tbuckley/cabot-search huggingface dataset:
Switching patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) with residual disease on long-term imatinib (IM) to nilotinib (NIL): ENESTcmr 24-mo follow-up.
Authors: Nelson Spector, Brian Leber, Jeffrey Howard Lipton, Carmino De Souza, Beatriz Moiraghi, Juan Luis Steegmann, Anthony P. Schwarer, Francisco Cervantes, Timothy P. Hughes, Das Purkayastha, LaTonya R Collins, Tomasz K. Szczudlo, Delphine Rea
Journal: Journal of Clinical Oncology (2013)

7053^ Background: The 12-mo results of ENESTcmr demonstrated that switching pts on IM with sustained BCR-ABL positivity to NIL leads to faster, deeper molecular responses (MRs)vs remaining on IM. These deeper molecular responses (MR 4.5 [BCR-ABL ≤ 0.0032% IS ] or greater) are a prerequisite to enter most treatment-free remission studies. Here, we report 24-mo f/u of ENESTcmr. Methods: Philadelphia chromosome–positive CML-CP pts (N = 207) who achieved a complete cytogenetic response, but had detectable BCR-ABL transcripts after ≥ 2 y on IM, were randomized to receive NIL 400 mg twice daily (BID; n = 104) or continue their IM dose (400/600 mg once daily [QD]; n = 103). Results: By 24 mo, significantly more pts achieved confirmed undetectable BCR-ABL (by RQ-PCR with ≥ 4.5 log sensitivity in 2 consecutive samples) with a switch to NIL vs continuing IM (22.1% vs 8.7%; P = .0087). The increase in the rate of undetectable BCR-ABL from mo 12 to 24 was higher for pts on NIL vs IM (9.6 vs 2.9 percentage points). In pts without MR 4.5 at baseline (BL), MR 4.5 was achieved by 24 mo in 42.9% vs 20.8% of pts (NIL vs IM; P = .0006). In pts without major molecular response (MMR; ≤ 0.1% IS ) at BL, MR 4.5 was achieved by 24 mo in 29.2% vs 3.6% of pts (P = .016). No progressions to accelerated phase/blast crisis or deaths occurred on study since the 12-mo f/u. Event-free survival at 24 mo was 96.6% vs 92.8% in the NIL and IM arms, respectively. Discontinuations due to adverse events occurred in 11.5% and 2.9% of pts in the NIL and IM arms. The NIL safety profile was consistent with prior switch studies. Conclusions: By 24 mo, significantly more pts achieved deeper responses (MR 4.5 and undetectable BCR-ABL) with switch to NIL vs remaining on IM, and the difference between arms in these endpoints increased between 12 and 24 mo. Clinical trial information: NCT00760877. [Table: see text]
CBIO-20GLIOBLASTOMA SPECIFIC PROTEINS IDENTIFIED THROUGH COMBINED IN VITRO AND IN VIVO PHAGE DISPLAY BIOPANNING
Authors: Ping Huang, Qiulian Wu, Jeremy Rich, James Liu
Journal: Neuro-Oncology (2015)

Glioblastomas are the most common and lethal primary brain tumor with conventional therapy offering only palliation. Their resistance to therapy has been hypothesized to be due in part to the cancer stem cell, the target of which the development of safe and effective future therapeutics will be focused on. As phage display technology has been used in cancer to identify, target, and image tumor cells, we employed phage display technology to identify novel proteins specific to the functioning of glioblastoma stem cells (GSCs). We have previously shown that in vivo phage display biopanning against primary glioblastoma cell lines xenografted in immunocompromised mice is an effective strategy for isolating glioma stem cell (GSC) specific peptides sequences. Using this strategy, we identified Vav3, a guanine exchange factor that plays a role in the maintenance of GSCs. In order to further identify novel proteins that may play a role in GSC maintenance, we have employed an in vitro biopanning strategy against GSCs isolated from patient derived glioblastoma cell lines grown in culture. Several peptides isolated using this strategy matched peptides that were separately isolated using the in vivo biopanning technique, validating the ability of these selection strategies to achieve consensus peptide sequences that are specific for GSC binding. In silico analysis of these peptides using a BLAST search as previously described revealed CD48. Analysis of CD48 showed that it is preferentially expressed in glioblastoma cells with a potential role in tumor maintenance. Together, these studies validate the effectiveness of utilizing different phage display biopanning strategies to isolate novel proteins that may play a vital role in maintenance of glioblastomas.
Breast carcinoma with amplified HER2: A gene expression signature specific for trastuzumab resistance and poor prognosis.
Authors: T. Khoury, K. Kanehira, D. Wang, F. O. Ademuyiwa, W. Mojica, J. Conroy, N. Nowak, S. Liu
Journal: Journal of Clinical Oncology (2010)

