Skip to main content
eScholarship
Open Access Publications from the University of California

Scholarly Works (10 results)

  • Article
  • Peer Reviewed
UC Davis Previously Published Works (2018)
    Cover page: Interfering RNA against PKC-α inhibits TNF-α-induced IP <sub>3</sub> R1 expression and improves glomerular filtration rate in rats with fulminant hepatic failure
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2015)
    Soil water storage is a fundamental signal in the land hydrological cycle and changes in soil moisture can affect regional climate. In this study, we used simulations from Coupled Model Intercomparison Project Phase 5 archives to investigate changes in the annual range of soil water storage under global warming at northern middle and high latitudes. Results show that future warming could lead to significant declines in snowfall, and a corresponding lack of snowmelt water recharge to the soil, which makes soil water less available during spring and summer. Conversely, more precipitation as rainfall results in higher recharge to soil water during its accumulating season. Thus, the wettest month of soil water gets wetter, and the driest month gets drier, resulting in an increase of the annual range and suggesting that stronger heterogeneity in global water distribution (changing extremes) could occur under global warming; this has implications for water management and water security under a changing climate.
      Cover page: Increases in the annual range of soil water storage at northern middle and high latitudes under global warming
      • Article
      • Peer Reviewed
      UC Davis Previously Published Works (2021)

      Introduction

      Stem-like cancer cells or cancer stem cells (CSCs) may comprise a phenotypically and functionally heterogeneous subset of cells, whereas the molecular markers reflecting this CSC hierarchy remain elusive. The glycolytic enzyme alpha-enolase (ENO1) present on the surface of malignant tumor cells has been identified as a metastasis-promoting factor through its function of activating plasminogen. The expression pattern of surface ENO1 (sENO1) concerning cell-to-cell or CSC heterogeneity and its functional roles await further investigation.

      Methods

      The cell-to-cell expression heterogeneity of sENO1 was profiled in malignant cells from different types of cancers using flow cytometry. The subcellular localization of sENO1 and its functional roles in the invadopodia formation and cancer cell invasiveness were investigated using a series of imaging, molecular, and in vitro and in vivo functional studies.

      Results

      We showed here that ENO1 is specifically localized to the invadopodial surface of a significant subset (11.1%-63.9%) of CSCs in human gastric and prostate adenocarcinomas. sENO1+ CSCs have stronger mesenchymal properties than their sENO1- counterparts. The subsequent functional studies confirmed the remarkable pro-invasive and pro-metastatic capacities of sENO1+ CSCs. Mechanistically, inhibiting the surface localization of ENO1 by downregulating caveolin-1 expression compromised invadopodia biogenesis, proteolysis, and CSC invasiveness.

      Conclusions

      Our study identified the specific expression of ENO1 on the invadopodial surface of a subset of highly invasive and pro-metastatic CSCs. sENO1 may provide a diagnostically and/or therapeutically exploitable target to improve the outcome of patients with aggressive and metastatic cancers.
        Cover page: A Novel Invadopodia-Specific Marker for Invasive and Pro-Metastatic Cancer Stem Cells
        • Article
        • Peer Reviewed
        UC Davis Previously Published Works (2015)

        Background

        We know little about patient-physician communication during visits to discuss diagnosis and treatment of prostate cancer.

        Objective

        To examine the overall visit structure and how patients and physicians transition between communication activities during visits in which patients received new prostate cancer diagnoses.

        Participants

        Forty veterans and 18 urologists at one VA medical centre.

        Methods

        We coded 40 transcripts to identify major communication activities during visits and used empiric discourse analysis to analyse transitions between activities.

        Results

        We identified five communication activities that occurred in the following typical sequence: 'diagnosis delivery', 'risk classification', 'options talk', 'decision talk' and 'next steps'. The first two activities were typically brief and involved minimal patient participation. Options talk was typically the longest activity; physicians explicitly announced the beginning of options talk and framed it as their professional responsibility. Some patients were unsure of the purpose of visit and/or who should make treatment decisions.

