tbuckley/cabot-search huggingface dataset:
Antimetastatic activity of Atu027, a liposomal small interfering RNA formulation, targeting protein kinase N3 (PKN3): Final results of a phase I study in patients with advanced solid tumors.
Authors: Dirk Strumberg, Beate Schultheis, W Meyer-Sabellek, C. Vank, F Gebhardt, A. Santel, O. Keil, K. Giese, J. Kaufmann, Joachim Drevs
Journal: Journal of Clinical Oncology (2012)

e13597 Background: Atu027 contains siRNA-lipoplexes, which elicits RNAi mediated suppression on PKN3 in vascular endothelial cells. In various xenograft mouse models, silencing of PKN3 expression and significant inhibition of invasive growth, lymph node and pulmonary metastasis formation was shown. Methods: Atu027 was applied to patients (pts) as a single 4h-infusion with subsequent follow-up for 3 wks. Thereafter pts were treated twice weekly for 4 weeks. In case of SD, pts were treated until PD. Dose escalation was associated with assessment of toxicity, pharmacokinetics (PK), and multiplex biomarker analyses in plasma from treated pts. Results: A total of 33 pts have received Atu027 of 11 dose levels (DL) up to 0.336 mg/kg. No pre-medication was required. No cytokine activation (TNF-α, IL-1β, IFN-γ, IL-6) was observed. In some subjects transient activation of the complement system (C3a, Bb, sC5b-9) was found, but without any clinical relevance. PK-data showed dose-dependent increase in plasma siRNA as well as lipid levels. Among various biomarkers tested, sVEGFR-1 plasma levels decreased significantly upon treatment. Across all dose levels, Atu027 was well-tolerated. Adverse events possibly related to Atu027 were fatigue grade G1 (6pts), hair loss G1 (2pts), sweating G1 (1pt), and abdominal pain G2 (1pt). G3 AEs not considered as DLTs were elevated lipase (2 pts, DL2+DL10) and diarrhea (1 pt, DL5). So far, no DLTs were seen in the last DL. Stable disease after 3 and 6 months was observed in 10 and 3 pts, respectively. Two pts with neuroendocrine cancer had disease stabilization for 9 and 12 months, respectively, including partial regression of pulmonary metastases in 1 pt. Another patient with breast cancer had regression of liver metastases. Conclusions: Atu027 is well-tolerated and anti-metastatic activity has been observed. Soluble VEGFR-1 might serve as a biomarker. So far, 0,336 mg/kg is the recommended dose for further phase II trials.
Treatment of advanced breast cancer with mitomycin C combined with vinblastine or vindesine.
Authors: H S Garewal, R J Brooks, S E Jones, T P Miller
Journal: Journal of Clinical Oncology (1983)

Mitomycin C together with either vindesine or vinblastine was given to 48 patients with previously treated advanced breast cancer. Thirteen (35%) of the 37 evaluable patients had a complete (one patient) or partial (12 patients) response. Overall median duration of response was 189 days (range, 90-700 days). Fifteen patients received mitomycin C and vindesine with six responses (40%) and a median response duration of 247 days (range, 162-700 days). Twenty-two patients received mitomycin C and vinblastine with seven responses (32%) and median response duration of 164 days (range, 90-330 days). Response duration for patients treated with mitomycin C plus vindesine was longer than that associated with mitomycin C plus vinblastine (p = 0.09). Significant toxicity included myelosuppression and neurologic symptoms, but was uncommon (less than 10% of patients). Therefore, the combination of mitomycin C and a vinca alkaloid appears to be useful in far-advanced refractory breast cancer.
Abstract 139: Protective Effects of Cyclosporine A on the Neuronal Mitochondrial Membrane Potential in Asphyxial Cardiac Arrest Model in Rats
Authors: Jie Liu, Qiwei Zhuang, Yue Wang, Fei Han
Journal: Circulation (2013)

Introduction: Opening mitochondrial permeability transition pore (MPTP) has been implicated as an important mitochondrial event during ischemia reperfusion injury. Cyclosporine A (CsA), as an inhib...
Impact of intensified therapy on clinical outcome in infants and children with neuroblastoma: the St Jude Children's Research Hospital experience, 1962 to 1988.
Authors: L C Bowman, M L Hancock, V M Santana, F A Hayes, L Kun, D M Parham, W L Furman, B N Rao, A A Green, W M Crist
Journal: Journal of Clinical Oncology (1991)