657 Background: Recent trials have demonstrated remarkable efficacy from combined trastuzumab and chemotherapy in the adjuvant setting of breast cancer. However, trastuzumab resistance continues to be problematic. We intended to explore the possibility of the presence of a gene expression signature for trastuzumab resistance. Methods: Forty-one consecutive breast carcinoma cases that had amplified HER2 and fresh frozen tissue available were collected. Twelve patients were treated with trastuzumab, 3 of which had recurrence. Eleven patients were not treated with trastuzumab, 6 of which had recurrence. Human genome-wide Illumina bead microarrays were used to identify differentially expressed genes (DEGs) for nonrecurrence versus recurrence in trastuzumab treated (TT) patients, and in trastuzumab nontreated (TNT) patients, respectively. Microarrays were also used to identify DEGs from separate comparisons involving collected patients' clinicopathologic data (age, race, tumor stage, hormonal status, and menopausal status). Results: TheDEGs for nonrecurrence versus recurrence in the TT group were distinct from those for nonrecurrence versus recurrence in the TNT group. They were also distinct from the DEGs obtained from comparisons involving other collected patients' clinicopathologic data. While DEGs in the TT group were enriched in the DNA binding, those in the TNT group are enriched in immunity and defense. The HER2 pathway was found to be significantly disregulated only in the TT group. None of the known genes that have been described to be involved in trastuzumab resistance showed any significant changes at transcriptional level. Conclusions: Differential expression of key genes indentified in this study might offer an insight into a possible mechanism of trastuzumab resistance in breast carcinoma, and might emerge as potential biomarkers for diagnosis and treatment of trastuzumab resistance. No significant financial relationships to disclose.
Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer: Results from the GeparQuattro study (GBG 40).
Authors: G. Von Minckwitz, S. Darb-Esfahani, S. Loibl, J. B. Huober, H. Tesch, C. Solbach, F. Holms, H. Eidtmann, K. Diedrich, M. Just, M. Clemens, C. Hanusch, I. Schrader, S. Henschen, G. Hoffmann, K. Tiemann, K. Diebold, M. Untch, C. Denkert
Journal: Journal of Clinical Oncology (2011)

6 Background: Adjacent ductal carcinoma in situ (DCIS) is in found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Methods: Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Results: Fifty nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (p=0.033). Presence of adjacent DCIS was an independent negative predictor of pCR (odds ratio 0.42 [95% CI 0.2-0.9], p=0.027). Adjacent DCIS area decreased from pre-treatment to surgery (r=0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r=0.892) and after treatment (r=0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (p=0.055). Conclusions: HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.
Impaired Activation of NFκB in T Cells From a Subset of Renal Cell Carcinoma Patients Is Mediated by Inhibition of Phosphorylation and Degradation of the Inhibitor, IκB
Authors: Weijun Ling, Patricia Rayman, Robert Uzzo, Peter Clark, Hyung Jin Kim, Raymond Tubbs, Andrew Novick, Ronald Bukowski, Thomas Hamilton, James Finke
Journal: Blood (1998)
Trends in the Severity of Self-Poisoning
Authors: J J A McAleer, G J J Murphy, R H Taylor, J L C Moran, F A O'Connor
Journal: Journal of the Royal Society of Medicine (1986)

Of 2947 patients admitted to a district general hospital over an 11-year period for the management of self-poisoning, 148 (5%) required intensive care unit (ICU) treatment. There was a significant increase in the number of self-poisonings admitted each year, whereas the number requiring ICU admission did not change. Therefore the proportion of patients requiring ICU admission fell significantly over the study period (P less than 0.0005). Of 898 patients admitted from 1973 to 1977, 62 (6.9%) were treated in ICU. Of 2049 patients admitted from 1978 to 1983, 86 (4.2%) required ICU treatment. It is felt that this trend is explained by a rise in parasuicidal self-poisonings. The impact of change in drug availability is evident in the significant reduction in ingestion of sedative barbiturates.
Colon Epithelium. II. In Vivo Studies of Colon Carcinogenesis. Light Microscopic, Histochemical, and Ultrastructural Studies of Histogenesis of Azoxymethane-Induced Colon Carcinomas in Fischer 344 Rats&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn4"&gt;4&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn5"&gt;5&lt;/xref&gt;
Authors: A K Shamsuddin, B F Trump
Journal: JNCI Journal of the National Cancer Institute (1981)

