tbuckley/cabot-search huggingface dataset:
A meta-analysis of systematic lymph node dissection in resectable NSCLC
Authors: H. Yang, Y. Wu, X. Yang, G. Chen
Journal: Journal of Clinical Oncology (2004)

7190 Background: It was performed a meta-analysis evaluating whether systematic nodal dissection (SND) is superior to mediastinal lymph nodal sampling (MLS) in surgical treatment of non-small cell lung cancer (NSCLC). Methods: Randomized trials published after 1995 addressing SND versus MLS in resectable NSCLC were included. Statistical analysis was performed using SPSS, including tests for homogeneity of studies and publication bias. Trials were analyzed by odds ratio (OR). Revman4.1 software was applied to process data. Results: Four trials (n=997) met inclusion criteria. The cumulative cases in SND were 481, in which 194 cases were dead; while in MLS were 496 and 247 respectively. The 5-yr overall survival (OS) for SND compared to MLS for all studies was 0.67 (95% confidence interval (CI) 0.52–0.87, p=0.002) indicating an increased 5-yr survival for SND versus MLS patients. Conclusions: There was a significant improvement in 5-yr OS for SND versus MLS in resectable NSCLC. The overall odds ratio for death is decreased 0.33 in patients with SND compared with MLS. No significant financial relationships to disclose.
Evaluation of ON 01910.Na, a novel modulator of polo-like kinase 1 (Plk1) pathway, and development of a cyclin-B1-based predictive assay in pancreatic cancer
Authors: A. Jimeno, A. Chan, X. Zhang, J. Wheelhouse, A. Solomon, S. C. Cosenza, M. Reddy, M. Rudek, P. Kulesza, E. Reddy, M. Hidalgo
Journal: Journal of Clinical Oncology (2007)

3569 Background: Plk1 is a key mitotic regulator of the transition through the G2/M checkpoint in the cell cycle. This work aimed to evaluate the activity of ON 01910.Na, a Plk1 pathway modulator, in in vitro and in vivo models of pancreatic cancer (PaCa) and to discover biomarkers predictive of efficacy. Methods: ON 01910.Na was tested in 12 PaCa cell lines. Studies assessing Plk1 related markers were conducted to identify biomarkers. For validation a live collection of PaCa xenografts from fresh tumor samples obtained at the time of surgical resection was used (PancXenoBank). The ex vivo assay was based on fine-needle aspirate (FNA) biopsies. Results: ON 01910.Na showed equal activity to gemcitabine against PaCa cell lines. The activity of ON 01910.Na correlated with suppression of two downstream mediators of PLK1, CDC25C and cyclin B1 (by mRNA and protein). ON 01910.Na was tested in xenografts from representative pancreatic cell lines. The selected markers were evaluated in an ex vivo assay, using intra-tumor pharmacokinetics to select the dose of the assay. Cyclin B1 mRNA evaluation yielded the most optimal combination of accuracy and reproducibility. Knockdown of cyclin B1 by siRNA had no effect per se or in the response of the resistant MiaPaca2 to either of the drugs. We next used the ex vivo assay to profile ten patient-derived cases from the PancXenoBank. Two cases were catalogued as potential responders. From each of these ten cases, a group of mice bearing at least 20 tumors received vehicle or ON 01910.Na for 28 days. There was a correlation between the ex vivo cyclin B1 assay and the sensitivity to the tested agent, as the 2 cases prospectively identified as sensitive met pre-specified criteria for response. Of the 8 tumors predicted to be resistant, only one was sensitive. In IHC testing cases showing ex vivo cyclin B1 down-regulation had also decreases in cyclin B1 protein, and there was a correlation between activity and IHC changes in cyclin B1. Conclusions: ON 01910.Na demonstrated significant activity in a preclinical model of PaCa. A rationally designed ex vivo cyclin B1-based assay not only identified cases sensitive to ON 01910.Na, but also replicated the pharmacodynamic events occurring after in vivo exposure. No significant financial relationships to disclose.
First-in-human study of AMG 386, a selective angiopoietin1/2-neutralizing peptibody, in adult patients with advanced solid tumors
Authors: L. S. Rosen, D. Hong, L. Chap, R. Kurzrock, A. Garcia, E. Rasmussen, L. Nguyen, Y. Hwang, C. Storgard, R. S. Herbst
Journal: Journal of Clinical Oncology (2007)

