tbuckley/cabot-search huggingface dataset:
Amphiregulin (AR) expression in the prediction of benefit from cetuximab plus irinotecan in KRAS wild-type metastatic colorectal cancer (mCRC) patients
Authors: F. Loupakis, C. Cremolini, G. Perrone, I. Stasi, L. Salvatore, B. Vincenzi, A. Ruzzo, M. Ronzoni, K. Bencardino, A. Falcone
Journal: Journal of Clinical Oncology (2009)

4021 Background: AR is an endogenous ligand of Epidermal Growth Factor Receptor (EGFR), whose binding is prevented in the presence of cetuximab. Methods: We retrospectively assessed KRAS mutational status and AR expression at immunohistochemistry (IHC) in 86 irinotecan-refractory EGFR-positive mCRC patients treated with cetuximab plus irinotecan. AR-IHC was performed on tissue sections from paraffin-embedded primary tumors. Specimens were defined AR-low or AR-high according to a score (range 0–300) obtained multiplying intensity (0 to 3+) by percentage of stained cells (0–100%). According to the results of a ROC analysis, we identified a cut-off value of 18. The association between AR-IHC and treatment outcome in terms of response rate (RR), PFS, and OS was investigated in the subgroup of KRAS wild-type patients. Results: Eighty-six consecutive patients were included. M/F = 44/42, median age = 67 (41–78), median number of previous lines of chemotherapy = 2 (1–5). Among 51 (59%) KRAS wild-type patients, 12 PRs and 1 CR were observed, for an overall RR of 25% (13/51). AR-IHC was high, low or unconclusive in 27, 22 and 2 cases respectively. AR-low patients reported a significantly worse RR (2/22, 9%) compared with AR-high (10/27, 37%) (p = 0.024) and a trend toward shorter PFS (3.5 vs 5.3 months, HR 0.88 [95%CI: 0.46–1.60], p = 0.628) and OS (8.8 vs 15.1 months, HR 0.60 [95%CI: 0.30–1.10], p = 0.106). Conclusions: These results underline the potential role of endogenous ligands in influencing the activity of anti-EGFR monoclonal antibodies. Absent or low AR expression at IHC may be related to resistance to cetuximab plus irinotecan. Further data regarding the prognostic impact of AR expression are needed. No significant financial relationships to disclose.
Persisting Long Term Benefits of Smoking Abstinence and Reduction in Asthmatic Smokers Who Have Switched to Electronic Cigarettes
Authors: Davide Campagna, Jaymin B. Morjaria, Pasquale Caponnetto, Massimo Caruso, Maria Domenica Amaradio, Giovanni Ciampi, Cristina Russo, Riccardo Polosa
Journal: Journal of Allergy and Clinical Immunology (2016)
Studies of Methotrexate-Monoclonal Antibody Conjugates for Immunotherapy
Authors: J Kanellos, G A Pietersz, I F McKenzie
Journal: JNCI Journal of the National Cancer Institute (1985)

Methotrexate (MTX) was covalently bound to two different murine monoclonal antibodies, one reactive with human colon carcinoma and the other reactive with the transferrin receptor. The drug-antibody complexes were examined for their in vitro and in vivo potency against tumors. The conditions of coupling were closely monitored, with particular attention being paid to the preservation of both drug and antibody activity. After activation of MTX with N-hydroxysuccinimide, MTX was bound to the antibodies under conditions leading to maximum protein and antibody recovery. Although the coupling conditions for both antibodies were different, up to 13 molecules of MTX-antibody molecule could be attached with retention of antibody activity. Such conjugates were active in vitro and could inhibit the growth [( 3H]deoxyuridine uptake) of cells in culture. The conjugates were highly specific, having no effect on tumors lacking the antigen; however, MTX complexed to antibody was less potent than the free drug. In vivo, the MTX-antibody impaired the growth of established tumors. Thus MTX-antibody complexes can be successfully produced and can be used for the immunotherapy of tumors.
Prolonged Survival of Skin and Tumor Allografts in Mice on High-Fat Diets: Brief Communication 2
Authors: Eduardo A. Santiago-Delpín, Josel Szepsenwol
Journal: JNCI Journal of the National Cancer Institute (1977)

