tbuckley/cabot-search huggingface dataset:
Identification of unique gene expression signatures in colon cancer stroma using microarray technology.
Authors: S. X. Wang, J. Wang, E. Ozhegov, R. Srinivasan, O. O. Olowokure, A. X. Qu, B. Aronow, V. Bogdanov
Journal: Journal of Clinical Oncology (2011)

447 Background: Microarrays are widely used to study gene expression patterns in cancer. In colorectal cancer, it has proven useful to predict recurrence. The majority of expression profiles are generated from the cancer itself. Given the increasing evidence of importance of the microenvironment for tumor invasion, progression and metastasis, we explored tumor stroma gene signature using microarrays. Methods: Four formalin-fixed paraffin embedded (FFPE) colon cancer specimen carrying a pathological stage of T3-4/N0-2 were retrieved. Tumor stroma and normal stroma were separated using microdissection technology. Random sampling was used to minimize sampling bias. Total RNA was extracted, amplified, and labeled using Nugene FFPE kit, with array analysis using Affymetrix Human Gene 1.0. Eight samples, four normal stroma and four tumor stroma, were analyzed and compared. Array data were balanced and analyzed using standard software. To identify gene signature differences in tumor vs normal stroma, ComparativeMarker analysis and unsupervised cluster analysis were carried out. Results: We identified a 969 Affymetrix probe set as a signature that is highly expressed in tumor stroma. The top 117 genes were further analyzed to carry out a pathway analysis. We found a strong signature evident in tumor stroma, and much of this signature comprised the genes of the extracellular matrix. The pathway analysis revealed evidence of the generalized IGF1/TGFbeta/CTGF/activin mediated effect on the stroma, raising the possibility that some of this derives from, or is accompanied by, angiotensin receptor signaling. Through literature search, we found that several upregulated genes (e.g., FAP) were reported to be associated with stroma activation in vitro and in vivo. Conclusions: In this study, we successfully applied microarrays to study reactive colon tumor stroma in FFPE samples. We identified a specific gene signature reflecting stromal reaction to tumor invasion. We further identified the potential pathway that was activated in the reactive tumor stroma. We provide evidence that microarrays are useful in stroma analysis and may help identify new stromal pathways with potential diagnostic and therapeutic value. No significant financial relationships to disclose.
Complete Reversion of Imatinib-Induced Hepatotoxicity in Chronic Myeloid Leukemia Patients by Low-Intermediate Dose Corticosteroid.
Authors: Dario Ferrero, Enrico M. Pogliani, Giovanna Rege-Cambrin, Carmen Fava, Giovanna Mattioli, Chiara Dellacasa, Valentina Giai, Mariella Genuardi, Paola Perfetti, Monica Fumagalli, Mario Boccadoro
Journal: Blood (2005)
BMET-21. USE OF TUMOR TREATING FIELDS IN BRAIN METASTASES FROM OVARIAN CANCER, A CASE REPORT
Authors: Manjari Pandey, Madison Michael, Jeffrey Sorenson, Brandon Baughman, Linda Smiley, Matthew Ballo
Journal: Neuro-Oncology (2016)

Ovarian cancer is the most common gynecologic cancer in United States. Central nervous system (CNS) metastases from ovarian cancer are uncommon, occurring in about 4% cases. Factors associated with increased survival are younger age, lower tumor grade, higher performance status and multimodality treatment. Standard treatment approaches include surgical resection, stereotactic radiosurgery, local radiation and medical therapy. 47 year old Caucasian woman with past medical history of hypertension presented with abdominal bloating and was diagnosed with adenocarcinoma of the ovary (stage IIIC). Neoadjuvant chemotherapy with carboplatin/paclitaxel was followed by total abdominal hysterectomy, bilateral salpingo-oophorectomy with sigmoid colectomy. Optimal debulking of her ovarian adenocarcinoma was followed by adjuvant carboplatin/paclitaxel x 1 cycle and 3 cycles of intravenous/intraperitoneal cisplatin/paclitaxel. She had no evidence of disease for over a year since initial diagnosis, but then presented with difficulty finding words. Magnetic Resonance Imaging of the brain showed over 30 intra-axial enhancing masses throughout both cerebral and cerebellar hemispheres, largest lesion measured 2.5 x 2.1 x 2.3 cm. She was started on dexamethasone and levetiracetam and was treated with whole brain radiation therapy, 30Gy in 10 fractions with some response. She was not a candidate for systemic therapy trials and was treated with continuous tumor treating fields (TTF) via the Optune device. She tolerated the treatment well and was able to taper off the steroids. She has been using the device for 5 months and has shown positive clinical and radiologic response to therapy. Use of TTFs for the treatment of brain metastases from ovarian cancer was feasible and well tolerated in this patient. This is the first case of TTF in brain metastases from ovarian cancer and showed good response with improved clinical and radiologic findings and should be further evaluated for this indication.
HER2/neu expression in locally advanced rectal cancer cUICC II/III and its correlation with long-term prognosis.
Authors: Lena-Christin Conradi, Hanna Styczen, Thilo Sprenger, Heinz Becker, Michael B. Ghadimi, Tim Beissbarth, Peter Middel, Torsten Liersch
Journal: Journal of Clinical Oncology (2012)

