tbuckley/cabot-search huggingface dataset:
Childhood wheeze phenotypes and atopy over adolescence
Authors: Caroline Lodge, Adrian Lowe, Katrina Allen, Melanie Matheson, Paul Thomas, Catherine Bennett, Christine Axelrad, Bircan Erbas, Cecilie Svanes, David Hill, Clifford Hosking, Michael Abramson, S. Dharmage
Journal: European Respiratory Journal (2014)

Background  Atopy is linked with asthma severity and persistence in childhood, but adolescent atopic outcomes of wheeze phenotypes defined by latent class analysis (LCA) are unknown.  Aim  Determine adolescent atopic outcomes of LCA defined childhood wheeze phenotypes (0-7 years)  Method  A high-atopy risk birth cohort recorded atopic outcomes (sensitization, eczema, hay fever and expired Nitric oxide [eNO]) at 12(N=375) and/or 18 years(N=411). Regression analyses investigated associations between atopic outcomes and phenotypes of: Early Transient, Early Persistent, Intermediate Onset and Late Onset wheeze, whilst adjusting for confounders including baseline 9atopic variables9.  Results  Although all persistent wheezing phenotypes had increased risk of atopy, Intermediate Onset (onset at ∼ 1.5-2years) was the most atopic group, whilst Early Transient had a reduced risk.  Conclusion  Adolescent atopy risk differs between childhood wheeze phenotypes. Intermediate onset wheeze is the most atopic, whilst findings on Early Transient wheeze may reflect protective effects of early life microbial exposure. These differences may inform long term prognosis and provide clues concerning aetiology.
A phase II trial of oral S-1 combined with gemcitabine in patients with unresectable biliary tract cancer
Authors: K. Nakamura, T. Yamaguchi, K. Sudo, T. Hara, T. Denda, R. Azemoto, T. Ishihara, T. Tsuyuguchi
Journal: Journal of Clinical Oncology (2009)

e15527 Background: Optimal chemotherapy for unresectable biliary tract cancer is yet to be defined. We have conducted the phase II trial of Gemcitabine (GEM) with S-1, oral fluorouracil prodrug tegafur combined with two modulators, 5-chloro-2, 4-dihydropridine and potassium oxonate to evaluate the activity and toxicity of such combination in patients with unresectable biliary tract cancer. Methods: Eligibility criteria were pathologically-proven biliary tract cancer, appropriate performance status 0 to 2, age 20 to 79 years, adequate hematological, renal and liver functions, no prior chemotherapy, and written informed consent. S-1 was given orally (30mg/m 2 ) bid for 14 consecutive days and GEM (1000mg/m 2 ) was given on day 8 and 15. Cycle was repeated every 21 days. Results: 30 patients with unresectable biliary tract cancer (Gall-bladder: intrahepatic bile ducts: extrahepatic bile ducts=7:16:7) were enrolled from March 2007 to December 2008. Patients characteristics were: median age; 67 (46–79), male/female; 20/10, PS 0/1/2; 16/13/1. Median number of cycles was 8 (range 1 to 14). Out of total 26 evaluable patients, objective responses were observed in 9 patients (30%); 16 patients achieved stable disease and 1 patients showed disease progression. Median survival was 390 days (95% c.i.: 290 - 490 days). The grade 3–4 toxicities observed were leucopenia (20%), neutropenia (40%), anemia (17%), thrombocytopenia (37%), anorexia (7%), fever (10%), rash (7%) and interstitial pneumonia (7%). Conclusions: The combination chemotherapy with GEM and S-1 was well tolerated and high response rate has been observed. This result is very promising but survival benefit against GEM monotherapy should be demonstrated in future phase 3 studies. No significant financial relationships to disclose.
Study of Human Rectal Epithelial Cells &lt;italic&gt;In Vitro&lt;/italic&gt;. II. H&lt;sup&gt;3&lt;/sup&gt;-Thymidine Incorporation Into Polyps and Adjacent Mucosa&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Eleanor E. Deschner, Martin Lipkin, Cyril Solomon
Journal: JNCI Journal of the National Cancer Institute (1966)