The cancer-promoting effect of fat-enriched diets on mice has been known for several years. We investigated the effect of this type of diet supplemented with corn oil (200-400 ng/mouse daily), on two allograft models in the mouse, to determine whether an immunologic phenomenon occurred. Control mice were fed a standard diet. Skin grafts transplanted from DBA/2J mice to BALB/c mice and from C57BL/6J mice to C57BR mice survived significantly longer on recipients fed fat-enriched diets than on those fed the control diet. Similarly, allogeneic tumor grafts (6C3HED on C57BR and BALB/c mice, and dbrB on BALB/c mice) survived longer on groups fed the experimental diet.
Abstract 230: Targeted Temperature Management: Exploring the Association Between Processes of Care and Outcomes After Out-of-Hospital Cardiac Arrest
Authors: Steve Lin, Damon C Scales, Paul Dorian, Alex Kiss, Matthew R Common, Steven C Brooks, Shaun G Goodman, Laurie J Morrison
Journal: Circulation (2013)

Introduction: Randomized trials have demonstrated that Targeted Temperature Management (TTM) improves functional survival in patients after out-of-hospital cardiac arrest (OHCA). However, the optimal process of implementation and delivery remains unclear, specifically how fast, how cold or how long to cool. The objective of this study was to evaluate the association of these processes of care with survival and neurological function in patients after OHCA. METHODS: We conducted a retrospective cohort study on consecutive adult (≥18 years) non-traumatic OHCA patients from November 1, 2007 to January 31, 2012. Eligible patients who were treated with TTM after return of spontaneous circulation were included. The primary and secondary outcomes were in-hospital survival and good neurological status (Modified Rankin Scale of 0-3) at hospital discharge, respectively. Bivariate and generalized estimating equation analyses were used to evaluate the associations between processes of care variables and patient outcomes. Results: There were 5770 consecutive OHCA patients, of whom 747 (12.9%) patients were eligible and received TTM; 365 (48.9%) patients survived to hospital discharge, of whom 241 (66.0%) patients had good neurological outcomes. After adjusting for the Utstein variables, a higher temperature prior to cooling was associated with improved survival [OR 1.26 per °C, 95% CI 1.09-1.46, p=0.002] and neurological outcomes [OR 1.27 per °C, 95% CI 1.08-1.50, p=0.004]. Moreover, a slower rate of cooling was associated with improved survival [OR 0.73 per °C/hr, 95% CI 0.54-1.00, p=0.05] and neurological outcomes [OR 0.74 per °C/hr, 95% CI 0.57-0.97, p=0.03]. The location of cooling initiation, coldest temperature, and cold duration ≤34°C were not associated with outcomes. CONCLUSION: A higher baseline temperature prior to cooling and a slower rate of cooling were associated with both improved survival and neurological outcomes. This may reflect the complex relationship between the extent of brain injury causing hypothalamic dysfunction and impaired thermoregulation, and the cooling techniques used in patients after cardiac arrest.
Intensive outpatient adjuvant therapy for breast cancer: results of dose escalation and quality of life.
Authors: S M Swain, J Rowland, K Weinfurt, C Berg, M E Lippman, L Walton, E Egan, D King, I Spertus, S F Honig
Journal: Journal of Clinical Oncology (1996)

