.05 ng/ml, as well as a CR of bone, nodal and prostate lesions continue for 54+ and 84+ wks, respectively. Conclusions: irAEs in the 10 mg/kg cohorts are similar in type and rate to IPI in melanoma. irAEs and PSA declines occurred in chemotherapy naïve and post chemotherapy patients, and with or without XRT. Addition of XRT to 10 mg/kg is well tolerated. Time to response can be delayed, with a durable median response of 23 wks. Further study of IPI in mCRPC is warranted, with or without XRT as a potential immunosupportive maneuver to augment clinical responses to IPI. [Table: see text] [Table: see text]
Estimating the need for palliative external beam radiotherapy in adult cancer patients
Authors: C. Nieder, A. Pawinski, E. Haukland, R. Dokmo, I. Philippi, A. Dalhaug
Journal: Journal of Clinical Oncology (2009)

e20599 Background: Older benchmark data suggest that 46–53% of all radiotherapy (RT) courses were administered with palliative intent. In the most comprehensive analysis from Sweden, 87 annual palliative RT courses per 100,000 inhabitants were registered in 2001, mainly for the treatment of bone and brain mets (95% CI 84–91). Despite an increase from Swedish data collected in 1992, continuous underuse could not be ruled out. Newer data accounting for the increasing life expectancy of patients with metastatic cancer are lacking. Methods: Prospective collection of data on palliative RT in adult cancer patients during a 12 months period in 2007/2008 in a well defined region of Norway. All patients (median age 70 years, 26% lung, 23% prostate, 11% breast, 7% bladder cancer, 33% others) were treated in one federal state with ∼234,000 inhabitants and had unlimited access to RT (no economical barriers, waiting time 0–14 days). Efforts were made to account for potential overuse, e.g., registration of patients who died within 2 weeks from the first RT fraction. Results: In the study population, 134 annual treatments per 100,000 inhabitants were registered (after correction for overuse, but not accounting for emerging treatment options, e.g., stereotactic RT for lung metastases; 95% CI 112–159). As some patients received simultaneous treatment to different target volumes, the annual number of target volumes amounted to 160.8 per 100,000 inhabitants (95% CI 137–188). Of these, 115.2 were related to skeletal lesions, 12.3 to thoracic tumors and 11.4 to brain mets. Due to the differences in fractionation and treatment technique from country to country and even between institutions in the same country, no data on number of fractions or fields were collected. However, each institution can easily calculate their own figures on the basis of the new data. Conclusions: To the authors’ best knowledge, this is the first patterns of care study in the last 5 years. The data derived from a region where underuse is not an issue anymore suggest that previous estimates were incorrect. If confirmed in other databases, resources for palliative RT need to be adjusted. In regions with significantly different cancer incidence, age structure and other socioeconomic factors then northern Europe, separate analyses need to be conducted. No significant financial relationships to disclose.
OP0021 Effects of tnf-alpha, il-1 beta and il-15 on the production/expression of opg and rankl by synovial fluid mononuclear cells and fibroblast-like synoviocytes isolated from patients with rheumatoid arthritis (ra)
Authors: M Zió³kowska, MS Kurowska, A Radzikowska, G £uszczykiewicz, W Dziewczopolski, J Kowalczewski, W Maslinski
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The receptor activator of nuclear factor κB (RANKL), its receptor RANK and osteoprotegerin (OPG) are key regulators of bone remodelling that influence immune functions as well. RANKL is responsible for the development and activation of osteoclasts. OPG, a soluble decoy receptor for RANKL, competes with RANK for RANKL binding. Proinflammatory cytokines (TNF-α, IL-1b and IL-15) play critical role in the pathogenesis of RA and bone erosions. <h3>Objectives</h3> To compare the effects of TNF-α, IL-1b and IL-15 on the production/expression of OPG and RANKL by synovial fluids mononuclear cells (SFMC) and fibroblast-like synoviocytes (FLS) isolated from RA patients. <h3>Methods</h3> SFMC and FLS were obtained from 8 RA patients. The isolated SFMC and FLS (cultured <i>in vitro</i> for 2–5 passages) were stimulated with recombinant human TNF-α, IL-1b or/and IL-15. The concentrations of OPG in culture supernatants were measured by a specific ELISA and the expression of surface RANKL and OPG was tested using flow cytometry. <h3>Results</h3> SFMC and FLS from RA patients spontaneously produced considerable levels of OPG. The production of OPG by FLS was strongly enhanced by TNF-α and IL-1b, but not by IL-15. In contrast, the production of OPG by SFMC was only slightly enhanced in the presence of TNF-α, IL-1b or IL-15. Interestingly, additive effects of IL-15 and IL-1b or IL-15 and TNF-α on OPG production by SFMC were observed. In addition to the soluble form, high levels of surface expressed OPG on CD33<sup>+</sup>/SFMC, but not on CD3<sup>+</sup>/SFMC, was observed. The high expression of RANKL was found on CD33<sup>+</sup>/SFMC, intermediate on CD3<sup>+</sup>/SFMC and low on FLS. Tested cytokines modulate the expression of RANKL and OPG, in a complex, cell type and time dependent manner. <h3>Conclusion</h3> TNF-α, IL-1b and IL-15 affecting balance between RANKL and OPG influence inflammation and bone destruction in RA patients.
Impressive survival data with semimetronomic oral chemotherapy with old agents in heavily treated metastatic breast cancer patients
Authors: H. Mutlu, H. Bozcuk, M. Ozdogan, M. Artac, H. S. Coskun, A. Kargi, M. Uysal, B. Savas
Journal: Journal of Clinical Oncology (2009)

