tbuckley/cabot-search huggingface dataset:
Pegylated liposomal doxorubicin (PLD) and gemcitabine in the treatment of metastatic breast cancer: A single-institution experience.
Authors: J. Espinós, A. Hernández, A. Castillo, M. Zudaire, O. Fernández-Hidalgo, J. M. Aramendia, M. Santisteban, J. Garcia-Foncillas
Journal: Journal of Clinical Oncology (2010)

e11510 Background: We retrospectively analyzed the efficacy and safety of the combination of PLD and gemcitabine in patients (pt) with metastatic breast cancer (MBC) treated in our institution. Methods: We identified in our database 51 women diagnosed of MBC and treated with PLD on day 1 plus gemcitabine days 1 and 8 every 21 days between July 2000 and August 2009. Results: Median age was 59 years (range 32-83). Histologically 82.4% were ductal carcinomas, 68.6% expressed estrogen receptor and 29.4% overexpressed HER2. The median of previous chemotherapy regimens was 2 (range 0-8). 78.4% pt received previous anthracyclines, 82.4% taxanes, 54.9% capecitabine and 16.7% trastuzumab. 2 pt had previously received PLD and 3 gemcitabine. Median number of metastatic sites was 3 and the most frequent sites were: bone 70.6%, liver 56.9%, lung 37.3% and lymphatics 25.5%. Median PLD dose was 25mg/m2 (range 15-45 mg) and median gemcitabine dose was 800mg/m2 (range 650-1,000 mg). Median number of cycles was 8 (CI95%: 1 - 36). ORR was 25% and 35% of pt achieved stable disease (clinical benefit 60%). Median time to progression (TTP) was 9 months (CI95%: 3.6-14.3) and median overall survival (OS) was 30.4 months (CI95%: 23.7-37.1). 20 pt (40%) needed PLD dose reduction and only 9 (17.6%) received gemcitabine on day 8. 28 pt (56%) experienced grade 3/4 toxicities; despite this, all but 1pt could continue treatment with PLD dose reduction after recovery. Grade 3/4 toxicities were neutropenia: 32% (13pt/3pt) with 2 febrile episodes, palmar-plantar erythrodysesthesia syndrome 18% (7pt/2pt), plaquetopenia 12% (4pt/2pt) with no severe bleeding episodes, oral mucositis grade 3 10% (5pt), left ventricular systolic dysfunction grade 3 2% (1pt), nausea grade 3 6% (3pt), anemia grade 3 6% (1pt) and renal failure grade 3 2% (1pt). No toxic deaths ocurred. In the correlation analysis PLD dose >25mg/m2 was associated with grade 3/4 toxicity. Conclusions: PLD and gemcitabine combination is an active regimen with superior TTP and OS than other third-line regimens. Toxicity grade 3/4 was related to PLD doses higher than 25 mg/m2 and that is the dosage we recomend. No significant financial relationships to disclose.
Usefulness of frailty markers in the assessment of the health and functional status in older cancer patient referred for chemotherapy
Authors: F. G. Retornaz, J. Monette, M. Monette, N. Sourial, D. Wan-Chow-Wah, G. Batist, H. Bergman
Journal: Journal of Clinical Oncology (2007)

19673 Background: In order to properly support clinical decisions, geriatric assessment (GA) is recommended for older cancer patients. However, the best form of GA remained unknown and recent studies demonstrated that usual GA tools may have a ceiling effect in detecting adverse outcomes to cancer treatment. Frailty has emerged as a concept characterizing cumulative declines across multiple physiologic systems, leading to increased vulnerability and risk of adverse outcomes. Consequently, the concept of frailty may represent a more sensitive way to better characterize health and functional status and to detect potential vulnerability to adverse outcomes in older cancer patients. The purpose of this pilot study was to explore the usefulness of frailty markers in older cancer patients. Methods: This cross- sectional study included 50 cancer patients, (70 years and older) referred to an oncology clinic for chemotherapy. Chronic diseases, IADL and ADL disabilities, and seven domains considered as frailty markers (nutrition, mobility, strength, energy, physical activities, mood and cognition) were assessed. Patients were classified into hierarchical groups based on the results of their assessment. Results: While 15 (30%) patients had at least one disability in IADL and 8 (16%) patients had at least one disability in ADL, 27 patients (54 %) were completely independent for IADL and ADL. Among those patients with no IADL nor ADL disability, 21 patients (42%) presented at least one frailty marker. In the whole cohort, 44 patients (88%) had at least one frailty markers. The most prevalent of the frailty markers were nutrition, mobility and physical activity (respectively 62%, 58% and 42%). Conclusion: Markers of frailty add substantial information to the usual GA tools in detecting potential vulnerability in older cancer patients. Additional studies are needed to determine if the addition of the frailty markers to the usual GA tools can help to better characterize the older cancer population and predict risk of toxicities and adverse outcomes due to cancer treatment. No significant financial relationships to disclose.
Cost-effectiveness and lifetime implications of using finasteride to reduce prostate cancer incidence and mortality
Authors: S. B. Zeliadt, R. Etzioni, D. F. Penson, S. D. Ramsey
Journal: Journal of Clinical Oncology (2004)

