tbuckley/cabot-search huggingface dataset:
Cancer pain: from curriculum to practice change.
Authors: R K Portenoy
Journal: Journal of Clinical Oncology (1992)

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.1992.10.12.1830 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 1453196 Cancer pain: from curriculum to practice change. R K PortenoyxR K PortenoySearch for articles by this author https://doi.org/10.1200/JCO.1992.10.12.1830 First Page PDF © 1992 by American Society of Clinical Oncology
Descriptive epidemiology of ependymal tumors in the United States.
Authors: B. J. McCarthy, T. A. Dolecek, O. C. Danciu, J. L. Villano
Journal: Journal of Clinical Oncology (2010)

e12524 Background: Ependymomas are rare tumors of the brain and spinal cord/cauda equina (SC). Population-based data from the Central Brain Tumor Registry of the United States (CBTRUS) and the Surveillance, Epidemiology, and End Results (SEER) program were used to conduct a descriptive epidemiology study of this heterogeneous subgroup of glial tumors. Methods: Ependymal tumors were defined as ICD-O-3 histology codes 9391-9394 in primary site codes C70.0-72.9, 75.1-75.3. Incidence patterns were evaluated using data for malignant and nonmalignant tumors diagnosed during 2002-2006 from 17 collaborating CBTRUS registries (n = 1,733). Survival was examined using data for malignant ependymal tumors diagnosed in 15 SEER regions during 1992-2006 (n = 1,658). Results: SC was the primary site for 98% of nonmalignant and 45% of malignant tumors. Other sites for malignant tumors were brain stem (15%), brain lobes (11%), and brain NOS (11%). Incidence rates were higher in males (0.40/100,000 person-years (p-y); 95% CI: 0.37-0.43) than in females (0.34; 95% CI: 0.32-0.36), and in whites (0.40; 95% CI: 0.38-0.42) than in blacks (0.20; 95% CI: 0.17-0.24) or other races (0.22; 95% CI: 0.16-0.29). A bimodal age distribution showed a peak in the 0-4 year age group (0.48/100,000 p-y), declining until the early 20s and then rising to a second peak in the 55-59 year age group (0.61/100,000 p-y). A significantly higher rate ratio (RR) of malignant to nonmalignant tumors was observed for cases aged 0-19 years (RR: 8.55; 95% CI: 6.18-12.13) than cases aged 20+ years (RR: 2.55; 95% CI: 2.26-2.88). 5- and 10-year relative survival rates for all malignant ependymal tumors were 81% and 76%, respectively, and did not differ by gender or race. 10-year relative survival for anaplastic ependymoma (46%) was significantly worse than that for ependymoma NOS (81%). For those with ependymoma NOS, tumors located in the SC (95%) had significantly better 10-year relative survival than tumors located in the brain lobes (67%), ventricles (73%), or brain stem (64%). Conclusions: Malignant ependymomas remain an aggressive disease, and differ in site and age of presentation to nonmalignant ependymomas. A higher incidence of malignant tumors accounts for poorer outcomes in pediatric patients. No significant financial relationships to disclose.
Discrepancy analysis of patient vs physician assessments of performance status in patients with advanced lung cancer
Authors: J. Cashy, D. Cella
Journal: Journal of Clinical Oncology (2005)