3522 Introduction: AMG 386 is a selective angiopoietin1/2-neutralizing peptibody that inhibits angiogenesis by preventing interaction of angiopoietins with Tie2 receptors. This first-in-human study evaluated the safety, pharmacokinetics (PK), and tumor response of AMG 386 in adults with advanced solid tumors. Methods: Patients (pts) in sequential cohorts received weekly IV AMG 386 at 0.3, 1, 3, 10, and 30 mg/kg. Safety assessments were adverse events (AEs), laboratory data, vital signs, ECGs, and anti-AMG 386 antibodies. Tumor response was assessed via RECIST criteria, DCE-MRI, FDG-PET, and volumetric CT. Results: As of Oct. 2, 2006, enrollment is complete with 32 pts (15 men, mean [SD] age 58 [12] years). One dose-limiting toxicity was seen at 30 mg/kg: respiratory arrest likely related to tumor burden, deemed possibly related to AMG 386. Other treatment-related toxicities were all = Grade 2; those observed in = 2 pts were fatigue (n=8), nausea (n=2), and peripheral edema (n=4). PK was dose-linear (mean terminal half-life, 3.1 to 6.3 days). AMG 386 appeared to reach a steady state after 3 doses, with minimal accumulation. Two pts developed binding antibodies to AMG 386; in 1 pt, they disappeared at wk 6. No neutralizing antibodies were seen. Sixteen pts had stable disease (4–52 wks, median 8 wks); 13 had progressive disease; 3 were not evaluable. One pt with ovarian cancer remains active at 52 weeks with 27% tumor shrinkage and investigator-reported reduction in serum CA-125 from 217 U/ml pretreatment to 73 U/ml (wk 4) and 31 U/ml (wk 48). A significant vascular effect (&gt; 20% reduction) was seen by DCE-MRI in 7 of 12 (58%) evaluable subjects. Reduction in SUVmax (FDG-PET) accompanied reduction in IAUC (DCE-MRI) in 5 of 6 evaluable patients. Conclusions: Weekly administration of AMG 386 appeared to be generally well tolerated, with 1 AE &gt; Grade 2 and no reports of the toxicities associated with VEGF blockade (hypertension, proteinuria, bleeding/clotting). Half of pts experienced stable disease; 1 has a sustained minor clinical response accompanied by a biologic response. Further clinical studies of AMG 386 in combination with chemotherapy and other targeted agents are warranted. No significant financial relationships to disclose.
GW26-e1069 Exendin-4, An Gulcagon-like Peptide 1 Analogue, Attenuates Cardiomyocyte Hypertrophy Via AMPK/mTOR Pathway
Authors: Yue Zhou, Xin He, Yiyi Huang, Yili Chen, Jiangui He
Journal: Journal of the American College of Cardiology (2015)
PTU-047 Acetic acid guided focal endoscopic resection without rfa remains an effective treatment for barrett’s neoplasia: time to reassess the role of rfa?: Abstract PTU-047 Table 1
Authors: FJQ Chedgy, P Basford, R Bhattacharyya, K Kandiah, P Bhandari
Journal: Gut (2015)

