tbuckley/cabot-search huggingface dataset:
Impact of U.S. Preventive Services Task Force recommendation on screening for prostate cancer in men age 75 or older.
Authors: Michael W. Drazer, Sandip M. Prasad, Dezheng Huo, Mara A Schonberg, Scott E. Eggener
Journal: Journal of Clinical Oncology (2012)

216 Background: In 2008, the U.S. Preventive Services Task Force (USPSTF) recommended against screening for prostate cancer in men age 75 years or older. We sought to determine the impact of this statement on utilization of prostate-specific antigen (PSA) testing in this patient group. Methods: Using the 2005 and 2010 National Health Interview Survey, a cross-sectional household interview survey providing a representative sample of the U.S. population, we analyzed the use of PSA testing in men age 40 years or older prior to and following the release of the USPSTF statement on prostate cancer screening. Results: In 2010, there were an estimated 2.0 million PSA tests ordered in men 75 years of age and older. In this group, PSA testing rates did not decline between 2005 and 2010 (40.4% vs. 40.6%). In 2010, PSA testing was more common in men aged 75 years and older than in men aged 40 to 49 (9.2%) and 50 to 59 (26.2%) (p &lt; 0.01 between groups). In both 2005 and 2010, PSA testing rates were lowest in men aged 40-49 and highest in men aged 60-74. Conclusions: Despite the USPSTF recommendation against prostate cancer screening in men age 75 or older, there was no decrease in PSA testing rates in these men. A significant proportion of elderly men continue to receive PSA screening despite a very low likelihood of benefit. [Table: see text]
Abstract 5566: Carnosic acid induces apoptosis through inhibition of STAT3 signaling and production of ROS in human colon cancer HCT116 cells
Authors: In Gyeong Chae, Mi-Hee Yu, Ki-Woong Park, Kyung-Soo Chun
Journal: Cancer Research (2015)

Abstract Carnosic acid (CA), the main antioxidant compound of Rosmarinus officinalis L., has been shown to display anticancer activity. However, the molecular mechanisms underlying the anticancer effects of CA remain poorly understood. This study revealed that treatment with CA significantly reduced the cell viability and induced apoptosis in HCT116 cells as evidenced by the induction of p53 and Bax, release of cytochrome c, cleavage of caspase-9, -7 and -3 and PARP and the inhibition of Bcl-2 and Bcl-xl expression. CA inhibited the constitutive phosphorylation, the DNA binding and the reporter gene activity of signal transducer and activator of transcription-3 (STAT3) in HCT116 cells by blocking the phosphorylation of upstream Janus-activated kinase-2 (JAK2) and Src kinases. Moreover, CA attenuated the expression of STAT3 target gene products, such as survivin, cylcin D1, D2, and D3. Since ROS is a universal entity mediating apoptosis, we examined whether CA induced apoptosis via ROS formation. Treatment with CA generated ROS and pretreatment with ROS scavenger N-acetyl cysteine (NAC) rescued cells from apoptosis by abrogating the inhibitory effect of CA on the activation of JAK2-STAT3 and Src-STAT3 signaling pathways and rescued cells from CA-induced apoptosis by blocking the induction of p53, and the cleavage of caspase-3 and PARP. In conclusion, CA induced apoptosis in HCT116 cells via generation of ROS, induction of p53, activation of caspases and inhibition of STAT3 signaling pathway. Citation Format: In Gyeong Chae, Mi-Hee Yu, Ki-Woong Park, Kyung-Soo Chun. Carnosic acid induces apoptosis through inhibition of STAT3 signaling and production of ROS in human colon cancer HCT116 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 5566. doi:10.1158/1538-7445.AM2015-5566
MicroRNAs 221 and 222 Inhibit Normal Erythropoiesis and Erythroleukemic Cell Growth Via Kit Receptor Downmodulation.
