tbuckley/cabot-search huggingface dataset:
Progression-free survival (PFS) in patient subgroups in RIBBON-2, a phase III trial of chemotherapy (chemo) plus or minus bevacizumab (BV) for second-line treatment of HER2-negative, locally recurrent or metastatic breast cancer (MBC).
Authors: A. Brufsky, R. R. Rivera, S. A. Hurvitz, I. N. Bondarenko, V. Smirnov, V. Valero, H. S. Rugo, R. Swamy, H. Mu, E. A. Perez
Journal: Journal of Clinical Oncology (2010)

1021 Background: Three prior phase III trials (E2100, AVADO, and RIBBON-1) established that combining BV with chemotherapy as first-line treatment for MBC leads to consistent improvement in PFS. In RIBBON-2, which evaluated the combination of BV with various chemotherapies to treat MBC in the second line, the addition of BV also improved PFS (Brufsky et al., SABCS 2009). Here we examine the consistency of this benefit in prespecified subgroups. Methods: Eligible patients were randomized 2:1 to chemo+BV vs. chemo+placebo (PL). Prior to randomization, investigators chose one of the following chemo agents: taxane, gemcitabine, capecitabine, or vinorelbine. The primary endpoint was investigator-assessed PFS pooled across all chemo cohorts. As prespecified exploratory analyses, hazard ratios (HRs) for the subgroups were estimated using an unstratified Cox regression model. Results: 684 patients (chemo+PL=225; chemo+BV=459) were enrolled. Addition of BV improved median PFS (chemo+PL=5.1 mo; chemo+BV, 7.2 mo; HR=0.78; p=0.0072). Subgroup analyses showed that HRs for PFS consistently favor the BV arms when pooled across all chemo cohorts (Table). Conclusions: These data are consistent with the primary results of RIBBON-2 and suggest that BV combined with standard chemotherapies provides PFS benefit to HER2-negative MBC patients with differing clinical characteristics and disease histories. Subgroup (n) HR (95% CI) All patients 0.78 (0.64–0.93) Age, yr <65 (539) 0.82 (0.66–1.00) ≥65 (145) 0.58 (0.38–0.88) Interval, MBC to first-line PD, mo <6 (192) 0.67 (0.47–0.97) ≥6 (492) 0.81 (0.66–1.01) No. of metastatic sites <3 (374) 0.76 (0.59–0.98) ≥3 (310) 0.74 (0.56–0.98) Visceral involvement Yes (500) 0.77 (0.62–0.96) No (184) 0.74 (0.50–1.07) Bone-only disease Yes (50) 0.65 (0.30–1.43) No (634) 0.75 (0.62–0.91) Hormone receptor status Positive (494) 0.89 (0.71–1.10) Negative (190) 0.53 (0.37–0.75) Prior taxane and anthracycline Yes (317) 0.70 (0.53–0.92) No (367) 0.80 (0.62–1.03) Prior metastatic hormone therapy Yes (375) 0.87 (0.68–1.12) No (309) 0.63 (0.47–0.84) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech Abraxis BioScience, Genentech Roche Abraxis BioScience, Genentech Genentech, Roche, sanofi-aventis
An Analysis of SV40-Induced Transformation of Hamster Kidney Tissue &lt;italic&gt;In Vitro&lt;/italic&gt;. III. Persistence of SV40 Viral Genome in Clones of Transformed Hamster Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Paul H. Black
Journal: JNCI Journal of the National Cancer Institute (1966)

Clones of SV40-transformcd hamster kidney cells were established from single cells isolated in microdrop cultures containing SV40 antiserum. Infectious SV40 was recoverable, by the overlay technique, from 11 of 12 clones from positive lines. Clones derived from the negative clone remained negative for SV40 but contained the SV40-specific T antigen in essentially all of the cells, as did the positive clones. No infectious virus or viral antigen was ever found in any of the clone lines, by methods other than the overlay technique, but small amounts of virus were occasionally recovered from hamster tumors induced with cells from positive clones. The results indicate that all the SV40-transformed hamster kidney cells have at least a part of the SV40 genome and that the vast majority contain the complete SV40 genome in the absence of synthesis of whole virus.
Human Papilloma Virus (HPV-16) as a <u>surrogate marker</u> for Schistosomiasis-Induced Bladder Cancer
Authors: A. O. Kaseb, D. M. Kurnit
Journal: Journal of Clinical Oncology (2005)