The sequential changes during histogenesis of colon carcinoma were studied with the use of 60 male inbred F344 rats given weekly im injections of 8 mg azoxymethane (ADM)/kg and serially killed at regular intervals. The malignant potentiality of induced carcinomas was confirmed by observation of invasion, metastases, and transplantation in inbred animals. The changes observed were mostly in the descending colon. Seemingly, the mucus initially increased but later decreased. The earliest changes observed by light microscopy were dilatation and distortion of colon crypts, hypercellularity of the crypts, and increased production of normally secreted sulfomucin. Later, the increased mucus secreted was sialomucin. Eventually, mucus production lessened, and the cells became more basophilic with high nucleocytoplasmic ratios. Ultrastructural examination revealed increased amounts of free cytoplasmic polysomes, diminished amounts of mucus, large nuclei with indentation of the nuclear membrane, and large, prominent nucleoli. The hypercellular crypts also showed an increased number of intestinal endocrine cells. Intestinal endocrine cells with dense core secretory granules were also frequent in the frankly carcinomatous lesions. Foci of atypical epithelium consisting of cells with basophilic cytoplasm and large nuclei were seen in grossly normal, flat mucosal areas in rats that received only a few doses of the carcinogen and that had not yet developed grossly visible tumors and also in rats bearing grossly obvious tumors in the colon. Several such foci were clearly invading the underlying submucosa and the muscle layers. Single cells in several such crypts were ultrastructurally seen to break the basal lamina and invade. Fully developed carcinomas were both polypoid and flat. No benign polyp-cancer sequence could be demonstrated in this model. Thus in this model predominance of sialomucin was associated with premalignant changes in colon epithelium, cells in the crypts either singularly or in multiple underwent carcinomatous changes de novo in the flat mucosa, and multiple foci of microcarcinomas developed during ADM carcinogenesis. Therefore, counting only the gross tumors may not reflect the true incidence of neoplasia.
Salmonella Montevideo infections associated with salami products made with contaminated imported black and red pepper - United States, July 2009-April 2010.
Authors: E. Julian, K. MacDonald, N. Marsden-Haug, R. Bonavolante, S. Otero, J. Nosari, C. Austin, D. von Stein, A. Garvey, G. Kline, C. Lord, R. Groepper, M. Parish, D. Elder, J. Pringle, J. Besser, S. Brown, K. Cooper, S. Sodha, I. Williams, C. Barton, L. B. Gieraltowski
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
ATPS-35RADIATION TREATMENT INCREASES PHOSPHATIDYLSERINE EXTERNALIZATION ON GLIOBLASTOMA CELLS – INDICATES POTENTIAL TARGET FOR THERAPY
Authors: Nida Hussain, Harold Davis, Subrahmanya Vallabhapurapu, Zhengtao Chu, Victor Blanco, Xiaoyang Qi
Journal: Neuro-Oncology (2015)

