tbuckley/cabot-search huggingface dataset:
Is tumor size important in HER2-positive breast cancer?
Authors: C. Parise, K. Bauer, V. Caggiano
Journal: Journal of Clinical Oncology (2010)

1582 Background: There is considerable interest in small size HER2-positive invasive breast cancer. We have previously shown that the HER2-positive subgroup is heterogeneous. We now examine the impact of tumor size on survival among the ER-/PR-/HER2+, ER+/PR+/HER2+, and ER-/PR-/HER2- subtypes. Methods: Using the California Cancer Registry 2000-2007 we studied 85,373 cases of stages 1-3 primary invasive breast cancer. Kaplan-Meier cause-specific 5-year overall survival (OS) was computed and the log-rank test was used to compare survival among the subtypes within each tumor size. Cox-proportional hazards analysis was used to determine the effect of tumor size within each of the subtypes after adjusting for age, race/ethnicity, stage, grade, and socioeconomic status. Anti-HER2 treatment information was not available. Hazard ratios (HR) and 95% confidence intervals were computed. Results: Approximately 24% of tumors were 10mm or smaller. About 1/3 of all cases were ER-/PR-/HER2+ (7%), ER+/PR+/HER2+ (10%), and ER-/PR-/HER2- (13%). For tumors of 5 mm or less (T1a), the ER+/PR+/HER2+ subtype had an OS of 99% compared with 95% for the ER-/PR-/HER2- (X2 = 4.79; p < 0.03) and 97% for the ER-/PR- /HER2+. For tumors 6-10 mm (T1b), there was a similar pattern. The ER+/PR+/HER2+ subtype had 98% OS whereas the ER-/PR-/HER2- (X2 = 13.98; p < 0.001) and ER-/PR-/HER2+ were 94%. For the three subtypes of interest, T1a and T1b tumors were not associated with increased likelihood of death. T1c tumors had statistically significant increased HRs for the ER-/PR-/HER2- (HR = 1.95; 95%CI = 1.07-3.58) and ER-/PR- /HER2+ (HR = 2.27; 95%CI = 1.18-4.36) subtypes. For the ER+/PR+/HER2+ subtype, only tumors 2.1-5 cm (T2), were associated with an increased likelihood of death (HR = 3.48; 95%CI = 1.23-9.86). Conclusions: For ER+/PR+/HER2+ tumors up to 10 mm, OS is excellent. For the ER-/PR-/HER2+ and ER-/PR-/HER2- subtypes, there is an increased likelihood of death for T1c and larger tumors but the risk of death does not increase for the ER+/PR+/HER2+ subtype until the tumor is greater than 20 mm. The effect of ER-postivity must be considered when discussing HER2-positive breast cancer. For small tumors, ER-negativity appears to be more important than HER2-positivity. No significant financial relationships to disclose.
Radical prostatectomy versus high intensity-focused ultrasound for localized prostate cancer: A matched-pair comparison.
Authors: Gilles Pasticier, Sebastien Crouzet, Marc Colombel, Olivier Rouviere, Muriel Rabilloud, Jean-Yves Chapelon, Florence Mege-Lechevallier, Helene Tonoli-Catez, Xavier Martin, Albert Gelet
Journal: Journal of Clinical Oncology (2015)

