tbuckley/cabot-search huggingface dataset:
Clinicopathologic significance of HER2 expression in gastric cancer: A retrospective study in Indian population.
Authors: Sudheer Reddy Kataru, Venkata Sampath Vankamamidi, Amit Kumar Chowhan, Meenakshisundaram Manickavasagam, Khajjayam Radhakrishna, Nadiminty Raghuvamsi, Dandugundu Bhargavi, Vindhya Vasini Andra
Journal: Journal of Clinical Oncology (2013)

e15143 Background: Gastric cancer is the second most common cause of cancer related death worldwide. HER2 expression is an important biomarker for identifying patients who could respond to targeted therapy. The purpose of this study was to evaluate the frequency of HER2 expression and its clinicopathological significance in Indian population with gastric cancer. Methods: In this retrospective study, clinicopathological details and formalin fixed embedded tissue from patients with gastric and gastro-esophageal junction Adenocarcinoma of all stages from August 2009 to January 2012 were collected. HER2 status in the tissue was evaluated by the validated methods. IHC (Immunohistochemistry) scores of 3+ were considered positive, 2+ equivocal, 1+ and 0 negative for HER2. Equivocal staining was further evaluated with FISH (Fluorescence In-situ Hybridization) testing. The significance of HER2 expression was correlated with epidemiological, clinical, pathological and biochemical parameters using Pearson’s test. Progression free survivals (PFS) were compared using Log Rank test (Mantel-Cox). Kaplan-Meier curves were determined for PFS. SPSS version 17.0 was used for statistical analysis. Results: We studied 135 patients, of which IHC for HER2 was 3+ in 8.8%, 2+ in 10.4%, 1+ in 8.9% and zero in 71.9%. Among HER2 equivocal samples (n=14), FISH showed HER2 gene amplification in 14.2%. HER2 status was negative in 89.6% and positive in 10.4%.HER2 status significantly correlated with stage (p=0.03), smoking status (p=0.022) and not correlated with Age, Gender, Site, Lauren’s classification, Albumin, Hemoglobin. HER2 negative patients have better PFS (13.1 versus 7.1 months; p=0.005) and the levels of HER2 expression significantly influenced the PFS (p=0.006).Median PFS in patients with 3+, 2+, 1+ and zero IHC scores were 8.2, 8.8, 9.3, and 14.2 months respectively. Conclusions: The frequency of HER2 expression in gastric cancer in Indian population is comparable to the published data. HER2 in Gastric cancer serves as a prognostic marker.
Colony‐stimulating factor 1 and its receptor are new potential therapeutic targets for allergic asthma
Authors: Hyung‐Geun Moon, Seung‐jae Kim, Myoung Kyu Lee, Homan Kang, Hak Soo Choi, Anantha Harijith, Jinhong Ren, Viswanathan Natarajan, John W. Christman, Steven J. Ackerman, Gye Young Park
Journal: Allergy (2019)

A new approach targeting aeroallergen sensing in the early events of mucosal immunity could have greater benefit. The CSF1-CSF1R pathway has a critical role in trafficking allergens to regional lymph nodes through activating dendritic cells. Intervention in this pathway could prevent allergen sensitization and subsequent Th2 allergic inflammation.To examine the therapeutic effectiveness of CSF1 and CSF1R inhibition for blocking the dendritic cell function of sensing aeroallergens.We adopted a model of chronic asthma induced by a panel of three naturally occurring allergens and novel delivery system of CSF1R inhibitor encapsulated nanoprobe.Selective depletion of CSF1 in airway epithelial cells abolished the production of allergen-reactive IgE, resulting in prevention of new asthma development as well as reversal of established allergic lung inflammation. CDPL-GW nanoprobe containing GW2580, a selective CSF1R inhibitor, showed favorable pharmacokinetics for inhalational treatment and intranasal insufflation delivery of CDPL-GW nanoprobe ameliorated asthma pathologies including allergen-specific serum IgE production, allergic lung and airway inflammation and airway hyper-responsiveness (AHR) with minimal pulmonary adverse reaction.The inhibition of the CSF1-CSF1R signaling pathway effectively suppresses sensitization to aeroallergens and consequent allergic lung inflammation in a murine model of chronic asthma. CSF1R inhibition is a promising new target for the treatment of allergic asthma.