INTRODUCTION: Glioblastoma Multiforme (GBM) is the most aggressive form of primary brain tumor with a median survival of <15 months from diagnosis. Cancer-selective nanotherapeutic agents such as SapC-DOPS, which targets phosphatidylserine (PS) on the cell surface, offer an alternative paradigm for treatment of intracranial neoplasms due to their ability to transverse the BBB without altering it. We have previously shown a strong association between surface PS levels and SapC-DOPS-induced killing of cancer cells. We hypothesized that radiation treatment would increase PS externalization in GBM cells which may enhance GBM cytotoxicity when combined with SapC-DOPS. METHODS: Cell Surface PS Analysis: Human derived GBM cells (U87ΔEGFR-Luc) were exposed to 0, 2, 6, 10 or 16 Gy then 24 hours later, the cells were stained with Annexin V-FITC and evaluated for cell surface PS using flow cytometry. Immunofluorescent Staining: Human GBM cells (U87ΔEGFR-Luc) were injected intracranially into nude mice and allowed to grow until ∼3 mm3. Microscope slide sections from these brains were probed with fluorescently labeled SapC-DOPS. The following day, slides were imaged using fluorescence microscopy. RESULTS: Our study showed that fluorescently labeled SapC-DOPS selectively targeted GBM cells but did not stain normal brain tissue. In addition, we demonstrated that GBM cell lines exhibited a positive correlation between surface exposed PS levels and radiation responses. A significant increase in PS externalization was demonstrated by U87ΔEGFR-Luc cells following ionizing radiation therapy at 6, 10 and 16 Gy (p = 0.009, 0.004 and 0.001); respectively, compared to non-irradiated cells. CONCLUSIONS: We have demonstrated that SapC-DOPS effectively and specifically targets cancer cells that express high PS on their surface and have shown that radiation increases PS expression on GBM cells. These studies provide a basis for combination therapies where increasing extracellular PS via radiation therapy, coupled with SapC-DOPS may enhance cancer cytotoxicity.
The Expansion Of CML Clones Initiates At The CMP Stage, and Is Associated With The Down-Regulation Of IRF8 and GFI1
Authors: Kohta Miyawaki, Hirotake Kusumoto, Tadafumi Iino, Kentaro Kohno, Hirofumi Tsuzuki, Takahiro Shima, Yoshikane Kikushige, Yojiro Arinobu, Katsuto Takenaka, Toshihiro Miyamoto, Hiromi Iwasaki, Koichi Akashi
Journal: Blood (2013)
Corrigendum to “Alternatively activated (M2) macrophages promote tumour growth and invasiveness in hepatocellular carcinoma” [J Hepatol 2015;62:607–616]
Authors: Oscar W.H. Yeung, Chung-Mau Lo, Chang-Chun Ling, Xiang Qi, Wei Geng, Chang-Xian Li, Kevin T.P. Ng, Stuart J. Forbes, Xin-Yuan Guan, Ronnie T.P. Poon, Sheung-Tat Fan, Kwan Man
Journal: Journal of Hepatology (2016)
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Suppression and Regression of a Transplanted Tumor in the Guinea Pig Colon Mediated by &lt;italic&gt;Mycobacterium bovis&lt;/italic&gt;, Strain BCG
Authors: R P Harmel, B Zbar, H J Rapp
Journal: JNCI Journal of the National Cancer Institute (1975)

The growth in the colon wall of a diethylnitrosamine-induced hepatocarcinoma was suppressed by BCG. Injection of BCG into established colon-wall tumors caused tumor regression. Successful therapy required a limited tumor burden. Guinea pigs in which growth of the neoplasm was suppressed at the site of BCG infection developed systemic tumor transplantation immunity.
Pharmacodynamic relationships between asparagine INPUT (Imax) post asparaginase (ASNase) therapy and outcome in SR ALL patients (CCG-1962)
Authors: V. I. Avramis, E. H. Panosyan, I. A. Avramis, F. Dorey, P. Gaynon
Journal: Journal of Clinical Oncology (2006)

9025 Background: ASNase is an important agent in the treatment of childhood acute lymphoblastic leukemia. Most other chemotherapeutic agents require entry into cells and some variety of activation. ASNase acts unmodulated and totally outside of cells, targeting extracellular ASN and glutamine. Several investigators have described a relationship between ASNase activity and ASN. In vivo, the equilibrium asparagine level depends on the input rate of ASN derived from the nutrients plus the de novo biosynthesis minus its deamination from the serum ASNase activity. Imax is a pharmacodynamic (PD) parameter developed in 1980’s representing the cumulative input of ASN from nutrients and de novo biosynthesis. Of note, glutamine is the amino group source for the synthesis of ASN from aspartate. In Enzyme-substrate relationships a sigmoid relationship exists that reaches a maximum product formation (Imax). We reported a link between Day 14 ASN depletion - not ASNase activity - and response for children with ALL in first marrow relapse (Jarrar et al, 2006). Methods: On CCG-1962, 117 children with standard risk ALL were randomly allocated to native or pegylated ASNase. Relevant PK-PD parameters have been reported (Avramis et al, Blood 2002). ASNase activity was not predictive of EFS. Induction (IND) Day 3 - 24 serum ASN levels were fitted into a PD model and the Imax values were evaluated for 112 patients. Results: The median Imax values were 1E-6 nmoles/ml/min in all 112 (range 2.0E-2 to 1.0E-7) and in the native or PEG-ASNase randomized patients. The mean values were 1.1E-3.1±3E-3 in 112 patients and 1.5E-3±4.0E-3 &amp; 1.1E-3±3.0E-3 nmoles/ml/min in the native or PEG-ASNase randomized patients. We examined EFS by Imax values in lifetable analyses. High Imax values predicted statistically poorer outcome (p&lt;0.00001) with various cut-off values (e.g., Imax ≥1x 10 −3 or Imax ≥5 × 10 −4 nmoles/ml/min. The effect was similar in the native and pegylated ASNase subsets. ASNase activity was not prognostic. Conclusions: Hence, ASN Imax in serum is a treatment-independent PD prognostic factor in a subset of children with standard risk ALL. Strategies to provide uniform therapeutic effect among patients with differing Imax are under consideration. No significant financial relationships to disclose.
Cigarette Smoke Carcinogenesis: Importance of Tumor Promoters&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Van Duuren, B. L., Sivak, A., Katz, C., Melchionne, S.
Journal: JNCI Journal of the National Cancer Institute (1971)