74 Background: Radical prostatectomy is the gold standard treatment for localized prostate cancer. HIFU is a treatment option with promising outcomes. No randomized study is available to compare those techniques. The goal of the study was to evaluate the oncologic outcome of patients treated with HIFU and radical prostatectomy by using a matched pair analysis to compare the 2 groups. Methods: A total of 710 patients treated between 2000 and 2005 were prospectively followed in our institutional database and matched to a 1:1 basis following know prognostic variables: prostate-specific antigen (PSA) level, Gleason score, and clinical stage. After matching, 588 patients (294 in each group) were further analysed. The starts of salvage external beam radiotherapy (S-EBRT) or definitive palliative androgen deprivation therapy (ADT) were primary endpoints. Other endpoints were overall, cancer specific and metastasis free survival rates: The survival rates were calculated with Kaplan-Meier estimate Results: The seven years S-EBRT free survival rate was significantly lower after HIFU than after RP (62% versus 78%, p=0.001). The palliative androgen deprivation free rate at nine years was not significantly different between HIFU and RP (86% versus 87%, p=0.271). At nine years the overall, cancer specific and metastasis free survival rates were similar: 89%, 97%, 94 % and 89%, 97% and 97% for HIFU and RP respectively (p=0.186, 0.312, 0.107). Conclusions: Matched pair comparison of HIFU and RP has shown a higher rate of S-EBRT for HIFU. At 9 years, the rate of patients who need palliative ADT, the overall cancer specific and metastasis free survival rates were not significantly different between HIFU and RP.
Pulmonary eosinophilic syndromes characterization. The role of peripheral eosinophilia as a marker of clinical evolution
Authors: Helder Novais e Bastos, Patrícia Mota, Natália Melo, Marília Beltrão, Oksana Sokhatska, Carmo Palmares, António Morais
Journal: European Respiratory Journal (2012)

INTRODUCTION: Pulmonary eosinophilic syndromes (ES) are a heterogeneous, rare and not fully characterized group of diseases. OBJECTIVES: Evaluation of ES patient9s clinical features and its evolution. METHODS: 47 patients with >20% BAL eosinophils or compatible histological features were included and its clinical files retrospectively analyzed. RESULTS: After excluding 19 patients that had other diseases and 9 because of lacking information, 19 patients were enrolled: 8 presented Chronic Eosinophilic Pneumonia (CEP), 6 Churg-Strauss Syndrome (CSS), 3 Acute Eosinophilic Pneumonia and 2 Allergic Bronchopulmonary Aspergillosis (ABPA). Mean age at symptoms onset 37±14.6 and at diagnosis 43±14.3 years. The majority was female (68.4%) and nonsmokers (76.5%). Peripheral eosinophilia was observed in 78.9% patients (1.73±1.32x109/L), mean eosinophilia in BAL was 51.1±29.16%, airflow obstruction was observed in 55.6% patients, 22.2% had restrictive pattern, 16.7% mixed pattern and 5.6% normal values, without significant differences among entities. Concerning CEP, CSS and ABPA cases after treatment, 83.3% presented obstructive pattern, 16.7% normal values and a significant increase of TLC (p=0.038) and RV (p=0.018) were observed. The RV raise was associated with mild peripheral eosinophilia or persistent eosinophilia (p=0.045). Mild peripheral eosinophilia at diagnosis was associated to its persistency after treatment (p=0.023). CONCLUSION: In this series, mild peripheral eosinophilia was associated with its persistency and respiratory hyperinflation after treatment, suggesting that the degree of peripheral eosinophilia is associated to a distinct clinical evolution.
Viruses in Human Tumors. I. Hodgkin's Disease
Authors: Sarah E. Stewart, Elisabeth Z. Mitchell, Jacqueline J. Whang, William R. Dunlop, Theresa Ben, Shigeko Nomura
Journal: JNCI Journal of the National Cancer Institute (1969)

