tbuckley/cabot-search huggingface dataset:
A phase I/II study of dovitinib (TKI258), a FGFR and VEGFR inhibitor, in patients (pts) with advanced or metastatic renal cell cancer: Phase I results.
Authors: E. Angevin, C. Lin, A. U. Pande, J. A. Lopez, J. Gschwend, A. L. Harzstark, M. Shi, O. Anak, B. J. Escudier
Journal: Journal of Clinical Oncology (2010)

3057 Background: TKI258 selectively targets FGFR1-3, in addition to VEGFR, PDGFR and other tyrosine kinases. FGF pathway has been reported as an important escape mechanism of anti-VEGFR therapies. We hypothesize that TKI258 would be active in VEGF refractory pts. Methods: Phase I aimed to determine the MTD and preliminary activity of TKI258, administered p.o. on a 5-day on/2-day off schedule in a repeated 28-day cycle, in mRCC pts refractory to standard therapies. Results: Pts were treated with 500 mg (n=15) or 600 mg (n=5) TKI258 qd doses. Pt characteristics (n=20): ECOG PS 0/1: 7/13, 65% received ≥3 prior therapy regimens, 80% previously received VEGFR TKI; 55% mTOR inhibitor (mTORi); 15% cyctokines, 75% had metastases to ≥2 organs at baseline. DLTs: G2 sinus bradycardia (n=1; 500 mg); G4 hypertension (n=1; 600 mg); G3 fatigue (n=1; 600 mg). Most common adverse events were nausea (80%; G3:5%), diarrhea (70%), vomiting (65%), asthenia (50%; G3:15%), anorexia (45%; G3:5%), headache (30%; G3:5%), hypertension (25%; G4:5%), and rash (23%; G3:5%). Confirmed partial response (PR) in 2(10%), stable disease (SD) in 7(35%) and disease progression (PD) in 8(40%) pts were observed at week 16 (3 pts discontinued at cycle 1 due to DLTs). Preliminary median progression free survival was 5.5 months (range 1– 446+ days). In a subset of 10 pts previously treated with VEGFR TKI and mTORi, 1 confirmed PR, 6 SD and 2 PD were observed at week 16 (1 pt discontinued due to DLT). Pts (n=20) had high baseline VEGF and bFGF levels, which may reflect failure of previous anti-VEGF agents. In pts treated at 500mg: plasma FGF23 levels increased 53% over baseline indicating FGFR1 inhibition, VEGF and PLGF increased 107% and 23%, respectively, sVEGFR2 decreased by 21%, and IHC of a paired tumor biopsies showed significant decrease in pERK expression and microvessel density at day 15 of TKI258 treatment. Conclusions: TKI258 MTD was defined as 500 mg qd for the schedule tested. TKI258 was well tolerated and encouraging antitumor activity was observed in heavily pretreated pts. Phase II part of the study is ongoing. A randomized phase III study is planned to start in 2010 in pts previously treated with VEGFR TKI and an mTORi. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline, Novartis, Pfizer, Roche Novartis
Efficacy of Goshajinkigan for prophylaxis against oxaliplatin-induced peripheral neuropathy.
Authors: Toru Kono, Yasuyuki Suzuki, Keita Mizuno, Chika Miyagi, Yuji Omiya, Hitomi Sekine, Yasuharu Mizuhara, Kanako Miyano, Yoshio Kase, Yasuhito Uezono
Journal: Journal of Clinical Oncology (2015)

576 Background: Oxaliplatin-induced peripheral neuropathy (OPN) is often observed and is the most frequent dose-limiting toxicity. However, there is no effective therapeutic option for preventing OPN. Goshajinkigan (GJG), a traditional Japanese herbal medicine, has widely been used for disease-assessed neuropathy in Japan. Recently, the preventive effect of GJG against OPN in a placebo-controlled double-blind randomized phase II study was reported (Kono T et al., Cancer Chemother Pharmacol. 2013, 72,1283-90). However, the precise mechanisms underlying preventive effect of GJG are unknown. Methods: To be established the OPN rat model, oxaliplatin (4 mg/kg) was injected intraperitoneally twice weekly for 8 weeks in rats. Animals were treated with oral administration of GJG (0.3, 1.0 g/kg) five times a week for 8 weeks. We performed behavioral tests (acetone test and hot plate test) and pathological examination of neuronal tissue using the OPN rat model. We carried out pharmacokinetic study of GJG and searched for active ingredients in GJG in order to explore the mechanism of GJG. Results: The rats injected with oxaliplatin for a long-term showed both cold hypersensitivity and heat hyposensitivity. Co-administration of GJG ameliorated OPN in the rat. In light and electron microscopic study, scattered axonal damages in sciatic nerve of oxaliplatin groups were observed, which were substantially suppressed by GJG. Pharmacokinetic study revealed that considerable neuroprotective and analgesic ingredients were detected after oral administration of GJG in rat plasma. Some ingredients in GJG significantly suppressed oxidative stress caused by oxaliplatin in the experiment using neuronal cells. Conclusions: Oxaliplatin-induced chronic neuropathy symptoms are similar to human symptoms caused by long-term oxaliplatin administration. Oral administration of GJG in rat substantially diminished OPN, and promises to provide an effective and convenient treatment at risk of developing peripheral neuropathy in oxaliplatin-treated patients.
Transplantability, Morphology, and Behavior of Polyoma Virus-Induced Hepatic Hemangiomas of Hamsters
Authors: Mearl F. Stanton
Journal: JNCI Journal of the National Cancer Institute (1965)