To gauge the impact of intensified therapy on the survival of infants (younger than 1 year, n = 129) and children (greater than or equal to 1 year of age, n = 275) with neuroblastoma, we analyzed the results of eight successive clinical trials comparing various combinations of antineoplastic drugs, surgery, and radiotherapy. Changes in treatment did not affect the survival of children with involved noncontiguous lymph nodes or distant metastatic disease until the combination of cisplatin and teniposide (CDDP/VM26) was added to a basic regimen of cyclophosphamide and doxorubicin (CTX/DOX). The resulting 4-year survival was 28% +/- 5% (SE) compared with 7% +/- 2% for previous treatments (P less than .001 by the log-rank test). The 4-year survival of infants with metastatic disease was improved by administering CTX/DOX to all patients, reserving CDDP/VM26 for those whose disease was resistant to the former combination: 82% +/- 6% versus 45% +/- 8% in earlier studies; P less than .001. In the subset of infants whose tumors had disseminated to bone or bone marrow at diagnosis, this therapeutic approach increased the probability of long-term survival from 48% +/- 10% to 85% +/- 9% (P = .01). The small group of children over 1 year of age with localized unresectable tumors also fared significantly better with the switch to CTX/DOX chemotherapy (4-year survival, 93% +/- 7% v 42% +/- 13%; P = .02). Multivariate analysis indicated that young age, limited-disease stage, nonadrenal primary site, and intensified treatment were independent predictors of a more favorable outcome. We conclude that substantial advances in the treatment of neuroblastoma have occurred over the past 25 years at this institution. The current overall 4-year survival probability of 57% +/- 4% compares favorably with estimates for most other common solid tumors of childhood.
The myelodysplastic syndromes: biology and implications for management.
Authors: A F List, H S Garewal, A A Sandberg
Journal: Journal of Clinical Oncology (1990)

Since the initial efforts to characterize the myelodysplastic syndromes in 1976, an extensive body of information has accumulated defining biologic features and the relation to clinical aspects of disease. While the pathogenesis of these disorders remains incompletely understood, laboratory investigations indicate that they are clonal disorders affecting hematopoietic stem cells characterized by a progressive imbalance between self-renewal and differentiation. Despite karyotypic resemblance to acute myeloid leukemia, fundamental biologic differences may underly the disappointing results achieved to date with intensive chemotherapy. The recent availability of recombinant hematopoietic growth factors for use in clinical trials has shown that the maturation defect in many instances can be overcome with administration of lineage-restricted recombinant hematopoietins. Routine use of these promising agents must await results of randomized clinical trials to determine the impact of prolonged treatment on leukemic evolution and disease-related morbidity.
Immune anemias in patients with chronic lymphocytic leukemia treated with chemoimmunotherapy regimen of fludarabine, cyclophosphamide and rituximab as initial therapy
Authors: G. Borthakur, S. O’Brien, W. G. Wierda, D. A. Thomas, J. E. Cortes, H. Kantarjian, S. Lerner, M. J. Keating
Journal: Journal of Clinical Oncology (2006)

6604 Background: Auto-immune hemolytic anemia (AIHA) has been reported with the use of fludarabine in the treatment of chronic lymphocytic leukemia (CLL). Since rituximab has been used to treat AIHA, it was anicipated that rituximab might reduce the incidence of AIHA when combined with fludarabine to treat CLL. We analyzed the incidence of immune anemias in 300 patients (pts) with CLL treated with fludarabine, cyclophosphamide and rituximab (FCR) as initial therapy. Methods: Diagnosis of AIHA was based on clinical evidence of hemolysis (elevated indirect bilirubin, reticulocyte count, lactate dehydrogenase) combined with positive Coomb’s test and/or low haptoglobin level. Pure red cell aplasia (PRCA) was diagnosed based on absence of erythroid precursors in bone marrow aspirate and/or biopsy. Results: 29 of 300 (9.5%) pts with CLL treated on a single-arm study of FCR showed evidence of immune anemias (age range18 to 86 years,median 62 years; 24 male and 5 female). 24 pts had AIHA, 3 had PRCA and 2 pts had positive Coomb’s test only (hemoglobin&gt;10 gm/dL). Higher beta2-microglobin and bone marrow lymphocyte percentage were associated with higher risk of developing AIHA in multivariate analysis. Immune anemia was present in 9 pts prior to FCR treatment, developed in 15 on FCR and in 5 after completion of FCR (1 month to 4 years later). AIHA was detected after a median of 4 cycles (range 1 to 6) in pts who developed it while on therapy. Coomb’s test was positive in 14 pts and negative in 15. Haptoglobin levels were low in 16, normal in 10 and not measured in 3 pts. Coomb’s test was negative in 14 of 16 pts with AIHA and low haptoglobin levels. 9 pts were treated with oral prednisone. Others treatments included cyclosporine, intravenous immunoglobulin, rituximab and splenectomy. 3 of 9 pts who had AIHA prior to starting FCR had sustained correction of anemia with FCR treatment alone. 2 pts had inadequate response to treatment of immune anemia; 1 of them developed myelodysplastic syndrome. Conclusions: The incidence of immune anemias in pts treated with FCR is comparable to other series. Low haptoglobin levels in appropriate clinical context can help to establish the diagnosis of AIHA in the face of negative Coomb’s test. [Table: see text]
Authors’ response ARTICLE
Authors: A Smyth, C Bertenshaw, S Lewis, I Choonara, A Watson
Journal: Thorax (2008)

