tbuckley/cabot-search huggingface dataset:
Abstract 66: BCG can subvert patients antitumor immune response by downregulating HLA-I expression on cancer cells
Authors: Mathieu Rouanne, Julien Adam, Camélia Radulescu, Séverine Mouraud, Delphine Bredel, Diane Letourneur, Tuan Zea Tan, Nicolas Signolle, Amélie Bigorgne, Michael Dussiot, Sandrine Susini, Lambros Tselikas, François-Xavier Danlos, Roman Chabanon, Anna K. Schneider, Sophie Vacher, Thierry Lebret, Ivan Bièche, Yves Allory, Jean-Charles Soria, Jean Paul Thiery, Laurence Zitvogel, Aurélien Marabelle
Journal: Cancer Research (2021)

Abstract Patients with high-risk non muscle-invasive bladder cancer (NMIBC) frequently relapse after standard BCG immunotherapy and have a dismal outcome after progression to muscle-invasive bladder cancer (MIBC). The mechanisms of tumor resistance to such immunotherapy remain elusive. We performed functional assays of fresh bladder tumors mixed with BCG, reinforced with in vitro experiments and in situ immune profiling of a cohort of MIBC pre- and post BCG therapy. Here, we demonstrate two distinct patterns of BCG-induced immune subversion. In the first pattern, intracellular BCG infection was associated with HLA-I loss and epithelial-to- mesenchymal transition (EMT) characteristics. HLA-I deficient tumors displayed a myeloid immunosuppressive microenvironment and dismal outcomes. Conversely, HLA-I+ BCG-treated tumors generated a Th1 type of immune response associated with an upregulation of exhaustion markers. Such patients had a very favorable outcome upon radical surgery. We surmise that HLA-I expression in bladder cancers does not result from immunoediting but rather from a BCG-induced EMT process that predicts dismal prognosis. Cancer cells HLA-I scoring by immunohistochemistry (IHC) staining can be easily implemented by pathologists in routine practice in order to stratify future urothelial cancer patient treatment strategies. Citation Format: Mathieu Rouanne, Julien Adam, Camélia Radulescu, Séverine Mouraud, Delphine Bredel, Diane Letourneur, Tuan Zea Tan, Nicolas Signolle, Amélie Bigorgne, Michael Dussiot, Sandrine Susini, Lambros Tselikas, François-Xavier Danlos, Roman Chabanon, Anna K. Schneider, Sophie Vacher, Thierry Lebret, Ivan Bièche, Yves Allory, Jean-Charles Soria, Jean Paul Thiery, Laurence Zitvogel, Aurélien Marabelle. BCG can subvert patients antitumor immune response by downregulating HLA-I expression on cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 66.
Covid-19: Biden renews vaccines push as cases and deaths rise among unvaccinated people
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

President Joe Biden has outlined the ways his team is pushing to get more Americans vaccinated, as the highly contagious delta variant spreads and is now causing half of all new SARS-CoV-2 infections in the US.

In a speech on 6 July Biden urged Americans to get vaccinated, calling it a “wartime effort.”

“Do it now for yourself and the people you care about, for your neighbourhood, for your country,” he said. “It sounds corny, but it’s a patriotic thing to do.”1

Biden added that vaccination worked and that numbers of covid-19 cases and deaths were down by 90% from January. He said that millions of fully vaccinated people …
Abstract 1928: Erdafitinib in combination with BCLXL/BCL2 inhibitor induce apoptosis in urothelial carcinoma cells without FGFR mutation
Authors: Akira ohtsu, Seiji Arai, Tatsuhiro Sawada, Kazuhiro Suzuki
Journal: Cancer Research (2021)

