bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B024: Nuclear size and nuclear shape instability in prostate cancer epithelial cells during metastatic progression
Authors: Cavassani Karen , Posadas Edwin , Teng Pai-Chi , Pustchi Sadaf Pustchi , Kim Minhyung , Bhowmick Neil , You Sungyong , Freeman Michael , Ellis Leigh , Vizio Dolores Di , Tseng Hsian-Rong , Chung Leland W. , Yao Susan , Grasso Catherine 
Published: June 2023

Abstract
Very small nuclear (vsn) circulating tumor cells (CTCs) are detected in a subgroup of metastatic, castration resistant prostate cancer (mCRPC) patients who develop visceral metastasis following intensive androgen receptor suppression. In addition, we have previously observed that nuclear shape instability (characterized by the loss and/or mis-localization of the nuclear envelop protein emerin) is present in human prostate cancer tissues, and in CTCs from patients with metastatic disease. Herein, we investigated the biological and clinical implications of the vsn phenotype in prostate CTCs. Patients with vsnCTCs had poor overall survival and low PSA response to androgen receptor suppression compared with non-vsnCTC patients. The vsnCTCs exhibited a loss/downregulation of emerin (EMD) and we found a direct correlation between emerin loss and nuclear size reduction in CTC from mCRPC patients. Further, in vitro studies revealed that the vsn phenotype was characterized by high invasive capacity, enhanced cellular plasticity, and resistance to AR target therapy. Finally, depletion of EMD in prostate tumor cells resulted in the vsn phenotype. Together, these findings demonstrate that the vsnCTC phenotype is characterized by deregulation of EMD expression, and the presence of these cells result in poor clinical outcomes in prostate cancer.
Citation Format: Karen Cavassani, Edwin Posadas, Pai-Chi Teng, Sadaf Pustchi Pustchi, Minhyung Kim, Neil Bhowmick, Sungyong You, Michael Freeman, Leigh Ellis, Dolores Di Vizio, Hsian-Rong Tseng, Leland W. Chung, Susan Yao, Catherine Grasso. Nuclear size and nuclear shape instability in prostate cancer epithelial cells during metastatic progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B024.
Abstract B052: Prostate cancer prevention is possible thanks to the evaluation of the primary exons of the BRCA1 biomarker in men
Authors: Moussa Haboubacar Elhadji Yaou , Chichi Callinis Capo 
Published: June 2023

Abstract
Prostate cancer is a public health concern among 50 year old the men worldwide and its incidence keep rising. It is triggered by genome instability or epigenetic modifications impacting DNA repair and tumor suppression genes and proteins. In African countries, little data is available on prostate cancer and the loss of BRCA1 exons responsible for tumor suppression. It is in this context that we undertook this study, the general objective of which is to assess the association between BRCA1 instability in patients with prostate cancer, These men with prostate cancer usually present with symptoms like nocturia and poor urinary flow, erectile dysfunction and visible hematuria.
Citation Format: Haboubacar Elhadji Yaou Moussa, Callinis Capo Chichi. Prostate cancer prevention is possible thanks to the evaluation of the primary exons of the BRCA1 biomarker in men [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B052.
Abstract B057: ZBTB7A as a novel vulnerability in neuroendocrine prostate cancer
Authors: Bae Song Yi , Bergom Hannah E. , Day Abderrahman , Greene Joseph T. , Freedman Tanya S. , Hwang Justin H. , Drake Justin M. 
Published: June 2023