The angiomatous lesions developing in the liver of hamsters within 30 days after inoculation with polyoma virus have a low incidence of transplantability. Those that do transplant develop as cystic hemangiomas composed of cells suggesting origin from phagocytic reticuloendothelium. During transplantation some of the tumors acquire further irreversible structural and behavioral characteristics of malignant tumors. The latent period, growth rate, structure, and incidence of metastases have been studied in cystic hemangioma 265 for more than 90 transplant generations. One line of this tumor acquired the ability to metastasize rapidly and consistently and to grow without inhibition in polyoma virus-infected hosts. Efforts to alter the inherent characteristics of the tumor have failed. Like other transplantable tumors, progression seems to occur in polyoma virus-induced tumors independent of the inciting cause.
W135 invasive meningococcal infections imported from Sub-Saharan Africa to France, January to April 2012
Authors: I Parent du Châtelet, P Barboza, M  K Taha
Journal: Eurosurveillance (2012)

From January to April 2012, 16 cases of W135 invasive meningococcal infection were reported in France. Of these, eight were linked to a recent travel history to Sub-Saharan Africa. These cases were reported in France concomitantly with the meningitis epidemic season in Sub-Saharan Africa. Considering the high number of travellers between France and West-African countries belonging to the so-called meningitis belt, the French recommendations for travellers stress the importance of vaccination before travelling to these countries.
Noninfectious infiltrative lung diseases after allogeneic hematopoïetic stem cell transplantation (HSCT)
Authors: Frédéric Schlemmer, Sylvie Chevret, Gwenael Lorillon, Cédric De Bazelaire, Régis Peffault de Latour, Véronique Meignin, Mauricette Michallet, Eric Hermet, Benjamin Wyplosz, Véronique Houdouin, Sylvain Marchand-Adam, Gérard Socié, Abdellatif Tazi, Anne Bergeron
Journal: European Respiratory Journal (2013)

Late onset noninfectious pulmonary complications (LONIPC) following allogeneic HSCT are a frequent cause of morbidity and mortality. Although half of LONIPC have been related to infiltrative lung diseases (ILD), very few data are available in regard to their clinical characteristics. We retrospectively analysed our cohort of 40 allogeneic HSCT recipients who were diagnosed with a noninfectious ILD between 2001 and 2010. Donor hematopoietic stem cell source was peripheral blood stem cells in 75% of the cases and conditioning regimen was nonmyeloablative in 57.5%. Median time from transplant to ILD was 11.3 months [IQR: 5.9-19.2]. 82.5% of the patients had extrathoracic chronic GVHD. We identified two computed tomography (CT) scan patterns according to the predominance of ground glass opacities (n=22) or alveolar consolidations (n=18). The predominant profile of pulmonary function tests was a restrictive lung defect and bronchoalveolar lavage mainly found lymphocytic alveolitis. Histological analysis was available for 7 patients that concluded to diffuse alveolar damage, non specific interstitial pneumonia, organizing pneumonia or lymphoid interstitial pneumonia. The median follow-up after ILD diagnosis was 9.3 months (IQR: 2.1-31.75). Thirty-five patients were treated with systemic steroids for their ILD. Thirteen patients died, 10 of respiratory failure. Median survival rate at 24 months was 61 % (IQR: 45.3-82.1%). No factors were associated with survival, and no significant difference in prognosis was observed between the two lung CT patterns Further studies are needed to identify the risk factors for such complications and to evaluate the best management of these patients.
Suppression of lung growth by environmental toxins
Authors: Jonathan Grigg
Journal: Thorax (2015)

