tbuckley/cabot-search huggingface dataset:
Abstract 3302: Subtype-specific radiation response in a mouse model of human breast cancer
Authors: Chen-Ting Lee, Yingchun Zhou, Sharareh Siamakpour-Reihani, Kingshuk R. Choudhury, Mark W. Dewhirst, Janet K. Horton
Journal: Cancer Research (2015)

Abstract Radiation therapy is an important component of multimodal treatment for women with breast cancer. However, breast radiotherapy is currently delivered uniformly, regardless of breast cancer subtype. Recent clinical data have suggested that different subtypes of breast cancer may respond differently to radiation. Understanding the intrinsic variation of radiation response in breast cancer subtypes would lay the foundation for individualized radiotherapy designed to limit toxicity in those with radiation responsive cancers. Furthermore, identification of molecular targets can be used to modulate treatment outcomes in patients with radiation resistant tumors. Our previous in vitro studies have identified an association between breast cancer subtype and gene expression profiles in response to radiation in breast tumor cell lines. Cell lines with the greatest response to radiation were luminal subtype and exhibited preferential induction of genes involved in programmed cell death, such as FAS. In this study, we investigated tumor growth and FAS induction in response to radiation in a mouse model of breast cancer. MCF7 (luminal) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of athymic nude mice. These mice were then treated with different doses of radiation. Our results showed that radiation treatment inhibited MCF7 tumor growth in a dose-dependent manner, while radiation treatment had little effect on SUM159 tumor growth. In addition, FAS was induced in MCF7 tumors 24 hour after radiation, but there was no change in FAS expression in SUM159 tumors. However, injection of FAS-stimulating antibody intratumorally led to downstream caspase 8 and PARP activation, suggesting that the FAS signaling pathway remains intact and can be used to modulate radiation response in the resistant SUM159 cells. In conclusion, these results suggest that there is intrinsic variation in radiation response among breast cancer subtypes and that stimulation of FAS may have the potential to modulate radiation response. Citation Format: Chen-Ting Lee, Yingchun Zhou, Sharareh Siamakpour-Reihani, Kingshuk R. Choudhury, Mark W. Dewhirst, Janet K. Horton. Subtype-specific radiation response in a mouse model of human breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3302. doi:10.1158/1538-7445.AM2015-3302
Response to Open Peer Commentaries on “Ethics Consultation Quality Assessment Tool: A Novel Method for Assessing the Quality of Ethics Case Consultations Based on Written Records”
Authors: Robert A. Pearlman, Mary Beth Foglia, Jennifer H. Cohen, Barbara L. Chanko, Kenneth A. Berkowitz
Journal: The American Journal of Bioethics (2016)

"Response to Open Peer Commentaries on “Ethics Consultation Quality Assessment Tool: A Novel Method for Assessing the Quality of Ethics Case Consultations Based on Written Records”." The American Journal of Bioethics, 16(3), pp. W1–W2
Early weaning is beneficial to prevent atopic dermatitis occurrence in young children
Authors: F. Turati, P. Bertuccio, C. Galeone, C. Pelucchi, L. Naldi, J.-F. Bach, C. La Vecchia, L. Chatenoud
Journal: Allergy (2016)

Epidemiological data on infant feeding practices and allergic diseases are controversial. The purpose of this study was to explore the association of early weaning with the occurrence of atopic dermatitis (AD).We conducted a matched case-control study on incident physician-diagnosed AD in early childhood including 451 cases and 451 controls. Data on several factors, including feeding practices, were collected through an interviewer-administered questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were estimated through logistic regression models, conditioned on study center, age, sex, and period of interview, and adjusted for potential confounders.Early weaning, defined as the introduction of solid foods at 4 or 5 months of age, was inversely related to the risk of AD, with children weaned at 4 months having lower AD risk (OR = 0.41, 95% CI, 0.20-0.87) compared to those exclusively breastfed. Similar results were observed for weaning started at 5 months of age (OR = 0.39, 95% CI, 0.18-0.83). This association persisted when children with and without family history of allergy were considered separately. Prolonged partial breastfeeding (breastmilk plus milk formulas) was not associated with AD. Consistently, the introduction of a high number of different solid foods reduced the risk of AD (P trend = 0.02 at 4 months of age and P trend = 0.04 at 5 months).Our data provide evidence against the preventing role of prolonged exclusive (but not partial) breastfeeding in AD occurrence and confirm recent results indicating a beneficial role of early weaning in AD.
First line treatment of HER-2/neu positive advanced breast cancer patients with liposomal doxorubicin (Myocet), docetaxel and trastuzumab. A phase I-II study
Authors: D. Amadori, G. Gasparini, M. O. Vannozzi, C. Milandri, P. Serra, F. Di Costanzo, B. Di Blasio, G. Lunardi
Journal: Journal of Clinical Oncology (2006)