A continuous cell culture designated SS5 was established from a lymph node biopsy specimen taken from a male with Hodgkin's disease. The cells grew in suspension as aggregates, in pairs, and singly. During their logarithmic growth the cell doubling time was approximately 24 hours. Chromosome studies were carried out on cells from the patient's bone marrow, the lymph node biopsy before culture, and again after 4 months' culture. On direct examination, the bone marrow and lymph node showed no abnormalities. After 4 months in culture, 89% of the cells examined had 46 chromosomes and were pseudodiploid. There were a low incidence of polyploidy (0.4%) and a low incidence of cells with aberrations (4%). Electron microscope examination showed that the cells carried two kinds of virus-like particles: the herpes-type virus which has been described for cultured Burkitt's tumor cells, and other particles of about the same size with morphology suggestive of a different type of virus. Since the herpes-type virus will not replicate in monolayer cultures, we could separate the two types by inoculating WI38 monolayer cultures with a cell-free concentrate from the SS5 line. Virus replication on passages in the WI38 cells was obvious by specific cellular changes, but only occasional virus-like particles were demonstrable by electron microscopy in the early passages. After 20 passages, abundant virus became evident as extracellular particles. When virus from the WI38 culture was introduced into a human lymphocyte suspension culture, massive virus budding from the cell membrane became evident. The virus ranged from 90–150 mμ, with most about 120 mμ in diameter, and produced a filamentous component 15 mμ in diameter. The filaments were shown to become the nucleoid of the budding virus. The virus was similar immunologically to simian virus SV5.
Abstract 12777: Pleiotropic Effects of Statin in Stabilization of Unstable Coronary Plaque - Direct Evidence from Low Density Lipoprotein Receptor Knockout Pig
Authors: Yuxin Li, Akira Onishi, Mitsumasa Sudo, Seiji Fukushima, Qingfei Lin, Shunichi Suzuki, Daiichiro Fuchimoto, Shoichiro Sembon, Masaki Iwamoto, Michiko Hashimoto, Hironori Haruta, Tadateru Takayama, Satoshi Kunimoto, Takafumi Hiro, Taro Matsumoto, Masako Mitsumata, Masahiko Sugitani, Satoshi Saito, Atsushi Hirayama
Journal: Circulation (2013)

Background: Lipid-lowering therapy with statins reduces the risk of cardiovascular events indicating that statins may stabilize coronary vulnerable plaque. However, no animal experiments have confi...
Effect of pH on Hyperthermic Cell Survival: Brief Communication 2
Authors: M. L. Freeman, W. C. Dewey, L. E. Hopwood
Journal: JNCI Journal of the National Cancer Institute (1977)

Chinese hamster ovary cells incubated with various concentrations of CO2, to obtain extracellular pH values in the range of 6.40–7.85, were heated at 45.5° C for 5, 10, or 20 minutes. Thermal sensitivity increased sharply from pH 7.35 to 6.65 (i.e., survival decreased from 1×10−2 to 3×10−5 for 20 minutes of heating), but remained constant from pH 7.35 to 7 .85. The enhanced thermal sensitivity at pH values below pH 7.35 suggested that tumors should be preferentially destroyed by heat relative to normal tissue, since reports indicated that tumors were more acidic than the surrounding normal tissue.
Targeting ctla-4 directly on melanoma cells: A possible novel perspective in the immunotherapy of cutaneous melanoma
Authors: P. Queirolo, S. Laurent, M. Boitano, P. Carrega, D. Saverino, F. Alviano, A. Caielli, M. Camoriano, G. Ferlazzo, M. P. Pistillo
Journal: Journal of Clinical Oncology (2009)