Abstract
Neuroendocrine prostate cancer (NEPC) is a lethal variant of aggressive prostate cancer. Hallmarks of NEPC include the loss of androgen receptor (AR) signaling and transdifferentiation toward small-cell neuroendocrine (SCN) phenotypes, which result in resistance to AR-targeted therapy. NEPC resembles other SCN carcinomas clinically, histologically and genomically. Here, we leveraged SCN phenotype scores of various cancer cell lines and gene depletion screens from the Cancer Dependency Map (DepMap) to identify vulnerabilities in NEPC. We discovered ZBTB7A, a transcription factor, as a candidate promoting the progression of NEPC. Cancer cells with high SCN phenotype scores showed a strong dependency with RET kinase, an emerging therapeutic target of NEPC, suggesting the NEPC-like phenotype of the cells. Then, we observed a strong correlation between dependencies of RET and ZBTB7A in these cells. Utilizing informatic modeling of whole transcriptome sequencing data from patient samples, we revealed distinct gene networking patterns of ZBTB7A in NEPC versus prostate adenocarcinoma. Specifically, we observed a robust association of ZBTB7A with genes promoting cell cycle progression in NEPC, and this result was confirmed through Gene Set Enrichment Analysis. Furthermore, we showed a potential interaction of ZBTB7A with apoptosis regulating genes. Silencing ZBTB7A in a NEPC cell line confirmed the dependency of cells on ZBTB7A for cell growth, and the role of ZBTB7A in regulating G1/S transition in cell cycle and inducing apoptosis. Collectively, our results highlight the oncogenic function of ZBTB7A in NEPC, and emphasize the value of ZBTB7A as a promising therapeutic strategy for targeting NEPC tumors.
Citation Format: Song Yi Bae, Hannah E. Bergom, Abderrahman Day, Joseph T. Greene, Tanya S. Freedman, Justin H. Hwang, Justin M. Drake. ZBTB7A as a novel vulnerability in neuroendocrine prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B057.
Abstract B069: SPOP loss places the prostate luminal epithelial cells at a selective disadvantage
Authors: Rizwan Kinza , Skapura Darlene , Mason Cammy , Coarfa Cristian , Mitsiades Nicholas , Young Damian , Kaochar Salma 
Published: June 2023

Abstract
Background: Prostate cancer (PC) is the single most common and second-most lethal cancer in men, with over 268,000 estimated cases and over 34,500 estimated deaths in the US in 2022. The Speckle-Type POZ protein (SPOP) mutant subclass of PC accounts for 10% to 15% of all primary PC cases. SPOP is an adaptor for Cullin3/Ring (CUL3-RING)-type E3 ubiquitin ligase complexes and provides substrate specificity. The Cancer Genome Atlas (TCGA) studies show that SPOP is the most frequently mutated gene in primary prostate cancer (PC). Interestingly, PC-associated SPOP mutations are always missense and occur in a heterozygous fashion. The current gap in knowledge is the lack of understanding of the role of wildtype SPOP in PC. Methods: By utilizing prostate specific SPOP knockout (KO) mice, we recently reported increased levels of AR and MYC protein and increased cellular turnover (both proliferation and apoptosis) in the prostate luminal epithelium compared to wildtype prostates. We now characterized these mice for the expression of Cre protein and SPOP mRNA at different age using immunohistochemistry and RNA in situ hybridization. Furthermore, we performed RNA-sequencing analysis in the SPOP knockout mice and matched control littermates. Moreover, we performed RNA-seq in LNCaP, LNCaP-Abl, and RWPE1 cells following SPOP inhibition via siRNA targeting SPOP. Finally, we compared our SPOP inhibition signature from in vitro cell lines and prostate specific SPOP knockout murine model to gain insights about the role of wildtype SPOP protein in the prostate epithelium. Result: Using our Spopfl/fl;PBCre+ model, we observed SPOP floxed cells are rapidly lost and the murine prostate epithelium was repopulated with SPOP wildtype carrying cells. Similarly, knockdown (KD) of SPOP through siRNA treatment in a panel of PC cell lines resulted in a significant reduction in cell viability. These observations suggest that SPOP is important for the normal prostate cell viability. Further transcriptomic profiling of SPOP KO (from transgenic murine model) as well as siSPOP treated in vitro prostate cell lines revealed a significant reduction in the transcriptional activity of the AR. Conclusion: Our data illustrate for the first time a critical role for SPOP in the growth and survival of the prostate epithelium and prostate cancer cell. Our findings further validates SPOP as a important therapeutic target for the treatment of prostate cancer.
Citation Format: Kinza Rizwan, Darlene Skapura, Cammy Mason, Cristian Coarfa, Nicholas Mitsiades, Damian Young, Salma Kaochar. SPOP loss places the prostate luminal epithelial cells at a selective disadvantage [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B069.
Abstract IA014: Drug sensitivity of multifocal primary prostate cancer
Authors: Kruithof-de Julio Marianna , Kang Juening , Karkampouna Sofia , Ovchinnikova Katja , Chouvardas Panagiotis , Thalmann George N 
Published: June 2023

