tbuckley/cabot-search huggingface dataset:
Efficacy and safety of raltitrexed combinations with uracil-tegafur or Mitomycin C as salvage treatment in advanced colorectal cancer patients.
Authors: Metin Ozkan, Oktay Bozkurt, Halit Karaca, Ersin Ozaslan, Osman Onur Daloglu, Aydin Ciltas, Mehmet Ali Kaplan, Mustafa Benekli, Alper Sevinc, Umut Demirci, Tulay Eren, Hilmi Kodaz, Abdurrahman Isikdogan, Suleyman Buyukberber
Journal: Journal of Clinical Oncology (2014)

662 Background: Oxaliplatin and irinotecan in combination with 5-fluorouracil and leucovorin for metastatic colorectal cancer (mCRC) accepted as the standard treatment. There is no standard treatment approach for patients after progression with these agents. In this study aimed to evaluate the efficacy and side effects of patients with previously treated metastatic colorectal cancer a salvage combination with oral 5-fluorouracil (tegafur-uracil UFT) or Mitomycin C and Raltitrexed. Methods: In the 7 centers, data of 62 patients who received Raltitrexed 2.6 mg/m2 (max. 5 mg) (day 1) and UFT 500 mg/day (1-14. days), or Mitomycin C 6mg/m2 (day 1) every 3 weeks, with a diagnosis of metastatic colorectal cancer, between December 2008 and June 2013 has been analyzed retrospectively. Overall survival (OS), progression-free survival (PFS), and toxicity profiles were evaluated. Results: The median age of patients was 51 (min-max: 18-76 years), and 35 (56%) were male and 27 (44%) were female. Thirty nine patients (63%) had ECOG performance status 0 and 1. Four patients (10%) received a combination of UFT and Raltitrexed at the second line and 38 patients (90%) had third, fourth, and fifth lines. Otherwise Mitomycin C plus Raltitrexed protocol used at the second and third lines. Twelve patients (19%) developed grade 3/4 toxicities as diarrhea and fatigue and 13 patients (21%) needed to dose reduction. In all patients the median PFS was 3 months (%95 CI, 2,65–3,34) and the median OS was 6 months (%95 CI, 2,09–9,90). Two groups were evaluated separately; the median PFS was 3 months (%95 CI, 2,60–3,39) and median OS was 6 months (%95 CI, 2,47–9,53) in UFT arm and, the median PFS was 3 months (%95 CI, 1,64–4,35) and median OS was 12 months (%95 CI, 2,83–21,1) in Mitomycin C arm. Statistical significance could not be determined (p&gt;0.05). Conclusions: Thecombination of Raltitrexed with UFT and Mitomycin C showed an acceptable survival time and toxicity in the treatment of patients with previously treated mCRC. It could be considered as a salvage treatment option in mCRC.
Extended survival and broad immune responses following vaccination of patients with metastatic melanoma with peptide-pulsed CD34+ progenitor derived dendritic cells (DCs)
Authors: J. Banchereau, A. K. Palucka, S. Paczesny, M. Dhodapkar, D. Johnston, H. Ueno, L. Pineiro, S. Burkeholder, J. Fay
Journal: Journal of Clinical Oncology (2005)