Authors: Nadia Felli, Laura Fontana, Elvira Pelosi, Rosanna Botta, Desirée Bonci, Francesco Facchiano, Francesca Liuzzi, Valentina Lulli, Ornella Morsilli, Simona Santoro, Mauro Valtieri, Chang-Gong Liu, Antonio Sorrentino, Carlo M. Croce, Cesare Peschle
Journal: Blood (2005)
Gastrointestinal stromal tumors (GIST) of the duodenum: A French Sarcoma Group (FSG) retrospective review of 90 patients (pts).
Authors: F. Duffaud, I. L. Ray-Coquard, A. Blesius, T. K. Huynh, E. Boucher, O. Bouche, J. Bay, F. Marchal, J. Spano, F. Bertucci, B. Bui Nguyen, O. Collard, L. Chaigneau, N. Isambert, A. Adenis, J. Mancini, A. Le Cesne, J. Blay
Journal: Journal of Clinical Oncology (2011)

10053 Background: Duodenal GIST (D-GIST) represents ≤ 5% of all GISTs, and clinicopathologic data are reported only from small series. We conducted a retrospective analysis of duodenal GIST over the past 17 years. Methods: Pts with D-GIST were identified either via survey from 19 FSG centers (71 pts) or as those enrolled in the BFR14 GIST trial (19 pts). Results: Pts were: 47 females, 43 males, with a median age of 57 years (30-84), and median ECOG 0 (0-3). Abdominal pain, anemia, and GI bleeding were the most common symptoms. Tumors (T) were localized (n=71) or metastatic (n=19), mainly D2 (30%), or D3/D4 (29%), with a median size of 6 cm (1.5-31). 78 pts had primary T resected; surgical procedures included local resection (LR) [segmental duodenectomy (n=23), wedge local resection (n=24), local excision (n=5)], and duodenopancreatectomy (DP, n=14). Resections were R0/R1 in 66 pts. T characteristics included: KIT+ (n=75), mitoses/50 HPF ≤ 5 (n= 48), or > 5 (n=20), necrosis (n=28), spindle cell (n=58). Mutations were documented in 22/29 cases, usually in KIT exon 11 (76%). 8 pts received neoadjuvant imatinib (IM) therapy (Rx) resulting in 4 PR, 3 SD, 1 PD. 10 pts received adjuvant IM Rx. With a median FU of 36 months (1-168), 78 pts (87%) are alive. 25/71 pts with localized T relapsed : 4 locally and 24 with metastases. The 4-year OS rates were 89% and 72% for localized and metastatic T. For localized T, the 4-years EFS rate was 58%. Univariate analysis showed that: age and ECOG PS have an impact on OS (p= 0.003, p <0.001), necrosis, spindle-cell type, T size, mitoses/50 HPF are predictive of relapse (p< 0.001). In multivariate analysis only mitoses/ 50 HPF predicted relapse (p< 0.001). Conclusions: Pts with completely resected primary D-GIST may have a reasonably favorable prognosis. LR rather than DP should be pursued if possible to preserve optimal pancreas function. Neoadjuvant IM should be considered to render LR feasible in pts with locally advanced D-GIST.
High dose rate brachytherapy as a single 15 Gy fraction combined with hypofractionated external beam radiotherapy for intermediate-risk prostate cancer.