1082 Background: To assess the efficacy of semi-metronomic regimen metronomic cyclophosphomide with oral etoposide in heavily treated patients with metastatic breast cancer. Methods: Consecutive metastatic breast cancer (MBC) patients predominantly refractory to antracyclines, taxanes, and antimetabolites receiving semi-metronomic regimen of metronomic cyclophosphomide with oral etoposide were evaluated for clinical efficacy and toxicity. This novel regimen comprised of continuous oral cyclophosphomide 50 mg/day, and oral etoposide given as 2 x 50 mg/day for 5 days. Results: A total of 42 MBC patients received this treatment in 2.5 years (May 2005-October 2008). The median age was 51.5 (29–81), ER and/or PR receptor status was positive in 67%, and c-erb-B2 overexpression existed in 50%. The biologically favorable group, hormone responsive and c-erb-B2 negative comprised of 36% of cases. The portions of patients with visceral metastases, cranial metastases, and 2 or more organ involvement were 82%, 24%, and 65%, respectively. Subjects had received this treatment in the fourth or more advanced setting in 50% of cases (after a median of 2.5 cycles). The median overall and progression free survival figures were 25 and 10.5 months, respectively. No toxic mortality occurred, and the treatment was well tolerated. Toxicity and response data are being updated currently. Conclusions: Semi-metronomic treatment with metronomic cyclophosphomide and oral etoposide is a novel and effective strategy in heavily pretreated MBC patients. Survival data and low cost may make this regimen a highly preferable option in this difficult patient group. No significant financial relationships to disclose.
Breastfeeding in India is disrupted as mothers and babies are separated in the pandemic
Authors: Neha Bhatt
Journal: BMJ (2020)

BABY HEALTH AND COVIDBreastfeeding in India is disrupted as mothers and babies are separated in the pandemic India's efforts to promote breastfeeding are threatened by covid-19, as misguided fears of infection see newborns separated from mothers and formula milk promoted.Neha Bhatt reports
Cellular Mechanisms of Conscious Processing
Authors: Jaan Aru, Mototaka Suzuki, Matthew E. Larkum
Journal: Trends in Cognitive Sciences (2020)

Recent breakthroughs in neurobiology indicate that the time is ripe to understand how cellular-level mechanisms are related to conscious experience. Here, we highlight the biophysical properties of pyramidal cells, which allow them to act as gates that control the evolution of global activation patterns. In conscious states, this cellular mechanism enables complex sustained dynamics within the thalamocortical system, whereas during unconscious states, such signal propagation is prohibited. We suggest that the hallmark of conscious processing is the flexible integration of bottom-up and top-down data streams at the cellular level. This cellular integration mechanism provides the foundation for Dendritic Information Theory, a novel neurobiological theory of consciousness.
Outcomes of small cell lung cancer (SCLC) patients treated with second-line chemotherapy (SL): A retrospective analysis of 166 patients
Authors: M. C. Garassino, G. Michetti, M. Lo Dico, R. Califano, S. Aglione, K. Borgonovo, A. Mancuso, D. Galetta, E. Gallerani, E. Collovà, V. Torri
Journal: Journal of Clinical Oncology (2009)