493 Background: With the implementation of multimodal treatment strategies including neoadjuvant radiochemotherapy (RCT), the prognosis of locally advanced rectal cancer has been improved over the last two decades. Most actual clinical trials aim to further develop therapy by intensification of agents administered. We examined Her2/neu in rectal cancer patients to evaluate its expression as a potential drug target as well as its capacity as predictive and prognostic biomarker. Methods: Two-hundred-seventy-seven patients (205 male, 72 female; median age 63.5 years) with locally advanced rectal cancer (cUICC-II/III) were included in this study. Preoperative RCT (50.4 Gy and concomitant either 5-FU or 5-FU and oxaliplatin) was administered in 236 patients followed by surgical resection with total mesorectal excision (TME). Another 41 patients received postoperative RCT. All patients were treated within phase-II/-III-trials of the German Rectal Cancer Study Group or analogous to these standardized protocols. Her2-/neu expression from pre-treatment biopsies and corresponding resection specimens were assessed by immunohistochemical staining and SISH-analysis. Results: A positive Her-2/neu expression was found in 12.3% of all pre-treatment tumor biopsy samples and in 28.7% of the resection specimens. The correlation of the pre-treatment Her-2/neu status did not show a significant correlation with the grade of tumor regression. However, patients with a higher Her-2/neu protein expression as measured in the resection specimen showed a significant survival benefit (p=0.0277) compared with patients having low intratumoral Her-2/neu expression during the follow-up (median 43 months). The 10-year survival rate was 73.2% (Her-2/neu positive) versus 60.1% (Her-2/neu negative). Conclusions: The proportion of patients with a positive Her-2/neu status is relevant in rectal cancer. Her-2/neu might potentially serve as a promising drug target in rectal cancer and should be further assessed within prospective clinical trials. Furthermore the Her-2/neu status seems to be a valuable prognostic marker within the multimodal treatment of advanced rectal cancer.
Fcγ Receptor Polymorphisms Do Not Influence Progression Free Survival (PFS) of Follicular NHL Pateints Treated with Chop Followed by Rituximab (SWOG 9800).
Authors: David G. Maloney, Barbara Pender-Smith, Joseph M. Unger, Rita M. Braziel, Jerald Radich, Oliver W. Press, Thomas P. Miller, Thomas M. Grogan, Michael LeBlanc, Richard I. Fisher
Journal: Blood (2004)
Plasma Levels of Human Neutrophil Peptides and Complement Activation Markers in Patients with Acquired Autoimmune Thrombotic Thrombocytopenic Purpura
Authors: Wenjing Cao, Huy Phu Pham, Lawrence A. Williams, Zheng Ping, Robin G. Lorenz, Marisa B. Marques, X. Long Zheng
Journal: Blood (2015)
Quality of life (QOL) analysis of the MITO8 phase 3 trial, a collaboration of MITO, Mango, AGO Study Group, BGOG, ENGOT, and GCIG
Authors: S.C. Cecere, L. Arenare, S. Signoriello, A. Bologna, I. Vergote, C. Kurzeder, G. Scambia, D. Lorusso, V. Murgia, D. Lombardi, C. Sacco, E. Breda, C. Pisano, V. Salutari, F. Raspagliesi, J. Bryce, G. Daniele, M.C. Piccirillo, C. Gallo, F. Perrone, S. Pignata
Journal: Annals of Oncology (2016)
Prediction of PARP inhibitor response and resistance utilizing a CTC phenotypic classifer in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): Results from the NCI 9012 trial
Authors: F.Y. Feng, S. Daignault-Newton, A. Jendrisak, Y. Wang, S. Greene, A. Rodriguez, J. Lee, L. Dugan, J. Siddiqui, J. Louw, C. Johnson, P. Twardowski, C. Albany, M. Stein, W.M. Stadler, L. Kunju, A.M. Chinnaiyan, M. Landers, R. Dittamore, M. Hussain
Journal: Annals of Oncology (2016)
CD49a Expression Defines Tissue-Resident CD8 + T Cells Poised for Cytotoxic Function in Human Skin
Authors: Stanley Cheuk, Heinrich Schlums, Irène Gallais Sérézal, Elisa Martini, Samuel C. Chiang, Nicole Marquardt, Anna Gibbs, Ebba Detlofsson, Andrea Introini, Marianne Forkel, Charlotte Höög, Annelie Tjernlund, Jakob Michaëlsson, Lasse Folkersen, Jenny Mjösberg, Lennart Blomqvist, Marcus Ehrström, Mona Ståhle, Yenan T. Bryceson, Liv Eidsmo
Journal: Immunity (2017)