PURPOSE A dose-escalation study was conducted to determine the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cyclophosphamide (CY) in combination with granulocyte colony-stimulating factor (G-CSF0 and doxorubicin (DOX) given every 2 weeks for eight cycles as outpatient adjuvant therapy for node-positive breast cancer. A pilot study to assess quality of life (QOL) was performed. PATIENTS AND METHODS From March 1991 to April 1993, 19 patients were entered. Patients received escalating doses of CY intravenously (i.v.) (1,000 mg/m2, 1,500 mg/m2, 2,000 mg/m2, or 2,500 mg/m2) with DOX 40 mg/m2, G-CSF 10 micrograms/kg/d on days 2 to 12, and mesna, every 2 weeks for eight cycles. QOL was measured by the Profile of Mood States (POMS), the Psychosocial Adjustment to Illness Scale-Self Report (PAIS-SR), and a 27-item QOL scale. RESULTS The CY dose of 2,500 mg/m2 every 2 weeks elicited toxicities that required dose reductions secondary to a combination of thrombocytopenia, hematuria, and anemia that required transfusion. The dose of 2,000 mg/m2 resulted in an acceptable toxicity profile. Ninety-two percent of cycles at the 2,000-mg/m2 dose were delivered on schedule and 77% without hospitalization. QOL assessments indicated high levels of distress measured by POMS in 47%, poor overall quality of life in 40%, and significant problems with physical symptoms in less than 27% of all patients for any given cycle. CONCLUSION A dose of CY at 2,000 mg/m2 can be administered every 2 weeks with DOX and G-CSF for eight cycles in the outpatient setting with manageable toxicity. The majority of women described levels of physical symptoms and emotional distress as tolerable during treatment.
Oropharyngeal cancer (OPC) and racial outcome disparities in squamous cell carcinoma of the head and neck (HNSCC): Ten-year experience at the University of Maryland Greenebaum Cancer Center (UMGCC).
Authors: Dan Paul Zandberg, Sandy Liu, Olga G. Goloubeva, Robert Ord, Scott E Strome, Mohan Suntharalingam, Rodney Taylor, Jeffrey S Wolf, Ann Zimrin, Joshua E Lubek, Lisa M Schumaker, Kevin J. Cullen
Journal: Journal of Clinical Oncology (2014)

6083 Background: Racial outcome disparities have been observed in head and neck cancer with diminished survival for black patients compared to whites. The etiology of this disparity appears to be multifactorial in origin. Methods: We retrospectively analyzed 1318 patients with primary HNSCC treated at the UMGCC from 2000 to 2010. Results: 65.9% of patients were white, 30.7% were black and 3.3% were other races. Black patients were far less likely to present with oral cavity cancer (15.6% of cases) and far more likely to present with laryngeal or hypopharyngeal cancers (47.9% and 65.6% of cases respectively). Whites were more likely to have early stage (I and II) disease, especially in the oral cavity. In the full cohort, overall survival (OS) for blacks was significantly worse than for whites (median 2.5 years vs. 4.8 years, p<0.0001). Multivariable Cox regression analysis showed black patients had significantly worse OS accounting for age, gender, stage, primary site, and tobacco and alcohol consumption. Black patients had worse OS in both oral cavity (medians 5.7 vs. 3.2 years, p<0.0001) and oropharynx (OPC) (medians 4.9 vs. 2.1 years p<0.0001). However, multivariable analysis showed that race was only significantly associated with survival in OPC. The difference in survival in oral cavity cancers resulted from the larger proportion of white patients with Stage I or II disease. White patients with oral cavity and OPC were more likely to have surgery as primary treatment than blacks reflecting the higher prevalence of early stage disease. There was no difference in OS between races in laryngeal or hypopharyngeal cancer with the majority of these patients presenting with locally advanced disease. Conclusions: We observed striking differences in site of disease, stage at presentation and survival comparing black and white patients. Survival disparity overall is driven by a large difference in OPC patients. This is consistent with previous reports of differences in the incidence of HPV in the two ethnic groups, but likely reflects other factors as well.
Feline Leukemia Virus Infection: Age-Related Variation in Response of Cats to Experimental Infection2
Authors: Edward A. Hoover, Richard G. Olsen, William D. Hardy, Joseph P. Schaller, Lawrence E. Mathes
Journal: JNCI Journal of the National Cancer Institute (1976)