e19093 Background: Patients with SCLC progressed after first-line chemotherapy (FL) have a poor prognosis and the evidence of a benefit of SL is still limited.This retrospective analysis evaluates the clinical outcomes of patients who received a SL treatment after failure of a FL for SCLC Methods: Retrospectively we reviewed 166 consecutive patients who failed a FL and received a second or third-line treatment, between 1993 and 2008 in 17 institutions. We divided patients for analysis in four subgroups, according to the type of SL administered: 1) Platinum-based (P) rechallenge 2) Non-platinum-based polichemotherapy 3) Non-topotecan monochemotherapy 4) topotecan monochemotherapy. Our endpoints were Overall survival (OS), Progression free survival (PFS) and Response Rate. Survival curves were designed with Kaplan-Meier method and Cox proportional hazard model was used for investigating factors which influence survival Results: Median age was 63 (range 25–86). Median OS from the SL was 6.2 months and PFS 2.9. 163 patients received a platinum based chemotherapy as FL, among them 67% obtained a response (CR=14%, PR=53.7%) and 19% had a progressive disease. 74% of patients had a PS 0–1 when started on SL. Moreover, 50 patients underwent also a third-line chemotherapy. Of the 23 CR at FL, 7 patients achieved a response in SL(30%), of the 85 PR only 19 (22%) and of the PD+SD only 6 (16%) (test for trend p=.03). No statistical differences among regimens groups were found; however, patients rechallenged with P went better then others when a long PFS in FL was demonstrated (p=.02) Conclusions: The clinical benefit of SL therapy for SCLC is poor and strictly dependent on response and on duration of response with FL treatment. Our retrospective analysis confirms that median OS for patients receiving SL is about 6 months and median PFS 2.9 months. A rechallenge with platinum should be the best options in patients with a long PFS in FL. Single agent topotecan, the most investigated agent in the literature, did not show evidence of superiority against other chemotherapy regimens No significant financial relationships to disclose.
Characterization of FLT3-ITDmut acute myeloid leukemia: molecular profiling of leukemic precursor cells
Authors: Serena Travaglini, Daniela Francesca Angelini, Valentina Alfonso, Gisella Guerrera, Serena Lavorgna, Mariadomenica Divona, Anna Maria Nardozza, Maria Irno Consalvo, Emiliano Fabiani, Marco De Bardi, Benedetta Neri, Fabio Forghieri, Francesco Marchesi, Giovangiacinto Paterno, Raffaella Cerretti, Eva Barragan, Valentina Fiori, Sabrina Dominici, Maria Ilaria Del Principe, Adriano Venditti, Luca Battistini, William Arcese, Francesco Lo-Coco, Maria Teresa Voso, Tiziana Ottone
Journal: Blood Cancer Journal (2020)

Acute myeloid leukemia (AML) with FLT3-ITD mutations (FLT3-ITDmut) remains a therapeutic challenge, with a still high relapse rate, despite targeted treatment with tyrosine kinase inhibitors. In this disease, the CD34/CD123/CD25/CD99+ leukemic precursor cells (LPCs) phenotype predicts for FLT3-ITD-positivity. The aim of this study was to characterize the distribution of FLT3-ITD mutation in different progenitor cell subsets to shed light on the subclonal architecture of FLT3-ITDmut AML. Using high-speed cell sorting, we sequentially purified LPCs and CD34+ progenitors in samples from patients with FLT3-ITDmut AML (n = 12). A higher FLT3-ITDmut load was observed within CD34/CD123/CD25/CD99+ LPCs, as compared to CD34+ progenitors (CD123+/-,CD25-,CD99low/-) (p = 0.0005) and mononuclear cells (MNCs) (p < 0.0001). This was associated with significantly increased CD99 mean fluorescence intensity in LPCs. Significantly higher FLT3-ITDmut burden was also observed in LPCs of AML patients with a small FLT3-ITDmut clones at diagnosis. On the contrary, the mutation burden of other myeloid genes was similar in MNCs, highly purified LPCs and/or CD34+ progenitors. Treatment with an anti-CD99 mAb was cytotoxic on LPCs in two patients, whereas there was no effect on CD34+ cells from healthy donors. Our study shows that FLT3-ITD mutations occur early in LPCs, which represent the leukemic reservoir. CD99 may represent a new therapeutic target in FLT3-ITDmut AML.
A phase IIb 4-arm open-label randomized study to assess the safety and efficacy of h-R3 monoclonal antibody against EGFR in combination with chemoradiation therapy or radiation therapy in patients with advanced (stage III or IVA) inoperable head and neck cancer
Authors: B. Krishnamurthyreddy, M. S. Vidyasagar, R. Koteshwar, A. Shenoy, L. Viswanath, N. Thimmaiah, G. Babu, B. Joseph, R. Bonnathiya, P. P. Bapsy
Journal: Journal of Clinical Oncology (2009)

