tbuckley/cabot-search huggingface dataset:
Use of Hematopoietic Progenitors in Whole Blood to Support Dose-Dense Chemotherapy: A Randomized Phase II Trial in Small-Cell Lung Cancer Patients
Authors: Penella J. Woll, Nicholas Thatcher, Lynn Lomax, Jackie Hodgetts, S. Ming Lee, Paul A. Burt, Ronald Stout, Tanya Simms, Rowena Davies, Ruth Pettengell
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Small-cell lung cancer (SCLC) is exquisitely chemosensitive, but few patients are cured by conventional chemoradiotherapy. Recent studies suggest that increased cytotoxic dose-intensity might improve survival. In this randomized phase II study, we tested the feasibility of dose intensification using sequential reinfusion of hematopoietic progenitors in whole blood. PATIENTS AND METHODS: SCLC patients with a favorable prognosis were treated with six cycles of ifosfamide, carboplatin, and etoposide (ICE), at 4-week (standard treatment) or 2-week (intensified treatment) intervals. Intensified treatment was supported by daily subcutaneous filgrastim injections and reinfusion of 750 mL of autologous blood collected immediately before each cycle. RESULTS: Fifty consecutive patients were randomized to standard (n = 25) or intensified (n = 25) ICE. A total of 94% completed at least three treatment cycles, and 70% completed six cycles; 96% of treatments were given at full dose. The planned dose-intensity was 1.0 for standard and 2.0 for intensified ICE. The median received dose-intensity for cycles 1 through 3 was 0.99 (range, 0.33 to 1.02) for the standard treatment arm and 1.80 (range, 0.99 to 1.97) for the intensified treatment arm (P &lt; .001). Over all six cycles, the median received dose-intensity was 0.95 (range, 0.17 to 1.03) for the standard treatment arm and 1.60 (range, 0.60 to 2.01) for the intensified treatment arm (P &lt; .001). Febrile neutropenia was more common on the standard treatment arm (84% v 56%), resulting in more days of intravenous antibiotics (median, 10 v 3 days; P = .035). Transfusion requirements were similar in the two groups. CONCLUSION: Sequential reinfusion of hematopoietic progenitors in whole blood can safely support substantial increases in dose-intensity of ICE chemotherapy for SCLC.
Adult survivors of childhood cancer are at high risk of cardiac abnormalities, study finds
Authors: Jacqui Wise
Journal: BMJ (2016)

Adult survivors of childhood cancer are at high risk of cardiovascular disease, research published in the Annals of Internal Medicine has shown. Often the survivors were asymptomatic with cardiac abnormalities occurring at a younger age than usual, and the authors said that research into screening this group of patients was needed.1

Improvements in cancer therapies mean that increasing numbers of patients live many …
<i>Helicobacter pylori</i>and CagA under conditions of iron deficiency
Authors: Jennifer M Noto, Richard M Peek
Journal: Gut Microbes (2015)

Iron deficiency is the most common nutritional deficiency worldwide and compelling evidence has demonstrated that this condition heightens the risk of gastric cancer. Infection with Helicobacter pylori is the strongest known risk factor for the development of gastric adenocarcinoma. Recent work has demonstrated that, under conditions of iron deficiency, H. pylori-induced gastric carcinogenesis is augmented through increased formation of the strain-specific cag type IV secretion system and enhanced delivery of the bacterial oncoprotein CagA into host cells. Although CagA is a potent virulence factor that promotes oncogenic responses, additional studies have now demonstrated that CagA modulates host cell iron homeostasis in vitro and fundamental metabolic functions of the bacterial cell in vivo. Here we discuss these findings and describe working models by which CagA exerts its effects on gastric epithelial cells, with particular emphasis on its potential role in modulation of host iron homeostasis.
Abstract 17516: Improvement of the Endothelial Function in Patients with Atrial Fibrillation: Effect of Sinus Rhythm Restoration by Catheter Ablation
Authors: Hisanori Kanazawa, Hiroshige Yamabe, Seigo Sugiyama, Satomi Iwashita, Tadashi Hoshiyama, Miwa Ito, Hisao Ogawa
Journal: Circulation (2014)