Journal Article Cigarette Smoke Carcinogenesis: Importance of Tumor Promoters Get access B. L. Van Duuren, B. L. Van Duuren Laboratory of Organic Chemistry and Carcinogenesis, Institute of Environmental Medicine, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Sivak, A. Sivak Laboratory of Organic Chemistry and Carcinogenesis, Institute of Environmental Medicine, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar C. Katz, C. Katz Laboratory of Organic Chemistry and Carcinogenesis, Institute of Environmental Medicine, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Melchionne S. Melchionne Laboratory of Organic Chemistry and Carcinogenesis, Institute of Environmental Medicine, New York University Medical Center, New York, New York 10016 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 47, Issue 1, July 1971, Pages 235–240, https://doi.org/10.1093/jnci/47.1.235 Published: 01 July 1971 Article history Received: 26 February 1971 Accepted: 31 March 1971 Published: 01 July 1971
Knife-assisted snare resection: a novel technique for resection of scarred polyps in the colon
Authors: Fergus Chedgy, Rupam Bhattacharyya, Kesavan Kandiah, Gaius Longcroft-Wheaton, Pradeep Bhandari
Journal: Endoscopy (2016)

<b>Background and study aims:</b> There have been significant advances in the management of complex colorectal polyps. Previous failed resection or polyp recurrence is associated with significant fibrosis, making endoscopic resection extremely challenging; the traditional approach to these lesions is surgery. The aim of this study was to evaluate the efficacy of a novel, knife-assisted snare resection (KAR) technique in the resection of scarred colonic polyps. <b>Patients and methods:</b> This was a prospective cohort study of patients, in whom the KAR technique was used to resect scarred colonic polyps > 2 cm in size. Patients had previously undergone endoscopic mucosal resection (EMR) and developed recurrence, or EMR had been attempted but was aborted as a result of technical difficulty. <b>Results:</b> A total of 42 patients underwent KAR of large (median 40 mm) scarred polyps. Surgery for benign disease was avoided in 38 of 41 patients (93 %). No life-threatening complications occurred. Recurrence was seen in six patients (16 %), five of whom underwent further endoscopic resection. The overall cure rate for KAR in complex scarred colonic polyps was 90 %. <b>Conclusions: </b>KAR of scarred colonic polyps by an expert endoscopist was an effective and safe technique with low recurrence rates.
Mice Homozygous for a Truncated Form of CREB-Binding Protein Exhibit Defects in Hematopoiesis and Vasculo-angiogenesis
Authors: Yuichi Oike, Nobuyuki Takakura, Akira Hata, Tadashi Kaname, Miwa Akizuki, Yuji Yamaguchi, Hirofumi Yasue, Kimi Araki, Ken-ichi Yamamura, Toshio Suda
Journal: Blood (1999)
The Clinical and Immunological Effects of Pru p 3 Slit on Peach and Peanut Tolerance in Patients with Systemic Allergic Reactions
Authors: Francisca Gómez, Gador Bogas, Miguel González, Paloma Campo, Maria Salas, J.A. Huertas, Araceli Diaz-Perales, Domingo Barber, María J. Rodriguez, Miguel Blanca, Cristobalina Mayorga, María José Torres
Journal: Journal of Allergy and Clinical Immunology (2016)