We welcome Dr Tai’s comments on our paper. We described a case control study of acute renal failure in cystic fibrosis (CF)1 and not a study designed to measure the prevalence, severity or risk factors for renal impairment. Patients with acute renal failure (ARF) were reported to us from 20 UK CF centres and clinical data were extracted retrospectively from the case notes. We therefore adopted a …
Continuous infusion carboplatin on a 21-day schedule: a phase I and pharmacokinetic study.
Authors: E F Smit, P H Willemse, D T Sleijfer, D R Uges, P E Postmus, S Meijer, P M Terheggen, N H Mulder, E G de Vries
Journal: Journal of Clinical Oncology (1991)

A phase I study with continuous infusion carboplatin for 21 days every 6 weeks using a venous access port and portable pump was performed over a dose range of 12 to 32 mg/m2/d, with increments of 2 mg/m2/d. Forty-four patients received 107 courses (median, two; range, one to nine). World Health Organization (WHO) grade III/IV leukopenia and thrombocytopenia occurred in one of seven patients at 30 mg/m2/d, and in two of six and four of six patients at 32 mg/m2/d. Cumulative platelet depression was found at dose levels of 28 mg/m2/d or more. Median glomerular filtration rate (GFR) and effective renal plasma flow, monitored by radioisotope clearances at doses greater than or equal to 20 mg/m2/d, decreased 8.2% (P less than .05) and 10.9% (P less than .01) after two courses. There was a relationship (r = .50, P less than .0002) between the percentage of platelet depression and GFR. No other toxicity was observed. Of the 17 patients who were evaluable, one complete response and four partial responses were observed. In addition, six patients had stable disease. Pharmacokinetic analysis of total and ultrafiltrable platinum (UFPt) was performed by atomic absorption spectrophotometry. Steady-state plasma levels for UFPt were reached after 8 hours. These levels could be detected from the 20 mg/m2/d dose. During steady state, carboplatin dose and UFPt plasma levels were not correlated, but steady-state UFPt and GFR (r = -.27, P less than .05) were. Twenty-four percent of total platinum (Pt) was present as UFPt during steady state (x = 160 +/- 10 micrograms/L). Total body clearance of UFPt exceeded GFR 2.2 times. Mean area under the curve (AUC) for UFPt during continuous infusion was 4,921.8 +/- 301.72 mg.min/L. For total Pt, steady-state plasma levels were not reached; total Pt plasma levels increased between day 7 and day 21 (P less than .0001). There was a significant relation between total Pt serum levels day 7, 14, and 21 and the drug dose administered. Immunohistochemical analysis of DNA-bound Pt in leukocytes showed a linear increase from day 7 to day 14 to day 21 (r = .97) between DNA-bound Pt and duration of infusion in individual patients. The maximum-tolerable dose of carboplatin is 30 mg/m2/d for 21 days (total dose 630 mg/m2) and is recommended for phase II studies.
Colorectal cancer: Autologous immunogenicity in chemotherapy (5FU) pre-treated patients
Authors: E. Lasalvia-Prisco, S. Cucchi, J. Vazquez, E. Lasalvia-Galante, W. Golomar, F. Cotto, R. Otero
Journal: Journal of Clinical Oncology (2004)

