tbuckley/cabot-search huggingface dataset:
723. Oncolytic Adenovirus Breaks Tumor Tolerance To Adoptive T-Cell Therapy By Recruiting Immune Cells To and Promoting Their Activity in the Tumor
Authors: Siri Tähtinen, Susanna Grönberg-Vähä-Koskela, Dave Lumen, Maiju Merisalo-Soikkeli, Mikko Siurala, Anu J. Airaksinen, Markus Vähä-Koskela, Akseli Hemminki
Journal: Molecular Therapy (2015)

Despite the fast growing rate in the development of novel adoptive T-cell therapies (ACT), the clinical benefit in established solid tumors has remained modest. Roadblocks to effective immune attack by infiltrating tumor-specific T-cells include several immune evasion mechanisms, which contribute to tumor tolerance. Oncolytic virotherapy on the other hand is the use of cancer cell specific, conditionally replicative viruses in the treatment of cancer. Oncolytic virotherapy has been suggested to enhance epitope spreading by direct oncolysis of tumor cells, leading to enhanced antigen presentation by dendritic cells and increased immunogenicity of the established tumor. Here, we studied the combination of these two established forms of immunotherapy in a highly resistant and poorly immunogenic B16. OVA mouse melanoma model. Immunocompetent B16. OVA bearing C57BL/6 female mice were adoptively transferred with CD8a+ enriched, OVA-specific OT-I lymphocytes and treated with intratumoral injections 5/3-fiber chimeric adenovirus (diluted in saline) on six consecutive days. Tumor growth of mice was monitored every 2-3 days by using electronic calipers. Mice were sacrificed on day 14 post-transfer and immune composition of harvested tumors was analyzed by flow cytometry. Following adoptive transfer of OT-I lymphocytes, superior tumor growth control was observed in adenovirus-treated mice compared to control mice, even in the absence of active oncolysis. Significant increase in infiltration of CD45+ leukocytes, CD8+ lymphocytes and F4/80+ macrophages was seen adenovirus-treated tumors suggesting enhanced tumor immunogenicity. Proinflammatory tumor microenvironment mediated by adenovirus infection led to expression of co-stimulatory signals on CD11c+ dendritic cells and subsequent activation of T-cells, thus breaking the tumor-induced peripheral tolerance of T-cells. Moreover, epitope spreading in the form of endogenous anti-melanoma T-cells was detected in the combination treated mice indicating that the dual approach can lead to systemic anti-tumor immunity. Treatment with oncolytic adenovirus can overcome resistance of B16. OVA murine melanoma tumors to T-cell therapy by recruitment and stimulation of tumor-infiltrating immune cells, thus resulting in improved efficacy of adoptive T-cell therapy. In our model, adenovirus was required to unleash the power of ACT for therapeutic effects. Importantly, these two modalities are not merely an attractive combination, but could represent a way to achieve "CD19-like" results in the treatment of solid tumors.
Breast milk polyunsaturated fatty acids: associations with adolescent allergic disease and lung function
Authors: N. T. Waidyatillake, R. Stoney, F. Thien, C. J. Lodge, J. A. Simpson, K. J. Allen, M. J. Abramson, B. Erbas, C. Svanes, S. C. Dharmage, A. J. Lowe
Journal: Allergy (2016)

Abstract Background It has been hypothesized that n −3 PUFA in breast milk may assist immune and lung development. There are very limited data on possible long‐term effects on allergic disease and lung function. The aim was to investigate associations of n −3 and n −6 PUFA levels in colostrum and breast milk with allergic disease and lung function at ages 12 and 18 years. Methods Polyunsaturated fatty acids were measured in 194 colostrum samples and in 118 three‐month expressed breast milk samples from mothers of children enrolled in the Melbourne Atopy Cohort ( MACS ) Study, a high‐risk birth cohort study. Associations with allergic diseases, skin prick tests and lung function assessed at 12 and 18 years were estimated using multivariable regression. Results Higher levels of n −3 but not n −6 PUFA s in colostrum were associated with a trend towards increased odds of allergic diseases, with strong associations observed for allergic rhinitis at 12 ( OR = 5.69[95% CI : 1.83,17.60] per weight%) and 18 years (4.43[1.46,13.39]) and eczema at 18 years (9.89[1.44, 68.49]). Higher levels of colostrum n −3 PUFA s were associated with reduced sensitization (3.37[1.18, 9.6]), mean FEV 1 (−166 ml [−332, −1]) and FEV 1 / FVC ratio (−4.6%, [−8.1, −1.1]) at 12 years. Conclusion Higher levels of colostrum n −3 PUFA s were associated with increased risks of allergic rhinitis and eczema up to 18 years, and sensitization and reduced lung function at 12 years. As residual confounding may have caused these associations, they should be replicated, but these results could indicate that strategies that increase maternal n −3 PUFA intake may not aid in allergic disease prevention.
