tbuckley/cabot-search huggingface dataset:
Advanced urethral carcinomas: A retrospective analysis of survival outcomes and the role of cisplatin-based chemotherapy—The M. D. Anderson experience.
Authors: Farshid Dayyani, Curtis A. Pettaway, Ashish M. Kamat, Mark F. Munsell, Lance C. Pagliaro
Journal: Journal of Clinical Oncology (2012)

330 Background: Primary carcinomas of the urethra (PCU) are rare and often advanced when diagnosed. Given the low incidence of this disease, there is a paucity of data regarding treatment standards. The purpose of this report was to study the treatment response and survival in a relatively large cohort of patients with PCU, with emphasis on modern platinum-containing chemotherapy regimens, in combination with surgery for (locally) advanced PCU. Methods: We performed a retrospective chart review of consecutive patients with PCU seen at the MD Anderson Cancer Center over a recent 5-year period (2005-2010). Clinical outcome was measured as best response to chemotherapy (either neo-adjuvant or for metastatic disease). Kaplan-Meier estimates were generated for survival and Cox proportional hazard was used for prognostic factors for survival. Results: We identified 44 consecutive pts with PCU. The majority (64%) were female, and the median age at diagnosis was 66.5 yrs. Squamous cell carcinoma and adenocarcinoma were the most common histologic subtypes of PCU in our cohort. 43% and 16% presented with lymph node–positive (LN+) and distant metastases, respectively. For all evaluable pts, the overall survival (OS) was 31.7 mo. Platinum-containing neoadjuvant chemotherapy achieved a response rate of 72%. 21/44 pts had locally advanced or LN+ PCU and were treated with chemotherapy followed by surgery. In this cohort, the median OS from chemotherapy initiation was 25.6 months. Among pts with LN+ PCU at diagnosis, 4/9 (44%) were alive as of July 2011, with a minimum follow-up of >3 years. Conclusions: We report the clinical outcomes in the to the best of our knowledge largest cohort of consecutive pts with PCU. Our data suggests that modern platinum-containing regimens are effective in a subset of advanced PCU. Neoadjuvant treatment leads to prolonged disease-free survival in a substantial proportion of lymph node positive cases.
Expression Profiling of CD34+ Cells in Patients with Myelodysplastic Syndromes with and without a del(5q).
Authors: Andrea Pellagatti, Aristotle Giagounidis, Sally Killick, Lisa J. Campbell, Vicki Wraight, Cordelia F. Langford, Carrie Fidler, David Oscier, Carlo Aul, James S. Wainscoat, Jacqueline Boultwood
Journal: Blood (2004)
A phase II study of sorafenib in patients with metastatic or unresectable gastrointestinal stromal tumors with failure of both imatinib and sunitinib: A KGSG study.
Authors: M. Ryu, S. H. Park, B. Ryoo, S. Im, H. Kwon, S. S. Lee, S. R. Park, B. W. Kang, Y. Kang
Journal: Journal of Clinical Oncology (2011)

10010 Background: This prospective, multicenter, phase II study evaluated the efficacy and safety of sorafenib in patients (pts) with advanced gastrointestinal stromal tumors (GISTs) who failed previous standard tyrosine kinase inhibitors (TKI). Methods: Thirty-one patients with pathologically proven metastatic or unresectable GISTs who failed both imatinib and sunitinib were accrued between Dec 2009 and Jun 2010. Sorafenib was administered orally at 400 mg twice daily. Results: Among 31 pts, 23 (74%) were male. The median age was 59 years (range, 31-78). All had metastatic disease in the liver (n=27), peritoneum (n=19), lung (n=4), or bone (n=1). Ten pts (32%) received nilotinib as a third line treatment after the failure of imatinib and sunitinib. The primary sites were stomach (n=10) and small bowel (n=21). With sorafenib, 3 pts (10%) achieved a partial response and 17 pts (55%) had stable disease. With a median follow-up of 7.5 months (range, 5.0-12.6), the median progression-free survival (PFS) was 4.9 months (95% CI, 1.6-8.2) and the disease control rate was 37.6% at 6 months. Pts with prior use of 3rd line nilotinib and primary genotypes other than mutations at KIT exon 11 showed significantly worse PFS (p=0.0085 and p=0.0341, respectively). Median OS has not been reached yet. Grade 3 or 4 adverse events of sorafenib with frequency > 5% of pts included hand-foot skin reaction (16%), fatigue (7%), hypertension (7%), and abdominal pain (7%). Those toxicities were manageable with dose modification (n=10), and there was no treatment-related death. The relative dose intensity during the first 6 cycles was generally over 80%. Conclusions: Sorafenib was effective as a salvage treatment with manageable toxicities in GIST pts who failed prior standard TKIs. With sorafenib, about one third of pts can maintain disease stabilization for more than 6 months. Further randomized controlled trials are needed to confirm the efficacy of our results.
Four questions for passive frame theory
Authors: David A Rosenbaum
Journal: Behavioral and Brain Sciences (2016)

