tbuckley/cabot-search huggingface dataset:
Development and validation of sensitive and selective biomarker for early detection and prognostic system of colorectal cancer using aptamer biochip.
Authors: Seung Kee Seo, Sungchun Kim, Jung Wook Huh, Hee C Kim
Journal: Journal of Clinical Oncology (2015)

e22124 Background: Colorectal cancer (CRC) is one of the most common cancer and the leading causes of cancer-related deaths worldwide. The identification and characterization of new molecular markers and the discovery of novel targeted therapies are two main goals in colorectal cancer research. Therefore, specific mapping of the molecular features can be potentially useful for both tumor classification and the development of appropriate therapeutic regimens. But this can be accomplished by developing high-affinity molecular probes with the ability to recognize specific markers associated with different tumors. Aptamers can play a key role to meet this challenge based on their target diversity, flexible manipulation and ease of use. Methods: Using a method known reverse-SELEX (Systematic Evolution of Ligands by Exponential enrichment), aptamer biochip and blood serum from 300 colorectal cancer patients in stage II and III, we selected a cluster of target-specific aptamers and evaluated its efficacy. The developed aptamers were tested with the colorectal cancer serum and compared with normal human colon specimen. Results: We have built up 1149 aptamer library which has diseases specificity and prepared biochip using selected aptamers. Colon cancer cell specific aptamers were discovered and we demonstrated it can be used for cancer prognostic system development. Aptamer as a screening tool for colorectal cancer is evaluated and the preliminary data showed that it could be promising tool for screening colorectal cancer and individual cancer tissue showed the distinct pattern of protein and aptamer expression. Also, aptamer expression profiling in aptamer chip in stage II and III colorectal cancer could predict the oncologic outcomes. That meant we could develop new chemotherapy indications for colorectal cancers. Conclusions: Our initial study of the aptamer biochip to colorectal cancer showed that it can provide key information regarding the potential possibility to determine prognosis and to monitor disease progress and therapy after curative resection and unique tools to profile the known mediators and identify newer biomarkers.
Heterogeneous growth rates of pancreatic adenocarcinoma by retrospective analysis of CT imaging data.
Authors: Tanner Mortenson, Allison Bigeh, Yighua Chen, Michael Malek-Ahmadi, Kewei Chen, Maddapa Kundranda, John Chang
Journal: Journal of Clinical Oncology (2017)

248 Background: Pancreatic ductal adenocarcinoma (PDAC) remains the fourth leading cause of cancer death in the United States. Despite its high mortality, there is no effective screening method or frequency. The purpose of this study is to retrospectively evaluate prediagnostic CT images in order to identify growth rate and determine a potential surveillance frequency for at risk patients. Methods: 188 PDAC patients were seen at Banner MD Anderson Cancer Center (BMDACC) from 1/1/2012 to 12/31/2015. 24 patients met the final inclusion and exclusion criteria. Tumor area on CT imaging was then evaluated for rate of change prior to diagnosis. Both absolute and relative areas were plotted against time prior to diagnosis at 3, 6, 9, 12, 24, 36, 48, 60, and 72 months. Results: With two exceptions, no evidence of malignancy was identifiable at two or more years prior to diagnosis. Growth rates per year varied significantly. Absolute area change ranged from 1.7 cm 2 /yr to 139.22 cm 2 /yr; relative area change ranged from 1.17 to 7.15. Assuming a spherical mass, these relative changes correspond to relative volume change (ratio) per year of 1.27 and 19.13; the equivalent linear tumor doubling times are 3.7 years and 20 days respectively. Student’s T-test yielded no significant difference for relative growth, absolute growth, PFS, or OS between male and female patients. Conclusions: The heterogeneity in growth rate has significant implications for potential screening of PDAC. Screening interval greater than 1 year is feasible with other slow growing tumors. However, annual screening is not feasible for rapidly growing PDAC. Based on our findings, screening may need to be as frequent as 3-month intervals which would incur significant economic cost. Further correlation of prediagnostic growth rate with molecular changes may be necessary to discover the driver of this heterogeneous growth pattern.
A phase I study of ISIS 481464 (AZD9150), a first-in-human, first-in-class, antisense oligonucleotide inhibitor of STAT3, in patients with advanced cancers.
Authors: David S. Hong, Anas Younes, Luis Fayad, Nathan Hale Fowler, Fredrick B. Hagemeister, Reena Mistry, John J. Nemunaitis, Mitesh J. Borad, Alan H. Bryce, Mason Yamashita, Steven George Hughes, Theodore Jesse Kwoh, A. Robert MacLeod, Dan Norris, Ron Baldwin, Gene Hung, Brett P. Monia, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2013)