Arthritis Therapy: An Injectable, Click-Cross-Linked Small Intestinal Submucosa Drug Depot for the Treatment of Rheumatoid Arthritis (Adv. Healthcare Mater. 24/2016)
Authors: Kyungsook Kim, Ji Hoon Park, Seung Hun Park, Hye Yun Lee, Jae Ho Kim, Moon Suk Kim
Journal: Advanced Healthcare Materials (2016)

A click-cross-linked small intestine submucosa (Cx-SIS) drug depot for methotrexate (Met) is developed for the treatment of rheumatoid arthritis (RA) on page 3105 by Moon Suk Kim and co-workers. The Met-loaded Cx-SIS depot is successfully formed after intraarticular injection of click crosslinkable SIS, and this formulation induces long-lasting Met release and allows Met to act effectively in the articular joint, resulting in RA repair.
A Multiple Myeloma Research Consortium (MMRC) Multicenter Phase I Trial of Perifosine (KRX-0401) in Combination with Lenalidomide and Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (MM): Updated Results.
Authors: Andrzej Jakubowiak, Todd Zimmerman, Melissa Alsina, Paul Richardson, Jonathan Kaufman, T. Kendall, C. Brozo, A. McAllister, C. Leister, T. Hideshima, P. Sportelli, L. Gardner, R. Birch, I.C. Henderson, K. Giusti, Kenneth Anderson
Journal: Blood (2007)
Efficacy and Toxicity of Rituximab and Brief Duration, High Intensity Chemotherapy with Filgrastim Support for Burkitt or Burkitt – Like Leukemia/Lymphoma: Cancer and Leukemia Group B (Calgb) Study 10002
Authors: David A. Rizzieri, Jeffrey L Johnson, John C. Byrd, Gerard Lozanski, Bayard L. Powell, Thomas C. Shea, Sreenivasa Nattom, Eva Hoke, Bruce D. Cheson, Richard Larson
Journal: Blood (2010)
Time until Transfusion Independence in Haplo-Cord Transplant Is Comparable to Matched Unrelated Stem Cell Transplant, a Single Institution Experience
Authors: Hamilton C. Tsang, Lohith S. Bachegowda, Ruchika Goel, Nebu V. Koshy, Usama Gergis, Yen-Michael S. Hsu, Sebastian A. Mayer, Tsiporah B. Shore, Koen van Besien, Melissa M. Cushing, Ljiljana V. Vasovic
Journal: Blood (2015)
Abstract 3544: Clinical applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem glioma
Authors: Seung Ah Choi, Young Eun Lee, Phil Ae Kwak, Youn Joo Moon, Ji Hoon Phi, Kyu-Chang Wang, Sung Su Kim, Kyu-Chang Wang, Kyeung Min Joo, Seung-Ki Kim
Journal: Cancer Research (2015)

Abstract Brainstem glioma is one of incurable malignancies in children due to its unique inoperable location. Regarding the extensive migratory ability toward cancer and the possible autologous transplantation, human adipose-derived mesenchymal stem cells (hAT-MSC) are attractive vehicles to deliver therapeutic genes to brainstem glioma. In this study, we established clinically applicable hAT-MSCs expressing therapeutic genes in a GMP facility and investigated the therapeutic efficacy against brainstem glioma preclinically. For the feasible clinical application, 1) hAT-MSCs were primarily cultured from the human subcutaneous adipose tissue for making autologous transplantation possible, 2) hAT-MSCs were genetically engineered to express two therapeutic genes, carboxyl esterase (CE) and a secreted form of the TNF-related apoptosis-inducing ligand (sTRAIL) for synergistic effects, 3) human CE and sTRAIL sequences were utilized to avoid immunological side effects, and 4) sTRAIL expression vector was delivered by non-gDNA integrating gene transfer technology. hAT-MSCs expressing sTRAIL ± CE showed significant therapeutic effects against brainstem gliomas in vitro and in vivo. However, simultaneous sTRAIL and CE