tbuckley/cabot-search huggingface dataset:
UGT1A1 genotype-based dose modification of irinotecan regimens: Impact on hematologic toxicities
Authors: B. R. Tan, B. Zehnbauer, J. Picus, C. Fournier, J. James, A. Brower, H. McLeod
Journal: Journal of Clinical Oncology (2008)

13500 Background: Patients homozygous for the UGTA1A*28 allele are at risk for severe neutropenia (ANC) with irinotecan (IRI) chemotherapy. Among these pts, grade 4 ANC rates were 50% with IRI [Innocenti, JCO 2004] and 18.2% -54.5% with IFL & IROX in the N9741 study [Mcleod, ASCO 2006]. Higher doses of IRI are associated with a higher toxicity[Hoskins, ASCO 2007]. The FDA mandated a change in the IRI package insert regarding genotype-based dose modifications but the impact of these recommendations has not been prospectively validated. Methods: We conducted a prospective registry of pts treated with IRI. After informed consent, blood was collected to determine UGT1A1 genotype. For pts with UGT1A1 *28/*28, IRI doses were reduced to minimize toxicity. Toxicities were monitored during the first 2 months of therapy. Results: The genotype frequencies of UGT1A1 polymorphism among 78 pts (M: F = 38:40) were 44.9% (35/78)*1/*1, 43.5% (34/78)*1/*28 and 10.2% (8/78) *28/*28. 88% had colorectal cancer. All pts had prior chemotherapy, (47% had ≥2). 60 pts treated were dosed according to guidelines. Dosing schedules were as follows: weekly (10), bi-weekly (48), q 3 weeks (2). For the 54 patients with complete records, the rate of all grade, gr 3 and gr 4–5 ANC are indicated in the table below. Only 5 of 8 patients with *28/*28 received IRI. All were treated with reduced starting doses (Dose - 1) and none developed grade 4–5 ANC. Three heavily pretreated pts (1 *1/*1; 2 *1/*28) developed Gr 4 ANC after only 1 dose of IRI 180 mg/m2, 2 died of neutropenic toxicities. Conclusions: Prospective genotyping to guide dosing decisions has a positive effect in reducing the incidence and severity of toxicities. This study is ongoing and will be expanded to other institutions to further validate these results. UGT1A1 n % all Gr ANC % Gr 3 ANC %Gr 4–5 ANC *1/*1 27 40.7% (11) 7.4% (2) 3% (1) *1/*28 22 59.1% (13) 13.6% (3) 9% (2) *28/*28 5 60% (3) 40% (2) 0 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Third Wave Technologies Pfizer, Third Wave Technologies Third Wave Technologies Pfizer
Reactions Between Benzo[a]pyrene and Nucleobases by One-Electron Oxidation234
Authors: Manfred Wilk, Wolfgang Girke
Journal: JNCI Journal of the National Cancer Institute (1972)

Adsorbed aromatic compounds were relatively easily oxidized. As active intermediates, radical cations occurred which, in carcinogenic compounds, preferred electrephilic substitutions to further oxidation. Benzo[a]pyrene in an adsorbed state could be oxidized by iodine in the presence of pyrimidines and purines. Some of the many products formed by adenine and purine were isolated and investigated spectroscopically. A 7- (or 9-) benzo[a]pyrenylpurine formed, and 6-aminobenzo[a]pyrene was a degradation product. The significance of oneelectron oxidation as a possible primary step in chemical carcinogenesis is discussed.
&lt;italic&gt;In Vitro&lt;/italic&gt; Sensitivity of Human Cells to Lymphocyte Proliferation Inhibitory Factor&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Green, Jon A., Green, Janet R., Cooperband, Sidney R., Kibrick, Sidney
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article In Vitro Sensitivity of Human Cells to Lymphocyte Proliferation Inhibitory Factor Get access Jon A. Green, Jon A. Green Departments of Microbiology and Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Janet R. Green, Janet R. Green Departments of Microbiology and Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sidney R. Cooperband, Sidney R. Cooperband Departments of Microbiology and Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar Sidney Kibrick Sidney Kibrick Departments of Microbiology and Medicine, Boston University School of Medicine, Boston, Massachusetts 02118 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 3, September 1972, Pages 631–638, https://doi.org/10.1093/jnci/49.3.631 Published: 01 September 1972 Article history Received: 10 February 1972 Accepted: 15 May 1972 Published: 01 September 1972
Outpatient antibiotic therapy in febrile neutropenic patients undergoing high-dose chemotherapy and autologous bone marrow support.
Authors: E B Rubenstein, K Rolston, L Elting
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.11.2516 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7964970 Outpatient antibiotic therapy in febrile neutropenic patients undergoing high-dose chemotherapy and autologous bone marrow support. E B RubensteinxE B RubensteinSearch for articles by this author , K RolstonxK RolstonSearch for articles by this author , L EltingxL EltingSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.11.2516 PDF "Outpatient antibiotic therapy in febrile neutropenic patients undergoing high-dose chemotherapy and autologous bone marrow support.." Journal of Clinical Oncology, 12(11), pp. 2516–2517© 1994 by American Society of Clinical Oncology
EORTC 18991: Long-term adjuvant pegylated interferon-alpha2b (PEG-IFN) compared to observation in resected stage III melanoma, final results of a randomized phase III trial
Authors: A. M. Eggermont, S. Suciu, M. Santinami, W. Kruit, A. Testori, J. Marsden, C. Punt, A. Hauschild, M. Gore, U. Keilholz
Journal: Journal of Clinical Oncology (2007)