8523 Background: ISIS 481464 is a synthetic bicyclic nucleic acid-containing antisense oligonucleotide that is complementary to the mRNA for signal transducer and activator of transcription 3 (STAT3). Methods: Primary objective of the dose-escalation study (3+3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). Secondary objectives included safety, tumor response, pharmacokinetics (PK), and pharmacodynamics (PD) using IL-6 and tumor markers. Patient (pt) eligibility included : &gt;18 yrs old, solid tumors or lymphomas refractory to at least 1 prior systemic therapy. ISIS 481464 was administered IV as a loading dose on Days 1, 3, and 5 and then weekly. Results: 15 pts were dosed (4 at 2 mg/kg and 11 at 4 mg/kg). 6 pts had advanced lymphoma (3 DLBCL, 2 Hodgkin’s lymphoma, 1 mantle cell lymphoma) and 9 pts solid tumors. There was one dose limiting toxicity (DLT), a possibly related thrombotic microangiopathy at 4 mg/kg. Treatment emergent thrombocytopenia was observed with an average reduction of approximately 70% from baseline. Three pts, 1 at 2 mg/kg and 2 at 4 mg/kg, experienced nadirs in platelet count below 50x10 9 /L (range 16 to 33x10 9 /L). MTD was not reached; however, given the thrombocytopenia at 4mg/kg, the RP2D was 2mg/kg. Partial responses were observed in 2/3 DLBCL pts. The 1st DLBCL pt (2 mg/kg) with 10 prior treatments had a durable 55% reduction in tumor size and is ongoing treatment at 11 months. This pt had a 76% reduction in IL-6. The 2nd DLBCL pt (4 mg/kg) with 2 prior treatments had a 65% reduction for 4 months and was able to undergo autologous stem cell transplantation. There were no responses in the solid tumor pts. PKs revealed increased plasma trough levels (indicative of tissue concentrations) with increased dose. Conclusions: ISIS 481462 was well-tolerated and the RP2D was determined to be 2 mg/kg. Initial tumor activity was observed in DLBCL pts and a dose expansion in advanced lymphomas is ongoing. Clinical trial information: NCT01563302.
Prognostic significance of lymph node retrieval in localized rectal cancer (RC): A registry analysis of 8,964 patients (pts).
Authors: Amandeep Gill, Ann Brunson, Primo Lara, Kristin Olson, Arta Monjazeb, Vijay P. Khatri, Thomas John Semrad
Journal: Journal of Clinical Oncology (2012)

3566 Background: In contrast to colon cancer, the prognostic implications of reduced lymph node retrieval in RC are unclear. We investigated the association between the total number of lymph nodes examined in early stage RC and disease specific survival (DSS) in two cohorts: 1) pts who underwent surgery and adjuvant (ADJ) chemoradiation (chemoXRT), and 2) those who received neoadjuvant (NEO) chemoXRT. Methods: Using the California Cancer Registry, we identified 8,946 pts with stage I – III RC diagnosed from 2000 to 2007. Of these, 4,790 underwent tri-modality therapy: 2,946 patients (61.5%) had NEO chemoXRT and 1,844 patients (38.5%) had ADJ chemoXRT. Multivariate Cox proportional hazards models were constructed for DSS, adjusting for age, sex, race, socioeconomic status, T-stage and lymph node number. DSS was compared between NEO and ADJ cohorts within separate subgroups of pathologic node positive and node negative RC. Results: Although there was no difference in overall DSS between the NEO and ADJ cohorts, the median number of lymph nodes examined was reduced in patients who had undergone NEO chemoXRT (8 vs. 11, p&lt;0.0001). For all pts treated with tri-modality therapy, advancing age and higher T-stage were associated with significantly reduced DSS. Positive lymph nodes were associated with worse DSS regardless of the timing of therapy, although the effect was stronger for residual lymph nodes in the NEO cohort (HR 2.8 vs. 1.8 in ADJ cohort, p&lt;0.001). For node negative pts in the ADJ cohort, increased lymph node retrieval was associated with improved DSS (HR per node 0.952, p=0.017); however, no association between lymph nodes examined and DSS was seen in the NEO cohort (p=0.282). Conclusions: Residual positive lymph nodes in pts treated with NEO chemoXRT are more strongly associated with poorer DSS than in pts treated with surgery and ADJ chemoXRT. NEO chemoXRT dissociates the connection between lymph node retrieval and survival in RC. This finding highlights a key difference between colon and RC and underscores the need for a different interpretation of the pathologic findings after NEO therapy.
Effect of estrogen receptor-positive progenitor cells on a tamoxifen resistance phenotype in breast cancer cells
Authors: J. Selever, I. Barone, M. T. Lewis, A. Corona-Rodriguez, A. Tsimelzon, A. Di Pietro, A. Boumemdjel, S. Fuqua
Journal: Journal of Clinical Oncology (2009)