expression failed to show synergistic effects in vivo. The results indicate that non-viral transient sTRAIL gene transfer to autologous hAT-MSCs is a clinically applicable stem cell-based gene therapy for brainstem gliomas in terms of therapeutic effects and safety. Citation Format: Seung Ah Choi, Young Eun Lee, Phil Ae Kwak, Youn Joo Moon, Ji Hoon Phi, Kyu-Chang Wang, Sung Su Kim, Kyu-Chang Wang, Kyeung Min Joo, Seung-Ki Kim. Clinical applicable human adipose tissue-derived mesenchymal stem cells delivering therapeutic genes to brainstem glioma. [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 3544. doi:10.1158/1538-7445.AM2015-3544
Abstract 3798: KHF16, a new cycloartane triterpenoid isolated from Cimicifuga foetida, suppresses triple-negative breast cancer by inhibiting the NF-κB signaling pathway
Authors: Yanjie Kong, Ceshi Chen
Journal: Cancer Research (2015)

Abstract Triterpenoids extracted from Cimicifuga foetida were reported to inhibit cancers by inducing cell cycle arrest and apoptosis. In this study, KHF16 (24-acetylisodahurinol-3-O-b-D-xylopyranoside), a new cycloartane triterpenoid isolated from the rhizomes of Cimicifuga foetida, showed potent anti-cancer activity in multiple ERa/PR/HER2 triple-negative breast cancer (TNBC) cell lines. KHF16 significantly induces cell cycle G2/M phase arrest and apoptosis in both MDA-MB-468 and SW527 TNBC cell lines. KHF16 reduces the expression levels of XIAP, Mcl-1, Survivin, Bcl-2 and Cyclin B1/D1 proteins. Importantly, KHF16 inhibits TNFα-induced IKKa/b phosphorylation, IKBa phosphorylation, p65 nuclear translocation and NF-κB downstream target gene induction in TNBC cells. These results suggest that KHF16 may inhibit TNBC through blocking the NF-κB signaling pathway. Citation Format: Yanjie Kong, Ceshi Chen. KHF16, a new cycloartane triterpenoid isolated from Cimicifuga foetida, suppresses triple-negative breast cancer by inhibiting the NF-κB signaling pathway. [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 3798. doi:10.1158/1538-7445.AM2015-3798
Abstract 1811: Correlations of COX2 expressions in circulating tumor cells (CTCs) and response to radiotherapy in head and neck squamous cell carcinoma (HNSCC)
Authors: Feng Wang, Xiaoqi Xie, Zhen Wang, Ping Li
Journal: Cancer Research (2015)

Abstract Head and neck squamous cell carcinoma (HNSCC) frequently involves metastasis at diagnosis. Circulating tumor cells (CTCs), captured as “liquid biopsy”, can provide real-time clinical information on prognosis, therapy choice and drug response and resistance. Cyclooxygenase 2 (COX-2), a key enzyme involved in prostaglandin production, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Previous study showed that expression of COX2 in HNSCC tumor tissue samples is associated with clinical response to radiotherapy. The aim of study is to investigate whether expression of COX2 in CTCs could be used as a predict factor to clinical response to radiotherapy.An multiplex RNA in situ hybridization (RNA-ISH) method, named CanPatrol CTC enrichment technique, was used to isolate and categorize CTCs as epithelial, biophenotypic epithelial/mesenchyma, and mesenchymal phenotypes. A total of 51 pateints with HNSCC were enrolled into this study and assessed for CTC levels. Of these 51 pateints, 13 patients were evaluated for COX2 expression in CTCs before and after radiotherapy. The COX2 expression in one CTC or more was defined as positive presence. Primary end point was the overall objective response rate. At