e22138 Background: CTLA-4 (CD152) is an omodimeric membrane glycoprotein which behaves as the major negative regulator of T cell-mediated immune response. CTLA-4 inhibitory function in T cells mainly occurs upon engagement with the B7 ligands expressed on antigen presenting cells, resulting in inhibition of cytokine production and T cell proliferation. CTLA-4 expression has also been documented in established human melanoma cell lines and primary melanoma tumours. The aim of this study was to investigate the expression and functional role of CTLA-4 in primary melanoma cultures derived from biopsies of metastatic melanoma patients. Methods: Seven primary cultures were derived from melanoma samples by mechanical tissue dissociation, enzymatic digestion and filtration of single cell suspensions. Flow cytometry (FACS) with an anti-melanoma (MCSP) mAb was used to assess the growth of melanoma cells. CTLA-4 expression analysis was performed by FACS and real-time PCR. Cytokine secretion and apoptotic cells were evaluated by Elisa and Annexin V/PI staining after treatment with an agonistic anti-CTLA-4 mAb (3D5). The angiogenic property of melanoma culture supernatants was evaluated on mesenchimal stromal cells (msc) isolated from human thoracic aortas. All the study was approved by our Institutional Ethics Committee and patients gave written informed consent. Results: Constitutive CTLA-4 expression was found on all melanoma cultures with variable intensity at both the protein and transcript levels. CTLA-4 expressed by these cells is functional as its ligation, with an anti-CTLA-4 agonistic mAb, is able to induce inhibition of cell proliferation, due to apoptosis induction, and of IL-8, TNF-alpha and VEGF cytokine secretion. Moreover, CTLA-4 ligation down-modulates the ability of melanoma culture supernatants to induce angiogenic differentiation of msc as detected by the acquisition of their endothelial phenotype. Conclusions: Given the physiologic inhibitory function of CTLA-4, our results suggest its possible role in the functional biology of melanoma and open up the possibility of an anti-melanoma immunotherapy based on targeting CTLA-4 directly on tumour cells as this might allow inhibition of tumour cell growth and angiogenesis. No significant financial relationships to disclose.
Anti-VEGF and anti-EGFR monoclonal antibodies (Mabs) in the first-line therapy for metastatic colorectal cancer: A meta-analysis
Authors: Z. Zhou, W. V. Walsh, V. G. Bathini, B. Piperdi
Journal: Journal of Clinical Oncology (2009)

e15012 Background: Anti-VEGF (VEGFi) and anti-EGFR (EGFRi) Mabs have increased options for patients with metastatic colorectal cancers (mCRC). The optimal class of antibody to combine with chemotherapy (Ctx) in the first-line treatment for mCRC remains less well defined. Results from randomized controlled trials (RCTs) are variable. Methods: Systematic review and meta-analysis were performed on the basis of previously released RCTs results. We searched the MEDLINE, Cochrane registry, proceedings from ASCO, ECCO, ESMO until 12/ 2008 for RCTs of Mabs in first-line mCRC. Summary statistics were pooled hazard ratio (HR) of progression-free survival (PFS), overall survival (OS) and odds ratio (OR) of Response rate (RR) and 60 day mortality (60d-M). Effect of k-ras wild type and mutation were stratified in trials involving EGFRi. Results: 7 trials with complete data were identified, including 3 Ctx ± VEGFi (AVF2107g, NO16966, JCO2005.05.122), n=2422; 2 Ctx±EGFRi (CRYSTAL, OPUS), n=1554; 2 Ctx/VEGFi ± EGFRi (PACCE, CAIRO-2), n=1789. Addition of VEGFi to Ctx offered 20–30% risk reduction in disease progression and overall mortality, a 30% higher RR and nonsignificant 60d-M. Benefit of EGFRi in addition to Ctx was seen only in k-ras wild type patients with 36% reduction in disease progression and doubling in RR. However, addition of EGFRi to Ctx+VEGFi caused increased risk of progression and death with no significant increase in RR and 60d-M. Conclusions: Benefit of VEGFi in addition to Ctx in first-line mCRC is well pronounced and persistent. In k-ras wild type patients, addition of EGFRi to Ctx results in significant increase in RR and PFS. Addition of EGFRi to Ctx+VEGFi appeared harmful regardless of k- ras status. [Table: see text] [Table: see text]
Phase II randomized trial of docetaxel plus cetuximab or bortezomib in patients with advanced NSCLC and performance status (PS) 2—CALGB 30402
Authors: R. Lilenbaum, X. Wang, L. Gu, J. Kirshner, E. Vokes
Journal: Journal of Clinical Oncology (2007)