Abstract Although Erdafitinib has recently emerged as a treatment for metastatic urothelial carcinoma, it has been shown to be effective against FGFR mutations, but the target patient population is small, and a new treatment for urothelial carcinoma without FGFR mutations is needed. We found that Erdafitinib degrades MCL1 in urothelial carcinoma cells. Furthermore, we found that in combination with Navitoclax, a BCLXL/BCL2 inhibitor, it induced potent apoptosis in urothelial carcinoma cell lines without FGFR mutation. This combination therapy may represent a new treatment for urothelial carcinoma without FGFR mutations. Citation Format: Akira ohtsu, Seiji Arai, Tatsuhiro Sawada, Kazuhiro Suzuki. Erdafitinib in combination with BCLXL/BCL2 inhibitor induce apoptosis in urothelial carcinoma cells without FGFR mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1928.
Reducing the frequency of follow up cystoscopies for recurrence through the utilization of the urinary biomarker test ADXBLADDER in patients with Low grade, Low stage non-muscle invasive bladder cancer
Authors: P. Gontero, M. Roupret, J. Witjes, E. Montanari, F. Longo, A. Kennedy, J. Stockley, M. Colombel, T. Dudderidge, S. Mccracken, J. Palou, R.J. Sylvester
Journal: European Urology (2021)
Abstract 907: XMT-1660, a B7-H4-targeted Dolasynthen antibody-drug conjugate for the treatment of breast cancer
Authors: Shawn P. Fessler, Jason Wang, Scott D. Collins, LiuLiang Qin, Kenneth Avocetien, Ling Xu, Ronald Eydelloth, Steven Vonderfecht, Chen-Ni Chin, Steven Bradley, Susan Clardy, Anouk Dirksen, Elizabeth Ditty, Bingfan Du, Dokyong Kim, Rebecca Mosher, Elena Ter-Ovanesyen, Kelly Slocum, Alex Uttard, Phonphimon Wongthida, Jeffrey Zurita, Dorin Toader, Marc Damelin, Timothy B. Lowinger
Journal: Cancer Research (2021)

Abstract XMT-1660 is a novel Dolasynthen-based antibody drug conjugate carrying a DolaLock payload with controlled bystander effect and targeting B7-H4, a tumor antigen that is broadly expressed on the cell surface in breast, ovarian and endometrial cancers. B7-H4 (VTCN1) exerts immunosuppressive effects by suppression of T cell proliferation and is expressed on tumor-associated macrophages (TAMs) as well as epithelial tumor cells. XMT-1660 is comprised of an anti-B7-H4 antibody site-specifically conjugated to Dolasynthen, with a total of 6 DolaLock Auristatin F-HPA (AF-HPA) anti-tubulin payloads per antibody (DAR-6). To select the optimal ADC, three ADCs using the same antibody and DolaLock payload were compared: site-specific Dolasynthen-based DAR-2 and DAR-6 ADCs, and a stochastically conjugated Dolaflexin-based DAR-12 ADC. In vitro, no significant differences were observed among the 3 ADCs: all exhibited specific recognition of B7-H4 and elicited potent cytotoxicity against B7-H4-expressing cancer cells. In vivo, XMT-1660 consistently exhibited more anti-tumor activity than the other ADCs in TNBC models and ER+/HER2- models after single, equivalent doses based on payload. XMT-1660 demonstrated dose-dependent anti-tumor activity and induced sustained tumor regressions after a single administration. XMT-1660 and the Dolasynthen DAR-2 ADC both exhibited improved pharmacokinetics in mouse relative to the Dolaflexin DAR 12 ADC. These data indicate that XMT-1660 exhibited a superior preclinical profile to the other ADCs and more generally demonstrate the importance of DAR-ranging studies to identify the optimal antibody-drug conjugate for a given target. These results, as well as results from exploratory toxicology studies in non-human primates, strongly support the clinical development of XMT-1660. Citation Format: Shawn P. Fessler, Jason Wang, Scott D. Collins, LiuLiang Qin, Kenneth Avocetien, Ling Xu, Ronald Eydelloth, Steven Vonderfecht, Chen-Ni Chin, Steven Bradley, Susan Clardy, Anouk Dirksen, Elizabeth Ditty, Bingfan Du, Dokyong Kim, Rebecca Mosher, Elena Ter-Ovanesyen, Kelly Slocum, Alex Uttard, Phonphimon Wongthida, Jeffrey Zurita, Dorin Toader, Marc Damelin, Timothy B. Lowinger. XMT-1660, a B7-H4-targeted Dolasynthen antibody-drug conjugate for the treatment of breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 907.
Abstract 2768: A novel non-terminal tumor sampling procedure using fine needle aspiration supports biomarker discovery
Authors: Suzanne I. Sitnikova, Sophie Munnings-Tomes, Stacy R. Kentner, Kathy Mulgrew, Judit Espana-Agusti, Tianhui Zhang, Kristina M. Ilieva, Hormas M. Ghadially, Matthew J. Robinson, Robert W. Wilkinson, Simon J. Dovedi
Journal: Cancer Research (2021)