8504 Background: EORTC 18991 is the largest adjuvant trial ever conducted in stage III melanoma. It assessed the efficacy and toxicity of long term PEG-IFN vs Observation (Obs.). Methods: PEG-IFN (Induction at 6μg/Kg/wk, sc, 8 weeks; followed by Maintenance at 3μg/Kg/wk, sc) for a total treatment duration of 5 years was compared to Obs. in 1256 patients (pts) with stage III melanoma (anyTN1–2M0 without in-transit metastases). Randomization was stratified for nodal involvement N1 (microscopic) vs N2 (palpable nodes), # of nodes, Breslow and ulceration of primary, sex and center. Distant Metastasis-Free Survival (DMFS) was the primary endpoint. Relapse-Free Survival (RFS) was the pre-specified regulatory primary endpoint. Overall survival (OS) was the secondary endpoint. Intent-to-treat analysis was performed. Results: Median follow-up was 3.8 yrs: HR = Hazard Ratio; NR = Not Reached In N1-pts (n=543) the benefit of PEG-IFN seemed more pronounced than in N2-pts (n=713): RFS (HR 0.73 p=0.02 and HR 0.86 p=0.12 for N1 and N2, respectively), DMFS (HR 0.75 p=0.03 and HR 0.94 p=0.53) and OS (HR 0.88 p=0.43 and HR 1.01 p=0.91). PEG-IFN therapy relative dose intensity (actual/planned dose while treated) reached median 88% (induction) and 83% (maintenance). 251 pts (40 %) stopped PEG-IFN because of toxicity. Grade 3–4 - mostly grade 3 - toxicities were reported in 45% (PEG-IFN), vs 12% (Obs.), including most frequently fatigue (15%), hepatotoxicity (10%) and depression (6%) with ECOG 0–1 Performance Status maintained in 83% of pts during maintenance. Conclusions: Long term PEG-IFN therapy in stage III melanoma had a significant and sustained impact on RFS, but not on DMFS and OS. Pts with only microscopic nodal involvement (Sentinel Node positive) seemed to have greater benefit in terms of both RFS and DMFS. Similar better effects of adjuvant IFN therapy in pts with lower disease burden are observed in 2 consecutive EORTC trials (18952 and 18991) involving 2644 pts. [Table: see text] [Table: see text]
Folic Acid Supplement Intake in Early Pregnancy Increases Risk of Gestational Diabetes Mellitus: Evidence From a Prospective Cohort Study
Authors: Beibei Zhu, Xing Ge, Kun Huang, Leijing Mao, Shuangqin Yan, Yeqing Xu, Sanhuan Huang, Jiahu Hao, Peng Zhu, Ying Niu, Shilu Tong, Fangbiao Tao
Journal: Diabetes Care (2016)

Folic acid (FA) is well known for its preventive effect on neural tube defects, and recommendations for FA supplement before and during pregnancy have been well established all over the world. Since increased consumption of FA has been prevalent, concerns about its negative consequences have been raised. Diverse adverse effects of FA have been identified, ranging from an increased risk of oral cleft malformations, asthma/respiratory tract infections, and small-for-gestational-age infants to the more serious effect of a potential increased risk of cancers.

