82 research outputs found
Social History of the People’s Republic of Poland Written by Film. Some Remarks on the Margins of Dorota Skotarczak’s Monograph, <i>Stanisław Bareja. Jego czasy i filmy</i> [Stanisław Bareja. His Times and Films] (Łódź, 2022, Wydawnictwo Uniwersytetu Łódzkiego, ‘PRL. Biografie’ Series, pp. 257)
No full textTekst omawia publikację naukową Doroty Skotarczak z 2022 r., pt. Stanisław Bareja. Jego czasy i filmy. Autor artykułu recenzyjnego wpisał swoje opracowanie w kontekst historii Polski Ludowej.The text discusses Dorota Skotarczak’s 2022 academic publication, entitled Stanisław Bareja. Jego czasy i filmy [Stanisław Bareja. His Times and Films]. The author of the review article placed his study in the context of the history of People’s Poland
Historia społeczna PRL filmem pisana. Kilka uwag na marginesie monografii Doroty Skotarczak, Stanisław Bareja. Jego czasy i filmy, Łódź 2022, Wydawnictwo Uniwersytetu Łódzkiego („PRL. Biografie”), ss. 257
No full textThe text discusses Dorota Skotarczak’s 2022 academic publication, entitled Stanisław Bareja. Jego czasy i filmy [Stanisław Bareja. His Times and Films]. The author of the review article placed his study in the context of the history of People’s Poland.Tekst omawia publikację naukową Doroty Skotarczak z 2022 r., pt. Stanisław Bareja. Jego czasy i filmy. Autor artykułu recenzyjnego wpisał swoje opracowanie w kontekst historii Polski Ludowej
The Immunogenomic Landscape of Neuroendocrine Prostate Cancer
No full textPurpose: Patients with neuroendocrine prostate cancer (NEPC) are often managed with immunotherapy regimens extrapolated from small cell lung cancer (SCLC). We sought to evaluate the tumor immune landscape of NEPC compared to other prostate cancer types and SCLC. Experimental design: In this retrospective study, a cohort of 170 patients with 230 RNA sequencing and 104 matched whole exome sequencing data were analyzed. Differences in immune and stromal constituents, frequency of genomic alterations, and associations with outcomes were evaluated. Results: In our cohort, 36% of the prostate tumors were identified as CD8+ T-cell inflamed, while the remaining 64% were T-cell depleted. T-cell inflamed tumors were enriched in anti-inflammatory M2 macrophages and exhausted T-cells and associated with shorter overall survival relative to T-cell depleted tumors (HR=2.62, p<0.05). Among all prostate cancer types in the cohort, NEPC was identified to be the most immune depleted, wherein only 9 out of the 36 total NEPC tumors were classified as T-cell inflamed. These inflamed NEPC cases were enriched in interferon gamma signaling and PD-1 signaling compared to other NEPC tumors. Comparison of NEPC with SCLC revealed that NEPC had poor immune content and less mutations compared with SCLC, but expression of checkpoint genes PD-L1 and CTLA-4 was comparable between NEPC and SCLC. Conclusions: NEPC is characterized by a relatively immune-depleted tumor immune microenvironment compared with other primary and metastatic prostate adenocarcinoma except in a minority of cases. These findings may inform development of immunotherapy strategies for patients with advanced prostate cancer
The DNA Helicase Hells Is a New Unconventional Player in ALK- Anaplastic Large Cell Lymphoma Biology.
No full textDeep learning for classification of breast cancer in optical coherence tomography (OCT) imaging (Conference Presentation)
No full textAbstract 992: Patient-derived tumor organoids of neuroendocrine prostate cancer
No full textAbstract
Background: The development of neuroendocrine prostate cancer (NEPC) is one mechanism of treatment resistance to androgen receptor (AR)-targeted therapies for a subset of patients with advanced prostate cancer. This is associated with transition from a prostate adenocarcinoma to small cell/NEPC histology, low AR signaling signaling, and expression of neuroendocrine markers as Chromogranin A (CGHA), Synaphophysin (SYP) and CD56). Patient derived preclinical models recapitulating the NEPC phenotype may be used to address NEPC pathogenesis and test emerging therapeutic targets.
