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Open Access Publications from the University of California

Scholarly Works (33 results)

  • Thesis
  • Peer Reviewed
UC Irvine Electronic Theses and Dissertations (2024)

Cancer health disparities in people with disability have received limited attention. This study aimed to investigate the barriers to accessing timely healthcare and health-related outcomes in cancer patients with disability. Cancer patients with a diagnosis of breast cancer, lung cancer, colorectal cancer, skin cancer, pancreatic cancer, gastric cancer and oesophageal cancer were extracted from the NIH All of Us Research Program. Participants were stratified by disability status and then matched by propensity scores. Survey responses were compared using Pearson’s chi-squared tests for categorical variables and t-tests for continuous variables. Patients with disability (N=4,546) were more likely to be non-White, unemployed for wages, uninsured, had less annual household income and less advanced education. Propensity score matching resulted in 4,437 participants in each cohort. The disability cohort was more likely to report delayed medical care due to high out-of-pocket (15%), feeling nervous about seeing a provider (12.2%), lacking transportation (10.8%), co-pay (7.1%) and distance (4.2%). In addition, the financial burden of accessing healthcare was more profound in patients with disability. Dental care (20.5%) was the most common unaffordable service, followed by eyeglasses (15.5%), prescription medicines (14.5%), specialty care (10.6%), follow-up care (8.1%), mental health care or counselling (7.1%) and emergency care (4.5%). Also, cost-related medical non-adherence was more frequent in the disability cohort, including delaying filling prescriptions (11.1%) and skipping doses (6.5%). Further, the disability cohort reported worse physical health, mental health and quality of life. In conclusion, this study demonstrated that cancer patients with disability face significant disadvantages and encounter significant barriers in accessing and affording healthcare, resulting in poorer overall health and quality of life.

    Cover page: Gaps in Accessibility and Affordability to Achieve Health Equity for Cancer Patients with Disability
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2018)

    The Golgi is the main hub for the modification, sorting, and transporting of proteins to various intra- and extracellular destinations. Against conventional belief that most of Golgi trafficking was constitutive, our data show regulation of Golgi morphology and trafficking in response to cell density, and extracellular cue.

    Studies in our lab showed that the Golgi phosphoprotein 3 (GOLPH3) functions at the Golgi in the GOLPH3 complex to regulate Golgi trafficking. GOLPH3 is recruited to the Golgi by binding to phosphatidylInositol-4-phosphate (PI(4)P) which is enriched at the trans-Golgi. GOLPH3 also interacts with Myosin 18A (MYO18A), which in turn binds to F-actin. The linkages of PI(4)P-GOLPH3-MYO18A-F-actin make the basis of the GOLPH3 complex, which provides a tensile force applied onto Golgi membrane to aid in vesicles budding for protein transport. The consequence of that process is Golgi being stretched like an extended ribbon that surrounds the nucleus. We have shown that interfering with the GOLPH3 complex reduces cellular transport and alters Golgi morphology.

    Here, we identify a signaling pathway that transduces cell density signal through the Hippo proteins MST1/2 and the STRIPAK complex to the GOLPH3 complex to regulate Golgi forward trafficking. In sparsely growing cells, MST1/2, independently of their kinase activity and the canonical Hippo pathway, act to promote the localization of Striatin 3 (STRN3) to the Golgi where STRN3 directly interacts with GOLPH3 bridging it with other members of the STRIPAK complex. The PP2A phosphatase activity of STRIPAK promotes GOLPH3’s interaction with MYO18A, which together drive Golgi forward trafficking and impart the Golgi’s normal, extended ribbon shape. On the other hand, high cell density inhibits interaction between STRIPAK complex to GOLPH3 taking away the effect of PP2A, which results in a weaken GOLPH3-MYO18A interaction. Inhibition of GOLPH3-MYO18A interaction results in compact Golgi and reduced Golgi trafficking in high cell density.

    Through control of secretion, cell density signaling through MST1/2, STRIPAK, and GOLPH3 complex regulate paracrine growth factor signaling, providing a means to affect the proliferation of neighboring cells.

      Cover page: Cell Density Regulates the Golgi through Hippo, the STRIPAK Complex, and GOLPH3
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2019)

      Background

      Adjuvant immunotherapy has improved outcomes in patients with advanced melanoma; however, the potential benefit for patients with pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was to determine the impact of adjuvant chemotherapy and immunotherapy (CTx-IT) compared with CTx alone on patient survival after resection of PDAC.

      Study design

      Patients who underwent resection of PDAC from 2004 to 2015 were identified from the National Cancer Database. Univariate and multivariate Cox proportional hazards models were used to determine predictors of overall survival (OS) based on the type of adjuvant therapy received. Patients who received adjuvant immunotherapy were compared with those who received adjuvant CTx alone by propensity score matching.

      Results

      Of 21,313 patients who received curative-intent resection for PDAC followed by adjuvant systemic therapy, 269 (1.3%) patients were treated with adjuvant CTx-IT. Propensity score matching resulted in a cohort of 477 patients: (229 CTx only and 248 CTx-IT). The 5-year OS was higher in the CTx-IT group compared with CTx alone (29.2% vs 18.3%; p = 0.0045). On multivariate analysis, the addition of adjuvant immunotherapy was associated was improved overall survival (hazard ratio 0.74; p = 0.007).

