tbuckley/cabot-search huggingface dataset:
Expression of nuclear factor Y, subunit C (NFY-C), and retinoic acid receptor-related orphan receptor alpha (RORA) in colorectal adenocarcinoma.
Authors: T. Makatsoris
Journal: Journal of Clinical Oncology (2010)

e14085 Background: NFY-C gene is one of the three subunits of nuclear factor Y, a highly conserved transcription factor, which binds with high specificity to CCAAT motifs in the promoters of various genes. RORA is a member of the NR1 subfamily of nuclear hormone receptors. It can bind as a monomer or a homodimer to hormone response elements upstream of several genes to enhance their expression. Methods: mRNA levels of NFY-C and RORA were evaluated by quantitative RT-PCR in 81 neoplastic colorectal tissue specimens and 51 normal tissue specimens from patients with colorectal adenocarcinoma. All patients had undergone curative resections at the University Hospital of Patras, between 1995 and 2005. mRNA levels were normalised to the Alu-Sq levels and were analysed in relation to clinicopathological parameters. Protein expression of NFY-C was assessed by immunochemistry in 60 malignant and 20 normal samples from patients with colorectal adenocarcinoma. Results: There was a significant difference in the mRNA expression levels of NFY-C and RORA between normal and malignant tissues (p < 0.001 and p = 0.015, respectively). The mRNA levels of NFY- C and RORA were also related to the primary site of the tumor (p = 0.05 and p = 0.03, respectively). A 3-year survival benefit was also observed in patients with high expression levels of NFY-C (p = 0.023). There was no correlation between the mRNA levels of NFY-C or RORA and age, gender, grade, stage and relapse of the disease. However, mRNA levels of NFYC of stage B patients were significantly correlated with time to disease progression (p = 0.035). NFY-C protein was detected only in the cytoplasm both in malignant and normal tissues, with strong and weak intensity respectively. NFYC protein expression levels were correlated with mRNA expression levels of NFYC in malignant tissues (p = 0.011) and with the primary site of the tumour (p < 0.001). Conclusions: NFY-C and RORA exhibited elevated levels in colon carcinomas compared to normal tissue samples indicating a possible role for these molecules in colon carcinogenesis. The role of NFY-C and RORA in colorectal cancer warrants further investigation. No significant financial relationships to disclose.
Perspectives Among Primary Care Providers and Hematologist/Oncologists in the Coordination of Care for Patients with Hematologic Malignancies
Authors: Haleh Kadkhoda, Clare Karten, Kevin C. Oeffinger, Kanti R. Rai, S. Frieda Pearce, Margaret Miller, Jennifer J. Brown, Nancy Roepke, Ryan Palmore, Jennifer Garick
Journal: Blood (2011)
The Pharmacogenetic Background of the Host Is An Independent Predictor of Outcome and Toxicity in Diffuse Large B Cell Lymphoma Treated with R-CHOP21
Authors: Davide Rossi, Silvia Rasi, Silvia Franceschetti, Daniela Capello, Andrea Castelli, Lorenzo De Paoli, Antonio Ramponi, Annalisa Chiappella, Enrico M. Pogliani, Umberto Vitolo, Ivo Kwee, Francesco Bertoni, Annarita Conconi, Gianluca Gaidano
Journal: Blood (2008)
Abstract A23: Characterization of diverging molecular and phenotypic responses under changing extracellular matrix stiffness in MCF10A cells
Authors: Sonya Liu, Russell Bainer, Yoshihiro Yui, Colin Flinders, Parag Mallick, Valerie Weaver, Shannon Mumenthaler
Journal: Cancer Research (2016)