Background: Endothelial dysfunction has been shown to be correlated significantly with the presence of atrial fibrillation (AF). However, it is not clear to what extent restoration of sinus rhythm by catheter ablation (CA) can improve the endothelial function in patients with AF. Objectives: The purpose of this study was to examine the serial change in the endothelial function for 6 months periods following CA in AF patients in whom the AF recurrence was not observed. Furthermore, we compared the endothelial functions of these AF patients obtained before and, 3 and 6 months after CA with that of normal control subjects. Methods: Forty-three normal control patients (control group) and 61 consecutive AF patients who underwent CA of AF and showed no AF recurrence for 6 months after the procedure (AF group) were included. AF group consisted of patients without structural heart disease and the history of AF was 4.7±4.9 years. Endothelial function of these two groups were assessed. All patients assessed their endothelial function by the reactive hyperemia-peripheral arterial tonometry (RH-PAT) and the RH-PAT index (RHI) was measured. The RHI was measured before and 3 month and 6 months after CA in AF group. Then the serial change in the RHI was elucidated in AF group. All measurement of RHI was performed during sinus rhythm both in control and AF groups. Results: The RHI in control group was 2.21±0.46. The RHI in the AF group before CA was significantly lower than that in control group (2.06±0.49 vs. 2.22±0.46, p=0.036). The RHI in AF group 3 months after CA was significantly improved compared with that before CA (2.40±0.59 vs. 2.06±0.49, p&lt;0.001). The RHI 6 months after CA in AF group was also significantly higher than that before CA (2.24±0.53, vs. 2.06±0.49, p=0.048). The RHI at 3 and 6 months after CA in AF group were not different from that of control group (3 months; 2.40±0.59 vs. 2.21±0.46, p=NS, 6 months; 2.24±0.53, vs. 2.21±0.46, p=NS). Conclusions: The endothelial dysfunction was present in AF patients even if the sinus rhythm was observed during measurement of RHI before CA. However, the endothelial function in AF patients was improved to the similar level of the normal control subjects when the sinus rhythm was maintained after CA.
Influence of Immunologic Competence of the Host on Metastases Induced by the 3LL Lewis Tumor in Mice2
Authors: Claude Carnaud, Baruch Hoch, Nathan Trainin
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Influence of Immunologic Competence of the Host on Metastases Induced by the 3LL Lewis Tumor in Mice Get access Claude Carnaud, Claude Carnaud Search for other works by this author on: Oxford Academic PubMed Google Scholar Baruch Hoch, Baruch Hoch Search for other works by this author on: Oxford Academic PubMed Google Scholar Nathan Trainin Nathan Trainin Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 395–399, https://doi.org/10.1093/jnci/52.2.395 Published: 01 February 1974 Article history Received: 01 May 1973 Revision received: 08 August 1973 Accepted: 19 October 1973 Published: 01 February 1974
A clinical phase II study of combination Cisplatinum and Vinorelbine followed by Docetaxel as first-line chemotherapy in metastatic breast cancer
Authors: N. S. El-Saghir, Z. Otrock, Z. Abdel Khalik, H. Yassine, M. Khalifeh, N. Bitar, M. Charafeddine, R. Jalloul, A. Dandashi, A. Shamseddine
Journal: Journal of Clinical Oncology (2006)