1028 Background: Preventive treatment with finasteride has been shown to reduce prostate cancer prevalence by 25% in a large randomized controlled trial. Potential implications include an increased rate of high-grade tumors and higher rates of sexual dysfunction among treated men. This decision analysis evaluates the long-term cost-effectiveness of finasteride. Methods: We estimate the lifetime impact of finasteride on prostate cancer incidence and mortality taking into account benign prostatic hyperplasia, erectile dysfunction, and associated lifetime medical care costs using a Markov process model. Prostate cancer incidence and survival estimates are based on SEER statistics. Incidence rates are adjusted by grade based on the results of the Prostate Cancer Prevention Trial (PCPT). An extensive sensitivity analysis was conducted to evaluate the influence of key assumptions including the impact of finasteride on high-grade tumors. Results: The gains in life-years and quality-adjusted life-years and associated cost-effectiveness estimates are provided in the table below. The incremental cost to gain one QALY fell below $100,000 when the price of finasteride was reduced to $0.86 from the current average wholesale price of $2.71. Conclusions: The cost burden associated with finasteride is substantial, while its survival benefit is small and only realized many years after initiating treatment. Further evidence is needed regarding the impact of finasteride on high-grade prostate cancer. However, our analysis suggests that even if the observed increase in high-grade tumors is a pathologic artifact, adoption of finasteride to prevent prostate cancer is unlikely to be cost-effective. No significant financial relationships to disclose.
Abstract 964: GATA3 modulates chromatin structure to establish active enhancers in breast cancer cells
Authors: Motoki Takaku, Sara A. Grimm, Takashi Shimbo, Lalith Perera, Shinichi Machida, Hitoshi Kurumizaka, Paul A. Wade
Journal: Cancer Research (2015)

Abstract Master transcription factors regulate cell-type-specific gene expression to define cellular identities. One such gene, GATA3, is a key regulator of multiple cellular programs, including T lymphocyte development, mammary luminal epithelial cell differentiation and trophoblast development. Recently, comprehensive genomic analysis has identified GATA3 as one of the most frequently mutated genes in breast cancer. It is also known that GATA3 expression levels directly correlate with favorable prognosis. These findings strongly suggest that GATA3 plays a critical role in tumorigenesis. However, the molecular mechanism(s) underlying GATA3-mediated gene regulation in breast cancer cells is not clearly defined. GATA3 participates in a complicated regulatory network with FOXA1 and ER-alpha, governing the transcriptional program in luminal tumors. Biochemical analyses indicate that: (1) GATA3 binds to chromatin in an estrogen-independent manner, (2) GATA3 acts upstream of FOXA1. These studies suggest GATA3 may act as a pioneer factor, which is capable of independently associating with closed chromatin and modulating chromatin structure to establish an active enhancer. In order to investigate GATA3 function as a pioneer transcription factor, we chose the MDA-MB-231 breast cancer cell line, which is GATA3, FOXA1 and ER-alpha negative, and established stable cell lines expressing wild-type GATA3 or GFP as a control. Consistent with previous results, GATA3-expressing cells represented an epithelial phenotype at the cellular and molecular level. To determine whether GATA3 can direct reprogramming of chromatin conformation, we performed genome-wide analyses of the chromatin binding activity of GATA3 and its impact on histone modifications and chromatin structure. We will present recent results describing how GATA3 licenses enhancer function to direct the luminal transcriptional program. Citation Format: Motoki Takaku, Sara A. Grimm, Takashi Shimbo, Lalith Perera, Shinichi Machida, Hitoshi Kurumizaka, Paul A. Wade. GATA3 modulates chromatin structure to establish active enhancers in breast cancer 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 964. doi:10.1158/1538-7445.AM2015-964
Comprehensive and Unbiased Integration Site Analysis in Clinical Gene Therapy.
Authors: Richard Gabriel, Anna Paruzynski, Ralph Eckenberg, Cynthia C. Bartholomae, Ali Nowrouzi, Wei Wang, Kerstin Schwarzwaelder, Anne Arens, Romy Kirsten, Annette Deichmann, Claudia Ball, Steven J. Howe, Alessandra Recchia, Claudia Cattoglio, Kamaljit S. Balaggan, Rafael J. Yáñez-Muñoz, Robin R. Ali, Fulvio Mavilio, Bobby Gaspar, Adrian Thrasher, Hanno Glimm, Christof von Kalle, William Saurin, Manfred Schmidt
Journal: Blood (2008)
Evolutionary stability of the R1 retrotransposable element in the genus Drosophila.
Authors: W C Lathe, W D Burke, D G Eickbush, T H Eickbush
Journal: Molecular Biology and Evolution (1995)