<h3>Introduction</h3> Endoscopic resection (ER) is an established effective treatment for Barrett’s neoplasia. ER can lead to recurrence due to residual neoplasia left behind, so it is suggested that all patients should undergo radiofrequency ablation (RFA) after ER. Acetic acid chromoendoscopy has been shown to be an effective method of localising and delineating dysplastic areas of Barrett’s oesophagus and we aim to review the outcome of Acetic Acid guided focal ER without RFA in our patients. <h3>Method</h3> All ER procedures between January 2005 and November 2014 were recorded in a prospective database which was analysed. Acetic acid guided focal ER was the treatment strategy with the aim of removing all neoplasia visible with acetic acid chromoendoscopy. RFA was not used in this group. <h3>Results</h3> 112 patients were treated for dysplastic Barrett’s oesophagus or early Barrett’s cancer by ER. The mean age at first procedure was 68 years and 82% of the patients were male. Mean initial Barrett’s length was 5.1 cm. 35 of 112 patients had advanced histological features on the initial ER specimen and were referred for radical cure. The remaining 77 cases showed; intramucosal cancer (IMC) in 46, high grade dysplasia (HGD) in 28 and low grade dysplasia in 3. All 77 cases have follow-up data with a mean duration of 5.4 years. 67 of 77 cases (87%) have sustained eradication of HGIN/IMC after focal ER. 10 patients (13%) developed further neoplasia during follow up. 5/10 patients (6.5%) developed invasive cancer in the residual Barrett’s, all were diagnosed endoscopically and successfully managed with radical curative treatment. Focal ER was successful in a mean of 1.3 procedures per patient (range 1–3). Complication rate was 4% (4 bleeds, 2 strictures). No additional RFA was performed in this patient group. Table 1compares our outcomes with UK HALO registry outcomes where all patients receive RFA. <h3>Conclusion</h3> Acetic acid guided ER is an effective and safe treatment for dysplastic Barrett’s oesophagus. Progression to cancer after acetic acid guided ER is equivalent to the reported rate of progression after EMR+RFA.<sup>1</sup>Equal rates of sustained eradication of HGIN/IMC are achieved. An acetic acid+ER strategy is potentially much cheaper than an ER+RFA strategy. This data calls for a better stratification of patients who require RFA after ER. <h3>Disclosure of interest</h3> None Declared. <h3>Reference</h3> Haidry, <i>et al</i>. <i>Gastroenterology</i>2013;<b>145</b>:87–95
Interleukin 21 Enhances the Expansion and Anti-Tumor Cytotoxic Activity of Cytokine-Induced Killer Cells Derived from Both Peripheral Blood and Cord Blood In Vitro.
Authors: Mingfeng Zhao, Qi Deng, Yuming Li, Xuemei Lin, Li Geng, Jinglan Li, Shujie Wang, Xinnv Xu, Zonghong Shao
Journal: Blood (2007)
Особливости лікування пацієнтів, інфікованих 1 и 4 генотипами вірусу гепатиту С, противірусними препаратами прямої дії
Authors: V.P. Shypulin, A.A. Kuzminets
Journal: GASTROENTEROLOGY (2016)

Лікування ВГС 1 і 4 генотипів є актуальною проблемою на сьогодні через високу стійкість до традиційної терапії. Вирішенням цієї проблеми, вочевидь, є застосування відносно нової групи противірусних препаратів прямої дії (ПППД). У даній статті розглядаються різні схеми лікування цими препаратами, механізм їх дії та ефективність, а також порівнюються два найбільш ефективні й перспективні із наявних сьогодні на світовому ринку ПППД — Harvoni (софосбувір/ледіпасвір) та Viekira Pak (омбітасвір/паритапревір/ритонавір + дасабувір). Порівнюються також наявні на сьогодні рекомендації Європейської асоціації з дослідження печінки (EASL), Американської асоціації з вивчення захворювань печінки (AASLD) та Канадської асоціації з дослідження печінки (CASL) щодо лікування пацієнтів із ВГС 1 та 4 генотипів.
Relationship between DNA Index and Cellular Drug Resistance in Children with Newly Diagnosed Acute Lymphoblastic Leukemia.
Authors: Zeynep Karakas, Selim Gokce, Serap Erdem Kuruca, Gulderen Yanikkaya Demirel, Ugur Ozbek, Arzu Akcay, Gonul Aydogan, Omer Devecioglu
Journal: Blood (2004)
Transcutaneous immunization via rapidly dissolvable microneedles protects against hand-foot-and-mouth disease caused by enterovirus 71
Authors: Zhuangzhi Zhu, Xiaohua Ye, Zhiqiang Ku, Qingwei Liu, Chaoyun Shen, Huafei Luo, Hansen Luan, Chenghao Zhang, Shaoqiong Tian, CheeYen Lim, Zhong Huang, Hao Wang
Journal: Journal of Controlled Release (2016)
Mandatory tuberculosis case notification in high tuberculosis-incidence countries: policy and practice
Authors: Mukund Uplekar, Sachin Atre, William A. Wells, Diana Weil, Rafael Lopez, Giovanni Battista Migliori, Mario Raviglione
Journal: European Respiratory Journal (2016)