10683 Background: Many chemotherapeutic options exist for metastatic breast cancer (MBC) but there is no standard regimen. We tested a sequential combination regimen using Cisplatinum and Vinorelbine (PVn) followed by Docetaxel as first-line chemotherapy in a phase II clinical trial. This is the first study using a non-anthracycline sequential combination chemotherapy of PVn with Docetaxelin MBC. Methods: Thirty-five patients were enrolled. Cisplatin 80 mg/m 2 , which was given on day 1 and Vinorelbine 30 mg/m 2 on days 1 and 8 q3 weeks for 4 cycles. After the 4 th cycle, responding patients received Docetaxel 75 mg/m 2 every 21 days for a maximum of 4 cycles. Patients were evaluated every two cycles and those who had no response were offered other therapy. Patients who showed progression after 2 cycles of PVn were offered Docetaxel but were considered off protocol. Three patients were excluded from analysis because of death unrelated to treatment. Results: After a median follow up of 14 months (range 1–36), 32 patients (91.4%) completed the study. Overall response rate was 53.1%. Complete remission was seen in 5 pts (15.6%), partial response in 12 patients (37.5%), stable disease in 6 patients (18.75%), and progressive disease in 9 patients (28.1%). 20 patients (62.5%) were alive at 12 months. Median time to disease progression was 8 months (range 1–24). At 24 months 37.5% (12 patients) were alive. Response rates to PVn were not significantly improved by sequential addition of Docetaxel. A total of 183 cycles were administered with a median of 6 cycles per patient. Delay of chemotherapy because of Grade II neutropenia occurred in 41/183 cycles (22.4%). Febrile neutropenia was observed in 4 patients (2.2%). Grade II anemia was observed in 40/183 cycles (21.8%) and Grade III in 24/183 cycles (13.1%). Grade II nephrotoxicity occurred in 12 cycles (6.5%) and Grade III vomiting was observed in 31/183 cycles (16.9%). No treatment-related mortality has been reported. Conclusions: Sequential PVn-Docetaxel is a feasible and effective non-anthracycline option as first-line chemotherapy in patients with MBC. More effective Docetaxel may be better used upfront and followed by PVn. This regimen has acceptable toxicity as well. No significant financial relationships to disclose.
Intentional isoniazid overdosage among southwestern American Indians
Authors: M L Sievers, M H Cynamon, T E Bittker
Journal: American Journal of Psychiatry (1975)

A 30-month study explored the degree to which self-destructive behavior compromised tuberculosis therapy and prophylaxis among southwestern American Indians. The frequency of isoniazid (INH) overdosage paralleled the extent of INH usage in each tribe and the entent to which INH was perscribed for each tuberculosis category. The authors recommend the careful selection of patients for INH prophylaxis, the dispensing of small amounts at short intervals, the close monitoring of patient compliance with the prescribed drug regimen, and, possiblly, the dispensing of individually wrapped tablets to inhibit the impulsive ingestion of massive amounts of the drug.
Intracellular Localization of Interleukin-6 in Eosinophils From Atopic Asthmatics and Effects of Interferon γ
Authors: Paige Lacy, Francesca Levi-Schaffer, Salahaddin Mahmudi-Azer, Ben Bablitz, Stacey C. Hagen, Juan Velazquez, A. Barry Kay, Redwan Moqbel
Journal: Blood (1998)
Phase I trial of bevacizumab plus sunitinib in patients with metastatic renal cell carcinoma
Authors: D. R. Feldman, M. S. Ginsberg, M. Baum, C. Flombaum, H. Hassoun, S. Velasco, P. Fischer, N. M. Ishill, E. A. Ronnen, R. J. Motzer
Journal: Journal of Clinical Oncology (2008)