1042 Background: The antiestrogen tamoxifen and aromatase inhibitors are the most frequently prescribed hormonal agents for the treatment of estrogen receptor (ER) α-positive breast cancer. An important question is whether there is a group of hormone resistant, ERα-positive patients who may derive additional benefit from the addition of chemotherapy to endocrine therapy, or who may be candidates for “targeted” biologics. Dicer1 is an RNase III-containing enzyme that processes microRNA precursors into mature microRNA, which have been implicated in breast tumor invasion and metastasis. BCRP1 is a transmembrane transport protein known to efflux a number of chemotherapeutic agents, but also steroid hormones. In the present study, we investigated whether Dicer might affect response to tamoxifen in breast cancer cells, and generated estrogen receptor-positive MCF-7 human breast cancer cells stably overexpressing Dicer1, and they exhibited elevated BCRP1 protein. Methods: We utilized preclinical approaches to study the function of BCRP1 in Dicer-overexpressing breast cancer cells using in vitro growth assays in soft agar, mammosphere formation assays, and in vivo tumor initiation. Results: Microarray analyses of human breast tumors, suggested that Dicer overexpression was associated with tamoxifen resistance. Dicer-overexpressing MCF-7 cells express elevated levels of BCRP1, ALDH, and cErbB2/HER-2 evident by immunoblot analysis. The Dicer1-overexpressing cells formed soft agar colonies in the presence of tamoxifen, however Fumitremorgin C (FTC) or MBLI-97, both BCRP inhibitors, reversed resistance, and sensitized cells to tamoxifen therapy. Preclinical in vivo tumor xenograft experiments confirmed the tamoxifen-resistant phenotype. Mammosphere potential was enhanced in Dicer-overexpressing cells suggesting an enrichment of stem-like breast cancer cells. Conclusions: Our results suggest that Dicer-overexpressing breast cancer cells are a novel preclinical model for an estrogen receptor-positive breast cancer progenitor phenotype and tamoxifen resistance. Based on our data Dicer1 is a potential predictive biomarker in breast cancer, and predicts that clinical BCRP1 inhibition may facilitate tumor sensitization to hormonal therapy. No significant financial relationships to disclose.
ETIOLOGY OF YELLOW FEVER
Authors: Alfred E. Cohn, Hideyo Noguchi
Journal: The Journal of Experimental Medicine (1921)

1. Slowing of the heart occurred in monkeys and guinea pigs during the febrile period of the experimental infection due to Leptospira icteroides. A similar reaction took place in animals inoculated with Leptospira icterohoemorrhagioe. 2. The mechanism of slowing was usually due to slowing of the whole heart. 3. Once incomplete heart block was seen. Changes in the ventricular complex occurred four times.
Factors associated with worse outcome for patients with AJCC stage IIC relative to stage IIIA melanoma.
Authors: Caroline C. Kim, Julie S. Najita, Sally Yi-Meng Tan, Sowmya Varada, Lana X. Tong, Haili Dunbar, Mee-young Lee, Virginia J. Seery, Elizabeth Iannotti Buchbinder, Nicholas E. Tawa, Jennifer Fuller, Robert Andrew Frankenthaler, David F. McDermott, Sandra J. Lee, Michael B. Atkins
Journal: Journal of Clinical Oncology (2015)