Mandatory tuberculosis (TB) notification is an important policy under the End TB Strategy, but little is known about its enforcement especially in high TB incidence countries. We undertook a literature search for selected high-incidence countries, followed by a questionnaire-based survey among key informants in countries with high-, intermediate- and low-TB incidence. Published literature on TB notification in high-incidence countries was limited, but it did illustrate some of the current barriers to notification and the importance of electronic systems to facilitate reporting by private providers. Required survey data were successfully gathered from 40 out of 54 countries contacted. TB is notifiable in 11 out of 15 high-incidence countries, all 16 intermediate-incidence countries, and all nine low-incidence countries contacted. TB case notification by public sector facilities is generally systematised, but few high-incidence countries had systems and tools to facilitate notification from private care providers. In the context of the new End TB Strategy aimed at eventual TB elimination, all countries should have TB on their national list of notifiable diseases. Enhancing the ease of notification by private providers is essential for effective implementation. To that effect, investing in strengthening disease surveillance systems and introducing digital tools to simplify notification are logical ways forward.
Estimating the population abundance of tissue-infiltrating immune and stromal cell populations using gene expression
Authors: Etienne Becht, Nicolas A. Giraldo, Laetitia Lacroix, Bénédicte Buttard, Nabila Elarouci, Florent Petitprez, Janick Selves, Pierre Laurent-Puig, Catherine Sautès-Fridman, Wolf H. Fridman, Aurélien de Reyniès
Journal: Genome biology (2016)

We introduce the Microenvironment Cell Populations-counter (MCP-counter) method, which allows the robust quantification of the absolute abundance of eight immune and two stromal cell populations in heterogeneous tissues from transcriptomic data. We present in vitro mRNA mixture and ex vivo immunohistochemical data that quantitatively support the validity of our method's estimates. Additionally, we demonstrate that MCP-counter overcomes several limitations or weaknesses of previously proposed computational approaches. MCP-counter is applied to draw a global picture of immune infiltrates across human healthy tissues and non-hematopoietic human tumors and recapitulates microenvironment-based patient stratifications associated with overall survival in lung adenocarcinoma and colorectal and breast cancer.
A phase II trial of first-line bevacizumab in combination with pemetrexed and carboplatin in advanced nonsquamous non-small cell lung cancer (NSCLC)
Authors: Z. G. Skaff, A. Hageboutros, K. Krieger, S. Coakley, R. Somer, J. Stevenson
Journal: Journal of Clinical Oncology (2009)

