tbuckley/cabot-search huggingface dataset:
Abstract P1-12-03: The STAGE Study: A Phase III Comparison of Anastrozole Plus Goserelin with Tamoxifen Plus Goserelin as Pre-Operative Treatments in Premenopausal Breast Cancer Patients
Authors: Y Sagara, N Masuda, T Kinoshita, H Iwata, S Nakamura, Y Yanagita, R Nishimura, H Iwase, S Kamigaki, H Takei, S. Noguchi
Journal: Cancer Research (2010)

Abstract Background: Although superior antitumor activity of anastrozole over tamoxifen has been well established in postmenopausal breast cancer patients, it still remains to be examined whether or not anastrozole is superior to tamoxifen in premenopausal breast cancer patients whose ovarian function is suppressed by goserelin to postmenopausal levels. The aim of this study was to compare anastrozole plus goserelin versus tamoxifen plus goserelin as pre-operative treatment for premenopausal Japanese women with breast cancer. Methods: Phase III, randomized, double-blind, parallel-group, multi-center study (D539BC00001). Premenopausal patients (pts) with ER-positive and HER2-negative breast cancer and with operable and measurable lesions (T [2-5 cm], N0, M0) were randomized 1:1 to receive a goserelin 3.6 mg depot injection once monthly plus either anastrozole 1 mg (A+G) or tamoxifen 20 mg (T+G) p.o. once daily. Treatment continued for 24 weeks prior to surgery or until any other criterion for discontinuation was met. Concomitant chemotherapy was not permitted during the pre-operative period. The primary objective was to assess the best overall tumor response (either a complete response [CR] or a partial response [PR]), according to modified RECIST criteria. Tumor size was measured by caliper and ultrasound every 4 weeks and by magnetic resonance imaging/computed tomography (MRI/CT) every 12 weeks. Tolerability (adverse events [AEs], laboratory tests, vital signs, WHO performance status) was assessed as a secondary objective. AEs were evaluated according to CTCAE v3.0. Results: In total, 197 pts were randomized (A+G: 98, T+G: 99) and 185 pts completed the 24-week pre-operative treatment period and went on to receive breast surgery. The remaining 12 pts discontinued study treatment due to disease progression (A+G: 1; T+G: 5), voluntary discontinuation (A+G: 2; T+G: 3) and AE (T+G: 1). Pt demographics were generally well balanced. Median duration of exposure was similar for A+G (171 days) and T+G (170 days); treatment compliance was 99% for both. A+G led to a statistically significantly higher overall response rate compared with T+G, by caliper as well as by ultrasound and MRI/CT. The safety profiles were consistent with the known safety profile of anastrozole, tamoxifen and goserelin. The incidence of AEs was similar for A+G (88.8%) vs T+G (85.7%); most AEs were mild or moderate (CTC grade 1 or 2). The most common AEs were hot flash (A+G: 52.0%; T+G: 53.1%) and arthralgia (A+G: 35.7%; T+G: 20.4%). Conclusion: This study has demonstrated that the A+G combination has a superior benefit-risk profile compared with T+G as pre-operative treatment in Japanese premenopausal women with ER-positive breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-12-03.
BM-21 * RISK OF NEOPLASTIC MENINGITIS FROM BRAIN METASTASES IN NSCLC INITIALLY TREATED WITHOUT WHOLE BRAIN IRRADIATION: A RETROSPECTIVE ANALYSIS OF A CASE SERIES
Authors: A. Muggeri, B. Calabrese, S. Cerrato, B. Diez
Journal: Neuro-Oncology (2014)

Characterize the risk of neoplastic meningitis (NM) in patients with brain metastasis from NSCLC. Determine site of relapse and cause of death. We analyzed 56 patients treated initially with surgery and / or radio surgery, with or without chemotherapy without WBI from July 2007 to May 2014, with a minimum follow-up of 4 months. The median age was 58 years (35-81), 30 male. The median follow up from diagnosis of brain metastases was 13 months (1-82). Twenty one patients had solitary metastasis. Median cerebral progression-free survival (PFSc) and survival from diagnosis of brain metastases (SVbm) were calculated by Kaplan-Meier. Initial treatment: 17 surgery, 11 surgery followed by radio surgery, 17 radio surgery and 11 surgery with adjuvant local radiation therapy. Thirty six (64%) had progression of CNS disease. Nine patients developed NM (16%), 5 of them contiguous to the surgical bed (neither of them have received focal radiotherapy) one patient after radiosurgery. Eleven patients underwent WBI at progression, 9 of them by NM, one patient with NM was lost in the follow up. The prognosis of the patients with NM was very poor with a median survival time of 4 months. Only three patients are alive with stable disease. One of the 11 patients that were treated with adjuvant focal radiotherapy relapsed locally or had NM. The median PFSc and SVbm were 9 and 13 months respectively. In 11 patients the cause of death was neurological progression, 5 of them by NM. Fifteen of 56 patients are alive. We must use adjuvant local radiotherapy on the surgical bed to decrease the risk of local relapse and NM if we chose to treat brain metastases without WBI.