Previous studies have suggested that a high maternal folate concentration is associated with an increased risk of insulin resistance in children and gestational diabetes mellitus (GDM) (1). In addition, animal experiments have reported that maternal high-FA supplement promotes glucose intolerance and insulin resistance in male mouse offspring fed a high-fat diet (2). However, …
The Mechanism of Carcinogenesis by Avian Sarcoma Viruses. I. Cell Multiplication and Differentiation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Howard M. Temin
Journal: JNCI Journal of the National Cancer Institute (1965)

Several types of cells were infected with different avian sarcoma viruses. The infected cells were then grown under diverse conditions, and the changes in their properties were compared to those of control uninfected cells. The viruses used were morphr, morphf, and hD Rous sarcoma virus, Schmidt-Ruppin Rous sarcoma virus, morphf and morphr Fujinami virus, myeloblastosis virus, and leukosis virus. The cells used were chicken embryo fibroblasts and iris epithelial cells, and duck embryo fibroblasts. The properties studied were increase in cell number, cell protein, cell ribonucleic acid, and cell deoxyribonucleic acid and production of acid mucopolysaccharides (AMPS), collagen, and pigment. The cells were grown under a fluid or an agar-containing medium. It was concluded that; 1) Conversion of cell morphology and increased rate of AMPS production are associated; 2) conversion of cell morphology and increased rate of AMPS production are not necessarily associated with altered multiplication; 3) altered growth in converted cells depends on environmental conditions; 4) specific cell functions are not all altered in the same way by conversion.
Dendritic cells transfected with allo-tumor mRNA as cancer vaccine in treatment of hormone resistant prostate cancer patients
Authors: S. Dueland, L.-J. Mu, G. Kvalheim, M. Hauser, H. Waehre, S. Aamdal, G. Gaudernack
Journal: Journal of Clinical Oncology (2005)

2541 Background: In this phase I/II trial, patients with hormone resistant prostate cancer and increasing PSA were vaccinated with autologous monocyte-derived dendritic cells (DCs) that have been transfected with mRNA from three prostate cancer cell lines (DU145, LNCaP and PC-3). By this strategy, we intend to make the DCs present a broad spectrum of tumor-associated antigens and elicit an immune response against tumor-associated proteins shared between the selected tumor cell lines and the individual patient. Methods: Twenty patients all with increasing PSA levels were included. Each patient received at least four weekly injections with 2x107 transfected DC. Ten patients had their DCs injected intranodally under ultrasonic guidance while 9 patients received the DCs intradermally. Safety and feasibility were evaluated, secondary end points were immune monitoring and PSA response. Immune responses were measured as DTH and by vitro immunoassays including ELISPOT, T cell proliferation test and cytotoxicity test in pre- and post-vaccination peripheral blood samples. Results: No grade II-IV toxicity and no serious adverse events were observed. Twelve patients developed a specific immune response to tumor mRNA transfected dendritic cells. In one patient HLA-A9 restricted CTL’s were generated that specifically killed an HLA-9 expressing prostate cancer cell line. Seven patients obtained stable disease by PSA evaluation (lPSA<50 % decrease and PSA< 25% increase). Ten patients showed a significant decrease in log slope PSA. Patients with lower PSA levels at inclusion had a better immunological response. Intranodal injection did not improve the results compared to intradermal vaccination. Conclusion: We conclude that our strategy of vaccinating with mRNA transfected DCs results in cellular immune responses specific for antigens encoded by mRNA derived from the prostate cancer cell lines. The observation that in some patients vaccination affected the PSA level, suggest that this approach might become potential useful as a treatment modality for prostate cancer patients. No significant financial relationships to disclose.
Radioimmunotherapy with 131-I tositumomab enhanced survival in good prognosis relapsed and high-risk diffuse large B-cell lymphoma (DLBCL) patients receiving high-dose chemotherapy and autologous stem cell transplantation
Authors: J. Vose, P. Bierman, G. Bociek, F. Loberiza, C. Enke, J. Hankins, J. Armitage
Journal: Journal of Clinical Oncology (2007)