The incorporation of H3-thymidine (H3TdR) into epithelial cells of colonic mucosal excrescences and mucosa adjacent to the excrescences was studied in vitro. The findings were compared with the incorporation pattern of H3T dR in normal rectal tissue. In all excrescences examined, epithelial cells located in the upper third and surface of the crypts incorporated H3TdR. In mucosa adjacent to excrescences containing evidence of hyperplasia, the same abnormality was always found. In mucosa adjacent to excrescences when no microscopic evidence of pathologic abnormality was present, this alteration was sometimes seen. These areas may, on occasion, be Foci of future polyp activity prior to the macroscopic appearance of newly formed excrescences. The data presented support the concept that papillomas and adenomas are derived from surface epithelium.
Transplacental Effects of Diethylnitrosamine in Syrian Hamsters as Related to Different Days of Administration During Pregnancy2
Authors: Ulrich Mohr, Hildegard Reznik-Schüller, Gerd Reznik, Jörn Hilfrich
Journal: JNCI Journal of the National Cancer Institute (1975)

Female Syrian hamsters were given a single sc dose of 45 mg diethylnitrosamine (DEN)/kg body weight on 1 of the 15 days of pregnancy. In the offspring of females treated on 1 of the first 11 days of pregnancy, no respiratory tract tumors were found. The offspring of mothers given DEN on 1 of the last 4 days (12-15) of pregnancy developed respiratory tract neoplasms at a rate of up to 95%. A lower incidence of tumors in other organs seemed independent of the day of DEN treatment.
Maintenance rituximab (MR) compared to observation (OBS) after R-CHOP or CHOP in older patients (pts) with diffuse large B-cell lymphoma (DLBCL): An Intergroup E4494/C9793 update
Authors: V. A. Morrison, E. A. Weller, T. M. Habermann, P. A. Cassileth, J. B. Cohn, R. D. Gascoyne, B. Woda, R. I. Fisher, B. A. Peterson, S. J. Horning
Journal: Journal of Clinical Oncology (2007)

8011 Background: Maintenance therapy is generally not used in treatment of DLBCL. However, older pts are a unique group in which to study this approach, due to poorer outcome. Methods: As part of intergroup trial E4494/C9793, 415 pts &gt;= 60 years (yr) of age with DLBCL who responded to induction therapy with CHOP or R-CHOP were randomized to MR (rituximab, 375 mg/m 2 weekly {wk} X 4 every 6 months for 2 yr) starting 4 wk after the last chemotherapy (n=207) or observation (OBS, n=208) in a prospective 2 × 2 randomized trial design (J Clin Oncol 2006;24:3121). Impact of MR on failure-free survival (FFS) was the primary objective, and impact on time to failure (TTF) and overall survival (OS) were secondary objectives. All p-values are two-sided. Results: Results are presented for 352 centrally reviewed evaluable pts, with a median follow-up after maintenance randomization of 5.5 yr. All results were similar for the intent-to-treat population. Baseline characteristics and response to induction therapy are balanced among the CHOP/R-CHOP pts. At 6 yr, FFS was 46% for those pt who received MR and 36% for the OBS cohort (p=0.005, hazard rate {HR} 0.64); 6-yr OS was 62% for MR and 64% for OBS (p=0.83, HR 0.96). Outcome was also examined in the four treatment subgroups. The 6-yr FFS were: CHOP+MR 44%, CHOP+OBS 35%, R-CHOP+MR 47%, and R- CHOP+OBS 40%. No differences in 6-yr OS were observed according to maintenance randomization following CHOP (57% MR vs 55% OBS) or R-CHOP (67% MR and 72% OBS). Median TTF after maintenance randomization following CHOP+MR was 5.2 yr vs 1.6 yr for CHOP-OBS (p=0.0004), and following R-CHOP+MR was 5.6 yr vs 5.4 yr with R-CHOP-OBS (p=0.50). Proportionately more of the treatment failures occurred within 2 yr after CHOP+OBS (85%) compared to CHOP+MR (61%), p=0.01. In contrast, the proportion of failures within 2 yr was similar for R- CHOP+OBS (47%) and R-CHOP+MR (53%), p=NS. Conclusions: MR after CHOP, but not after R-CHOP, significantly prolongs TTF, but fails to prolong OS, possibly due to a delayed pattern of relapse and/or the efficacy of rituximab in the salvage setting. As 6-yr FFS declined to &lt;50% among R-CHOP responders, with or without MR, there is a need for more effective treatment strategies in older DLBCL pts. No significant financial relationships to disclose.
Impact of age on chemoradiation (CRT) for locally advanced non-small cell lung cancer (NSCLC).
Authors: J. L. Dallas, J. E. Sullivan, C. E. Riggs, W. Hou, K. D. LaPlant, T. J. George, P. Louzon, J. W. Lynch, J. L. Close
Journal: Journal of Clinical Oncology (2010)