5100 Background: Bevacizumab and sunitinib both have activity in metastatic renal cell carcinoma (mRCC). Combining bevacizumab and sunitinib may increase antitumor efficacy by maximizing inhibition of the VEGF pathway. The safety and maximum tolerated dose (MTD) of sunitinib in combination with bevacizumab was assessed in this Phase I trial. Methods: Cohorts of 3–6 patients (pts) with mRCC received escalating doses of sunitinib (dose levels: 25, 37.5, and 50 mg po) daily for 4 weeks (wks) followed by 2 wks off with fixed-dose bevacizumab (10 mg/kg iv) every 2 wks continuously. Pre- determined dose-limiting toxicities (DLTs) were assessed in the first 6-wk cycle. Results: Of 26 pts (median age 57) enrolled, 25 were treated including 7 (1 replaced) in cohort 1 (sunitinib 25 mg, bevacizumab 10 mg/kg), 6 in cohort 2 (sunitinib 37.5 mg, bevacizumab 10 mg/kg) and 12 (6 for MTD, additional 6 for safety) in cohort 3 (sunitinib 50 mg, bevacizumab 10 mg/kg). Two DLTs of G4 hemorrhage occurred (1 cohort 2, 1 cohort 3). Therefore, the MTD was sunitinib 50 mg plus bevacizumab 10 mg/kg. However, with chronic treatment, additional toxicities were observed, many overlapping, including G3/4 HTN (14/25 overall, 9/12 cohort 3), G3/4 proteinuria (6/25 overall, 4/12 cohort 3), G3 thrombocytopenia (6/12 cohort 3), G3 RPLS (2/12 cohort 3) and G3 microangiopathic hemolytic anemia (2/12 cohort 3). One pt in cohort 2 died of an MI; autopsy showed tumor involvement of the myocardium. Other toxicities were reversible. In total, 10/25 (40%) pts required sunitinib dose reductions (2/6 cohort 2, 8/12 cohort 3) and 11/25 (44%) pts were withdrawn for toxicity (2/7 cohort 1, 2/6 cohort 2, 7/12 cohort 3). The median number of treatment cycles received was 7 for cohort 1 (range 1–14), 3 for cohort 2 (range 1–9) and 4 for cohort 3 (range 1–8). Of 25 pts, 13 (52%) had a confirmed objective response (1 complete response and 12 partial responses). Conclusions: While active, the combination of bevacizumab plus sunitinib in this phase I trial was poorly tolerated at full doses. Chronic therapy resulted in a high proportion of pts experiencing toxicity requiring sunitinib dose reductions and/or study discontinuation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology, Pfizer Oncology
Imexon and gemcitabine are synergistic against human pancreatic cancer cells in vitro and in vivo
Authors: Nicholas O. Roman, Shoji Fukushima, Mary Ann Raymond, Terry Landowski, Robert T. Dorr
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

5884 

Imexon (M.W. 111.1) is an iminopyrolidone aziridine which previously has shown activity against a variety of human cancer types, including multiple myeloma and pancreatic adenocarcinoma. Recently, mechanistic studies in MIA PaCa-2 cells have demonstrated binding to sulfhydryls, buildup of reactive oxygen species (ROS), perturbations in mitochondrial membrane potential, leading to cytochrome C release, activation of caspases 3, 8 and 9, and induction of apoptosis. Since imexon binds sulfhydryls and generates ROS, it was hypothesized that imexon may augment the effects of gemcitabine in two ways: 1) promoting increased oxidative stress in oxidatively challenged cells and 2) interacting with key sulfhydryl-dependent enzymes involved in gemcitabine metabolism. The mean IC50 values for imexon and gemcitabine in four human pancreatic cancer cell lines were 54.2 ± 6.7 μM and 9.2 ± 5.6 nM, respectively. Initially, interactions between imexon:gemcitabine were assessed at a fixed ratio of 1:1, 1:2, and 2:1 using median effect analysis. The PANC-1 human pancreatic cancer cell line demonstrated greater synergy at a fixed ratio of 1:1 of imexon:gemcitabine. When cells were pretreated with imexon or gemcitabine for 24 h, no significant difference was observed compared to concomitant dosing. SCID mice bearing PANC-1 cells were treated with imexon, gemcitabine, or a combination 24 h or 40 d after tumor inoculation. At day 100, the Tumor Growth Inhibition value (T/C) for combination treated mice was 24.4 % and 25.4 % for 24 h and 40 d post tumor inoculation, respectively. To better understand the molecular basis of synergy, cell lysates containing deoxcytidine deaminase (dCD) and ribonucleotide reductase (RNR) were obtained from PANC-1 cells. Imexon concentrations up to 1 mM had no effect on dCD activity, whereas the thiol oxidant, chloromercuri benzoate (CMB), significantly inhibited dCD activity at concentrations ≥ 10 μM. Thus, imexon does not enhance the major inactivation route of gemcitabine. In contrast, recent experiments show that imexon may augment the biochemical pathways which mediate gemcitabine’s cytotoxic activity. Overall, these data demonstrate that imexon is uniquely synergistic with gemcitabine in vitro and in vivo and support the rationale for combining the agents in clinical trials.
Efficacy of the combination of ABT-888 (veliparib) and carboplatin in patients with BRCA-associated breast cancer.
Authors: George Somlo, Paul Henry Frankel, Thehang H. Luu, Cynthia Ma, Banu Arun, Agustin Garcia, Tessa Cigler, Gini F. Fleming, Harold A. Harvey, Joseph A. Sparano, Rita Nanda, Helen K. Chew, Timothy Jerome Moynihan, Linda T. Vahdat, Matthew P. Goetz, Arti Hurria, Joanne E. Mortimer, David R. Gandara, Alice P. Chen, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2013)

