bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationships among Seepage, Water Level, and Rainfall of a Fill Dam by Decision Tree Analysis
Authors: Yun Seong-Kyu , Kim Jiseong , Im Eun-Sang , Kang Gichun
Published: June 2022

This study is to present acceptable measurement values through decision tree analysis for the seepage, which is an important measuring item of the fill dam. The seepage of the dam under study increases rapidly when rainfall occurs, when the direct inflow of rainfall from the downstream slope and both sides occur. Therefore, the allowable seepage of fill dam considering rainfall and water level is required. Decision tree analysis was conducted for one domestic fill dam by setting the seepage as a response variable and setting rainfall and water level as explanatory variables. At this time, in order to analyze the effects of rainfall on the seepage more closely, the data subject was classified into two groups consisting of a rainfall-free group and a rainfall-occurring group. Group A, which is a rainfall-free group, had 97.7% of the seepage data distributed under the conditions of 98.50 mm/day of the antecedent 5-day rainfall selected as the first explanatory variable. The average seepage of the group was between 12.01 L/min and 26.35 L/min. Group B, which is a rainfall-occurring group, had 85.7% of the water leakage data distributed under conditions of 38.50 mm/day of daily rainfall selected as the first explanatory variable, with an average of 23.70 L/min.
Cooperative Disengagement of Fas and Intercellular Adhesion Molecule-1 Function in Neoplastic Cells Confers Enhanced Colonization Efficiency
Authors: Liu Kebin , Caldwell Sheila A. , Abrams Scott I.
Published: June 2022

Understanding the mechanisms of tumor progression is crucial toward the development of therapeutic interventions. Although the loss of sensitivity to cell death is a hallmark of neoplastic progression, it is likely one of several essential features that underlie a malignantly proficient or aggressive tumorigenic phenotype. Here, we identified intercellular adhesion molecule-1 (ICAM-1) as a molecule with expression coordinately regulated with Fas and inversely correlated with malignant phenotype between matched pairs of differentially aggressive malignant subpopulations in three mouse models. To determine whether coordinate expression of Fas and ICAM-1 regulated malignant behavior, tumor sublines were produced that expressed either lower levels of both Fas and ICAM-1, lower levels of Fas, or lower levels of ICAM-1 and then assessed for metastatic lung tumor growth. Tumor sublines rendered both Fas incompetent and ICAM-1 incompetent displayed significantly higher numbers of tumor nodules compared with tumor sublines separately expressing low levels of Fas or ICAM-1. However, all tumor sublines regardless of their Fas and ICAM-1 levels comparably infiltrated the lung, suggesting that Fas- and ICAM-1–based interactions ultimately influenced lung colonization efficiency. Overall, these data suggested that both Fas and ICAM-1 pathways cooperated to regulate tumor progression and that the coordinate down-regulation of Fas and ICAM-1 intensified malignant progression at the level of colonization. Thus, a FasloICAM-1lo phenotype may be characteristic of at least certain advancing, immune-resistant neoplastic subpopulations.
Up-Regulation of the Error-Prone DNA Polymerase κ Promotes Pleiotropic Genetic Alterations and Tumorigenesis
Authors: Bavoux Clarisse , Leopoldino Andréia Machado , Bergoglio Valérie , O-Wang Jiyang , Ogi Tomoo , Bieth Anne , Judde Jean-Gabriel , Pena Sérgio Danilo Junho , Poupon Marie-France , Helleday Thomas , Tagawa Masatoshi , Machado CarlosRenato , Hoffmann Jean-Sébastien , Cazaux Christophe
Published: June 2022

It is currently widely accepted that genetic instability is key to cancer development. Many types of cancers arise as a consequence of a gradual accumulation of nucleotide aberrations, each mutation conferring growth and/or survival advantage. Genetic instability could also proceed in sudden bursts leading to a more drastic upheaval of structure and organization of the genome. Genetic instability, as an operative force, will produce genetic variants and the greater the instability, the larger the number of variants. We report here that the overexpression of human DNA polymerase κ, an error-prone enzyme that is up-regulated in lung cancers, induces DNA breaks and stimulates DNA exchanges as well as aneuploidy. Probably as the result of so many perturbations, excess polymerase κ favors the proliferation of competent tumor cells as observed in immunodeficient mice. These data suggest that altered regulation of DNA metabolism might be related to cancer-associated genetic changes and phenotype.
Nitric Oxide Reverts the Resistance to Doxorubicin in Human Colon Cancer Cells by Inhibiting the Drug Efflux
Authors: Riganti Chiara , Miraglia Erica , Viarisio Daniele , Costamagna Costanzo , Pescarmona Gianpiero , Ghigo Dario , Bosia Amalia
Published: June 2022