Abstract Immunotherapy is part of the standard of care for oncology however, durable objective responses remain limited to a subset of patients. As such there is a crucial need to identify biomarkers that can predict/enrich for treatment response. So far, the majority of proposed biomarkers consist of features of the tumor microenvironment (TME). However, in preclinical mouse models, the collection of tumor tissue for this type of analysis is a terminal procedure obviating the ability to directly link potential biomarkers to response/outcome following treatment. Therefore, we have developed and validated a novel non-terminal tumor sampling method to biopsy the TME in mouse models based on fine needle aspiration. We show that this technique enables repeated in-life sampling of subcutaneous flank tumors without impacting tumor growth or animal welfare. This method yields sufficient sample for flow cytometric analysis of tumor-infiltrating immune cells and we demonstrate that it is able to recapitulate results obtained with the current methodology of whole tumor analysis. We propose that this method represents a simple, fast, minimally invasive technique to enable analysis of the TME, reduction in the number of animals used for preclinical oncology studies and refinement of pharmacodynamic analysis. Additionally, its unique ability to provide longitudinal TME sampling can support investigation of biomarkers of response to treatment. Citation Format: Suzanne I. Sitnikova, Sophie Munnings-Tomes, Stacy R. Kentner, Kathy Mulgrew, Judit Espana-Agusti, Tianhui Zhang, Kristina M. Ilieva, Hormas M. Ghadially, Matthew J. Robinson, Robert W. Wilkinson, Simon J. Dovedi. A novel non-terminal tumor sampling procedure using fine needle aspiration supports biomarker discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2768.
Sexual adverse events-related to dutasteride e finasteride: Analysis of real-life data from EudraVigilance database
Authors: C. De Nunzio, A. Nacchia, R. Lombardo, A. Franco, G. Tema, V. Baldassarri, L. Rovesti, E. Mancini, G. Guarnotta, O.A. Voglino, S. D’Annunzio, F. Di Giacomo, G. Disabato, A. Cicione, A. Tubaro
Journal: European Urology (2021)
Morbidity and mortality after Percutaneous Nephrolithotomy (PCNL) in patients with urolithiasis: Analysis of 16,201 patients from a nationwide German health insurance database
Authors: B. Becker, C. Schulz, T.R.W. Herrmann, C.M. Rosenbaum, A.J. Gross, H. König, C. Netsch
Journal: European Urology (2021)
PD-1<sup>+</sup>CXCR5<sup>−</sup>CD4<sup>+</sup> Th-CXCL13 cell subset drives B cells into tertiary lymphoid structures of nasopharyngeal carcinoma
Authors: Jiang-Ping Li, Chang-You Wu, Ming-Yuan Chen, Shang-Xin Liu, Shu-Mei Yan, Yin-Feng Kang, Cong Sun, Jennifer R Grandis, Mu-Sheng Zeng, Qian Zhong
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background A major current challenge is to exploit tertiary lymphoid structures (TLSs) to promote the lymphocyte infiltration, activation and differentiation by tumor antigens to increase antitumor immune responses. The mechanisms that underlie the role of TLS formation in the adaptive immune responses against nasopharyngeal carcinoma (NPC) remain largely unknown. Methods Cell populations and the corresponding markers were identified by single-cell RNA sequencing and fluorescence-activated cell sorting analysis. In vitro differentiation experiments were used to simulate the generation, regulation and function of the Th-CXCL13 cell subset in the tumor microenvironment of NPC. These were followed by histological evaluation of the colocalization of tumor-associated B cells (TABs) and Th-CXCL13 cells within TLSs, and statistical analysis of the relationship between the cells in TLSs and overall survival. Results A PD-1 + CXCR5 − CD4 + Th-CXCL13 cell subset was identified in NPC. This subset was a major source of CXCL13, representing the majority of the CD4 + T cells at levels comparable with Th1 and Tfh cells present in the TLSs. Monocytes activated by toll-like receptor 4 agonists served as the antigen-presenting cells that most efficiently triggered the expansion of Th-CXCL13 cells. Transforming growth factor beta 1 (TGF-β1) stimulation and activation of Sox4 were critical for the induction and polarization of Th-CXCL13 cells in this process. The potential functional contributions of TABs recruited by Th-CXCL13 cells which induced plasma cell differentiation and immunoglobulin production via interleukin-21 and CD84 interactions in the TLSs demonstrated improved survival. Conclusions Induction of Th-CXCL13 cells links innate inflammation to immune privilege in tumor-associated TLSs and might predict better survival.
Anticoagulant Hydrogel Tubes with Poly(ɛ‐Caprolactone) Sheaths for Small‐Diameter Vascular Grafts
Authors: Chunliang Zhang, Qian Xie, Ruitao Cha, Li Ding, Liujun Jia, Lei Mou, Shiyu Cheng, Nuoxin Wang, Zulan Li, Yang Sun, Chuanjue Cui, Yu Zhang, Yan Zhang, Fengshan Zhou, Xingyu Jiang
Journal: Advanced Healthcare Materials (2021)