2525 Background: Culture of CD34+ blood cells with GM-CSF, Flt-3 ligand and TNF yield distinct dendritic cell (DC) subtypes including Langerhans and interstitial DCs. Such composite DC vaccine was loaded with melanoma peptides (MART-1, tyrosinase, MAGE-3, gp100) and control antigens flu-matrix and KLH, and administered subcutaneously to patients with metastatic melanoma in a Phase I trial. Methods: HLA-A0201+patients received 4 DC vaccinations every 2 weeks followed by additional 4 monthly DC vaccinations. All DCs were pulsed with KLH, 20% of cells were pulsed with flu-matrix peptide and 80% with melanoma peptides. IFN-gamma ELISPOT and tetramer staining were used to measure specific CD8+ T cells. Spearman correlation was used with non-transformed data. Patient survival was calculated using Kaplan-Meier estimation based on log-rank analysis of difference. Results: There were 18 patients: 10 male with median age (range) was 53 (40–73) years. 6 patients had progressive melanoma after 4 vaccines and were removed from study. 12 patients received 5–8 consolidation DC vaccinations. There were no significant adverse events. The median (range) overall survival was 20 (2–69) months. At present there are 5 patients (27.7%, [95% c.i. 19.3–39.6]) who are alive at 55+, 61+, 61+, 61+ and 69+ months after their last vaccine. Production of IFN-gamma determined by ELISPOT to 3–4 melanoma antigens after 4 DC vaccinations correlated with overall survival (p=0.0065). Peptide tetramers of CD8+ T-cells validated Mart-1 and flu ELISPOTS. 5/5 long-term survivors had immunity to greater than 3 melanoma antigens after 4 vaccinations and at least 2 antigens after their last vaccination. Conclusions: Vaccination of patients with metastatic melanoma with melanoma peptide- loaded DCs made from CD34+ progenitor cells resulted in a broad melanoma antigen-specific CD8+ T-cell immune response that correlated with survival in a significant number of patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Argos Therapeutics, ODC Therapy
Correlation of Cocarcinogenic Activity Among n-Alkanes With Their Physical Effects on Phospholipid Micelles 2
Authors: A. Wesley Horton, D.N. Eshleman, A.R. Schuff, W.H. Perman
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Correlation of Cocarcinogenic Activity Among n-Alkanes With Their Physical Effects on Phospholipid Micelles Get access A. Wesley Horton, A. Wesley Horton 3Division of Environmental Medicine, University of Oregon Health Sciences Center, Portland, Ore. 97201.4Department of Biochemistry, University of Oregon Health Sciences Center Search for other works by this author on: Oxford Academic PubMed Google Scholar D.N. Eshleman, D.N. Eshleman 3Division of Environmental Medicine, University of Oregon Health Sciences Center, Portland, Ore. 97201. Search for other works by this author on: Oxford Academic PubMed Google Scholar A.R. Schuff, A.R. Schuff 3Division of Environmental Medicine, University of Oregon Health Sciences Center, Portland, Ore. 97201. Search for other works by this author on: Oxford Academic PubMed Google Scholar W.H. Perman W.H. Perman 3Division of Environmental Medicine, University of Oregon Health Sciences Center, Portland, Ore. 97201. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 2, February 1976, Pages 387–391, https://doi.org/10.1093/jnci/56.2.387 Published: 01 February 1976 Article history Received: 09 June 1975 Accepted: 12 September 1975 Published: 01 February 1976
Pilot phase I study of gefitinib (GEF) in combination with paclitaxel (PAC) and radiation therapy (RT) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) and effects on epidermal growth factor receptor (EGFR) signaling pathway
Authors: J. C. Morris, C. Allen, D. Citrin, D. Gius, Z. Chen, A. D. Colevas, N. Harold, S. Rudy, A. K. Singh, C. VanWaes
Journal: Journal of Clinical Oncology (2007)