9078 Background: Sentinel lymph node (SLN) status is used in melanoma AJCC staging to distinguish between stage I or II and stage III disease. However patients (pts) with stage IIC (Breslow > 4 mm, ulcerated, SLN -, T4bN0) have worse survival than pts with stage IIIA (any Breslow, nonulcerated, SLN +, Txa,N1a or N2a) disease. We sought to identify factors beyond stage criteria associated with worse outcomes for Stage IIC pts and to compare a matched IIIB population (T4bN1a or N2a). Methods: We performed a retrospective chart review of pts diagnosed with T4b (stage IIC and IIIB) or IIIA melanoma in the BIDMC Cutaneous Oncology Program between 1998-2011. Demographics, risk factors, tumor characteristics and outcomes were collected. Groups were compared using a Wilcoxon rank sum test or Fisher’s exact test. Log-rank testing and Cox regression modeling were performed. Results: 162 pts with stage IIC (56), IIIA (80) and matched Stage IIIB (26) melanoma were identified. Median follow-up time was 5.6 years. The estimated 5-year survival rate for pts with IIC vs IIIA disease was 56% (38-70, 95% CI) vs. 79% (67-87, 95% CI). Besides stage criteria, significant differences between IIC vs. IIIA cohorts included: age at diagnosis (62 vs. 51, p < 0.001), amelanotic tumors (45% vs. 22%, p = 0.03), mitotic rate (10 mits/mm2 vs. 2 mits/mm2, p < 0.001), nodular subtype (71% vs. 24%, p < 0.001), radial growth (23% vs. 55%, p < 0.001) and presence of precursor lesion (6% vs. 22%, p = 0.02). Regression modeling revealed that older age at diagnosis ( > 55, p < 0.001) and higher mitotic rate ( > 5 mits/mm2, p = 0.001) were associated with worse survival in pts with stage IIC disease. Of note, pts with matched stage IIIB disease had similar 5-yr survival (52% [29-74, 95% CI])) to pts with IIC disease. Conclusions: Our study suggests that aside from stage criteria, there are inherent differences between the IIC and IIIA melanoma population, and older age and higher mitotic rates are associated with worse prognosis for IIC vs. IIIA pts. Further, the similar survival for IIC pts with matched IIIB (T4bN1a or N2a) pts calls into question the value of SLN biopsy as a staging tool in this population. These factors merit consideration in the management of pts with T4b primary lesions.
Effect of grade (G) 3 fibrosis on clinical outcome of patients (Pts) with myelodysplastic syndromes (MDS): Mayo Clinic Experience.
Authors: Naveed Cheema, Firas Baidoun, Darci Zblewski, Shahrukh Hashmi, Naseema Gangat, Alexandra P. Wolanskyj, William J. Hogan, Mark Robert Litzow, Dong Chen, Aref Al-Kali
Journal: Journal of Clinical Oncology (2015)

7085 Background: There have been renewed attempts at characterizing the clinicopathological findings of MDS with fibrosis (MDS-F) in order to determine if it warrants a distinct entity. Most of these studies were small while few studied clinical outcome of MDS-F. Aim: To studyclinical outcomes of patients with MDS-F. Methods: A retrospective, single-institution study of MDS cases per WHO classification from 1993-2014 was done. Bone marrow biopsy (BMB) fibrosis was identified as G 1, 2, or 3 on reticulin stain. Wilcoxon, Pearson tests, Kaplan Meier, multivariant analysis were done via JMP. Results: Initial screen of our database revealed 108 (13%) of 835 pts with MDS as MDS-F. On follow up, 49/108 (45%) had subsequent BMB. In 33/49 (67%) pts, diagnosis changed (median time 7 months, m) into AML,RAEB,RCMD in 17 (52%), 10 (30%), and 2 (6%) pts. A second change was in 5/14 pts. Final diagnoses in 49 pts were AML/RAEB/RCMD in 18 (37%), 15 (31%), and 8 (17%) (rest were atypical/ CMML/MDS MPN/RARS/MDS-F). Comparison between fibrosis (n = 108) and non-fibrosis groups (n = 727) showed no statistically significant difference in survival or time to AML. Statistically significant variables between the groups were age (p = 0.0002), platelet (p < 0.0001), multilineage dysplasia (p < 0.0001), dysmegakaryopoiesis (p < 0.0001), peripheral blasts (p = 0.01), cellularity (p < 0.0001) and IPSS-R group (p = 0.01). There was a statistically significant difference in mOS across all grades of fibrosis (33 in G1, 39 in G2, 8 m in G3, p = 0.001). Pts with G3 fibrosis vs all others had a statistically significant lower mOS of 8 vs 29 m (p < 0.0001). In multivariate analysis, only age (p < 0.0001), IPSS-R (p < 0.0001) and G3 fibrosis (p = 0.018) were found to have a statistically significant effect on mOS (but not blast or gender). JAK2 status and CD34 clustering had no significance on survival amongst the fibrosis group. Conclusions: MDS-F is a small entity with distinct lab and BMB findings. Only G3 fibrosis had a significant negative impact on mOS. On follow up, 55% progressed into AML or RAEB. Age, IPSS-R and G3 fibrosis were the only significant contributors to mOS. Our finding needs to be further investigated within larger sets of MDS pts.
Concurrent Radiotherapy and Dexamethasone, Etoposide, Ifosfamide, and Carboplatin (DeVIC) for Patients with Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Single Institution Analysis in Japan
Authors: Eriko Nara, Masahiro Yokoyama, Kengo Takeuchi, Kenji Nakano, Kyoko Ueda, Noriko Nishimura, Sakura Sakajiri, Yuko Mishima, Naoko Tsuyama, Masahiko Oguchi, Shunji Takahashi, Yasuhito Terui, Kiyohiko Hatake
Journal: Blood (2011)
Low-dose budesonide treatment reduces severe asthma-related events in patients with infrequent asthma symptoms at baseline: A post-hoc analysis of the start study
Authors: H. K. Reddel, W. W. Busse, Søren Pedersen, W. C. Tan, Y. Z. Chen, C. Jorup, D. Lythgoe, P. M. O'Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2015)
CURVA DE APRENDIZAJE DE LA COLANGIOPANCREATOGRAFIA ENDOSONOGRAFICA (CPES)
Authors: E Vázquez Sequeiros, SS López-Durán, L Aguilera, J González-Martín, J Foruny, D Boixeda, D Juzgado-Lucas, M Pérez-Miranda, A Albillos
Journal: Endoscopy (2015)

