tbuckley/cabot-search huggingface dataset:
How is the clinical practice? Pegylated liposomal doxorubicin in the therapy of patients with recurrent ovarian cancer: Results of a German observational study
Authors: R. Chekerov, G. Oskay-Oezcelik, B. Otremba, G. Seipelt, O. Camara, M. Schmidt, B. Schmalfeldt, E. Lorsbach, J. Sehouli
Journal: Journal of Clinical Oncology (2008)

16552 Background: Pegylated liposomal doxorubicin (PLD) has demonstrated activity and been approved for the treatment of platinum-pretreated relapsed ovarian cancer when given at a dose of 50 mg/m2/q28d. Methods: This German observational multicenter study was intended to analyse the toxicity profile and the efficacy in the clinical day without the constrictions due to defined inclusion and exclusion criteria of clinical studies. A maximum of 12 courses of PLD-therapy per patient could be applied. All relevant clinical date were analyzed. The statistical analyses were performed by an independent clinical research organization. Results: 190 patients with a median age of 64 years (23–86) were analysed. ECOG status 0 and I was 26.3% and 48.9%, respectively. All patients were pre-treated whereby 53% had more than 2 prior chemotherapies. Overall, 1098 courses (median: 4, range: 1–12) of PLD with a dose of 40 mg/m2/q28d was the most frequently-used schedule besides other regimens. Treatment was generally well tolerated with 8.7% delays and 3% dose reductions only. Severe hematological toxicities were observed only in 4 patients (grade III Leucopoenia) and only one patient suffered from grade IV thrombopenia. Nausea, pain and skin toxicity were the most common non-hematological toxicities but these were generally mild and occurred in 86, 78 and 74 patients, respectively (Grade III in 2, 3 and 6 patients, respectively. 24.2% of all patients showed a response to therapy with 6.8% having achieved complete response, and 17.4% having achieved PR. In 32.1% SD, and in 29.5% PD was documented. Response correlated significantly with the number of prior chemotherapies and platinum-free intervals. Median progression-free interval and overall survival were 5.9 (95% CI: 5.1–6.6) and 16.6 months (95% CI: 14.2–22.6), respectively. Conclusions: In connection with the phase-III studies published, PLD at a dose of 40mg/m2/q28d seems to be an effective and well-tolerated therapeutic option in recurrent ovarian cancer with a high therapeutic index. Nevertheless, only a direct comparison with the approved 50 mg dose with a randomized trial can strengthen these assumptions. No significant financial relationships to disclose.
Genomic Profiling of Large-Cell Neuroendocrine Carcinoma of the Lung
Authors: Tomohiro Miyoshi, Shigeki Umemura, Yuki Matsumura, Sachiyo Mimaki, Satoshi Tada, Hideki Makinoshima, Genichiro Ishii, Hibiki Udagawa, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Kanji Nagai, Koichi Goto, Masahiro Tsuboi, Katsuya Tsuchihara
Journal: Clinical Cancer Research (2016)

Abstract Purpose: Although large-cell neuroendocrine carcinoma (LCNEC) of the lung shares many clinical characteristics with small-cell lung cancer (SCLC), little is known about its molecular features. We analyzed lung LCNECs to identify biologically relevant genomic alterations. Experimental Design: We performed targeted capture sequencing of all the coding exons of 244 cancer-related genes on 78 LCNEC samples [65 surgically resected cases, including 10 LCNECs combined with non–small cell lung cancer (NSCLC) types analyzed separately, and biopsies of 13 advanced cases]. Frequencies of genetic alterations were compared with those of 141 SCLCs (50 surgically resected cases and biopsies of 91 advanced cases). Results: We found a relatively high prevalence of inactivating mutations in TP53 (71%) and RB1 (26%), but the mutation frequency in RB1 was lower than that in SCLCs (40%, P = 0.039). In addition, genetic alterations in the PI3K/AKT/mTOR pathway were detected in 12 (15%) of the tumors: PIK3CA 3%, PTEN 4%, AKT2 4%, RICTOR 5%, and mTOR 1%. Other activating alterations were detected in KRAS (6%), FGFR1 (5%), KIT (4%), ERBB2 (4%), HRAS (1%), and EGFR (1%). Five of 10 cases of LCNECs combined with NSCLCs harbored previously reported driver gene alterations, all of which were shared between the two components. The median concordance rate of candidate somatic mutations between the two components was 71% (range, 60%–100%). Conclusions: LCNECs have a similar genomic profile to SCLC, including promising therapeutic targets, such as the PI3K/AKT/mTOR pathway and other gene alterations. Sequencing-based molecular profiling is warranted in LCNEC for targeted therapies. Clin Cancer Res; 23(3); 757–65. ©2016 AACR.
Effect of Priming with Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Younger Adults with Newly Diagnosed Acute Myeloid Leukemia (AML): A Trial by the Acute Leukemia French Association (ALFA) Group.
Authors: Xavier Thomas, Emmanuel Raffoux, Stephane De Botton, Cecile Pautas, Philippe Arnaud, Thierry De Revel, Oumedaly Reman, Christine Terre, Bernadette Corront, Claude Gardin, Isabelle Plantier, Quoc-Hung Le, Bruno Quesnel, Catherine Cordonnier, Jean-Henri Bourhis, Mohamed Elhamri, Pierre Fenaux, Claude Preudhomme, Mauricette Michallet, Sylvie Castaigne, Herve Dombret
Journal: Blood (2005)
Abstract 155: The analysis of the genomic evolution of squamous cell carcinoma of the lung
Authors: Arthur Krause, Thomas Lorber, Valeria Perrina, Tanja Dietsche, Michael Barrett, Christian Ruiz, Lukas Bubendorf
Journal: Cancer Research (2016)