Unconventional ST2- and CD127-negative lung ILC2 populations are induced by the fungal allergen Alternaria alternata
Authors: Kellen J. Cavagnero, Jana H. Badrani, Luay H. Naji, Michael B. Amadeo, Veranca S. Shah, Suzanna Gasparian, Alexa Pham, Alice W. Wang, Grégory Seumois, Michael Croft, David H. Broide, Taylor A. Doherty
Journal: Journal of Allergy and Clinical Immunology (2019)
Incidence of thromboembolic events (TEEs) before and during chemotherapy of patients with advanced gastric and gastroesophageal junction carcinoma (AG-GEJC) on clinical trials
Authors: E. D. Tetzlaff, J. Baker, J. A. Ajani
Journal: Journal of Clinical Oncology (2006)

4073 Background: TEEs are associated with AG-GEJC and chemotherapy can further increase its incidence. We assessed TEEs before and during protocol chemotherapy for AG-GEJC patients. Methods: Patients with AG-GEJC on four approved protocols between August 1997 and September 2003 were assessed for baseline TEEs, new TEEs during therapy, histology, location of the primary, and overall survival. Three protocols evaluated camptothecin-based chemotherapy (irinotecan, peg-camptothecin, and rubitecan) and one evaluated non-camptothecin-based chemotherapy. Results: We studied 191 patients. Median age was 56 (range 20–80), Male:Female 151:40, chemotherapy naïve 132 (69%). 136 patients received irinotecan-based therapy and 55 patients received non-camptothecin-based therapy. Overall, TEEs occurred in 13.6% of patients. At baseline, TEEs were diagnosed in 5.3% of untreated patients and were diagnosed in 8.5% of patients with one prior chemotherapy regimen. During protocol therapy, TEEs occurred in 6.8% of untreated patients and 10.2% of previously treated patients. The most common TEE during protocol treatment was deep vein thrombosis (46.7%). First-line camptothecin-based chemotherapy was associated with TEEs in 6.5% of the patients. Non-camptothecin-based chemotherapy was associated with TEEs in 7.3% of the patients. Untreated patients receiving irinotecan plus cisplatin had the lowest incidence of TEEs (2.6%) during treatment. TEEs increased to 10.3% in second-line therapy with irinotecan plus cisplatin. Age, gender, location of the primary tumor, and histology did not differ between patients with or without a TEE during treatment. Survival data was available for 67 patients. The median survival of patients with a TEE at anytime was 3.7 months while it was 8.1 months for patients with no history of TEE. Conclusions: This is the first report describing TEEs at baseline and during chemotherapy for patients with AG-GEJC treated on chemotherapy protocols. The data show that chemotherapy is associated with higher risk of TEEs and TEEs influence survival. No significant financial relationships to disclose.
Tubular carcinomas of the breast: A comparison of features and survival outcomes versus low grade ductal and lobular carcinomas in the SEER database.