baseline, CTCs, ranging from 1 to 15, were identified from 36(70.59%) patients, and the median and mean values were 2 and 3(±3 SD) respectively. No significant correlations were observed between CTCs amounts and clinicopathological parameters. Thirteen (25.49%) patients had ≥2 CTCs both at the beginning and the end of treatment. COX2 expressions was identified in 6(46.15%) patients, which associated with ascending mesenchymal rate afterwards, and indicate a trend of less response to radiotherapy. Compared to 46.15% (6/13) of COX2-positive patients, disease control characterized as decreased CTCs/ mesenchymal CTCs after systemic radiotherapy was obtained in 53.85% (7/13) of COX2-negative (p&amp;lt; 0.05). In summary, COX2-positive CTCs is a promising predictive factor for response to radiotherapy. Citation Format: Feng Wang, Xiaoqi Xie, Zhen Wang, Ping Li. Correlations of COX2 expressions in circulating tumor cells (CTCs) and response to radiotherapy in head and neck squamous cell carcinoma (HNSCC). [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 1811. doi:10.1158/1538-7445.AM2015-1811
Efficacy and Safety of Dasatinib in Late Suboptimal Response CML Patients a Its Relation with Lymphocytosis, Lymphocyte Migration and Chemokine Receptor Expression
Authors: Valentín García-Gutierrez, Beatriz Colom-Fernandez, Anna Kreutzman, Luis Felipe Casado, Fermín Sánchez-Guijo, Rosa M. Ayala, Concepcion Boque, Blanca Xicoy, Isabel Montero, Cesar Soto, Raquel De Paz, Joaquin Martinez Lopez, Cecilia Muñoz-Calleja, Juan Luis Steegmann
Journal: Blood (2015)
Utility of concomitant chemoradiotherapy with 5-fluorouracil (5-FU) single agent as neoadjuvant treatment regimen in mexican patients with stage III rectal cancer: Experience in the Oncology Hospital
Authors: J. Gomez Rangel, O. Alvarez Ordorica, R. Villalobos Valencia, J. A. Silva
Journal: Journal of Clinical Oncology (2009)

e15144 Background: To analyze overall survival, free disease survival, complete and partial pathologic response, effect of stage reduction, toxicity profile and number of anus preservative surgery in patients treated with concurrent chemo radiotherapy with a modified 5-FU single agent regimen as neoadjuvant modality treatment. Methods: Historic Cohort of patients treated in the Oncology Hospital, CMNSXXI between January 1999 to December 2004. The scheme used was a bolus of 5FU 425mg/m2 without leocovorin in three consecutive days each two weeks (days 1–3, 15 -17 and 29–31). Results and Conclusions: There were identified 96 consecutive patients with clinical stage III. The median age was 57.5 years. Ninety and two patients were operated and 51% was candidates to conservative surgery. There were 12.5% of complete pathologic responses and 35% of partial responses. The median of survival has not been reached. The five years of overall survival was 62% and the five-years of disease free survival was 55%. Stage reduction had impact in overall survival with 65% vs 40% at 9.5 years of follow up, and DFS was 58% vs 48% at 9.5 years. We report 16 cases of gastrointestinal toxicity grade 3 and two cases with grade 4. There was reported fourth cases of afebril neutropenia grade 4. Results in OS, DFS and number of complete pathological response were similar to reported by another oncology groups. Stage reduction was traduced in an increased of OS. This schedule can be feasible and applicable in another institutions in develop countries. No significant financial relationships to disclose.