10744 Background: Our preclinical data showed synergic effect of Adriamicyn followed by Taxotere in BC cell lines. The combination of anthracyclines, taxanes and trastuzumab could potentially obtain a high number of objective responses and a consistent impact on the time to progression and on the overall survival. The aim of this phase I-II study was to assess the maximum tolerated dose (MTD) of liposomal doxorubicin (Myocet-M) and Taxotere (T) in combination with Herceptin (H). A reduction of cardiotoxicity risk without reducing chemotherapy activity was supposed. Methods: Locally advanced or metastatic her-2/neu positive BC patients (pts) with LVEF ≥ 60% were enrolled in an open, single arm, non-randomized phase I-II escalation trial in 3 to 6 pts/cohorts. The treatment schedule was: M 50 mg/m 2 (or 60, depending on dose level assignment) on day 1, T 30 mg/m 2 on day 2 and 9, H 4 mg/kg on day 2 followed by weekly dose of 2 mg/kg, every three weeks. MTD dose was identified on the basis of DLT defined according to WHO grade classification of toxicity or specific conditions of LVEF decrease. A pharmacokinetic (PK) analysis of doxorubicin until 72 hours after M administration was planned. Results: Seven pts, median age 63 yrs, were enrolled. Four pts were allocated to dose level 50/30 (M/T) and other 3 pts to dose level 60/30. At the dose level 60/30 febrile neutropenia (DLT) occurred in 2 pts. Other 2 pts experienced febrile neutropenia (no DLT). One event of tachicardia (WHO grade 1) at maximum tolerated dose level was completely recovered without treatment. LVEF values were unmodified. Six patients were enrolled in the PK analysis. T pharmacokinetic data obtained on day 2 and on day 9 were not statistically different. Conclusions: The MTD was defined at M 50 mg/m 2 in combination with T 30 mg/m 2 . The cardiac tolerability was good, with no significant change in LVEF values from baseline to the end of therapy. PK data indicated that the residual concentration of M found on day 2 was did not influence T pharmacokinetics, according to literature data. A phase II study is ongoing to assess activity and PK interactions between drugs. Till now 25 patients have been enrolled, the planned sample size is 45. No significant financial relationships to disclose.
Molecular profiling of breast cancer via targeted tissue proteomics.
Authors: D. J. Johann, S. Mukherjee, J. Rodriguez-Canales, J. Hanson, T. D. Veenstra, M. Emmert-Buck, J. Blonder
Journal: Journal of Clinical Oncology (2010)