4687 Background: Schsitosomiasis is the second most prevalent tropical disease after Malaria. It is a parasitic disease that can chronically infect the urinary bladder leading to squamous cell carcinoma. Only one study, done at the National Cancer Institute in Egypt, reported the association between HPV and Schisotsomiasis-Induced Bladder Cancer (SIBC) using In-Situ hybridization analysis of tumor tissue specimens. Methods: We collaborated with the National Cancer Institute in Egypt and applied a more sensitive analysis, Quanititative Polymerase Chain Reaction (QPCR), to the same specimens using a degenerate probe that detects oncogenic strains of HPV. Also, we requested to apply our analysis to: serum, urine and peripheral blood specimens taken from the same patients at the same time and also sera from: the same patients after surgical removal of the tumor and from patients with Schistosomiasis but no cancer, also from normal controls and patients with non SIBC. Results: HPV-16, identified by sequencing, was found in: 17/22 (77%) of tumor specimens, compared to 46% in the Egyptian study, 20/22 (91%) of sera specimens and 9/22 (41%) of urine specimens. In contrast, HPV was absent in the rest of the speciemns. Conclusions: HPV-16 may thus be strongly implicated in the etiology of SIBC, accelerating the carcinogenic process. QPCR for HPV-16 is a sensitive and non-invasive test that can be used as a surrogate marker for SIBC. We recommend screening all patients with Schistosomiasis for HPV-16. Seronegative patients will qualify for HPV vaccination (100% protective) and seropositive patients will need more follow up as warranted and if they developed cancer the test can be used to monitor their response to therapy. No significant financial relationships to disclose.
Is response rate or stable disease rate a surrogate endpoint for survival in the treatment of advanced non-small cell lung cancer using epidermal growth factor receptor tyrosine kinase inhibitors?
Authors: K. Tsujino, T. Kawaguchi, A. Kubo, N. Aono, K. Nakao, T. Kurata, Y. Koh, Y. Kusunoki, M. Kawahara, M. Takada
Journal: Journal of Clinical Oncology (2008)

14600 Background: Clinical trials have been intensively conducted on advanced non-small cell lung cancer (NSCLC) using epidermal growth factor tyrosine kinase inhibitors (EGFR-TKIs). In these trials, molecular biomarkers have been often examined with response rate (RR) as a surrogate endpoint instead of survival time. However a relationship between RR and survival time has not been determined in patients treated with EGFR-TKIs. The purpose of this study is to clarify the significance of RR and stable disease rate (SDR) as a surrogate endpoint for survival in the treatment of advanced NSCLC with EGFR-TKIs, through a systematic review of publications. Methods: Prospective trials of EGFR-TKIs monotherapy in NSCLC were extracted from MEDLINE, EMBASE, and the grand meetings in 2007 of the American Society of Clinical Oncology, European Cancer Conference, and World Conference on Lung Cancer. Correlation between clinical response and survival was examined in each study using SAS Version 8.2. Because of the presence of interaction for RR and SDR, two covariate analysis was applied. Multiple regression analysis was also performed on a per study basis to adjust imbalance of such patient characteristics in each study as gender, performance status (PS), histologic subtypes of cancer, number of prior chemotherapies, ethnicity, and types of EGFR- TKIs. Results: We identified 17 phase II trials, 4 phase III trials and 7 prospective trials with a total of 6163 patients and 30 treatment arms including 22 arms for gefitinib group and 8 arms for erlotinib group. In the two covariate analysis, RR strongly correlated with MST (P<0.0001), while SDR did not. In the multiple regression setting, only RR and PS significantly contributed to MST prolongation (P=0.003 and 0.04, respectively), and MST increased 0.21 month with each 1% increase in RR. RR had also significant correlation with median time to progression (MTTP, P=0.002), and SDR did (P=0.04) in the multiple regression setting. Conclusions: We found a significant relationship between RR and MST in clinical trials with EGFR-TKIs. SDR was a surrogate endpoint just for MTTP in this study. No significant financial relationships to disclose.
Cytotoxic Antibody Reactive With Cultures of Lymphoid Cells: Occurrence in Disease and Normal Human Sera
Authors: Ronald B. Herberman, Jun-Mo Nam
Journal: JNCI Journal of the National Cancer Institute (1971)