Sixty-seven specific-pathogen-free cats of various ages (newborn, 2 wk, 1 mo, 2 mo, 4 mo, and 1 yr) were inoculated ip with either the Rickard (R) or the Kawakami-Theilen (KT) strain of feline leukemia virus (FeLV). Susceptibility to FeLV was judged by induction of a) FeLV group-specific antigens (gsa) in leukocytes, b) FeLV-related disease, c) antibody to feline oncornavirus-associated cell membrane antigen (FOCMA), and d) virus-neutralizing (VN) antibody. Susceptibility to FeLV-decreased with age. Persistent viremia and FeLV-related disease developed in 100% of cats inoculated as newborns, in 85% of cats inoculated at 2 weeks to 2 months of age, and in 15% of cats inoculated at 4 months or 1 year of age. Cats susceptible to FeLV leukemogenesis became persistently FeLV gsa-positive (viremic) at 4 weeks post inoculation and thereafter and produced little or no FOCMA or VN antibody. Cats that resisted leukemogenesis by FeLV all developed persistent FOCMA and VN titers and never became FeLV gsa-positive. The disease in inoculated cats was influenced by virus strain; FeLV-R induced predominantly thymic lymphosarcoma, whereas FeLV-KT caused fatal nonregenerative anemia without concurrent neoplasia.
SAT0378 Autophagy is Up-Regulated in the Salivary Glands of Primary Sjogren's Syndrome Patients and Correlates with the Focus Score and Disease Activity
Authors: C. Alessandri, F. Ciccia, R. Priori, E. Astorri, G. Guggino, R. Alessandro, A. Rizzo, F. Conti, A. Minniti, C. Barbati, M. Vomero, M. Pendolino, E. Ortona, T. Colasanti, M. Pierdominici, W. Malorni, G. Triolo, G. Valesini
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Autophagy is now considered as a major regulator in trafficking events that activates innate and adaptive immunity and consistent evidence supports its role in autoimmunity (1). Primary Sjogren9s syndrome (pSS) is a systemic autoimmune disease characterized by infiltration of exocrine glands by T and B cells that, producing chemokines and cytokines, coordinate the chronic inflammatory process. No data on the role of autophagy in pSS are available in humans, although studies in mice demonstrated its involvement in the salivary and lacrimal gland homeostasis (2,3). <h3>Objectives</h3> We investigated the autophagy process in salivary gland tissue and in peripheral T lymphocytes from pSS patients to evaluate its possible implication in the pathogenesis of the disease. <h3>Methods</h3> 30 patients with pSS, 20 patients with sicca syndrome or non-specific-chronic-sialoadenitis and 30 healthy donors were studied. Peripheral T lymphocytes were isolated by standard procedures. Salivary gland biopsies were evaluated by i) H&amp;E to assess histological pattern, the severity of inflammatory infiltrate and the presence of germinal centers, ii) RT-PCR for the expression of autophagy-related genes and IL-23p19 and IL-21 mRNA. Autophagy-related proteins (LC3, Atg5, p62/SQSTM1) were detected in peripheral T lymphocytes by western blot and in salivary gland by immunohistochemistry and immunofluorescence. IL-21 and IL-23p19 serum levels were measured by ELISA. <h3>Results</h3> Autophagy is up-regulated in T cells from the salivary glands, but not from the peripheral blood, of pSS patients and it is correlated with disease activity and damage indexes. Autophagy is also correlated with the local expression of the pro-inflammatory cytokines IL-21 and IL-23p19, but not with serum levels of these cytokines. <h3>Conclusions</h3> Our data show that, in pSS, T cells present high levels of autophagy, which may up-regulate the expression of pro-inflammatory cytokines, providing evidence for a role of this process in the pathogenesis of pSS and identifying a possible therapeutic target. <h3>References</h3> Pierdominici M, Vomero M, Barbati C et al. FASEB J. 2012; 26: 1400-1412. Morgan-Bathke M, Lin HH, Chibly AM et al. J Dent Res. 2013; 92: 911-917. Seo Y, Ji YW, Lee SM, et al. Cell Death Dis. 2014; 5: e1309. <h3>Disclosure of Interest</h3> None declared
GALNT1-Mediated Glycosylation and Activation of Sonic Hedgehog Signaling Maintains the Self-Renewal and Tumor-Initiating Capacity of Bladder Cancer Stem Cells
Authors: Chong Li, Ying Du, Zhao Yang, Luyun He, Yanying Wang, Lu Hao, Mingxia Ding, Ruping Yan, Jiansong Wang, Zusen Fan
Journal: Cancer Research (2015)