Abstract Tissue stiffness has emerged as an important regulator in the maintenance of normal cellular processes. In general, solid tumors are known to be much stiffer than normal tissue, with increased extracellular matrix (ECM) density being indicative of a higher risk for many cancers, including those of the breast. Over the course of breast cancer progression, the ECM becomes increasingly stiffer, a phenomenon which is known to be a driver of malignancy. In a 3D culture system using self-assembling peptide (SAP) gels, we grew MCF10A acini under a dynamic range of stiffness environments (140-5800 Pa). Under normal breast tissue elasticity, mammary epithelial cells form rounded, polarized acini with cleared lumens. However, in tumor-like stiffnesses, the same cells form non-polarized, collapsed structures that invade into the gel. To investigate the specific genes and pathways affected by stiffness, we have conducted tandem mass spectrometry to identify protein expression changes in MCF10A cells grown on SAP gels of increasing stiffness. Interestingly, the resulting analysis showed that cells grown on higher stiffnesses exhibit greater variation in protein expression. These divergent force-regulated molecular pathways are involved in a variety of cellular functions, including cell adhesion and migration, metabolism, and the immune response, among others. This study underscores the significance of mechanical forces exerted by the ECM, and signifies the first large-scale proteomic screen carried out to analyze heterogeneous cellular responses to changing stiffness environments. Citation Format: Sonya Liu, Russell Bainer, Yoshihiro Yui, Colin Flinders, Parag Mallick, Valerie Weaver, Shannon Mumenthaler. Characterization of diverging molecular and phenotypic responses under changing extracellular matrix stiffness in MCF10A cells. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr A23.
GW26-e4800 Relation of resistin to proprotein convertase subtilisin-kexin type 9 levels in coronary artery disease patients with different nutritional status
Authors: Sha Li, Ruixia Xu, Yan Zhang, Yuanlin Guo, Chenggang Zhu, Geng Liu, Qian Dong, Jianjun Li
Journal: Journal of the American College of Cardiology (2015)
Accumulation of lymphocytes following adoptive transfer of allogeneic T lymphocytes equipped with an HLA-A2 restricted, MART-1 reactive T Cell Receptor
Authors: L. Duval, H. Schmidt, T. Steiniche, K. Kaltoft, K. Fode, J. J. Jensen, S. M. Soerensen, M. I. Nishimura, H. von der Maase
Journal: Journal of Clinical Oncology (2007)

3050 Background: Adoptive transfer of cytotoxic, antigen specific lymphocytes represents an immunotherapeutic approach currently investigated for the ability to reinforce immunologic reactivity against tumor cells in cancer patients. The present study aimed to elucidate immunological reactions during a phase I immunotherapeutic trial with receptor modified T lymphocytes in stage IV melanoma. The aim was in particular to assess if treatment induced a local immunologic response in terms of accumulation of immune cells in metastases used for injection of cells, and if such a response propagated to metastases not used for injection of cells. Treatment consisted of intra-tumoral injections of allogeneic, cytotoxic T lymphocytes equipped with a MART-1 antigen recognizing T cell receptor. Expression of the T cell receptor was obtained through transduction with the receptor-encoding gene. Methods: Core needle were sampled both from metastases used for injection of cells, and from metastases not used for injection of cells. Biopsies were sampled at day 1, before any administration of cells, and at day 14 following the first 4 injections administered at day 1, 4, 7 and 10. Hereafter, biopsies were formalin fixed, paraffin embedded and immunohistochemically stained by a two layer detection technique with antibodies against; CD4, CD8 and CD57, before enumeration by a stereological counting technique.Wilcoxon matched pairs signed rank-sum test was used for comparison. Results: A total of forty six biopsies were sampled from twelve patients without complications. The number of CD8 positive T lymphocytes and NK cells (CD57+) was shown to increase significantly from day 1 to 14 in metastases used for injection. Analyses of the number of cells in metastases which were not directly used for injection of cells showed differences in some patients but overall, changes were not significant. Conclusions: The current study showed a statistically significant accumulation of immune cells in metastases following intra-tumoral injections of allogeneic, antigen specific, cytotoxic T lymphocytes in stage IV melanoma patients. The number of immune cells in metastases not used for injection did not change significantly during treatment. No significant financial relationships to disclose.
Sunitinib in patients with multiply relapsed or cisplatin-refractory germ cell cancer: A CUOG/GTCSG cooperative phase II study.
Authors: C. K. Kollmannsberger, K. Oechsle, T. Cheng, F. Mayer, P. Czaykowski, E. Winquist, L. Wood, M. Fenner, K. N. Chi, C. Bokemeyer
Journal: Journal of Clinical Oncology (2010)