Abstract Background: Genomic tumor heterogeneity is one reason for recurrence and resistance to cancer therapy. It is still not known what leads to the relapse or the emergence of metastasis in individual patients. To contribute to answer this question, we investigated the evolutionary patterns in squamous cell carcinoma of the lung (SCC) in 10 patients with multiple matched tumors (primary vs recurrence/metastasis). Methods: To identify the genomic profile, frozen tissues from SCC patients were subjected to multiparameter ploidy profiling (MPP). Tumor populations were sorted based on ploidy (DNA-content using DAPI) and p40 was used to control for diploid tumor populations. Subsequent genomic profiling by array comparative genomic hybridization (aCGH) and targeted massive parallel sequencing (Ion Torrent Comprehensive Cancer Panel with an all-exon coverage of 409 cancer genes) was applied. Results: The usage of MPP enabled the determination of the clonal composition of the SCC and define genomic characteristics. Due to flow sorting the tumor populations were effectively isolated and existence of distinct clonal populations was indicated. Aneuploid and diploid tumors were successfully revealed using the additional marker p40. Therefore, the absence of non-malignant cells increased the precision in the genomic analyses Conclusion: The study uncovered the composition of human SCC in the sense of different clonal populations, which harbor private genomic aberrations and mutations confirmed by aCGH and NGS. Even if our data is still preliminary we provide evidence that applying MPP increases the precision of aCGH and sequencing analysis. Genomic analyses of sorted pure tumor population allows to reconstruct the clonal evolution and facilitates the understanding of tumor heterogeneity and their evolutionary pattern, which could have potentially an impact on therapeutic response or metastasis development. Citation Format: Arthur Krause, Thomas Lorber, Valeria Perrina, Tanja Dietsche, Michael Barrett, Christian Ruiz, Lukas Bubendorf. The analysis of the genomic evolution of squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 155.
Abstract 1980: Long-range regulation of HOTAIR identifies novel biomarkers of breast cancer outcome and suggests a role in genome instability
Authors: Michael J. Milevskiy, Fares Al-Ejeh, Jodi M. Saunus, Korinne S. Northwood, Amy E. McCart-Reed, Eloise Dray, Kenneth Nephew, Peter J. Bailey, Joshua A. Betts, Andrew Stone, Julia M W Gee, Annette M. Shewan, Juliet D. French, Stacey L. Edwards, Susan J. Clark, Sunil R. Lakhani, Melissa A. Brown
Journal: Cancer Research (2016)