Tissue-resident memory T (Trm) cells form a heterogeneous population that provides localized protection against pathogens. Here, we identify CD49a as a marker that differentiates CD8+ Trm cells on a compartmental and functional basis. In human skin epithelia, CD8+CD49a+ Trm cells produced interferon-γ, whereas CD8+CD49a− Trm cells produced interleukin-17 (IL-17). In addition, CD8+CD49a+ Trm cells from healthy skin rapidly induced the expression of the effector molecules perforin and granzyme B when stimulated with IL-15, thereby promoting a strong cytotoxic response. In skin from patients with vitiligo, where melanocytes are eradicated locally, CD8+CD49a+ Trm cells that constitutively expressed perforin and granzyme B accumulated both in the epidermis and dermis. Conversely, CD8+CD49a– Trm cells from psoriasis lesions predominantly generated IL-17 responses that promote local inflammation in this skin disease. Overall, CD49a expression delineates CD8+ Trm cell specialization in human epithelial barriers and correlates with the effector cell balance found in distinct inflammatory skin diseases.
Epicardial Fat Volume and the Risk of Atrial Fibrillation in the General Population Free of Cardiovascular Disease
Authors: Daniel Bos, Meike W. Vernooij, Rahil Shahzad, Maryam Kavousi, Albert Hofman, Theo van Walsum, Jaap W. Deckers, M. Arfan Ikram, Jan Heeringa, Oscar H. Franco, Aad van der Lugt, Maarten J.G. Leening
Journal: JACC. Cardiovascular imaging (2017)
Transarterial Chemoembolization using Polythylene Glycol drug-eluting beads pre-charged with irinotecan (LIFIRI®) for the treatment of Metastatic liver cancer: preliminary results
Authors: C. Aliberti, R. Carandina, D. Sarti, P. Giordani, V. Catalano, L. Mulazzani, G. Fiorentini
Journal: Annals of Oncology (2016)
OS4.8 Improving the intra-operative diagnosis of high-grade glioma using a fluorescence biomarker - A Progress Report of The GALA-BIDD Study
Authors: C. Watts, M. Jenkinson, K. Ashkan, K. Kurian, W. Qian, A. Machin, S. Price, T. Matys, G. Doughton
Journal: Neuro-Oncology (2016)

RESULTS: Mean CXCL13 concentrations in CSF were 964.2 pg/ml (475.3~1481.1 pg/ml) and 54.9 pg/ml (<1~999.7 pg/ml) in PCNSLs and other brain diseases, respectively.CXCL13 levels in CSF were significantly increased in PCNSLs compared with other brain diseases (p<0.0001).At a CXCL13 cutoff level of 475 pg/ml, the sensitivity and specificity were 100 % and 98 %, respectively.CXCL13 levels were correlated with CSF IL-10 levels (p=0.0003) and CSF IL-6 levels (p=0.0053).Median OS and PFS in all patients with PCNSL were 36 months and 25 months, respectively.And CXCL13 levels in CSF were statistically associated with OS (p=0.02) and PFS (p=0.01) in the patients with PCNSL.CONCLUSION: These results indicate that the CSF CXCL13 levels are quite useful biomarker for PCNSLs.To validate a usefulness of CSF CXCL13 for diagnosis of PCNSL, multicenter prospective large study is necessary.OS4.
Multi-Organ Involvement of Multiple Myeloma Cells In the Cases of Recent 10 Years: A Clinicopathologic Study of 81 Consecutively Autopsied Cases
Authors: Shotaro Hagiwara, Makoto Mochizuki, Hisako Endo, Risen Hirai, Akira Tanimura, Masataka Takeshita, Hirokazu Murakami, Akiyoshi Miwa
Journal: Blood (2010)
Hyperplasia of the Prostate
Authors: J. V. Frei
Journal: JNCI Journal of the National Cancer Institute (1975)