2593 Background. -In cancer patients, including colorectal cancer, we have previously reported that vaccination with an Autologous Hemoderivative (AH) elicits Delayed Type Hypersensibility (DTH) associated with an anti-tumoral effect. (E. Lasalvia-Prisco et al, Cancer Biology & Therapy, 2003; ASCO 2003). It was also shown that 5-fluorouracil (5-FU) can upregulate the expression of malignant neo-antigens and MHC molecules in colon cancer cell lines, enhancing their sensitivity to the Cytotoxic T-lymphocytes, suggesting that chemotherapy (5FU) could increase the efficacy of cancer vaccines (PP Correale et al, Int J Cancer, 2003). This study describes the effect of pre-treatment with 5FU upon the immune response elicited by AH in colorectal cancer patients. Methods.-Patients with Metastatic Colorectal Cancer (n=50), 5FU-Leucovorine (NCCTG protocol) resistant, performance status 1–2 (ECOG scale), were included. Written informed consents were obtained and the institutional ethical committee approved the study. The patients were selected and grouped by number of series of 5FU received (2,4,6,8 and 10 series). Induction of immuno-response with AH was performed in each patient with the vaccination procedure above referred. Twenty days after induction, DTH intradermal test with AH was performed. As it was reported, the DTH tested with intradermal AH is concordant with the response upon the autologous tumor target according with the pathology of remnant lesions in responder patients (CD3+ infiltrating lymphocytes). Results- DTH positive responses (≥ 5 mm) were 1 of 10, 2 of 10, 4 of 10, 5 of 10 and 7 of 10 in the groups pre-treated respectively with 2,4,6,8 and 10, 5FU series. There is a statistically significant relationship between the variables: 5FU series and DTH response (P<0.01). Conclusions.-These clinical results are consistent with the reported in vitro results that 5FU enhances the antigenicity of colorectal malignant cells and it suggests that pre-treatment with this chemotherapy agent could enhance the efficacy of malignant cell derivatives as autologous cancer vaccines. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration PharmaBlood, Inc.
Abstract 16878: Cardiomyogenesis in the Aging and Failing Human Heart
Authors: Barbara OgOrek, Marcello Rota, Donato Cappetta, Christian Arranto, Yingnan Bai, Sergio Signore, Fumihiro Sanada, Alex Matsuda, James Kostyla, Maria-Virginia Caballero, Ewa Wybieralska, Matteo Valle, Francesca Polverino, Piotr Filipczak, David A D'Alessandro, Robert E Michler, Federica del Monte, Toru Hosoda, Roberto Boli, Annarosa Leri, Bruce A Buchholz, Joseph Loscalzo, Piero Anversa, Jan Kajstura
Journal: Circulation (2012)

The extent of myocyte formation occurring physiologically and pathologically is controversial. Recently, based on the integration of atmospheric 14C into DNA, the turnover of myocytes in the human ...
Prospective assessment and validation of renal prognostic scores in oncology patients with acute renal failure
Authors: J. Lavilla, J. L. Perez-Gracia, A. Gurpide, E. Rossich, V. Navarro, A. P. Hernandez, L. Arbea, N. Garcia Fernandez, J. M. Aramendia, S. Martin-Algarra
Journal: Journal of Clinical Oncology (2004)

8098 Background: Cancer patients are prone to develop renal complications due to their disease or to treatment. Some prognostic scores have shown to be useful to assess the risk of patients with Acute Renal Failure (ARF). However, none of them has been validated specifically in cancer patients. Therefore, we performed a prospective study to validate in cancer patients commonly used ARF prognostic scores. Methods: Cancer patients with ARF (>20% creatinine increase over baseline), were prospectively included. We collected clinical data (ARF etiology, Karnofsky performance status score -KPSS-, underlying disease and treatment), renal prognostic scores (Liaño's Individual Severity Index -ISI- and Multiorgan Dysfunction Index -MFI-) and analytical parameters (serum creatinine and urine n-acetyl glucosaminidase -NAG-). Statistical analysis (chi-square, ANOVA, multiple regression analysis and logistic regression) was performed with SPSS 9.0. Results: From January 02 to April 03, 149 patients were assessed. Mean age was 57 years and 77% were male. Etiology of ARF was: pre-renal 17%; renal 27%; mixed: 49%; obstructive 3%; unknown 4%. Tumor types were: genitourinary 43%; skin 16%; gastrointestinal 15%; lung: 9%; breast 5%; and others 9%. Specific ARF-related mortality rate was 17% and the main causes of death were cardiovascular (50%) and respiratory diseases (25%). Mean KPSS was 76 (SD 1.26). KPSS was associated (p<0.001) with basal (r = −0.365) and peak creatinine (r = −0.355) and urine levels of NAG, a marker of tubular damage (p<0.001, r =−0.617). KPSS was also associated (p<0.001) with validated renal prognostic scores ISI (r = −0.298) and MFI (r = −0.479). MFI index significantly correlated with survival (p<0.0001) and ISI prognostic value was of borderline significance (p=0.065). Conclusions: MFI index is a useful tool to assess ARF specific mortality risk in cancer patients with ARF. Low KPSS in cancer patients with ARF is associated with greater tubular damage and worse evolution, including higher mortality and risk of multiple organ failure. Adequate preventive measures, early diagnosis and management are crucial in these patients. No significant financial relationships to disclose.
Abstract P049: Meeting Aerobic Physical Activity Guidelines And Hypertension Status Among Us Adults - NHANES, 1999-2006
Authors: Fleetwood Loustalot, Cathleen Gillespie, Zefeng Zhang, Paula W Yoon, Janet E Fulton, Dianna D Carroll
Journal: Circulation (2012)

