tbuckley/cabot-search huggingface dataset:
PWE-018 Endoscopic submucosal dissection and hybrid endoscopic submucosal dissection piecemeal endoscopic mucosal resection
Authors: N Suzuki, B P Saunders
Journal: Gut (2010)

<h3>Introduction</h3> Endoscopic submucosal dissection (ESD) is recognised in Japan as an effective therapeutic modality for the clearance of gastrointestinal neoplasms, providing an en bloc specimen to confirm lateral and deep resection margins and minimising the risk of recurrence. However, due to the technical complexity, prolonged procedure time and risk of complications, few European centres have introduced this technique. This study assessed the feasibility and efficacy of ESD and hybrid ESD/P-EMR (piecemeal endoscopic mucosal resection) in a UK setting. <h3>Methods</h3> ESD was performed with either a “Flex knife” (Olympus) in the earliest cases and a “Flush knife” (Fujinon) in the later cases. After initial experience of five ESD procedures, in order to accelerate the procedure time, a decision was made to convert to hybrid ESD/P-EMR for the cases in which submucosal dissection was not progressing rapidly, that is &lt;30% of a lesion had been resected at 1 h after starting the procedure. The following factors; patient and lesion characteristics, sedation used, achievement of en-bloc resection, histology, complications and follow-up data were recorded prospectively. <h3>Result</h3> Twenty-six colorectal and four gastric lesions were removed by ESD. The resected lesions were between 10 mm and 90 mm in diameter (median 50 mm) and included six “salvage” procedure where recurrence had occurred after previously attempted endosocpic snare resection. Three patients received propfol sedation and 27 patients received conscious sedation with midazolam (mean 2.52 mg) and pethidine (mean 50 mg). ESD was completed in 18 cases and ESD abandoned in one case due to suspecting deep cancer invasion. The rest (11) was treated with ESD/EMR hybrid. The mean procedure time was 120 min (20–300 min) for ESD and 111 min (49–172 min) for ESD/P-EMR hybrid. En-bloc resection was achieved in 20/30 patients. 18 patients were hospitalised overnight and the rest were treated as a day case. The only major complication was post polypectomy bleeding in two patients 14 days and 10 days after the procedure, respectively, which required a 2-unit blood transfusion in one case but no endoscopic or surgical intervention. Histopathologically, 28 lesions were benign and two lesions were adenocarcinomas. One of which was sm1 cancer which was completely removed. In the other case, the procedure was abandoned and sent for surgery. Twenty-five out of 30 patients had follow-up examinations between 3–6 months after the initial procedure and 23/25 patients were free of recurrence. <h3>Conclusion</h3> ESD appears to be feasible and effective for the excision of selected colorectal and gastric lesions with an acceptable safety profile. After introducing the ESD/P-EMR hybrid policy, no procedure time exceeded 3 h apart from one case with a 9 cm rectal lesion.
Abstract 2809: Chemopreventive studies of multiple agents in the methylnitrosourea-induced ER+ mammary cancer model in animals on standard and Western diets
Authors: Clinton J. Grubbs, Mark S. Miller, Vernon E. Steele, Fariba Moeinpour, Harold Seifried, Brandy M. Heckman-Stoddard, Ronald A. Lubet
Journal: Cancer Research (2015)

Abstract Multiple positive and negative preventive agents [tamoxifen, vorozole (aromatase inhibitor), targretin (RXR agonist), gefitinib (EGFR inhibitor), metformin, and Lipitor] were examined for efficacy in rats given either standard Teklad (4% fat) diet or a modified Western diet [high fat (42%)]. Female Sprague Dawley rats were placed on the high fat or standard diet at 43 days of age, and administered methylnitrosourea (MNU) at 50 days of age. Rats on high fat diet vs standard diet gained approximately 40% more weight, exhibited a 50% increase in cancer multiplicity, and a decrease in cancer latency. The strong preventive agents (tamoxifen, vorozole, targretin, and gefitinib) were highly effective in animals on standard or high fat diets (reducing cancer multiplicity &amp;gt;75% in rats on either diet). It was unclear whether the altered physiology of animals on high fat diet or altered PK of agents in animals with higher fat content might alter activity of these agents. We had previously found that both metformin and Lipitor were ineffective in rats on a standard fat diet, but thought that they might be effective in rats on a high fat diet. Interestingly, neither compound decreased tumorigenesis; but, at least marginally, increased tumor incidence and final tumor weights in rats on both diets. The ability of the various agents to alter proliferation of normal mammary epithelium in MNU-treated rats exposed for 2 weeks to the various agents was