Abstract The existence of bladder cancer stem cells (BCSC) has been suggested to underlie bladder tumor initiation and recurrence. Sonic Hedgehog (SHH) signaling has been implicated in promoting cancer stem cell (CSC) self-renewal and is activated in bladder cancer, but its impact on BCSC maintenance is unclear. In this study, we generated a mAb (BCMab1) against CD44+ human bladder cancer cells that recognizes aberrantly glycosylated integrin α3β1. The combination of BCMab1 with an anti-CD44 antibody identified a BCMab1+CD44+ cell subpopulation as BCSCs with stem cell–like properties. Gene expression analysis revealed that the hedgehog pathway was activated in the BCMab1+CD44+ subpopulation and was required for BCSC self-renewal. Furthermore, the glycotransferase GALNT1 was highly expressed in BCMab1+CD44+ cells and correlated with clinicopathologic features of bladder cancers. Mechanistically, GALNT1 mediated O-linked glycosylation of SHH to promote its activation, which was essential for the self-renewal maintenance of BCSCs and bladder tumorigenesis. Finally, intravesical instillation of GALNT1 siRNA and the SHH inhibitor cyclopamine exerted potent antitumor activity against bladder tumor growth. Taken together, our findings identify a BCSC subpopulation in human bladder tumors that appears to be responsive to the inhibition of GALNT1 and SHH signaling, and thus highlight a potential strategy for preventing the rapid recurrence typical in patients with bladder cancer. Cancer Res; 76(5); 1273–83. ©2015 AACR.
Demographics of patients with chronic obstructive pulmonary disease (COPD) being referred and set up on home mechanical ventilation (HMV) between 2000 and 2013
Authors: Saba Bokhari, Andrew Bentley, Nauman Chaudhry
Journal: European Respiratory Journal (2014)

Introduction  The number of referrals to our unit for setting up patients with chronic respiratory failure due to COPD on HMV is increasing. However limited data exists as to which groups of patients with COPD are being referred for set up.   Methods  A retrospective review was undertaken of the demographics of all patients with a primary diagnosis of COPD set up on HMV in our service from 2000 to 2013.   Results  213 patients (112 male) with chronic respiratory failure due to COPD were set up on HMV. Mean age at set up was 64 (40-84). 75% (99/ 132) had a BMI greater than 30. 11% of patients had cor pulmonale at the time of referral and 6.6% subsequently were investigated for lung cancer. Median FEV1 (n=120) was 0.85 (0.3-2.3). Exercise tolerance at time of referral (n=72) indicated 31% were housebound, 50 had a median value of 27.5 yards (5-500).The median arterial pressure of carbon dioxide at time of referral (n=100) was 8.2 (5.7-12.8). 71% of patients (n=101) were referred due to a previous admission requiring acute non invasive ventilation (NIV) - the median number of admissions (n=59) was 1 (1-9). 32% (68/213) of patients set up on HMV for COPD have died. In this group the median number of months on HMV (n=60) was 19.5 (1-99) compared to 23 (2-131) (n=132) in those still alive.   Conclusions   Our data suggests that there are increasing numbers of referrals for set up on HMV for patients with chronic respiratory failure due to COPD. It is possible that there is a survival advantage in patients with such advanced disease. We need to better understand whether the benefits are conferred by identifiably different clinical subgroups.
Ultrasound evaluation of diaphragm mobility according to body positions in healthy subjects
Authors: Letícia Z. Cardenas, Elena Prina, Pauliane V. Santana, Luiz Fernando Orlandin, Ozires Ramos, Mayra Caleffi Pereira, Jeferson Ferreira, Marcelo Macchione, Pedro Caruso, Carlos Carvalho
Journal: European Respiratory Journal (2014)