Abstract
Prostate cancer (PCa) is a highly heterogeneous disease with multiple and distinct cancer foci within the same prostate gland. We hypothesize that heterogeneous lesions, in terms of genomic aberrations and tumour staging, may be linked to different functional properties e.g. differential drug response sensitivity. We investigate which histopathological and molecular properties are associated with ability to maintain PCa cells as ex vivo organoid cultures and possibly specific drug responses. Interestingly, the majority of primary PCa cases showed genetic and histopathological multifocality, representing a highly heterogeneous cohort. PDOs recapitulated the genetic signature of the parental tissues. Drug responses of PDOs did not follow patient-specific patterns but rather revealed high inter- and intra-patient heterogeneity. Therapy response could be predicted based on transcriptomic profile for personalized treatment decision. The transcriptomic profile of each case was overall preserved among different cores. Drug responses in PDOs revealed not only inter- but also intra-patient heterogeneity with only 2 patient cases having positive correlation within the different cores of the same case. Statistically significant correlations were found among 8 genomic mutations and sensitivity to 5 drug compounds. Different features were tested for ML model, with RNA-seq outperforming the rest features; on average 260-1800 genes per drugs were selected for the drug prediction. ML linear regression models showed high Pearson’s correlation between predicted and observed drug response values.
Citation Format: Marianna Kruithof-de Julio, Juening Kang, Sofia Karkampouna, Katja Ovchinnikova, Panagiotis Chouvardas, George N Thalmann. Drug sensitivity of multifocal primary prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA014.
Abstract PR009: Basal cell lineage plasticity in prostate homeostasis, repair and tumor initiation
Authors: Gao Dong 
Published: June 2023

Abstract
Androgen deprivation is the paradigm of prostate cancer treatment. It is often linked to the loss of luminal cells, but the basal cell fates under androgen deprivation, prostatitis and cancer initiation remain unclear. Using a genetic proliferation tracer (ProTracer) system, we found that adult prostate basal cells also had extensive cell loss and proliferation during androgen-mediated prostate regression and regeneration. A rare basal population that expresses luminal cell genes (termed Basal-B) and a large basal population (termed Basal-A) were identified in the mouse prostate by single-cell RNA sequencing. Basal-B cells exhibited greater capacity for organoid formation and luminal cell differentiation in vitro. Basal-A and Basal-B cells were specifically tracked at the same time in vivo using a genetic lineage-tracing system that uses dual recombinases (Cre and Dre). Fate-mapping showed that prostate basal regeneration is not driven by rare Basal-B cells. Clonal analysis showed that Basal-B cells had the better tendency to generate luminal cells under bacteria-induced prostatitis. Moreover, oncogenic transformation of basal cells promoted the Basal-B cell marker gene expression in vivo. This study provides genetic evidence of a bona fide of basal cell lineage plasticity under androgen deprivation, prostatitis and oncogenic transformation contexts.
Citation Format: Dong Gao. Basal cell lineage plasticity in prostate homeostasis, repair and tumor initiation [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR009.
Abstract PR010: First-in-class TRPV6 inhibitors for the treatment of prostate cancer
Authors: Beaumont Kimberley , Pouwer Rebecca , Rahmani Raphael , McLachlan Matthew , Levrier Claire , Farrow Rebecca , Yeh Mei , Johnson Therese , Kumarasiri Malika , Wijesekera Hasanthi , Stuchbury Grant , Cock Terrie-Anne , Harvey Andrew , Monteith Gregory , Dymock Brian 
Published: June 2023

