tbuckley/cabot-search huggingface dataset:
Abstract 4239: Immunomodulatory effects of topotecan augment the effectiveness of chemotherapy-immunotherapy combination
Authors: Jeong-Mi Lee, Kwang-Soo Shin, Choong-Hyun Koh, Insu Jeon, Tae-Seung Kang, Boyeong Song, Chang-Yuil Kang
Journal: Cancer Research (2020)

Abstract Combination therapy is a cornerstone of anticancer therapy, suggesting potential therapeutic benefit to nonresponders to single-agent treatment. BVAC, a B-cell-and-monocyte-based vaccine loaded with alpha-galactosylceramide(α-GC) and tumor antigen as reported in our previous studies, can be successfully combined with other treatments. Here we found out a novel synergistic regimen in TC-1 tumor model which combines BVAC with topotecan, a chemotherapeutic agent as a topoisomerase I inhibitor. We demonstrated some significant alteration in the immunoprofiles of topotecan-treated mice. We observed increased tumor recruitment of monocytes and CD8+ T cells, and decreased frequencies in regulatory T cells in tumor. Accordingly, we are currently investigating how topotecan-induced changes in immune cell composition could lead to improvement of antitumor effect. These data indicate that topotecan not only has cytotoxicity to tumor but can contribute to modulating tumor immune microenvironment. We anticipate that this study could provide a rationale for combination of cancer vaccine and chemotherapy and define future optimal treatment regimens in cancer patients. Citation Format: Jeong-Mi Lee, Kwang-Soo Shin, Choong-Hyun Koh, Insu Jeon, Tae-Seung Kang, Boyeong Song, Chang-Yuil Kang. Immunomodulatory effects of topotecan augment the effectiveness of chemotherapy-immunotherapy combination [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4239.
Exercise Training Reverses Gut Dysbiosis in Patients With Biopsy-Proven Nonalcoholic Steatohepatitis: A Proof of Concept Study
Authors: Alexa Hughes, Jessica Dahmus, Gloriany Rivas, Breianna Hummer, Jeremy R. Chen See, Justin R. Wright, Regina Lamendella, Kathryn H. Schmitz, Christopher Sciamanna, Mack Ruffin, Andrew D. Patterson, Rohit Loomba, Jonathan G. Stine
Journal: Clinical Gastroenterology and Hepatology (2020)
Abstract 2746: PET-CT/FACS platform to detect the biodistribution of radioisotope 89Zr PD-1 inhibitor in syngeneic tumor models
Authors: Xuzhen Tang, Fuyang Wang, Junyi Chen, Xuanming Zeng, Zhibo Liu, Qunsheng Ji
Journal: Cancer Research (2020)

Abstract Cancer treatment has been revolutionized by targeting the interaction between tumors and immune system. For instance, PD-1/PD-L1 mono- or combo-therapy has achieved great success in clinics, and patient responsiveness is closed associated with PD-L1 expression in cancer cells, tumor infiltration leukocytes, and drug bio-distribution in the tumor microenvironment. We established a method to label PD-1 inhibitor with radioisotope 89Zr for in-life imaging (PET-CT). Anti-PD-1 sensitive mouse colorectal cell line MC38 and resistant mouse melanoma cell line B16F10 were implanted to C57BL/6 mice, which were then treated with 89Zr PD-1 inhibitor. PET imaging was performed at multiple time points to detect the bio-distribution of anti-PD-1, while the infiltrated immune cells were identified by FCM and PD-L1 expression measured by IHC. Notable tumor uptake of 89Zr PD-1 inhibitor was observed in mouse liver and tumor grafts. The uptake in tumor increased over time and plateaued 24 hours post-injection. MC38 and B16F10 tumor grafts showed difference in uptake levels. Blood and tumor at both flanks were removed for leucocyte phenotyping, and compared with B16F10, MC-38 tumors exhibited higher percentage of total lymphocytes and cytotoxic T lymphocytes, equivalent number of dendritic cells and less myeloid cells. Further phenotyping indicates that compared to MC-38, B16F10 tumors contain higher percentage of MDSC, most of which are monocytic myeloid derived suppressor cells. With our PET-CT/FACS platform, we can evaluate immunotherapy response and microenvironment changes in different tumors in “one-mouse” system. The unique immune microenvironment (high TIL, high CD8+ T and low MDSC) may contribute to the notable and sustainable uptake of PD-1 inhibitor and the corresponding efficacy. This system can act as a good translational platform to monitor the PK-PD readout of immune therapy. Citation Format: Xuzhen Tang, Fuyang Wang, Junyi Chen, Xuanming Zeng, Zhibo Liu, Qunsheng Ji. PET-CT/FACS platform to detect the biodistribution of radioisotope 89Zr PD-1 inhibitor in syngeneic tumor models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2746.