Methods: Tumor organoids were developed according to protocols previously described (Gao et al, Cell 2015). Briefly the tissue biopsies (liver and bone biopsy) were washed, enzymatically digested and then seeded in Matrigel (BD) droplets. Organoids were characterized at genomic (WES), RNA and protein level (IHC) to confirm the expression of specific markers. Lentiviral infections were performed using shRNAs against EZH2 to knock down EZH2 in organoids. Organoids were also subcutaneously injected in NSG mice to generate patient derived xenografts (PDXs) for drug treatment in vivo.
Results: We developed and characterized two NEPC tumor organoids from tumor biopsies (liver and bone) of two patients both in vitro and in vivo (as PDXs). NEPC tumor organoid models retained the molecular and histological characteristic of their matched patient samples. We successfully manipulated the activity of the histone methyltransferase EZH2 by using a catalytic inhibitor and its expression by infecting organoids with shEZH2. We showed that the absence of EZH2 affects the expression of neuroendocrine-associated programs as stem cell and neuronal pathway. Moreover treatment with EZH2 inhibitor decreased tumor organoids viability and PDXs tumor volume. Drug screening approaches on NEPC organoids were used to discovery novel drug targets and combinations that could potentially benefit NEPC patients. Top single agent hits included previously identified targets such as EZH2, AURKA, as well as novel synergies.
Conclusions NEPC patient tumor organoids are clinically relevant tumor models to study the NEPC phenotype in advanced prostate cancer and may be used to elucidate novel drug targets.
Citation Format: Loredana Puca, Rohan Bareja, Reid Shaw, Wouter Karthaus, Dong Gao, Chantal Pauli, Juan Miguel Mosquera, Joanna Cyrta, Rachele Rosati, Rema Rao, Andrea Sboner, Carla Grandori, Giorgio Inghirami, Yu Chen, Mark A. Rubin, Himisha Beltran. Patient-derived tumor organoids of neuroendocrine prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 992. doi:10.1158/1538-7445.AM2017-992</jats:p
The Buddhist Tale of a Maudgalyayana Traveling to Hells in Search of His Mother: Text editing, translation, historical and literary analysis of the Mongolian manuscript
No full textWydział NeofilologiiCelem dysertacji jest dokonanie krytycznej edycji rękopisu zatytułowanego Yeke red qubilɣan-du Molon toyin taɣuǰi orušibai („Opowieść o obdarzonym magicznymi mocami Molon-toyinie”), zachowanego w spuściźnie prof. Władysława Kotwicza i przechowywanego w Archiwum Nauki PAN i PAU w Krakowie. Bohaterem mongolskiej opowieści jest Molon (lub Molon-toyin, czyli 'mnich Molon’) – powszechnie znany z literatury buddyjskiej Maudgaljajana, obok Siariputry najbliższy uczeń Buddy Siakjamuniego. Siariputra słynął z wiedzy i mądrości (prajñā), a Maudgaljajana z mocy magicznych (ṛddhi) i to te niezwykłe zdolności wykorzystał, aby przenieść się, między innymi, do buddyjskich piekieł w poszukiwaniu grzesznej matki. Opowieść o tej podróży przez piekła i ratowaniu matki z nieszczęsnego wcielenia sięga swoim rodowodem dawnych Indii i Chin. Została przetłumaczona na język tybetański, a potem przełożono i adaptowano ją na potrzeby czytelnika mongolskiego. W literaturze mongolskiej mamy do czynienia z kilkoma tradycjami przekazu tej opowieści, ale żadna z nich nie została poddana wyczerpującej analizie filologicznej i literaturoznawczej. Aby wypełnić tę lukę w historii badań nad omawianą opowieścią, autorka podjęła się porównania wybranych świadków jednej z tradycji, tzn. tej, do której przynależy rękopis krakowski. Dokonanie takiej edycji nie jest możliwe w całkowitej izolacji od pozostałych tradycji przekazu opowieści, dlatego omówiono historię badań oraz genezę opowieści z uwzględnieniem pozostałych tradycji.The aim of the dissertation was to make a critical edition of the manuscript entitled Yeke red qubilɣan-du Molon toyin taɣuǰi orušibai ("The Story of Molon-Toyin endowed with magical powers"), preserved in the legacy of Prof. Władysław Kotwicz and stored in the Archives of the Polish Academy of Sciences in Krakow under the inv. K III–19, 126. The hero of the Mongolian story is Molon (or Molon-toyin, meaning 'molon monk') – commonly known from Buddhist literature Maudgalyāyana, next to Śāriputra the closest disciple of Buddha Śākyamuni. Śāriputra was famous for his knowledge and wisdom prajñā, and Maudgalyāyana for his magical powers ṛddhi, and it was these extraordinary abilities that he used to travel, among other things, to Buddhist hells in search of his sinful mother. The story of this journey through hells and saving Maudgalyāyana’s mother from her unfortunate incarnation goes back to ancient India and China. It was translated into Tibetan, and then translated and adapted for the needs of the Mongolian reader. In Mongolian literature, we deal with several traditions of transmission of this story, but none of them has been subjected to an exhaustive philological and literary analysis. In order to fill this gap in the history of research on the discussed story, the author collated selected witnesses of one of the traditions, i.e. the one to which the Krakow manuscript belongs. Making such an edition was not possible in complete isolation from other traditions of storytelling, which is why the history of research and the genesis of the story were discussed, taking into account other traditions
Role of specialized composition of SWI/SNF complexes in prostate cancer lineage plasticity.