Multidrug resistance (MDR) is a phenomenon by which cancer cells evade the cytotoxic effects of chemotherapeutic agents. It may occur through different mechanisms, but it often correlates with the overexpression of integral membrane transporters, such as P-glycoprotein (Pgp) and MDR-associated proteins (MRPs), with resulting decrease of drug accumulation and cellular death. Doxorubicin is a substrate of Pgp; it has been suggested that its ability to induce synthesis of nitric oxide (NO) could explain, at least in part, its cytotoxic effects. Culturing the human epithelial colon cell line HT29 in the presence of doxorubicin, we obtained a doxorubicin-resistant (HT29-dx) cell population: these cells accumulated less intracellular doxorubicin, were less sensitive to the cytotoxic effects of doxorubicin and cisplatin, overexpressed Pgp and MRP3, and exhibited a lower NO production (both under basal conditions and after doxorubicin stimulation). The resistance to doxorubicin could be reversed when HT29-dx cells were incubated with inducers of NO synthesis (cytokines mix, atorvastatin). Some NO donors increased the drug accumulation in HT29-dx cells in a guarosine-3′:5′-cyclic monophosphate–independent way; this effect was associated with a marked reduction of doxorubicin efflux rate in HT29 and HT29-dx cells, and tyrosine nitration in the MRP3 protein. Our results suggest that onset of MDR and impairment of NO synthesis are related; this finding could point to a new strategy to reverse doxorubicin resistance in human cancer.
Cdk Inhibition in Human Cells Compromises Chk1 Function and Activates a DNA Damage Response
Authors: Maude Shannon L. , Enders Greg H.
Published: June 2022

Cyclin-dependent kinases (Cdk) promote cell proliferation, are often deregulated in human cancers, and are targets of ongoing cancer chemotherapy trials. We show here that Cdk activity is also required in human cells to maintain function of the Chk1 pathway, a key component of the response to DNA damage or stalled replication. Chk1 expression was markedly reduced in primary fibroblasts and U2OS osteogenic sarcoma cells by treatment with small molecule Cdk inhibitors or induction of a dominant-negative mutant of Cdk2. The findings of decreased Chk1 activity and accumulation of Cdc25A, a protein targeted for degradation by Chk1, confirmed that Chk1 function was impaired. Furthermore, Cdk inhibition triggered a DNA damage response, characterized by the accumulation of activated forms of ATM and Chk2 as well as nuclear foci containing phosphorylated substrates of ATM/ATR, including histone H2AX (γH2AX). Time course experiments showed that the bulk of ATM activation followed Chk1 down-regulation. Chk1 RNA interference combined with partial inhibition of DNA replication was sufficient to evoke the DNA damage response. Conversely, ectopic expression of Chk1 blunted induction of γH2AX foci by Cdk inhibitors, indicating that Chk1 down-regulation was necessary to elicit the full phenotype. Finally, both Cdk and Chk1 inhibitors enhanced the cytotoxity of etoposide, a DNA-damaging agent. These results define a pathway through which Cdk inhibition can mediate DNA damage and potentially enhance the efficacy of extant cancer chemotherapies.
Vascularization of Melanoma by Mobilization and Remodeling of Preexisting Latent Vessels to Patency
Authors: Lu Weixin , Schroit Alan Jay
Published: June 2022

Tumors must manipulate the host vasculature to provide a blood supply adequate for their proliferation. Although tumors may arise as avascular masses, there is increasing evidence that some tumors begin to proliferate by first co-opting preexisting host blood vessels. By fluorescent vascular imaging, we provide evidence that the vasculature in orthotopically implanted melanoma arises from a preexisting red cell–deficient vascular network that remodels to patency to accommodate the requirements of the expanding tumor mass. Topical application of vascular endothelial growth factor to vascular beds generated immediate and robust vascular transitions that were morphologically similar to tumor-induced transitions. Nφ-nitro-l-arginine, a nitric oxide inhibitor, significantly inhibited the growth of a syngeneic K1735M2 melanoma by reducing blood supply to the tumor by a mechanism independent of endothelial cell proliferation. These findings suggest that tumor-induced remodeling of red cell–deficient vessels to patency contributes to tumor vascularization and growth.
Abstract 6287: Comparison of multiple myeloma provider for Black Americans and Caucasian Americans
Authors: Cheung Christian S. , Sweeney Nathan W. , Tiu Zena M. , Chmielewski Cynthia , Ahlstrom Jennifer M.
Published: June 2022

Background: Although Black Americans have 2-3 times multiple myeloma (MM) incidence and mortality as compared to Whites, increasingly research is demonstrating that many may have genetic characteristics that have better survival outcomes. Yet delayed diagnoses and inappropriate first lines of therapy often wipe out whatever “advantages” they may have had, keeping mortality statistics higher than would be expected (PMID: 25469920). For underserved populations, a number of commonly accepted disparities exist in myeloma, and more broadly, cancer care. Patients who receive treatment by a high-volume provider (myeloma specialist) is a factor that can help patients with MM to have a longer life expectancy (PMID: 31487686). Therefore, we analyzed whether there is a disparity between race and receiving care from a myeloma specialist which may contribute to the differences in survival that is being seen.

Methods: Validated real-world (RW) MM patient data was collected through HealthTree Cure Hub for Multiple Myeloma (healthtree.org). We examined the patient’s race which was either Caucasian American or Black American and whether or not they were being treated by a myeloma specialist. The association between race and specialist was examined by a chi-squared (X2) test.

Results: In this retrospective analysis of 2,871 MM patients, we compared Caucasian Americans (n= 2716) and Black Americans (n=155). Our analysis revealed a significant association between the two races and whether or not they had a myeloma specialist, X2(1, N = 2,871) = 5.85, p = 0.015. Black Americans were less likely to be treated by a myeloma specialist.

Conclusion: The findings of this RW analysis identify a glaring disparity in Black American MM patients and receiving care from a myeloma specialist. Addressing the underlying cause of the findings could extinguish other MM-related issues, such as delays in getting a correct diagnosis, lack of access to myeloma specialists, and many other non-medical issues leading to less-than-optimal outcomes from the majority of these Black American patients.