SAT0244 Correlation between circulating TFH cells and disease activity as well as autoantibody production in chinese patients with systemic lupus erythematosus
Authors: X. Feng, D. Wang, J. Chen, L. Liu, Z. Lu, X. Li, L. Sun
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Previously we have shown that interleukin-21 (IL-21) level was tightly associated with anti-nuclear antibody (ANA) production in cultured peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE) [1], suggesting a role for this cytokine in the disease onset. In addition to working on the expansion and maintenance of the Th17 lineage, IL-21 is also an important growth factor for T follicular helper (TFH) cells, thus could accelerate the production of pathogenic autoantibodies. <h3>Objectives</h3> To detect the levels of IL-21 and TFH cells as well as Th17 cells in Chinese SLE patients and to find out their relationships with disease activity, plasma cells and autoantibody levels. <h3>Methods</h3> Sixty-two adult SLE patients and 23 healthy subjects matched for gender and age were recruited. Disease activity was evaluated by the SLE disease activity index (SLEDAI) score. Proportion of circulating TFH cells (CXCR5+PD1+/CD4+), Th17 cells (CCR6+/CD4+) and plasma cells (CD19+CD138+) were measured by flow cytometry. Serum levels of IL-21, ANA and anti-double strand DNA (dsDNA) antibody were assessed by ELISA. To determine the effect of IL-21 on TFH cells, PBMCs from SLE patients were collected and cultured with or without human recombinant IL-21 (200ng/ul) in a tissue culture incubator and then harvested for TFH measuring at 24 and 72 hours. <h3>Results</h3> Proportion of circulating TFH cells and serum IL-21 levels were elevated in SLE patients comparing to those in normal controls, while there was no difference of Th17 cells between the two groups. TFH cells, but not IL-21 levels, were positively correlated with SLEDAI score, CD19+CD138+ plasma cells, serum ANA and anti-dsDNA titers in SLE patients. When recombinant IL-21 was added to PBMC culture systems, there was a significant increase of TFH cell proportions. <h3>Conclusions</h3> TFH cells contribute to disease activity and autoantibody production in SLE patients. IL-21 may act through the upregulation of TFH cells to play a role in the pathogenesis of SLE. <h3>References</h3> Feng X, Li R, Huang J, Zhang H, Zhu L, Hua B, Tsao BP, Sun L. Olf1/EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus. Arthritis Res Ther. 2010;12(2):R59. <h3>Disclosure of Interest</h3> None Declared
B-TYPE NATRIURETIC PEPTIDE LEVELS PREDICT VENTRICULAR ARRHYTHMIA POST LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION
Authors: Yaron Moshe Hellman, Azam Hadi, Milena Jani, Hongbo Lin, Changyu Shen, I-Wen Wang, Thomas Wozniak, Zubair Hashmi, Jeanette Pickrell, Marco Caccamo, Irmina Gradus-Pizlo, dnan Malik
Journal: Journal of the American College of Cardiology (2014)
F-18 FDG PET/CT for Detection of Malignant Involvement of Peripheral Nerves
Authors: Yulia Bronstein, Sudhakar Tummala, Eric Rohren
Journal: Clinical Nuclear Medicine (2011)

To evaluate the role of positron emission tomography plus computed tomography (PET/CT) scans in detecting malignant involvement of the peripheral nerves (PNs).We retrospectively reviewed medical records of all PET/CT studies performed at The University of Texas MD Anderson Cancer Center between 2003 and 2009, and selected patients in whom F-18 fluorodeoxyglucose (FDG) PET/CT findings were suspicious for malignant involvement of the PNs. We identified 26 cases of suspected tumorous involvement of the PNs that was subsequently confirmed by either biopsy or clinical follow-up. We evaluated the value of PET/CT in diagnosing malignant involvement of the PNs.Of the 26 patients, 12 had lymphoma, 10 had breast cancer, 2 had lung cancer, 1 had colon cancer, and 1 had melanoma. In 21 patients, magnetic resonance imaging (MRI) was performed, either for follow-up of the PET/CT finding or to find an explanation for symptoms. MRI confirmed the presence of disease in only 9 patients, was interpreted as normal in 7 patients, and was inconclusive in 5 patients. FDG PET/CT was able to differentiate an active tumor from post-treatment fibrosis and could assess response to therapy with a high degree of confidence.Our results indicate that FDG PET/CT is helpful in diagnosing malignant involvement of the PNs, especially when findings from anatomic imaging (MRI or CT) are negative. In cases of known treated malignancy involving the PNs, follow-up by PET/CT has the advantage of high sensitivity for local recurrence.