e21026 Background: The analysis of clinical breast tissue specimens that includes a functional coupling of laser capture microdissection (LCM) and mass spectrometry (MS) for molecular profiling of breast tumors, is the purpose of this study. A heterogeneous architecture is a common characteristic of all solid tumors. Cancer is a product of the tissue microenvironment, and is composed of a diverse set of cells with distinct morphologies and proteomic elements. The microenvironment, which includes both modified and unmodified stromal elements serves to nurture the malignant process. Innovative proteomic approaches are needed to facilitate better understanding of breast cancer solid tumor heterogeneity and in particular, the microenvironment. Methods: Tissue proteomics methods were employed including LCM. Homogeneous regions of cells exhibiting uniform histology were isolated and captured from fresh frozen tissue specimens, which were obtained from human breast carcinoma samples. Results: Prepared samples were analyzed by LC-MS/MS resulting in more than 500 unique protein identifications. High confidence measures were employed by including only proteins identified by ≥ 2 unique peptides. Decoy database searching was used to reduce the false-positive rate. Molecular profiling data was subjected to machine learning methods to better discern the complex proteomic expression of the multiple cellular phenotypes due to the heterogeneity of the solid tumor. Cross validation via Western Blot analysis confirmed specific linkage of 12 validated proteins to underlying pathology and their potential role in solid tumor heterogeneity. Conclusions: New methods that facilitate biomarker discovery are needed. Tissue proteomic methods including a functional-linkage of LCM with LC/MS-MS are being pursued to better understand solid tumors. Tumor heterogeneity may be viewed as a memory map of the malignant process and thus effective study may yield insights regarding cancer development and therapy. The biological background of such heterogeneity is not well understood. With continued research and optimization, this approach may lead to an improved understanding of tumor heterogeneity, and serve as a platform for solid tumor biomarker discovery. No significant financial relationships to disclose.
Antitumor effects of new proline analogs on cancer cell lines in vitro
Authors: G. Hamilton, U. Olszewski, E. Ulsperger, G. Baumgartner
Journal: Journal of Clinical Oncology (2004)

3164 Background: Components of the extracellular matrix (ECM), especially collagens, are involved in tumor cell development, proliferation and dissemination and therefore represent a potential target for tumor therapy. The ECM-associated proline-rich structures are susceptible to suitable toxic proline analogs, which disrupt protein assembly and functions. Methods: An extensive panel of proline analogs (lead compound: cis-4-hydroxy-L-proline; CHP) and the collagen inhibitor L-azetidine-2-carboxylic acid were tested for cytotoxicity against a large panel of cell lines. In addition to a tetrazolium-based assay (MTT), cell cycle analysis (propidium iodide) and apoptosis assays (annexin V) were performed. Amino acid uptake was studied using radioactive proline and differentiation was assessed by measuring induction of alkaline phosphatase (ALP). Results: Antiproliferative activity of CHP was found in cell lines derived from colon carcinomas, pancreatic, prostatic, and breast cancer as well as osteosarcoma and glioma (IC50: 35 - 175 μg/ml) and increased activity was detected under acidic extracellular conditions prevailing in solid tumors. Cell cycle arrest was found preferentially in G2M and apoptotic cells were detectable following prolonged exposure (7 - 10 days). CHP treatment of 2 colon carcinoma cell lines (HT29, CaCo-2) resulted in induction of the differentiation marker ALP. Proline competition tests indicated uptake of CHP via alpha-(methylamino)-isobutyric acid (MeAIB)-sensitive amino acid transport. Extensive testing of other cytotoxic proline-related compounds led to the characterization of N-methylated CHP derivatives, which show no interference with transport of proline, and proved to be capable of enhancing the CHP-induced toxicity by up to 30 %. Conclusions: Highly efficient proline analogs in combination exhibit considerable toxicity in vitro against diverse cell lines and should be studied in extended clinical CHP trials as agents modulating tumor cell growth by targeting ECM and/or critical proline residues of tumor-associated proteins. No significant financial relationships to disclose.
Hypopigmentation of newborn skin
Authors: Jennifer L H Peterson
Journal: BMJ (2016)

A full term baby girl was initially seen on the neonatal unit with respiratory distress, thought to be transient tachypnoea of the newborn. While on the unit she was noted to have a hypopigmented, whorl-like pattern extending over her right arm, leg, torso, and back. Examination was otherwise normal, with good tone, active movements, and a good suck.



She was diagnosed with the condition discussed below, and by …
Admissions for chemotherapy-related serious adverse effects (CR-SAEs) and rates of mortality among community cancer center patients
Authors: S. R. Rao, M. Hassett, J. H. Schwartz, B. Maloney, J. O. Jacobson
Journal: Journal of Clinical Oncology (2009)