determined. It was found that inhibition of proliferation in mammary epithelium corresponded well to the efficacy of these agents in long-term chemopreventive assays. These results demonstrated that: (1) a high fat diet can be employed in this rat model to increase tumor multiplicity; (2) tamoxifen, vorozole, targretin and gefitinib were highly effective in rats on standard or high fat diet; (3) metformin and Lipitor were ineffective with either diet; and (4) there is a correlation between inhibition of proliferation in normal mammary epithelium and long-term preventive efficacy of agents; but this may reflect the homogeneity of the rat mammary cancers. Supported by NCI contract HHSN261201200021I. Citation Format: Clinton J. Grubbs, Mark S. Miller, Vernon E. Steele, Fariba Moeinpour, Harold Seifried, Brandy M. Heckman-Stoddard, Ronald A. Lubet. Chemopreventive studies of multiple agents in the methylnitrosourea-induced ER+ mammary cancer model in animals on standard and Western diets. [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 2809. doi:10.1158/1538-7445.AM2015-2809
Abstract 1018: Role of Stat3 vs Stat5 in the differentiation of HC11, mouse breast epithelial cells
Authors: Jamaica Cass, Maximilian Niit, Rozanne Arulanandam, Bruce Elliott, Leda Raptis
Journal: Cancer Research (2015)

Abstract The Signal Transducer and Activator of Transcription (Stat)3 and Stat5 are transcription factors involved in normal breast development, and are hyperactivated in 30-50% of breast cancers. Stat5 is required for breast epithelial cell differentiation and is over-expressed in breast cancers with a more differentiated phenotype. On the other hand, constitutive over-activation of Stat3 can drive expression of genes involved in survival, migration and angiogenesis, while mutationally activated Stat3 (Stat3C) can transform cultured cells, indicating that Stat3 may play an important role in cancer etiology. Following activation of a number of growth factor or cytokine receptors such as interleukin-6 or expression of oncogenes such as Src, Stat3 is phosphorylated at tyr-705, dimerizes and migrates to the nucleus where it activates transcription from a number of genes involved in cell division and survival, such as survivin, Bcl-xL, Mcl1 and myc, while it downregulates expresssion of the tumor suppressor p53. We recently discovered a novel pathway of activation of Stat3: Engagement of cadherins (E-, N-cadherin or cadherin-11), cell to cell adhesion proteins induces a dramatic increase in the levels of the Rac1 and Cdc42 small GTPases, and this leads to interleukin-6 transcription, hence Stat3 activation. The differentiation of HC11, nonneoplastic mouse breast epithelial cells requires prolactin, hydrocortisone and insulin, added at confluence. Since confluence activates Stat3, we examined the role of Stat3 upon breast epithelial cell differentiation, measured by cellular morphology and expression of the milk proteins, β-casein or whey acidic protein. Through pharmacological inhibition with CPA7 or S3I-201, our results demonstrate that Stat3 is, in fact, required for HC11 cell differentiation. In contrast, constitutive expression of mutationally activated Rac1 was found to block differentiation while inducing transformation. In sharp contrast, our results indicate that Stat5 is upregulated by the differentiation cocktail but is unaffected by cell density, while expression of activated Stat5 promotes a more differentiated phenotype. Taken together, our results demonstrate that Stat3 and Stat5 may constitute independent prognostic markers as well as treatment targets for breast cancer. Citation Format: Jamaica Cass, Maximilian Niit, Rozanne Arulanandam, Bruce Elliott, Leda Raptis. Role of Stat3 vs Stat5 in the differentiation of HC11, mouse breast epithelial cells. [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 1018. doi:10.1158/1538-7445.AM2015-1018
Elevated Cell-Derived Microparticles (C-MP) in Myeloproliferative Disorders (MPD): High Red Cell Microparticles (RMP) as Risk Factor for Thrombosis.
Authors: Vincenzo Fontana, Wenche Jy, Pamela Dudkiewicz, Bidot Loreta, Martha Gonzalez, Myriam Yaniz, Yeon-Soong Ahn
Journal: Blood (2006)
Predictors of Outcome and Response to Therapy in Primary Autoimmune Hemolytic Anemia: A Gimema Study of 307 Patients
Authors: Barcellini Wilma, Bruno Fattizzo, Anna Zaninoni, Tommaso Radice, Ilaria Nichele, Eros Di Bona, Monia Lunghi, Cristina Tassinari, Fiorella Alfinito, Antonella Ferrari, Anna Paola Leporace, Pasquale Niscola, Monica Carpenedo, Carla Boschetti, Nicoletta Revelli, Maria Antonietta Villa, Dario Consonni, Laura Scaramucci, Paolo De Fabritiis, Giuseppe Tagariello, Gianluca Gaidano, Francesco Rodeghiero, Agostino Cortelezzi, Alberto Zanella
Journal: Blood (2014)
Loss of CD20 Expression and Exhaustion of Effector Cells Limit ADCC in CLL Patients Treated with Rituximab.