Abstract
TRPV6, a calcium channel, is an oncochannel that is overexpressed in epithelial cancers including prostate cancer. We have developed a novel series of first-in-class small molecule TRPV6 inhibitors for the treatment of advanced prostate cancer. Our preclinical candidate QED-203 has been shown to inhibit calcium influx at low nM potency in TRPV6 cellular assays (FLIPR, electrophysiology), and has low nM potency in a TRPV6-driven NFAT assay (NFAT luciferase reporter). Inhibition of TRPV6 with our TRPV6 inhibitors or by siRNA knockdown causes changes in genes related to NFAT and WNT signalling, ER stress and the cell cycle (RNAseq and qPCR analysis), and causes cell cycle arrest, decreased proliferation and apoptosis in prostate cancer cells (demonstrated via imaging and FACS analysis). Importantly, QED-203 demonstrates potency in enzalutamide resistant cell lines (in vitro proliferation inhibition) and has superior potency over enzalutamide and darolutamide [androgen receptor targeting agents (ARTA)] in prostate cancer cell lines with clinically relevant AR mutations or the ARV7 splice variant. The ARV7 variant in particular is represented in a significant portion of patients no longer responding to ARTA SoC interventions. QED-203 has high bioavailability with a pharmacokinetic profile amenable to once-a-day oral dosing. QED-203 is well tolerated in rodents and has similar in vivo efficacy (tumour growth and PSA inhibition) to enzalutamide in a castrated LNCaP mouse model of prostate cancer. We have also shown QED-203 target engagement in rodents by demonstrating a change in calcium levels in the urine, and have observed changes in genes consistent with a TRPV6-specific mode of action in xenograft tumours (demonstrated via qPCR). QED-203 targets a novel, non-hormonal mechanism in prostate cancer, and could be used to treat prostate cancer patients who have developed resistance to AR therapies, where there is a large unmet need.
Citation Format: Kimberley Beaumont, Rebecca Pouwer, Raphael Rahmani, Matthew McLachlan, Claire Levrier, Rebecca Farrow, Mei Yeh, Therese Johnson, Malika Kumarasiri, Hasanthi Wijesekera, Grant Stuchbury, Terrie-Anne Cock, Andrew Harvey, Gregory Monteith, Brian Dymock. First-in-class TRPV6 inhibitors for the treatment of prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR010.
Pancreatic Neoplasms Are Frighteningly Common: A Role for Immune Surveillance?
Authors: Hoffman Megan T. , Dougan Stephanie K. 
Published: June 2023

Summary:Carpenter and colleagues analyze organ donors to find that pancreatic intraepithelial neoplasia (PanIN), the precursor lesions of pancreatic ductal adenocarcinoma, are highly prevalent in the average healthy adult starting from a young age. Why these precursor lesions do not progress to cancer in most people is a mystery.See related article by Carpenter et al., p. 1324 (1).
Melanoma Genomics: Shifting Focus from Inter- to Intrapatient Variation
Authors: Shain A. Hunter 
Published: June 2023

Summary:Traditionally, omic studies have prioritized the number of patients over the number of tumors per patient, but in a reversal of this study design, Spain and colleagues performed the largest intrapatient analysis of melanoma to date. Their work reveals mechanisms of treatment resistance, patterns of metastatic dissemination, and new insights into the evolutionary trajectories of melanoma.See related article by Spain et al., p. 1364 (1).
Power Analysis for Ordinal Analyses of the Modified Rankin Scale and an Online and Downloadable Tool for Practical Use
Authors: Johns Hannah , Campbell Bruce , Turc Guillaume , Churilov Leonid 
Published: June 2023

BACKGROUND:
Several methods for conducting power analysis of studies with outcomes across the full ordinal modified Rankin Scale are proposed in the literature. No systematic comparison of accuracy, agreement, and sensitivity to small changes in hypothesized effect sizes for these methods is available. Our aim is to conduct such a systematic comparative analysis and to introduce a comprehensive freely available online tool to facilitate appropriate power analyses for ordinal outcomes.

METHODS:

We performed simulation studies utilizing the control arm modified Rankin Scale distributions from the AVERT (A Very Early Rehabilitation Trial), EXTEND (Extending the Time for Thrombolysis in Emergency Neurological Deficits), and HERMES (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) studies, as well as a uniform distribution, in combination with hypothetical treatment effects. We systematically evaluated published power formulas for Ordinal Logistic Regression and Tournament Methods (generalized odds ratio; Win Probability; Win Ratio; and Wilcoxon-Mann-Whitney
U
test). We also developed an online and downloadable Shiny R app facilitating sample size calculation for, and ordinal analysis of, modified Rankin Scale data.