R1 is a non-long terminal repeat (non-LTR) retrotransposable element that inserts into a specific sequence of insect 28S ribosomal RNA genes. We have previously shown that this element has been maintained through vertical transmission in the melanogaster species subgroup of Drosophila. To address whether R1 elements have been vertically transmitted for longer periods of evolutionary time, the analysis has been extended to 11 other species from four species groups of the genus Drosophila (melanogaster, obscura, testecea, and repleta). All sequenced elements appeared functional on the basis of the preservation of their open-reading frames and consistently higher rate of substitution at synonymous sites relative to replacement sites. The phylogenetic relationships of the R1 elements from all species analyzed were congruent with the species phylogenies, suggesting that the R1 elements have been vertically transmitted since the inception of the Drosophila genus, an estimated 50-70 Mya. The stable maintenance of R1 through the germ line appears to be the major mechanism for the widespread distribution of these elements in Drosophila. In two species, D. neotestecea of the testecea group and D. takahashii of the melanogaster group, a second family of R1 elements was also present that differed in sequence by 46% and 31%, respectively, from the family that was congruent with the species phylogeny. These second families may represent occasional horizontal transfers or, alternatively, they could reflect the ability of R1 elements to diverge into new families within a species and evolve independently.
Febrile cancer patients seeking acute care: How tired are they?
Authors: C. P. Escalante, R. Valdres, T. P. Lam, E. Manzullo
Journal: Journal of Clinical Oncology (2005)

8252 Background: Fever is a very common symptom in cancer patients and the leading cause of emergency center (EC) visits at M.D. Anderson Cancer Center. Cancer-related fatigue is also common among cancer patients, affecting approximately 70–100%. Our objectives are to describe clinical factors in oncology patients with fever and fatigue and to determine fatigue levels in EC patients presenting with fever. Methods: A retrospective cohort of 247 cancer patients with a chief complaint of fever or T>38oC admitted to our EC from 5/1/01 to 8/15/01 was studied. Data abstracted from the medical records included demographics and clinical and cancer treatment factors. Descriptive statistics and univariate analysis were utilized. Fatigue was measured by asking the patient at triage, “What is your worst fatigue in the last 24 hours on a 0 - 10 scale with 10 being the worst fatigue?” Results: The mean age was 53 years (range 18–86). About half (53%) of patients had solid tumors and the rest hematologic malignancy. The overall median fatigue level was 7.0 and 82% had moderate to severe fatigue (4 -10). (Table) Conclusions: This is the first report of fatigue levels in febrile cancer patients. The majority of febrile cancer patients seeking acute care had severe levels of fatigue. Poorer performance status and female gender were associated with more severe levels of fatigue. Interventions to assess and reduce fatigue in this group may be warranted; however, further prospective studies are necessary. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho-Biotech Ortho-Biotech Ortho-Biotech
Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG-PET after the first course.
Authors: H. Kolesnikov-Gauthier, L. Vanlemmens, M. Baranzelli, P. Carpentier, S. Habbas, P. Vennin, V. Servent, C. Fournier, J. Bonneterre
Journal: Journal of Clinical Oncology (2010)