Authors: Berengere Vire, Justin SA Perry, Elinor Lee, Lawrence S Stennett, Leigh Samsel, Philip McCoy, Wyndham H Wilson, Bibiana Bielekova, Adrian Wiestner
Journal: Blood (2009)
Low-Intensity Fludarabine, Cyclophosphamyde, Rituximab (FCR) as Front-Line Treatment for Follicular Lymphoma. Efficacy and Toxicity Profile of the Oral Versus Intravenous Administration.
Authors: Ana Marin-Niebla, Eduardo Rios-Herranz, Fáatima de la Cruz Vicente, Paula Cerezuela, Jose Francisco Falantes, Mariluz Martino, Ildefonso Espigado, Alvaro Urbano Ispizua
Journal: Blood (2009)
Targeting Unmet Social Needs—Next Steps Toward Improving Chronic Disease Management
Authors: Ashley M. McMullen, Mitchell H. Katz
Journal: JAMA Internal Medicine (2016)

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An Amplicon-Targeted Ultra-Deep Sequencing Approach Reveals the Presence at the Onset of Multiple Myeloma and the Selection over Time of TP53 Sub-Clonal Variants, Which Adversely Influence Patients' Overall Survival
Authors: Carolina Terragna, Marina Martello, Mauro Procacci, Flavio Mignone, Annalisa Pezzi, Barbara Santacroce, Lucia Pantani, Igor Saggese, Torsten Haferlach, Elena Zamagni, Enrica Borsi, Paola Tacchetti, Beatrice A Zannetti, Serena Rocchi, Katia Mancuso, Flores A Dico, Giovanni Martinelli, Michele Cavo
Journal: Blood (2015)
A randomized phase II trial of cetuximab-based induction chemotherapy followed by concurrent cetuximab, 5-FU, hydroxyurea, and hyperfractionated radiation (CetuxFHX), or cetuximab, cisplatin, and accelerated radiation with concomitant boost (CetuxPX) in patients with locoregionally advanced head and neck cancer (HNC).
Authors: T. Y. Seiwert, D. J. Haraf, E. E. Cohen, E. A. Blair, K. Stenson, J. K. Salama, M. Kocherginsky, V. M. Villaflor, M. Witt, R. Williams, A. Dekker, E. E. Vokes
Journal: Journal of Clinical Oncology (2011)

5519 Background: Cetuximab is commonly used in combination with either chemotherapy or radiation in the treatment of HNC, although the optimal way to integrate cetuximab with concurrent chemoradiation (CRT) remains unclear. We explored the addition of cetuximab to induction chemotherapy and two established CRT platforms in a randomized phase II trial. Methods: Patients with locoregionally advanced HNC were treated with cetuximab, carboplatin, paclitaxel induction chemotherapy for 2 cycles. Patients were randomized to A: cetuximab, 5-FU, hydroxyurea, and hyperfractionated week-on week-off RT (72-74Gy) (CetuxFHX), or B: cetuximab, cisplatin, accelerated radiation with concomitant boost (CetuxPX)(72Gy). Primary endpoints were 1- and 2-year progression-free (PFS), and overall survival (OS). Results: 110 patients with locoregionally advanced HNC (108 with Stage IV) were enrolled. 57.3% of patients had oropharyngeal (OP) primaries (A: 49%, B: 66%, p16 staining is pending). Induction response rate was 91.8%. 99.1% of patients developed a rash (≥grade 3 in 16.4%); ≥grade 3 neutropenia developed in 36.3% of patients. Overall 1- and 2-year survival rates were 98.3% and 89.5% in CetuxFHX, and 94.2% and 91.4% in CetuxPX arm, with 21.1months median follow-up (not statistically significant, p=0.27, logrank test). Progression free survival at 1 and 2 years was 86.0% and 82.3% in CetuxFHX, and 95.9% and 89.7% in CetuxPX (p=0.18). Grade ≥3 mucositis was present in 91.1%(A) and 94.3%(B) of patients; grade ≥3 dermatitis in 82.1% and 50.9% of patients. 95% of patients completed therapy. Treatment failures occurred in both OP and non-OP tumors. Conclusions: Cetuximab-based induction chemotherapy is well tolerated and active. Cetuximab can safely be integrated with both FHX and cisplatin based CRT with acceptable toxicities. Survival is favorable on both study arms suggesting that either platform could be investigated further. Data on HPV versus non-HPV-related tumors will be available.