Abstract Small‐diameter vascular grafts (inner diameter &lt; 6 mm) are useful in treating cardiovascular diseases. The off‐the‐shelf small‐diameter vascular grafts for clinical applications remain a great limitation owing to their thrombogenicity or intimal hyperplasia. Herein, bilayer anticoagulant hydrogel tubes with poly( ε ‐caprolactone) (PCL) sheaths are prepared by freeze‐thawing and electrospinning, which contain nanofibrillated cellulose (NFC)/poly(vinyl alcohol) (PVA)‐heparin/poly‐ L ‐lysine nanoparticles tube as an inner layer and PCL sheath as an outer layer. The structure, anticoagulant property, and biocompatibility of the inner layer are studied. The effects of thickness of the outer layer on perfusion performance and mechanical property of hydrogel tubes with PCL sheaths (PCL‐NFC/PVA‐NPs tubes) are investigated. The effect of compliance of PCL‐NFC/PVA‐NPs tubes on their blood flow is studied by numerical simulation. The tissue compatibility and the patency of PCL‐NFC/PVA‐NPs tubes are evaluated by implantation in subcutaneous tissue of rats and carotid artery of rabbits. PCL‐NFC/PVA‐NPs tubes have prominent anticoagulation, sufficient burst pressure and good compliance similar to native arteries. PCL‐NFC/PVA‐NPs tubes facilitate infiltration of host cells and achieve active proliferation of recruited cells, which will be a promising candidate for small‐diameter vascular grafts.
CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants
Authors: Oluwabunmi O. Olaloye, Peng Liu, Jessica M. Toothaker, Blake T. McCourt, Collin C. McCourt, Jenny Xiao, Erica Prochaska, Spenser Shaffer, Lael Werner, Jordan Gringauz, Misty Good, Jeffrey D. Goldsmith, Xiaojing An, Fujing Wang, Scott B. Snapper, Dror Shouval, Kong Chen, George Tseng, Liza Konnikova
Journal: The Journal of Experimental Medicine (2021)

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes IL8, CXCL1, CXCL2, CXCL5 and had enrichment of gene sets in pathways involved in chemotaxis, migration, phagocytosis, and reactive oxygen species generation. In summary, we identify a novel subtype of inflammatory monocytes/Mϕ associated with NEC that should be further evaluated as a potential biomarker of surgical NEC and a target for the development of NEC-specific therapeutics.
Evaluating Patient-Reported Outcomes Measures (PROMs) for localised prostate cancer: A systematic review using the Consensus-based Standard for the selection of health Measurement Instruments (COSMIN) methodology
Authors: M.M. Ratti, G. Gandaglia, L. Leardini, S. Mazzoleni Ferracini, E.S. Sisca, A. Derevianko, S. Furnari, K. Beyer, F. Pellegrino, G. Sorce, S. Scuderi, F. Barletta, V. Cucchiara, M.I. Omar, S. Maclennan, J. Zong, S.J. Maclennan, O.L. Aiyegbusi, M. Van Hemelrijck, J. N’dow, F. Montorsi, A. Briganti
Journal: European Urology (2021)
Abstract 2461: SIRT1 regulates ovarian cancer metastasis via altering the exosome release and glycogen deposition
Authors: Sraddhya Roy, Ananya Das, Manisha Vernekar, Subhadip Das, Nabanita Chatterjee
Journal: Cancer Research (2021)

Abstract Ovarian cancer is the lethal most gynaecological malignancy which exhibits high metastatic rate in peritoneal cavity, especially leading to metastasis including omentum. According to the histopathological segregation of ovarian cancer, epithelial ovarian cancer (EOC) is considered as the most metastatic in both pre- or post-menopausal state, thus several changes in hormonal level such as estrogen, progesterone etc., increase the risk of developing ovarian cancer in women. Obesity or fat deposition are observed to be the after effects of hormonal transition mainly due the depletion of estrogen level. In this context, stored glycogen or deposited fat in the cancer cells has recently drawn the research concern. Few studies suggested that hypoxic environment (HIF-1) could regulate the accumulation of glycogen in cancer cells leading the metastatic micro-environment. The level of HIF-1 could coordinate with the SIRT1 status in tumor dormancy via regulating oxidative stress and metabolic alterations that confers the ovarian cancer stem cell like properties. Interestingly, SIRT1 also controls the secretion of pro-tumorigenic exosomes in cancer invasion. Exosomes, small bioactive extracellular vesicles, can migrate expediently through body barriers and promotes the homing of migrating cancer cells. We observed that the overexpressed SIRT1 in EOC patients has increased concentration of secreted exosomes as compared to heathy individuals. Simultaneously, we have shown how SIRT1 level in ovarian cancer cells co-relate with exosome secretion in regulating glycogen deposition of post-menopausal females. Furthermore, we also found that post-menopausal EOC patients have shown an increased expression of lipids and glycogen in the cancer cells. Therefore, we can conclude that ovarian cancer cell derived exosomes might facilitate fat deposition via regulating their oncogenic cargoes to metastasize ovarian cancer. Citation Format: Sraddhya Roy, Ananya Das, Manisha Vernekar, Subhadip Das, Nabanita Chatterjee. SIRT1 regulates ovarian cancer metastasis via altering the exosome release and glycogen deposition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2461.
Progress in the Application of Machine Learning Algorithms to Cancer Research and Care
Authors: Neal J. Meropol, Janet Donegan, Alexander S. Rich
Journal: JAMA Network Open (2021)