Authors: G. Morton, D. A. Loblaw, H. T. Chung
Journal: Journal of Clinical Oncology (2011)

66 Background: High dose rate (HDR) brachytherapy for prostate cancer is commonly given in multiple fractions combined with external beam radiotherapy (EBRT) over 5 weeks. We report results of a phase II clinical trial of single fraction HDR combined with hypofractionated EBRT over 3 weeks. Methods: Eligible patients had T1 or T2 carcinoma of the prostate with a PSA &lt; 20 and Gleason score of 7 or less, without use of androgen deprivation. The trial accrued 125 patients with a median PSA of 6.8 ng/ml; 93% had Gleason 7. Single 15 Gy HDR was delivered to the prostate, followed 2-weeks later by EBRT to 37.5 Gy in 15 fractions. Patients were followed for toxicity (CTCAE v 3.0), health related quality of life (EPIC), urinary symptoms (IPSS), and clinical and biochemical control. Results: Median follow-up is 3 years (range: 1-4.5 years), with no biochemical failures. Median PSA at 3 years is 0.24 ng/ml. One of 38 biopsies at 2 years had persistent cancer. Two patients (1.6%) had acute grade 3 urinary toxicity, and median IPSS score returned to within 2 points of baseline by 3 months. The prevalence of grade 2 rectal and urinary toxicity at 2 years was 2% and 25%, respectively. Mean EPIC urinary and bowel domain scores decreased in the first 2 years, but returned to within 5 points of baseline at 3 years. Mean sexual function scores declined over the first 4 years although sexual bother scores returned to baseline at 3 years. On multivariate analysis, baseline IPSS score (p=0.0125), V100 (p=0.0002) and V200 (p=0.0141) were associated with acute grade 2 urinary toxicity. Decline in EPIC urinary quality of life domain was associated with HDR dose to 10% of urethra (p=0.0168), with a threshold of 120%. Decline in sexual scores was associated with smaller prostates and high baseline erectile functioning. Conclusions: Single fraction 15 Gy HDR combined with hypofractionated external beam radiotherapy is a well tolerated and effective treatment for intermediate risk prostate cancer. No significant financial relationships to disclose.
Long-term maintenance of human naïve T cells through in situ homeostasis in lymphoid tissue sites
Authors: Joseph J. C. Thome, Boris Grinshpun, Brahma V. Kumar, Masaru Kubota, Yoshiaki Ohmura, Harvey Lerner, Gregory D. Sempowski, Yufeng Shen, Donna L. Farber
Journal: Science Immunology (2016)

Naïve T cells develop in the thymus and coordinate immune responses to new antigens; however, mechanisms for their long-term persistence over the human lifespan remain undefined. Here, we investigated human naïve T cell development and maintenance in primary and secondary lymphoid tissues obtained from individual organ donors aged 3 months-73 years. In the thymus, the frequency of double-positive thymocytes declined sharply in donors over age 40 coincident with reduced recent thymic emigrants (RTE) in lymphoid tissues, while naïve T cells were functionally maintained predominantly in lymph nodes (LN). Analysis of TCR clonal distribution by CDR3 sequencing of naïve CD4+ and CD8+ T cells in spleen and LNs reveal site-specific clonal expansions of naïve T cells from individuals >40 years of age with minimal clonal overlap between lymphoid tissues. We also identified biased naïve T cell clonal distribution within specific lymph nodes based on VJ usage. Together these results suggest prolonged maintenance of naïve T cells through in situ homeostasis and retention in lymphoid tissue.
PAX6 maintains β cell identity by repressing genes of alternative islet cell types
Authors: Avital Swisa, Dana Avrahami, Noa Eden, Jia Zhang, Eseye Feleke, Tehila Dahan, Yamit Cohen-Tayar, Miri Stolovich-Rain, Klaus H. Kaestner, Benjamin Glaser, Ruth Ashery-Padan, Yuval Dor
Journal: Journal of Clinical Investigation (2016)

Type 2 diabetes is thought to involve a compromised β cell differentiation state, but the mechanisms underlying this dysfunction remain unclear. Here, we report a key role for the TF PAX6 in the maintenance of adult β cell identity and function. PAX6 was downregulated in β cells of diabetic db/db mice and in WT mice treated with an insulin receptor antagonist, revealing metabolic control of expression. Deletion of Pax6 in β cells of adult mice led to lethal hyperglycemia and ketosis that were attributed to loss of β cell function and expansion of α cells. Lineage-tracing, transcriptome, and chromatin analyses showed that PAX6 is a direct activator of β cell genes, thus maintaining mature β cell function and identity. In parallel, we found that PAX6 binds promoters and enhancers to repress alternative islet cell genes including ghrelin, glucagon, and somatostatin. Chromatin analysis and shRNA-mediated gene suppression experiments indicated a similar function of PAX6 in human β cells. We conclude that reduced expression of PAX6 in metabolically stressed β cells may contribute to β cell failure and α cell dysfunction in diabetes.