6571 Background: Data regarding CR-SAE's come predominantly from clinical trials; little is known about the experiences of cancer patients treated in community settings. Our goals were to describe admissions for CR-SAE's among cancer patients treated in a community setting and to identify rates and predictors of mortality for admitted patients. Methods: We conducted a prospective cohort study of adult cancer patients (excluding acute leukemia and stem cell transplant patients) admitted to a community hospital January 2003-December 2006. A multidisciplinary panel of cancer providers determined which admissions were chemotherapy-related. We identified the type of SAE, outcome of each admission, time form chemotherapy to admission and from admission to discharge/death, and the disease and treatment characteristics of each patient. Statistical analyses included Chi-square, ANOVA, and logistic regression. Results: 227 patients experienced 258 admissions for CR-SAE's (55.5% female; median age 68, range 17–89). The most common cancers were colorectal (18.5%), lung (18.1%), lymphoma (16.3%), and breast (13.7%). Most chemotherapy was palliative (53.5%). SAE's were categorized as gastrointestinal (46.1%), infectious (31.4%), hematologic (9.3%), cardiac (8.1%), and other (5.0%). Approximately 7.4% of admissions led to fatalities, with a median of 9 days (range 1–35) from admission to death. Fatalities were more frequent among patients receiving palliative versus adjuvant/curative chemo (10.1% vs. 4.2%; p = 0.07) and among patients experiencing infectious vs. other SAE's (13.6% vs. 0–9.5%; p = 0.07). On multivariable analysis, palliative therapy was a borderline-significant predictor of mortality (OR 2.8; 95% CI 0.9–8.4; p = 0.07). The average time from chemotherapy to admission was shorter for fatal vs. non-fatal admissions (3.6 vs. 7.7 days; p&lt;.01). Conclusions: Fatalities during admissions for CR-SAE's in a community cancer center are relatively uncommon and are not associated with age or type of SAE/cancer. Further investigation regarding predictors of mortality following palliative chemo may be warranted. Chemotherapy-related mortality in the palliative care setting may be a valid quality indicator. [Table: see text]
STUDIES ON HOST-VIRUS INTERACTIONS IN THE CHICK EMBRYO-INFLUENZA VIRUS SYSTEM
Authors: Norman B. Finter, Oscar C. Liu, Melvin Lieberman, Werner Henle
Journal: The Journal of Experimental Medicine (1954)

The usefulness of the deembryonation technic has been analyzed as a tool in the study of various problems in the growth cycle of influenza virus in the entodermal cells of the allantoic of chick embryos. Various improvements in the deembryonation technic have been described. The method readily permits repeated sampling of the medium at various stages after infection (cumulative growth curves) or frequent exchanges of the medium (differential growth curve). However, the yield of infectious virus or of hemagglutinins is less than that observed in the intact chick embryo. The difference observed is greater than can be accounted for by the reduction in the available host cells and is assumed, therefore, to be due in part to interruption of blood and nutrient supply to the cells. This handicap can be overcome by the combined in ovo-deembryonation technic, in which deembryonation is performed at any desired time after infection of the intact chick embryo, and the medium is collected and analyzed after 1 to 3 hours of further incubation. The value of the technic is demonstrated by the fact that liberation of virus from infected cells can be detected earlier than in the intact egg. Furthermore, it continues at a nearly constant rate for many hours, thus proving to be erroneous previous inference which had been based upon in ovo experiments. The technic also permits readily the addition and subsequent removal of substances that might interfere with viral propagation. As an example a study was made of the effect of the receptor-destroying enzyme of V. cholerae (RDE) when added to the medium of eggs infected prior to deembryonation. By carefully grading the dose of virus and using an appropriate amount of RDE, one-step growth curves were obtained indicating that those cells not directly invaded by the seed virus were subsequently protected against infection by action of the enzyme. The smaller the amount of virus the less RDE was required in order to note a protective effect. With a decrease in the period of exposure to RDE regeneration of cell receptors became increasingly more apparent in that correspondingly greater amounts of virus were produced and liberated late in the incubation periods. These results confirmed and extended those reported by Stone. More extensive applications of these technics will be reported in subsequent papers of this series.
AVATAXHER: An open-label, randomized, multicenter study investigating the addition of bevacizumab (B) to neoadjuvant trastuzumab (T) plus docetaxel (D) in patients with early stage HER2-positive breast cancer (HER2+ BC) stratified according to PET change after one therapy cycle.
Authors: Bruno P. Coudert, Jean-Yves Pierga, Marie-Ange Mouret-Reynier, Khaldoun Kerrou, Jean-Marc Ferrero, Thierry Petit, Pierre Kerbrat, Pierre-Francois Dupre, Thomas Denis Bachelot, Philippe Gabelle, Sylvia Giard, David Coeffic, Philippe Bougnoux, Jean Briac Prevost, Gilles Paintaud, Gilles Thibault, Juana Hernandez, Mathieu Coudert, Laurent Arnould, Alina Berriolo-Riedinger
Journal: Journal of Clinical Oncology (2014)