Abstract Long-range regulators of gene expression are emerging as promising new biomarkers and therapeutic targets for human diseases including cancer. As current breast cancer biomarkers have limited power for predicting disease progression and response to therapy, we have explored the potential of long-range regulators of non-coding RNAs to be useful in the prognostication of breast cancer. HOTAIR is a long non-coding RNA that is overexpressed, promotes metastasis, and is predictive of poor prognosis in breast cancer. Here we describe a long-range transcriptional enhancer of the HOTAIR gene that binds several hormone receptors and associated transcription factors, interacts with the HOTAIR promoter and augments HOTAIR transcription. This enhancer is dependent on FOXA1 and FOXM1 transcription factors and functionally interacts with a novel alternate HOTAIR promoter. Analysis of breast cancer gene expression data indicates that HOTAIR is co-expressed with FOXA1 and FOXM1 in HER2-enriched tumours, and these factors enhance the prognostic power of HOTAIR in this subtype of breast cancer. The combination of HOTAIR and FOXM1 also enables better predictions of response to endocrine therapy for ER+ breast cancer. FOXM1 is a member of the recently described chromosome instability module and consistent with this, the expression of HOTAIR and FOXM1 is associated with increased frequency of copy number alterations and somatic non-synonymous mutations. Our study corroborates the importance of enhancers in breast cancer, elucidates the transcriptional regulation of HOTAIR, suggests HOTAIR as a novel biomarker of patient response to endocrine therapy, and implicates HOTAIR in chromosome instability. Citation Format: Michael J. Milevskiy, Fares Al-Ejeh, Jodi M. Saunus, Korinne S. Northwood, Amy E. McCart-Reed, Eloise Dray, Kenneth Nephew, Peter J. Bailey, Joshua A. Betts, Andrew Stone, Julia M W Gee, Annette M. Shewan, Juliet D. French, Stacey L. Edwards, Susan J. Clark, Sunil R. Lakhani, Melissa A. Brown. Long-range regulation of HOTAIR identifies novel biomarkers of breast cancer outcome and suggests a role in genome instability. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1980.
Abstract 2971: Optides (optimized knottin peptides) computationally designed to target the oncogenic HIPPO pathway
Authors: Zachary R. Crook, Philip Bradley, Chris King, Andrew J. Mhyre, David Baker, James M. Olson
Journal: Cancer Research (2016)

Abstract The HIPPO pathway plays a critical role in contact inhibition, a pathway that is commonly dysregulated in many human cancers (including liver, colon, ovarian, and lung) and which relies on the intranuclear interaction of the transcriptional coactivator YAP and the transcription factor TEAD(1-4). This pathway also plays a crucial role in recovery from injury; for example, its regulated repression allows hepatocytes to divide and replace tissue lost to a partial hepatectomy, after which its activation suppresses cell growth and prevents tissue overgrowth. While small molecule enzyme inhibitors have proven to be a revelation in cancer therapy, cell growth signaling via protein-protein interactions has proven much more difficult to drug. While Antibodies can be effective in targeting extracellular or cell surface epitopes, intracellular targets, such as the interaction between YAP and TEAD, are not amenable to antibody-based therapeutics. Optides are small disulfide-knotted peptides (knottins) and serve to bridge these capabilities; they are large enough to interfere with protein-protein interactions, but small enough to penetrate into the cytosol. Examples include imperatoxin, an activator of mitochondrial ryanodine receptors, and Tumor Paint, which contains an optimized variant of chlorotoxin conjugated to a fluorescent probe and is capable of accumulating in a wide range of tumor types. To test whether Optides can abrogate oncogenic signaling mediated by protein-protein interactions, we created libraries of computationally designed candidates to target the TEAD/YAP interface. The library is expressed on the surface of mammalian cells, chosen for the improved fidelity of disulfide bridge connectivity observed in the mammalian secretory pathway as compared to that found in yeast. By repetitive screening against soluble TEAD protein, we are optimizing the pool of candidates for targeting TEAD. The lead Optides will be characterized for their ability to reduce YAP-TEAD interaction, and to impair YAP-mediated cell growth. Owing to the wide variety of knottin scaffolds, both natural and in silico designed, this flexible technology could be applied to other targets in order to impair oncogenic protein-protein interactions. Citation Format: Zachary R. Crook, Philip Bradley, Chris King, Andrew J. Mhyre, David Baker, James M. Olson. Optides (optimized knottin peptides) computationally designed to target the oncogenic HIPPO pathway. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2971.
Risk Model Incorporating Donor IL6 and ifng Genotype and Gut Gvhd Can Discriminate High Risk Patients For Steroid Refractory Acute Gvhd
Authors: Naheed Alam, Eshetu G Atenafu, Wei Xu, Jieun Uhm, Vikas Gupta, John Kuruvilla, Hans A. Messner, Jeffrey H. Lipton, Dennis Kim
Journal: Blood (2013)
Male Lower Urinary Tract Symptoms and Cardiovascular Events: A Systematic Review and Meta-analysis
Authors: Mauro Gacci, Giovanni Corona, Arcangelo Sebastianelli, Sergio Serni, Cosimo De Nunzio, Mario Maggi, Linda Vignozzi, Giacomo Novara, Kevin T. McVary, Steven A. Kaplan, Stavros Gravas, Christopher Chapple
Journal: European Urology (2016)
Inflammatory Fibroid Polyp of the Stomach Mimics Malignancy on 18F FDG PET/CT Imaging
Authors: Sabriye Sennur Bilgin, Mehmet Bilgin, Recep Savas, Ezgi Basak Erdogan
Journal: Clinical Nuclear Medicine (2016)