Type 2‐low asthma phenotypes by integration of sputum transcriptomics and serum proteomics
Authors: Nazanin Zounemat Kermani, Mansoor Saqi, Paul Agapow, Stelios Pavlidis, Chihhsi Kuo, Kai Sen Tan, Sharon Mumby, Kai Sun, Matthew Loza, Frederic Baribaud, Ana R. Sousa, John Riley, Asa M. Wheelock, Craig E. Wheelock, Bertrand De Meulder, Jim Schofield, Stephany Sánchez‐Ovando, Jodie Louise Simpson, Katherine Joanne Baines, Peter A. Wark, Charles Auffray, Sven‐Erik Dahlen, Peter J. Sterk, Ratko Djukanovic, Ian M. Adcock, Yi‐ke Guo, Kian Fan Chung
Journal: Allergy (2020)

Ratko Djukanović has consulted and presented at symposia organised by TEVA, Novartis, GlaxoSmithKline and AstraZeneca and has shares in and consults for Synairgen; Dr Asa Wheelock report remuneration from AstraZenica and Harvard Medical School for speaking engagements on SNF-clustering in COPD.; Charles Auffray reports grants from Innovative Medicine Initiative; Kian Fan Chung has received honoraria for participating in Advisory Board meetings of the pharmaceutical industry regarding treatments for asthma and chronic obstructive pulmonary disease and has also been remunerated for speaking engagements; Ian Adcock has received grants from Advisory Board meetings with pharmaceutical companies GSK, A-Z, Novartis, Boehringer Ingelheim and Vectura, and grants on asthma and COPD from Pfizer, GSK, MRC, EU, BI and IMI; Peter Sterk reports grants from IMI Innovative Medicines Initiative, during the conduct of the study; Matthew Loza and Frederic Baribaud are Employees and Shareholders of Janssen Research and Development, a Johnson and Johnson company; John Riley and Ana R Sousa are employees of GSK; the rest of the authors have nothing to disclose. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
AB0160 The influence of different kinds of theraphy on oxidative-antioxidative balance in children with juvenile idiopathic arthritis/jia/
Authors: J Postêpski, V Opoka-Winiarska, E Tuszkiewicz-Misztal, M Wawrzyszuk
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The aim of this study was to investigate the influence of different kinds of theraphy on oxidative-antioxidative balance in children with rheumatoid idiopatic arthritis. <h3>Objectives</h3> In our study the intensity of peroxide lipid oxidation was calculated by the contents of malonic dialdehyde (MDA) in plasma. At the same time antioxidant activity was evaluated. We measured the content of vitamin E (Vit. E) in plasma, the total antioxidant status (TAS), as well as the activity of glutathion peroxidase (GPX) and superoxide dismutase (SOD). In our study we examined 39 children with JIA aged 4–18 years and 27 healthy subjects aged 4–16 years. 8 patients were treated with glicocorticosteroids administered 1–2 mg/kg/24 h in relation to the prednisone standard. 8 children received Methtrexatein the dose of 10–15 mg/m<sup>2</sup>/week. 9 children were treated with Sulphasalazine in the dose of 20–40 mg/kg/24 h. 14 children were treated with non-steroid anti-inflammatory agents (naproxen 10 mg/kg/24 h). The examination was performed 4–6 weeks after the beginning of the treatment. The results obtained after the treatment were compared with those obtained before the treatment and those in the control group. <h3>Methods</h3> We used colorymetric and fluorometric methods. <h3>Results</h3> The level of MDA before the treatment, i.e. 2,32 ± 0,86 nM/ml, was significantly higher than that in the control group, i.e. 1,32 ± 0,38 nM/ml (p &lt; 0,05). After the treatment with Mtx, Sulphasalazine and non-steroid anti-inflammatory agents, the values of MDA were still significantly higher than those in the control group and equalled, respectively, 2,32 ± 0,71 nM/ml, 2,14 ± 0,1 nM/ml, and 2,14 ± 0,1 nM/ml (p &lt; 0,05). After the treatment with glicocorticosteroids, the values of MDA approximated to those in the control group and averaged 1,72 ± 0,17 nM/ml (p &lt; 0,05). Before the treatment, the activity of GPX was significantly lower than those in the control group (4,75 ± 2,59 U/ml vs 7,06 ± 1,99U/ml (p &lt; 0,05)). The values of the other parameters did not appear to depend on the treatment. <h3>Conclusion</h3> 1. Our results confirmed the existence of oxidative stress in children with juvenile idiophatic arthritis. 2. The strongest inhibitory effect on peroxide lipid oxidation is exerted by glicocorticosteroids, which conforms to their strongest anti-inflammatory activity. No significant influence of non-steroid anti-inflammatory agents on peroxide lipid oxidation was observed, despite their generally-acknowledged, weak antioxidative activity. No influence of Mtx and Sulphasalazine on peroxide lipid oxidation was observed in the period of examination.