Quality of gastrointestinal cancer care at a community hospital under the paradigm of multidisciplinary care.
Authors: Laurence E. McCahill, Sunil Konduri, Alan T. Davis, Mary May, Coralyn Martinez, Wendy K. Taylor, Gerald P. Wright
Journal: Journal of Clinical Oncology (2012)

133 Background: Benefits of MDC have been established for other cancers but not GI malignancies. Benefits of GI NDC cancer care for underserved populations is yet to be quantified. Our GI-MDC was established to provide efficient, evidenced-based, high quality cancer care to patients of all ethnic and socioeconomic backgrounds. Methods: We prospectively identified underserved patients in seven categories. A GI nurse navigator (NN) contacted patients, coordinated appointments /diagnostic studies and prepared for prospective case evaluation and weekly multidisciplinary GI clinic. Health care efficiency/quality data was abstracted by an R.N. quality analyst. Outcomes were compared between underserved and non-underserved populations. Percentages were compared using Chi square and medians by Mann-Whitney U test. Results: From Jan 2010-July 2011, 208 patients were evaluated, with 137 confirmed new cancers, clinically estimated as Stage I=31, II=30, III=26, and IV=47. Among underserved patients, categories included age &gt;80(n=26), public aid (n=28), uninsured (n=12), mental disability/impairment (n=15), incarcerated/institutionalized (n=4), and language barrier (n=2), more then one category could be selected. Outcomes are listed in the Table. Conclusions: A model of GI cancer care including a GI NN, treatment planning conference, and MDC clinic is feasible in a community cancer center. Preliminary data demonstrates small differences between underserved and non underserved patient populations. This model of health care may help to reduce disparities in cancer care. [Table: see text]
Predictive Value of Minimal Residual Disease: Analysis By Flow-Cytometry in Children with Relapsed Acute Lymphoblastic Leukemia
Authors: Myriam Ruth Guitter, Jorge Gabriel Rossi, Elisa Sajaroff, Carolina Carrara, Pizzi Silvia, Raquel Staciuk, Eduardo Lagomarsino, Natalia Millan, Patricia Rubio, Cristina Noemi Alonso, Pedro Zubizarreta, Maria Sara Felice
Journal: Blood (2015)
Comparable Outcomes After Sibling and Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplantations (HCT) In Adult Acute Lymphoblatic Leukemia (ALL) With First Complete Remission (CR)
Authors: Betul Oran, Michelle Poon, Julianne Chen, Gabriela Rondon, Sairah Ahmed, Borje S. Andersson, Qaiser Bashir, Stefan O. Ciurea, Chitra M. Hosing, Simrit Parmar, Muzaffar H. Qazilbash, Uday R Popat, Yago Nieto, Amin Alousi, Roy B Jones, Katy Rezvani, Marcos de Lima, Elizabeth J Shpall, Richard E Champlin, Partow Kebriaei
Journal: Blood (2013)
Burden of Pneumococcal Disease in Cancer Patients: A 20 Year Single Center Study at Memorial Sloan-Kettering Cancer Center
Authors: Yeon Joo Lee, Yao-Ting Hayden Huang, Seong Jin Kim, Marina Kerpelev, Victoria Gonzalez, Genovefa A Papanicolaou, Anna Kaltsas
Journal: Blood (2015)
Methylation RE in serum of patients with breast cancer and relation with molecular phenotype and worse prognostic factors.
