tbuckley/cabot-search huggingface dataset:
Abstract 1679: Innate immunity and cytokine signaling pathways drive resistance to HSV-1 oncolytic immunovirotherapy in glioblastoma
Authors: Dileep D. Monie, Cristina Correia, Cheng Zhang, Choong Ung, Richard G. Vile, Hu Li
Journal: Cancer Research (2021)

Abstract Glioblastoma multiforme (GBM) is a particularly aggressive primary brain tumor that is relatively common in adults. The disease comes with a dismal prognosis, often with expected survival just over a year when treated with surgery, chemotherapy, and radiation. A promising addition to our GBM treatment arsenal are oncolytic viruses (OVs), a class of immunotherapy now in clinical trials. The most effective OVs home in on tumor cells, killing them and releasing tumor-associated antigens that elicit antitumor immunity. This effectiveness, however, varies depending on the cell state—a property that may be influenced by the composition of the extracellular matrix (ECM) of GBM. Cellular communication network factor 1 (CCN1) is found in the ECM of the majority of GBMs and is predictive of resistance to OVs, particularly those derived from herpes simplex virus type 1 (HSV-1). In this study, our aim is to understand how extracellular CCN1 alters the GBM intracellular state in a manner that confers resistance to OVs. We began by using our NetDecoder platform to build CCN1-specific prioritized protein-protein interaction (PPI) networks from published LN229 human GBM transcriptomic datasets. From this network, we identified 12 PPI edges that dominate the network flow in CCN1-high LN229 cells when compared to CCN1-low controls. The 21 unique nodes that comprise these binary PPI edges were extracted and subjected to downstream biological process overrepresentation analyses using Gene Ontology. We found that the cytokine-mediated signaling pathway (FDR = 4.2 x 10-11; enrichment ratio = 15.8) and the cellular response to cytokine stimulus (FDR = 3.1 x 10-9; enrichment ratio = 10.9) were highly enriched when mapped to these nodes. We conclude that CCN1, acting as a paracrine signal in the GBM tumor microenvironment, primes the cell to inhibit HSV-1 and other candidate OV replication prior to any virus interactions, thus contributing to immunovirotherapy resistance. While CCN1 and its cell surface integrin binding partners are ostensible drug targets for overcoming this resistance, pharmacologic interventions that target CCN1-specific high flow edges in our prioritized PPI network may be more effective. Citation Format: Dileep D. Monie, Cristina Correia, Cheng Zhang, Choong Ung, Richard G. Vile, Hu Li. Innate immunity and cytokine signaling pathways drive resistance to HSV-1 oncolytic immunovirotherapy in glioblastoma [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 1679.
Mental and physical health problems before and after detention: A matched cohort study
Authors: Anja J.E. Dirkzwager, Robert Verheij, Paul Nieuwbeerta, Peter Groenewegen
Journal: The Lancet Regional Health - Europe (2021)

Individuals with poor health are largely overrepresented in prison populations. However, it remains unclear whether their poor health status already exists prior to their detention or reflects an effect of detention. We examined the health of detainees in the year before and after their detention and compared this with the health of matched non-detainees.In this matched cohort study, we linked national data on all persons detained in the Netherlands in 2014/2015 to electronic health records (EHR's) of a representative sample of general practitioners in the Netherlands. Participants include 952 detained persons and 4760 matched non-detained persons (matched on age, sex and general practice). Prevalence rates of health problems in the year before and after detention and odds ratios with 95% confidence intervals were calculated. Rates for a variety of physical and mental health problems are presented.Detainees and matched controls differed statistically significant in their pre-detention health status. Compared with controls, male detainees were more likely to report psychological (odds ratio [OR] 3·64 [95% CI 3·11-4·26]), social (1·96 [1·46-2·64]), neurological (1·34 [1·02-1·76]), digestive (1·23 [1·02-1·49]), genital system-related (1·36 [1·07-1·72]), and unspecified health problems (1·32 [1·10-1·59]) in the year before their detention. For example, 43·7% of detainees and 17·6% of controls reported psychological problems in this pre-detention year. To some extent these pre-detention health differences were related to socioeconomic differences. Nevertheless, after taking these characteristics into account, a number of pre-detention health differences between detainees and controls remained statistically significant. No statistically significant changes in prevalence rates from pre- to post-detention and no differences in the levels of change across detainees and controls were observed. For female detainees a similar pattern was found.People who experience detention have high and complex health needs both pre- and post-detention. While this study did not show a health deteriorating effect of detention, it also did not show a health improving effect. This latter finding may indicate a missed opportunity for health care services to address detainees' health, especially since persons entering detention have elevated health problems. Knowledge on detainees' specific health problems may help health care providers in prisons and in the community to adequately address the health care needs of this vulnerable group.None.
The treatment of hairy cell leukemia with a focus on long lasting responses to cladribine: A 30‐year experience
Authors: Alessandro Broccoli, Lisa Argnani, Laura Nanni, Carolina Terragna, Elena Sabattini, Giulia Gabrielli, Vittorio Stefoni, Cinzia Pellegrini, Beatrice Casadei, Alice Morigi, Ginevra Lolli, Matteo Carella, Paolo Elia Coppola, Pier Luigi Zinzani
Journal: American Journal of Hematology (2021)

