tbuckley/cabot-search huggingface dataset:
Locally advanced squamous cell carcinoma of the head and neck (SCCHN): Can the treatment results achieved in clinical trials be reproduced in an unselected patient population?
Authors: S. Corsini-Munt, I. Gauthier, S. Laurie, V. Gallant, G. Goss
Journal: Journal of Clinical Oncology (2005)

5548 Background: Clinical trials performed in highly selected patients demonstrate that concurrent chemo-radiotherapy (CCRT) improves outcome compared to radiotherapy alone in locally advanced SCCHN. We reviewed the experience at the Ottawa Hospital Regional Cancer Centre, an academic comprehensive cancer centre, to determine how outcomes of CCRT in a less selected patient cohort compare with the published literature. Methods: Eligible patients were those diagnosed with SCCHN who received CCRT between 01/00 and 12/03, excluding salivary primaries and WHO type III nasopharyngeal carcinoma. The charts were reviewed for patient demographics, staging, prognostic factors, toxicity and treatment outcome. Results: Among 200 patient charts screened, 70 were eligible. Seven patients did not begin treatment: 2 opted for a clinical trial, 4 refused, 1 had disease progression. Sixty-three patients received CCRT (median age 56, 68% male, 84% oropharyngeal primary). Clinical stages were III/IVA/IVB in 7/48/8 patients. The median radiotherapy dose was 70 Gy (44–70 Gy), and the majority received platinum-based chemotherapy, as a single agent (49) or in combination with 5-FU (10). Due to toxicity, only 48% received all planned courses of chemotherapy; there was one toxic death (sepsis). Thirty-three patients required a feeding tube, upon which 10 remained dependent 3 months following completion of therapy; 24 had a >10% loss of pre-treatment weight. The clinical complete and partial response rates were 67% and 25%. With a median follow-up of 14 months, the median survival was 23 months and the 2-year overall survival rate was 48%. Conclusions: Published data suggest a 2- year overall survival rate of 42 to 60% for locally advanced SCCHN. In a non-clinical trial patient cohort, CCRT was acceptable in terms of outcome, safety and tolerance. CCRT is a feasible treatment option for carefully monitored patients with SCCHN in a tertiary care setting. No significant financial relationships to disclose.
Rosette-Forming Human Lymphoid Cell Line (T-Cell Line MOLT). II. Ability for Clonal Growth2
Authors: U. Itoh, J. Minowada, G. E. Moore, D. Pressman
Journal: JNCI Journal of the National Cancer Institute (1974)

A unique, permanent T-lymphocyte cell line, designated MOLT-4, which originated from blood from a patient with acute lymphoblastic leukemia, could form colonies in soft agar medium. The cloning efficiency of MOLT-4 was compared with 2 lymphoblastoid cell lines having B-cell characteristics, 1 of which, B35M, had been derived from a biopsy specimen of Burkitt's lymphoma and regarded as a malignant cell line, and the other, B411-4, derived from the peripheral blood of a normal individual and regarded as a “normal” cell line. The cloning efficiencies of MOLT-4 and B35M in soft agar medium were in the range of 8-10% and 26-31%, respectively, in contrast to the 0.1–0.2% shown by the B411-4 cells. This observation suggested that the MOLT-4 cells might be malignant.
Sensitivity of surveillance mammography for contralateral breast cancers and ipsilateral recurrences in survivors under 50
Authors: C. Weinstock, R. Bigenwald, S. Narod, P. Sun, T. Hochman, E. Warner
Journal: Journal of Clinical Oncology (2007)

11009 Background: Annual mammography is currently the gold standard for surveillance of breast cancer survivors for both ipsilateral recurrence and contralateral new primaries. The risk of either of these events occurring has been found to be inversely proportional to age and is at least 1% per year if breast cancer was diagnosed before age 50. (Chen et al 1999) (Komoike et al 2006). However, the sensitivity of screening mammography is significantly lower in young women. We therefore sought to determine the effectiveness of surveillance mammography according to age of diagnosis using a prospective database. Methods: The Henrietta Banting Database prospectively follows all new cases of operable breast cancer diagnosed from 1987 - 2004 at Women’s College Hospital. From the 1992 women in the database, we selected all patients diagnosed before age 60 who subsequently developed non-metastatic contralateral cancers (n=71 ) or ipsilateral recurrences (n=11 ). Records were obtainable for 59 of these 82 patients. Results: Method of detection and stage of diagnosis are listed in table below for the 59 patients according to age of diagnosis of second cancers. Overall, mammography was less effective at detecting contralateral and recurrent breast cancers in younger women, detecting only 24% of these cancers in women under 50 compared to 74% in patients 50 and older (Chi-Square, p&lt;0.001). In addition, 77% of patients under 50 whose second cancers were detected by methods other than mammography had negative surveillance mammograms in the 15 months prior to diagnosis. Conclusion: Since mammography detected only 24% of second primary breast cancers/ recurrences in survivors &lt; age 50 and almost one third of all detected cancers were locally advanced, more sensitive imaging modalities such as breast MRI should be considered for surveillance of young survivors. [Table: see text] No significant financial relationships to disclose.
The rape victim: psychodynamic considerations
Authors: M T Notman, C C Nadelson
Journal: American Journal of Psychiatry (1976)