4582 Background: Patients (pts) with multiply relapsed or cisplatin-refractory metastatic germ cell cancer (GCT) have limited treatment options and a very poor prognosis. We investigated the efficacy and toxicity of sunitinib, an oral multikinase inhibitor, in these pts. Methods: Cisplatin-refractory disease was defined as progression or relapse within 4 weeks after cisplatin-based chemotherapy or relapse after salvage high-dose chemotherapy (HDCT). Sunitinib was administered at a dose of 50 mg daily for 4 weeks followed by a 2 week break. Response was evaluated every 6 weeks. A Simon 2-stage design with type I and II errors of ≤ 20% and ≤ 5%, respectively, was used. Results: A total of 33 pts, 88% nonseminoma and 12% seminoma, with a median age of 32 years [22-54] were included. Pts were pretreated with a median of 2 [1-6] cisplatin containing regimens, 67% had had prior HDCT and 33% were late relapses. 55% were considered cisplatin-refractory or absolute cisplatin-refractory. A total of 66 cycles were administered. Toxicity in these heavily pretreated pts was generally acceptable. The most common sunitinib-related toxicities included fatigue (36%), anorexia (21%), diarrhea (27%), stomatitis (39%), nausea (33%), hand-foot syndrome (12%), dyspepsia (27%) and skin rash (18%). Grade 3/4 toxicities, most frequently myelotoxicity, mucositis, and hand-foot syndrome, occurred in 13 patients. No unexpected side effects were observed. 32/33 pts were evaluable for response. Two confirmed partial responses (PRs) were seen (one in seminoma, one in nonseminoma) and 2 unconfirmed PRs (one in seminoma, one in nonseminoma) for a total response rate of 12%. Disease stabilization of short duration was seen in 13 pts (median 2.34 [1.61-6.48] months). Three months progression-free survival rate was 26% [14-47%]. Six month survival rate was 36% [23.2%-57.1%] and 1 year survival rate was only 5% [0.8%-31.0%]. Conclusions: This is one of the first completed phase II studies of a targeted agent in GCT. Treatment with sunitinib is feasible in these heavily pretreated GCT pts, although exhibiting modest activity as monotherapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer
Topotecan therapy as salvage in heavily pretreated ovarian cancer patients (hpocp)
Authors: G. B. Wcislo, L. Bodnar, A. Nasilowska, K. Szarlej-Wcislo, C. Szczylik
Journal: Journal of Clinical Oncology (2006)

15057 Background: Topotecan is utilized as to a second-line chemotherapy agent in ovarian cancer. The third or more line of chemotherapy is possibly to use against ovarian cancer which is chemosensitive even when this malignancy progressed. Methods: Prior chemotherapy with platinum compounds, paclitaxel, doxorubicin was used. Topotecan was given as 30-minute infusion at the dose of 1.5 mg/m 2 through 5 consecutive days every 21 days. Toxicity profile was assessed according to NCI CTC and response was measured while met RECIST and CA-125 criteria described by Rustin et al. Results: Between 2001 and 2005, 22 hpocop were enrolled onto the study and received at least two cycles of topotecan salvage, median 6 (range 2–6). The patients were previously treated with chemotherapy and characterised 37% (8/22) as platinum-sensitive, 9% (2/22) as partial platinum- sensitive, 27% (6/22) as platinum-resistant and 27% (6/22) as platinum-refractory. Twenty hpocp of the total number of 22 were monitored after chemotherapy through fulfilling RECIST criteria: 7/20 (35%) -PR, 7/20 (35%)-NC, 8/20 (40%)-PD. The clinical response rate in 20 patients with assessable CA 125 levels was 30% (6/20) with 75% response, and 15% (3/20) with 50% response by Rustin et al. criteria. Time to progression of ovarian cancer was median 5,0 months, SD ± 2.0 (range from 2 to 7) and median survival 8 months, SD ± 21 (range from 2 to 39). Toxicity profile was recorded as following: neutropenia 3/4th grade in 8/22 (36%), anaemia 3/4th grade in 9/22 (41%), thrombocytopenia 4th grade in 6/22 (27%), and non-hematologic toxicity relied on alopecia 7/22 (32%). We have not observed fatal outcome after topo salvage therapy. Conclusions: Topotecan could be involved in therapy of patients with ovarian cancer previously heavily pretreated. It offers clinical benefits in ovarian cancer course as to be a stabilised disease despite prior chemotherapy but reliable management alleviates hematologic toxicity. No significant financial relationships to disclose.
Spice and all things nasty: the challenge of synthetic cannabinoids
Authors: Nicola J Kalk, Alastair Boyd, John Strang, Emily Finch
Journal: BMJ (2016)

An evolving problem that is difficult to detect and treat

The Psychoactive Substances Act 2016, which came into force in May, signals a new approach to drug controls in the UK. For the first time, the basis for illegality is pharmacological action rather than chemical structure. The act made it illegal to produce or supply “spice” or synthetic cannabinoids and to possess them in a custodial setting.