7595 Background: There is no standard treatment for patients (pts) with advanced NSCLC and PS 2. Docetaxel (D) is active and well tolerated on a weekly schedule. Cetuximab (C) and Bortezomib (B) are new agents with activity in NSCLC. We explored these two new combinations in PS 2 pts. Methods: In a multi-center randomized phase II trial, untreated pts with advanced NSCLC and PS 2 were randomized to D 30 mg/m 2 d1,8,15 q. 28 days in combination with either C 400 mg/m 2 week 1 then 250 mg/m 2 weekly, or B 1.6 mg/m 2 d1,8,15 q. 28 days for 4 cycles. Pts with CR/PR/SD were allowed to continue C or B until PD. The study was non-comparative and the primary endpoint was progression-free survival (PFS) rate at 6 months. The trial had a type I error of 0.0746 and power of 0.9 to differentiate a 6-mo PFS of &lt;20% vs. &gt;42%. Results: 64 pts were enrolled between 7/05 and 9/06. 5 were ineligible and 3 never received protocol treatment. Results are reported for 55 pts (27 D+C; 28 D+B). Most pts had stage IV adenoCa and 13% had brain metastases. Median age was 70 (range, 35–88) and 65% were male. Response: 10.5% for D+C and 13.6% for D+B. Median PFS was 3.1 mo for D+C and 1.8 mo for D+B. PFS rates at 4 mo (data not yet mature for 6-mo): 33% and 28%, respectively. Median survival: 3.8 mo for D+C and 3.3 mo for D+B. Gr 3/4 hematologic toxicity was 17% in both arms. Gr 3/4 non-heme toxicities were 44% in D+C and 36% in D+B arm. 5 pts died of treatment-related toxicities (3 D+C; 2 D+B). Conclusions: These results confirm the poor prognosis associated with a PS of 2. Based on our preliminary analysis, neither combination produced results that justify further research in this subset of patients. The treatment of PS 2 patients with advanced NSCLC remains a vexing problem and new approaches are urgently needed. No significant financial relationships to disclose.
Pharmacogenomic analysis to predict relapse in curatively resected gastric cancer patients treated with adjuvant 5-fluorouracil/cisplatin (FP) chemotherapy
Authors: J. S. Kim, M. A. Kim, D. W. Kim, S. A. Im, T. Y. Kim, H. K. Yang, W. H. Kim, D. S. Heo, Y. J. Bang, N. K. Kim
Journal: Journal of Clinical Oncology (2005)

4057 Background: Thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) are known to be key enzymes in 5-FU metabolism and play a role in resistance to fluoropyrimidines. Excision repair cross complementing 1 (ERCC1) is essential for nucleotide excision repair pathway and is thought to play key role in platinum resistance. The aim of this study was to analyze pharmacogenomic influence on the efficacy of adjuvant chemotherapy with 5-fluorouracil and cisplatin (FP) after curative gastric resection. Methods: Normal and cancer tissue were separately obtained from surgically resected samples with primary gastric cancer of patients with AJCC stage III-IV (M0), treated with adjuvant FP chemotherapy. TS tandem repeats, DPD exon 14 mutation, and ERCC1 8092/19007 single nucleotide polymorphism (SNP) were analyzed using extracted DNA from both tissues. TS, DPD, TP, and ERCC1 protein contents were measured by immunihistochemistry. The percentage of stained cells was multiplied by the staining intensity (0 to 3+). Results: Genotypes of TS, DPD, and ERCC1 were not significantly different between normal and cancer tissue. But TS, TP and ERCC1 protein were significantly over-expressed in cancer tissue. TS genotypes were as follows: 2R/2R 5.5%, 2R/3R 25.5%, and 3R/3R 69.1%. Exon 14 mutation of DPD was not observed. ERCC1 genotypes at 8092 were as follows: CC 44.2%, AC 46.8% and AA 9.1%. ERCC1 genotypes at 19007 were as follows: GG 69.3%, GA 28% and AA 5.3%. Although other protein expressions were not different from genotype to genotype, the ERCC1 protein expression was significantly lower in AA genotype of ERCC1 19007 than GA/GG genotypes. ERCC1 G19007A was significant predictor of relapse by stages (50.0% vs. 30.7% vs 0%, p<0.01). ERCC1 expression was significantly lower in relapse than in non-relapse (p=0.022). Conclusions: ERCC1 G19007A polymorphism is predictor of relapse according to the stages. ERCC1 expression was significantly lower in relapse than in non-relapse, that was opposite to previous reports. Pharmacogenetic genotyping appears to predict relapse in curatively resected stage III-IV gastric cancer patients. No significant financial relationships to disclose.
Abstract P185: Investigation of Community and Home Factors in Child Physical Activity Levels
Authors: MIchael Graham, Vanessa Shannon, Christa Ice, Lesley Cottrell
Journal: Circulation (2012)