507 Background: T-based neoadjuvant chemotherapy achieves pCR rates of ~50% in HER2+ BC, enabling frequent conservative surgery. Pre-clinical and clinical data support the synergistic combination of B and T. The ph II AVATAXHER trial (EUDRACT 2009-013410-26) investigated whether adding B to neoadjuvant T+D improved pCR rates in tumors with a low likelihood of attaining pCR (predicted based on relative change in FDG tumoral uptake [ΔSUV] after one cycle of T+D). Methods: Patients were ≥18 yrs old with stage T2/3, N0/1 HER2+ BC. Patients received two 3-weekly cycles of T (8 mg/kg, then 6 mg/kg) and D (100 mg/m2). Those with ≥70% ΔSUV in PET values between cycle 1 and 2 received four more cycles of T+D, one cycle of T, then surgery (standard arm). Those with <70% ΔSUV were randomized 2:1 to four cycles of T+D+B (15 mg/kg; arm a) or T+D (arm b), then one T cycle and surgery. The primary endpoint was pCR rate at surgery. The positive (PPV) and negative predictive value (NPV) of ΔSUV on pCR rate and safety were also investigated. Results: 152 patients were recruited at 26 sites (10 were withdrawn pretreatment; ITT=142). 37/69 (53.6%) patients in the standard arm achieved pCR, 21/48 (43.8%) in arm a and 6/25 (24.0%) in arm b. pCR rates in patients with hormone receptor –ve/+ve disease were: 69.0%/42.5% (standard arm), 57.9%/34.5% (arm a), and 40.0%/13.3% (arm b). Surgery (133 pts) was conservative in 84.8% of patients with surgery in the standard arm, 67.4% in arm a, and 62.5% in arm b. In patients without B, ΔSUV after one cycle predicted pCR with a PPV of 52.9% and a NPV of 75%. Toxicity was mild and included asthenia, myalgia, and increased lacrimation (all pts had ≥1 AE). Grade 3/4 AEs (in 31% of pts) included neutropenia (8.6% pts), febrile neutropenia (3.6%), myalgia (3.6%), asthenia (2.9%), and nail toxicity (2.9%). Conclusions: Adding B to neoadjuvant T+D, in tumors with a low likelihood of pCR predicted by PET ΔSUV, increased the pCR rate from 24.0% to 42.5%. PET ΔSUV, by selecting low responding HER2+ tumors, may be a useful tool for optimizing neoadjuvant therapy for HER2+ BC. Clinical trial information: 2009-013410-26.
Brief Communication: Tumor-Associated Antibodies to Ocular and Cutaneous Malignant Melanomas: Negative Interaction With Normal Choroidal Melanocytes2
Authors: J. L. Federman, M. G. Lewi, W. H. Clark
Journal: JNCI Journal of the National Cancer Institute (1974)

Tumor-associated humoral antibodies in the serum of patients with ocular melanomas and those with cutaneous melanomas were studied by indirect cytoplasmic immunofluorescence. Positive autologous reactions were observed in the 4 patients with primary ocular choroidal melanomas and in 2 patients with primary cutaneous melanomas. Allogeneic reactions were noted among the ocular patients, among the cutaneous patients, and between the 2 groups. Metastatic ocular melanoma cells showed allogeneic immunofluorescence with the serum from the 4 ocular patients and from 1 of the 3 cutaneous patients. The tumor-associated antibodies from both groups failed to react with allogeneic normal choroidal melanocytes. The normal choroidal melanocytes failed to show autologous reactivity. Normal serum and serum from a patient with mucoepidermoid carcinoma failed to react with the melanoma cells.