8103 Background: Performance status (PS) is a measure of a patient’s ability to function normally without rest. PS has prognostic significance for many tumor types. It has been shown that patient self-assessments of PS are reliable and provide important prognostic information, despite differences between assessments made by patients and those made by physicians. The current analysis was undertaken to explore the relationship between patient and physician assessments of PS in patients with advanced lung cancer. Methods: Patient data from two databases (BIOQOL and Q-score), maintained by Evanston Northwestern Healthcare, were pooled for analysis. The data reflect survey results from physicians and their patients who were treated as outpatients or inpatients at five participating institutions. The current analyses were performed on the entire population (N = 3329) and the results from the subset of patients with advanced lung cancer (n = 493) are highlighted. Good PS was defined as PS 0–1 while poor PS was defined as PS 2–4. Results: Across solid tumors studied, patients with advanced lung cancer were at high risk for poor PS (relative risk compared with early localized breast cancer was 5.36). The most common PS rating by lung-cancer-patient assessment was PS2 (32.5%); the most common rating by physician assessment was PS1 (41.8%). Overall, 49.3% of lung cancer patients rated themselves as PS ≥2, compared with 33.9% of physicians (weighted Kappa coefficient = 0.39). In general, patients rated their PS higher (i.e., worse) than their providers did. Conclusions: The current analysis suggests that concordance between patient assessments and physician assessments of PS is only moderate. The PS of patients is worse than what is routinely indicated to providers, and this discrepancy may have important implications in treatment planning, clinical trial eligibility and interpretation of results. Given the prevalence of poor PS in patients with advanced lung cancer, research specifically designed for these patients should be encouraged, and their treatment response compared to good PS patients. No significant financial relationships to disclose.
Knockdown Of The Piwi - Like Protein 4 (PIWIL4) Delays Leukemic Growth and Is Associated With Gross Changes In The Global Histone Methylation Marks In Human MLL - Rearranged AML
Authors: Shiva Bamezai, Medhanie M Mulaw, Fengbiao Zhou, Christian Rohde, Carsten Muller-Tidow, Konstanze Dohner, Hartmut Dohner, Michaela Feuring Buske, Christian Buske, Vijay P.S Rawat
Journal: Blood (2013)
Clinical validation of in vitro drug sensitivity microarray data: Regimen-specific signatures predict pathological complete response to neo-adjuvant chemotherapy for breast cancer in a randomized trial (EORTC 10994/BIG 00–01)
Authors: H. R. Bonnefoi, A. Potti, M. Piccart, L. Mauriac, M. Tubiana-Hulin, D. Cameron, J. Bergh, M. Delorenzi, J. R. Nevins, R. Iggo
Journal: Journal of Clinical Oncology (2007)

544 Background: We previously described gene expression signatures that predict sensitivity to common chemotherapeutic agents and published promising results of their applicability in patients (Nature Med 2006). The goal of this study was to confirm their validity in a larger series of breast cancer patients with hormone-receptor negative (HR negative) since these tumours are more sensitive to chemotherapy. We used pathological complete response as a surrogate for chemosensitivity. We analyzed samples from a subset of patients included in a recently completed large neoadjuvant phase III trial. The trial compares a non-taxane regimen (fluorouracil + epirubicin + cyclophosphamide × 6; FEC arm) with a taxane regimen (docetaxel × 3 then epirubicin + docetaxel × 3; T-&gt;ET arm). Methods: RNA prepared from frozen samples obtained at diagnosis were hybridized to Affymetrix arrays. In vitro single agent signatures generated using a metagene approach were combined to obtain a FEC and a T-&gt;ET regimen-specific signatures. Predictions were blinded to patient outcome. With both signatures we calculated the receiver operating curve, its AUC, and the cut-point with maximal Youden index- accuracy, positive predictive value (PPV), sensitivity (Sens), negative predictive value (NPV) and specificity (Spec). Results: Samples from 124 patients (55 pCR) with HR negative tumours underwent a successful gene-expression array: 65 patients were treated in FEC arm and 59 patients in T-&gt;ET arm. The results are summarized below. Conclusions: We have validated the approach of using regimen-specific genomic signatures developed in vitro, in the context of a multicenter randomized trial. These results support the activation of a prospective trial comparing the conventional random choice of chemotherapy versus a specific array based approach. [Table: see text] [Table: see text]
Abstract 299: Simultaneous Cardiac And Adrenal Small Molecule GPCR-Gβ? Inhibition Halts The Progression Of Pressure Overload Heart Failure
Authors: Fadia A Kamal, Deanne Mickelsen, Jacob Moalem, Stephen R Hammes, Alan V Smrcka, Burns C Blaxall
Journal: Circulation Research (2013)