Cytomegalovirus Infection after Unrelated Cord Blood Transplantation (CBT) for Adults with Hematological Diseases.
Authors: Tomohiro Myojo, Tomoko Matsumura, Hiroto Narimatsu, Kazuhiro Masuoka, Chiho Inokuchi, Masahiro Kami, Yuji Miura, Daisuke Kato, Eiji Kusumi, Koichiro Yuji, Atsushi Wake, Junichi Ueyama, Shigesaburo Miyakoshi, Akiko Yoneyama, Michio Matsuzaki, Shinichi Morinaga, Shuichi Taniguchi
Journal: Blood (2004)
Abstract 2938: BMI-1 inhibition by PTC-209 induces mitochondrial apoptosis in acute myeloid leukemia cells
Authors: Kensuke Kojima, Yuki Nishida, Aya Maeda, Dhruv Chachad, Hiroaki Kitamura, Jo Ishizawa, Michael Andreeff, Shinya Kimura
Journal: Cancer Research (2015)

Abstract Leukemia stem cells play important roles in leukemia initiation, progression, and relapse, and represent a critical target for therapeutic intervention. BMI-1 is essential for the self-renewal of normal hematopoietic and leukemia stem cells. High expression of BMI-1 has been associated with poor prognosis in AML. PTC-209 is a novel transcriptional inhibitor of BMI-1, which has been reported to exhibit antitumor activity against cancer-initiating cells in colorectal cancer. We investigated anti-leukemia effects of the BMI-1 inhibitor PTC-209 on AML cells. A total of 8 AML cell lines (MOLM-13, OCI-AML3, MV4-11, NB4, HL-60, U-937, MOLM-14, OCI-AML2) were treated with different concentrations of PTC-209 for 48 hours and the IC50 values (concentration at which cell growth is inhibited by 50% at 48 hours of exposure) and the ED50 values (effective concentration inducing 50% killing as measured by Annexin V positivity) were determined. The IC50 values were 0.38 ± 0.07 μM (mean ± SEM), indicating high anti-proliferation effect. The ED50 values ranged from 1.2 to 2.6 μM in 7 cell lines (1.97 ± 0.22 μM) and the remaining cell line (NB4) showed relative resistance to PTC-induced apoptosis (&amp;gt; 10 μM). PTC-209 exhibited dose- and time-dependent anti-proliferative and cytotoxic activities, by inducing G1-S transition delay and apoptosis. PTC-209 induced conformational change of BAX (i.e., BAX activation), loss of mitochondrial membrane potential (MMP), caspase-3 activation and DNA fragmentation in addition to phosphatidylserine (PS) externalization, indicating mitochondrial apoptosis. PTC-209 induced Annexin V in primary AML cells (23.4 ± 4.6% after 48-hour treatment with 1 μM PTC-209, n = 23) in a dose-dependent manner, which is more prominent in immature CD34+CD38- population (33.7 ± 6.0%; P = 0.0036). In accordance with its high anti-leukemia activity, PTC-209 strongly reduced cellular BMI-1 levels in CD34+CD38- AML cells. Higher reduction of BMI-1 expression was positively correlated with higher susceptibility to PTC-209 in CD34+CD38- AML cells (r = 0.88; P = 0.047). The apoptotic activity was observed independent of p53 or FLT3 mutational status of the leukemia cells. Our data suggest that BMI-1 inhibition by small molecule inhibitors may be developed into a novel therapeutic strategy for AML. (Drs M. Andreeff and S. Kimura are co-senior authors with equal contribution to the work) Citation Format: Kensuke Kojima, Yuki Nishida, Aya Maeda, Dhruv Chachad, Hiroaki Kitamura, Jo Ishizawa, Michael Andreeff, Shinya Kimura. BMI-1 inhibition by PTC-209 induces mitochondrial apoptosis in acute myeloid leukemia cells. [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 2938. doi:10.1158/1538-7445.AM2015-2938
In Vivo Permanent Marking of Cells with RAG1 Activation History Demonstrates Only a Minor Contribution of the Lymphoid Pathway to Dendritic Cell Development.