        Conclusion

        Visits to deliver the diagnosis of early stage prostate cancer follow a regular sequence of communication activities. Physicians focus on discussing treatment options and devote comparatively little time and attention to discussing the new cancer diagnosis. Towards the goal of promoting patient-centred communication, physicians should consider eliciting patient reactions after diagnosis delivery and explaining the decision-making process before describing treatment options.
          Cover page: Patient–physician communication about early stage prostate cancer: analysis of overall visit structure
          • Article
          • Peer Reviewed
          UC Davis Previously Published Works (2014)

          The mechanism of renal failure during fulminant hepatic failure (FHF) or end-stage of liver disease is not fully understood. The present study aims to delineate the mechanisms of decreased glomerular filtration rate (GFR) in acute hepatic failure. A rat model of renal insufficiency in severe liver injury was established by lipopolysaccharide (LPS) plus D-galactosamine (GalN) exposure. GFR was evaluated by continuous infusion of fluorescein isothiocyanate-inulin with implanted micro-osmotic pumps. GalN/LPS intoxication resulted in severe hepatocyte toxicity as evidenced by liver histology and biochemical tests, whereas renal morphology remained normal. GFR was reduced by 33% of the controls 12 h after GalN/LPS exposure, accompanied with a decreased serum sodium levels, a marked increase in serum TNF-α and ET-1 levels as well as significantly upregulated renal type 1 inositol 1,4,5-trisphosphate receptor (IP3R1) expression. The upregulated IP3R1 expression was abrogated by the treatment of anti-TNF-α antibodies, but not by 2-aminoethoxydiphenylborate (2-APB), which blocks the inositol 1,4,5-trisphosphate signaling pathway. Treatments with either TNF-α antibodies or 2-APB also significantly improved the compromised GFR, elevated serum urea nitrogen and creatinine levels, and reversed the decrease in glomerular inulin space and the increase in glomerular calcium content in GalN/LPS-exposed rats. The extent of acute liver injury as reflected by serum ALT levels was much more attenuated by anti-TNF-α antibodies than by 2-APB. Liver histology further confirmed that anti-TNF-α antibodies conferred better protection than 2-APB in GalN/LPS-exposed rats. LPS-elicited TNF-α over-production is responsible for decreased GFR through IP3R1 overexpression, and the compromised GFR resulted in the development of acute renal failure in rats with FHF.