Citation Format: Christian S. Cheung, Nathan W. Sweeney, Zena M. Tiu, Cynthia Chmielewski, Jennifer M. Ahlstrom. Comparison of multiple myeloma provider for Black Americans and Caucasian Americans [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6287.
Abstract 6297: New biomarker in liquid biopsies from breast and ovarian cancers
Authors: Ibrahim Safaa A. , Riehl Valerie , Beaman Kenneth D.
Published: June 2022

Breast and ovarian cancer (BOC) are among the top ten common cancers in females worldwide and remain important causes of death in women. There are shared risk factors between breast and ovarian cancer such as, BRCA1 and BRCA2. Detecting those risk factors are not enough to detect cancer early as approximately half of breast cancers develop in women who have no identifiable breast cancer risk factor other than gender (female) and age (over 40 years). Identification of specific biomarkers in liquid biopsies is required for early detection of BOC. BOC secretes exosomes in large quantities to blood circulation to communicate with different cell types such as immune cells to support cancer growth and metastasis. We detect a significant and readily measurable expression of a specific peptide from the a2 isoform vacuolar ATPase (a2NTD) in the exosomes isolated from the plasma collected from BOC patients. We found that a2NTD is highly expressed in stage III ovarian cancer. In this stage, the tumor spread outside of the abdomen and/or nearby lymph nodes. a2NTD positively correlates with the CA125 levels in plasma. These data show that plasma a2NTD correlates with tumor cell growth and metastasis. In addition, a2NTD associated breast cancer exosome can contribute to the pathophysiology of the disease as it induces PBMCs to secrete cancer promoting factors such as IL-8, CCL-2, and MMP-9. Importantly, those secreted factors promote angiogenesis and tumor cell migration. a2NTD promotes the immunosuppressive properties of neutrophils by stimulating arginase-1 release. Together, this data shows that a2NTD can be a potential diagnostic biomarker and therapeutic target in breast and ovarian cancer.

Citation Format: Safaa A. Ibrahim, Valerie Riehl, Kenneth D. Beaman. New biomarker in liquid biopsies from breast and ovarian cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6297.
Abstract 6299: Population kinetics (PopKin) of non-small cell lung cancer (NSCLC) adjuvant therapy
Authors: Stewart David J.
Published: June 2022

Background: Disease-free survival (DFS) and overall survival (OS) follow 1st order kinetics. Curve Popkin assessment yields biological insights. Chemotherapy (chemo) improves outcome in resected NSCLC. We performed adjuvant DFS and OS PopKin assessments.

Methods: We digitized published DFS and OS curves. We used GraphPad Prism for curve exponential decay nonlinear regression analysis (EDNLRA).

Results: We assessed 1 trial with adjuvant osimertinib and 5 with platinum-based postoperative chemo and control arms. With osimertinib, DFS and OS curves were convex on log-linear plots, suggesting rapid tumor regrowth once therapy is discontinued. In chemo trials, 10 of 10 DFS curves and 9 of 10 OS curves fit 2-phase decay EDNLRA models (Table 1). Popkin calculations indicate that of control patients destined to recur, 12% would recur by 2 months after surgery, 22% by 4 months and 31% by 6 months.

Conclusion: PopKin suggests osimertinib delays recurrence rather than preventing it. Combined chemo analyses suggest chemo converts 15% of patients from rapidly to slowly recurring, but many “shifted” patients eventually recur. Hence, chemo may induce reversible tumor senescence rather than eradicating micrometastases. Anti-senescent cell strategies might prove beneficial. Frequent scans are warranted in the 1st postoperative year for early detection of recurrences.

Table 1. EDNLRA of adjuvant chemo and control DFS and OS curves Arm Overall t1/2 a % Fastb Fast group t1/2 c % Slowd Slow group t1/2 e Control DFS 40.1 57 11.0 43 212.7 Chemo DFS 47.2 42 11.7 58 120.8 Control OS 51.9 69 25.8 31 1.3 x 1012 Chemo OSf 61.4 75 45.9 25 1.3 x 1012 aMedian t1/2 (half-life, months) on 1-phase decay EDNLRA. bMedian % of all patients in rapidly recurring/dying subgroup on 2-phase decay EDNLRA. cMedian t1/2 in rapidly recurring/dying subgroup on 2-phase decay EDNLRA. dMedian % in slowly recurring/dying subgroup. eMedian t1/2 in slowly recurring/dying subgroup. fIn 1 study, OS curve did not fit a 2-phase decay model

Citation Format: David J. Stewart. Population kinetics (PopKin) of non-small cell lung cancer (NSCLC) adjuvant therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 6299.
Abstract ND12: Discovery and First Structural Disclosure of EZM0414: A potent and selective small molecule inhibitor of the histone methyltransferase SETD2
Authors: Kutok Jeffery L.
Published: June 2022