Introducción: En estos últimos años hemos asistido al nacimiento y consolidación paulatina de técnicas híbridas de CPRE y ecoendoscopia (colangiopancreatografía-endosonográfica o "CPES"), que nos permiten tratar a pacientes con patología biliar/pancreática(tumores/litiasis/pancreatitis) en los que la CPRE ha sido fallida. Se desconoce cuáles son los requerimientos para realizar CPES con solvencia.
MicroRNA regulation of radiation sensitivity in colorectal cancers.
Authors: Shushan Rajesh Rana, Katherine Kelley, Rebecca Ruhl, Charles R. Thomas, Vassiliki Liana Tsikitis, Sudarshan Anand
Journal: Journal of Clinical Oncology (2017)

608 Background: Patients with locally advanced colorectal cancer (T3/T4/Node positive) receive neoadjuvant chemoradiation therapy (CRT) and subsequent surgery. While 10-25% of patients have complete response to CRT, the remaining patients undergo extensive tumor excision that leads to quality of life issues. Response to CRT is an independent predictor of overall survival highlighting the importance of improving CRT response rates. Several tumor intrinsic factors govern responses to CRT including specific gene expression programs. Emerging evidence suggests that microRNAs (miRs) modulate gene expression programs in response to radiation. Moreover, miR-processing machinery is frequently mutated in colorectal cancers (TCGA, 2016 provisional). miRs have been implicated in several pathological processes associated with colorectal cancer progression including cancer stemness and epithelial-to-mesenchymal transition (EMT). In this context, we hypothesized that differential expression of miRs regulates colorectal cancer radiation sensitivity and therefore can be used as a biomarker to predict therapeutic responses to radiation. Methods: To investigate the differences in miR profiles between rectal cancer patients that had either a pathological partial response (PR) or no response (NR), we isolated RNA from FFPE biopsies using the miRvana microRNA isolation kit (Life Technologies). We used the Nanostring miR profiling platform and obtained absolute counts for &gt; 700 human miRs of which ~500 miRs were expressed above detection limits (cut-off of 20 counts after normalization to the top-100 miRs). We performed in vitro gain and loss of studies with miR transfections in human CRC cell lines with RNAimax reagent and used a luminescence-based assay for proliferation (Cell titer glo, Promega). We performed surviving fraction assays by seeding cells on 6 well plate and counting colonies stained with Methylene Blue. Results: We identified seventeen miRs that were differentially expressed. Among the most upregulated in this group, miR-451a, inhibited proliferation and colony formation in 2D and 3D assays in the presence of radiation. Conclusions: Our data suggests miRs may alter cell survival pathways and affect tumor radiosensitivity.