The effect of disease and other factors on the expression of a natural cytotoxic antibody in human serum was studied. The incidence and titer of the antibody were higher in the sera of patients with Burkitt's lymphoma. In contrast, reactivity in the sera of patients with leukemia was lower than that in normal controls. The antibody level in chronic leukemia was inversely related to the peripheral leukocyte count. During the acute phase of infectious mononucleosis, antibody levels were low. The possibility of in vivo absorption of the cytotoxic antibody by the abnormal cells is discussed. Present evidence indicates that the cytotoxic antibody is an IgG immunoglobulin.
The effect of fixed mandibular advancement on regional upper airway geometry in OSA patients
Authors: Olivier M. Vanderveken, Wim Vos, Jan De Backer, Kristien Wouters, Wilfried De Backer, Marijke Dieltjens, Marc Braem
Journal: European Respiratory Journal (2014)

Rationale 

Obstructive sleep apnea (OSA) severity correlates with upper airway (UA) morphology. UA collapsibility however does not respond to mandibular advancement (MA) in an homogeneous way. This study investigates the regional effects in the UA of MA in a large population of OSA patients.

Methods 

100pts were consecutively enrolled. At present baseline polysomnography (PSG) data in terms of apnea-hypopnea index (AHI) is available for 86pts. For 81pts functional CT scan analysis (FRI) is performed without and with MA set in 75% of maximal protrusion (MP). UA volume (iVuaw), resistance (iRuaw), minimal area (Amin) and the distance hyoid-spina mentalis (H-SM) are assessed (see figure). Response is defined as an increase in Amin with MA.

![Figure][1] 



Results 

Baseline AHI values correlate with iRuaw (R=0.38), Amin (R=-0.29) and the distance H-SM (R=0.24). MA does increase Amin (+1cm2, p=0.005). Responders (resp) have a larger forward+downward motion of the SM as compared to non-responders (nresp). iVuaw change was predominantly found in responders and was located posterior of the uvula (see figure).

Conclusions 

Amin and iRuaw do correlate with the severity of OSA. MA does improve these parameters. The largest changes in UA geometry were found posterior of the uvula. Next step is to investigate how these regional geometric changes with MA in situ do relate to clinical outcome.

This study was funded by IWT.

 [1]: pending:yes
Acute toxicity of epirubicin.
Authors: G B Zulian
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.1986.4.12.1867 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3465877 Acute toxicity of epirubicin. G B ZulianxG B ZulianSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.12.1867 PDF "Acute toxicity of epirubicin.." Journal of Clinical Oncology, 4(12), pp. 1867–1868© 1986 by American Society of Clinical Oncology
Combination of CpG7909 and rituximab in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL): A phase I, open label dose-escalation study of safety and tolerability
Authors: G. J. Weiner, B. K. Link, J. Leonard, C. Emmanouilides, G. Albert, T. Schmalbach
Journal: Journal of Clinical Oncology (2004)

6594 Background: CpG ODN are a class of chemically synthesized oligodeoxynucleotides that activate B-cells and plasmacytic dendritic cells through the pattern receptor Toll-like receptor 9. CpG ODN can increase CD20 expression on malignant B-cells in vitro and have been shown to enhance the efficacy of antibody therapy in murine models. An early clinical trial showed responses to CpG 7909 (ProMune) in two NHL patients treated with single agent IV CpG 7909. We report a phase I trial of escalating doses of CpG, administered IV or SC, in combination with standard dose rituximab (Rituxan [R]) to assess safety of the combination. Methods: Patients with relapsed or refractory NHL who were candidates for [R] as a single agent were enrolled in one of three cohorts. All received [R] weekly times 4, with each dose of [R] followed by a dose of CpG. Cohort 1 (19 subjects) received 4 weekly doses of CpG SC (0.01, 0.04, 0.08, or 0.16 mg/kg). Cohort 2 (19 subjects) received 4 weekly doses of CpG IV (0.04, 0.16, 0.32, or 0.48 mg/kg). Cohort 3 (12 subjects) received 0.24 mg/kg SC weekly for 20 weeks. Subjects were monitored for toxicity and tumor response. Histologically, 24 of 50 subjects had follicular lymphoma. Thirty-three patients had received prior [R], and a number were refractory to their most recent [R]. Results: The combination of CpG + [R] was well tolerated with transient Grade 1 and 2 local injection site reactions, arthalgias, and myalgias. Significant adverse events included lymphopenia (2= Gr3), neutropenia (1=Gr3, 1=Gr4), diarrhea (1=Gr3), and dehydration (1= Gr3). There were 7 objective responses within 50 days of the initiation of therapy (Cohort 1 - 1CR and 1PR; Cohort 2 - 2 CR and 3 PR;) and 5 responses (Cohort 3 - 1 CR and 4 PR) within 20 weeks. Cytokine and chemokine measurements demonstrated biological activity in the SQ cohorts. Conclusions: CpG can be given safely in combination with [R] in NHL patients by both the IV and SQ route, without apparent exacerbation of [R] related infusion toxicity. Further follow-up is needed to determine the response rate and duration of response to this combination immunotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmacutical Group
Abstract 12786: Renal Denervation Reduces Pulmonary Vascular Remodeling in Experimental Pulmonary Arterial Hypertension
Authors: Denielli da Silva Goncalves Bos, Chris Happé, Ingrid Schalij, Wioletta Pijacka, Julian F. Paton, Harm-Jan Bogaard, Nico Westerhof, A.C. (Bert) van Rossum, Anton Vonk-Noordegraaf, Frances S. de Man, M. Louis Handoko
Journal: Circulation (2014)