Introduction: One in three adults in the United States has hypertension, and no significant changes in the prevalence of hypertension have been noted in the past decade. Participation in physical activity can aid in the prevention and control of hypertension, yet prevalence of physical activity participation remains low. The purpose of this study was to assess the prevalence of meeting aerobic guidelines for physical activity by hypertensive status, and to examine the associations between physical activity and hypertension treatment and control. Methods: Data from the National Health and Nutrition Examination Survey 1999-2006 were used to allow for more detailed analyses and due to consistency of physical activity measures. Hypertension was defined by blood pressure (BP) ≥140/90mmHg or taking BP medications; treated (i.e., BP medications) and controlled (&lt;140/90mmHg) hypertension was defined among those with hypertension. Physical activity was categorized by minutes per week of aerobic physical activity based on 2008 Physical Activity Guidelines for Americans (2008 Guidelines) (inactive, &lt;10; insufficiently active, 10-149; active, ≥150-300; highly active, &gt;300). Additional variables included sociodemographic and lifestyle characteristics (i.e., smoking, alcohol, sodium intake, fruit and vegetable intake). Participants &lt;18 years of age, pregnant, or missing data for study variables were excluded, resulting in an analytic sample of 12,040. Univariate analysis was used to calculate prevalence estimates and 95% confidence intervals (95%CI). Multivariable logistic regression analysis was used for calculating odds ratios (OR). Results: Significantly fewer adults with hypertension were active or highly active (31.9%, 95%CI: 29.4, 34.0) compared to those without hypertension (45.3%, 95%CI: 43.3, 47.4) (p&lt;0.01). Among those with treated hypertension, 30.1% (95%CI: 27.7, 32.6) were active or highly active, compared to 34.5% (95%CI: 30.8, 38.3) who were not treated (p&lt;0.05). Following adjustments for sociodemographic and lifestyle characteristics, adults meeting 2008 Guidelines (i.e., active or highly active) were less likely to be hypertensive compared to adults who did not meet 2008 Guidelines (OR: 0.77, 95%CI: 0.67, 0.87). Meeting 2008 Guidelines was not significantly associated with either treatment or control of hypertension. Discussion: Adults with hypertension are less likely to meet the 2008 Guidelines , compared to those without hypertension. Those with treated hypertension were less likely to meet 2008 Guidelines than those not treated. Clinicians should counsel all of their patients about physical activity as recommended in clinical guidelines, and evidence-based community-wide efforts and policies that support opportunities to participate in physical activity should be encouraged.
Lymphatic Tissue Changes in Lethally Irradiated Mice Given Spleen Cells Intravenously
Authors: Congdon, C. C., Makinodan, T., Gengozian, N., Shekarchi, I. C., Urso, I. S.
Journal: JNCI Journal of the National Cancer Institute (1958)

Journal Article Lymphatic Tissue Changes in Lethally Irradiated Mice Given Spleen Cells Intravenously Get access C. C. Congdon, C. C. Congdon Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Makinodan, T. Makinodan Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar N. Gengozian, N. Gengozian Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar I. C. Shekarchi, I. C. Shekarchi Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar I. S. Urso I. S. Urso Biology Division, Oak Ridge National Laboratory,2Oak Ridge, Tennessee Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 21, Issue 1, July 1958, Pages 193–211, https://doi.org/10.1093/jnci/21.1.193 Published: 01 July 1958 Article history Received: 22 January 1958 Published: 01 July 1958
Partial restoration of the microbiota of cesarean-born infants via vaginal microbial transfer
Authors: Maria G Dominguez-Bello, Kassandra M De Jesus-Laboy, Nan Shen, Laura M Cox, Amnon Amir, Antonio Gonzalez, Nicholas A Bokulich, Se Jin Song, Marina Hoashi, Juana I Rivera-Vinas, Keimari Mendez, Rob Knight, Jose C Clemente
Journal: Nature Medicine (2016)