Heart failure (HF) is a progressive disease with rapidly increasing rates of morbidity and mortality. Elevated sympathetic nervous system activity, a salient feature of HF progression, leads to pathologic attenuation and desensitization of β-adrenergic receptors (β-ARs) due in part to Gβγ-mediated signaling. In the current study, we assessed the hypothesis that the small molecule Gβγ inhibitor “gallein” is salutary in treating pre-existing HF in a clinically relevant model (pressure-overload HF model of mouse transverse aortic constriction (TAC)) by simultaneously normalizing adrenergic receptor signaling in the heart and the adrenal gland. Four weeks post-TAC, mice received daily i.p. injections of vehicle or gallein for eight weeks (n=6-8 per group). Serial echocardiography was performed through out the study. At the end of the experiment, hemodynamic studies were performed, mice were sacrificed, blood, heart, and adrenal glands were harvested for further analysis. Gallein treatment improved survival and cardiac function and reduced cardiac hypertrophy, remodeling, and fetal genes expression in TAC mice. On the molecular level, gallein recovered membrane β-AR density and attenuated GRK2-PI3Kγ membrane recruitment, and Akt-GSK-3β signaling in TAC hearts. A salutary adrenal effect of gallein was obtained in cultured mice adrenal glands and human pheochromocytoma tissue (n=3), where direct gallein treatment restored α2-AR feedback inhibitory function and concurrently reduced catecholamine production. Moreover, gallein treatment attenuated adrenal hypertrophy in TAC mice and downregulated tyrosine hydroxylase and chromogranin A protein expression in adrenal glands from TAC mice and cultured pheochromocytoma tissue as well. In summary, our data suggest gallein as a systemic pharmacologic therapy with substantial therapeutic benefit in HF by simultaneously normalizing pathologic Gβγ-GRK2 signaling and recovering AR signaling in both the heart and the adrenal gland. In the heart, gallein mediated attenuation of cardiac remodeling probably involves inhibiting GRK2-PI3K-Akt signaling. Our data also suggest a role for small molecule Gβγ inhibition in other diseases of elevated catecholamine release, such as pheochromocytoma.
Tumor response to imatinib mesylate in advanced GIST
Authors: P. G. Casali, E. Fumagalli, A. Messina, C. Spreafico, D. Comandini, A. Comandone, U. De Giorgi, S. Frustaci, V. Vinaccia, M. C. Marré Brunenghi
Journal: Journal of Clinical Oncology (2004)

9028 Background: As from the first patients treated in 2000–2001, Imatinib mesylate was shown to be highly effective in advanced GIST, but patterns of tumor response were seen to be peculiar. Methods: From March to December 2002, 135 Italian patients with metastatic and/or locally advanced, inoperable, KIT-positive GIST entered a prospective clinical study on the best clinical use of Imatinib mesylate, organized by Novartis Pharma in cooperation with the Italian Sarcoma Group. A total of 129 patients were evaluable for tumor response at 9 months. Median age is 65 yrs; M:F ratio is 70:59; ECOG PS was 0–1 in 88% of patients, and 2–3 in 12%. Results: At 9 months, PR+CRs according to RECIST criteria were 44% in the whole group of 129 evaluable patients. At the same interval, the progression-free rate was substantially higher, i.e. >70%. In a single-institution subset of patients, the patterns of tumor response were reviewed and could be temptatively codified as one of the following: 1a) Pathologic complete response; 1b) Clinical complete response; 2a) Partial volume response; 2b) Partial tissue response; 2c) Partial functional response; 3) Stable disease; 4a) Partial lesion progression; 4b) Partial disease progression; 4c) Complete disease progression (the worst to best response going from 4c to 1). Conclusions: As previously observed in other series of GIST patients, in this study the early tumor response rate as assessed through standard tumor response criteria proved inadequate to render the impact of therapy on the disease, highlighted by the progression-free rate at 9 months. Patterns of tumor response to Imatinib mesylate in GIST need to be described through criteria which must in part differ from those conventionally used for cytotoxics in solid tumors and lymphomas, in order to make any response rate meaningful. Therefore, it was decided to centrally review the medical images of all patients enrolled in this study and codify their reviewed “best responses” according to a working classification employing the aforementioned criteria. A centralized review based on these criteria is ongoing on the whole group of 135 patients, and its results will be presented by crossing them with the standard RECIST evaluation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Pharma Novartis Pharma Novartis Pharma Novartis Pharma Novartis Pharma Novartis Pharma
Selection in operant learning may fit a general model
Authors: Julian C. Leslie
Journal: Behavioral and Brain Sciences (2001)

The generic account of selection proposed by Hull et al. readily fits operant learning where, by comparison with natural selection, the process is well understood but little is known about the mechanism. Objections within psychology, that operant learning ignores internal processes, fail to recognise the general significance of behaviour-environment interactions. Variation within operant response classes requires further investigation.
Childhood acute myeloid leukemia: outcome in a single center using chemotherapy and consolidation with busulfan/cyclophosphamide for bone marrow transplantation.
Authors: P J Shaw, M E Bergin, M A Burgess, L Dalla Pozza, S J Kellie, G Rowell, M M Stevens, B H Webster, K F Bradstock
Journal: Journal of Clinical Oncology (1994)