Four questions are raised about the passive frame theory of Morsella et al.: (1) What is the relation of the theory to the response-selection-bottleneck view of attention? (2) Does the theory accommodate the contents of consciousness? (3) What about animals without skeletal muscles? (4) How do the contents of consciousness change with the development of automaticity?
Sustained Complete Molecular Response to Imatinib in Chronic Myeloid Leukemia (CML): a Target Worth Aiming and Achieving?.
Authors: Dushyant Verma, Hagop M Kantarjian, Jenny Shan, Susan O'Brien, Amit Verma, Elias Jabbour, Srdan Verstovsek, Tapan Kadia, Mary Beth Rios, Jorge Cortes
Journal: Blood (2009)
Nutritional Assessment As Predictor of Complications Post Hematopoietic Cell Transplantation
Authors: Pablo Ramirez, Roberto Olmos, Javiera Perelli, Jessica Liberona, Julieta Klaassen, Mauricio E Ocqueteau, Mauricio Sarmiento, Pablo A Bertin, Daniel M Ernst, Veronica Jara, Marcela Espinoza
Journal: Blood (2014)
Intrinsic Subtype Switching and Acquired <i>ERBB2</i>/<i>HER2</i> Amplifications and Mutations in Breast Cancer Brain Metastases
Authors: Nolan Priedigkeit, Ryan J. Hartmaier, Yijing Chen, Damir Vareslija, Ahmed Basudan, Rebecca J. Watters, Roby Thomas, Jose P. Leone, Peter C. Lucas, Rohit Bhargava, Ronald L. Hamilton, Juliann Chmielecki, Shannon L. Puhalla, Nancy E. Davidson, Steffi Oesterreich, Adam M. Brufsky, Leonie Young, Adrian V. Lee
Journal: JAMA Oncology (2016)

Patients with breast cancer (BrCa) brain metastases (BrM) have limited therapeutic options. A better understanding of molecular alterations acquired in BrM could identify clinically actionable metastatic dependencies.
Heterogeneity of metastatic behavior among high-grade pleomorphic soft tissue sarcomas identified by gene expression analysis.
Authors: K. M. Skubitz, P. Francis, A. Skubitz, X. Luo, M. Nilbert
Journal: Journal of Clinical Oncology (2011)