8013 Background: The 5-year overall survival (OS) for pts with relapsed chemosensitive DLBCL with standard transplantation is approximately 40–50%. We previously piloted the addition of standard outpatient radioimmunotherapy (RIT) with 131-I tositumomab to the transplant regimen for patients with relapsed chemoresistant NHL. This phase I study demonstrated a 3 yr OS of 55% in these poor prognosis patients (JCO 23: 461–467, 2005). The current study is a follow-up phase II study in good prognosis relapsed and high risk DLBCL patients using 131-I tositumomab with BEAM (BCNU, etoposide, cytarabine, and melphalan) followed by an autologous stem cell transplant. Methods: Forty patients were accrued to the study between 2000–2005. The patients had a median age of 54 yrs (26–75) and all had a diagnosis of DLBCL. The patients had a median of two prior chemotherapies before transplant and 88% had received prior Rituximab. All patients had chemotherapy sensitive disease at the time of stem cell transplant. Following stem cell collection, all patients received a stem cell preparative regimen of 75 cGy total body dose of 131-I tositumomab (dosimetric dose day -19 and therapeutic day -12) followed by a standard BEAM transplant regimen. Autologous unpurged stem cells were infused on day 0. The median time of follow-up of the survivors is 28 months (3–68). Results: Seventy eight percent of the patients had a complete remission following the transplant. The 3 year progression free survival (PFS) is 70% (95% CI - 48 - 84%) and the 3 year OS is 81% (95% CI - 61 - 91%). The entire transplant can be delivered on an outpatient basis. No increased toxicity compared to a similar cohort receiving BEAM alone could be detected. Conclusions: The addition of 131-I tositumomab to BEAM and autologous stem cell transplant for relapsed or high-risk chemosensitive DLBCL produces a 3-yr OS of 81% without excess toxicity. This compares favorably to historical controls. This regimen is currently being tested in a phase III trial in the BMT/CTN of Rituximab/BEAM vs. 131-I tositumomab/BEAM in patients with relapsed chemosensitive DLBCL. No significant financial relationships to disclose.
Forecasting the Development of Primary Hepatocellular Carcinoma by the Use of Risk Factors: Studies in West Africa 2 3
Authors: Bernard Larouzé, Baruch S. Blumberg, W. Thomas London, Edward D. Lustbader, Marc Sankalé, Maurice Payet
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Forecasting the Development of Primary Hepatocellular Carcinoma by the Use of Risk Factors: Studies in West Africa Get access Bernard Larouzé, Bernard Larouzé Search for other works by this author on: Oxford Academic PubMed Google Scholar Baruch S. Blumberg, Baruch S. Blumberg Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Thomas London, W. Thomas London Search for other works by this author on: Oxford Academic PubMed Google Scholar Edward D. Lustbader, Edward D. Lustbader Search for other works by this author on: Oxford Academic PubMed Google Scholar Marc Sankalé, Marc Sankalé Search for other works by this author on: Oxford Academic PubMed Google Scholar Maurice Payet Maurice Payet Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1557–1561, https://doi.org/10.1093/jnci/58.6.1557 Published: 01 June 1977 Article history Received: 02 August 1976 Accepted: 21 December 1976 Published: 01 June 1977
Abstract MP57: The Association Between Anthropometrics and Different Measures of Cardiac Structure and Function - The Echo-SOL Study
Authors: Matthew A Allison, Jianwen Cai, Ankit Desai, Barry Hurwitz, Ai Ni, Neil Schneiderman, Sanjiv Shah, Daniel Spevack, Greg Talavera, Carlos Rodriguez
Journal: Circulation (2015)