e19615 Background: Nearly 25% of patients with NSCLC are diagnosed with locally advanced (surgically unresectable, stage IIIA and IIIB) disease, for which CRT is considered to be the standard of care. A commonly used regimen combines weekly paclitaxel and carboplatin (PC) CRT followed by two cycles of consolidative PC, and showed a median survival of around 16 months. The majority of the patients in the trial were aged less than 70 years, although SEER data suggests that more than one third of patients with NSCLC are older than 70. Methods: Retrospective data from 100 patients with locally advanced NSCLC treated at the VA Medical Center in Gainesville, Florida from 2005 to 2009 were analyzed to determine the overall survival in this population as well as to evaluate for prognostic factors. Age, BMI (body mass index) and weight change, baseline hemoglobin values, and PFTs (pulmonary function tests, FEV1 and DLCO) were evaluated. Results: The median age for our sample was 65 with 38% 70 years or older. The median overall survival (OS) was 12.3 months with 50% alive at one year and 18% at three years. Median OS for patients receiving CRT was 14.8 months and 4.8 for those not receiving CRT (includes sequential therapy). Results by age group are included in the Table. 80% of patients <70 years received CRT, compared with only 47% of patients ≥70 years. Multivariate analyses showed no significant correlation between survival and BMI, weight loss, hemoglobin, and PFTs. Conclusions: The data suggest a trend toward worsened survival in patients ≥70 years. Patients who received CRT showed improved survival, irrespective of age. This is likely impacted by selection bias. More tolerable and effective therapies for the elderly are needed. Median OS 1-year OS 3-year OS Age < 70 years 14.8 60% 16% Age ≥ 70 years 9.7 38% 10% p = 0.0792 No significant financial relationships to disclose.
Cytogenetically aberrant cells in the stem cell compartment (CD34+lin-) in acute myeloid leukemia
Authors: Bhoomi Mehrotra, Tracy I. George, Kris Kavanau, Herve Avet-Loiseau, Dan Moore, Cheryl L. Willman, Marilyn L. Slovak, Susan Atwater, David R. Head, Maria G. Pallavicini
Journal: Blood (1995)
Correlation of expression of haptoglobin and recurrence in head and neck squamous cell cancer.
Authors: Y. Su, C. Lee, S. Hong, H. Lin, S. Li, C. Yu, Y. Tung
Journal: Journal of Clinical Oncology (2010)

5543 Background: The aim of this study was to determine whether cellular expression of haptoglobin in is associated with prognosis head and neck squamous cell carcinoma (HNSCC). Methods: Western blotting was carried out to investigate the expression of haptoglobin in oral cancer cell lines. We studies patients with HNSCC without distant metastasis at diagnosis. The cellular expression of haptoglobin was determined and the prognostic significance of cellular haptoglobin was further analyzed. Pearson's χ2-test was used to analyze the correlations between cellular haptoglobin and clinical characteristics of HNSCC. 72 patients with newly diagnosed HNSCC who were treated with curative modality were enrolled in this study. Kaplan-Meier survival curves and log-rank test were used to compare recurrence, distant metastasis, and overall survival of patients according to cellular expression of haptoglobin in cancer tissues. Survival analysis was completed with Cox proportional hazard models. Results: Western blotting analysis showed that haptoglobin protein was expressed in four oral cancer cell lines and the expression increased in serum-free state. Furthermore, tumor over-expression of haptoglobin (i.e., >50%) had significantly more recurrences than those with low- level expression (i.e., <25%) (p=0.045). However, there were no significant differences noted in distant metastasis, and death (p=0.173, and 0.181, respectively). HNSCC patients with high-level expression of haptoglobin had poor recurrence-free survival rates, compared with low-level expression patients (p=0.044). Cox regression model showed that over-expression of haptoglobin was associated with an increased risk for recurrence (hazard ratio [HR] 3.2; 95% confidence interval [CI], 1.127-8.895; p=0.029) after adjusting age, gender, disease site, stage, and treatment modality. Conclusions: Altogether, the data presented show that cellular expression of haptoglobin is closely related to recurrence rate in HNSCC patients. The elevated risk of relapse was confirmed in a multivariate analysis. The cellular expression of haptoglobin may be a prognostic factor in HNSCC No significant financial relationships to disclose.
Development and validation of a prediction model for early death among cancer patients participating in phase I clinical trials of new cytotoxic agents
Authors: M. E. Bonneterre, N. Penel, T. Bachelot, L. Pascal, J. Y. Blay, J. Delord, A. Adenis, J. Bonneterre
Journal: Journal of Clinical Oncology (2008)