SETD2 is the only known histone methyltransferase (HMT) capable of catalyzing H3K36 trimethylation (H3K36me3). It plays a critical role in several biological processes such as DNA damage repair and B cell development. Dysregulation in H3K36 methylation can occur in B cell malignancies, including multiple myeloma (MM) and diffuse large B cell lymphoma (DLBCL), often as a result of mutational events incurred during normal B cell development. For example, 15%-20% of MM patients harbor the high risk (4;14) chromosomal translocation (t), resulting in high expression of the multiple myeloma SET domain (MMSET) gene. MMSET (also known as NSD2) is an HMT that catalyzes H3K36me1 and H3K36me2 formation, which leads to increased levels of H3K36me2 in t(4;14) MM patients. Because H3K36me2 is the substrate of SETD2, we hypothesized that inhibiting SETD2 could target the underlying oncogenic mechanism driven by the dysregulated H3K36 methylation from MMSET overexpression in t(4;14) MM patients, and would establish proof of concept in this and other B cell malignancies (e.g. DLBCL) that may demonstrate dysregulated H3K36me3 or a dependency on SETD2. In this presentation, we will describe the discovery and structure of our clinical candidate EZM0414, a first-in-class, potent, selective, orally bioavailable small molecule inhibitor of the enzymatic activity of SETD2; robust anti-tumor effects of SETD2 inhibition with EZM0414 in MM (including t(4;14) MM) and DLBCL preclinical studies; and the outline of the ongoing first-in-human Ph1/1b open-label, multicenter study of EZM0414 in patients with relapsed/refractory MM or DLBCL.

Citation Format: Jeffery L. Kutok. Discovery and First Structural Disclosure of EZM0414: A potent and selective small molecule inhibitor of the histone methyltransferase SETD2 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr ND12.
Abstract PL02-01: The pathogenesis of cancer susceptibility due to inherited DNA repair defects
Authors: Stratton Michael R.
Published: June 2022

The landscapes of somatic mutation in the genomes of normal human cells have, until recently, been poorly described compared with those of cancer cells. However, advances in technology are now changing this picture and are enabling exploration of the earliest stages of cancer development. In this talk, the patterns of somatic mutation found in normal colorectal epithelial cells are outlined and serve as a backdrop to understanding the pathogenesis of colorectal cancer susceptibility syndromes. Multiple mutational signatures are present in normal colorectal epithelial cells indicating that multiple mutational processes are operative in them during the course of life. Some of these mutational signatures are ubiquitous, present in every colorectal epithelial cell, with mutations generated at constant rates throughout life. Others are sporadic, found only in some cells or in some people, with mutations generated in bursts. Some are of endogenous origins whereas others are caused by exogenous exposures. Several inherited colorectal cancer predisposition syndromes are known to be mediated by DNA repair deficiencies that ultimately generate elevated somatic mutation rates. The results presented here show that in some of these syndromes all normal colorectal cells, and probably all cells in the body, have markedly elevated somatic mutation rates throughout life with mutational signatures not found in healthy individuals. Conversely, in other syndromes normal cells have normal mutation rates with standard mutational signatures but a small minority of cells acquire elevated mutation rates during the course of life. In both scenarios only a small proportion of cells with elevated mutation rates ever become adenomas or carcinomas. The results elucidate the different ways in which elevated somatic mutation rates due to DNA repair deficiencies lead to cancer and potentially offer a new modality contributing to clinical management of colorectal cancer susceptibility. They also provide a new perspective on the role of somatic mutations in ageing.

Citation Format: Michael R. Stratton. The pathogenesis of cancer susceptibility due to inherited DNA repair defects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr PL02-01.
Abstract SY06-03: Development of novel therapeutic strategies to target the DNA damage response in the clinic
Authors: Yap Timothy A.
Published: June 2022

The clinical benefit observed with PARP inhibitors, and their subsequent regulatory approval in multiple tumor indications, have provided clinical proof of concept for a synthetic lethal approach in molecularly selected tumors and beyond. Now, we need to build on the success of such first generation PARP inhibitors through the use of rational evidence-based biomarker-driven strategies in the clinic. We can potentially accomplish this through the development of novel potent PARP1-selective inhibitors, which may lead to an improved therapeutic index and patient benefit, and the development of rational PARP inhibitor combinations with other molecularly targeted agents or immunotherapeutics, taking in consideration potential supra-additive toxicities. Finally, given recent advances in drug discovery efforts, we now have the opportunity to go beyond PARP by drugging other key DNA Damage Response (DDR) targets in the clinic, including ATR, WEE1, DNA-PK, RAD51, POLQ and USP1. I will discuss the progress we have made in the clinic, the potential pitfalls, and the promise that such novel approaches hold in improving patient outcomes.

Citation Format: Timothy A. Yap. Development of novel therapeutic strategies to target the DNA damage response in the clinic [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY06-03.
Abstract SY22-02: Aneuploidy and 3D tissue rigidity
Authors: Discher Dennis
Published: June 2022

Sequence differences between normal cells of the same person are increasingly evident (e.g. Yizhak Science 2019), and such somatic variations across different tissues increase from liquid to solid tissues, consistent with similar trends across liquid and solid tumors. Further analyses suggest changes increase with high levels of both replication-division (R=0.24) and the stiffness E of each tissue (R=0.6). Chromosome copy number gains and losses – aneuploidy – follow these trends, which prompted our hypothesis that stiff 3d microenvironments could increase aneuploidy of dividing cells moreso than less confining or microenvironments. We developed a method of live-cell monitoring of changes to chromosome copy numbers and used it to study diverse perturbations, particularly compressed mitosis seen in vivo. Many dividing cells die when squeezed, but rare stem cells and cancer cells show heritable loss of mono-allelic, GFP/RFP-tagged constitutive genes that function as Chromosome-reporters (ChReporters). Flattening spreads mitotic chromatin, favors chromosome mis-segregation, and increases ChReporter loss independent of an established spindle assembly checkpoint. Inhibiting the high level of Topoisomerase in such cells impedes chromosome compaction, division, and ChReporter loss, whereas the proposed tumor suppressor Myosin-IIA stabilizes chromatin against fragmentation, with knockdown increasing ChReporter loss. Solid human tumors and teratomas show similar ChReporter trends in mice, and single-cell-sequencing identifies rare chromosome changes exclusively in normal 3D-infiltrative cells while also relating specific chromosome losses to altered growth and motility. 3D rigidity thus gives rise to heritable aneuploidy as a mechanogenetic change.