Emergence and Apparent Transmission of Rimantadine-Resistant Influenza A Virus in Families
Authors: Frederick G. Hayden, Robert B. Belshe, Richard D. Clover, Alan J. Hay, Marion G. Oakes, Whaijen Soo
Journal: New England Journal of Medicine (1989)

To determine whether rimantadine can protect family members from acquiring influenza A viral illness and to assess the possible selection of drug-resistant strains of virus, we conducted a randomized, double-blind, placebo-controlled study in three communities during two influenza seasons. When influenza A occurred in a family, the members (including the index patient) were given either rimantadine (adult oral dose, 200 mg per day) or placebo for 10 days. The presence of illness was monitored by daily recording of symptoms and temperature measurements; infection was determined by isolation of the virus and by serologic studies. Among households with documented influenza A infections, symptomatic illness occurred in one or more contacts in 10 of 28 families treated with rimantadine and in 10 of 209 families treated with placebo. Asymptomatic secondary influenza A infections were found in five families assigned to receive rimantadine and in four families assigned to receive placebo. Rimantadine-resistant strains of influenza A virus (H3N2 subtype) with mutations consisting of single amino acid changes in the M2 protein (residue 27, 30, or 31) were recovered from eight index patients and five contacts treated with rimantadine. There was apparent transmission of drug-resistant strains of virus in six contacts with secondary illnesses in five families. We conclude that when index patients are treated concurrently, rimantadine is ineffective in protecting household members from influenza A infection. If rimantadine is used for both treatment and postexposure prophylaxis in families, rapid selection and apparent transmission of drug-resistant influenza A viruses can occur.
P01.11 * ATF4 AS A MEDIATOR OF RESISTANCE TO TARGETED THERAPY IN HIGH-GRADE GLIOMAS
Authors: S. Moeckel, B. Neyns, E. Pan, M. Riemenschneider, A. Bosserhoff, A. Vollmann-Zwerenz, P. Hau
Journal: Neuro-Oncology (2014)

Small molecule inhibitors have been investigated in a large set of clinical trials in malignant gliomas. Despite promising preclinical studies, results of pilot trials have been generally disappointing. A deeper understanding of the complex biology of malignant glioma cells, and their adaptation to targeted agents is therefore critical for further therapy development. We analyzed gene expression in 18 short-term serum-free cultures of high-grade gliomas enhanced for brain tumor initiating cells (BTIC) before and after in vitro treatment with the tyrosine kinase inhibitor Sunitinib. Geneset enrichment analysis (GSEA) revealed that some of the regulated patterns are associated to the amino acid metabolism. In gene ontology annotations, additional evidence was raised that ER-stress response signaling which is connected to the amino acid metabolism is induced by Sunitinib. Based on the observation of gene network analysis (STRING) we hypothesize that the central mediator of the integrated stress response ATF4 (activating transcription factor 4) plays an important role in the regulation of the Sunitinib induced expression profiles and probably in the adaptation to treatment conditions. First, we confirmed a concentration dependent induction of ATF4 protein expression in Sunitinib treated BTICs. For further evaluation, we analyzed the expression of ATF4 in paraffin embedded tissue blocks from high grade glioma patients treated with Sunitinib by immunohistochemistry. ATF4 significantly correlated with shorter overall survival from the beginning of Sunitinib treatment. Interestingly, expression data from high grade gliomas retrieved from a public platform (REMBRANDT) revealed that transcription of the ATF4-induced TRB3 pseudokinase is negatively correlated with overall survival independent of treatment. In summary our data suggest that ATF4 expression may be predictive for response to Sunitinib and might also be involved in general resistance mechanisms in high grade gliomas. Further studies are planned to elucidate the induction of apoptosis and autophagy in dependence of ATF4 expression and its contribution to therapy resistance.