16526 Background: The over expression of EGFR in HNSCC stimulates tumor cell proliferation, inhibits apoptosis, and increases resistance to chemotherapy and radiation. We examined the toxicity and maximum tolerated dose (MTD), and the downstream signaling and cellular effects in tumor biopsies in locally advanced HNSCC patients (Pts.) treated with GEF+PAC and RT. Methods: Pilot phase I dose escalation study initiated at GEF 250 mg/d + PAC 45 mg/m 2 weekly x 6 with concurrent RT to 72 Gy. Eligibility: Stage III-IVB HNSCC, age=18 years, no prior RT or chemotherapy, ECOG =2, adequate organ function and informed consent. Endpoints: MTD determination, analysis of tumor biopsies for treatment effect on phospho-EGFR, Akt, Erk1/2, STAT3, NF-κB p65, Ki67 expression, TUNEL assay, serial measurement of serum IL-6, IL-8, VEGF, HGF and GROa. Results: 10 Pts., median age 60.7 yrs. (range, 41–83), 7 men and 3 women were treated. The MTD was GEF 250 mg/d + PAC 36 mg/m 2 weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (&gt;8 wk duration) mucositis in 7 Pts., infection (1) and interstitial pneumonitis (1). Two Pts. experienced protracted painful oral dysesthesia. There were 5 CR's and 1 PR. Of 7 Pts. undergoing serial biopsy, 1 Pt. showed a significant decrease in phosphorylated-EGFR expression, decreased downstream phosphoprotein signaling and cellular proliferation within 8 days of initiating GEF. Conclusions: Severe and prolonged mucositis was dose-limiting for this schedule of GEF+PAC and RT in locally advanced HNSCC. Inhibition of EGFR activation and downstream signaling by GEF was observed in a minority of Pts. on serial tumor biopsy specimens obtained during treatment. No significant financial relationships to disclose.
Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes
Authors: Konstantinos Samitas, Nikolaos Poulos, Maria Semitekolou, Ioannis Morianos, Sofia Tousa, Erasmia Economidou, Douglas S. Robinson, Harsha H. Kariyawasam, Eleftherios Zervas, Christopher J. Corrigan, Sun Ying, Georgina Xanthou, Mina Gaga
Journal: European Respiratory Journal (2016)

Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro . Expression of soluble/immunoreactive activin-A and its receptors was measured in serum, bronchoalveolar lavage fluid (BALF) and endobronchial biopsies from 16 healthy controls, 19 patients with mild/moderate asthma and 22 severely asthmatic patients. In vitro effects of activin-A on baseline and vascular endothelial growth factor (VEGF)-induced human endothelial cell angiogenesis, signalling and cytokine release were compared with BALF concentrations of these cytokines in vivo . Activin-A expression was significantly elevated in serum, BALF and bronchial tissue of the asthmatics, while expression of its protein receptors was reduced. In vitro , activin-A suppressed VEGF-induced endothelial cell proliferation and angiogenesis, inducing autocrine production of anti-angiogenic soluble VEGF receptor (R)1 and interleukin (IL)-18, while reducing production of pro-angiogenic VEGFR2 and IL-17. In parallel, BALF concentrations of soluble VEGFR1 and IL-18 were significantly reduced in severe asthmatics in vivo and inversely correlated with angiogenesis. Activin-A is overexpressed and has anti-angiogenic effects in vitro that are not propagated in vivo , where reduced basal expression of its receptors is observed particularly in severe asthma.
A phase I dose escalation study of the matrix metalloproteinase inhibitor BAY 12-9566 administered orally in patients with advanced solid tumours
Authors: H. Hirte, R. Goel, P. Major, L. Seymour, S. Huan, D. Stewart, J. Yau, A. Arnold, S. Holohan, B. Waterfield, S. Bates, K. Bennett, W. Walsh, I. Elias
Journal: Annals of Oncology (2000)
Relationship Between Drug Exposure and Clinical Response Observed in the Phase 1b Study of DX-2930 in Subjects with Hereditary Angioedema
Authors: Joshua S. Jacobs, Paula J. Busse, Aleena Banerji, Mustafa Shennak, William R. Lumry, Mark A. Davis-Lorton, H. James Wedner, James W. Baker, Jonathan A. Bernstein, Richard F. Lockey, H. Henry Li, Timothy J. Craig, Marco Cicardi, Marc A. Riedl, Ahmad Al-Ghazawi, Carolyn Soo, Ryan Iarrobino, Daniel Sexton, Christopher TenHoor, Ryan Faucette, Joseph C. Biedenkapp, Yung H. Chyung, Burt Adelman
Journal: Journal of Allergy and Clinical Immunology (2016)
Inhibition Of Erythropoiesis By Iron Overload Is Mediated Through TGFβ Signaling
Authors: Krishna Gundabolu, Huiyong Chen, Huihui Li, Lohith Shakaladevanapura, Tushar D. Bhagat, Nishant Vallumsetla, Yelena Ginzburg, Amit Verma
Journal: Blood (2013)
Abstract 823: Mechanisms of Septal Flash in Left Bundle Branch Block
Authors: Ola Gjesdal, Espen Remme, Anders Opdahl, Helge Skulstad, Kristoffer Russell, Erik Kongsgard, Otto Smiseth, Thor Edvardsen
Journal: Circulation (2008)