Rape challenges a woman's ability to maintain her defenses and thus arouses feelings of guilt, anxiety, and inadequacy. Women's individual responses are determined by life stage considerations as well as their defensive structures: concerns about separation-individuation may be aroused in the young woman; a divorced or separated woman may find her credibility questioned; older women's fears of sexual inadequacy may be compounded. In counseling, the victim's previous adjustment should be assessed, she should be given support and reassurance, and specific considerations related to her life circumstances should be acknowledged and dealt with.
Pilot phase II study of preoperative gefitinib in early stage non-small cell lung cancer with assessment of intratumor gefitinib levels and tumor target modulation
Authors: E. B. Haura, E. Sommers, A. Becker, D. McKillop, G. Bepler
Journal: Journal of Clinical Oncology (2007)

7603 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) can provide clinical benefit in advanced non-small cell lung cancer patients. Here we examined the effect of single agent gefitinib in patients with early stage NSCLC with additional assessment of plasma and tumor concentrations of gefitinib. Previous studies have suggested considerably higher tumor concentrations of gefitinib compared to levels identified in blood, yet the results in human lung cancers is unknown. Methods: We conducted a pilot phase II study of a 28 day preoperative course of gefitinib 250 mg PO daily followed by surgical resection for patients with stage IA to selected IIIA non-small cell lung cancer. Response was assessed by RECIST using CT and changes in FDG metabolism were assessed using PET. Tumor penetration of gefitinib was assessed in surgically resected tumor samples along with plasma assessment on day 28. Results: Sixteen patients (7 men, 9 women) completed therapy on protocol and all who started on gefitinib were able to undergo a complete surgical resection. There were 0/16 objective responses (CR/PR), 14/16 SD, and 2/16 PD. Three of the 6 patients had more than 20% reductions in FDG SUV max assessed by PET scanning. Day 28 plasma concentrations of gefitinib averaged 531 ± 344 nM (range 65 to 1,211 nM) while tumor concentrations of gefitinib averaged 33,108 ± 44,312 nM (range 474 to 134,669 nM). Conclusions: Our results demonstrate that NSCLC tumor penetration of gefitinib is much higher than concentrations found in plasma. Assessment of pharmacodynamic markers including tumor EGFR and downstream signaling pathways is ongoing. PET scanning may be an early marker of clinical benefit of EGFR TKI. No significant financial relationships to disclose.
Abstract 18828: Comprehensive Lipidomic Analysis of Myocardial and Circulating Acylcarnitine Levels in Patients With Advanced Heart Failure Before and After Mechanical Unloading and Controls
Authors: D’Vesharronne Moore, Hongfeng Jiang, Serge Cremers, Christina Wu, Hirokazu Akashi, Hiroo Takayama, Yoshifumi Naka, Isaac George, Ira Goldberg, Paul Christian Schulze
Journal: Circulation (2013)