1024 Background: The combination of platinum agents and PARP inhibitors may benefit patients (pts) with BRCA-associated metastatic breast cancer (MBC). We report on the response and clinical benefit rates when combining the PARP inhibitor veliparib (V) and carboplatin (carb) in a phase I trial. Methods: BRCA carriers with MBC were eligible. Carb starting at an AUC of 6 was given IV in 21-day cycles (C) and V was given orally twice daily (BID) at dose levels (L) L1 through L5. Results: Twenty-eight pts (26 eligible) carrying BRCA1 (12) or BRCA2 (15), or both (1) mutations were accrued between June 2010 and June 2012. The median age (32-66) was 45 years. The number (#) of prior chemotherapy regimens given for MBC was 1 (0-5); 70% of BCs were ER+, and 7% were HER2+. The schema, dose limiting toxicities (DLT) during C 1, median # of Cs on trial, and maximum tolerated dose (MTD) are shown. There were 3 (12%) complete and 9 (35%) partial responses (PR). Unconfirmed PR or stable MBC (median duration: 8 months [6-10+]) were seen in 7 pts (27%); the clinical benefit rate was74%. The median progression-free survival (PFS) is 7.8 months (95% CI 7.3-9.5). The pt with Fallopian tube cancer had a CR. DLTs with C 1 were seen in 2/6 evaluable pts at L1 (1 pt w/grade 3 hyponatremia and dehydration, and 1pt w/grade 4 thrombocytopenia [PLT]), leading to de-escalation of carb. At L2, 1 pt had grade 4 PLT. At L5, 1 pt had grade 4 PLT, and 2 pts grade 3 PLT (1 pt also experienced grade 4 granulocytopenia [ANC]), defining the MTD at carb AUC 5 and V 150 mg BID (L4). Dose delays and/or dose adjustments due to grade ≥ 2 toxicities for ANC or PLT were seen during the first 3 Cs at L1 (100%), L2 (50 %), L3 (67%), L4 (83 %), and at L5 (67%). Conclusions: The combination of carb and V is active, and is associated with substantial clinical benefit rate and managable hematologic toxicities in BRCA carriers with MBC. Further definition of the role of V is warranted. [Table: see text]
Abstract 44: A Slowly Inactivating Sodium Current Contributes to the Prolongation of the Action Potential in Aging Cardiomyocytes
Authors: Kazuya Isobe, Sergio Signore, Andrea Sorrentino, João Ferreira-Martins, Mehrdad Shafaie, Elisabeth Steadman, Christian Arranto, Fumihiro Sanada, James Kostyla, Hanqiao Zheng, Fabio Del Ben, Claudia Fiorini, Ewa Wybieralska, Anna Sanarico, Polina Goihberg, Marcello Rota
Journal: Circulation Research (2012)