2537 Background: Selecting cancer patients for phase I clinical trials of new cytotoxic agents remains an ethical and clinical dilemma. Given the lack of clear and reliable guidance for the estimation of life expectancy, we retrospectively assessed predictive factors for early death (within 90 days following inclusion) among these patients. Methods: 137 consecutive cancer patients enrolled in cytotoxic phase I studies at Oscar Lambret Cancer Centre were included in the model development database. Univariate and multivariate analysis (logistic regression model) were undertaken to determine the predictive factors. A probability tree described the rate of early death in the different prognostic subgroups. This score was then evaluated on a second independent cohort of 128 patients treated at Léon Berard Cancer Centre and checked for consistency. Results: The median overall survival was 8.3 months in the development dataset population; the rate of early death was 17%. The univariate analysis identified the following poor prognostic factors: Melanoma (OR=4.06), Pancreas cancer (OR=3.02), Performance status>0 (OR=2.15), lymphocytes<700/mm3 (OR=2.20), granulocytes ≥ 5,000/mm3 (OR=2.55) and albumin<38 g/l (OR=4.34). In multivariate analyses, the 2 predictive factors for early death were: albumin <38 g/l (OR=5.01 [1.97–10.2],p=0.0001) and lymphocytes count up to 700/mm3 (OR=3.45 [1.39–6.71], p=0.0008). According to these 2 parameters, 3 prognostic subgroups were defined with early death rates of, respectively 6/81 (7%), 6/43 (14%) and 12/13 (92%). In the validation dataset, the rates in the 3 subgroups were, respectively, 13/68 (19%), 20/57 (35%) and 3/3 (100%), thus confirming the value of both predictive factors. Conclusions: According to these results, we do not recommend the trial enrollment of patients with albumin < 38g/l and lymphocytes < 700/mm3. Our model is helpful to objectively discriminate ‘patients with reasonable life expectancy‘ as defined in most protocols. Similar studies are necessary for phase I clinical trials investigating molecular targeted therapies and those investigating immunotherapies. No significant financial relationships to disclose.
Abstract 203: Differences Between Mammalian and <i>Drosophila</i> Mitochondrial Calcium Handling Help Identify Mechanisms Regulating the Permeability Transition.
Authors: Dipayan Chaudhuri, David E Clapham
Journal: Circulation Research (2014)

Studies of cardiomyocyte death during calcium overload induced by ischemia-reperfusion injury or heart failure have implicated the mitochondrial permeability transition as a key pathway. During the permeability transition, an opening of a channel in the inner membrane leads to mitochondrial depolarization and swelling. Despite extensive studies in mammalian systems, the machinery responsible for this phenomenon remains only partially identified. If present in non-mammalian species, the components of the permeability transition may be further elucidated, given potential advantages within these systems for high-throughput screens. However, the existence of a permeability transition remains controversial in non-mammalian organisms. In Drosophila , prior studies have documented calcium-induced mitochondrial depolarization, but no obvious swelling. Here we show that Drosophila S2R+ cells do possess the machinery for permeability transition, but that the threshold for a calcium trigger is significantly higher than in mammalian systems. Using a calcein-loading method, we show that Drosophila permeability transition can be triggered by calcium overload, using ionomycin, and by cysteine oxidation, using phenylarsine oxide. As in mammalian systems, blockade of mitochondrial cyclophilin or the ATP/ADP transporter appears to inhibit the Drosophila permeability transition. Finally, we examine three alternative hypotheses that may explain these differences in permeability transition. First, we test if perturbing the pathways for calcium influx into S2R+ mitochondria can trigger this phenomenon. Second, we test if the discrepancy in the calcium threshold is due to structural differences in the key regulators, particularly the mitochondrial cyclophilin. Third, we compare Drosophila and human genomes to see if any novel molecules may be responsible for setting the lower threshold for calcium-induced permeability transition in mammalian cells. Since the Drosophila cells possess such significant resistance to permeability transition, the results of our investigations suggest potential new strategies for the development of therapeutics inhibiting mitochondrial permeability transition in cardiac calcium-induced injury.
Targeting of glioblastoma with activated T cells armed with anti-CD3xanti-HER2/neu (HER2Bi) and anti-CD3xanti-EGFR (EGFRBi) bispecific antibodies
Authors: I. M. Zitron, O. Norkina, Z. Al-Kadhimi, G. R. Barger, L. G. Lum, S. Mittal
Journal: Journal of Clinical Oncology (2009)