Background : Ultrasound (US) has been proved a simple, well tolerated and reproducible method of assessing diaphragmatic movement. The influence of body postures on diaphragmatic mobility in healthy subjects by US evaluation is not fully established. Aims: To describe the right diaphragmatic mobility by US and to compare the effects of different postures (sitting and supine) on diaphragm motion. Methods: In12 healthy volunteers we performed an US of the right diaphragmatic to evaluate mobility during quiet breathing (QB) and deep breathing (DB) both in supine and sitting position. We also evaluated the superficial electromyography (EMG) of external oblique abdominal muscle and sternocleidomastoid (Sc). Results: There were 6 male, age 31 ±7 yrs and BMI 23 ±2kg.m-2. The mobility of the right diaphragmatic in supine was higher than in sitting position during QB (1.83±0.7 cm vs 1.37±0.54cm p=0.006) and DB (7.48±0.81 vs 5.17±1.48cm p<0.001) respectively (figure1). All individuals increased mobility in supine position, and it was approximately 36% at QB and 54% in DB higher than in sitting. Abdominal recruitment was not significantly different but the Sc was more active in supine (p= 0.07). Conclusions: In healthy subjects, diaphragmatic mobility is significantly influenced by body position and is higher in supine position. The active mechanisms still need further studies.

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Changing ER, PgR, and HER2 status between primary and recurrent breast cancer.
Authors: Akiko Matsumoto, Maiko Takahashi, Tetsu Hayashida, Shigemichi Hirose, Hiromitsu Jinno, Yuko Kitagawa
Journal: Journal of Clinical Oncology (2012)

92 Background: Estrogen receptor (ER), progesterone receptor (PgR), and HER2 status are important biological markers for making decisions about breast cancer treatments. Although changes of hormone receptor (HR) and HER2 status with recurrence of breast cancer are clinically experienced, the frequency of discordance and clinical significance are still unknown. Thus, we investigated ER, PgR, and HER2 status with primary tumors and recurrent lesions, and assessed discordance rates and prognosis. Methods: We retrospectively identified recurrent breast cancer patients who had biopsies or resections of recurrent lesions between January 2007 to April 2012 at Keio University Hospital. HR status was assessed by immunohistochemistry (IHC) and determined using the Allred score. HR status was defined as positive when score was 3 and more. HER2 status was assessed by IHC and fluorescence in situ hybridization (FISH) analysis. We defined HER2 positivity as 3+ staining intensity by IHC or the presence of HER2 gene amplification by FISH. Results: Among 32 recurrences, 40% (13) were loco-regional recurrences (LLR) and 60% (19) were distant metastases (DM) (lung 14; liver 3; brain 1; pleura 1). Discordance rates in ER, PgR and HER2 status between the primary tumors and the recurrence lesions were 12.5%, 31.3%, and 13.8%, respectively. The most common change was loss of PgR. Changings from negative to positive in ER, PgR and HER2 status were found in 6.3%, 3.1%, and 3.4% of the patients, respectively. All gains were found in distant metastases. Discordance in ER and HER2 were more common in DM (15.8% and 17.6%) comparing with LRR (7.7% and 8.3%). Loss of HR status was not associated with a shorter time to progression (TTP) (ER: 19.3 vs. 8.5 months, p=0.185; PgR: 4.4 vs. 11.5 months, p=0.907). Patients with discordant HER2 status had significantly shorter TTP than with concordant status (0.9 vs. 11.5 months, p=0.012). Conclusions: Discordance of biological markers between primary and recurrent breast cancers were seen in 10-30%. Although HR discordance was not associated with prognosis, patients with HER2 discordance had poorer TTP. Tissue confirmation should be considered for making effective treatment decisions in recurrent breast cancer.
Abstract 14958: The Effect of Early Phase of Ischemic Preconditioning on the Leptin Resistant Diabetic Heart
Authors: Yiru Guo, Michael J Book, Junjie Du, Wen-Jian Wu, Xiaoping Zhu, Qianhong Li, Aruni Bhatnagar, Roberto Bolli
Journal: Circulation (2013)

Ischemic Preconditioning (PC) is a powerful cardioprotective phenomenon which has been demonstrated in many healthy species including human beings. However, it is unknown whether this protective ef...