Abstract The treatment of hairy cell leukemia (HCL) has considerably changed over years. Purine analogues, namely cladribine, now represent the treatment of choice. One hundred and eighty‐four patients were followed between 1986 and 2018 and treated according to era‐specific guidelines. Responses were classified by combining Consensus Resolution criteria and marrow immunohistochemistry. Patients were grouped according to the number of treatment lines they received. Patients treated first line responded in 86% of cases, with complete response (CR) in 44% of cases. Response rates remained high throughout the first four lines (84%, 81%, 79% for the second line onward, with CR in 38%, 37%, 15% of cases respectively). One hundred and twenty‐two patients received cladribine as first line treatment, with a response rate of 86% and a CR rate of 54%. Among the 66 CR patients, 45 (68%) have never received further therapy: 11 patients are in continuous CR between 5 and 10 years after treatment, 14 between 10 and 20 years and three patients at more than 20 years. Median time‐to‐next treatment (TTNT) for frontline cladribine‐treated patients was 8.2 years: partial responders had a significantly shorter median TTNT than CR patients (5.3 years vs median not reached at 25.8 years, p &lt; 0.001). Patients with HCL require subsequent lines of therapy in more than 50% of cases. Purine analogues allow significant response rates when applied first line and upon retreatment. Some patients may enjoy long lasting treatment‐free intervals after one course of cladribine.
Abstract 799: Reduced diversity of <i>HLA</i> class II alleles may contribute to the early manifestation of breast cancer in <i>BRCA1</i> mutation carriers
Authors: Ekaterina ShKuligina, Alexandr A. Romanko, Tatjana Jankevic, Aleksandr S. Martianov, Tatyana N. Sokolova, Alexandr O. Ivantsov, Evgeny N. Imyanitov
Journal: Cancer Research (2021)