Authors: J. Martínez-Galan, B. Torres-Torres, R. Del Moral, M. I. Núñez, S. Ríos, P. Ballesteros, J. R. Delgado
Journal: Journal of Clinical Oncology (2011)

224 Background: To determine whether Estrogen Receptor (ESR1) (+) and ESR1(-) status relates to epigenetic changes in breast cancer-related genes and to correlate with molecular breast cancer subtypes. Methods: Since January/02 to June/05, we quantified methylation levels ERS1 gene in serum of 92 pts breast cancer. A PCR quantitative technique was used to analyze levels of methylation gene. We also examined and correlationed the expression of ESR1 in tumors by immunohistochemistry with molecular phenotype. Results: Median age was 58 years (32-88); 69% were postmenopausal women. Nodal involvement (N0; 63%, N1; 30%, N2; 7%), tumor size (T1; 58%, T2; 35%, T3; 4%, T4; 4%) and grade (G1; 20%, G2; 37%, G3; 30%). Of the cases, 37 pts (40%) were Luminal A (LA), 32 pts (33%) Luminal B (LB), 14 pts (15%) Triple-negative (TN) and 9pts (10%) HER2+. The methylated ESR1 in serum was significantly associated with ESR1(-) in breast tumors &gt;80% (p=0.0179). Methylation ESR1 was preferably associated with TN (80%) and HER2+ (60%) subtype. Nevertheless unmethylation ESR1 was found more frequently in LA (71%) and LB (59%) phenotype. With a median follow up of 5 years, we found worse overall survival (OS) with more frequent ESR1 methylation gene (p&gt;0.05), Luminal A; ESR1 Methylation OS at 5 years 81% vs 93% when was ESR1 Unmethylation. Luminal B; ESR1 Methylation 86% SG at 5 years vs 92% in Unmethylation ESR1. Triple negative; ESR1 Methylation SG at 5 years 75% vs 80% in unmethylation ESR1. HER2; ESR1 Methylation SG at 5 years was 66.7% vs 75% unmethylation ESR1. Conclusions: Gene promoter region hypermethylation is a significant event in primary breast cancer. However, its impact on tumor progression and potential predictive implications remain relatively unknown. Our study identifies the presence of variations in global levels of methylation promoters ESR1 genes in breast cancer with different phenotype classes and shows that these differences have clinical significance. Although numerous issues remain to be resolved, quantitative measurement of circulating methylated DNA may be of significance in the assessment and search of targeted therapy resistance related to ESR1 and HER2 status by epigenetic or transcriptional cancer therapy.
Brachytherapy as salvage treatment for local nodular recurrence of prostate cancer.
Authors: A. M. Kumar, K. Traudt, J. P. Ciezki, C. A. Reddy, E. A. Klein
Journal: Journal of Clinical Oncology (2011)

86 Background: Men diagnosed with adenocarcinoma of the prostate treated with radical prostatectomy (RP) have a 10% risk of developing local recurrence within 10 years. While the majority of these recurrences are biochemical failures with no foci of disease, we report on a series of 7 patients who had nodular recurrences in the post-surgical bed and subsequently underwent low-dose rate (LDR) brachytherapy as salvage therapy. Methods: Patients who were initially treated with RP and subsequently with salvage LDR I-125 brachytherapy for a nodular recurrence were included in this series. All patients failed biochemically within 10 years of RP and received no other adjuvant or salvage treatment by choice. Nodular recurrences were biopsy confirmed adenocarcinoma, and patients had no evidence of nodal or distant metastasis on imaging or bone scan. All patients consented to salvage with LDR brachytherapy. Follow up post-salvage was at least every 6 months with a serial PSA. Results: Seven patients underwent salvage LDR brachytherapy with median age of 74 (range 63-77) at time of salvage. The median pre-salvage PSA was 4.56. The biopsy Gleason score of the nodular recurrences was 7 or 8. Median volume of nodular recurrence was 16cc, median number of sources was 30, median D90 for nodule was 155.02 Gy, and median rectum V100 was 0.01. Compared to baseline prior to salvage, patients have reported no additional urinary symptoms or sexual side effects from salvage. Patients have been followed for a median of 28 months post-salvage (range 4-48 months) with a median PSA at last follow up of 1.05. Conclusions: This report presents the first known case series of prostate cancer patients treated with RP who developed local nodular recurrences which were then treated with LDR brachytherapy. For patients who develop a nodular recurrence with no other evidence of distant metastases, LDR brachytherapy offers a novel salvage option. No significant financial relationships to disclose.