Aging is associated with alterations in the electrical properties of the heart resulting in an increased incidence of arrhythmic events and perturbation of cardiac performance. The aim of the present study was to determine whether the late sodium current (I NaL ), which presents slow inactivation kinetics, is upregulated in myocytes from old hearts contributing to the electrical remodeling of the senescent myocardium. For this purpose, the electrical profile of young (3-5 months) and old (24-30 months) C57BL6 mice was established at the organ and cellular levels. In comparison to young mice, old animals presented enlarged left ventricles and declined systolic and diastolic functions. The QRS complex and QT interval of the ECG were significantly prolonged in old animals, indicating that aging delays the electrical activation and recovery of the myocardium. The latter property was confirmed by slower repolarization phases of epicardial monophasic action potentials (AP) in old hearts, using perfused Langendorff preparations. Moreover, old hearts were more prone to develop arrhythmia by programmed electrical stimulation. By patch-clamp technique, myocytes from old mice showed a 2- and 1.7-fold increase in the time to 50% and 90% repolarization of the AP, respectively, than cells from young animals. In voltage-clamp mode, I NaL , which is operative during the repolarization phase of the AP, was 1.7-fold larger in cells obtained from old hearts with respect to young. Activation, steady state inactivation and time constants for I NaL were comparable in young and old myocytes, indicating that the enhanced late current was mediated by an increased maximal conductance. In old myocytes, blockade of I NaL with low doses of tetrodotoxin or mexiletine reduced by 24-48% the intermediate and late repolarization phases of the AP, whereas in young cells this intervention affected to a lesser extent only the late repolarization phase. Finally, administration of mexiletine in old mice shortened the QT interval by 25%, restoring ventricular electrical recovery. In conclusion, the late sodium current I NaL is upregulated with aging and contributes to the slower repolarization of the senescent myocardium.
Improved Immune Recovery after Transplantation of TCRαβ/CD19 Depleted Allografts from Haploidentical Donors in Pediatric Patients
Authors: Peter Lang, Tobias Feuchtinger, Heiko-Manuel Teltschik, Wolfgang Schwinger, Patrick Schlegel, Michael Schumm, Anne-Marie Lang, Barbara Lang, Carl Philipp Schwarze, Martin Ebinger, Christian E. Urban, Rupert Handgretinger
Journal: Blood (2014)
Specific Impaired CD56+ NK Cell Development in GATA2 Deficiency As Revealed By Ex Vivo NK Expansion
Authors: Moonjung Jung, Jan K. Davidson-Moncada, Chuanfeng Wu, Samson Koelle, Thomas Winkler, Danielle M. Townsley, Amy Hsu, Keyvan Keyvanfar, Steven M. Holland, Dennis D. Hickstein, Richard W. Childs, Cynthia E. Dunbar
Journal: Blood (2014)
Unusual Presentations of Lung Cancer
Authors: Giordano Galeazzi, Anna Di Russo, Roberto Boffi, Franco De Conno
Journal: Journal of Clinical Oncology (2002)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.23.4601 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12454121 Unusual Presentations of Lung Cancer Case 4. Palliative Radiotherapy in Eyelid Non-Hodgkin's Lymphoma Giordano GaleazzixGiordano GaleazziSearch for articles by this author , Anna Di RussoxAnna Di RussoSearch for articles by this author , Roberto BoffixRoberto BoffiSearch for articles by this author , Franco De ConnoxFranco De ConnoSearch for articles by this author Show More National Cancer Institute, Milan, Italy https://doi.org/10.1200/JCO.2002.20.23.4601 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology