tbuckley/cabot-search huggingface dataset:
Abstract P6-13-01: Lyso-thermosensitive liposomal doxorubicin + local hyperthermia for radiation-pretreated chest wall recurrence
Authors: S Formenti, H Rugo, R Myerson, C Diederich, W Straube, B O'Conner, AJ Matzkowitz, RL Goodman, F Muggia
Journal: Cancer Research (2012)

Abstract Background: Chest wall recurrence (CWR) causes much morbidity when not controlled by local measures. Lyso-thermosensitive liposomal doxorubicin (LTLD) provides accelerated release of doxorubicin (Dox) at ≥ 39° C, and is being studied for CWR based on the pioneering thermochemotherapy work of Dewhirst and colleagues at Duke. We now report on its tolerance, pharmacology, and preliminary antitumor effects in a dose-escalation study combined with local hyperthermia (LH) for radiation-refractory CWR. LH selectively increases liposomal permeability in tumor microvasculature, and promotes release of Dox from LTLD, and Dox tumor uptake, in addition to LH anti-tumor effects. Methods: This phase I study entered patients (pts) with CWRs &amp;lt; 3 cm deep failing all standard Tx including surgery, radiation, and chemotherapy: pts received up to 6 LTLD/LH treatments every 21 days at a starting dose of 40 mg/m2 (cohort 1) and escalated to 50 mg/m2 (cohort 2). LTLD was infused IV over 30 minutes (min); followed within 30 min by microwave or ultrasound LH. The thermal dose goal was 40°C-42°C for 60 min. Pharmacokinetic samples for total plasma Dox and doxorubicinol (Doxol) were taken at 0.5, 5, 10 and 24 hours after starting infusion. Left ventricular ejection fraction was monitored every other cycle. Results: Eleven pts with a median of 4 prior chemotherapy regimens (range 2 — 12) were enrolled; all but one had prior anthracycline (AC). All pts received ≥ 2 cycles. The within subject variability in Dox and Doxol exposure was small with mean Cycle 2 vs Cycle 1 ratios ranging from 0.99 to 1.06. Cmax/dose (ng/ml)/(mg/m2) Cycle 1 Cycle 2 Dox 499.82 512.00 Doxol 0.46 0.45 AUClast/dose ((ng*hr/ml)/(mg/m2) Dox 1338.12 1381.82 Doxol 7.96 8.04 Grade 3 and 4 toxicities included reversible neutropenia in 17 (40.5%) and one case (each) of mucositis (grade 1), chest wall thermal burn, and chest wall cellulitis (both grade 4); these occurred in only ≥ 5% of 42 cycles given. No cardiomyopathy or hand-foot toxicity occurred. The rate of clinically-significant (≥ 6 point) QoL improvement on the FACT-B after 2 cycles was 54.5% (95% CI: 25.1%–83.9%), including 1 lasting &amp;gt; 3 months. The local objective response rate was encouraging: 45.5% (95% CI: 16.1%–74.9%), with 1 complete and 4 partial local responses. Conclusion: LTLD + LH is safe in CWR after prior radiation and doxorubicin. A phase II study is planned for pharmacologic evaluations and to add pts with less or no anthracycline treatment. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-13-01.
Hypertension and oral contraceptives.
Authors: S Oparil
Journal: BMJ (1978)

Large prospective epidemiologic studies have shown that long-term use of oral contraceptives containing estrogen induce an increase in blood pressure and sharply increase the risk of hypertension. Susceptibility to the hypertensive effects of oral contraceptives is heightened where risk factors such as age, family history of hypertension, preexisting or occult renal disease, parity and obesity exist. Hypertension among pill users usually develops within the first 6 months of usage and occasionally is delayed for as long as 6 years. Anitihypertensive therapy is seldom needed as the hypertension that developes is generally mild and uncomplicated, and rapidly reverses when the pills are discontinued. However, a small percentage of patients develop severe, even life-threatening hypertension and the hypertensive effects are felt long after the pills are discontinued. Cases of malignant hypertension and irreversible renal failure requiring maintenance hemodialysis, bilateral nephrectomy, and renal transplantation have occurred following administration of oral contraceptive pills. The mechanism by which oral pills induce hypertension in susceptible women is not known and needs further research. Before oral contraceptives are prescribed, physicians should take a careful history and perform a detailed physicial examination with special attention to the cardiovascular system. Multiple blood pressure measurements should be made and routine laboratory studies including urinalysis, blood urea and nitrogen and serum creatinine should be performed. It is preferable to start with a relatively low (50 mcg) estrogenic content preparation. Patients who develop hypertension (diastolic pressure, 90 mm Hg) on oral contraceptives should stop taking the pills immediately, and should be considered to have estrogen-induced hypertension. They should never again receive estrogen-containing oral pills, although they can try pills containing only progestogen. There is no contraindication to pregnancy in these patients, as most women who become hypertensive on oral pills go on to have normotensive pregnancies. Pregnancy in women who are susceptible to essential hypertension however should be treated as high risk.
Effect of radium-223 dichloride (Ra-223) on risk for and duration of hospitalization in ALSYMPCA by docetaxel (D) subgroup.
Authors: Paul Cislo, Jonathan D. Reuning-Scherer
Journal: Journal of Clinical Oncology (2015)

254 Background: In ALSYMPCA, the first-in-class alpha-emitting radiopharmaceutical Ra-223 significantly improved overall survival vs placebo (pbo) and was well tolerated in patients (pts) with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no visceral metastases regardless of prior D use. To understand whether treatment (tx) benefit in prior and no prior D subgroups relates to differences in health care resource utilization, hospitalization and other resource use were evaluated. Methods: Hospitalization, nursing home visit, home health care and adult day care services use, and physician visit data were captured. To account for differences in observation time due to differing survival, resource use was annualized for each pt. Mean number and duration of encounters/year were compared using t-tests. To compare tx groups based on rate of use/year, incidence rates and ratios were calculated using a generalized estimating equation regression model with covariates. Results: For prior D pts, hospitalization incidence rates for Ra-223 vs pbo were 1.18 vs 1.70 (incidence rate ratio = 0.69; 95% CI, 0.53-0.90; P = 0.006) and mean hospitalization days/year were 8.53 vs 16.51 (P = 0.001). Among prior D pts with ≥1 hospitalization, mean hospitalization days/year for Ra-223 vs pbo were 19.65 vs 33.02 (P = 0.003). For no prior D pts, hospitalization incidence rates for Ra-223 vs pbo were 1.02 vs 1.10 (incidence rate ratio = 0.92; 95% CI, 0.66-1.29; P = 0.643) and mean hospitalization days/year were 7.53 vs 12.11 (P = 0.027). Among no prior D pts with ≥1 hospitalization, mean hospitalization days/year for Ra-223 vs pbo pts were 19.12 vs 26.61 (P = 0.063). The only other tx differences were nursing home days/year and day care services/year in the no prior D subgroup, but t-test and regression results were inconsistent. Conclusions: In the prior D subgroup, Ra-223 pts experienced 8.0 fewer hospitalization days/pt/year, driven by a 31% reduction in hospitalization and shorter duration among pts hospitalized. In the no prior D subgroup, Ra-223 pts experienced 4.6 fewer hospitalization days/pt/year, primarily driven by a shorter duration among pts hospitalized. Clinical trial information: NCT00699751.
Pharmacokinetics of albumin-bound paclitaxel (ABX) in combination with temozolomide (TMZ) and oblimersen sodium (OBL) in patients with advanced melanoma
Authors: M. J. Seidman, A. C. Pavlick, A. Gandhi, J. Escalon, K. Madden, J. Staha, E. Yepes, S. Mendoza, L. F. Liebes
Journal: Journal of Clinical Oncology (2008)

20030 Background: ABX is a novel formulation of paclitaxel which has improved tolerability and can be given at higher doses than paclitaxel. Preclinical data has demonstrated synergy when ABX was added to OBL and TMZ in an A375 melanoma cell line. This Phase I/II study was performed to evaluate the safety, efficacy, and pharmacokinetics of ABX combined with TMZ and OBL in advanced melanoma. Methods: To date, 14 chemotherapy-naïve patients with unresectable stage III or stage IV melanoma and a normal LDH have been enrolled. The treatment consists of TMZ 75mg/m2 orally on days (d) 1–42, OBL 7mg/kg/d by continuous IV infusion on d 1–7 & 22–28, and ABX as a 30 minute IV infusion at 175 mg/m2 (Cohort 1) on d 8 & 29, every 8 weeks. Samples for determination of plasma paclitaxel concentration were taken on day 8 at 0, 0.5, 1, 2, 3, 4, and 6 hours (hr) after the start of the ABX infusion, and on day 9 at 24 hr after the start of the ABX infusion. The assay of paclitaxel employed solid-phase extraction of the drug from plasma and reverse-phase high-performance liquid chromatography. Pharmacokinetic parameter estimates of the decay data employed a two-compartment continuous-infusion model available in WinNonlin, Ver 5.2. Results: The results of the key pharmacokinetic estimates for paclitaxel for 10 patients who were evaluable are summarized in Table 1 along with a comparison of the 175 mg/m2 dose level from the Phase I trial of weekly ABI-007 (Nyman et al, JCO 23:7785–7793, 2005). The AUC estimates of paclitaxel exposure after 7 days of OBL and TMZ demonstrated reasonable agreement with the exposure of patients who received ABX alone. The lower elimination half-life estimates are due to the 24 hr PK sampling in our study compared to the additional sampling points evaluated in the 48 hr collections carried out in the Phase I study with ABX. Conclusions: In this first reported trial of ABX in combination with TMZ and OBL in advanced melanoma, no alterations in paclitaxel pharmacokinetics have been observed. Study Cmax, μg/ml AUC (μg *hr/ml) t ½(hr) ATG (n=10) 6.11 ± 2.73 9.37 ± 4.17 7.89 ± 3.25 Phase I ABI-007 (weekly 175 mg/m2), n=3 9.8 ± 6.2 6.87 ± 2.05 18.5 ± 1.73 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genta Abraxis Oncology, Genta
Expression of CD24 as a predictor of prognosis of hepatocellular carcinoma after operation
Authors: J. Fan, X. Yang, Y. Xu, Y. Shi, J. Zhou, S. Qiu
Journal: Journal of Clinical Oncology (2009)

e22043 Background: CD24 expression has previously been reported in hepatocellular carcinoma (HCC), although little is known about its prognostic significance. The aim of this study is to evaluate the relation of CD24 expression and its prognostic significance in HCC. Methods: CD24 expression in stepwise metastatic HCC cell lines and tumor tissues from 50 HCC patients was investigated by quantitative real-time reverse transcription-PCR and Western blot analyses. The role of CD24 was investigated by depletion CD24 expression in HCC cells through small-interfering RNA. Tumor tissue microarrays of 314 HCC patients who underwent resection between 1997 and 2000 were used to detect the expressions of CD24, β-catenin and PCNA expression. The prognostic significance was assessed using Kaplan-Meier survival estimates and log-rank tests. Results: CD24 was overexpressed in the high metastatic HCC cell line and in tumor tissues of recurrent patients. Depletion of CD24 caused a notable decrease in cell proliferation, migration and invasiveness in vitro. CD24 was confirmed as an independent predictor for overall survival (p&lt;0.001) and relapse-free survival (p&lt;0.001), regardless of recurrence time, AFP level, TNM stage and Edmondson stage. High expression of CD24 in HCC tissues was significantly associated cytoplasmic/nuclear accumulation of β-catenin (p=0.023), high tumor proliferate status (p=0.018) and diffused intrahepatic recurrence and distance metastasis (p=0.026). Adjuvant TACE after operation reduced the early recurrence (≤1 year) in CD24 + HCC patients (p=0.024), while there had no significant changes in CD24 - patients (p=0.284). Conclusions: High expression levels of CD24 were related with high invasive and metastatic potential, high tumor proliferation status and activation of Wnt/β-catenin pathway. The expression of CD24 provides new prognostic information about HCC prognosis and targeted therapy to CD24 + fraction in HCC may comprise a promising anti-recurrence strategy for HCC patients after surgery. No significant financial relationships to disclose.
Reversal of murine alcoholic steatohepatitis by pepducin-based functional blockade of interleukin-8 receptors
Authors: Verena Wieser, Timon E Adolph, Barbara Enrich, Athan Kuliopulos, Arthur Kaser, Herbert Tilg, Nicole C Kaneider
Journal: Gut (2016)

<h3>Objective</h3> Alcoholic steatohepatitis is a life-threatening condition with short-term mortality up to 40%. It features hepatic neutrophil infiltration and blood neutrophilia, and may evolve from ethanol-induced breakdown of the enteric barrier and consequent bacteraemia. Signalling through CXCR1/2 G-protein-coupled-receptors (GPCRs), the interleukin (IL)-8 receptors, is critical for the recruitment and activation of neutrophils. We have developed short lipopeptides (pepducins), which inhibit post-ligand GPCR activation precisely targeting individual GPCRs. <h3>Design</h3> Experimental alcoholic liver disease was induced by administering alcohol and a Lieber–DeCarli high-fat diet. CXCR1/2 GPCRs were blocked via pepducins either from onset of the experiment or after disease was fully established. Hepatic inflammatory infiltration, hepatocyte lipid accumulation and overall survival were assessed as primary outcome parameters. Neutrophil activation was assessed by myeloperoxidase activity and liver cell damage by aspartate aminotransferase and alanine aminotransferase plasma levels. Chemotaxis assays were performed to identify chemoattractant signals derived from alcohol-exposed hepatocytes. <h3>Results</h3> Here, we show that experimental alcoholic liver disease is driven by CXCR1/2-dependent activation of neutrophils. CXCR1/2-specific pepducins not only protected mice from liver inflammation, weight loss and mortality associated with experimental alcoholic liver disease, but therapeutic administration cured disease and prevented further mortality in fully established disease. Hepatic neutrophil infiltration and triglyceride accumulation was abrogated by CXCR1/2 blockade. Moreover, CXCL-1 plasma levels were decreased with the pepducin therapy as was the transcription of hepatic IL-1β mRNA. <h3>Conclusions</h3> We propose that high circulating IL-8 in human alcoholic hepatitis may cause pathogenic overzealous neutrophil activation, and therapeutic blockade via pepducins merits clinical study.
pVAC-Seq: A genome-guided in silico approach to identifying tumor neoantigens
Authors: Jasreet Hundal, Beatriz M. Carreno, Allegra A. Petti, Gerald P. Linette, Obi L. Griffith, Elaine R. Mardis, Malachi Griffith
Journal: Genome Medicine (2016)

Cancer immunotherapy has gained significant momentum from recent clinical successes of checkpoint blockade inhibition. Massively parallel sequence analysis suggests a connection between mutational load and response to this class of therapy. Methods to identify which tumor-specific mutant peptides (neoantigens) can elicit anti-tumor T cell immunity are needed to improve predictions of checkpoint therapy response and to identify targets for vaccines and adoptive T cell therapies. Here, we present a flexible, streamlined computational workflow for identification of personalized Variant Antigens by Cancer Sequencing (pVAC-Seq) that integrates tumor mutation and expression data (DNA- and RNA-Seq). pVAC-Seq is available at https://github.com/griffithlab/pVAC-Seq .
Migration-Inhibiting Effect of Sera From Patients With Burkitt's Lymphoma 2
Authors: Alistair J. Cochran, George Klein, Rolf Kiessling, Peter Gunvén
Journal: JNCI Journal of the National Cancer Institute (1973)

Sera from 25 of 30 Burkitt's lymphoma (BL) patients inhibited the migration of cell suspensions from BL biopsies and tissue cultures in a capillary tube migration assay. Leukemic peripheral blood-cell migration was inhibited by 13 of 21 BL sera. Weak migration inhibition was seen only occasionally with sera from clinically disease-free Europeans, from African patients with nasopharyngeal carcinoma, and from African patients with tonsillitis. Inhibitory activity was found in sera from 24% of relatives and neighbors of BL patients. The donors of positive sera tended to be <10 years old and showed sometendency to geographic clustering. Inhibitory activity was maximum in the macroglobulin fraction in the 3 sera fractionated on Sephadex, but subsidiary activity was noted in 2 of these sera in the post-albumin fraction. Administering 2-mercaptoethanol and heating the serum to 56° C for 30 minutes abolished inhibitory activity. We could not identify the specificity of the active fraction, nor could we relate inhibitory activity to levels of antibody to Epstein-Barr virus-related antigens. The inhibitory factor(s) may be part of an inhibitory feedback mechanism.
The Role of CD27, CD40 and CD117 in the Diagnosis and Prognosis of Multiple Myeloma Established by Flow Cytometry
Authors: Giacoma De Tullio, Nicola Sgherza, Rosa Angarano, Vincenza De Fazio, Simona Serratì, Giacomo Loseto, Antonello Rana, Angela Iacobazzi, Attilio Guarini
Journal: Blood (2014)
Clinical Impact of <sup>18</sup>F Fluorodeoxyglucose Positron Emission Tomography in Patients With Non–Small-Cell Lung Cancer: A Prospective Study
Authors: Victor Kalff, Rodney J. Hicks, Michael P. MacManus, David S. Binns, Allan F. McKenzie, Robert E. Ware, Annette Hogg, David L. Ball
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To prospectively study the impact of 18 F fluorodeoxyglucose (FDG) positron emission tomography (PET) on clinical management of patients with non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred five consecutive patients with NSCLC undergoing 18 F FDG PET were analyzed. Before PET, referring physicians recorded scan indication, conventional clinical stage, and proposed treatment plan. PET scan results were reported in conjunction with available clinical and imaging data, including results of computed tomography (CT). Subsequent management and appropriateness of PET-induced changes were assessed by follow-up for at least 6 months or until the patient’s death. RESULTS: Indications for PET were primary staging (n = 59), restaging (n = 34), and suspected malignancy subsequently proven to be NSCLC (n = 12). In 27 (26%) of 105 of cases, PET results led to a change from curative to palliative therapy by upstaging disease extent. Validity of the PET result was established in all but one case. PET appropriately downstaged 10 of 16 patients initially planned for palliative therapy, allowing either potentially curative treatment (four patients) or no treatment (six patients). PET influenced the radiation delivery in 22 (65%) of 34 patients who subsequently received radical radiotherapy. Twelve patients considered probably inoperable on conventional imaging studies were downstaged by PET and underwent potentially curative surgery. PET missed only one primary tumor (5-mm scar carcinoma). CT and PET understaged three of 20 surgical patients (two with N1 lesions &lt; 5 mm and one with unrecognized atrial involvement), and PET missed one small intrapulmonary metastasis apparent on CT. No pathological N2 disease was missed on PET. CONCLUSION: FDG PET scanning changed or influenced management decisions in 70 patients (67%) with NSCLC. Patients were frequently spared unnecessary treatment, and management was more appropriately targeted.
Colony formation in vitro as a prognostic indicator for primary breast cancer.
Authors: M S Aapro, J F Eliason, F Krauer, P Alberto
Journal: Journal of Clinical Oncology (1987)

Cells from some, but not all, tumor biopsy samples form colonies when cultured in semi-solid media. The possibility that colony formation by progenitor cells in these tumors may reflect a more "aggressive" phenotype bearing clinical implications was examined in a series of 61 patients with primary breast cancer. Tumor cells from 32 samples formed colonies in vitro. There was no correlation between colony formation and any of the standard clinical parameters such as tumor size, nodal status, metastatic spread, or hormone receptor levels. Eighteen patients had inflammatory, locally advanced and/or detectable metastatic breast cancer at the time of surgery. Sixteen of these patients have progressed and 15 have died, with no relationship between colony formation and survival. For the 43 remaining patients, 23 had a tissue sample that gave rise to colonies in vitro; 14 of these have relapsed, with a median relapse-free survival (RFS) of 37.6 months, and eight have died with a median survival time of 46.8 months. This is compared with four relapses (median RFS not reached, P = .0043, Peto-Pike), and four deaths (median not reached, P = .1175) in the group without growth of the tumor specimen. These results indicate that colony formation is an independent prognostic parameter for breast cancer, which may be useful for selecting patients who would benefit from more intensive therapy.
The serum hyaluronan is a potential marker for epithelial ovarian cancer
Authors: M. Anttila, E. Hiltunen, R. Tammi, S. Heinonen, M. Yliskoski, M. Juhola, V.-M. Kosma, M. Tammi
Journal: Journal of Clinical Oncology (2005)

5066 Background: We have previously shown, that the stromal expression of hyaluronic acid (HA), a glycosaminoglycan, is an independent prognostic factor of poor survival in epithelial ovarian cancer. It’s concentration was also significantly elevated in malignant epithelial ovarian tumors compared to other non-malignant lesions of the ovary analyzed by quantitative ELISA-like assay. In this pilot study, we assessed the value of HA concentration in sera as a biomarker for ovarian cancer. Methods: The blood samples were collected from 81 patients before surgery. The study included malignant (n=24), and semimalignant (n=8) epithelial ovarian tumors, benign lesions of the ovary (n=45), and normal ovary (n=3). The concentration of HA was determined by a sandwich type ELISA-like assay in triplicates. The coefficient of variation for repeated assays on the same samples was 12.65% and that for replicates within an assays 2.90%. Results: Median HA concentration in normal serum was 25.4 ng/ml (range, 15.3–50.1). HA concentrations in the serum of patients with benign lesions of the ovary, borderline and malignant tumors were 19.7 ng/ml (0.0–126.1), 22.1 ng/ml (0.0–76.0) and 63.7 ng/ml (7.0–8037.5), respectively. The concentration of HA in the serum of patients with malignant tumors was significantly higher than in other groups (p < 0.0005). The approximate area under the ROC curve (AUC) was 0.83 (p <0.0005, 95% CI 0.71–0.94). CA125 was a better diagnostic tool with AUC of 0.936, but the combination of HA and CA125 was able to predict ovarian cancer with specificity of 100% and sensitivity of 83% (AUC=0.96, p<0.0005, 95% CI 0.91–1.0). Conclusions: Serum HA may have potential as a tumor marker in epithelial ovarian cancer. It is possible to increase the diagnostic specificity and sensitivity of CA125 by measuring serum HA. No significant financial relationships to disclose.