10082 Background: Heterogeneity in clinical behavior of soft tissue sarcomas (STS), even within histological subtypes, complicates treatment. Metastatic propensity may be determined by gene expression patterns that do not correlate well with morphology. In earlier studies, we identified gene expression patterns that distinguished two subsets of clear cell renal cell carcinoma (ccRCC), serous ovarian carcinoma (OVCA), and aggressive fibromatosis (AF). In this study, we combined these three gene sets into one “pooled gene set” and used a set of clinically well defined STS for analysis. Methods: Gene expression patterns for 73 samples of high-grade STS were examined using cDNA microarray slides containing ~16,000 unique UniGene clusters. Clinical data, such as time to development of metastatic disease, was linked to each sample. Results: Half of the genes in the “pooled gene set” were represented in the current data, and these were combined to form a composite set of genes. Hierarchical clustering using this composite gene set suggested the existence of subsets of the STS samples. Kaplan-Meier analysis revealed differences in the time to development of metastatic disease between the clusters defined by the first branch point of the clustering dendrogram (p=0.01), and also among the four different clusters defined by the second branch points (p=0.001). Conclusions: This approach may allow the identification of more than two subsets of high-grade STS, each with distinct clinical behavior, and may be useful to stratify STS in clinical trials and in patient management.
Agonist for Toll-Like Receptor (TLR) 9 Amplifies as Well as Inhibits the Differentiation of FVIII-Specific Memory B Cells into Antibody-Producing Plasma Cells in Vitro and in Vivo.
Authors: Peter Allacher, Christina Hausl, Aniko Ginta Pordes, Rafi Uddin Ahmad, Hartmut J Ehrlich, Hans Peter Schwarz, Birgit M Reipert
Journal: Blood (2008)
Human Mesenchymal Stem Cells Isolated from Bone Marrow and Lymphoid Organs Support Tumor B-Cell Growth: Implications in Follicular Lymphoma Pathogenesis.
Authors: Karin Tarte, Patricia Ame-Thomas, Hélène Maby-El Hajjami, Céline Monvoisin, Rachel Jean, Thierry Lamy, Thierry Fest
Journal: Blood (2006)
Gene Deletions of 17p or 11q Are Independent Predictors of Decreased Progression-Free Survival and Overall Survival Following Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia
Authors: Julio Chavez, Jongphil Kim, Samir Dalia, Mohamed A. Kharfan-Dabaja, Javier Pinilla-Ibarz, Claudio Anasetti, Frederick L Locke
Journal: Blood (2012)
Outcomes of Grades II-IV Acute Graft-Versus-Host Disease Post-Allogeneic Hematopoietic Stem Cell Transplantation: How Much Progress Was Achieved?
Authors: Hanna Jean Khoury, Tao Wang, Mukta Arora, Michael Hemmer, Stephen R. Spellman, Corey S Cutler, Daniel R. Couriel, Amin M. Alousi, Joseph A. Joseph
Journal: Blood (2015)
Generics have a chequered recent history
Authors: Shyan Goh
Journal: BMJ (2016)

I’m surprised that McCartney didn’t mention the US version of the phenytoin fiasco1; Martin Shkreli, the chief executive officer of Turing Pharmaceuticals was dubbed the most hated man in America in 2015 after a 5556% price hike of the antiparasitic drug Daraprim (pyrimethamine), from $13 (£10; €12) to $750 a tablet. He …
Evidence of a Significant Contribution of Thymic Output to T Cell Reconstitution Following Full Haplotype Mismatched Stem Cell Transplant (HSCT) Leading to a Predominantly Naïve Phenotype.
Authors: Maria V.D. Soares, Rita I Azevedo, Rita Tendeiro, Rui S Soares, Rui MM Victorino, Joao F Lacerda, Ana E Sousa
Journal: Blood (2008)
What are the limiting factors related to discontinuance of chemotherapy after failure of first-line S-1 plus CDDP in Japanese patients with advanced gastric cancer?
Authors: Yoshihito Ohhara, Keisho Chin, Mariko Ogura, Mitsukuni Suenaga, Eiji Shinozaki, Satoshi Matsusaka, Nobuyuki Mizunuma, Toshiharu Yamaguchi, Kiyohiko Hatake
Journal: Journal of Clinical Oncology (2012)