It is not unreasonable to expect that all children achieve their full lung growth potential. An important dimension of children's lung growth is growth of lung function. Over the last decade, long-term prospective studies have revealed that environmental toxins are an important threat to children's lung function growth. For example, the Southern California Children's Health Study found lower lung function growth in children living in communities with high background concentrations of fossil-fuel-derived particulate matter and nitrogen dioxide.1 The cumulative effect of small annual deficits in lung function growth in highly polluted communities is an increased proportion of young adults with clinically low lung function (<80% predicted)1—a deficit that increases the risk of respiratory symptoms in adult life. The high prevalence of air pollution therefore means that most children growing up in medium-income and high-income countries will fail to achieve their maximum lung function growth potential. The difficulty of measuring FEV1, and FVC from birth to 6 years of age …
The Tc17 Population Required For Sclerodermatous Chronic Gvhd Represents a Non-Cytolytic, Pluripotent Inflammatory Effector T Cell Lineage
Authors: Kate H Gartlan, Kate A Markey, Katie E Lineburg, Antiopi Varelias, Stuart D Olver, Neil C Raffelt, Rachel D Kuns, Bianca E Teal, Mary Lor, Geoffrey R Hill, Kelli PA MacDonald
Journal: Blood (2013)
Useful of Quantiferon G in managing solitary pulmonary nodule of less than 3 cm
Authors: Sawang Saenghirunvattana, Kasem Saenghirunvattana, Patchamol Masakul, Chuchart Vinitwatanakhun
Journal: European Respiratory Journal (2011)

Introduction:  Development of new tools for the rapid diagnosis of tuberculosis is a priority. There are few data from high burden countries on the utility of Quantiferon G for the rapid diagnosis of solitary pulmonary nodule.   Material and methods:  We evaluated the utility of Quantiferon G in 30 patients with solitary pulmonary nodule which was less than 3 cm. All were Thai people, and all got BCG vaccination. Bronchoscopy with Autofluorescense was done, bronchial washing was sent for AFB stain, TB culture, PCR-TB and cytology. Tuberculin test was also performed.   Results:  Tuberculosis test was positive in 16 patients (53%), Quantiferon G was positive in 19 patients (63%)and PCR-TB was positive in 2 patients (6.7%).  Those with positive Quantiferon G were treated with anti tuberculosis drugs for 9 months, all showed satisfactory response.  Among those with negative Quantiferon G,1 year follow up was provided; one turned to be Mycobacterium avium intracellulare, another one developed adenocarcinoma.   Conclusion:  Quantiferon G may provide additional useful tool in making decision in managing solitary pulmonary nodule in countries with high incidence of tuberculosis.
Platelet Factor 4 Modulates Fibroblast Growth Factor 2 (FGF-2) Activity and Inhibits FGF-2 Dimerization
Authors: Catherine Perollet, Zhong Chao Han, Catherine Savona, Jacques Philippe Caen, Andreas Bikfalvi
Journal: Blood (1998)

Abstract Platelet factor 4 (PF-4) inhibits angiogenesis in vitro and in vivo. The mechanism of inhibition is poorly understood. We have investigated the mechanism of inhibition by examining the interaction of PF-4 and the fibroblast growth factor-2 (FGF-2)/fibroblast growth factor receptor (FGFR) system. PF-4 inhibited the binding of FGF-2 to high-affinity and low-affinity binding sites in murine microvascular endothelial cells (LEII cells) and proliferation. Maximum inhibition of binding to endothelial FGF receptors was observed at PF-4 concentrations between 5 and 10 μg/mL (half maximum inhibition at 0.6 μg/mL), and proliferation was completely inhibited at 2 μg/mL. At this concentration, PF-4 reduced internalization of125I–FGF-2 by threefold and delayed degradation. To gain insight into the mechanism of inhibition, we have analyzed the interaction of PF-4 with FGF-2/FGFR by using mutant heparan sulfate–deficient Chinese hamster ovary (CHO) cells transfected with the FGFR-1 cDNA (CHOm–FGFR-1) and by examining the direct interaction with FGF-2. In the absence of heparin, PF-4 inhibited binding of 125I–FGF-2 to CHOm–FGFR-1 cells in a concentration-dependent manner, although not completely. In the presence of heparin, PF-4 abolished totally the stimulatory effect of heparin. Furthermore, PF-4 complexed to FGF-2 and inhibited endogenous or heparin-induced FGF-2 dimerization. These results indicate that PF-4 interacts with FGF-2 by complex formation, inhibiting FGF-2 dimerization, binding to FGF receptors, and internalization. This mechanism most likely contributes to the antiangiogenic properties of PF-4.
A Large Liver Mass With Acute Hemorrhage
Authors: Sonia T. Orcutt, Mark A. Sultenfuss, Daniel A. Anaya
Journal: JAMA Surgery (2015)