Background: The purpose of this study was to determine the magnitudes and significances of the associations between adiposity and echocardiographically determined measures of left ventricular (LV) structure and function in a diverse cohort of Hispanic/Latino adults. Methods: Subjects were 1,350 adult men and women participants of the Hispanic Communities Health Study - Study of Latinos (HCHS-SOL) who enrolled in an ancillary study to determine cardiac structure and function by echocardiography. In addition to echocardiography, subjects were evaluated by extensive survey information, relevant physical measurements (to include bioelectrical impedance) and fasting blood assays. Results: The mean age was 56.1 years and 57% were female. Twenty-six percent were Mexican American, 25% Cuban American, 18% Dominican American, 17% Puerto Rican American, 8% Central American and 7% South American. Overall, the mean ejection fraction was 60.5%, while the mean stroke volume was 70 ml, end diastolic volume 83 ml, fractional shortening 31% and cardiac output 4.5 L/min. Results of multivariable linear regression adjusted for age, gender, hypertension, diabetes, dyslipidemia, cigarette smoking, family history of coronary heart disease, C-reactive protein and chronic kidney disease revealed that each 1-unit increment in body mass index (BMI) and fat mass (FM) by impedance was associated with 0.64 and 0.25 (p &lt; 0.01 for both) higher LV mass index (to height), while a 0.1 unit increment in the waist to hip ratio (WHR) was associated with 3.2 higher LV mass index. Concomitantly, each 1-unit increment in BMI and FM was associated with 7 and 3% (p &lt; 0.01 for each) higher odds of LV hypertrophy, while a 0.1 unit increment in WHR was associated with 78% higher odds for LV hypertrophy (p &lt; 0.01). On the other hand, none of these variables were significantly associated with ejection fraction. There were no significant interactions between the anthropometric variables and the different Hispanic groups for LV mass index or hypertrophy. Conclusions: Among Hispanics/Latinos from different cultural backgrounds, and by three measures of body composition (BMI, FM and WHR), higher levels of adiposity are significantly associated with higher LV mass indexed for height and the odds for hypertrophy, while not being associated with better or worse ejection fraction.
Measurement of Cancer Incidence in the United States: Sources and Uses of Data&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: E R Greenberg, T Colton, C Bagne
Journal: JNCI Journal of the National Cancer Institute (1982)

Since 1937, investigations have compiled a vast amount of information on cancer incidence in the United States. Three national cancer surveys were conducted in 1937, 1947, and 1969-71; each used somewhat different methods but covered populations who overlapped greatly. Concurrently, population-based tumor registries were developed that were capable of measuring cancer incidence. Since 1973, the Surveillance, Epidemiology, and End Results Program, an amalgam of such registries, had generated cancer incidence data for the United States. Available data provide a rough measure of the size of the cancer problem and may help those who direct prevention programs and those who plan studies of cancer etiology. Because the completeness and validity of existing incidence data are not known with certainty, comparisons among these incidence data are not known with certainty, comparisons among these incidence rates require cautious interpretation.
Limited penetration of anticancer drugs to cells in solid tumors: A neglected and modifiable cause of drug resistance
Authors: I. F. Tannock, A. Primeau, R. Grantab, C. Lee
Journal: Journal of Clinical Oncology (2005)

9563 Background: Regardless of the drug sensitivity of tumor cells, treatment of solid tumors will only be effective if drugs delivered in the blood penetrate tissue to achieve adequate concentration in the tumor microenvironment. Here we report studies of the penetration of anticancer drugs through tumor tissue in a model system and in solid tumors of mice. Methods: Tumor cells were grown on collagen-coated porous teflon membranes to form multicellular layers (MCL) up to 200μm thick, that resemble tissue in solid tumors. We studied the time-dependent penetration through MCL of several anticancer drugs. Immunohistochemistry was used to study distribution of fluorescent doxorubicin in murine tumors and human tumor xenografts in relation to blood vessels (stained with anti CD-31) and hypoxic regions (identified by uptake of EF-5). Results: Penetration of drugs through MCL is slow compared with that through the teflon membrane, especially for the weak bases doxorubicin and mitoxantrone (<10% penetration relative to the teflon membrane alone). Weak bases are sequestered in acidic endosomes, and strategies to raise endosomal pH leads to less drug uptake into cells without loss of cytotoxicity and improved penetration of tissue. Modification of extracellular matrix also influences penetration in MCL. Doxorubicin has very poor penetration in solid tumors of mice, with a decrease in mean concentration to ∼50% of that in blood over about 3 cell layers. The concentration of doxorubicin remains at background in large areas of viable tumor tissue following a single i.v. injection into mice. Conclusions: Limited distribution of drugs from blood vessels in solid tumors is an important and neglected cause of drug resistance. Several strategies might be used to improve drug penetration and hence therapeutic index. Supported by a grant from CIHR. No significant financial relationships to disclose.