Inflammatory fibroid polyps (IFPs) are rare non-neoplastic and proliferating submucosal lesions of the gastrointestinal tract. The classic IFP, which was first described by Vanek, consists of prominent blood vessels and is characterized by a heavy inflammatory infiltrate, which is rich in eosinophilic granulocytes. The clinical presentation depends on the size and location. Inflammatory fibroid polyps cannot be differentiated from malignancy without histological examination. We report a case of IFP in the stomach that mimicked a primary gastric malignancy showing an increased 18F-FDG uptake.
Abstract 767: TCR sequencing can identify and track tumor-specific T cell populations and is a predictive biomarker of response to DC vaccination in glioblastoma patients
Authors: Shaina Sedighim, Melody Hsu, Tina Wang, Richard G. Everson, Alex Tucker, Joseph P. Antonios, Lin Du, Ryan Emerson, Erik Yusko, Catherine Sanders, Harlan Robins, William Yong, Tom B. Davidson, Gang Li, Linda M. Liau, Robert Prins
Journal: Cancer Research (2016)

Abstract While immunotherapeutic strategies are emerging adjunctive treatments for cancer, sensitive methods of monitoring the immune response after treatment remain to be established. We used a novel next generation sequencing (NGS) approach to determine whether quantitative assessments of tumor infiltrating lymphocyte (TIL) content and the degree of overlap of T cell receptor (TCR) sequences in brain tumors and peripheral blood were predictors of immune response and overall survival in glioblastoma (GBM) patients treated with autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy. A significant correlation was found between a higher estimated TIL content and increased time to progression (TTP) and overall survival (OS). In addition, we were able to assess the proportion of shared TCR sequences between tumor and peripheral blood at time points before and after therapy, and found the level of TCR overlap to correlate with survival outcomes. Higher degrees of overlap, or the development of an increased overlap following immunotherapy, correlated with improved clinical outcome, and may provide insights into the successful, antigen-specific immune response. Citation Format: Shaina Sedighim, Melody Hsu, Tina Wang, Richard G. Everson, Alex Tucker, Joseph P. Antonios, Lin Du, Ryan Emerson, Erik Yusko, Catherine Sanders, Harlan Robins, William Yong, Tom B. Davidson, Gang Li, Linda M. Liau, Robert Prins. TCR sequencing can identify and track tumor-specific T cell populations and is a predictive biomarker of response to DC vaccination in glioblastoma patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 767.
A randomized trial comparing two different retention periods of intravesical pirarubicin instillation for intermediate risk non-muscule invasive bladder cancer (NMIBC) after transurethral resection.
Authors: Yutaka Kasejima, Wataru Takahashi, Yoshiaki Kawano, Takahiro Yamaguchi, Ken-ichiro Tanoue, Hiroshi Sakakida, Junji Yatsuda, Youji Murakami, Yutaka Sugiyama, Masatoshi Eto
Journal: Journal of Clinical Oncology (2016)

384 Background: Anthracyclines are recommended reagents for one immediate intravesical instillation after transurethral resection (TUR) and additional adjuvant instillation in intermediate risk NMIBC to reduce the risk of recurrence. Several studies have showed that Pirarubicin (THP), an anthracycline analogue, can rapidly penetrate tumor tissue after intravesical instillation. Therefore long instillation time (e.g. 120 min) may not be required for its prophylactic effect against recurrence without compromising its efficacy. Methods: This randomised, prospective, open-label trial intended to enroll 160 pts with primary NMIBC with intermediate risk based on EORTC criteria. Pts who seemed likely to be at intermediate risk were provisionally registered and then randomised into two groups with different intravesical THP retention times before TUR, (a) 30 min versus (b) 120 min. The registration was finally confirmed by pathology results of TUR. All registered pts received initial THP instillation within 24 hr after TUR and then intended to continue weekly repetitive THP instillation for a total of 9 treatments. Follow-up period is 4 years. Primary endpoint is change from baseline in quality of life measurements (e.g. OABSS and I-PSS), which were evaluated prior to each THP intravesical instillation. Secondary endpoint is recurrence-free survival. Results: 126 pts were enrolled for provisional registration. After excluding pts due to the result of pathology by TUR, 29 pts were assigned to group (a), and 26 pts to group (b). Although not statistically significant, there is a trend that group (a) is less prone to increase in OABSS after 3 rd instillation compared to group (b). Log-rank test shows that there is no significant difference in recurrence-free survival between the groups during follow-up period (HR = 2.161, 95% C.I.: 0.4317-10.82, p= 0.3484). Conclusions: Shortening intravesical instillation period to 30 min has little effect on reducing the adverse effect of THP. However, it does not compromise the prophylactic effect on recurrence in intermediate risk NMIBC pts. Clinical trial information: UMIN000006861.
P0388 : Surgical resection versus radiofrequency ablation for single hepatocellular carcinoma ≤2cm in a propensity score model
Authors: P.-H. Liu, C.-Y. Hsia, C.-Y. Hsu, Y.-H. Lee, Y.-H. Huang, Y.-Y. Chiou, H.-C. Lin, T.-I. Huo
Journal: Journal of Hepatology (2015)
Venous Leg Ulcers
Authors: Alejandra Vivas, Hadar Lev-Tov, Robert S. Kirsner
Journal: Annals of Internal Medicine (2016)