To report the impact of bone marrow transplantation (BMT) with busulfan/cyclophosphamide (BuCy) as end consolidation in a cohort of consecutively diagnosed children with acute myeloid leukemia (AML).Between May 1987 and November 1992, 43 patients were diagnosed with AML. Tissue typing at diagnosis determined whether patients would proceed to autologous or allogeneic BMT as end consolidation after six cycles of chemotherapy. Conditioning for BMT was with BuCy, followed by allogeneic or unpurged autologous marrow infusion.Of 37 patients who received chemotherapy, 35 achieved remission (95%) after one to six courses of treatment and 34 (92%) were transplanted. Five relapsed before BMT, four were subsequently transplanted in second complete remission (CR2) (n = 3) or untreated first relapse (n = 1), and one failed to respond to further therapy. All other patients proceeded to BMT in first complete remission (CR1). Eleven patients received allografts: one relapsed and one died of graft-versus-host disease (GvHD), for a leukemia-free survival rate of 90% at a median of 41 months after BMT (range, 3 to 60). For 23 autografts, there were two toxic deaths and eight relapses, with a leukemia-free survival rate of 61% at a median of 11 months after BMT (range, 0 to 66). The high relapse rate following autologous BMT led us to escalate the dose of Bu from 16 mg/kg to 600 mg/m2 using a single daily dose of Bu.With modern supportive therapy, most newly diagnosed children with AML will enter remission and are eligible for intensification therapy. BuCy is well tolerated in children, which allowed us to escalate the dose of Bu in recent patients. Further follow-up is needed to determine whether this has an impact on the relapse rate following autologous BMT.
Targeting tumor metabolism: biguanides as anti-neoplastic agents
Authors: R. E. Knoblauch, C. B. Thompson
Journal: Journal of Clinical Oncology (2009)

e14592 Background: During the process of malignant transformation, the tumor cell adopts a new form of metabolism, characterized by aerobic glycolysis and altered TCA cycle flux, that enable it to meet the energetic and biosynthetic demands of proliferation. This shift to anabolic metabolism results from oncogene-driven activation of signaling pathways, and therefore represents a potential therapeutic target that lies downstream of these genetic events. Methods: We have characterized the proliferative and metabolic effects of phenformin, a member of the biguanide family of compounds used in the treatment of diabetes, on the bcr-abl expressing K562 erythroleukemia cell line, and compared the resulting phenotype to those of imatinib and rapamycin, two targeted agents used in the treatment of malignant disease. Results: Phenformin induced the most profound growth inhibition of K562 cells, in a manner distinct from the targeted agents. Phenformin treatment eliminated the mitochondrial contribution to anabolic metabolism, through inhibition of Complex I of the Electron Transport Chain, as demonstrated by reduced oxygen consumption and intracellular ATP levels. Glutamine metabolism was also inhibited, consistent with TCA cycle inhibition as a secondary effect. The phenformin-induced mitochondrial dysfunction made K562 cells dependent upon glycolysis for survival. In contrast, the growth arrest resulting from imatinib treatment was associated with a complete reversion from the anabolic phenotype, as demonstrated by dramatically decreased glucose and glutamine consumption. Rapamycin, a poor inhibitor of K562 proliferation, decreased glycolysis but left mitochondrial function intact. Conclusions: Our results confirm the importance of metabolism to the proliferation of malignant cells, thereby validating anabolic metabolism's potential for therapeutic intervention. The direct inhibition of tumor cell metabolism by phenformin warrants further clinical study as a promising new approach to cancer therapy. No significant financial relationships to disclose.
The Association Of Dasatinib-Induced Lymphocytosis With Treatment Outcome In Patients With Chronic Myeloid Leukemia (CML)
Authors: Charles A. Schiffer, Jorge E. Cortes, Giuseppe Saglio, Philipp D. le Coutre, Kimmo Porkka, Satu Mustjoki, Hesham Mohamed, Neil P. Shah
Journal: Blood (2013)
The impact of residual cancer removed during subsequent surgeries on the outcome of patients with localized breast cancer
Authors: N. B. Kouzminova, A. Aggarwal, S. Aggarwal, A. Y. Lin
Journal: Journal of Clinical Oncology (2009)