Abstract Female carriers of germline BRCA1 mutation almost inevitably develop breast cancer (BC). However, the age of BRCA1-associated cancer onset varies widely. We hypothesize that age-related penetrance of BRCA1 mutations may depend on the inherited variability in the host immune system. We utilized high-throughput HLA-typing to describe 10 classical HLA class I/II loci for 90 young (&amp;lt;38 y.o.) and 73 elderly (&amp;gt;57 y.o.) BRCA1-mutated BC patients. 39% of young females were homozygous for two or more HLA-II loci; this was significantly higher than in the “elderly” cohort [OR = 3.23; p = 0.002]. In contrast, women who harboured identical alleles at HLA-B locus (class I) had increased chances to stay tumour-free to their older ages [OR = 3.02; p = 0.077]. Allele HLA-DBR1*11:03/04 was overtly overrepresented in elderly BRCA1-driven BC [11% vs. 3%, p = 0.006]. The frequencies of HLA-DRB1*01:01 and HLA-DQB1*05 were significantly higher in group of “young” patients [p = 0.020 and p = 0.011, correspondently]. The tumour immunogenicity was analyzed in early-onset and late-onset BC patients through the evaluation of the intratumoral density of cytotoxic T-lymphocytes (TILs) with anti-CD8 IHC staining. 5/10 carcinomas arisen in young BRCA1-carriers were classified as a “hot” phenotype with a high density of TILs across the tumour. Inversely, the BC developed in “elderly” women was characterized by the reduced levels of TILs. Conclusions: 1) the limited repertoire of HLA peptides caused by the homozygosity for HLA II loci may increase susceptibility to BC in BRCA1-carriers and manifest by early disease onset; 2) tumours from “elderly” BRCA1-associated patients have reduced levels of lymphocytic infiltration compared to “young” patients. The research is supported by RSF grant #19-15-00207 Citation Format: Ekaterina ShKuligina, Alexandr A. Romanko, Tatjana Jankevic, Aleksandr S. Martianov, Tatyana N. Sokolova, Alexandr O. Ivantsov, Evgeny N. Imyanitov. Reduced diversity of HLA class II alleles may contribute to the early manifestation of breast cancer in BRCA1 mutation carriers [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 799.
Abstract PL02-02: Harnessing the value of mutational signatures in whole cancer genomes
Authors: Serena Nik-Zainal
Journal: Cancer Research (2021)

Abstract Mutational signatures are the imprints of DNA damage and DNA repair processes that have been operative during tumorigenesis. They are biologically informative, reporting on the processes that have contributed to the developmental history of each patient's cancer. In this lecture, on behalf of my team and my collaborators, I shall provide an update on the field, focusing on validation of these abstract mathematical concepts, untangling the mechanisms underpinning mutation patterns in human somatic cells, and describing the new insights that we have gained through combinations of computational analysis and experiments in cell-based systems. We showcase how mutational-signature-based clinical algorithms have been developed, describe the path taken in translating these towards medical utility and for balance, highlight some of the hurdles that need to be navigated in this type of translational research. Citation Format: Serena Nik-Zainal. Harnessing the value of mutational signatures in whole cancer genomes [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 PL02-02.
Assessment of Apparent Diffusion Coefficients and SUVs as Predicators of Histological Differentiation in Anal Squamous Cell Carcinoma
Authors: Arman Parsai, Imene Zerizer, Hikmat Jan, Adrian Kastler, Sana Subhan, Petra Balogh, Ewa Nowosinska, Mohammed Thaha, Marc. E. Miquel
Journal: Clinical Nuclear Medicine (2021)

Aim The study aims to assess minimal apparent diffusion coefficient (ADC min ) and SUV max as predictors of histological differentiation in patients with anal squamous cell carcinoma (ASCC) and to determine cutoff values for each histopathological tumor grade. Patients and Methods A retrospective study of 41 ASCC patients (14 males, 27 females; mean age, 65 ± 13 years) staged with FDG PET/CT and MRI (mean scan time interval, 21 ± 11 days). SUV max and ADC min values were measured and compared with histopathological tumor grading obtained from biopsy. Results The mean size and tumor volume were 3 ± 2 cm and 16.5 ± 27.3 cm 3 , respectively. The mean ADC min values for well-, moderately, and poorly differentiated ASCC were 935 ± 179, 896 ± 123, and 637 ± 114, respectively. The mean SUV max for well-, moderately, and poorly differentiated ASCC were 6.9 ± 1.8, 11.5 ± 4.1, and 13.4 ± 2.6, respectively. The difference in mean ADC min values between poorly and moderately/well-differentiated tumors was statistically significant, whereas this was not significant between moderately and well-differentiated tumors. Differences in SUV max values were statistically significant between poorly/moderately and well-differentiated tumors, whereas there was no statistical significance between poorly and moderately differentiated tumors. By combining the 2 modalities using cutoff values of 675 × 10 −6 mm 2 ·s −1 for ADC min and 8.5 for SUV max , it was possible to differentiate the tumor categories with a sensitivity, specificity, positive predictive value, and negative predictive value, respectively, of 84.6%, 96.4%, 91.7%, and 93.1% for well-differentiated ASCC, 76.5%, 87.5%, 81.3%, and 84% for moderately, and 90.9%, 89.3%, 76.9%, and 96.2% for poorly differentiated ASCC, respectively. Conclusions ADC min and SUV max values correlated with the degree of differentiation in ASCC and can be used as predictors of tumor grading and aggressiveness. Combined ADC min and SUV max cutoff values can therefore be used for early patient risk stratification and treatment decision making.
Abstract 1229: Novel Arf1-targeting ã-dipeptides counteract triple negative breast cancer by inducing autophagic death
Authors: Leilei He, Alain Chavanieu, Yen Vo-Hoang, Yong Teng
Journal: Cancer Research (2021)