149 Background: Recently, it is suggested that second-line chemotherapy improved survival in advanced gastric cancer (AGC) and it is commonly performed in Japanese daily practice in these several years. We investigated the limiting factor not to be able to receive second-line chemotherapy in Japanese patients with AGC. Methods: Between 2007 and 2009, 155 patients received S-1 plus cisplatin (SP) treatment as first-line chemotherapy in Cancer Institute Hospital of JFCR, Japan. Among them, 148 patients could not continue SP treatment because of disease progression or unacceptable toxicity. 109 patients could receive second-line chemotherapy (Group A), while 39 patients could not (Group B). We evaluated the clinicopathologic factors that affected not to receive second-line chemotherapy, retrospectively. Univariate and multivariate analyses were performed on the baseline factors before starting first-line chemotherapy. Results: Characteristics of patients were below (Group A vs B): median age, 60 vs 66 (years); gender (male), 71.6 % vs 66.7 %. Median progression-free survival were not different in both Group statistically (6.5 vs 7.2 months; log-rank, p=0.861). Median overall survival were 16.5 vs 10.3 months (log-rank, p&lt;0.001), respectively. Univariate analyses found 4 limiting factors not to initiate second-line chemotherapy: age over 65 years old (p=0.025), performance status&gt;1 (p=0.017), alkaline phosphatase (ALP) &gt;400 IU/l (p&lt;0.001), C-reactive protein (CRP) &gt;1.0 mg/dl (p=0.004). Multivariate analyses showed ALP elevation was a limiting factor (HR 4.122, p=0.003). Conclusions: Alkaline phosphatase can be an uncomplicated and potent limiting factor of discontinuance of chemotherapy after failure of the first line S-1 plus CDDP in Japanese patients with AGC.
Natural history of skeletal disease in primary biliary cancers. National survey on behalf of GICO group (Gruppo Italiano Colangiocarcinoma – Onlus)
Authors: G. Brandi, S. Cereda, F. Pantano, M. Russano, S. Lonardi, F. Leone, M. Reni, V. Marsico, R. Filippi, S. Delcuratolo, L. Fornaro, E. Vasile, C. Vivaldi, G. Aprile, S. Pisconti, F. Luca, M. Aieta, G. Tonini, D. Santini
Journal: Annals of Oncology (2015)
Predictive factors for oligometastatic versus non-oligometastatic involvement of the central nervous system by brain metastases from breast cancer.
Authors: S. Garg, J. C. Marsh, R. D. Rao, K. L. Griem
Journal: Journal of Clinical Oncology (2011)

123 Background: To assess rates of oligometastatic (1-3 metastases) versus non-oligometastatic (4 or more) involvement of the central nervous system (CNS) from breast cancer and determine whether rates vary for different breast cancer subtypes. Methods: We reviewed records of 65 patients with brain metastases from breast cancer. Fisher’s Exact Test compared incidence of oligometastatic versus nonoligometastatic CNS involvement and presence of visceral metastatic disease between groups. Paired Student's t test compared mean age and interval from initial diagnosis to development of brain metastases. Results: 25 patients (38.5%) developed oligometastatic and 40 (61.5%) developed non-oligometastatic CNS disease. Subtypes predictive of oligometastatic disease included ER+ (p .04) and PR+ (p .008). Subtypes predictive of non-oligometastatic disease included HER2+ (p .05). HER2+ patients trended toward a lower incidence of visceral metastases compared to ER+ or PR+ patients (p .07). Non-oligometastatic and HER2+ patients developed brain metastases sooner after initial diagnosis (p .046 and .03, respectively). Conclusions: ER+ breast cancer patients are more likely to develop oligometastatic CNS involvement and may be excellent candidates for stereotactic radiosurgery (SRS) alone. HER+ patients are likely to develop non-oligometastatic CNS involvement and may be better treated initially with whole brain radiotherapy (WBRT) even with apparent initial oligometastatic CNS involvement.
The effect of the diagnosis and treatment of lower urinary tract symptoms (LUTS) on the diagnosis of prostate cancer in a population cohort with 20-year follow-up.
Authors: Christopher J. Weight, Simon P. Kim, Stephen A. Boorjian, R. Jeffrey Karnes, Debra Jacobson, Michaela McGree, Jennifer St. Sauver
Journal: Journal of Clinical Oncology (2012)