      Conclusions

      The addition of adjuvant immunotherapy to chemotherapy is associated with improved survival compared with chemotherapy alone after curative-intent resection of pancreatic adenocarcinoma. Future research is warranted to match specific immunotherapy agents with susceptible patient populations to improve outcomes for this aggressive disease.
        Cover page: Impact of Immunotherapy after Resection of Pancreatic Cancer
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2013)
        Small cell, neuroendocrine tumors, and melanoma of the anus are rare. Limited data exist on the incidence and management for these rare tumors. A large, prospective, population-based database was used to determine incidence and survival patterns of rare anal neoplasms. The Surveillance, Epidemiology and End Results registry was queried to identify patients diagnosed with anal canal neoplasms. Incidence and survival patterns were evaluated with respect to age, sex, race, histology, stage, and therapy. We identified 7078 cases of anal canal neoplasms: melanoma (n = 149), neuroendocrine (n = 61), and small cell neuroendocrine (n = 26). Squamous cell carcinoma (SCC) (n = 6842) served as the comparison group. Anal melanoma (AM) demonstrated the lowest survival rate at 2.5 per cent. Neuroendocrine tumors (NETs) demonstrated similar survival as SCC (10-year survival for regional disease of 25 and 22.3%, respectively). Ten-year survival of small cell NETs resembled AM (5.3 vs 2.5%). Age 60 years or older, sex, black race, stage, and surgery were independent predictors of survival. This study presents the largest patient series of rare anal neoplasms. NETs of the anal canal demonstrate similar survival patterns to SCC, whereas small cell NETs more closely resemble AM. Accurate histologic diagnosis is vital to determine treatment and surgical management because survival patterns can differ among rare anal neoplasms.
          Cover page: Incidence and Survival Patterns of Rare Anal Canal Neoplasms Using the Surveillance Epidemiology and End Results Registry
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2016)
          It is unclear whether differential roles of CD4(+) versus CD8(+) T-cell senescence/exhaustion and effects of antiretroviral therapy (ART) on these processes may contribute to morbidity in treated human immunodeficiency virus type 1 (HIV) infection. In a prospective 96-week trial, 328 HIV-infected ART-naive participants were randomly assigned to receive tenofovir-emtricitabine plus either atazanavir/ritonavir, darunavir/ritonavir, or raltegravir. Markers of CD4(+) T-cell senescence (ie, the percentage of CD28(-)CD57(+) cells among CD4(+) T cells ) and CD4(+)/CD8(+) T-cell exhaustion (ie, the percentage of PD-1(+) cells among CD4(+)/CD8(+) T cells) decreased after ART. There were no changes in markers of CD8(+) T-cell senescence after ART and no differential changes in all markers in ART groups. Senescent CD4(+) and CD8(+) T cells may have differential roles in HIV pathogenesis.
            Cover page: Changes in Markers of T-Cell Senescence and Exhaustion With Atazanavir-, Raltegravir-, and Darunavir-Based Initial Antiviral Therapy: ACTG 5260s
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2017)

            Background

            The role of oxidized lipoproteins (high-density [HDLox] and low-density [LDLox]) and total lipoprotein particle (Lp) number and size in HIV-related cardiovascular disease (CVD) is unclear. The goal of this study was to evaluate changes of these biomarkers and their associations with rate of carotid intima media thickness progression over 3 years (ΔCIMT) in chronic HIV infection.

            Methods

            Prospective study of 234 HIV-infected antiretroviral treatment-naive participants without CVD who were randomized to receive tenofovir-emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir or raltegravir (RAL) and achieved plasma HIV-1 RNA <50 copies/ml by week 24 and thereafter. Biomarker changes over 24, 48 or 96 weeks from baseline and pairwise treatment group comparisons were examined. Associations of these biomarkers with ΔCIMT were analysed with mixed effects linear regression.

            Results

            HDLp number increased with both protease inhibitors (PIs) over 48 weeks, while LDLp number declined with RAL; Lp size did not change. Over 96 weeks, normalized HDLox declined with both PIs; LDLox increased in all groups. Few treatment group differences were observed across all biomarkers. Associations between ΔCIMT and oxidized lipoproteins at all time points were not apparent (P≥0.10). There was some evidence of slower ΔCIMT for higher HDLp number (P=0.06) and for lower LDLp number (P=0.08) measured at baseline.