A man in his 60s presents to the emergency department after collapsing with sudden-onset back and abdominal pain; computed tomography shows a large right hepatic mass with intrahepatic and intraperitoneal hemorrhage. What is your diagnosis?
Combined inhibition of DDR1 and Notch signaling is a therapeutic strategy for KRAS-driven lung adenocarcinoma
Authors: Chiara Ambrogio, Gonzalo Gómez-López, Mattia Falcone, August Vidal, Ernest Nadal, Nicola Crosetto, Rafael B Blasco, Pablo J Fernández-Marcos, Montserrat Sánchez-Céspedes, Xiaomei Ren, Zhen Wang, Ke Ding, Manuel Hidalgo, Manuel Serrano, Alberto Villanueva, David Santamaría, Mariano Barbacid
Journal: Nature Medicine (2016)
Lethal Infection and Pathological Findings in A × C Rats Inoculated With H Virus and RV&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Alice E. Moore, Anthony D. Nicastri
Journal: JNCI Journal of the National Cancer Institute (1965)

Four different strains of H virus, representing both H-1 and H-3 serologic types, killed newborn A × C rats when inoculated intracerebrally, intraperitoneally or subcutaneously. The disease differed from the infection in hamsters in that facial deformities were rare, large quantities of virus were necessary for a lethal infection, and the incubation period was longer and failed to decrease with continued passage. Titrations showed virus in practically all organs, but the liver, spleen, and intestinal tract contained the most. Type-A inclusions were also noted in all organs except the brain. Identical inclusions were found in hamsters that had died with the infection. The main objective of this study was to determine if any of the 4 strains would produce tumors in the A × C rats. These animals seemed like good candidates for oncogenesis, since they have no antibodies to either type of virus and can be infected. However, animals inoculated as newborns, whose littermates died of disease, failed to develop any more tumors than the expected number. Only a rhabdomyosarcoma was readily transferable, and filtrates inoculated into newborn rats, mice, and hamsters failed to produce tumors. Therefore, despite their many similarities to polyoma, these viruses apparently are not oncogenic in the A × C rats.
Genetic Control of Hapten-Reactive Helper T-Cell Responses and Its Implications for the Generation of Augmented Antitumor Cytotoxic Responses&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Y Mizushima, H Fujiwara, Y Takai, G M Shearer, T Hamaoka
Journal: JNCI Journal of the National Cancer Institute (1985)

The genetic control of hapten-reactive helper T-cell activity involved in cytotoxic T-lymphocyte (CTL) responses and its implications for augmenting tumor-specific immunity were studied. C57BL/6N mice were immunized to trinitrophenyl (TNP) or N-iodoacetyl-N'-(5-sulfonic l-naphthyl)ethylenediamine (AED) hapten by inoculation of hapten-modified syngeneic spleen cells. Spleen cells from these hapten-immunized mice were tested for hapten-reactive helper T-cell activity for generation of CTL. TNP-primed spleen cells resulted in only marginal help for the generation of anti-TNP-modified syngeneic spleen cell (TNP-self) CTL response when cocultured with normal C57BL/6N spleen cells (responding cells) in the presence of TNP-self. In contrast, AED-primed spleen cells exhibited appreciable help for AED-induced CTL responses. Furthermore, AED-helper, but not TNP-helper, T-cell activity was demonstrated to augment the generation of antitumor (RBL-5 leukemia) CTL responses from normal syngeneic spleen cells when stimulated with the corresponding hapten-self plus RBL-5 tumor cells. These results indicate that the successful augmentation of syngeneic tumor immunity through T-T-cell interaction with the use of hapten-reactive helper T-cells can depend on selection of the appropriate haptenic reagent in an individual expressing a given major histocompatibility haplotype.
Recurrent wheeze in children with Down syndrome: Is it asthma?
Authors: Michel Weijerman, Paul Brand, Marceline van Furth, Chantal Broers, Reinout Gemke
Journal: European Respiratory Journal (2011)