Objective: Septal beaking or flash (SF) is seen in LBBB as abrupt leftward preejection displacement of septum, and has been suggested as predictor of successful CRT-treatment. Similar septal motion...
Immunotherapy of Murine Leukemia. V. Protection Against Friend Leukemia Virus-Induced Immune Complex Glomerulonephritis by Passive Serum Therapy&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: F Sanfilippo, E V Genovesi, J J Collins
Journal: JNCI Journal of the National Cancer Institute (1981)

The development of immune complex glomerulonephritis in DBA/2 mice infected with Friend murine leukemia virus (F-MuLV) was compared with that in mice protected against virus-induced disease by administration of chimpanzee anti-F-MuLV antiserum (CaF-MuLV). Morphologic analysis of glomeruli from viremic (infected) normal chimpanzee serum-treated animals revealed significant renal disease within 2 weeks following virus inoculation, with glomerular immune complex deposits and C-type viral particles seen by electron microscopy. Localization of F-MuLV envelope and core antigens (gp71 and p30, respectively) was also detected by immunofluorescence, as was murine IgG and C3. However, age-matched DBA/2 mice treated with CaF-MuLV antiserum alone or following F-MuLV inoculation showed no evidence of systemic disease and neither localization of F-MuLV antigens nor detectable virus particles. These data indicate that in addition to erythroleukemia, F-MuLV infection results in severe immune complex glomerulonephritis and that passive immunotherapy can protect susceptible mice from both aspects of viral pathogenesis.
Randomized trial of interferon maintenance in multiple myeloma: a study of the National Cancer Institute of Canada Clinical Trials Group.
Authors: G P Browman, D Bergsagel, D Sicheri, S O'Reilly, K S Wilson, S Rubin, A Belch, C Shustik, R Barr, I Walker
Journal: Journal of Clinical Oncology (1995)

PURPOSE To determine whether interferon maintenance therapy improves overall survival and response duration in patients with multiple myeloma who have responded to induction therapy with melphalan and prednisone. PATIENTS AND METHODS In a multicenter trial, patients with symptomatic clinical stage I and stage II and III multiple myeloma were registered at diagnosis and those who responded to melphalan-prednisone (MP) were randomized either to receive interferon (2 mU/m2) subcutaneously three times per week or no maintenance. MP was discontinued in both groups once a stable response plateau of the monoclonal protein was reached. Interferon was continued until relapse, and then was restarted on subsequent response to MP. Interferon toxicity was recorded using a self-report diary. Survival and response duration were calculated using life-table methods, and were adjusted in the analysis for imbalances in baseline prognostic factors. RESULTS Four hundred two patients were registered and 176 responders were randomized (85 to interferon and 91 to control). At a median follow-up time of 43 months, the median survival duration was 43 months for interferon and 35 months for control (P = .16), but when adjusted for chance imbalances in baseline prognostic factors (mainly performance status), the median survival duration was 44 months and 33 months for interferon and control, respectively (P = .049). Progression-free survival from randomization to first relapse also favored interferon (unadjusted P &lt; .002; adjusted P &lt; .003). Interferon toxicity caused 58% of patients to reduce their dose, of which 84% were able to return to the initial dose; 14% had to discontinue interferon treatment. CONCLUSION Interferon maintenance therapy improves progression-free and overall survival of patients with multiple myeloma who respond to melphalan and prednisone. Toxicity is substantial and must be weighed by patients against the potential benefits in response duration and survival.
SEQUENTIAL PEGINTERFERON ALPHA-2A AND TELBIVUDINE OR VICE VERSA FOR HBEAG-NEGATIVE CHRONIC HEPATITIS B: PRELIMINARY END-OF-TREATMENT RESULTS OF THE TEL-B-PEG RANDOMIZED TRIAL
Authors: Paola Piccolo, Ilaria Lenci, Di Paolo Daniele, Luigi Demelia, Orazio Sorbello, Lorenzo Nosotti, Mario Angelico
Journal: Hepatology (2011)
A phase II trial of celecoxib in PSA recurrent prostate cancer after definitive radiation therapy or radical prostatectomy
Authors: R. S. Pruthi, E. Derksen
Journal: Journal of Clinical Oncology (2004)