Background: Advanced heart failure (HF) is associated with myocardial metabolic derangements and insulin resistance. Acylcarnitine (AC) accumulation has been suggested to be a marker of abnormal fatty acid metabolism and mitochondrial dysfunction. We hypothesized that ACs accumulate in the failing myocardium and blood of patients with HF compared to controls. Methods: Myocardial and plasma samples were obtained from HF patients during ventricular assist device (VAD) placement and explantation. Control (CON) samples were obtained from hearts not used for heart transplantation. CON plasma was collected from healthy donors. After methanol extraction of total lipids, ACs were measured by LC/MS/MS (MS ACQUITY UPLC). Results: Our study included 11 patients with HF (age 61±8 yrs, EF 17±5%, BMI 28±4 kg/m2) before and after LVAD placement and 6 CON (age 41 ±2 yrs, EF&gt;60%, BMI 26±5 kg/m2). Free carnitine levels decreased in failing myocardium compared to CON (15.7±11.8 vs 16.2±93.0 ng/mg, p&lt;0.001) without plasma changes. Total ACs decreased in failing myocardium compared to CON (45.9±35.9 vs 132.2±94.0 ng/mg, p&lt;0.01). Of note, the cardiac AC/carnitine ratio was higher in HF compared to CON (387% of con, p&lt;0.001) and remained unchanged post-VAD. Circulating total AC levels were higher in HF compared to CON (7.7±2.8 vs 4.7±2.7 ng/ml, p&lt;0.05) with a decrease post-VAD (5.7±1.6 ng/ml, p&lt;0.05 vs pre-VAD). Short chain (C2+C3), medium chain (C4-C12) and long chain ACs (C14-C18) were found increased in HF plasma (+162%, +158% and +174% vs CON, respectively; all p&lt;0.05) with subsequent decrease post-VAD (-73%, -66% and -81% vs pre-VAD, respectively; all p&lt;0.05). The circulating total AC/free carnitine ratio trended to be higher in HF (1.0±0.3 vs 0.7±0.4 in CON, p=0.1) without changes post-VAD. Conclusion: Metabolic derangements in HF include changes in circulating and cardiac ACs with a distinct response to mechanical unloading. An increased ACs/carnitine ratio suggests impaired fatty acid metabolism and mitochondrial dysfunction leading to accumulation of ACs in the failing myocardium. These novel findings implicate abnormal AC metabolism in the metabolic abnormalities and insulin resistance of patients with advanced HF.
Phase Ib/II pharmacokinetic/pharmacodynamic (PK/PD) study of combination voreloxin and cytarabine in relapsed or refractory AML patients
Authors: J. E. Lancet, J. Karp, L. Cripe, G. Roboz, M. Wollman, C. Berman, A. Conroy, R. Hawtin, J. Fox, G. Michelson
Journal: Journal of Clinical Oncology (2009)

7005 Background: Voreloxin is a naphthyridine analog that intercalates DNA and inhibits topoisomerase II, inducing apoptosis. Clinical activity is observed in ovarian cancer and AML. Voreloxin combined with cytarabine (Ara-C) show supra-additive activity preclinically. Interim results from a phase Ib/II study in relapsed or refractory AML are reported. Methods: Dose-escalation in relapsed/refractory AML patients (pts) with ≤ 3 prior induction regimens; phase II expansion in first-relapse pts (CR1 ≥ 3 months) at MTD. Voreloxin given d1 and d4, combined with: A) continuous infusion 400 mg/m 2 /d x 5d Ara-C (CIV), or B) bolus 1 g/m 2 /d IV x 5d Ara-C. Voreloxin starting dose: A) 10 mg/m 2 /dose; B) 70 mg/m 2 /dose. Treatment: induction, reinduction if needed, and up to 2 courses for consolidation. DLT, PK, and PD were assessed in cycle 1. Pts’ PBMC were evaluated for induction of DNA damage response markers. Ex vivo sensitivity of pt BMA to voreloxin and Ara-C were evaluated by CellTiter-Glo proliferation assay. Results: 52 pts treated to date (A: 41 pts, dose-escalation; 5 pts Phase 2; B: 6 pts dose-escalation). A) MTD is 80 mg/m 2 /dose voreloxin. Infections are the most common G3 or higher toxicity. Voreloxin PK were dose proportional to 50 mg/m 2 , then plateaued. Evaluation of PBMC pre- and posttreatment suggests modulation of pDNA-PKcs and pChk2 may reflect response. Ex vivo BMA assay results suggest that voreloxin is the primary contributor to the majority of CRs observed. Phase Ib: 9 CRs + CRp were observed in multiply relapsed or 1° refractory pts. B) 70 mg/m 2 /dose voreloxin, no DLT; too early to evaluate activity. Conclusions: Voreloxin in combination with CIV Ara-C is generally well-tolerated, with CR in relapsed/refractory pts. Enrollment continues: A) phase II; B) phase Ib. Ex vivo activity assay results suggest that voreloxin is the primary contributor to the majority of CR. Induction of pDNA-PKcs and pChk2 in PBMCs from treated pts may reflect response. [Table: see text]
Survey of hospice referral practices among 541 pediatric oncologists
Authors: H. Frangoul, K. Fowler, R. Hamilton, D. Billheimer, H. Wu, E. Mullins, J. Mulder, K. Poedling
Journal: Journal of Clinical Oncology (2004)