Journal Article Hyperplasia of the Prostate Get access J. V. Frei, M.D., Ph.D., F.R.C.P.(C) J. V. Frei, M.D., Ph.D., F.R.C.P.(C) The University of Western OntarioLondon, Canada Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 54, Issue 2, February 1975, Page 524, https://doi.org/10.1093/jnci/54.2.524 Published: 01 February 1975
Efficacy of Second Line Agents Dapsone &amp; Azathioprine in Children &amp; Adults with Immune Thrombocytopenia: Single Centre Experience from India
Authors: Venkatesh Shreeganesh Ekbote, Biju George, Vikram Mathews, Kavitha Lakshmi, Abhijeet Ganapule, Fausia N Abubacker, Anu Korula, Alok Srivastava
Journal: Blood (2015)
Genomic analysis of 63,220 tumors reveals insights into tumor uniqueness and targeted cancer immunotherapy strategies
Authors: Ryan J. Hartmaier, Jehad Charo, David Fabrizio, Michael E. Goldberg, Lee A. Albacker, William Pao, Juliann Chmielecki
Journal: Genome Medicine (2017)

The integration of genomics with immunotherapy has potential value for cancer vaccine development. Given the clinical successes of immune checkpoint modulators, interest in cancer vaccines as therapeutic options has been revived. Current data suggest that each tumor contains a unique set of mutations (mutanome), thus requiring the creation of individualized cancer vaccines. However, rigorous analysis of non-individualized cancer immunotherapy approaches across multiple cancer types and in the context of known driver alterations has yet to be reported. We therefore set out to determine the feasibility of a generalizable cancer vaccine strategy based on targeting multiple neoantigens in an HLA-A/B subtype-directed manner.A cancer gene-focused, hybrid capture-based genomic analysis was performed on 63,220 unique tumors. Neoantigens were predicted using a combined peptide processing and MHC-I binding prediction tool (IEDB) for all recurrent (>10 tumors) missense alterations and non-frameshift indels for the two most common HLA-A/B subtypes in North American/European populations.Despite being overwhelmingly unique overall, many mutanomes (~45%) contain at least one mutation from a set of ten mutations chosen to maximize the number of unique tumors. This held true for tumors driven by KRAS G12C (n = 1799), PIK3CA E545K (n = 1713), or EGFR L858R (n = 478) alterations, which define distinct sample subsets. We therefore hypothesized that sets of carefully selected mutations/neoantigens may allow the development of broadly applicable semi-universal cancer vaccines. To test the feasibility of such an approach, antigen processing and MHC-I binding prediction was applied for HLA subtypes A*01:01/B*08:01 and A*02:01/B*44:02. In tumors with a specific HLA type, 0.7 and 2.5% harbored at least one of a set of ten neoantigens predicted to bind to each subtype, respectively. In comparison, KRAS G12C-driven tumors produced similar results (0.8 and 2.6% for each HLA subtype, respectively), indicating that neoantigen targets still remain highly diverse even within the context of major driver mutations.This "best case scenario" analysis of a large tumor set across multiple cancer types and in the context of driver alterations reveals that semi-universal, HLA-specific cancer vaccine strategies will be relevant to only a small subset of the general population. Similar analysis of whole exome/genome sequencing, although not currently feasible at scale in a clinical setting, will likely uncover further diversity.
Decreased body mass index (BMI) associates with impaired survival from diagnosis of brain metastases in lung cancer patients: analysis of 624 patients
Authors: E.K. Masel, A.S. Berghoff, G. Widhalm, U. Dieckmann, B. Gatterbauer, P. Birner, R. Bartsch, S. Schur, H.H. Watzke, C. Zielinski, M. Preusser
Journal: Annals of Oncology (2016)
ACTR-14. DISULFIRAM SENSITIZES GLIOBLASTOMA TO ABRAXANE AND TEMOZOLOMIDE TREATMENT THROUGH INHIBITION OF MGMT AND ALDEHYDE DEHYDROGENASE
Authors: Amin Kassam, Santhi Konduri
Journal: Neuro-Oncology (2016)