4593 Purpose: COX-2 inhibitors have also been shown to have anti-neoplastic effects in a variety of tumor types including prostate cancer. This trial evaluated the efficacy of COX-2 inhibitor celecoxib in PSA-recurrent prostate cancer after radiation therapy (XRT) or radical prostatectomy (RP). Methods: 24 patients with rising PSA after definitive XRT (n=4) or RP (n=20) were treated with celecoxib at 400 mg/day (n=12) or 800 mg/day (n=12) (bid dosing). PSA levels were obtained at 3, 6, and 12 months after initiation of treatment. Data was evaluated by calculating 1) PSA doubling times (PSADT) and 2) slope of logPSA vs. time before and after celecoxib treatment at each time point. Testosterone levels were also obtained. Results: 22 of 24 (92%) patients had an inhibitory effect on their serum PSA after 3 mos of treatment: 8/24 had a decline and 3/24 had stabilization of their PSA. Of the remaining 13 patients, 11 had slowing of their PSADT - mean increase (i.e. slowing) in PSADT of 4.5-fold from pre-treatment. Only 2 patients (12%) had no initial change in their PSADT at 3 mos., yet both patients eventually showed increase of PSADT (2.2-fold and 4.0-fold) by 12 mos. Short-term responses at 3 mos. continued at 6 and 12 mos. of treatment. There was a significant shift of patients with rapid towards slower/stable PSADT at all time points (p = 0.008) (table). Comparison of rate of PSA rise before vs. after celecoxib treatment showed significant flattening of mean slope of logPSA vs. time from pre-treatment (1.48) vs. 3 mos. (0.09), 6 mos. (0.35) and 12 mos. (0.46) (p < 0.05 for each time point), There was no significant change in testosterone levels suggesting an androgen-independent mechanism. Conclusions: COX-2 inhibitors may decrease serum PSA levels in patients with biochemical progression after XRT or RP. These results suggest that COX-2 inhibitors may help delay disease progression in these patients. No significant financial relationships to disclose.
Urgent action on UK air pollution is needed, say experts
Authors: Gareth Iacobucci
Journal: BMJ (2016)

The United Kingdom needs to take urgent action on air pollution, which contributes to 40 000 deaths a year, says a report from two royal colleges.

The report from the Royal College of Physicians and the Royal College of Paediatrics and Child Health showed evidence that air pollution causes harm “from a baby’s first weeks in the womb all the way through to the years of older age.”1

The report described the adverse effects of air pollution on the development of the fetus, including lung and kidney development and risk of miscarriage; the link between air pollution and asthma, diabetes, dementia, obesity, and cancer; and the increased risks of heart attacks and strokes in later life.

As well as looking at outdoor pollution, the report highlighted the effects of indoor air pollution—caused …
Predicting the biologic classification of phyllodes tumors from preoperative core needle biopsy and imaging findings.
Authors: Saba Yasir, Erica L Martin-Macintosh, Edwin O Onkendi, Rafael E. Jimenez, Robert T. Fazzio, Grant M. Spears, Sarah Jenkins, Tina J. Hieken
Journal: Journal of Clinical Oncology (2014)