e11533 Background: A close or positive margin after breast cancer surgery is an important risk factor for local recurrence. A significant percentage of breast cancer patients need additional surgeries to obtain clear margins. This study evaluated the impact of residual cancer (RC) found upon subsequent operations on the outcome of the patients with localized breast cancer. Methods: Under IRB approved protocol, we retrospectively analyzed data on 573 patients with stage I-IIIA breast cancer treated at our institution during 1994–2004. 202 patients had complete tumor removal at single procedure with clear margins, 319 patients had subsequent surgery due to initially compromised margins and 52 patients with compromised margins did not have second surgery. Cox Proportional Hazard regression test was performed to evaluate the effect of RC found on subsequent surgery on distant recurrence (DR) and disease specific survival (DSS). Results: Median follow-up was 5.4 years. Among 319 patients who underwent second surgery, 57.7% did not have any RC; 13.1% had in situ RC and 29.2% had invasive RC. 12.9% (74/573) patients had DR. The risk of DR was higher in patients with RC found upon second surgery compared to those who had single procedure breast cancer removal (22.6% vs. 9.9%; HR 2.4, 95% CI 1.3–4.4, p=0.006). Similarly, finding of RC was a significant predictor of DSS (80.6% vs.92.6%; HR 2.9, 95% CI 1.4–5.7, p=0.003). Multivariate analysis revealed that tumor size above 5 cm, lymph nodes involvement and grade III were significant predictors of DR and DSS along with invasive RC found during subsequent surgeries. Delay in adjuvant chemotherapy due to need for subsequent surgeries strongly correlated with earlier DR in patients with invasive RC found on subsequent operations (r S = - 0.55, p = 0.019, two-tailed). Conclusions: Invasive residual carcinoma found during subsequent surgery after initial compromised margin is an important prognostic factor for DR and DSS, even after clear margins are eventually achieved. No significant financial relationships to disclose.
Serum Cholesterol and Colon Cancer Incidence in Hawaiian Japanese Men&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: G N Stemmermann, A M Nomura, L K Heilbrun, E S Pollack, A Kagan
Journal: JNCI Journal of the National Cancer Institute (1981)

A prospective study of cancer and coronary heart disease (CHD) in 8,006 Hawaiian Japanese men, aged 45-68 years, showed that serum cholesterol levels below 180 mg/dl predicted low rates of CHD and high rates of colon cancer. Men with colon cancer had lower mean serum cholesterol levels than did other members of the cohort, including those with cancer at other sites. The lowest serum cholesterol levels were obtained from men who died as a result of colon cancer. The lack of such an association with other cancers and the persistence of this inverse association in colon cancer patients diagnosed 5-9.9 years after examination suggest that the low serum cholesterol was not due to preexisting disease. Right colon tumors showed the strongest inverse association with serum cholesterol. The differences between CHD and colon cancer in respect to serum cholesterol indicate that different subsets of the westernized Japanese population are affected.
Hospitals are “gaming” data on common operations, leading surgeon says
Authors: Nigel Hawkes
Journal: BMJ (2016)

Attempts by the NHS in England to measure the benefits to patients from common operations could be undermined by hospitals artificially boosting their results, a leading orthopaedic surgeon has warned.

Angus Wallace, recently retired as a consultant orthopaedic surgeon at Nottingham University Hospitals NHS Trust, said that the NHS’s patient reported outcome measures (PROMs) could be “gamed” by hospitals contacting patients shortly before they were due to complete their follow-up questionnaire.

PROMs assess benefits of hip and knee replacement operations, hernia repair, and varicose vein surgery by comparing patients’ responses before and after the procedure. For orthopaedic operations, the follow-up questionnaire is completed six months after the operation. Since 2012 PROM data have been released as official statistics by the Health and Social Care Information Centre and are used to compare the performance of healthcare provider trusts.

“There is a centre in the south of England that has …
Usefulness and technique of axillary dissection in primary breast cancer.
Authors: B Cady, H F Sears
Journal: Journal of Clinical Oncology (1986)

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.1986.4.5.623 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3701385 Usefulness and technique of axillary dissection in primary breast cancer. B CadyxB CadySearch for articles by this author , H F SearsxH F SearsSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.5.623 PDF "Usefulness and technique of axillary dissection in primary breast cancer.." Journal of Clinical Oncology, 4(5), pp. 623–624© 1986 by American Society of Clinical Oncology