563 Background: To prospectively evaluate the predictive value of FDG-PET to detect the absence of clinical and pathological response to preoperative chemotherapy in patients (pts) with breast cancer. Methods: 63 consecutive pts with nonmetastatic, noninflammatory advanced breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 docetaxel) were enrolled. Fifty-two were assessable (4 non eligible, 7 non evaluable). Median age of assessed pts was 49 years. There were 63% T2 and 37% T3, with 98% invasive ductal carcinomas. FDG-PET was performed before the first and the second course. Metabolic activity (tumor FDG uptake) was measured by standardized uptake value (SUVmax). Patients were classified as non responders (NR) when the decrease of SUVmax in the primary tumor was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG-PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after 3 cycles, pathologic complete response (pCR) after surgery (according to Sataloff classification) and patient disease free survival. Results: Out of the 38 patients with a PET response (SUV decrease more than 15%), 25/38 (66%) had a clinical response after the third cycle and 10/33 (30%) had a pCR. Out of the 14 patients with no PET response, (SUV decrease less than 15%), only 1/14 (7%) had a clinical response after the third cycle and no pCR was observed. The 3-year disease-free survival (DFS) rate was significantly longer for metabolic responders than for non responders (respectively 94±4% vs. 69±13%; p = 0.0008). In this population the pCR, as expected, was also a significant prognostic factor on 3 year- DFS rate (p = 0.02). Conclusions: This prospective study shows that a decrease in the SUV less than 15% after the first chemotherapy course is a very potent predictor of failure to neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this has been shown despite the fact that the chemotherapy regimen was changed after the third course. No significant financial relationships to disclose.
Prospective evaluation of a “Watchful Waiting” program using initial pathology criteria and PSA-doubling time monitoring for patients with stage T1c prostate cancer
Authors: Y. Kakehi, T. Kamoto, O. Ogawa, K. Tobisu, Y. Saito, H. Fukuda, T. Kakizoe
Journal: Journal of Clinical Oncology (2006)

14651 Background: “Watchful waiting (WW)” is becoming a common treatment option for patients (pts) with screening detected prostate cancer. There is, however, no consensus about which pts are suitable for WW and how pts are monitored. Methods: Eligibility criteria: 1) stage T1c prostate cancer pts, 2) age 50–80, 3) serum PSA: 20 ng/ml or less, 4) 1 or 2 positive cores per 6 to 12 systematic core biopsies, 5) Gleason score of 6 or less, 6) 50% or less maximum % cancer occupation in a positive core. The criteria of 4), 5), 6) were confirmed by a central pathologist before pts registration. Registered patients chose either WW or immediate aggressive treatment. In patients who chose WW, serum PSA was monitored every 2 months for 6 months and PSA-doubling time (PSADT) was calculated centrally. Those who showed PSADT 2y and re-biopsy at 13 months fit the initial pathology criteria again. Primary endpoint was “% PSADT &gt; 2 y”, which was defined as proportion of patients who showed PSADT at 6 months &gt; 2 y out of all patients who chose WW. Point estimate of “% PSADT &gt; 2 y” was expected to be higher than 80%. The planned sample size was 100 pts who chose WW, which gives the width of 95% confidence intervals for % PSADT &gt; 2 y within 10%. Results: 134 pts were enrolled from 01/2002 to 12/2003 and 118 pts chose WW while 13 pts chose aggressive treatment (surgery, radiotherapy, hormonal therapy). The initial 6 months’ PSADT could be assessed in 106 patients (measurement point error in 6, early dropout in 6). Of 106 patients, 22 showed PSADT &lt; 2 y (“rapid riser”) while 84 showed PSADT &gt; 2 y. “% PSADT &gt; 2 y” was 71.2% (84/118, 95% CI: 62.1–79.2%). 84 pts have continued WW with median follow-up of 27 months. Neither metastasis nor cancer-death was observed until 06/2005. As to health-related QOL, any domain of SF-36 was not impaired in patients who continued WW at least for 1 year. Conclusion: Our initial selection criteria for WW may include at least 20% of “rapid riser”, hence need further modification. Additionally, it should be confirmed by further follow-up of 84 pts whether eliminating “rapid riser” from WW by initial 6 months’ PSADT is appropriate. No significant financial relationships to disclose.
Effect of glucose states on renal cell carcinoma growth.
Authors: S. Kruss, B. Finnerty, J. Cabrera, D. Mehta, K. Valyi-Nagy, S. Setty
Journal: Journal of Clinical Oncology (2010)