8074 Background: Cancer is the leading cause of non-accidental death in childhood. The majority of children with terminal cancer continue to die in the hospital and experience substantial suffering in the last month of life. The objective of this study was to determine potential barriers to hospice referral among pediatric oncologists. Methods: A survey was sent to 1200 pediatric oncologists who are members of the Children's Oncology Group. The survey was developed, pre-tested, and modified for item clarification by pediatricians and pediatric oncologists with clinical and research experience. Results: Of the 1200 oncologists surveyed, 194 indicated that they were not eligible to complete the survey, and 541 replied for a response rate of 53.8%. Eighty-two percent practiced in an academic center and 66% have practiced for >10 years. Sixty-five percent had access to an established palliative care program and 85% had access to hospice services. For 62% percent of those surveyed, at least half of their patients died in the hospital. Although 24% reported formal training in end-of-life care, 87% felt comfortable or very comfortable in managing end-of-life pain. Logistic regression analysis showed that the probability of hospice referral was positively associated with the presence of a hospice facility (p < 0.0001), and with the size of the oncology group (p = 0.015). These associations were present after controlling for physician gender, formal end-of-life training, and years of clinical practice. The physician's level of comfort in managing end-of-life pain increased with number of years of clinical practice (p = 0.019), and with formal end-of-life training (p = 0.024). Only 2% of those surveyed referred patients at the time of relapse, and the majority did so when there was progressive disease, no further therapeutic options, or when death was imminent. Fifty-five percent reported that their local hospice did not admit patients who were receiving chemotherapy. Conclusions: Hospice referral for children with cancer is usually made late in the course of their disease and seems to be directly related to the availability of such services. No significant financial relationships to disclose.
Abstract B2-28: The development of an individualized Boolean network model for targeted anticancer therapy of glioblastoma
Authors: Hwang-Yeol Lee, Kwang-Hyun Cho
Journal: Cancer Research (2015)

Abstract Understanding the complexity of a cancer signaling network contributed to the discovery of potential targets for therapeutic intervention. Mathematical and computational models have been developed and investigated to predict the molecular dynamics during cancer development and drug treatment. Recent studies analyzing large-scale patient data, however, showed that genetic alterations are dramatically different among patients even for the same type of cancer, and that different therapeutic strategies should be employed for the patients. To resolve this problem using Boolean network modeling and analysis, we have integrated genome-wide data of glioblastoma patients from TCGA database and constructed an individualized network model for each patient. We defined three attractor states that represent different cell fates: proliferation, cell cycle arrest, and apoptosis. We then applied the information of patient-specific genetic alterations to the Boolean model by adjusting the interaction weights of the mutated molecules, and investigated the change of attractors for each patient. Finally, we have investigated the targeted therapy for each patient by performing perturbation analysis of the individualized network model to find the optimal drug combination. Together, our study provides a new insight into the impact of genetic alterations on the drug responses and the patient-specific therapeutic strategies. Acknowledgements: This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea Government, the Ministry of Science, ICT &amp; Future Planning (2014R1A2A1A10052404, 2013M3A9A7046303, and 2010-0017662) and by the KUSTAR-KAIST Institute, Korea, under the R&amp;D program supervised by the KAIST. Citation Format: Hwang-Yeol Lee, Kwang-Hyun Cho. The development of an individualized Boolean network model for targeted anticancer therapy of glioblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Computational and Systems Biology of Cancer; Feb 8-11 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 2):Abstract nr B2-28.
Genetic variants in human carbonyl reductase 3 (CBR3) and their influence on doxorubicin pharmacokinetics in Asian breast cancer patients
Authors: L. Fan, J. Y. Guo, C. I. Wong, R. Lim, H. L. Yap, Y. M. Khoo, P. Iau, B. C. Goh, H. S. Lee, S. C. Lee
Journal: Journal of Clinical Oncology (2007)