Abstract LB-135: Stanniocalcin 2 attenuates tumor cell proliferation but suppresses apoptosis in nutrient-deprived conditions.
Authors: Shuo Qie, Lifeng Tian, Chenguang Wang, Nianli Sang
Journal: Cancer Research (2013)

Abstract High levels of stanniocalcin2 (STC2), a member of the STC secreted glycoprotein family, correlates with tumor progression and poor prognosis. It has been reported that STC2 is over-expressed in response to various stresses, including hypoxia, endoplasmic reticulum stress, oxidative stress and irradiation. Glutamine (Gln) and glucose (Glc) are important nutrients for tumor cells, playing important roles as nitrogen and carbon sources to meet the bioenergetic, biosynthetic and reductive needs. Defective blood supply in solid tumors may result in nutrient insufficiency, including Gln and Glc insufficiency. It remains unknown how tumor cells respond to Gln- and Glc- insufficient microenvironment and regulate their viability and proliferation. Using gene profiling analysis with microarrays, we have identified STC2 as one of the most up-regulated genes in response to either Gln- or Glc- deprivation. We confirm that Gln-deprivation stimulates STC2 expression at both mRNA and protein levels in various human tumor cells by quantitative reverse transcription-real-time PCR and Western blot, respectively. Furthermore, we find that Gln-insufficiency activates both nuclear factor-κB (NF-κB) and ATF4 signaling pathways, which synergistically up-regulates STC2. Finally, we demonstrate that up-regulation of STC2 attenuates tumor cell proliferation but reduces apoptosis in Gln-insufficient conditions. These findings suggest a novel model that STC2 reprograms the priority of tumor cells from rapid proliferation to survival under stress conditions, indicating that STC2 may be a novel target for cancer therapy. Citation Format: Shuo Qie, Lifeng Tian, Chenguang Wang, Nianli Sang. Stanniocalcin 2 attenuates tumor cell proliferation but suppresses apoptosis in nutrient-deprived conditions. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-135. doi:10.1158/1538-7445.AM2013-LB-135
Circulating Tumor Cells as a Prognostic Marker in Metastatic Non-Small-Cell Lung Cancer Patients Receiving Chemotherapy
Authors: Y. Sakamori, Y. Kim, H. Yoshioka, M. Hirabayashi, K. Onaru, M. Fukui, T. Hirata, H. Nagai, H. Ozasa, M. Mishima
Journal: Annals of Oncology (2013)
Admixture mapping to identify breast cancer susceptibility loci in African American women.