86 Background: Phyllodes tumors (PT) are rare breast neoplasms confounding their systematic study and evidence-based management guidelines. There is little data on the sensitivity of preoperative core needle biopsy (CNB) and imaging findings in establishing a correct preoperative diagnosis. We undertook this study to evaluate the sensitivity of CNB histologic findings and imaging findings in preoperatively categorizing tumors as benign or borderline/malignant. Methods: We identified 47 patients who underwent surgical resection of a PT at our institution after a preoperative CNB between 6/2000-3/2012. Statistical analysis utilized Wilcoxon rank-sum, chi-square or Fisher’s exact tests, and 95% confidence intervals (CI) are reported. Results: 30 patients had a final diagnosis of benign and 17 of borderline/malignant PT. The latter were significantly more often palpable (76.5% vs 36.7%, p=0.01). No other clinical or radiologic feature predicted borderline/malignant subtype, although irregular shape on US was suggestive (70.6% vs 44.8%, p= 0.09). CNB diagnosis by tumor type is summarized in the table. No benign PT had ≥10 mitoses, necrosis or marked stromal atypia on CNB. No case with absent mitoses on preoperative CNB was a borderline/malignant PT; however 77% of benign PT did exhibit mitoses on CNB. Sensitivity of CNB for PT overall was 48.9% (95% CI: 35.3-62.8%) while it was 40% (24.6-57.7%) for benign PT and 17.6% (6.2-41.0%) for borderline/malignant PT. Conclusions: Marked stromal atypia, ≥10 mitoses and necrosis were rare on CNB, but suggestive of malignancy. No imaging or histology feature reliably distinguished between tumor types. Over one-third of borderline/malignant PT had a preoperative CNB diagnosis of fibroadenoma or cellular fibroepithelial lesion emphasizing the low sensitivity of CNB and the need for judicious consideration of definitive surgical excision. [Table: see text]
Phase II study of combination therapy with liposomal doxorubicin and carboplatin in patients with previously untreated small cell lung cancer
Authors: B. L. Rapoport, C. Slabber, D. A. Vorobiof, A. S. Alberts, A. Uys
Journal: Journal of Clinical Oncology (2004)

7349 Background: A recent phase I study of the combination of CBDCA and Caelyx conducted at The Medical Oncology Centre of Rosebank, Johannesburg has shown that CBDCA at area under the curve (AUC) 5 and Caelyx 50mg/m2 given every 4 weeks, could be combined with acceptable toxicity. Methods: The objective of this phase II study is to determine efficacy and toxicity of Caelyx at a dose of 50mg/m2 in combination with CBDCA (AUC = 5), in patients with chemo-naïve small cell lung cancer. Cycles are repeated every 28 days. Results: Twenty-three patients have been entered to date. There are 17 males and 6 females. The median age is 63 years (range 42–73). The majority of patients (77%) presented with an ECOG PS of 0 - 1, despite the fact that more than 80% of patients had extensive disease at onset of treatment. A total of 86 cycles have been administered, with a median of 4 cycles (range 1–6). At this stage 17of the 23 patients are evaluable for response. One patient withdrew consent, one patient died of pneumonia after 1 cycle and 4 patients are too early for evaluation. Documented responses include 3 complete and 6 partial responses. Five patients have stable disease and 3 patients progressed. Haematological toxicity includes anaemia (grade I-II: 8 patients; grade III: 5 patients), neutropenia (grade I-II: 8 patients; grade III-IV: 4 patients) and thrombocytopenia (grade -II: 5 patients; grade III-IV: 3 patients). One patient developed febrile neutropenia. Non haematological toxicity includes PPE (grade I-II: 11 patients), nausea and vomiting (grade I - II in 4 patients), stomatitis (grade I-II: 6 patients; grade III-IV: 1 patient) and aesthenia (grade I-III: 10 patients). No renal toxicity has been observed. Conclusions: The combination of Caelyx at a dose of 50mg/m2 with CBDCA at AUC = 5 appears to be a safe and active first line chemotherapy regime for extensive disease small cell lung cancer. Treatment is well tolerated. The study is ongoing. No significant financial relationships to disclose.