e19091 Background: Combining bevacizumab (Bev) with platinum doublet yields a survival benefit in previously untreated patients with advanced nonsquamous non-small cell lung cancer. Carboplatin with pemetrexed is an efficient combination that is potentially less toxic. This phase II trial evaluates the efficacy and the safety of adding bevacizumab to carboplatin and pemetrexed in advanced non-small cell lung cancer. Methods: This is a single arm, open-label phase II trial. Eligibility stipulated enrollment of patients with stage IIIB/IV non-squamous non-small cell lung cancer with an ECOG PS 0–1 and no other contraindications to Bev. Treatment consisted of pemetrexed 500 mg/m 2 , carbo AUC 6 and Bev 15mg/kg on day 1, repeated every 3 weeks. If clinical benefit was proven, patients received Bev maintenance until progression. The response was evaluated every two cycles. The primary endpoint was time to progression (TTP); secondary endpoints included overall survival, response rate (RR) and grade 3–4 toxicities. Results: As of September 2008, 27 out of 42 projected patients were enrolled of which, 14 were males and 13 females; median age 68 (72% older than 60); IIIB/IV 5/22; median number of cycles 9 (range 2–33). At the time of analysis, 25 patients were evaluable. Preliminary results show a median time to progression of 7.25 months (95% CI, 6.4 to 8.2). 23 patients (92%) had disease control (95%, CI 82–96%) with an overall response rate of 36% (95%, CI 25–47%).14 patients had stable disease (56%), 8 had partial response (32%) and one achieved a complete response (4 %). Median survival has not yet been reached. Grade 3/4 adverse events include: Cerebral ischemic event (N=1), Anorexia (Gr 3: N= 5/ Gr 4: N= 4), gastrointestinal fistula (N=1), hypertension (Gr3: N=3), epistaxis (Gr 3 N=1), vomiting (Gr 3; N= 3), fever (Gr 4: N=1) and neuropathy (Gr 3: N=2). Conclusion: The addition of bevacizumab to carboplatin and pemetrexed appears to be an active first line treatment with a high disease control rate and an acceptable toxicity profile in the setting of advanced non-small cell lung cancer. No significant financial relationships to disclose.
Phase I trial of panobinostat (LBH589) in combination with trastuzumab in pretreated HER2-positive metastatic breast cancer (mBC): Preliminary safety and tolerability results
Authors: P. Conte, M. Campone, P. Pronzato, D. Amadori, R. Frank, F. Schuetz, D. Rea, A. Wardley, C. Britten, A. Elias
Journal: Journal of Clinical Oncology (2009)

1081 Background: Panobinostat is a potent inhibitor of histone deacetylase (HDAC) and has demonstrated single-agent activity and synergistic effects in combination with trastuzumab or docetaxel in HER2 positive BC xenografts. Methods: Previously treated mBC patients (pts), who progressed on or within 6 months of trastuzumab-based therapy, were enrolled in this multicenter study. Pts were dosed with either i.v. (Day 1+8) or oral panobinostat (three times per week, continuously) every three weeks in combination with standard weekly dose trastuzumab. To establish maximum tolerated dose, three (10, 15, and 20 mg/m 2 ) and four (15, 20, 30 and 40 mg) cohorts are planned for treatment with i.v. and oral panobinostat, respectively. The pharmacokinetic (PK) profile is also measured. Results: Eighteen pts have been enrolled in this ongoing trial. Median age 54 yrs (33–60). Six pts were ER and PR negative, eight pts had liver metastasis, eight pts had lung metastasis, and two pts had central nervous system metastasis. All patients received prior taxanes and/or anthracyclines. All progressed on or within 6 months of trastuzumab-based treatment. The first cohort completed accrual with 13 pts (seven received oral and six received i.v. panobinostat). No dose-limiting toxicity (DLT) was reported in the i.v. arm, and only one DLT, uncomplicated grade 4 thrombocytopenia, was reported in the oral arm. The second cohort is ongoing, eight pts have been enrolled (five in i.v. and three in oral), and no DLTs have been reported yet. Additional safety results include: one pt with grade 3 leucopenia and grade 1 or 2: nausea in six pts; vomiting, four pts; diarrhea, five pts; stomatitis, three pts; and fatigue, three pts. One pt had grade 2 asymptomatic QT prolongation. In the first cohort, two pts experienced tumor reduction of 29% (both had liver metastasis), and four pts received over eight cycles of the combination. Conclusions: The preliminary results in the first cohort demonstrated that the combination is well tolerated and shows promising activity. Additional patient safety and full PK data will be presented. [Table: see text]
Significance of palpability in invasive lobular carcinoma of the breast.
Authors: M. Iyer, F. Zhu, E. A. Ross, E. R. Sigurdson, G. M. Freedman, R. J. Bleicher
Journal: Journal of Clinical Oncology (2010)