Ectopic Expression of CDX2 Perturbs HOX Gene Expression in Murine Progenitors Depending on Its N-Terminal Transactivation Domain and Is Closely Correlated with Deregulated HOX Gene Expression in Human Acute Myeloid Leukemia.
Authors: Vijay P.S. Rawat, Silvia Thoene, Vegi M. Naidu, Natalia Arseni, Bernhard Heilmeier, Klaus Metzeler, Konstantin Petropoulos, Aniruddha Deshpande, Leticia Quintanilla-Martinez, Stefan Bohlander, Karsten Spiekermann, Wolfgang Hiddemann, Michaela Feuring-Buske, Christian Buske
Journal: Blood (2007)
Abstract 1862: Discerning the role of USP22 in prostate cancer development and progression
Authors: Jennifer Jones, Jeffry L. Dean, Randy S. Schrecengost, Karen Knudsen
Journal: Cancer Research (2015)

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related death for men in the United States. While organ-confined disease is manageable, advanced and disseminated PCa currently has no durable treatment options. Thus, understanding the causes and consequences of the transition from early stage to late stage castrate-resistant PCa (CRPC) are critical. While this transition has a requisite for the androgen receptor (AR) activity, the mechanisms by which AR and other oncogenes are functionally increased, even after initial treatment with androgen deprivation therapy (ADT) have not been completely characterized. USP22, a known deubiquitinase associated with the SAGA transcriptional activation complex, was originally designated in a “death from cancer” gene signature. Importantly, USP22 is significantly upregulated in PCa patients with late-stage disease, and specifically indicates for poor outcome in PCa patients. Moreover, tumor-associated USP22 increases AR levels and activity as well as the oncogene MYC function, partially defining the mechanism by which tumor-associated USP22 drives PCa progression. Thus, while certain consequences of tumor-associated USP22 expression have been elucidated, the remaining downstream effects have not been thoroughly characterized. Newly generated data begin to establish the biochemical events controlled by USP22 that confer proliferation and survival on PCa cells. Through use of novel proteomic technology, specifically Ubiscan analysis, tumor-associated USP22 will be shown to participate in driving PCa development and progression as well as therapeutic bypass through differential regulation of the ubiquitylome. Citation Format: Jennifer Jones, Jeffry L. Dean, Randy S. Schrecengost, Karen Knudsen. Discerning the role of USP22 in prostate cancer development and progression. [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 1862. doi:10.1158/1538-7445.AM2015-1862
The Prevalence of Reduced VWF Survival Phenotype (Type 1C VWD) in Type 1 Index Cases Recruited into the TS Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCB - VWD).
Authors: Sandra L. Haberichter, P.A. Christopherson, C.L. Perry, A. Lee, P.A. Morateck, D.B. Bellissimo, J.C. Gill, T.C. Abshire, J.A. Di Paola, W.K. Hoots, C. Leissinger, J.M. Lusher, M.V. Ragni, Ad Shapiro, R.R. Montgomery
Journal: Blood (2007)
Abstract 1407: Identification of sialylated glycoproteins in doxorubicin-treated hepatoma cells with glycoproteomic analyses
Authors: Eiji Miyoshi, Kanako Azuma, Shinji Takamatsu, Naoko Terao, Satoshi Serada, Tetsuji Naka, Yoshihiro Kamada
Journal: Cancer Research (2015)