Citation Format: Dennis Discher. Aneuploidy and 3D tissue rigidity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY22-02.
Abstract SY30-03: Colorectal cancer screening in underserved populations: COVID, silver linings, and challenges ahead
Authors: Martinez Maria Elena
Published: June 2022

Colorectal cancer (CRC) screening and appropriate follow-up can reduce incidence and mortality, but screening and abnormal test follow-up rates are suboptimal among medically underserved populations. The United States Preventive Services Task Force (USPSTF) recommends CRC screening through a variety of invasive and noninvasive tests for adults aged 50 to 75 years (grade A) and for individuals aged 45 to 49 years (grade B). Evidence-based interventions and other strategies exist to promote CRC screening, but adoption and implementation of these are limited, especially among medically underserved individuals and those receiving care at community health centers (CHCs) in the United States. Aside from low screening uptake, low colonoscopy follow-up of abnormal stool tests is common in CHCs, estimated to be approximately 50%. Lack of colonoscopy completion for abnormal stool tests defeats the purpose of screening because early-stage cancers go undetected, resulting in higher CRC mortality. Reasons for lack of colonoscopy completion are poorly understood. Cancer screening rates have plummeted as a result of the coronavirus disease 2019 (COVID-19) pandemic, resulting in an estimated 10,000 deaths from breast and CRC alone in the U.S. over the next 10 years. The impact of this drop specific to racial/ethnic groups and communities facing barriers prior to the pandemic is unknown. Prior to the onset of the pandemic, the National Cancer Institute invested in CRC screening research as a result of the Cancer Moonshot’s Blue Ribbon Panel recommendation through its Accelerating Colorectal Cancer Screening and Follow-up through Implementation Science (ACCSIS) initiative. ACCSIS supports research to build the evidence base on multilevel interventions to increase CRC screening, follow-up, and referral to care. Five ACCSIS research projects and a 3-site American Indian project are supported through this initiative, all focusing on underserved populations across the US. This presentation will provide an overview of the key components of the ACCSIS program, challenges faced resulting from the pandemic, and opportunities for overcoming these. In its 2022 report, the President’s Cancer Panel called for equitable cancer screening as a top public health priority. The report emphasizes that overcoming barriers to CRC screening and follow-up among underserved populations must be addressed to ensure that the benefits reach all populations. This provides a timely opportunity to address the extraordinary CRC screening challenges and disparities faced by vulnerable populations.

Citation Format: Maria Elena Martinez. Colorectal cancer screening in underserved populations: COVID, silver linings, and challenges ahead [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY30-03.
Abstract SY42-01: Tumor-initiating stem cells shape the microenvironment into an immunosuppressive barrier and a pro-tumorigenic niche
Authors: Li Linheng
Published: June 2022

Tumor-initiating stem cells shape microenvironment into an immunosuppressive barrier and a pro-tumorigenic nicheLinheng Li Stowers Institute for Medical Research, Kansas City MO 64110Kansas University of Cancer Center, Kansas City KS 66160

Accumulated evidence supports the concept that tumor-initiating stem cells (TSCs) are at the root of tumor/cancer and are largely responsible for the commonly observed resistance to chemoradiotherapy (CRT) and frequent relapse of disease. How a subset of TSCs, or therapy resistant TSC (TrTSC), survives and supports tumor regrowth post treatment is a fundamental biological question and clinically unsolved problem. Recently, we utilized single-cell RNA-sequencing to identify therapy resistant TSCs (or TrTSCs) in mouse models of CRT-challenged intestinal adenoma, followed by bioinformatics analysis to reveal the bidirectional crosstalk that occurs between TSCs and the tumor microenvironment (TME). The results of the analysis indicate that TSCs shape the TME into an immunosuppressive barrier. Particularly, TrTSCs recruit tumor-associated monocytes and macrophages (TAMMs), which in turn, via Cox-2 dependent prostaglandin E2 (PGE2)-PTGER4(EP4) signaling, induce Akt-mediated phosphorylation of β-catenin and thus enhance the β-catenin activity. Furthermore, we show that enhanced β-catenin signaling upregulates multiple immune-checkpoint genes, thus empowering the immune escape capabilities of TSCs. Taken together, overcoming both the extrinsic immunosuppressive barrier and intrinsic immune escape has the potential to increase the efficacy of checkpoint inhibition therapies against cancers in the future.