e11092 Background: Invasive lobular carcinoma's (ILC's) growth pattern makes it more difficult to feel on physical examination than other histologic types of breast cancer. We reviewed palpable and nonpalpable ILCs to determine what clinicopathologic features predict palpability, and whether palpability is associated with patient outcomes. Methods: A prospectively collected database under an IRB- approved clinical protocol for data collection and outcomes research was retrospectively reviewed. Clinicopathologic features, including body mass index (BMI) and bra cup size, surgical therapy, and outcomes were evaluated. Results: There were 227 ILCs treated between 1970 and 2009 of whom 175 (77.1%) underwent lumpectomy and 52 (22.9%) had a mastectomy. 109 tumors were palpable and 118 nonpalpable. On univariate analysis, ILCs were more frequently palpable in patients who were pre/perimenopausal (p = 0.01), with a lower BMI (25.4 vs. 27.96, p = 0.001), and smaller bra cup size (p = 0.001). On univariate analysis, larger tumor size (1.2 vs. 1.5 cm, p = 0.008), higher grade (p = 0.003) and nodal positivity (p = 0.05) predicted palpability, while estrogen receptor status, progesterone receptor status, and lymphovascular invasion were not associated with palpability. Multivariate analysis, including age, menopausal status, race, tumor size, nodal positivity, and bra cup size, demonstrated that palpable ILCs were more likely to be associated with a lower BMI (p = 0.006) and higher grade (p = 0.04). A lower bra cup size predicted palpability in pre/perimenopausal women only (p = 0.002). Excisional biopsy (p = 0.007) and mastectomy (p = 0.01) were performed more commonly when ILCs were palpable. When adjusting for pathologic T stage, nodal status, ER status and grade, palpable ILCs had worse overall survival (HR = 3.1, CI 1.33-7.23, p = 0.03) but local recurrence was unaffected (p = 0.73). Conclusions: ILCs were more likely to be palpable when larger and found in pre/perimenopausal women with a lower BMI and bra cup size. However, while ILCs are harder to detect clinically than other types of breast cancer, palpability was a negative independent prognostic factor associated with higher tumor grade and poorer survival. No significant financial relationships to disclose.
Maintenance Chemotherapy (MC) after Autotransplantation in First-Remission Acute Lymphoblastic Leukemia (ALL): Single-Center Experience of 100 Patients.
Authors: Bhawna Sirohi, Ray Powles, Jennifer Treleaven, Samar Kulkarni, Radovan Saso, Mike Potter, Mark Ethell, Gareth Morgan, Seema Singhal, Jayesh Mehta
Journal: Blood (2007)
Race and prostate cancer: Attitudes toward diagnosis and treatment among newly diagnosed patients
Authors: P. A. Godley, J. A. Clark, D. D. Gellatly, S. T. Jackson, J. A. Talcott
Journal: Journal of Clinical Oncology (2004)

6056 Background: Patient factors potentially affecting prostate cancer (PC) screening and treatment behavior may differ by race. Methods: Using Rapid Case Identification in the North Carolina Tumor Registry, we identified 84 newly diagnosed African American (AA) and 253 Caucasian (C) PC patients. Interviews assessed their socioeconomic position, health attitudes, access to care, pretreatment symptoms and treatment choices. Most men had begun their treatment. Results: AA men were younger, had less education, and lower income compared to C men (all P<0.001), but racial groups did not differ in insurance coverage or their proximity to their site of care. However, AA men more often reported foregoing a doctor's care even when they perceived a need, less often saw the same MD regularly, and reported less trust in their MD about cancer. AA men reported more relatives with prostate cancer, greater risk of and fear of prostate cancer than other men, and greater belief that fear causes most men to put off checking their prostate. AA and C men did not differ on the first evidence for their cancer, although it arose more often at special screening sessions for AA men. Their treatment choices did not differ from C men, despite a greater preference to avoid surgery. AA men reported a lower self-assessment of global health, but their self-reported ability to perform social roles without physical or mental health limitations, and their urinary, bowel and sexual function were the same as those of C men. Conclusions: Although less well educated, AA men in North Carolina are aware of their greater risk of PC and the need for treatment when diagnosed, and they tend to assume greater responsibility for getting cancer and delaying diagnosis. However, absence of strong ties to a primary physician, mistrust of physicians in general, constrained opportunities to utilize needed care, and fear of prostate cancer may present barriers to timely diagnosis. No significant financial relationships to disclose.