Bone Marrow Mesenchymal Stem Cells Are Altered in B-Cell Chronic Lymphocytic Leukemia.
Authors: Céline Pebrel-Richard, Richard Veyrat Masson, Frédérique Dubois-Galopin, Jean-Jacques Guérin, Laurent Guillouard, Jacques Chassagne, Jacques-Olivier Bay, Olivier Tournilhac, Karin Tarte, Marc G Berger
Journal: Blood (2008)
Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk locally advanced/inflammatory and metastatic breast cancer.
Authors: A. M. Vanderwalde, W. Ye, P. H. Frankel, D. G. Asuncion, R. D. Pezner, T. H. Luu, S. Shibata, L. A. Leong, K. A. Margolin, R. Morgan, M. Koczywas, W. A. Chow, P. Twardowski, J. Y. Wong, J. H. Doroshow, S. J. Forman, G. Somlo
Journal: Journal of Clinical Oncology (2011)

1048 Background: Patients (pts) with high-risk (HR) locally advanced/inflammatory breast cancer (LABC/IBC), and oligometastatic (≤ 3 sites) stage IV metastatic breast cancer (MBC) are likely to relapse/progress early. High dose chemotherapy (HDCT) followed by stem cell rescue (SCR) may prolong progression/relapse-free (PFS/RFS) and overall survival (OS) in selected pts. Methods: Between 1998 and 2009, 104 eligible pts were consented and treated sequentially on 2 City of Hope Cancer Center IRB-approved HDCT protocols. HDCT consisted of carboplatin, thiotepa, and cyclophosphamide (STAMP-V), doxorubicin, paclitaxel, and cyclophosphamide (ACT), or tandem melphalan and STAMP-V (administered to all pts with MBC and followed by targeted radiation therapy), supported by SCR. Results: Ninety-two pts were diagnosed with LABC/IBC (16 IBC), and 12 had MBC. Among the 92 HR pts, by AJCC 7th edition criteria,14 pts were treated for IIIA, 10 for IIIB, and 68 for IIIC BC. The median age for pts with LABC/IBC was 50 years (range 28−66). Neoadjuvant chemotherapy (NCT) was prescribed to 34% of pts. HDCT was prescribed a median of 8.1 (range 4.4−14.5) months (mos) after diagnosis. The median follow-up of alive LABC/IBC patients was 84 mths (range 6−136). Hormone receptors (HR) were positive in 74% of LABC/IBC pts, and HER2 was overexpressed in 23%. Hormone receptor status (HR) positively impacted the likelihood of RFS and OS (HR+ vs HR- 5-yr RFS 61% vs 32%, p=.008). Tumor grade, histopathology including IBC, HER2 and triple negative status, or receipt of NCT had no statistically significant effect on survival, although higher stage disease led to worse long term outcomes (5-yr RFS for Stage IIIA, IIIB, IIIC was 85%, 68%, 45%, p=.051, with 5-yr OS 92%, 90%, and 64%, respectively, p=.051). For MBC (12 pts), the median follow-up of alive pts is 40 months, (range 24−62), resulting in a 3-yr PFS of 49% 95% CI (19%−73%), and 3−yr OS of 73% 95% CI (38%−91%). One pt died of HDCT-associated sepsis, and 1 pt developed papillary thyroid cancer. Conclusions: The favorable long term PFS/RFS and OS in this selected pt population warrants validation in molecularly defined subgroups with LABC/IBC/MBC.
Analysis of the Genetic Expression of Inflammatory Mediators From Patients with Spontaneous Deep Venous Thrombosis
Authors: Aline Barnabé, Fernanda Dutra Santiago-Bassora, Andrey dos Santos, Marcelo Falsarella Carazzolle, Gonçalo AG Pereira, Fernanda Loureiro de Andrade Orsi, Erich V de Paula, Nelci Fenalti Höehr, Joyce M Annichino-Bizzacchi
Journal: Blood (2011)