Citation Format: Linheng Li. Tumor-initiating stem cells shape the microenvironment into an immunosuppressive barrier and a pro-tumorigenic niche [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY42-01.
Financiamento de campanha e fidelidade partidária: Desafio intransponível?
Authors: Assis Luiz Gustavo Bambini de
Published: June 2022

O presente artigo tem como objetivo analisar a forma como o financiamento de campanha pode influenciar a fidelidade partidária, assim como o papel da pressão ou lobby de financiadores. Na primeira parte do artigo, foi trabalhada a idéia de partido político e seu papel no funcionamento da política e elaboração de políticas públicas. Na segunda parte, explorou-se a noção de titularidade do mandato na relação entre candidatos e partidos políticos, haja vista recente judicialização da questão. Na terceira parte, tratou-se do tema fidelidade partidária, relacionando-o com a reforma política. O cerne da quarta parte do artigo foi analisar a relação entre o financiamento e o lobby. Por fim, a quinta parte conjuga a noção de lobby, políticas públicas e analisa de que maneira podem ser condizentes com a noção de fidelidade partidária.
O desenvolvimento do socialismo de mercado
Authors: Barbieri Fabio
Published: June 2022

O artigo analisa o debate entre economistas neoclássicos que ocorreu na terceira década do século XX a respeito da possibilidade de planejamento central de uma economia. Traçamos o desenvolvimento dos modelos de “socialismo de mercado” – a tentativa de usar a teoria de equilíbrio para criar mecanismos alocativos que poderiam simular mercados reais. Defendemos a tese metodológica de que tal tentativa fracassou porque seus defensores desconsideraram assimetrias entre explicação e previsão existentes na teoria econômica: em cada passo, elementos de mercados reais negligenciados pelas simplificações teóricas impediam que o modelo funcionasse adequadamente, convidando a novas modificações que reintroduziam elementos dos mercados reais.
Atuação do Psicólogo na Visita Domiciliar
Authors: Aron Mariana Luzia , Dos Santos Nanci Cosme Damiã
Published: June 2022

Este artigo discute a importância da visita domiciliar, os efeitos benéficos para o usuário do sistema de saúde e a função do psicólogo nesse contexto, tomando como base as vivências práticas de estagiárias e supervisora em um programa de estágio em visita domiciliar, bem como as reflexões então decorrentes. A visita domiciliar consiste em contribuir para a prevenção da doença, promoção da saúde, assistência para doenças já instaladas, liberação de leitos hospitalares, atendimento digno a pessoas que não podem se locomover até os hospitais, sendo uma importante ferramenta para auxiliar as famílias no desenvolvimento da autonomia no processo saúde-doença, permitindo aos profissionais de saúde maior compreensão da realidade do sujeito e suas relações. O objetivo do psicólogo é capacitar as famílias a utilizarem seus recursos para a resolução dos problemas enfrentados, garantindo maior autonomia aos sujeitos envolvidos. Entretanto, tal modalidade não é tradicionalmente ensinada nos cursos de psicologia, o que traz mais dúvidas e insegurança para a prática profissional.
Consciência Política e Corrupção em Moçambique: entre a subalternidade e a transformação
Authors: Ba-Senga Rogério , Silva Alessandro Soares da
Published: June 2022

Este artigo discute a importância da Visita Domiciliar, os efeitos O presente artigo aborda a corrupção em Moçambique a partir do olhar de pessoas que nem estudam e nem têm papel de destaque na sociedade moçambicana. Para essa análise utilizou-se do referencial psicopolítico da consciência política e observou-se como a questão da etnicidade e da sobrevivência ganham força a hora de entender a vida cotidiana em uma sociedade pluriétnica e marcada pelos traumas de uma guerra civil. Subalternidade e transformação se revelam como elementos espaço-temporais da cotidianidade moçambicana.
Construcciones sobre la Gestión Integrada de los Recursos Hídricos en el Perú: una aproximación desde el estudio de comunidades epistémicas
Authors: Vila Gisselle
Published: June 2022

Construcciones sobre la gestión integrada de los recursos hídricos en el Perú: Una aproximación desde el estudio de comunidades epistémicasConstructions of integrated water management in Peru: Approximations from the study of epistemic communitiesConstruções de gestão integrada da água no Peru : Aproximações do estudo de comunidades epistêmicasResumenLa gestión integrada de los recursos hídricos (GIRH) como “concepto nirvana” (Molle, 2007) se remite a un marco de referencia ideal cuya aplicación, en la práctica, variará según las apropiaciones que se realicen de él en función de intereses priorizados. Si bien la intervención de comunidades epistémicas como traductoras de intereses ha sido explorada desde la sociología y antropología del desarrollo (Mosse, 2006; Long, 2003; Hobart, 1993), las investigaciones que tratan el tema a partir de la inserción de la GIRH aún son limitadas. Bajo ese marco, esta investigación tiene por objetivo identificar las construcciones sobre la GIRH en el caso peruano a partir del análisis de los perfiles ideales de los gestores del agua según son concebidos por dos sectores, el Estado y el sector minero. Los hallazgos subrayan que en ambos sectores la GIRH es apropiada en función de agendas particulares, definiendo otros espacios como portadores de problemas. En contraste, cada sector se autodefine como el portador de soluciones, amparadas en el conocimiento científico y la intervención de brokers que medien la transmisión de mensajes.Palabras clave: GIRH, Perú, comunidades epistémicas, Estado, minería.ResumoA Gestão Integrada dos Recursos Hídricos (GIRH) como “conceito nirvana” (Molle, 2007) remete a um marco de referência ideal, cuja aplicação prática varia segundo as apropriações nele utilizadas em função de interesses priorizados. Embora a intervenção de comunidades epistemológicas como tradutoras deste tipo de conceito tenha sido explorada pela sociologia e antropologia do desenvolvimento (Mosse, 2006; Long, 2003; Hobart, 1993), as pesquisas que tratam o tema a partir da inserção da GIRH ainda são limitadas. Baseada nesse marco, esta pesquisa objetiva analisar as construções sobre a GIRH, no caso peruano, a partir da análise dos perfis ideais dos gestores da água segundo a concepção de dois setores: o Estado e o setor de mineração. Os resultados assinalam que em ambos setores a GIRH supõe concepções semelhantes pela predominância de agendas próprias, onde a definição de outros espaços como portadores de problemas e a autodefinição, em contraste, como os portadores de soluções se amparam no conhecimento científico e na intervenção de agentes mediadores da transmissão de mensagens.Palavras-chaves: gestão integrada da água, Peru, comunidades epistêmicas, Estado, mineração.
Educação Superior e Novo Desenvolvimentismo: uma análise das políticas de expansão e reestruturação das universidades federais entre 2007 e 2010
Authors: Silva Ivan Henrique de Mattos e
Published: June 2022