Synthetic cannabinoids are a group of structurally unrelated compounds that act at the cannabinoid receptors CB1 and CB2. Spice is the commonest UK term, but there are more than 500 other street names, including black mamba and annihilation.1 The chemicals are synthesised in a laboratory, dissolved in a solvent, then sprayed onto plant material, which is smoked or, less commonly, taken orally or injected. Previous attempts to ban synthetic cannabinoids failed because compounds with novel structures could be produced quickly. The clinical challenge of these substances mirrors the legislative challenge in that the severity of harms demands a substantial response while their chemical variety makes monitoring …
NT-Probnp as a Marker of Cardiopulmonary Compromise and Exercise Limitation In Adults with Sickle Cell Anemia In the Walk-PHaSST Study
Authors: Mehdi Nouraie, Robyn J. Barst, Erika Berman Rosenzweig, Vandana Sachdev, Roberto F. Machado, Kathryn Hassell, J. Simon R. Gibbs, Jane A. Little, Dean E. Schraufnagel, Lakshmanan Krishnamurti, Enrico M Novelli, Reda E. Girgis, Claudia R. Morris, David B. Badesch, Sophie Lanzkron, Oswaldo Castro, Jonathan C. Goldsmith, Mark Gladwin, Victor R. Gordeuk, Gregory J. Kato
Journal: Blood (2010)
Second-line systemic therapy for esophageal cancer
Authors: M. G. Martin, A. Wang-Gillam, M. A. Waqar, T. H. Fong, F. Gao, R. Govindan, D. Morgensztern
Journal: Journal of Clinical Oncology (2008)

15623 Background: Esophageal cancer is a highly lethal malignancy. Virtually all patients with metastatic disease will develop progressive disease (PD) after initial therapy and are often considered for subsequent treatment. There are only limited data available regarding the efficacy of second-line chemotherapy for advanced esophageal cancer. Methods: We conducted a retrospective review of all patients with esophageal cancer who received second-line systemic therapy at Washington University from 1996 to 2006. We report here the preliminary descriptive analysis of our data Results: Seventy-two esophageal cancer patients who received second-line chemotherapy were identified. Of these, 41 (56.9%) received chemoradiation therapy and 31 (43.1%) received chemotherapy alone as the first- line treatment. Sixty-one (84.7%) patients achieved clinical benefit (defined as complete response, partial response and stable disease), while 11 patients experienced disease progression. In the second-line setting, 32 (44.4%) received monotherapy, 35 (48.6%) received doublets and 5 received three drug combination (7%). The most commonly used single agents were paclitaxel (37.1%), vinorelbine (27.2%) and docetaxel (24.2%) whereas the most common used doublets were carboplatin/paclitaxel (31.4%) and cisplatin/irinotecan (28.6%). Median overall survival (OS) from the start of 2nd line therapy was 7.0 months. Overall clinical benefit (stable disease and partial response) of the second- line chemotherapy was 56.4% with a median time to progression (TTP) of 3.3 months. Patients achieving clinical benefit from 1st line therapy has a longer TTP of 3.9 months compared to a 2.6 months in patients progressed on 1st line. Thirty-six (50%) patients received third line treatment with marginal benefit suggested by a clinical benefit of 21.6% and TTP of 1.85 months. Conclusions: Benefit from second-line chemotherapy in esophageal cancer is modest and usually brief. Whenever possible, these patients should be enrolled in clinical trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Aventis, Genentech, Lilly, Pfizer Merck
Gene Expression Profiling Identifies Oncogenic Molecular Pathways in T-Lymphoma Induction by SL3-3 Retrovirus Insertional Mutagenesis in Inbred NMRI Mice.
Authors: Karen Dybkaer, Karina D. Sørensen, Jörg Schmidt, Francesco d’Amore, Finn S. Pedersen
Journal: Blood (2005)
Significant Effect of Polymorphisms in<i>CYP2D6</i>on Response to Tamoxifen Therapy for Breast Cancer: A Prospective Multicenter Study
Authors: Hitoshi Zembutsu, Seigo Nakamura, Sadako Akashi-Tanaka, Takashi Kuwayama, Chie Watanabe, Tomoko Takamaru, Hiroyuki Takei, Takashi Ishikawa, Kana Miyahara, Hiroshi Matsumoto, Yoshie Hasegawa, Goro Kutomi, Hiroaki Shima, Fukino Satomi, Minoru Okazaki, Hisamitsu Zaha, Mai Onomura, Ayami Matsukata, Yasuaki Sagara, Shinichi Baba, Akimitsu Yamada, Kazuhiro Shimada, Daisuke Shimizu, Koichiro Tsugawa, Arata Shimo, Ern Yu Tan, Mikael Hartman, Ching-Wan Chan, Soo Chin Lee, Yusuke Nakamura
Journal: Clinical Cancer Research (2016)