Abstract Sialylation is one of the most important types of glycosylation involved in carcinogenesis and establishment of cancer stemness. We previously showed that increased sialylation is a characteristic glycan change in cancer stem cells (CSCs) from hepatocellular carcinoma (Cancer Science 2011, Moriwaki et al). However, the identities of glycoproteins targeted for sialylation remain unknown. CSC fraction is too small to identify target proteins with glycol-proteomics analyses. In the present study, we identified glycoproteins targeted for sialylation in doxorubicin (DXR)-treated hepatocarcinoma cell line, Huh7, using glycoproteomic analyses. Since CSCs constitute a small subset of cells within carcinoma cell lines, it is difficult to identify sialylated proteins using general glycoproteomic strategies. It is known that treatment with anti-cancer drug can condense CSCs, we used DXR to concentrate CSCs. In DXR-treated Huh7 cells, isobaric tag for relative and absolute quantitation (iTRAQ) analysis identified 17 sialylated glycoproteins. Most of the identified glycoproteins were cancer-associated proteins. Furthermore, two proteins of approximately 70 kDa were detected using Sambucus sieboldoana agglutinin (SSA) blot analysis and identified as beta-galactosidase and alpha-2-HS-glycoprotein (fetuin-A) by SSA precipitation followed by liquid chromatography-tandem mass spectrometry analyses. Sialylation levels of fetuin-A were increased in DXR-treated Huh7 cell lysates. Furthermore, intracellular localization of fetuin A with sialylation was changed in DXR-treated Huh7 cells under observation with confocal microscopy These changes in sialylation of glycoproteins might be involved in the establishment of cancer stemness. Citation Format: Eiji Miyoshi, Kanako Azuma, Shinji Takamatsu, Naoko Terao, Satoshi Serada, Tetsuji Naka, Yoshihiro Kamada. Identification of sialylated glycoproteins in doxorubicin-treated hepatoma cells with glycoproteomic analyses. [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 1407. doi:10.1158/1538-7445.AM2015-1407
Steroid-Sparing Effect of 0.1% Tacrolimus Eye Drop for Treatment of Shield Ulcer and Corneal Epitheliopathy in Refractory Allergic Ocular Diseases
Authors: Dai Miyazaki, Atsuki Fukushima, Yuichi Ohashi, Nobuyuki Ebihara, Eiichi Uchio, Shigeki Okamoto, Jun Shoji, Etsuko Takamura, Yayoi Nakagawa, Kenichi Namba, Hiroshi Fujishima
Journal: Ophthalmology (2016)

To evaluate the effects of 0.1% topical tacrolimus alone or in combination with steroids for the treatment of shield ulcers and corneal epitheliopathy in patients with refractory allergic ocular diseases.Open cohort study.Patients with refractory allergic conjunctivitis epitheliopathy, shield ulcers, or corneal plaques (N = 791).The 791 patients were treated with topical tacrolimus alone or in combination with topical or oral steroids. The effectiveness of the treatments was determined by a corneal epitheliopathy score during the 3-month follow-up period. The clinical signs were rated on a 4-grade scale. Corneal epitheliopathy with no corneal staining was graded as 0, and shield ulcers or plaques were graded as 3, the highest grade. The effects of tacrolimus with and without topical steroids on the epitheliopathy scores were assessed after adjustments for the severity of the clinical signs and characteristics.Changes in the corneal epitheliopathy score.Adjusted mean epitheliopathy score at the baseline was 1.73 (95% confidence interval [CI], 1.65-1.81) for patients treated with tacrolimus alone, and this was significantly reduced by -0.93 at 1 month. The reduction of the score by topical and oral steroids was -0.02 for fluorometholone, 0.02 for betamethasone, and -0.02 for oral steroids, and these reductions were not significant compared with the reduction effect of topical tacrolimus alone at -0.93. The 238 patients with shield ulcer (score 3) were analyzed with adjustments, and the mean epitheliopathy score at 1 month was reduced to 1.38 with tacrolimus alone (95% CI, 1.24-1.51), 1.41 (95% CI, 1.26-1.56) with adjuvant fluorometholone, and 1.46 (95% CI, 1.32-1.61) with adjuvant betamethasone. No significant difference was observed in the adjunctive topical steroids. The presence of severe palpebral conjunctival symptoms, including giant papillae, was a significant resisting factor for topical tacrolimus.The significant effects of topical tacrolimus alone on shield ulcers and corneal epitheliopathy suggest that it may be used without the need for steroids.