O presente trabalho tem como objetivo uma análise quantitativa e qualitativa das políticas voltadas às universidades federais entre 2003 e 2010 (período que representa os dois mandatos do presidente Lula). A hipótese é que estas, especialmente após o ano de 2007, se configuram dentro do arcabouço político e institucional do que a literatura vem chamando de novo desenvolvimentismo, compreendido como um rearranjo político do projeto desenvolvimentista sobre bases democráticas e inclusivas. Embora essa associação entre novo desenvolvimentismo e políticas de educação superior possa ser feita desde 2003, a publicação do Plano de Desenvolvimento da Educação, e a aprovação do Reuni (ambos em 2007), aprofundaram essa associação estratégica.
Por uma Concepção Abrangente de Cultura para as Políticas Culturais e para a Promoção da Diversidade
Authors: Oliveira Danilo Junior de
Published: June 2022

A análise é guiada pela concepção de cultura adotada pelas políticas públicas de cultura e pelo tratamento dado aos direitos culturais, em especial à promoção da diversidade cultural. O sentido abrangente de cultura é analisado de maneira relacional ao conceito proposto por Raymond Williams no âmbito dos Estudos Culturais e aos direitos culturais. Ambas perspectivas buscam construir uma ampliação democrática no conceito de cultura para reconhecê-la como direito de todos. A ampliação do conceito de cultura potencialmente oferece mais condições para a promoção da diversidade cultural e dos direitos cultuais como um todo.
Avaliação Econômica de Projetos Sociais
Authors: Carvalho Maria Regina , Rufino Gomes Danusa Fernandes , Oliveira Mariano Laio
Published: June 2022

Resenha da obra: Avaliação Econômica de Projetos SociaisAutor: vários autores, organizado por Naércio Menezes FilhoCidade: São PauloEditora: Fundação Itaú SocialAno: 2016Páginas: 294ISBN: 978-85-66932-07-2
Globalización, Reforma del Estado y Transformaciones Laborales: Reflexiones acerca del Futuro del Trabajo
Authors: Machado Jorge
Published: June 2022

El desarrollo de los medios productivos y de los avances tecnológicos en la economía globalizada creó el paradójico del aumento de productividad, con consecuente menos necesidad de mano de obra y el alivio para el ser humano. Sin embargo, los gaños de productividad no llevaron beneficios para el conjunto de la sociedad, sino que solamente a una pequeña capa privilegiada de la población. Los "ajustes" de las reformas económicas llevaron al desmonte del Estado de bienestar; a la dificultad de acceso a servicios antes públicos ahora privatizados; y, en última instancia, al aumento de las desigualdades sociales, la anomía y la marginación. El objetivo de este artículo es tractar de la asociación entre la reforma del Estado operada a lo largo de los años 90 – la década del neoliberalismo – y los cambios en el espacio laboral y en las perspectivas del trabajo humano.
Participação Política e Formação do Conselho Consultivo no Parque Natural Municipal da Ronda em São Francisco de Paula, RS, Brasil
Authors: Binkowski Patrícia , Souza Túlio Garcia de
Published: June 2022

O Parque Natural Municipal da Ronda (PNMR) localiza-se no município de São Francisco de Paula, no Rio Grande do Sul (RS), onde foi criado em 29 de fevereiro de 1996, pelo Decreto Municipal nº 1.671 e substituído pela Lei Municipal nº 2.425, de 27 de março de 2007, possui 1.448 hectares e teve como objetivos desde a sua criação como unidade de conservação: preservação das nascentes de água da região e desenvolver atividades de educação ambiental, pesquisa científica e ecoturismo. Mesmo o PNMR tendo sido criado há quase duas décadas, ele é considerado um “paper park”, pois a unidade de conservação não foi implantada pelo poder público municipal, sendo considerado, portanto, um parque que ainda não saiu do papel. Durante esses anos foi possível observar que os maiores entraves para a implementação do PNMR por parte do poder público foram: a) a ocupação irregular das bordas do parque; b) a não construção de infraestruturas (trilhas, sanitários, placas indicativas, etc.); c) as inúmeras indenizações que deveriam ter sido realizadas aos proprietários das áreas internas ao parque; e, d) a não participação da sociedade civil na luta para implementação do parque; e) a inexistência de gestor para o parque; d) a não formação de um conselho consultivo que desse suporte à gestão do parque. Em 2017 algumas instituições do município tencionaram para que houvesse a constituição de um Grupo de Trabalho (GT) para impulsionar a formação desse conselho consultivo do PNMR. Portanto, este artigo pretende responder ao seguinte questionamento: Qual a potencial rede de agentes locais à organização de um conselho consultivo no PNMR em São Francisco de Paula/RS? A pesquisa realizada segue a abordagem qualitativa, do tipo pesquisa-ação, desdobrada inicialmente em duas etapas: 1ª) Mapeamento da rede de potenciais agentes participantes do conselho consultivo e 2ª) Contato com os agentes sociais potenciais para compor o conselho consultivo do PNMR. A partir do trabalho realizado pelo GT, pelas ações do poder público e do gestor indicado ao parque foi possível organizar um edital para constituição do conselho consultivo que tende a se constituir como um canal de representação e participação, possibilitando à população acesso a tomadas de decisão referentes à gestão da UC e seu entorno.
A Pastoral Carcerária e a Luta por Justiça e Dignidade no Sistema Prisional Brasileiro
Authors: Costa-Chicareli Semiramis , Silva Alessandro Soares da
Published: June 2022