Purpose: CYP2D6 is the key enzyme responsible for the generation of the potent active metabolite of tamoxifen, "endoxifen." There are still controversial reports questioning the association between CYP2D6 genotype and tamoxifen efficacy. Hence, we performed a prospective multicenter study to evaluate the clinical effect of CYP2D6 genotype on tamoxifen therapy.Experimental Design: We enrolled 279 patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative, invasive breast cancer receiving preoperative tamoxifen monotherapy for 14 to 28 days. Ki-67 response in breast cancer tissues after tamoxifen therapy was used as a surrogate marker for response to tamoxifen. We prospectively investigated the effects of allelic variants of CYP2D6 on Ki-67 response, pathological response, and hot flushes.Results: Ki-67 labeling index in breast cancer tissues significantly decreased after preoperative tamoxifen monotherapy (P = 0.0000000000000013). Moreover, proportion and Allred scores of estrogen receptor-positive cells in breast cancer tissues were significantly associated with Ki-67 response (P = 0.0076 and 0.0023, respectively). Although CYP2D6 variants were not associated with pathologic response nor hot flushes, they showed significant association with Ki-67 response after preoperative tamoxifen therapy (P = 0.018; between two groups, one with at least one wild-type allele and the other without a wild-type allele).Conclusions: This is the first prospective study evaluating the relationship between CYP2D6 variants and Ki-67 response after tamoxifen therapy. Our results suggest that genetic variation in CYP2D6 is a key predictor for the response to tamoxifen in patients with breast cancer. Clin Cancer Res; 23(8); 2019-26. ©2016 AACR.
Abstract C10: The role of FIH in macrophage function
Authors: Milos Gojkovic, Helene Rundqvist, Pedro Veliça, Randall S. Johnson
Journal: Cancer Research (2016)

Abstract The cells of the immune system have to be able to exert its functions in areas of low oxygen tension. In macrophages, functions such as phagocytosis, migration and antigen presentation has been shown to be partly dependent on the hypoxia sensitive transcription factor HIF-1 activation. Previous studies on tissue specific deletion of HIF-1 in macrophages showed decreased infiltration, activation and bacterial killing, as well as decreased cancer progression and growth in the MMTV-PyMT mouse model of breast cancer. However, the effects of increased HIF-1 expression and activity in macrophages are not fully understood. In light of the current literature, we hypothesize that increased activity of HIF-1 may lead to enhanced immunological activity in macrophages. When we knock down FIH (a hydroxylase that inhibits HIF-1 activity) in Raw cells, migration towards a PyMT derived tumor cell line increases. FIH knock down macrophages was characterized by increased MHC Class II surface expression and improved phagocytosis under normoxic conditions, however the difference between knock down FIH and wild type macrophages are less in hypoxic conditions, indicating that the enhanced immunological function may depend on increased HIF-1 activity. Future work includes the use of a conditional cre-loxP knockout mouse, with cre expression driven by the myeloid specific promoter for LysM, knocking out either VHL (a negative regulator of HIF stability) or FIH. These mice will also be used to investigate the role of constitutively active myeloid HIF-1 in tumor progression. Citation Format: Milos Gojkovic, Helene Rundqvist, Pedro Veliça, Randall S. Johnson. The role of FIH in macrophage function. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr C10.
A Critical Role of Blockade of Cell Differentiation in BCR-ABL-Induced B-Cell Acute Lymphoblastic Leukemia (B-ALL): Basis for Superb Therapeutic Effect on B-ALL in Mice by Promotion of Pro-B Leukemic Cell Differentiation and Treatment with Imatinib.
Authors: Yiguo Hu, Linghong Kong, Kevin Staples, Kevin Mills, John G. Monroe, Shaoguang Li
Journal: Blood (2005)