e15106 Background: In the present study we developed a three dimensional model of primary and metastatic renal cell carcinoma (PRCC and MRCC) in culture. We studied the effects of high glucose states on tumor growth and differentiation. In addition we report the effects of matrix glycation on tumor aggregate size. Methods: A heightened glucose milieu was created by culturing tumor cells in 12.5 and 25 mM glucose as compared to the normal 5 mM glucose and an osmotic control (cells grown in five mM glucose with 20 mM mannitol) (OC). The cells were cultured in flasks in two dimensions, for at least three passages and a minimum of twelve days in the four glucose states prior to harvest. An equal number of disaggregated cells were placed in wells plated with matrigel (a matrix composed predominantly of tumor collagen and laminin) to create a three-dimensional culture state. Results: Both PRCC and MRCC tumor cells replicated and created spherical aggregates with focal luminal differentiation. Growth was studied for twenty days at which time complex aggregates formed which were on average larger in 12.5 and 25 mM glucose medium than in 5 mM glucose and the OC. The increase in average diameter in higher glucose medium was observed starting at five days of culture. Use of a preglycated matrix accentuated differences in aggregate size at an earlier time. At twenty days the larger aggregates showed outgrowth of tumor cells into the surrounding matrix. Metastatic tumor cells migrated throughout the depth of the gel indicating a greater ability to invade through the matrix than the primary tumor. Conclusions: Three-dimensional culture of primary and metastatic renal cell carcinoma in increased glucose states is associated with accelerated replication of tumor cells and rapid creation of complex aggregates. Preglycation of matrix further accentuates replication. This system mimics tumor growth and differentiation in vivo and provides a model for further investigation of tumor cell biology and therapeutics. No significant financial relationships to disclose.
Expression of the plasminogen activator inhibitor-1 RNA binding protein (PAI-RBP1) in epithelial ovarian cancer (OC)
Authors: D. Koensgen, S. Jalid, A. Mustea, E. Dahl, I. Klaman, B. Petschke, P. Sun, W. Lichtenegger
Journal: Journal of Clinical Oncology (2005)

9628 Background: The plasminogen activator-plasmin cascade plays a central role in tumor cell invasion and metastasis of solid tumors. The type-1 plasminogen activator inhibitor (PAI-1) is the major physiologic regulator of the plasminogen activation. The novel PAI-RBP1 is suggested to play a crucial role in cyclic nucleotide-mediated regulation of PAI-1 mRNA stability. The expression of PAI-RBP1 in OC is unknown. We are the first working group to analyse the expression of PAI-RBP1 in OC. Methods: Identification of overexpressed genes in OC by in-silico analysis (AUTEX, e-NORTHERN, BLAST). In a second step analysis of the expression of PAI-RBP1 by in-situ hybridization was performed. Tissue sections of paraffin-embedded tumor specimens from patients (pts) with benign and malignant ovarian tumors (OT), who underwent surgical intervention in the Department of Gynaecology and Obstetrics, Charité, from 02/01 to 06/02, were used. Correlation analysis with conventional clinical factors was performed by using SPSS (SPSS Inc., V.11,0; Chicago 2001). Results: 57 pts (28 primary OC, 15 recurrent OC, 3 low-malignant potential OT, 6 benign OT, 5 normal ovary) were allocated to this trial. Median age was 57 years (range, 34–86). Median follow-up was 20 months (range, 0–64). The distribution of tumor stage FIGO of all primary OC was: I=16.2%, II=3.2%, III=45.2% and IV=35.5%. PAI-RBP1 was significantly overexpressed in tumor epithelium of OC in comparison to ovarian epithelium of benign OT and normal ovary (p=0.002). In statistical analysis a significant correlation between the PAI-RBP1 expression and FIGO-stage was observed (p=0.014). Conclusions: PAI-RBP1 is significantly overexpressed in OC and correlates with the clinical tumor stage FIGO. Based on these results the prognostic role of PAI-RBP1 will be analysed. No significant financial relationships to disclose.