Neste artigo, realizamos uma investigação qualitativa da trajetória de participação política da Pastoral Carcerária, como forma de compreender como ocorre e se desenvolve essa luta direta contra o Estado penal brasileiro. Para isso, realizamos entrevistas semi abertas com três atores da organização, por meio de um roteiro semiestruturado, e as análises foram realizadas a partir da articulação entre os referenciais teórico-metodológicos da História Oral Temática, da Análise de Discurso e do Modelo de Análiseda Consciência Política. Para abordar essa realidade na qual se desenvolve a participação política da Pastoral Carcerária, é necessária a compreensão do que significa Estado Penal, criminalização seletiva e encarceramento em massa.
Retrocessos do Projeto de Lei nº 3.729/2004: A Flexibilização do Licenciamento Ambiental como um obstáculo para o cumprimento da Agenda 2030
Authors: Araújo Gabriel Pires de , Almeida Paulo Santos de
Published: June 2022

Este artigo é um aperfeiçoamento do trabalho “Retrocessos na Legislação que rege o Licenciamento Ambiental como um obstáculo para o cumprimento da Agenda 2030”, apresentado no III Encontro Nacional de Políticas Públicas na Escola de Artes, Ciências e Humanidades da Universidade de São Paulo. Tem como objetivo analisar e discutir o Projeto de Lei nº 3.729/2004 que está em tramitação no congresso nacional e que, de acordo com órgãos ambientais, propõe a flexibilização do instrumento de licenciamento ambiental, algo que pode ser caracterizado como um retrocesso na legislação ambiental. Busca-se desta forma refletir acerca de como essa alteração legislativa pode vir a ser um impeditivo para que o Brasil construa um desenvolvimento sustentável conforme preconizado na Agenda 2030, considerando que historicamente o instrumento de licenciamento ambiental tende a buscar a compatibilização entre desenvolvimento econômico e proteção ambiental, sendo importante, portanto fortalecer o licenciamento e torna-lo eficiente, visando construir instituições eficazes com legitimidade e capacidade de promover o desenvolvimento sustentável através de uma política de comando e controle.
Da Invisibilidade à Participação Política: experiências e discursos sobre a luta de travestis e transexuais
Authors: Campos Gustavo de Aguiar , Hur Domenico Uhng
Published: June 2022

Este trabalho objetiva conhecer os discursos sobre os movimentos trans, para discutir as distintas dimensões das políticas da transexualidade. Realizamos uma revisão bibliográfica da literatura especializada, focalizando os estudos que abordam as diversas formas de atuação e participação política dos movimentos sociais trans. A partir da análise do conteúdo categorial temática foi realizada uma discussão teórica crítica dos 61 artigos encontrados sobre o tema nas bases de dados Scielo, Pepsic e Portal de Periódicos da CAPES. Elaborou-se três categorias: (1) políticas da identidade; (2) saúde trans e Estado; (3) lutas sociais trans. A primeira categoria engloba estudos que discorrem sobre a construção das identidades, corporalidades trans e suas configurações de forças, focados na identidade de gênero. A segunda categoria traz as questões referentes às diversas formas de estatização da transexualidade, desde a saúde até as articulações por ONGs. Por fim, a última engloba os estudos que trazem contribuições históricas e analíticas sobre os movimentos sociais de pessoas trans e travestis. Com esse estudo apresenta-se um panorama geral da participação política nos movimentos trans, envolvendo os diferentes processos internos e externos ao grupo, traçando as pautas, as formas de se fazer política e as (in)visibilidades presentes nos diferentes âmbitos das políticas trans.
Docência no Ensino Superior em Tempos de Escola Sem Partido
Authors: Gonçalves Priscila Leite , Bizama Erika Alicia Budin , Sartori Giselle Pacifico , Rubio Natalia Afonso , Russo Diego Rafael Betti
Published: June 2022

Este artigo buscou apresentar uma revisão sistemática da produção científica nacional sobre o Movimento Escola sem Partido, visando a identificar as temáticas mais frequentes da referida produção, bem como com as questões de gênero nela imbricadas, configurando um recorte específico para a discussão do impacto do Movimento Escola sem Partido na formação dos professores no Ensino Superior. Os dados foram coletados durante o mês de abril de 2018 junto ao Portal de Periódicos da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, totalizando 31 estudos incluídos na análise qualitativa. Evidenciou-se que a produção científica na área é incipiente, e a temática de maior relevância se dá em torno da problematização e crítica do Movimento Escola sem Partido. A questão de gênero aparece de forma fragmentada e não aprofundada.