6041 Background: Patients (pt) with advanced inoperable squamous cell carcinoma of the head and neck (SCCHN) have poor radiotherapy alone (RT) outcome. EGFR is over-expressed in &gt;90% SCCHN. h-R3mAb (BIOMAb/nimotuzumab/TheraCIM) is a humanized monoclonal antibody, a validated oncotherapeutic-targeting EGFR. Objective: To investigate the safety and efficacy of concurrent h-R3mAb in combination with chemoradiotherapy of SCCHN. Methods: September 2004–2005, pt 18–70 yrs, SCCHN stageIII-IVA, 113 screened, 92 enrolled and randomly asssigned to, Group A: radical radiotherapy (pt) and Group B: chemoradiotherapy (pt). Randomization within Group A: [RT]v/s[RT+h-R3mAb] and within Group B: [RT+CT]v/s[RT+CT+ h-R3mAb] (n = 23 in each arm). Protocol: Radiotherapy: TD: 66 Gy,2Gy/Fr,5Fr/w,6.5wks. Radiation sensitizer (chemotherapy): CDDP-50mg/wk x 6wks. Study Drug (h-R3mAb): 200 mg/wk I.V.60min x 6weeks. Results: Evaluable (n = 76) in Group A-36 and Group B-40. F/u Analysis at 30 months after end of RT. Survival rate ITT: Group B: CT+RT+hR3- 69.5% v/s CT+RT-21.7% (p - 0.0011), Group A: RT alone - 21.7% v/s RT+ hR3–39.1% (ns). Progression-free survival: RT alone - 3(13.04 %) v/s RT+hR3mAb-8 (34.78 %), RT+CT-5 (21.74 %) v/s RT+CT+hR3mAb-13 (56.52%). Median overall survival (OS): CT+RT+hR3 - NR* v/s CT+RT- 21.96 months (hazard ratio [HR]-0.337, p - 0.0018) and RT alone - 25.02 v/s RT+hR3 - NR*(HR-0.678, p - 0.39). Disease-free survival: CT+RT+hR3- NR*v/sCT+RT-21.30 mths (HR-0.344, p - 0.0052) and RT alone-25.02 v/s RT+hR3- NA* (HR-0.599, p - 0.32). (NR*- median OS is yet to be reached). Safety: few grade - 1/2AE, no HAMA observed. OS per protocol - adding h-R3mAb to chemoradiation resulted in a reduction in risk of death (rrd) by 85% (HR 0.15, p - 0.0006) and to RT a 36 % rrd (HR0.64, p - 0.33). Conclusions: Concurrent use of h-R3mAb with RT or RT+CT is safe and efficacious. It enhances radiation and chemotherapy responses. Concurrent use of h-R3mAb with chemoradiotherapy enhances long-term loco-regional control and survival. Adding biological agents to physically targeted modality improves long-term therapeutic outcome of SCCHN. No significant financial relationships to disclose.
THU0002 Il-10 and il-6 polymorphisms are not related to erosive disease in early rheumatoid arthritis
Authors: C Orellana, R Sanmartí, JD Cañete, J Yagüe, G Ercilla, A Gómez, G Salvador, J Muñoz-Gómez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To assess the prevalence of IL-10 and IL-6 polymorphisms in patients with early rheumatoid arthritis (RA) in our population and investigate whether there is an association with radiographic severity. <h3>Methods</h3> 68 patients with early RA (49F/19M, mean age 51 ± 15 y, mean disease duration 15 ± 13 mo, RF+ 72%, mean number of swollen joints at entry 8.23 ± 7.33). Patients were genotyped for HLA-DRB1 and IL-10 and IL-6 alleles and results compared with the control population (n = 110). Hands and feet radiographs were taken at entry and then yearly during follow-up. The Larsen method was used to assess radiographic damage. <h3>Results</h3> There were not differences in the distribution of IL-6 alleles in the RA patients compared with controls. A difference was found in the distribution of IL-10 polymorphism at position ?592 between patients with RA and the control population: 592CC, 592CA and 592AA were found in a 40%, 54% and 6% of patients with RA versus a 55%, 33% and 12% respectively among controls (p = 0.018). No other differences were found in the frequency of the IL-10 alleles between RA and controls. No associations related to IL-6 or IL-10 polymorphisms were found in relation to radiographic damage. <h3>Conclusion</h3> The IL-10 polymorphism at position ?592 showed a greater proportion of the CA allele in AR compared with the control population, although the clinical implications if any of this difference remains to be determined. No IL-6 nor any other IL-10 polymorphisms either were found to be associated to RA. No IL-10 nor IL-6 polymorphisms were found to be related to erosive disease in early rheumatoid arthritis.