This issue provides a clinical overview of venous leg ulcers, focusing on prevention, diagnosis, treatment, and practice improvement. The content of In the Clinic is drawn from the clinical information and education resources of the American College of Physicians (ACP), including MKSAP (Medical Knowledge and Self-Assessment Program). Annals of Internal Medicine editors develop In the Clinic in collaboration with the ACP's Medical Education and Publishing divisions and with the assistance of additional science writers and physician writers.
Abstract 4138: Immunological profile of metastatic or recurrent breast cancer patients
Authors: Shigeru Imoto, Takayuki Ueno, Hirotsugu Isaka, Hiroki Ito, Kaisuke Miyamoto, Tomohiro Chiba, Hiroshi Kamma
Journal: Cancer Research (2016)

Abstract Background: We previously reported about immune suppression in breast cancer patients at this meeting. In brief, tumor tissue specimens and peripheral blood mononuclear cells (PBMC) were analyzed in 50 early or advanced breast cancer (BC) patients. To compare between 38 early and 12 advanced BC cases, CD163-positive tumor cells and CCR4-positive tumor cells were detected more frequently in advanced cases than in early cases. Regulatory T (Treg) cells in PBMC significantly increased in percentage of the population in 37 BC patients than in 21 healthy volunteers (AACR 2011). In addition, several cytokines were examined in that cohort and plasma IL-17A had significantly higher levels in early BC than in advanced BC (AACR 2013). Then, we examined their prognosis and immunological profile. Patients and methods: Treg cells were examined by counting CD4+CD25highCD127low/-cells in PBMC with flow cytometry analysis. Immunohistochemical evaluation of tumor specimens was performed with monoclonal antibodies of HLA-ABC and DR, CD56, CD68, CD83, CD163 and CCR4. The number of stained cells was analyzed using a semiquantitative ordinal scale ranging from 0 to 3 (0, +/-, ++, +++). Human IL-2, IL-4, IL-6, IL-10, TNF, INFγ and IL-17A were measured using cytometric beads array system. Most patients received chemotherapy, hormonal therapy, and/or anti-HER2 therapy on the basis of intrinsic subtype and breast irradiation after breast-conserving surgery. Results and discussions: At the median follow-up of 7 years after blood sample collection, only 2 operable patients relapsed and 3 patients including 2 cases of stage IV died of disease. Of 5 cases of stage IV or recurrent BC, CD163 and/or CCR4 were strongly stained positive in tumor cells. There were significant differences of staining intensity in CD163 and CCR4-positive tumor cells between those cases and the rest 45 cases (p&amp;lt;0.01 at Chi-square test). However, other immune cell profiles, Treg cells in PBMC and cytokines in plasma had no trend between them. Several reports demonstrated that cancer patients with CD163-positive tumor-infiltrating macrophages and CD163-positive tumor cells had poor prognosis due to tumor-associated macrophage. Phenotypic macrophage traits in cancer cells, like CD163 expression, may be explained by heterotypic cell fusion between monocytes/macrophages and cancer cells. Conclusion: Targeted therapy against M2 macrophage or CCR4 is considered as a promising strategy of advanced breast cancer. Citation Format: Shigeru Imoto, Takayuki Ueno, Hirotsugu Isaka, Hiroki Ito, Kaisuke Miyamoto, Tomohiro Chiba, Hiroshi Kamma. Immunological profile of metastatic or recurrent breast cancer patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4138.
Patients Prescribed Warfarin with Poor Time in Therapeutic Range (TTR) Have Different Beliefs about Their Illness and Anticoagulation Therapy Compared to Those with a Good TTR - Early Results from the Switching Study
Authors: John K Abdou, Jignesh P Patel, Bipin Vadher, Alison Brown, Lara N Roberts, Raj K Patel, Roopen Arya, Vivian Auyeung
Journal: Blood (2015)