Background:  Clinical experience shows that wheeze is common in children with Down syndrome (DS), but that treatment with anti-asthmatic drugs is usually disappointing.   Aim:  To compare the prevalence of current wheeze in children with DS, their siblings, and general population controls.   Methods:  This was a case control study in which the International Study of Asthma and Allergy in Childhood questionnaire for respiratory symptoms was completed by parents for 130 children with DS and 167 of their siblings, and for 119 age and sex matched control subjects from the general population.   Results:  Both wheeze ever and wheeze during the last 12 months was more commonly reported in DS than in their siblings or controls. The relative risk (RR) of current wheeze in DS was 2.8 (95% CI 1.42-5.51) compared to siblings, and 2.75 (95% CI 1.28-5.88) compared to controls. Children with DS were less likely to have received a doctor9s diagnosis of asthma (3.1%) than siblings (4.2%) or controls (6.7%, p=0.04). During 4-yr follow-up, the diagnosis of asthma was confirmed in none of the 24 DS children with current wheeze, and atopy was found in none of them. Chronic rhinitis occurred more frequently in children with DS (40%) than in their siblings (17.3%); eczema did not (14.6 vs 19.2%).   Conclusion:  Wheeze is common in children with DS. This is likely to be related to factors specific for DS, and probably unrelated to asthma.
Phase I study of YM155, a first-in-class survivin suppressant, in patients with advanced solid tumors in Japan
Authors: K. Nakagawa, T. Satoh, I. Okamoto, M. Miyazaki, R. Morinaga, A. Tsuya, Y. Hasegawa, M. Terashima, S. Ueda, M. Fukuoka
Journal: Journal of Clinical Oncology (2007)

3536 Background: YM155 is a small molecule expected to induce apoptosis in tumor tissue by suppressing survivin. In the US, a phase I study was conducted with a 168-hr continuous infusion every 3 wks. In Japan, we conducted a similar phase I study to evaluate toxicity profile of YM155 compared with the results of the US study. Methods: The objectives were to determine the MTD, characterize the pharmacokinetics (PK) and observe anti-tumor activity. A standard 3+3 dose escalation scheme was utilized. Results: 34 pts (M/F: 24/10, median age 60, range 26 - 81) were enrolled into 6 dose cohorts [1.8 mg/m 2 /day (N=3), 3.6 (6), 4.8 (6), 6.0 (8), 8.0 (6), and 10.6 (5)]. 2/5 pts experienced dose-limiting toxicities (DLT) during cycle (C) 1 at 10.6 mg/m 2 /day (blood creatinine increased (2), lymphocyte count decreased (1)), thus the MTD was 8.0 mg/m 2 /day. Both pts experienced a DLT (56 yo female, 57 yo male), reached to NCI-CTC grade 2 blood creatinine level at the end of infusion. One of them developed to grade 3 blood creatinine level on day10. They recovered to grade 1 or below in 2 wks without plasma dialysis, so that they continued YM155 infusion decreased to 8.0 mg/m 2 /day. Renal parameters of them changed in a regular manner, as urine microalbumin increased from day 3 to 7, protein urine from day 6 to 8, and blood creatinine from day 8 to 10. As the other DLT during C1, 1/6 pt experienced AST increased at 6.0 mg/m 2 /day.. The most frequent AEs were: fatigue (39%), urine microalbumin present (39%), pyrexia (33%), and anemia / haemoglobin decreased (30%). At the MTD, the median YM155 clearance was 39 L/hr with a median steady state concentration of 13 ng/mL and a median terminal half-life of 20 hours. 9/33 pts showed stable disease (SD) and minor tumor shrinkage was observed in 5 of them. One pt (thyroid carcinoma) is ongoing (40 wks) and has had disappearance of pleural effusion. Another patient (malignant fibrous histiocytoma) showed tumor regression in abdominal cavity confirmed by CT scan. Conclusions: YM155, the first survivin suppressant, was well tolerated and the MTD was 8.0 mg/m 2 /day x 168-hr in Japan. The contribution of YM155 to the treatment of advanced solid tumors should be evaluated in further trials. No significant financial relationships to disclose.
Abstract 15103: Inefficient Ventilation is an Easily Derived Marker of Cardiovascular Reserve Capacity in Heart Failure With Preserved Ejection Fraction: A RELAX Trial Ancillary Study
Authors: Gregory D Lewis, Ryan M Murphy, Steven McNulty, Marc J Semigran, Barry A Borlaug, Selma F Mohammed, Lynne W Stevenson, Anita Deswal, Martin LeWinter, Kevin Anstrom, Adrian F Hernandez, Eugene Braunwald, Margaret M Redfield
Journal: Circulation (2013)

Background: Ventilatory efficiency, assessed by minute ventilation (VE)-carbon dioxide (VCO2) slope, predicts outcome in heart failure (HF). We hypothesized that VE/VCO2 slope is correlated with in...