Abstract 6232: Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization
Authors: Maria F. Gottardo, Johanna E. Sidabra, Carla S. Capobianco, Juan Garona, Silvio Perea Rodriguez, Daniel F. Aonso, Hernan G. Farina
Journal: Cancer Research (2020)

Abstract CK2 is a serine/threonine kinase that is overexpressed in breast cancer and its inhibition is associated to reduced tumor growth and disease progression. With more than three hundred substrates, this kinase is involved in a large number of cellular functions, such as replication, cell proliferation, differentiation, regulation of apoptosis and angiogenesis. CIGB-300 is an antitumor peptide with a novel mechanism of action, since it binds to the phospho-acceptor domain of CK2 substrates impairing the correct phosphorylation by the enzyme. Our aim was to evaluate the potential therapeutic benefits of CIGB-300 on breast cancer disease using experimental models with translational relevance. We demonstrated that CIGB-300 reduces breast cancer cell growth in MDA-MB-231, MCF-7 and F3II cells, exerting a pro-apoptotic action. We found that CIGB-300 increased Bax and decreased Bcl-2 expression, so the intrinsic pathway was involved in the proapoptotic effect of CIGB-300 in breast cancer cells. Moreover, CIGB-300 inhibits the CK2-mediated phosphorylation of B23, such phosphorylation impairment was correlated with the ability of CIGB-300 to induce nucleolar disassembly. Also, we investigate whether CIGB-300 affects the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects of the combination of CIGB-300 and cisplatin on cell viability and apoptosis. We demonstrated that CIGB-300 sensitize breast cancer cells to cisplatin, reducing cell viability and increasing apoptosis. In vivo, the effect on experimental breast cancer lung metastasis was evaluated after surgical removal of primary F3II tumors or after tail vein injection of tumor cells. Systemic CIGB-300 treatment inhibited breast cancer colonization of the lung, reducing the size and number of metastatic lesions. The present preclinical study establishes for the first time the efficacy of CIGB-300 on breast cancer. These encouraging results suggest that CIGB-300 could be used for the management of breast cancer as an adjuvant therapy after surgery, limiting tumor metastatic spread and thus protecting the patient from distant recurrence. Citation Format: Maria F. Gottardo, Johanna E. Sidabra, Carla S. Capobianco, Juan Garona, Silvio Perea Rodriguez, Daniel F. Aonso, Hernan G. Farina. Preclinical efficacy of CIGB-300, an anti-CK2 peptide, on breast cancer metastasic colonization [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6232.