Introduction and Hypothesis: We have previously shown that neurohormonal over-activation (i.e. sympathetic nervous system and renin-angiotensin-aldosteron system) accelerates disease progression in pulmonary arterial hypertension (PAH). Renal denervation is a new clinical modality, which may have therapeutic potential in PAH, as it suppresses both neurohormonal systems. Here, we tested the hypothesis that renal denervation ameliorates pulmonary vascular remodeling in experimental PAH. Methods: PAH was induced in male Wistar rats by a single injection of monocrotaline (60mg/kg; s.c.). Twelve days later, development of PAH was confirmed by echocardiography. PAH-rats were then randomized for renal denervation or sham operation (n=9 /group). At end-of-study (body mass loss >5%), echocardiography was repeated, with additional right ventricular (RV) pressure-volume measurements and histological analysis was performed on lung tissue. Results: Renal denervation was successful, indicated by a reduction of the nora...
Selected Biochemical Actions of Ovarian Hormones
Authors: Kenneth S. Korach
Journal: Environmental Health Perspectives (1981)

This review is concerned with a general discussion of the actions of ovarian hormones, including relaxin, a polypeptide hormone, and estrogens and progestogens, which are two types of steroid hormones. Particular emphasis is placed on describing the sites of action and target organ responses induced by the two steroid hormones. A detailed description of estrogen activity in reproductive tract tissue is given as an example of the intracellular mechanism of action of this steroid hormone.
Functional and prognostic influence of receptor polymorphisms in the vascular endothelial growth factor system in colorectal cancer
Authors: T. Hansen, K. G. Spindler, D. A. Olsen, R. F. Andersen, J. Lindebjerg, I. Brandslund, A. Jakobsen
Journal: Journal of Clinical Oncology (2009)

e15032 Background: The vascular endothelial growth factor (VEGF) system plays a key role in the angiogenic process ensuring a sufficient blood supply to the growth of malignant tumours. The clinical importance of single nucleotide polymorphisms (SNP's) in the VEGF receptors is still unknown. The aim of this study was to investigate the functional and prognostic influence of the V297I C/T and the -604 T/C SNP's in the VEGFR-2 gene, in tumour and normal tissue from colorectal cancer patients. Methods: Blood samples and tissue were collected from 110 patients, surgically resected for colorectal cancer. Genomic DNA was isolated from whole blood, and SNP's were analysed by PCR. Gene expression analysis was performed by RT-PCR and protein analysis was performed by ELISA. Progression free survival according to genotypes was compared using the Kaplan-Meier method and the logrank test. Results: Median gene expression according to the CC genotype of the -604 T/C SNP, were significantly higher than the median gene expression of the TT genotype (p = 0.045) and the TC genotype (p = 0.033) in CRC tissue. Regarding the V297I C/T SNP, median protein concentration according to the CT genotype was significantly higher than the median protein concentration of the CC genotype, p = 0.005. The CC genotype held prognostic information compared to CT and TT genotypes for both SNP's, p&lt;0.05. Conclusions: The V297I C/T SNP seems to have a functional influence on the VEGFR-2 protein level, and the -604 T/C SNP on the gene expression level in CRC patients. The results furthermore indicate a prognostic influence of both SNP's on progression-free survival. No significant financial relationships to disclose.
Reply
Authors: Mark H. Kuniholm, Kenrad E. Nelson
Journal: Hepatology (2016)