Authors: Yong Chong, Shin-ichi Mizuno, Hirokazu Shigematsu, Yojiro Arinobu, Tadafumi Iino, Hiromi Iwasaki, Koichi Akashi
Journal: Blood (2006)
Genome-Wide Association Study for Anthracycline-Induced Congestive Heart Failure
Authors: Bryan P. Schneider, Fei Shen, Laura Gardner, Milan Radovich, Lang Li, Kathy D. Miller, Guanglong Jiang, Dongbing Lai, Anne O'Neill, Joseph A. Sparano, Nancy E. Davidson, David Cameron, Irmina Gradus-Pizlo, Ronald A. Mastouri, Thomas M. Suter, Tatiana Foroud, George W. Sledge
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Anthracycline-induced congestive heart failure (CHF) is a rare but serious toxicity associated with this commonly employed anticancer therapy. The ability to predict which patients might be at increased risk prior to exposure would be valuable to optimally counsel risk-to-benefit ratio for each patient. Herein, we present a genome-wide approach for biomarker discovery with two validation cohorts to predict CHF from adult patients planning to receive anthracycline. Experimental Design: We performed a genome-wide association study in 3,431 patients from the randomized phase III adjuvant breast cancer trial E5103 to identify single nucleotide polymorphism (SNP) genotypes associated with an increased risk of anthracycline-induced CHF. We further attempted candidate validation in two independent phase III adjuvant trials, E1199 and BEATRICE. Results: When evaluating for cardiologist-adjudicated CHF, 11 SNPs had a P value &amp;lt;10−5, of which nine independent chromosomal regions were associated with increased risk. Validation of the top two SNPs in E1199 revealed one SNP rs28714259 that demonstrated a borderline increased CHF risk (P = 0.04, OR = 1.9). rs28714259 was subsequently tested in BEATRICE and was significantly associated with a decreased left ventricular ejection fraction (P = 0.018, OR = 4.2). Conclusions: rs28714259 represents a validated SNP that is associated with anthracycline-induced CHF in three independent, phase III adjuvant breast cancer clinical trials. Clin Cancer Res; 23(1); 43–51. ©2016 AACR.
Research authors’ reply to Barlow and Barr and Taylor-Robinson
Authors: Charitini Stavropoulou, Divya Parmar, John P A Ioannidis
Journal: BMJ (2016)

Zambia has one of the most liberal abortion laws in sub-Saharan Africa.However, rates of unsafe abortion remain high with negative health and economic consequences.Little is known about the economic burden on women of abortion care-seeking in low income countries.The majority of studies focus on direct costs (e.g.: hospital fees).This paper estimates the individual-level economic burden of safe and unsafe abortion care-seeking in Zambia, incorporating all indirect and direct costs.It uses data collected in 2013 from a tertiary hospital in Lusaka, (n=112) with women who had an abortion.Three treatment routes are identified: i) safe abortion at the hospital ii) unsafe clandestine medical abortion initiated elsewhere with post-abortion care at the hospital and iii) unsafe abortion initiated elsewhere with post-abortion care at the hospital.Based on these three typologies, we use descriptive analysis and linear regression to estimate the costs for women of seeking safe and unsafe abortion and to establish whether the burden of abortion care-seeking costs is equally distributed across the sample.Around 39% of women had an unsafe abortion, incurring substantial economic costs before seeking post-abortion care.Adolescents and poorer women are more likely to use unsafe abortion.Unsafe abortion requiring post-abortion care costs women 27% more than a safe abortion.When accounting for uncertainty this figure increases dramatically.For safe and unsafe abortions, unofficial provider payments represent a major cost to women.This study demonstrates that despite a liberal legislation, Zambia still needs better dissemination of the law to women and providers and resources to ensure abortion service access.The policy implications of this study include: the role of pharmacists and mid-level providers in the provision of medical abortion services; increased access to contraception, especially for adolescents; and, elimination of demands for unofficial provider payments.
Comparable Toxicity and Outcome of Acute Myeloid Leukemia (AML) Fit Patients Therapy Independently If Daunorubicin or Idarubicin Were Added to Cytarabine/Cladribine Induction Regimens – the Single Centre Study
Authors: Sebastian Grosicki, Marek Kriegler, Ewa Bodzenta, Maja Twardosz, Ilona Szypula, Marcin Fejklowicz, Olga Haus, Teresa Kurzawa, Agnieszka Barchnicka
Journal: Blood (2012)
Lenalidomide/Dexamethasone Improves Response and Prolongs Time to Progression, Even in Patients with IgA Multiple Myeloma: A Sub-Analysis of the MM-009/010 Studies.
Authors: Robert Foa, Donna Weber, Meletios Dimopoulos, Marta Olesnyckyj, Zhinuan Yu, Jerome Zeldis, Robert Knight, Asher Alban Chanan-Khan
Journal: Blood (2007)