Abstract ADP-ribosylation factor 1 (Arf1) is a crucial regulator in vesicle-mediated membrane trafficking and involved in the activation of signaling molecules. However, the molecular mechanisms underlying Arf1-dependent cancer development and progression are far from understood. We report here that Arf1 is the most amplified gene in Arf gene family in breast cancer, and knocking it down leads to an induction of autophagy via the AMPK pathway. To effectively target Arf1, we rationally designed and synthesized constrained ATC-based (4-amino-(methyl)-1,3-thiazole-5-carboxylic acid) γ-dipeptides, which can block Arf1 activation more efficiently than other commercially available Arf1 inhibitors through targeting the Arf1-GDP/ARNO complex at the Golgi. The anticancer effects of these γ-dipeptides were evaluated in triple native breast cancer MDA-MB-231 cells and their bone-seeking and lung-seeking sublines, showing reduced cell viability along with significant increased autophagy following treatment in both 2D and 3D cell cultures. Among these new inhibitors, the γ-dipeptide 10b displayed strongest cytotoxicity. The orthotopic NSC mouse model for breast cancer further showed the γ-dipeptides 10b exhibited a superior anticancer effects by inducing autophagic cell death in breast tumor, with no significant systemic toxicity. These findings reveal that Arf1-targeting γ-dipeptides developed by our collaborative team may represent a promising targeted therapeutic to improve treatment of breast cancer. Citation Format: Leilei He, Alain Chavanieu, Yen Vo-Hoang, Yong Teng. Novel Arf1-targeting ã-dipeptides counteract triple negative breast cancer by inducing autophagic death [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 1229.
Abstract 579: Multiplex digital PCR combined with melting curve analysis for detecting <i>KRAS</i> mutations towards pancreatic cancer diagnosis
Authors: Junko Tanaka, Tatsuo Nakagawa, Takeshi Ishida, Yoshio Kamura, Akiko Shiratori, Kunio Harada, Chihiro Uematsu
Journal: Cancer Research (2021)