            Conclusions

            Unexpectedly, LDLox increased modestly in all treatment groups after ART initiation. Associations of plasma HDLox and LDLox with ΔCIMT were not apparent. While plasma levels of abnormal lipoproteins have been shown to be associated with CVD outcomes, clear associations with sub-clinical atherosclerosis progression were not apparent in our study.
              Cover page: Changes in Plasma Levels of Oxidized Lipoproteins and Lipoprotein Subfractions with Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy and Associations with Common Carotid Artery Intima-Media Thickness: ACTG 5260s
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2016)
              Antiretroviral therapy (ART) can minimize HIV transmission. Prevention benefits may be compromised by barriers to virologic suppression, and by increased condomless sex among those initiating ART. We evaluated condomless sex in a cohort of HIVinfected US individuals poised to initiate ART in a clinical trial. We assessed partner and sex act type, condom use, and perception of infectiousness. Six percent of participants reported as not infectious; men who have sex with men were more likely to perceive high infectivity. Prevalence of condomless sex was 44 %; 74 % of those also reported homosexual acquisition of HIV. Predictors of increased risk of condomless sex included greater numbers of lifetime partners, recent stimulant drug use and an HIV-positive or unknown serostatus partner. In the context of serodifferent partners, lower perception of infectiousness was also associated with a higher risk of condomless sex. Results highlight opportunities for prevention education for HIV infected individuals at ART initiation.
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2015)

                Objective

                This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years.

                Design

                Randomized clinical trial.

                Setting

                Multicenter (26 institutions).

                Patients

                ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus.

                Intervention

                Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL).

                Main outcome measures

                Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression.

                Results

                HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) μm/year] than DRV/r [12.9 (10.3, 15.5) μm/year, P = 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) μm/year, P = 0.15 vs. ATV/r; P = 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates.

                Conclusion

                In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.
                  Cover page: A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2015)

                  Background

                  It is unclear whether the integrase inhibitor raltegravir (RAL) reduces inflammation and immune activation compared with ritonavir-boosted protease inhibitors (PIs).

                  Methods

                  In a prospective, randomized, multicenter clinical trial that included 328 human immunodeficiency type 1 (HIV-1)-infected, treatment-naive participants were randomized to receive tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) plus atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or RAL. A total of 234 participants (71%) with HIV-1 RNA levels <50 copies/mL by week 24 were included. Plasma biomarkers of inflammation and coagulation that were analysed included high-sensitivity C-reactive protein, interleukin-6 (IL-6), GlycA, D-dimer, soluble CD14 (sCD14), sCD163, and sIL-2r; blood cellular markers included %CD38+DR+ of T-cell subsets and %CD14+CD16+ and%CD14(dim)CD16+ monocyte subsets. Changes from baseline were examined at earlier (24 or 48 weeks) and later (96 weeks) time points, with 95% confidence intervals on fold-change. Pairwise treatment groups were compared using Wilcoxon rank sum tests, with P values adjusted for false discovery rate control.

                  Results

                  Changes in biomarkers varied by regimen during the 96 weeks of follow-up as follows: hsCRP declined with ATV/r and RAL, IL-6 declined only with RAL, and GLycA decreased in all groups. D-dimer declined with ATV/r and DRV/r and was unchanged with RAL. Markers of T-cell activation and sCD163 (but not sCD14 and CD14-+CD16+) declined in all groups.

                  Conclusions

                  Despite some differences in specific markers of inflammation and immune activation between the antiretroviral therapy (ART) regimens, we found no consistent evidence that the reduction of inflammation and immune activation with ART initiation was different between RAL and PI-based regimens.

                  Clinical trials registration

                  NCT00811954 and NCT00851799.
                    Cover page: Changes in Inflammation and Immune Activation With Atazanavir-, Raltegravir-, Darunavir-Based Initial Antiviral Therapy: ACTG 5260s
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2016)

                    Background

                    Adrenocortical carcinoma (ACC) is an aggressive malignancy typically resistant to chemotherapy and radiation. Surgery, even in the setting of locally recurrent or metastatic disease, remains the only potentially curative option. However, the subset of patients who will benefit from repeat resection in this setting remains ill defined. The objective of this study was to propose a prognostic clinical score that facilitates selection of patients for repeat resection of recurrent ACC.

                    Study design

                    Patients who underwent curative-intent repeat resection for recurrent ACC at 1 of 13 academic medical centers participating in the US ACC Study Group were identified. End points included morbidity, mortality, and overall survival.

                    Results

                    Fifty-six patients underwent repeat curative-intent resection for recurrent ACC (representing 21% of 265 patients who underwent resection for primary ACC) from 1997 to 2014. Median age was 52 years. Sites of resected recurrence included locoregional only (54%), lung only (14%), liver only (12%), combined locoregional and lung (4%), combined liver and lung (4%), and other distant sites (12%). Thirty-day morbidity and mortality rates were 40% and 5.4%, respectively. Cox regression analysis revealed that the presence of multifocal recurrence, disease-free interval <12 months, and extrapulmonary distant metastases were independent predictors of poor survival. A clinical score consisting of 1-point each for the 3 variables demonstrated good discrimination in predicting survival after repeat resection (5-year: 72% for 0 points, 32% for 1 point, 0% for 2 or 3 points; p = 0.0006, area under the curve = 0.78).

                    Conclusions

                    Long-term survival after repeat resection for recurrent ACC is feasible when 2 of the following factors are present: solitary tumor, disease-free interval >12 months, and locoregional or pulmonary recurrence.
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