RESULTS:

Power formulas for Tournament Methods performed well, while the formula for ordinal logistic regression was inaccurate. Tang’s Wilcoxon-Mann-Whitney
U
test sample size formula exhibited the highest accuracy. All methods, including ordinal logistic regression, had almost identical empirical power for a given sample size. All power methods exhibited sensitivity to small changes in hypothesized effect size. The developed freely available online app supports analytical and visualization requirements for all investigated methods for power and statistical analyses of ordinal modified Rankin Scale outcomes.

CONCLUSIONS:

As Tournament Method sample size formulas are assumption-free and accurately calculate power, stroke researchers should use these methods when designing studies with outcomes measured on the full or partially collapsed modified Rankin Scale as well as other ordinal scales, even if they intend to use ordinal logistic regression for analysis. Conducting sensitivity analyses of the effect size assumptions are essential for appropriate sample size estimation. Our developed tool supports both of these recommendations (
https://www.thembc.com.au/tournamentmethods
).
Voices of the Dying
Authors: Kucharski Janek 
Published: June 2023

Abstract
This paper discusses the convention of off-stage cries deployed in Greek tragedy and satyr play chiefly to represent violent events. Unlike other studies dedicated to this topic, it is primarily focused on the cries themselves and to a lesser extent on their context, both dramatic and theatrical. Using the familiar distinction between word and action, it begins with a simple question: how exactly does an off-stage cry represent a violent event taking place within? Examined first as textual phenomena the voices from within are found to acquire their meaning through the discourse of the characters, and not as cries per se. The performative approach, however, also brings their auditory dimension into perspective. Although the evidence is mostly circumstantial, its cumulative weight does suggest that the vocal qualities of the off-stage cries could endow them with meanings unaccounted for in the textual perspective.
Two new species of sedentary nematodes of the genus Meloidodera Chitwood, Hannon & Esser, 1956 (Tylenchida: Heteroderidae) from Mexico
Authors: Cid del Prado Vera Ignacio , Subbotin Sergei A. 
Published: June 2023

Summary
Two new species of the genus Meloidodera collected in Mexico are described here: M. ferrisi sp. n. parasitising roots of an oak tree in the State of Mexico and M. tecoacensis sp. n. parasitising roots of buffalo bur nightshade in the Tlaxcala State. Meloidodera ferrisi sp. n. is characterised by a spherical female body covered completely by a dark thick cuticular layer, length/width of the female body = 0.8-1.6, stylet = 35-43 μm and second-stage juvenile with average body = 340 μm and average tail length = 35.6 μm. Meloidodera tecoacensis sp. n. is characterised by the female having a spherical body covered with a yellow transparent material, length/width of the female body = 1.1-2.8, stylet = 20-33 μm and second-stage juvenile with average body = 340 μm and average tail length = 29.8 μm. These two species were molecularly characterised using the D2-D3 expansion segments of 28S rRNA, ITS rRNA and COI gene sequences. Phylogenetic analysis revealed that the two new species represent a separate evolutionary lineage within the subfamily Meloidoderinae. An identification key for 12 Meloidodera species is provided.
Difference analysis of respiratory pore flora between dolphins in the wild and in captivity
Authors: Li Siyao , Liao Jianxun , Liu Xiaodan , Zhang Lihuan , Luo Zhanqing , Zhang Huixiang , Cao Xue 
Published: June 2023

Abstract
Dolphins are marine mammals with unique anatomical structures in their airways. These particular respiratory structures make dolphins very sensitive to microorganisms in the air, and the habitats of dolphins in captivity and in the wild are quite different. This causes captive dolphins to suffer from illnesses, especially respiratory diseases. Previous studies have shown that the respiratory flora plays an essential role in the health of humans and animals. Therefore, by comparative analysis of the respiratory flora of wild dolphins and dolphins in captivity, we want to find the flora related to dolphins’ respiratory diseases, and try to improve dolphin health through flora homeostasis. For this purpose, we performed 16S rRNA gene sequencing and analyses. We found that Proteobacteria, Firmicutes, Actinobacteria, Campilobacterota, Paracoccus, and other flora differed between wild and healthy and sub-healthy captive dolphins. Some of them are the dominant flora for promoting health, and the others may be essential pathogenic bacteria in the sub-healthy state of dolphins in captivity.