Potential conflict of interest: Nothing to report. We appreciate the interest of Gupta et al. in our article describing hepatitis E virus (HEV) coinfection in human immunodeficiency virus (HIV)‐infected U.S. women.1 Gupta et al. tested 459 Nepalese HIV patients and 587 blood donors from the Kathmandu Valley for hepatitis E virus (HEV) antibody (anti‐HEV) immunoglobulin (Ig) M—15% of HIV patients versus 4% of blood donors were anti‐HEV IgM+ (p < 0.001). Among the HIV patients, those with CD4 count >200 cells/μL were more likely to be anti‐HEV IgM+ whereas those with hepatitis C virus (HCV) antibody were less likely to be anti‐HEV IgM+. Although interesting, these observations do not resolve a long‐standing controversy in HEV epidemiology—is risk of HEV infection higher in HIV‐infected individuals, as compared to HIV‐uninfected individuals, and if so, why? Conflicting data have been reported from Zambia2 and the United Kingdom.3 HIV patients often differ from the general population and from blood donors in a variety of ways (e.g., by income, racial/ethnic group, educational attainment, number of sexual partners, and use of illicit drugs). Therefore, it is difficult to discern whether the association between HIV and HEV observed in Nepal may be attributed to household characteristics (e.g., differences in availability of purified drinking water), HIV risk behaviors (e.g., anal sex and potential exposure to fecal material), or to a biological consequence of HIV infection itself (e.g., loss of adaptive immunity in the gut‐associated lymphoid tissue). Studies of carefully characterized control populations recruited from the same communities as HIV patients may help clarify whether these patients are at increased risk of HEV infection. Regarding differences in anti‐HEV IgM positivity by CD4 count, our data1 and those of others suggest that appearance of HEV antibodies in blood can be delayed or absent in HIV patients with low CD4 counts. We speculate that high CD4 count is not a risk factor for HEV acquisition in Nepalese HIV patients, but rather high CD4 count is associated with a detectable immune response to HEV infection. The inverse association between anti‐HEV IgM positivity and HCV seroprevalence in Nepal is puzzling—we observed the opposite association in the United States.4 However, relationships between incidence of HEV and other hepatitis viruses may vary by region and HEV genotype.
Spontaneous Tumor Incidence in Female Brown Norway Rats After Lifelong Diets High and Low in Linoleic Acid&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: W J Kort, P E Zondervan, L O Hulsman, I M Weijma, W C Hülsmann, D L Westbroek
Journal: JNCI Journal of the National Cancer Institute (1985)

High linoleic acid (C18:2) (group I; 17.7 cal%) and low C18:2 (group II; 3.3 cal%) diets were given to groups of inbred Brown Norway virgin female rats (100 animals/group), during their whole life-span. A total of 140 tumors were found in group I and 123 tumors in group II; the median survival times of the 2 groups were 124.2 and 118.5 weeks, respectively. Total spontaneous tumor incidence and median survival times were not significantly different. However, significant differences were found in the incidences of some specific tumors: The numbers of reticuloendothelial tumors and adrenocortical carcinomas were significantly higher in the group of animals receiving the low-C18:2 diet. A high incidence of tumor multiplicity, however, resulted in a significantly greater number of mammary tumors in the high-C18:2 diet group.
M-VAC combination in locally advanced, locally recurrent or metastatic breast carcinoma. A phase II study
Authors: G Bisagni, G Cocconi, G Ceci, V De Lisi, B Di Blasio, R Lottici, R Passalacqua, C Finardi
Journal: Annals of Oncology (1994)

The M-VAC combination is very effective in bladder carcinoma, as are all four drugs, as single-agent, in advanced breast carcinoma.M-VAC was given in 27 patients, 4 with locally advanced breast carcinoma, 3 with local recurrence and 20 with distant metastases. The median age was 51 (range 25; 70). Eleven of the 20 patients with metastatic disease has been previously treated with a different chemotherapy.15 of 26 evaluable patients responded, with 9 (35%) complete remissions and 6 partial responses. The overall response rate (CR plus PR) was 57% (95% confidence interval 38% to 76%). In patients with metastatic disease the median duration of response was 7 months (range 4+; 36+), median time to progression 5 months (range 1; 36+) and median duration of survival 17 months (range 1; 40+).The M-VAC combination is very effective in locally advanced, locally recurrent and metastatic breast carcinoma. Further trials are warranted to evaluate whether the activity of this combination is partially schedule-dependent.