Abstract Background Digital PCR (dPCR) is a promising method for liquid biopsies and is able to quantify nucleic acids more sensitively than real-time PCR. However, dPCR has a large fluctuation in the fluorescence intensity of the droplets or wells due to insufficient PCR in the small partitions, limiting the multiplexing capability of using the fluorescence intensity. In this study, we propose a measurement method that combines dPCR with melting curve analysis for highly multiplexed genotyping. Methods A sample is digitized into a silicon chip with up to ~104 wells in which asymmetric PCR was performed to obtain more single-stranded amplicons that are complimentary to molecular beacon probes. Fluorescence images were captured while controlling the temperature of the chip, and melting curve was measured for each well. Then, genotyping was performed by using the fluorescence intensity, dye color of the probe, and melting temperature (Tm). Because the Tm of the PCR products does not considerably depend on the amplification efficiency of PCR, genotyping accuracy is improved by using Tm values, enabling highly multiplexed genotyping. Results The concept was confirmed by simultaneously identifying wild-type KRAS, BRAF and, eight mutants of these genes (G12D, G12R, G12V, G13D, G12A, G12C, G12S, and V600E) through four-color melting curve analysis. G12D, G12V and G12R-mutant KRAS alleles were detected with FAM-labeled probes, G13D-mutant KRAS allele and wildtype KRAS allele were detected with HEX-labeled probes, G12S and G12C-mutant KRAS alleles were detected with Cy5-labeled probes, and V600E-mutant BRAF allele and wildtype BRAF allele were detected with CAL Fluor Red 610-labeled probes. The results showed that the peaks of the Tm distributions of the DNA groups were separated by 3.5 °C on average, while the standard deviation of the Tm distributions was 0.23 °C on average. The difference in Tm was 15 times larger than the standard deviation, enabling more accurate genotyping than when using the fluorescence intensity. Conclusion We have proposed a measurement method that combines dPCR with melting curve analysis, and successfully performed the multiplexed genotyping assay. We plan to evaluate the effect of this method on measurement using clinical specimens of pancreatic cancer patients in the future. Citation Format: Junko Tanaka, Tatsuo Nakagawa, Takeshi Ishida, Yoshio Kamura, Akiko Shiratori, Kunio Harada, Chihiro Uematsu. Multiplex digital PCR combined with melting curve analysis for detecting KRAS mutations towards pancreatic cancer diagnosis [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 579.
Transperineal vs. transrectal MRI-targeted prostate biopsy: Evaluation of cancer detection risk and biopsy accuracy for clinical significant prostate cancer
Authors: F. Zattoni, G. Marra, V. Kasivisvanathan, A. Kretschmer, M. Apfelbeck, F. Barletta, G. Cirulli, A. Marquis, P. Gontero, H. Guo, J. Zhuang, A. Morlacco, M. Soligo, F. Dal Moro, G. Gandaglia
Journal: European Urology (2021)
Ways to Quit Smoking
Authors: Kristin Walter
Journal: JAMA (2021)

Ryan J. Courtney, PhD; Hayden McRobbie, PhD; Piotr Tutka, MD; Natasha A. Weaver, PhD; Dennis Petrie, PhD; Colin P. Mendelsohn, MBBS; Anthony Shakeshaft, PhD; Saki Talukder, MPH; Christel Macdonald, BPsych; Dennis Thomas, PhD; Benjamin C. H. Kwan, PhD; Natalie Walker, PhD; Coral Gartner, PhD; Richard P. Mattick, PhD; Christine Paul, PhD; Stuart G. Ferguson, PhD; Nicholas A. Zwar, PhD; Robyn L. Richmond, DSc; Christopher M. Doran, PhD; Veronica C. Boland, PhD; Wayne Hall, PhD; Robert West, PhD; Michael Farrell, MB
Bio-printing of aligned GelMa-based cell-laden structure for muscle tissue regeneration
Authors: Hanjun Hwangbo, Hyeongjin Lee, Eun-Ju Jin, JaeYoon Lee, Yunju Jo, Dongryeol Ryu, GeunHyung Kim
Journal: Bioactive Materials (2021)

Volumetric muscle loss (VML) is associated with a severe loss of muscle tissue that overwhelms the regenerative potential of skeletal muscles. Tissue engineering has shown promise for the treatment of VML injuries, as evidenced by various preclinical trials. The present study describes the fabrication of a cell-laden GelMa muscle construct using an in situ crosslinking (ISC) strategy to improve muscle functionality. To obtain optimal biophysical properties of the muscle construct, two UV exposure sources, UV exposure dose, and wall shear stress were evaluated using C2C12 myoblasts. Additionally, the ISC system showed a significantly higher degree of uniaxial alignment and myogenesis compared to the conventional crosslinking strategy (post-crosslinking). To evaluate the in vivo regenerative potential, muscle constructs laden with human adipose stem cells were used. The VML defect group implanted with the bio-printed muscle construct showed significant restoration of functionality and muscular volume. The data presented in this study suggest that stem cell-based therapies combined with the modified bioprinting process could potentially be effective against VML injuries.
効果的な変形性関節症治療のための移植可能で分解性の抗酸化ポリ(ε-カプロラクトン)-リグニンナノファイバー膜【JST・京大機械翻訳】
Authors: Liang Ruiming, Zhao Jinmin, Li Bo, Cai Peian, Loh Xian Jun, Xu Chuanhui, Chen Peng, Kai Dan, Zheng Li
Journal: Biomaterials (2020)