Authors: Andrew Michael Romano, Mark E Smolkin, Patrick Michael Dillon
Journal: Journal of Clinical Oncology (2013)

e11596 Background: Tubular carcinoma of the breast (TC) is a rare histologic subtype of breast cancer considered to have a favorable prognosis relative to other histologies. TC is by definition low grade. TC is described to have clinical behavior similar to low grade ductal and lobular breast cancers, but due to its infrequent presentation, long-term follow-up studies of TC are lacking. Methods: The Surveillance, Epidemiology and End Results database was queried to include the years 1988-2009, selecting for patients with either grade 1 TC or grade 1 ductal and lobular breast cancer (G1BC). Data collected included age at diagnosis, race, stage, receptor status, overall survival, and surgery type. Two Cox proportional hazard models were assessed for differences between TC and G1BC, adjusting for age at diagnosis. Results: In SEER 18, 115,945 cases of TC+G1BC breast cancer are found, with 6.1% classified as TC. Of TC cases, 91% are stage 1, while 71% of GIBC are stage 1. Presenting stage 3 or 4 disease occurred in only 4.7% of G1BC versus 0.68% of TC cases. Due to the rarity of advanced disease, we analyzed early stage disease. For early Stage (1-2) breast cancer, mean age was 61.5 years for TC and 63.5 years for G1BC. The TC cases were 92% white, 4% black, 97% Estrogen Receptor (ER) positive, 82% Progesterone Receptor (PR) positive. Of G1BC cases, 88% were white, 5% black, 96% ER positive, 84% PR positive. Treatment differed with 76% of TC patients receiving lumpectomy versus G1BC where 65% received lumpectomy (p&lt;0.001). There was no significant difference in overall survival between Stage I TC and G1BC (p=0.98), or between Stage II TC and G1BC (p=0.075), with the survival estimate higher for TC. Conclusions: In this large-scale analysis, TC was limited to early stage disease and there was no difference in overall survival between patients with early stage TC and early stage GIBC. There were similar receptor statuses and baseline characteristics, but more conservative surgical treatment in TC. Because no survival difference exists for early stage disease, the finding of tubular histology to guide treatment decisions may not be warranted.
R-DHA-Oxaliplatin before Autologous Stem Cell Transplantation Prolongs PFS and OS As Compared to R-DHA-Carboplatin and R-DHA-Cisplatin in Patients with Mantle Cell Lymphoma, a Subgroup Analysis of the LyMa Trial
Authors: Steven Le Gouill, Catherine Thieblemont, Lucie Oberic, Krimo Bouabdallah, Emmanuel Gyan, Gandhi Damaj, Thomas Gastinne, Vincent Ribrag, Carla Araujo, Eric Deconinck, Joel Fleury, Pierre Morel, Emmanuelle Nicolas-Virelizier, Reda Bouabdallah, Jamilé Frayfer, Eric Jourdan, Richard Delarue, Laurence Sahnes, Alain Delmer, Anne Moreau, Marie C Bene, Gilles Andre Salles, Herve Tilly, Thierry Lamy, Remy Gressin, Olivier Hermine
Journal: Blood (2017)
Genome-wide association study of post-traumatic stress disorder reexperiencing symptoms in &gt;165,000 US veterans
Authors: Joel Gelernter, Ning Sun, Renato Polimanti, Robert. Pietrzak, Daniel F. Levey, Julien Bryois, Qiongshi Lu, Yiming Hu, Boyang Li, Krishnan Radhakrishnan, Mihaela Aslan, Kei-Hoi Cheung, Yuli Li, Nallakkandi Rajeevan, Frederick Sayward, Kelly Harrington, Quan Chen, Kelly Cho, Saiju Pyarajan, Patrick F. Sullivan, Rachel Quaden, Yunling Shi, Haley Hunter-Zinck, J. Michael Gaziano, John Concato, Hongyu Zhao, Murray B. Stein
Journal: Nature Neuroscience (2019)
Chat-based instant messaging support integrated with brief interventions for smoking cessation: a community-based, pragmatic, cluster-randomised controlled trial
Authors: Man Ping Wang, Tzu Tsun Luk, Yongda Wu, William H Li, Derek Y Cheung, Antonio C Kwong, Vienna Lai, Sophia S Chan, Tai Hing Lam
Journal: The Lancet Digital Health (2019)