137 Background: LUTS are one of the most common reasons patients visit urologists. These symptoms have not been typically associated with the development of prostate cancer (CaP). However, we hypothesized that visiting a physician for LUTS may modify the diagnostic intensity for CaP compared to population controls. Methods: We examined data from a longitudinal, population-based cohort of 2,447 men between 40 and 79 years old who were followed prospectively from 1990 to 2010. Participants completed the American Urological Association Symptom Index (AUASI) every two years. Self-reported moderate/severe LUTS were defined as an AUASI score &gt;7 (n=1627). Data including the treatment for LUTS (n=874), prostate biopsy (PBx), family history of CaP and diagnosis of CaP were obtained through self-report and review of medical records. Associations between self-reported LUTS, treatment for LUTS, and risk of PBx or CaP were estimated using multivariate Cox proportional hazard models. Results: An interaction was noted between age and LUTS and PBx and CaP diagnosis. In younger men, the diagnosis and treatment of LUTS was associated with increased risk of PBx (HR 2.39: 95% CI 1.83, 3.13) and CaP (HR 3.47: 95% CI 2.38, 5.07). Conversely in older men, treatment for LUTS was associated with a decreased risk of PBx and CaP (Table). Self reported LUTS was not significantly associated with CaP diagnosis in younger men and was protective in older men (Table). Conclusions: There is a differential effect of LUTS on prostate cancer testing and diagnosis when stratified by age. The reason for this difference is unclear, but appears to be due largely to diagnostic intensity rather than a true biologic association between LUTS and CaP. [Table: see text]
Primary systemic therapy with metronomic doxorubicin, cyclophosphamide, and capecitabine in locally advanced and metastatic triple-negative breast cancer.
Authors: M. Skrypnikova, M. Frolova, E. Ignatova, I. Pokataev, M. Stenina, S. Tjulandin
Journal: Journal of Clinical Oncology (2011)

1110 Background: Triple-negative breast cancer (TNBC) is one of the most aggressive breast cancer subtypes. The results of treatment with standard chemotherapy regimens remain unsatisfactory. Dose-dense and metronomic schedules may be more effective in these high proliferative tumors. We performed a prospective pilot trial to evaluate efficacy of metronomic schedule of doxorubicin, cyclophosphamide and capecitabine in triple-negative breast cancer patients. Methods: 18 pts with locally advanced (LABC) and 20 chemotherapy naïve pts with metastatic TNBC were treated with doxorubicin 25 mg/m2 iv weekly, cyclophosphamide 50 mg po daily and capecitabine 1,650 mg/m2 po daily. Results: Overall response rate was 58% with 24% of complete responses and 34% of partial responses. Eighteen pts with LABC by now completed induction chemotherapy and all but one, who had a disease progression, underwent surgery. Five pts (29.4%) achieved a pCR according to the Chevallier pathologic classification (4 pts class 1 and 1 pts class 2). All but 2 pts who underwent surgery are alive without progression with median follow-up of 9 months. In metastatic breast cancer median TTP was 8.3 months with follow up from 1 to 20+ months. The median cumulative dose of doxorubicin was 350 mg/m2. The most common toxicities were hand-foot syndrome (28.8% grade 3) and mucositis (17.7% grade 3), which resulted in discontinuation of doxorubicin in 7 pts. There was 26.4% of grade 3-4 neutropenia (no cases of febrile neutropenia). Conclusions: Metronomic doxorubicin, cyclophosphamide and capecitabine regimen shows promising activity in treatment of locally advanced and metastatic triple-negative breast cancer.
Vitamin E Succinate Induces Remission and Prolongs Survival in a Syngenic Transplant Model of Acute Promyelocytic Leukemia.
Authors: Rodrigo S. Abreu e Lima, Priscila S. Scheucher, Bárbara A.A. Santana, Ana Carolina T. Pintão, Ana Sílvia G. Lima, Aglair B. Garcia, Fabiano P. Saggioro, Roberto P. Falcao, Eduardo M. Rego
Journal: Blood (2004)
Dabigatran Etexilate or Warfarin in the Treatment of Acute Venous Thromboembolism in Western European Patients: A Pooled Analysis of RE-COVER® and RE-COVER II™
Authors: Sebastian Schellong, Henry Eriksson, Samuel Z. Goldhaber, Martin Feuring, Stefan Hantel, Jörg Kreuzer, Sam Schulman, Ajay K Kakkar
Journal: Blood (2015)
Pancreatic β cell identity requires continual repression of non–β cell programs
Authors: Giselle Domínguez Gutiérrez, Aaron S. Bender, Vincenzo Cirulli, Teresa L. Mastracci, Stephen M. Kelly, Aristotelis Tsirigos, Klaus H. Kaestner, Lori Sussel
Journal: Journal of Clinical Investigation (2016)