3038 Background: Malignant gliomas are the most common primary brain tumors in adults. The prognosis for patients with glioblastoma remains poor despite aggressive multimodality treatment including surgery and chemoradiotherapy. The receptor tyrosine kinases EGFR, mutant EGFR (EGFRvIII), and HER2/neu are expressed on the majority of glioblastomas and are potential targets for activated T cells (ATCs) armed with bispecific antibodies (BiAbs). Methods: ATCs were generated from human peripheral blood mononuclear cells (PBMC) by culture for 14 days with monoclonal anti-CD3 and interleukin-2 and armed with HER2Bi and/or EGFRBi. HER2Bi- and/or EGFRBi-armed ATCs were examined for in vitro cytotoxicity (MTT and 51 Cr release assays) against long-term malignant glioma lines (U87MG, U118MG, and U251MG) as well as primary glioblastoma lines derived from surgical specimens. Expression of EGFR and HER2/neu were evaluated by FACS. Anti-CD133 coated magnetic microbeads were used to separate CD133-positive and CD133-negative cell populations. Results: EGFRBi-armed ATCs killed up to 85% of U87, U118, and U251 targets. HER2Bi-armed ATCs exhibited comparable cytotoxicity against U118 and U251, but did not kill HER2-negative glioma U87. Cytotoxicity exhibited by either HER2Bi- or EGFRBi-armed ATCs against four primary glioblastoma cell lines was 50–80%. We found that both CD133-negative and CD133-positive cell populations were susceptible to killing by armed ATCs. When we armed ATCs simultaneously with HER2Bi and EGFRBi, killing by doubly armed ATCs was equal to or greater than that by EGFRBi-armed ATCs against the tested cell lines. Conclusions: BiAbs efficiently target ATCs to kill EGFR and/or HER2/neu expressing glioblastomas. Long-term malignant glioma cell lines and primary lines derived from surgical specimens are equally susceptible. Both CD133-negative and CD133-positive (the putative glioma stem cells) are killed. ATCs armed with BiAbs represent a potentially valuable adjuvant to current treatment. No significant financial relationships to disclose.
Phase I and pharmacokinetic study of NC-6004, a new platinum entity of cisplatin-conjugated polymer forming micelles
Authors: R. H. Wilson, R. Plummer, J. Adam, M. M. Eatock, A. V. Boddy, M. Griffin, R. Miller, Y. Matsumura, T. Shimizu, H. Calvert
Journal: Journal of Clinical Oncology (2008)

2573
Hepatic artery ligation and portal vein infusion for liver metastases from colon cancer.
Authors: L R Laufman, T A Nims, J T Guy, J F Guy, S Courter
Journal: Journal of Clinical Oncology (1984)

Localized treatment of liver metastases from colon cancer has yielded better results than has systemic therapy. We report 19 patients with metastatic colon cancer whose bulk disease was limited to the liver, but was not amenable to surgical resection. Many of these patients had poor prognostic features: 14 had greater than 30% replacement of the liver, five had poorly differentiated tumor, and five had previously failed to respond to systemic chemotherapy. All were treated with hepatic artery ligation and portal vein infusion of chemotherapy (mitomycin C and 5-fluorouracil). Two patients (10%) died within one month postoperatively. The remaining 17 patients all improved clinically and demonstrated a marked decrease in carcinoembryonic antigen (CEA) levels. Based on follow-up physical exam, liver function tests, computed tomographic scan, and/or laparotomy, there were two complete responses, ten partial responses, four improved, and one indeterminate, for an objective response rate of 63%. Median survival of all patients was 13 months after hepatic artery ligation, and 14 months after diagnosis of liver metastases, with four patients still alive at 13+, 16+, 41+, and 61+ months after hepatic artery ligation. We believe that this form of therapy is an effective, well-tolerated alternative for patients with unresectable liver metastases.