2505 Background: Human carbonyl reductase 3 (CBR3) is one of the main metabolizing enzymes to extensively reduce doxorubicin to its major active metabolite, doxorubicinol in normal and tumor tissues. Recently, the CBR3 958G&gt;A (V244M) genetic variant has been described to alter function in vitro. We postulate that CBR3 genetic variants could contribute to the inter-individual variability of doxorubicin pharmacokinetics in breast cancer patients. Methods: We studied 101 female breast cancer patients (66 Chinese, 26 Malay, 7 Indian and 2 of other ethnic origins) who were treated with doxorubicin at 75mg/m 2 every 3 weeks. Comprehensive sequencing of the 3 exons of CBR3, including the splice-site junctions was performed. Plasma concentrations of doxorubicin and doxorubicinol were analyzed during the first doxorubicin cycle. Results: Five CBR3 coding region variants (239G&gt;A, 483C&gt;T, 507C&gt;T, 598G&gt;A and 958G&gt;A) were detected, of which 239G&gt;A, 598G&gt;A and 958G&gt;A were non-synonymous. 598G&gt;A was novel, and was found in 1 Malay patient who was heterozygous. The genotype distributions of 239G&gt;A and 958G&gt;A were 36%/30%/34%, and 40%/36%/24% respectively for GG/AG/AA. The 239GG variant was associated with significantly higher AUC of doxorubicinol and AUC ratio of doxorubicinol to doxorubicin than the AG and AA variants (AUC of doxorubicinol 2.18±1.37ug/ml*h (GG) vs 2.04±2.11ug/ml*h (AG), p=0.05, and 1.55±0.61ug/ml*h (AA), p=0.004; AUC ratio of doxorubicinol to doxorubicin 1.90±1.29 (GG) vs 1.72±1.34 (AG), p=0.025, and 1.45±0.67 (AA), p=0.006). Patients with the 958AA variant had significantly higher AUC of doxorubicinol than those with the 958GG variant (2.29±1.60ug/ml*h vs 1.56±0.60ug/ml*h, p=0.009). The 239GG variant was more common in our population than in Caucasians (36% vs 20%. p=0.027), while the 958AA variant was more common than reported in Caucasians (24% vs 8%, p=0.014) and Japanese (24% vs 7%, p=0.016). Conclusions: CBR3 genetic variants may influence the pharmacokinetics of doxorubicin and its major metabolite doxorubicinol. Inter-ethnic differences in frequencies of CBR3 genetic variants exist and may account for differences in pharmacokinetics and pharmacodynamics of doxorubicin between different populations. No significant financial relationships to disclose.
Antibodies Unrelated to Epstein-Barr Virus in Human Sera Which Precipitate Soluble Components of Cultured Lymphoblasts2
Authors: Angel Guerra, Ursula Koldovsky, Werner Henle
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Antibodies Unrelated to Epstein-Barr Virus in Human Sera Which Precipitate Soluble Components of Cultured Lymphoblasts Get access Angel Guerra, Angel Guerra Search for other works by this author on: Oxford Academic PubMed Google Scholar Ursula Koldovsky, Ursula Koldovsky Search for other works by this author on: Oxford Academic PubMed Google Scholar Werner Henle Werner Henle 4Division of Virology, The Children's Hospital of Philadelphia and School of Medicine, University of Pennsylvania, Philadelphia, Pa. 19146. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 5, November 1974, Pages 1193–1200, https://doi.org/10.1093/jnci/53.5.1193 Published: 01 November 1974 Article history Received: 30 April 1974 Accepted: 26 July 1974 Published: 01 November 1974
Schedule-Dependent Potentiation of Lomustine Cytotoxicity by Amphotericin B in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: F Valeriote, J Dieckman, G Chabot
Journal: JNCI Journal of the National Cancer Institute (1986)

The sensitivity of leukemia cells of AKR/J mice to subsequent lomustine [1-(2-chloroethy1)-3-cyclohexyl-1-nitrosourea (CCNU)] exposure was found to vary with time following the ip administration of a single dose or multiple doses of amphotericin B (AmB) (0.5 mg/mouse/dose). Following 1 dose of AmB, leukemia cell sensitivity to CCNU, as measured by a spleen colony assay, reached a maximum by 24 hours with a tenfold increase in cell killing noted over cell killing with CCNU alone (0.15 mg/mouse). Two pretreatments with AmB separated by 24 hours led to a hundredfold increase in cell killing, whereas 4 pre-treatments, each separated by 24 hours, gave more than a thousandfold increase in cytotoxicity by 8 hours. Increasing the AmB dose, given as a single injection 24 hours before CCNU, resulted in increased potentiation of CCNU cytotoxicity, which reached a maximum at 0.5 mg/mouse. The kinetics of cell killing following either CCNU alone or the combination of AmB and CCNU were similar, although the extent of cell killing was greater with the combination. The AmB plasma pharmacokinetics for single doses showed a dose-dependent serum peak level and a half-life of about 24 hours for doses up to 1 mg/mouse. Nonlinearity was noted at the dose level of 2 mg/mouse because of saturation of absorption from the peritoneal cavity. These data are of importance for the optimal sequencing and dosing of these drugs for future clinical trials.