Loss of β cell identity, the presence of polyhormonal cells, and reprogramming are emerging as important features of β cell dysfunction in patients with type 1 and type 2 diabetes. In this study, we have demonstrated that the transcription factor NKX2.2 is essential for the active maintenance of adult β cell identity as well as function. Deletion of Nkx2.2 in β cells caused rapid onset of a diabetic phenotype in mice that was attributed to loss of insulin and downregulation of many β cell functional genes. Concomitantly, NKX2.2-deficient murine β cells acquired non–β cell endocrine features, resulting in populations of completely reprogrammed cells and bihormonal cells that displayed hybrid endocrine cell morphological characteristics. Molecular analysis in mouse and human islets revealed that NKX2.2 is a conserved master regulatory protein that controls the acquisition and maintenance of a functional, monohormonal β cell identity by directly activating critical β cell genes and actively repressing genes that specify the alternative islet endocrine cell lineages. This study demonstrates the highly volatile nature of the β cell, indicating that acquiring and sustaining β cell identity and function requires not only active maintaining of the expression of genes involved in β cell function, but also continual repression of closely related endocrine gene programs.
Which benefit from subsequent chemotherapy lines beyond the second for women with metastatic breast cancer? Evidence from a single-center retrospective analysis of survivorship.
Authors: G. Bernardo, R. Palumbo, A. Bernardo, C. Teragni, F. Sottotetti, B. Tagliaferri, M. R. Strada
Journal: Journal of Clinical Oncology (2011)

255 Background: Although the true impact of chemotherapy (CT) in metastatic breast cancer (MBC) is still debated, in the routine clinical practice an increasing number of women asking for further treatment after progression receive subsequent CT lines. This study aimed to assess which benefit could be brought by the succession of CT lines in patients treated for MBC and to identify women who benefit from these treatments. Methods: This retrospective analysis included 980 women treated with CT for MBC at our Institution over a 7-year period (May 1999-July 2006). With overall survival (OS) data updated at December 1, 2008, the median follow-up was 125 months (range 48-192), OS and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: Median OS evaluated from day 1 of each CT line decreased with the line number from 34.8 months (980 patients, 1st line, range 4-208) to 22.6 months (838 patients, 2nd line), 14.6 months (684 patients, 3rd line), 12.4 months (302 patients, 4th line), 9.4 months (88 patients, 5th line), 8.2 months (45 patients, seven or more lines). Median TTF ranged from 9.2 months to 7.8 and 6.4 months for the first, second and third line, respectively, with no significant decrease observed beyond the 3rd line (median 5.2 months, range 4.8-6.2). In univariate analysis factors positively linked to a longer duration of TTF for each CT line were positive hormonal receptor status, absence of liver metastasis, adjuvant CT exposure, response to CT for the metastatic disease; in the multivariate analysis the duration of TTF for each CT line was the only one factor with significant impact on survival benefit for subsequent treatments (p&lt;0.001). Conclusions: CT beyond the 2nd line may be beneficial in a significant subset of women treated for MBC, with improved TTF and OS. These findings could help physician in planning an appropriate strategy of subsequent schedules for women with symptomatic MBC who responded to their 1st line CT, while non responder patients should be considered for clinical trials.
Outcome and Prognosis of 1955 Patients with Chronic Myeloid Leukemia: First Results of the CML-Registry of the European Treatment and Outcome Study EUTOS.
Authors: Joerg Hasford, Gianantonio Rosti, Doris Lindoerfer, Michele Baccarani, Joelle Guilhot, Lara Montrucchio, Francesca Rancati, Bengt Simonsson, Franck Emmanuel Nicolini, Gert Ossenkoppele, Ruediger Hehlmann
Journal: Blood (2009)