<h2>Summary</h2><h3>Background</h3> Mobile instant messaging apps offer a modern way to deliver personalised smoking cessation support through real-time, interactive messaging (chat). In this trial, we aimed to assess the effect of chat-based instant messaging support integrated with brief interventions on smoking cessation in a cohort of smokers proactively recruited from the community. <h3>Methods</h3> In this two-arm, pragmatic, cluster-randomised controlled trial, we recruited participants aged 18 years or older who smoked at least one cigarette per day from 68 community sites in Hong Kong, China. Community sites were computer randomised (1:1) to the intervention group, in which participants received chat-based instant messaging support for 3 months, offers of referral to external smoking cessation services, and brief advice, or to the control group, in which participants received brief advice alone. The chat-based intervention included personalised behavioural support and promoted use of smoking cessation services. Masking of participants and the research team was not possible, but outcome assessors were masked to group assignment. The primary outcome was smoking abstinence validated by exhaled carbon monoxide concentrations lower than 4 parts per million and salivary cotinine concentrations lower than 10 ng/mL at 6 months after treatment initiation (3 months after the end of treatment). The primary analysis was by intention to treat and accounted for potential clustering effect by use of generalised estimating equation models. This trial is registered with ClinicalTrials.gov, number NCT03182790. <h3>Findings</h3> Between June 18 and Sept 30, 2017, 1185 participants were randomly assigned to either the intervention (n=591) or control (n=594) groups. At the 6-month follow-up (77% of participants retained), the proportion of validated abstinence was significantly higher in the intervention group than in the control group (48 [8%] of 591 in intervention <i>vs</i> 30 [5%] of 594 in control group, unadjusted odds ratio 1·68, 95% CI 1·03–2·74; p=0·040). Engagement in the chat-based support in the intervention group was low (17%), but strongly predicted abstinence with or without use of external smoking cessation services. <h3>Interpretation</h3> Chat-based instant messaging support integrated with brief cessation interventions increased smoking abstinence and could complement existing smoking cessation services. <h3>Funding</h3> Hong Kong Council on Smoking and Health.
Abstract 189: The Effects of Fw-ii Axial Blood Pump on Cardiogenic Shock After Acute Myocardial Infarction in a Sheep Model
Authors: Haibo Chen, Jianye Zhou, Hansong Sun, Yue Tang, Guangmao Liu, Yan Zhang, Shengshou Hu, Shengshou Hu
Journal: Circulation (2013)

Background: High-risk percutaneous coronary interventions (PCI), refractory cardiogenic shock and in-lab cardiac arrest are all associated with a high mortality rate in patients with acute myocardial infarction (AMI). The extent to which the use of FW-II axial pump can improve outcomes in cardiogenic shock is not known. Methods: In 12 adult male sheep, cardiogenic shock was induced by circumflex coronary artery ligation for 90 min, followed by 240 min of reperfusion. The animals were divided into two groups: control group had non-mechanic supportive care including dopamine, dobutamine and other drugs; FW-II axial pump group was supported with FW-II axial pump from 90 min after ischemia to 240 min after reperfusion. Hemodynamic efficacy (mean arterial pressure (MAP), cardiac index (CI), pulmonary artery pressure (PAP) and systemic vascular resistance (SVR)), left ventricular systolic / diastolic diameter, carotid artery blood flow velocity were measured at 3 specific conditions: preligation, postligation and before being euthanasiaed. Reperfusion area was detected by Evans blue, and apoptosis detection included TUNEL staining, caspase-3 activity, bax and bcl-2 relative expression in normal, borderline and infarcted myocardium. Results: Animals in control group survived for an average of 24 ± 9.6 hours, and Animals in FW-II group survived 72 hours and were euthanasiaed. Compared with control group, MAP, CI, artery diastolic velocity, and oxygen delivery index (DO2I and VO2I) were significantly higher (P &lt;0.05) in FW-II pump group; PAP and SVR was significantly lower than the control group (P &lt;0.01); Infarct ratio (percentage of the infarct area relative to the area at infarct risk) was significantly reduced in FW-II pump group with a significant difference from control group (P &lt; 0.001). Apoptotic index and bax expression of border zone myocardium were significantly lower in FW-II pump group (P&lt;0.01). However, there were no difference between control group and FW-II pump group for apoptotic index and bax expression in normal and infarcted myocardium (P &gt;0.05). Conclusion: Short-term assistance of FW-II axial pump improved the survival of cardiogenic shock by increasing systemic organ perfusion and reducing myocardial apoptosis.