Trial of Sodium Phenylbutyrate–Taurursodiol for Amyotrophic Lateral Sclerosis
Authors: Sabrina Paganoni, Eric A. Macklin, Suzanne Hendrix, James D. Berry, Michael A. Elliott, Samuel Maiser, Chafic Karam, James B. Caress, Margaret A. Owegi, Adam Quick, James Wymer, Stephen A. Goutman, Daragh Heitzman, Terry Heiman-Patterson, Carlayne E. Jackson, Colin Quinn, Jeffrey D. Rothstein, Edward J. Kasarskis, Jonathan Katz, Liberty Jenkins, Shafeeq Ladha, Timothy M. Miller, Stephen N. Scelsa, Tuan H. Vu, Christina N. Fournier, Jonathan D. Glass, Kristin M. Johnson, Andrea Swenson, Namita A. Goyal, Gary L. Pattee, Patricia L. Andres, Suma Babu, Marianne Chase, Derek Dagostino, Samuel P. Dickson, Noel Ellison, Meghan Hall, Kent Hendrix, Gale Kittle, Michelle McGovern, Joseph Ostrow, Lindsay Pothier, Rebecca Randall, Jeremy M. Shefner, Alexander V. Sherman, Eric Tustison, Prasha Vigneswaran, Jason Walker, Hong Yu, James Chan, Janet Wittes, Joshua Cohen, Justin Klee, Kent Leslie, Rudolph E. Tanzi, Walter Gilbert, Patrick D. Yeramian, David Schoenfeld, Merit E. Cudkowicz
Journal: New England Journal of Medicine (2020)

Sodium phenylbutyrate and taurursodiol have been found to reduce neuronal death in experimental models. The efficacy and safety of a combination of the two compounds in persons with amyotrophic lateral sclerosis (ALS) are not known.
Validation of the TREAT-B score for hepatitis B treatment eligibility in a large Asian cohort: TREAT-B improves with age
Authors: Jessica Howell, David Anderson, Stephen Bloom, John Lubel, William Kemp, James Williams, Sally Bell, Catherine Croagh, Barbara Demediuk, Paul Desmond, Sam Hall, Jacinta Holmes, Thai Hong, David Iser, Lucy Lim, Timothy Papaluca, Marno Ryan, Kumar Visvanathan, Yinzong Xiao, Caroline van Gemert, Margaret Hellard, Alexander Thompson
Journal: Journal of Hepatology (2020)
Abstract 1717: Targeted NanoSpheres (TNS): An effective, non-toxic nano-formulated therapeutic platform for broad use in cancer treatment
Authors: Hyunggyoo Kang, Jon Nagy, Timothy Triche
Journal: Cancer Research (2020)

Abstract Current cancer therapy relies on the use of cytotoxic agents (‘chemotherapy') that was developed over 50 years ago. These agents are very effective, but efficacy is limited by off-target toxicity to normal tissues. It is widely recognized that chemotherapy could be far more effective if higher doses could be delivered to the tumor and not to normal tissues. By refining the early formulations and after extensive testing, we developed a novel targeted nanoparticle called Targeted NanoSpheres or TNS. We showed this novel nano-formulated platform can overcome many deficiencies of conventional nanoparticles and therefore has enhanced potential as an effective delivery vehicle for virtually any type of cancer for which a suitable tumor cell surface antigen is present. We are exploring the development of NV103, a first-in-class anti-CD99 TNS (CD99-TNS/Ir), for the treatment of Ewing Sarcoma (EWS), a highly lethal pediatric and young adult bone and soft tissue tumor driven by a fusion protein, typically EWS/FLI1 in over 85% of cases. This platform is also being investigated for other types of cancer that either express CD99, or other tumor antigens like GD2 and B7-H3. In addition, a variety of payloads, including small molecules chemotherapeutics like irinotecan and doxorubicin, as well as plasmids, siRNA, ASOs, and mRNA, have been successfully incorporated and effectively delivered with documented superior anti-tumor effect. NV103 itself showed significant anti-tumor effect in hepatocellular carcinoma and prostate tumor cell lines and xenografts. In all cases, systemic toxicity is minimized by use of targeting antibodies that enhance tumor delivery while minimizing systemic exposure of normal tissues. Citation Format: Hyunggyoo Kang, Jon Nagy, Timothy Triche. Targeted NanoSpheres (TNS): An effective, non-toxic nano-formulated therapeutic platform for broad use in cancer treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1717.