O6methylguanine DNA methyltransferase (MGMT) repairs the DNA damage caused by temozolomide (TMZ) thereby blunting clinical efficacy. Members of the aldehyde dehydrogenase (ALDH) family of isoenzyes serve as markers of cancer stem cells and contribute to chemotherapy resistance. Disulfiram (DSF) inhibits MGMT through ubiquitin mediated degradation; it is also a specific inhibitor of ALDH. Abraxane (ABX) enhances TMZ cytotoxicity. We therefore hypothesized that DSF through MGMT and ALDH inhibition will sensitize GBM cells to TMZ and ABX. Normal astrocytes as well as MGMT expressing and nonexpressing HGG cell lines (LN18, T98G, U138, LN229, A-172, U87, U251, U118, SNB19, SW1088, Hs683) were treated with DSF, ABX and TMZ in various doses and combinations. Cell proliferation was measured using a luminescence assay. ABX and TMZ has very minimal effect on normal astrocyte growth, whereas DSF inhibited (~25%) normal astrocyte growth at higher concentrations. ABX at low doses significantly inhibited proliferation in all HGG cell lines dose dependently. Similarly, DSF at low doses significantly inhibits MGMT negative cell lines (LN229, A-172, U87, U251, U118, SW1088) compared to MGMT positive cell lines (T98G, U138). DSF plus Abraxane decreases the proliferation of MGMT negative HGG cell lines by 80–90% and MGMT positive cells 30–40% compared to untreated controls. ABX plus TMZ inhibited cell line growth 40–60% compared to untreated controls, and 20–30% more than temozolomide alone. DSF, ABX and TMZ significantly inhibited MGMT negative brain tumor cell growth by 90–95%. Our findings suggest that DSF treatment, through dual inhibition of MGMT and ALDH, is a novel therapeutic approach to inhibit glioblastoma growth. It synergistically enhances both ABX and TMZ activity. Furthermore, our results suggest that combination of ABX, TMZ and DSF significantly inhibited glioblastoma growth compared to TMZ alone.
A phase II clinical trial involving the use of low-dose daily oral cyclophosphamide, weekly vinblastine and rofecoxib in patients with advanced solid tumors
Authors: S. D. Young, C. J. Germond, J. C. Noble, P. O. Cano, P. G. Lopez
Journal: Journal of Clinical Oncology (2004)

3137 Background: Preclinical studies indicate the conventional chemotherapeutic agents given continuously at low doses may provide an improved therapeutic index (RS Kerbel et al, Annals of Oncology 13:12–15, 2002). Cyclophosphamide and vinblastine have been best studied in experimental models where tumor growth retardation is achieved, at least in part, through antiangiogenic mechanisms. Methods: 50 with advanced solid tumors were enrolled (26 male and 24 female, median age 63 years - range 24 - 85). 43 patients had received at least one prior chemotherapy regimen. Patients were required to have ECOG performance status < 2, a life expectancy of > 3 months and at least one measurable lesion. All patients received cyclophosphamide 50 mg PO daily, weekly injections of vinblastine 3 mg/m2, and rofecoxib 25 mg PO daily. Results: Of the 45 evaluable patients, there were 2 complete responses (CR) (4%), 4 partial responses (PR) (9%) for an overall objective response rate of 13%. An additional 6 patients achieved disease stabilization (SD) ≥ 6 months (13%). The primary endpoint of clinical benefit (CR + PR + SD ≥ 6 months) was, therefore, 26%. The median progression-free survival for all patients was 105 days, and 240 days for patients experiencing clinical benefit. The incidence of grade 3/4 toxicities were as follows: neutropenia 12/2, anaemia 2/0, and thrombocytopenia 1/0. No patients developed grade 3 or 4 nausea, vomiting, mucositis or alopecia. Conclusions: This low-dose regimen consisting of daily oral cyclophosphamide and weekly vinblastine injections given concurrently with rofecoxib is associated with minimal toxicity and provides significant clinical benefit to patients with advanced solid tumors. These results are particularly encouraging given the nature of the study population, and indicate that this regimen merits further investigation in specific disease site studies. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration This clinical research was supported only by the Northern Cancer Research Foundation - a non-profit, regional charitable organization. No personal income was included in this support.
Pharmacokinetics (PK) and PK modeling of the first-in-class HBV core inhibitor NVR 3-778 dosed once-(QD) or twice daily (BD) in healthy volunteers (HVs) and HBeAg-positive patients with chronic HBV infection (CHBV)
Authors: Thomas Kakuda, Francesca Del Bene, Man-Fung Yuen, Edward J. Gane, Stuyckens Kim, Sandy Liaw, Nathaniel Browns, Klaus Klumpp, Lalo Flores, Sushmita Chanda
Journal: Hepatology (2016)