Qianyu Yuan, PhD; Tianrun Cai, MD; Chuan Hong, PhD; Mulong Du, PhD; Bruce E. Johnson, MD; Michael Lanuti, MD; Tianxi Cai, SD; David C. Christiani, MD
Abstract 1807: T cell conditional knockout mouse model of the mitochondrial branched chain aminotransferase (BCATm) responds with delayed tumor growth to a lymphoma challenge
Authors: Christie Adam, Alexander Martin, Rebekah Betar, Mercedes Foster, Michael Boyer, Elitsa Ananieva
Journal: Cancer Research (2021)

Abstract Enzymes in amino acid catabolism are emerging as attractive targets for cancer therapies. The mitochondrial branched-chain amino transferase (BCATm), an enzyme catalyzing the first step in leucine, valine, and isoleucine degradation, has been recently implicated in cancer growth but its role in T cell driven anti-cancer immunity has never been explored. To fulfill the gap in current scientific knowledge and address some of the challenges with lymphoma immunotherapies, we used the CD4-Cre-Lox recombination to create a conditional knockout mouse (T-BCATmKO) with CD4+ and CD8+ T cells deficient in the Bcat2 gene that encodes BCATm. Based on initial studies showing that a deletion of BCATm from T cells leads to increased glycolytic and oxygen metabolism and up-regulation of complex 1 of the mammalian target of rapamycin (mTORC1) signaling, we hypothesized that if BCATm is absent from T cells, this would stimulate T cell activation leading to improved T cell function in mice challenged with lymphoma. For this purpose, T-BCATmKO and T-BCATmfl/fl male mice (15-16 weeks old) were subcutaneously injected with 2.5x105 mouse lymphoma EG7-OVA cells. Tumor growth, animal weight, and food intake were recorded daily for a period of 20 days. Mice developed tumors around day 10 and this was not associated with weight loss or poor feeding of the mice as no changes in body weights or food intake between the different mouse groups were observed. Statistical analysis via one-way ANOVA revealed that T-BCATmKO mice had significantly delayed tumor growth compared to T-BCATmfl/fl mice (P= 0.05). In addition, CD4+ T cells isolated from T-BCATmKO mice released significantly more IFNγ after 48-72 hours of activation suggesting that CD4+ T cells from T-BCATmKO mice were more active than T cells from T-BCATmfl/fl mice. This study revealed that targeting BCATm in T cells may offer an advantage in mice to better fight lymphoma cancer and represents an attractive target for future immunotherapeutic anti-cancer approaches. Citation Format: Christie Adam, Alexander Martin, Rebekah Betar, Mercedes Foster, Michael Boyer, Elitsa Ananieva. T cell conditional knockout mouse model of the mitochondrial branched chain aminotransferase (BCATm) responds with delayed tumor growth to a lymphoma challenge [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1807.
Covid-19: Turkmenistan becomes first country to make vaccination mandatory for all adults
Authors: Owen Dyer
Journal: BMJ (2021)

Covid-19: Turkmenistan becomes first country to make vaccination mandatory for all adultsOwen Dyer Turkmenistan will legally require all residents over 18 to be vaccinated against the coronavirus, the country's health ministry said on 7 July.Only those with medical contraindications will be exempted.Turkmenistan's vaccine laws will be the strictest in the world, surpassing those of Saudi Arabia, which since March has operated a broad "no jab, no job" policy in both public and private sectors.Turkmenistan also announced new mask and social distancing requirements, although it has yet to acknowledge any covid-19 deaths.The government of President Gurbanguly Berdymukhamedov has drawn criticism from the World Health Organization for its refusal to provide data on covid cases and deaths, a stance it now shares only with North Korea.Other formerly reluctant countries like Tanzania and Nicaragua have begun reporting.