No full textAdvanced prostate cancer initially responds to hormonal treatment, but ultimately becomes resistant and requires more potent therapies. One mechanism of resistance observed in around 10-20% of these patients is lineage plasticity, which manifests in a partial or complete small cell or neuroendocrine prostate cancer (NEPC) phenotype. Here, we investigate the role of the mammalian SWI/SNF (mSWI/SNF) chromatin remodeling complex in NEPC. Using large patient datasets, patient-derived organoids and cancer cell lines, we identify mSWI/SNF subunits that are deregulated in NEPC and demonstrate that SMARCA4 (BRG1) overexpression is associated with aggressive disease. We also show that SWI/SNF complexes interact with different lineage-specific factors in NEPC compared to prostate adenocarcinoma. These data point to a role for mSWI/SNF complexes in therapy-related lineage plasticity, which may also be relevant for other solid tumors
Ensemble deep learning for breast cancer segmentation in optical coherence tomography (OCT) images
No full textKaiso (ZBTB33) subcellular partitioning functionally links LC3A/B, the tumor microenvironment, and breast cancer survival
No full textThe use of digital pathology for the histomorphologic profiling of pathological specimens is expanding the precision and specificity of quantitative tissue analysis at an unprecedented scale; thus, enabling the discovery of new and functionally relevant histological features of both predictive and prognostic significance. In this study, we apply quantitative automated image processing and computational methods to profile the subcellular distribution of the multi-functional transcriptional regulator, Kaiso (ZBTB33), in the tumors of a large racially diverse breast cancer cohort from a designated health disparities region in the United States. Multiplex multivariate analysis of the association of Kaiso’s subcellular distribution with other breast cancer biomarkers reveals novel functional and predictive linkages between Kaiso and the autophagy-related proteins, LC3A/B, that are associated with features of the tumor immune microenvironment, survival, and race. These findings identify effective modalities of Kaiso biomarker assessment and uncover unanticipated insights into Kaiso’s role in breast cancer progression.Fil: Singhal, Sandeep K.. North Dakota State University; Estados UnidosFil: Byun, Jung S.. National Institutes of Health; Estados UnidosFil: Park, Samson. National Institutes of Health; Estados UnidosFil: Yan, Tingfen. National Institutes of Health; Estados UnidosFil: Yancey, Ryan. Columbia University; Estados UnidosFil: Caban, Ambar. Columbia University; Estados UnidosFil: Hernandez, Sara Gil. National Institutes of Health; Estados UnidosFil: Hewitt, Stephen M.. U.S. Department of Health & Human Services. National Institute of Health. National Cancer Institute; Estados UnidosFil: Boisvert, Heike. Ultivue, Inc; Reino UnidoFil: Hennek, Stephanie. Ultivue Inc.; Reino UnidoFil: Bobrow, Mark. Ultivue Inc.; Reino UnidoFil: Ahmed, Md Shakir Uddin. Tuskegee University; Estados UnidosFil: White, Jason. Tuskegee University; Estados UnidosFil: Yates, Clayton. Tuskegee University; Estados UnidosFil: Aukerman, Andrew. Columbia University; Estados UnidosFil: Vanguri, Rami. Columbia University; Estados UnidosFil: Bareja, Rohan. Columbia University; Estados UnidosFil: Lenci, Romina. Columbia University; Estados UnidosFil: Farré, Paula Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: de Siervi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Nápoles, Anna María. National Institutes of Health; Estados UnidosFil: Vohra, Nasreen. East Carolina University; Estados UnidosFil: Gardner, Kevin. Columbia University; Estados Unido
- …