It is known that physical activity (PA) behavior is influenced by many factors within the social ecological model. Using results from parent surveys distributed after their children’s completion of a cardiovascular risk screening program, we explored the relationship between home and community environments on the amount of PA in which children engaged. Our hypothesis was that more immediate factors such as parent activity would have a greater impact on child activity than factors in their community environments. A large sample (n=450) of children (ages 5-10 years) were examined. Children’s physical activity was assessed by adding the total minutes of active time weekly. Parent physical activity was measured with two self report items regarding the number of days per week they were active . Two scales were constructed to evaluate to effects of the home (9 items; α = .829) and community (16 items; α = .868). The home environment scale measured elements related to activity opportunities and home schedules; the community scale assessed presence of playgrounds, or safe sidewalks, for example. To assess associations between factors and children’s PA, we conducted a linear stepwise regression with child age, parent PA, Home scale, and Community scale as predictors and the log transformed total weekly activity time as the dependent variable. Sixteen percent of children’s PA was explained by the tested model. Figure 1 provides specific information about each variable. The home scale had the greatest weight (β=0.360, p&lt;.001), and proved to have a larger predictive effect than parent PA. These findings are significant for identifying which aspects of a child’s surrounding to intervene for maximum impact on physical activity. Figure 1. R² Change between model levels
Sexual dysfunction in women with breast cancer: Prevalence and severity
Authors: S. B. Goldfarb, M. Dickler, L. Sit, M. Fruscione, T. Barz, T. Atkinson, C. Hudis, E. Basch
Journal: Journal of Clinical Oncology (2009)

9558 Background: Sexual dysfunction (SD) is reported after chemotherapy and endocrine therapies, and causes a substantial burden on women with breast cancer. However, the prevalence and severity of SD in this population is not well defined. Improved understanding of SD may allow for enhanced treatment and interventions in patients with breast cancer undergoing active treatment, and in survivors of this disease. Methods: We developed a survey that includes a previously validated questionnaire, the female sexual function index (FSFI), and disease-specific items to characterize SD and its causes based on literature review and expert consultations. Anonymous administration of the surveys was conducted in outpatient clinic waiting areas of the M64/Breast Center Memorial Sloan-Kettering Cancer Center (MSKCC), under an IRB waiver of consent. Results: During November-December 2008, 100 women with breast cancer of any stage were each queried once. The mean age was 52 (range 26–75). 68% reported current or past hormonal treatment, and 63% reported current or past chemotherapy (84% adjuvant; 16% for metastatic disease). SD attributed to breast cancer or its treatment, defined as an FSFI score &lt;26, was reported by 75% of respondents. Among these women, severe symptoms were noted by 38/75 (51%), and moderate by 37/75 (49%). 87/95 (92%) patients considered their sexual symptoms to be bothersome, with 59/95 (62%) noting moderate or severe levels of bother (score &gt;=5/10). Patients attributed their SD to chemotherapy in 52/63 (83%) of cases; to hormonal therapy in 56/68 (82%) of cases; and to surgery in 68/92 (74%) of cases. Other contributors to SD were felt to include anxiety by 83% of respondents, and change in relationship with a partner by 46%. Conclusions: SD is prevalent in women treated for breast cancer and should be discussed with patients as a potential adverse effect of therapy. Assessment of sexual symptoms throughout treatment and beyond may facilitate the use of potential interventions such as lubricants, dilators, treatment modification, topical estrogens, and counseling. A longitudinal prospective trial is planned to further characterize the etiologies of these symptoms. No significant financial relationships to disclose.