Amelioration of ulcerative colitis <i>via</i> inflammatory regulation by macrophage-biomimetic nanomedicine
Authors: Tianlei Sun, Cheryl H. T. Kwong, Cheng Gao, Jianwen Wei, Ludan Yue, Jianxiang Zhang, Richard Dequan Ye, Ruibing Wang
Journal: Theranostics (2020)

Ulcerative colitis (UC) is featured with relapsing inflammation in the colon, where macrophages are recruited and polarized locally into M1 type to drive further inflammation. Pharmacotherapy of UC has exhibited limited efficacy, mostly due to the poor specificity. Methods: A macrophage-biomimetic nanomedicine was developed for targeted treatment of UC, which was derived from reactive oxygen species (ROS)-sensitive β-cyclodextrin, loaded with rosiglitazone, and coated with macrophage membrane. The ability of the nanomedicine in regulating macrophage polarization was examined at cellular level, and the macrophage-tropism driven targeted delivery into the inflammatory colon was investigated by ex vivo bio-imaging distribution assay. Furthermore, the nanomedicine's therapeutic efficacy was systemically examined in dextran sulfate sodium (DSS)-induced colitis model in mice. Results: The nanomedicine effectively polarized macrophages to M2 and protected epithelial cells from oxidative stress in vitro. In addition, macrophage-membrane led the nanomedicine to the inflammatory colon with a high targeting efficiency. In response to the elevated ROS in the inflammatory tissue, the nanomedicine released rosiglitazone specifically and regulated macrophage polarization in vivo. Macrophage membrane also assisted inflammation suppression by sequestering proinflammatory cytokines. Working in such a synergy, the nanomedicine exhibited significant therapeutic effects against UC in mice. Conclusions: This macrophage-biomimetic nanomedicine leverages the inflammatory tropism and inflammatory cytokine sequestration effects of macrophage membrane for targeted delivery and local inflammation suppression, the ROS-responsiveness of β-cyclodextrin-based matrix for specific payload release, and the macrophage-polarizing effect of rosiglitazone for inflammatory regulation, thereby exhibiting considerable therapeutic efficacy against UC in mice. This study offers important new insights on the design and development of biomimetic nanomaterials for inflammation regulations.
Abstract 508: A novel orally available Wnt-pathway inhibitor for the treatment of metastatic cancers
Authors: Kun Zhou, Jae Eun Cheong, Catherine Alix-Panabières, Lijun Sun, Bruce R. Zetter
Journal: Cancer Research (2020)

Abstract We have developed a novel drug compound (OBD9) which blocks growth of metastatic cancer cells both in vitro and in vivo. We now identify OBD9 as an effective Wnt-signaling inhibitor targeting TNIK (TRAF2 And NCK Interacting Kinase) and we hypothesize that OBD9 represent a novel therapeutic option for patients with tumors that have an activated Wnt signaling pathway. To find novel drug candidates that selectively inhibit metastatic tumor cell viability, a drug screen was firstly performed and results of the screen identified members of the FDA-approved benzimidazole methylcarbamate family (e.g. mebendazole (MBZ) and albendazole (ALB)) as potential therapies for metastatic cancer. Earlier work also supports a role for this chemical family in the potential treatment of multiple cancers, but progress has been stalled by their poor water solubility and poor bioavailability for systemic delivery to disseminated tumors. We therefore synthesized a novel compound (OBD9) containing the scaffold of MBZ coupled to an oxetane group to enhance aqueous solubility to 361μM. OBD9 demonstrates significant cytotoxicity toward a variety of cancer cell types including colon, lung, and prostate cancers (IC50: 0.9-2μM). In a mouse xenograft model using highly aggressive PCMLN3 prostate cancer cells, OBD9 at 30 mg/kg significantly repressed growth of established tumors with no visible toxicity. In a mouse xenograft model of human A549 lung cancer cell line, orally delivered OBD9 also dramatically inhibited the growth of established tumors at 30 or 90μM without noticeable toxicity. Mechanistically, we find that OBD9 treatment significantly reduces TNIK levels as early as 4 hours at 1uM via an autophagy-dependent protein degradation pathway. TNIK functions as an activator of Wnt signaling pathway via phosphorylation of the beta-catenin/TCF4 complex that regulates Wnt downstream targets. We show that OBD9 treatment inhibits colon cancer cell growth and both qPCR and Western blot data suggest that Wnt signaling downstream targets, such as TCF4, AXIN2 and cMyc, are all significantly suppressed by OBD9 via the inhibition of TNIK. Overall, our in vitro and in vivo data suggest that OBD9 potentially represents a novel therapeutic option for multiple cancers including but not limit to colon, lung and prostate cancer. Citation Format: Kun Zhou, Jae Eun Cheong, Catherine Alix-Panabières, Lijun Sun, Bruce R. Zetter. A novel orally available Wnt-pathway inhibitor for the treatment of metastatic cancers [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 508.