Occurrence of HER2 amplification in EGFR-mutant lung adenocarcinoma with acquired resistence to EGFR-TKIs.
Authors: Giuseppe Altavilla, Carmela Arrigo, Chiara Tomasello, Mariacarmela Santarpia, Patrizia Mondello, Sara Benecchi, Vincenzo Pitini
Journal: Journal of Clinical Oncology (2013)

8047 Background: Patients with EGFR-mutant lung adenocarcinoma develop progression of disease on TKIs therapy after a median of 12 months;this acquired resistance is mainly due to a secondary mutation in EGFR (T790 M) in about 50% of patients, amplification of MET in 15%, PIK3CA mutations in 5%, an unknown mechanism in almost 30% and a SCLC transformation in some pts. Recently, Takezawa and colleagues pointed out that HER2 amplification is a mechanism of acquired resistance to EGFR inhibition in EGFR-mutant lung cancers without EGFR T790M mutation. To aid in identification and treatment of these patients we examined a cohort of patients whose cancers were assessed with tumor biopsies at multiple times before and after their treatment with TKIs. Methods: 41 lung adenocarcinomas pts. (20 male, 21 female, median age 55 years) with EGFR mutations at 19 or 21 exons received TKIs as first line of treatment. 31 pts. (75%) showed a clinical response and relapsed after a mTTP of 12 months. At the time of relapse a new biopsy was performed, histologic samples were reviewed to re-confirm the diagnosis, EGFR, MET and HER-2 amplification were identified by FISH, while EGFR mutations have been tested by DNA sequencing. Results: At the time that drug resistence was acquired all 31 pts. retained their original activating EGFR mutations, 16 pts. developed EGFR T790M resistance mutation with pronunced EGFR amplification in 5, 4 pts. developed MET amplification, 3 pts. were found to have a diagnosis of small cell lung cancer. HER2 amplification was observed in four pts. (13%), with dramatic progression and a median OS of 5 months after treatment with CDDP + pemetrexed. Notably all 4 cases were EGFR T790M negative. Conclusions: Among pts. with acquired resistence to EGFR TKIs the presence of HER2 amplification defines a clinical subset with a more adverse prognosis and rapid progression. Interestingly, recent data suggest that afatinib combined with cetuximab could have promising activity in pts. with acquired resistance due to HER2 amplification.
Neoadjuvant chemotherapy (NACT) with prolonged high-dose (HD) doxorubicin (A) and cyclophosphamide (C) with G-CSF support in locally advanced breast cancer (LABC): Long-term follow-up data
Authors: S. Altintas, M. T. Huizing, I. Spoormans, J. Van den Brande, P. Wilmes, W. Tjalma, D. Van den Weyngaert, M. Van Goethem, J. B. Vermorken
Journal: Journal of Clinical Oncology (2007)

11090 Background: NACT improves survival in LABC. The optimal regimen, dose and duration is still under study Objective: To determine the efficacy and safety of prolonged preoperative HD-AC plus G-CSF. Methods: LABC patients (pts) were treated with AC for 6 cycles (Cy): Cy 1: A 90 mg/m 2 , C 1000 mg/m 2 ; Cy 2–3: A 82.5 mg/m 2 , C 875 mg/m 2 ; Cy 4–6: A 75mg/m 2 , C 750 mg/m 2 ) with prophylactic (peg)filgastrim q3wks. In case of cardiotoxicity or poor tumor response (TR) pts switched to Docetaxel (D) 100mg/m 2 q3wks. Within 5 weeks after NACT, pts underwent mastectomy with axillary lymph node dissection followed by radiotherapy. In case of positive estrogen (ER) or progesteron receptor (PgR), hormonal treatment was given for 5 yrs. Toxicity was scored weekly (NCI-CTC 2), response every 3 wks (WHO). Kaplan-Meier analysis was performed to calculate disease free survival (DFS) and overall survival (OS). Results: Between 8/1997 and 10/2003 21 pts (median age 55 years, range 22–74) were enrolled. One pt had stage IIB, 6 stage IIIA, 14 stage IIIB disease (10 T4d). 10 tumors were ER+, 5 PgR+, none overexpressed Her-2/Neu. A total of 130 NACT Cy was given. 