            Cover page: Tumor necrosis factor-alpha-induced reduction of glomerular filtration rate in rats with fulminant hepatic failure.
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2017)
            Adolescence and young adulthood, a period essential for determining exposures over the life-course, is an ideal time to intervene to lower cancer risk. This demographic group can be viewed as both the target audience and generator of messages for cancer prevention, such as skin cancer, obesity-, tobacco-, and human papillomavirus-related cancers. The purpose of this paper is to encourage innovative health communications that target youth; youth behavior; and the structural, environmental, and social determinants of youth behavior as critical areas of focus for cancer prevention and disparities reduction. The authors describe the rationale, processes, products, and early impacts of an award-winning youth diabetes prevention communication campaign model (The Bigger Picture) that harnesses spoken-word messages in school-based and social media presentations. The campaign supports minority adolescent and young adult artists to create content that aligns with values held closely by youth-values likely to resonate and affect change, such as defiance against authority, inclusion, and social justice. This campaign can be leveraged to prevent obesity, which is a cancer risk factor. Then, the authors propose concrete ways that The Bigger Picture's pedagogical model could be adapted for broader cancer prevention messaging for youth of color and youth stakeholders regarding tobacco-related cancers, skin cancers, and human papillomavirus-related cancers. The goal is to demonstrate how a youth-generated and youth-targeted prevention campaign can: (1) reframe conversations about cancer prevention, (2) increase awareness that cancer prevention is about social justice and health equity, and (3) catalyze action to change social norms and confront the social and environmental drivers of cancer disparities.
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2020)
              G protein-coupled estrogen receptor-1 (GPER), a member of the G protein-coupled receptor (GPCR) superfamily, mediates estrogen-induced proliferation of normal and malignant breast epithelial cells. However, its role in breast cancer stem cells (BCSCs) remains unclear. Here we showed greater expression of GPER in BCSCs than non-BCSCs of three patient-derived xenografts of ER- /PR+ breast cancers. GPER silencing reduced stemness features of BCSCs as reflected by reduced mammosphere forming capacity in vitro, and tumor growth in vivo with decreased BCSC populations. Comparative phosphoproteomics revealed greater GPER-mediated PKA/BAD signaling in BCSCs. Activation of GPER by its ligands, including tamoxifen (TMX), induced phosphorylation of PKA and BAD-Ser118 to sustain BCSC characteristics. Transfection with a dominant-negative mutant BAD (Ser118Ala) led to reduced cell survival. Taken together, GPER and its downstream signaling play a key role in maintaining the stemness of BCSCs, suggesting that GPER is a potential therapeutic target for eradicating BCSCs.
                Cover page: GPER‐induced signaling is essential for the survival of breast cancer stem cells
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2022)
                Resistance to antitumor treatment contributes to patient mortality. Functional proteomic screening of organoids derived from chemotherapy-treated patients with breast cancer identified nuclear receptor corepressor 2 (NCOR2) histone deacetylase as an inhibitor of cytotoxic stress response and antitumor immunity. High NCOR2 in the tumors of patients with breast cancer predicted chemotherapy refractoriness, tumor recurrence and poor prognosis. Molecular studies revealed that NCOR2 inhibits antitumor treatment by regulating histone deacetylase 3 (HDAC3) to repress interferon regulatory factor 1 (IRF-1)-dependent gene expression and interferon (IFN) signaling. Reducing NCOR2 or impeding its epigenetic activity by modifying its interaction with HDAC3 enhanced chemotherapy responsiveness and restored antitumor immunity. An adeno-associated viral NCOR2-HDAC3 competitor potentiated chemotherapy and immune checkpoint therapy in culture and in vivo by permitting transcription of IRF-1-regulated proapoptosis and inflammatory genes to increase IFN-γ signaling. The findings illustrate the utility of patient-derived organoids for drug discovery and suggest that targeting stress and inflammatory-repressor complexes such as NCOR2-HDAC3 could overcome treatment resistance and improve the outcome of patients with cancer.
                  Cover page: Screening of organoids derived from patients with breast cancer implicates the repressor NCOR2 in cytotoxic stress response and antitumor immunity
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2018)
                  HIV posttreatment controllers (PTCs) represent a natural model of sustained HIV remission, but they are rare and little is known about their viral reservoir. We obtained 1,450 proviral sequences after near-full-length amplification for 10 PTCs and 16 posttreatment noncontrollers (NCs). Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups. Quantification of total but not intact proviral genome copies predicted sustained HIV remission as 81% of NCs, but none of the PTCs had a total proviral genome greater than 4 copies per million peripheral blood mononuclear cells (PBMCs). The results highlight the restricted intact and defective HIV reservoir in PTCs and suggest that total proviral genome burden could act as the first biomarker for identifying PTCs. Total and defective but not intact proviral copy numbers correlated with levels of cell-associated HIV RNA, activated NK cell percentages, and both HIV-specific CD4+ and CD8+ responses. These results support the concept that defective HIV genomes can lead to viral antigen production and interact with both the innate and adaptive immune systems.
                    Cover page: HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2016)
                    Although traditional chemotherapy kills a fraction of tumor cells, it also activates the stroma and can promote the growth and survival of residual cancer cells to foster tumor recurrence and metastasis. Accordingly, overcoming the host response induced by chemotherapy could substantially improve therapeutic outcome and patient survival. In this study, resistance to treatment and metastasis has been attributed to expansion of stem-like tumor-initiating cells (TICs). Molecular analysis of the tumor stroma in neoadjuvant chemotherapy-treated human desmoplastic cancers and orthotopic tumor xenografts revealed that traditional maximum-tolerated dose chemotherapy, regardless of the agents used, induces persistent STAT-1 and NF-κB activity in carcinoma-associated fibroblasts. This induction results in the expression and secretion of ELR motif-positive (ELR+) chemokines, which signal through CXCR-2 on carcinoma cells to trigger their phenotypic conversion into TICs and promote their invasive behaviors, leading to paradoxical tumor aggression after therapy. In contrast, the same overall dose administered as a low-dose metronomic chemotherapy regimen largely prevented therapy-induced stromal ELR+ chemokine paracrine signaling, thus enhancing treatment response and extending survival of mice carrying desmoplastic cancers. These experiments illustrate the importance of stroma in cancer therapy and how its impact on treatment resistance could be tempered by altering the dosing schedule of systemic chemotherapy.
                      Cover page: Metronomic chemotherapy prevents therapy-induced stromal activation and induction of tumor-initiating cells
                      Top