Authors: DT Croft, X Mao, JA Hooke, CD Shriver, MD Shriver, RE Ellsworth
Journal: Cancer Research (2009)

Abstract Abstract #2090 Background: The incidence of breast cancer in young women is higher in African American (AAW) compared to Caucasian (CW) and is associated with an aggressive phenotype, including high-grade, ER/PR and HER2 negative status and p53 positive characteristics. The aggressive tumor behavior and pathological features of AAW are also seen in women from the Bite of Biafra, an area of Western Africa that was the predominant source of the American slave trade. Similar tumor characteristics and shared ancestry suggest that population-specific molecular factors contribute to the aggressive tumor phenotypes associated with AAW. Therefore, a method of admixture mapping is proposed for this study. Admixture mapping is also known as mapping by admixture linkage disequilibrium. It assumes in a recent admixed population, if certain phenotype or the prevalence of a disease is mainly caused by one of the ancestral groups, the genetic variant can be located by the elevated ancestry from that group.&amp;#x2028; Methods: Pathological characterization was performed histology specimens from 91 self-described AAW diagnosed with invasive breast cancer enrolled in the Clinical Breast Care Project. Genomic DNA was isolated and SNP data generated using the Affymetrix Mapping 100K arrays. African ancestry was determined using maximum likelihood estimator and chromosomal regions associated with disease identified using AncestryMap and AdmixMap.&amp;#x2028; Results: The average age of diagnosis was 51 years. 25% of patients had poorly-differentiated, triple negative tumors. All 91 patients had significant African ancestry, with a mean level of Nigerian ancestry of 0.3857. Results from both AncestryMap and AdmixMap suggest loci on chromosomal regions 5q32.2, 9q13.1 and 17p13.3 are associated with the development of breast cancer.&amp;#x2028; Discussion: Recently, admixture mapping was used to successfully identify a prostate cancer gene to chromosome 8q24 in African American men. Using a similar approach, we identified three chromosomal regions associated with the presence of invasive breast cancer in AAW with significant Western African ancestry. Of note, loss of 9q13 has been associated with poor survival, and allelic imbalance of 17p13.3 has been associated with loss of hormone receptor expression and poor prognosis. Thus, the use of admixture mapping may aid in the identification of genes involved in the development of the aggressive form of breast cancer associated with AAW. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2090.
P15.12 * SURVIVAL AND QUALITY OF LIFE AFTER SURGERY FOR BENIGN INTRACRANIAL TUMOURS: AGE MATTERS?
Authors: N. Nocchi, M. Iacoangeli, M. Dobran, A. Di Rienzo, L. di Somma, L. Alvaro, D. Nasi, R. Benigni, F. Sessa, M. Scerrati
Journal: Neuro-Oncology (2014)

INTRODUCTION: Intracranial benign tumours are an increasingly common condition in the elderly population (>70 years) thanks to the prolonged life expectancy and the improvement of neuroradiological studies. Surgical resection in these patients, even if indicated, could be controversial due to patient's ageing physiology and eventual comorbidities, so it is difficult for surgeons to compare the advantages of a surgical removal against radiosurgery or a “wait and see” behaviour. We report our experience in dealing with patients (>70 years) surgically treated for benign intracranial neoplastic lesions (deep-seated and/or located in eloquent areas). We report how surgery in the elderly could be effective as in younger patients with no higher incidence of complications and reduction of the quality of life and/or survival. METHODS: From January 2010 to January 2014, 42 patients (12 male and 30 female with a mean age of 75 years) were submitted to a benign intracranial tumours surgical removal. The oldest patient was 86 years old. Neurological and physical conditions were assessed preoperatively and neuroradiological examination (MRI or, if it is contraindicated, a CT scan) revealed size and location of the lesions. Intraoperatively we used neuronavigation and neurophysiological monitoring. Outcome data included mortality, recurrence, complications and length of hospital stay (LoS). RESULTS: The patients' pathologies were: meningiomas in 32 patients, followed by 7 pituitary adenomas and 3 acoustic neuromas. In 35 pts a gross total removal was obtained whereas a sub total removal and partial removal were achieved in 5 and 2 pts respectively. Patients had a mean length of hospital stay of 9,7 days. Postoperative complications were observed in 6 patients, represented by CSF leaks (4 pts) and intracerebral haemorrhage (2 pts). There were better postoperative results in patients with few comorbidities and tumours of small dimensions and accessible location. The mortality rate was 2,4 %. Neurological symptoms improved in 38 patients and deteriorated in 4 pts. Patients with recurrent tumours seems to have a higher operative risk. CONCLUSIONS: While in the past age itself often represented a contraindication to surgical removal of benign intracranial tumours, nowadays, thanks the improvements in surgical technique and the minimally invasive attitude along with tailored surgical instruments (microneurosurgery or endoscopy) and new technologies such as neuronavigation and intraoperative brain mapping, these surgical procedures could be effectively performed without higher incidence of postoperative complications, when compared to the same surgery performed in younger patients. Obviously a careful preoperative anaesthetic evaluation is mandatory, and above all a meticulous postoperative management. Patients too long intubated or kept in bed easly develop complications.