15 pts completed all 6 AC Cy, 6 switched to D because of a decrease in left ventricular ejection fraction (LVEF? &gt;10%, n=2) or insufficient TR (n=4). Dose reduction of AC was needed in 1 pt (last Cy), dose delays in 4 pts. Nausea and vomiting were generally mild; grade 4 anorexia occured in one pt. Grade 4 leucopenia and neutropenia in 14 and 18 pts, respectively. Neutropenic fever requiring hospitalization occurred in 5 pts, thrombocytopenia grade 4 in 7 pts and grade 3 anemia in 3 pts. Two pts developed cardiomyopathy (9.5%) &lt; 2 years after NACT. The overall TR rate (PR and CR) was 81%, clinical CR rate 14%, pathologic CR rate 10% and 14% had minimal residual disease. Three pts showed SD and only 1 pt had PD. The median follow up of all pts was 51 months (range 9–110), 5 yrs DFS 47%, OS 56%. 5 yrs DFS and OS for pT4d pts was 50% and 56%, respectively. Conclusions: NACT with HD-AC plus G-CSF for 6 Cy in this poor risk population is active and further supports the use of prolonged preoperative CT. The routine use of D after a restricted number of AC Cy may further improve results and decrease (cardio)toxicity. No significant financial relationships to disclose.
Economic impact of mortality risk reduction with first-line imatinib (IM) versus interferon-α (IFN) in patients newly diagnosed with chronic phase (CP) chronic myeloid leukemia (CML) under the Brazilian public healthcare system perspective over a 5-year period
Authors: F. D. Mataveli, A. Calabró, W. Mendes, D. Vianna, P. Dorlhiac-Llacer, R. Bigni, V. Hungria
Journal: Journal of Clinical Oncology (2007)

17068 Background: Patients receiving imatinib had a significant survival advantage compared with patients receiving IFN therapy (Roy et al. Blood 2006; Kantarjian et al. Blood 2006). Although reimbursed as second line therapy for CP CML patients who did not respond to INF-a, IM was not considered for public reimbursement as first line treatment in Brazil based on drug costs. An economic evaluation considering the mortality risk reduction with first line IM versus INF was performed under the Brazilian Public Healthcare System perspective, comparing the costs to avoid one death of a chronic phase CML patient over a 5-year period. Methods: Risk of death in 5 years was defined by survival rates in the 60 month follow-up of IRIS for IM (R im = 10%) (Druker et al. JCO 2006), MD Anderson cohort of CML patients treated with INF-a for INF-a (R INF-a = 38%) (Cortes et al. American J. Med 1996) and a population based-survey in Norway for the natural course of the disease (R non-treatment = 67%). IRIS INF group survival rate was not used due to high crossover to IM in the trial. Risk of death in the natural course of the disease was the basis for the absolute risk reduction (ARR) calculation (ARR im = 57%; ARR INF-a = 29%). Number need to treat (NNT) was obtained by the inverse of ARR value for each first line treatment (NNT =1/ARR). Costs were estimated based on the Brazilian public healthcare reimbursement payment (APAC-SUS) for chronic phase CML treatment. A base case economic model of 100 patients for each treatment option was constructed focused on drug costs and adverse events (AE) from the IRIS study for both groups. Clinical guidelines from two public hematology centers were used to estimate AE treatment costs. Costs were discounted at a 6% annual rate. Results: The treatment costs and NNTs for a 5-year period are US$ 62,135 and 3.45 for INF-a, and US$ 93,397 and 1.75 for IM, respectively. The costs to avoid one death over a 5-year period are US$ 214,368 for INF-a and US$ 163,445 for IM. Conclusions: The costs for avoiding one death of a chronic phase CML patient over a 5-year period is US$ 50,923 higher with first line INF-a than it would be with first line imatinib. [Table: see text]