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Open Access Publications from the University of California

Scholarly Works (18 results)

  • Article
  • Peer Reviewed
UCLA Previously Published Works (2008)

Melanoma antigen recognized by T cells 1 (MART-1) and tyrosinase-related protein-2 (TRP-2) are two useful markers for immunohistochemical detection of melanocytic tumors. However, these markers may be passively acquired (phagocytosed) rather than actively synthesized. Reverse transcriptase in situ polymerase chain reaction (RT in situ PCR) can amplify even small amounts of specific mRNA in cells and therefore confirm the cellular source of a marker. We developed a one-step RT in situ PCR procedure in which Thermus thermophilus DNA polymerase synthesizes and amplifies cDNA from mRNA in a single reaction mixture. To examine its practicability and feasibility with formalin-fixed, paraffin-embedded (FFPE) tissue, we compared the results of one-step RT in situ PCR with those of immunohistochemistry (IHC). MART-1 mRNA was identified in the cytoplasm of lesional cells from 23/26 primary melanomas (92%), 9/9 metastatic melanomas (100%) and 5/6 nevi (83%). MART-1 epitope was detected by IHC in 23/24 primary melanomas (96%), 9/9 metastatic melanomas (100%) and 5/6 nevi (83%). TRP-2 mRNA was identified in the cytoplasm of lesional cells from 17/26 primary melanomas (65%), 6/9 metastatic melanomas (67%) and 4/6 nevi (67%). TRP-2 epitope was detected by IHC in 20/24 primary melanomas (83%), 9/9 metastatic melanomas (100%) and 4/6 nevi (67%). Both techniques detected MART-1 and TRP-2 in FFPE melanoma cell lines. Neither marker was detected in squamous cell carcinomas or basal cell carcinomas by RT in situ PCR or IHC. We conclude that the RT in situ PCR technique can be successfully applied to FFPE tissue to determine the cellular sources of gene expression observed by conventional PCR approaches.

    Cover page: RT in situ PCR detection of MART-1 and TRP-2 mRNA in formalin-fixed, paraffin-embedded tissues of melanoma and nevi.
    • Article
    UC Irvine Law Review , Volume 8, Issue 1 (2018)
      Cover page: (Choice) Blind Justice: Legal Implications of the Choice Blindness Phenomenon
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2020)
      The current research investigated the role that a person's race, gender, and emotional expressions play in workplace evaluations of their competence and status. Previous research demonstrates that women who express anger in the workplace are penalized, whereas men are not, and may even be rewarded. Workplace sanctions against angry women are often attributed to a backlash resulting from the violation of gender stereotypes. However, gender stereotypes may differ by race. The present study addressed this question using a between-subjects experimental design where participants (N = 630) read a vignette describing a new employee, which varied with respect to the employee's race (White, Black, Asian, and Latino/a/x), gender (male and female), and a prior emotional response (anger and sadness). Participants then evaluated the employee's competence and status. Findings revealed that men and women were both viewed as more competent when expressing anger relative to sadness, and this pattern did not differ across employee race. However, despite anger being associated with greater competence, women who violated stereotypes (i.e., expressed anger) were accorded lower status than stereotype-inconsistent (sad) men. Furthermore, exploratory analyses revealed that this pattern was consistent regardless of target and participant race. The current study replicates and extends previous research by employing an intersectional perspective and using a large, ethnically diverse sample to explore the interaction between gender and emotional expression on workplace evaluations across races.
        Cover page: Workplace Anger Costs Women Irrespective of Race
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2016)
        Choice blindness refers to the finding that people can often be misled about their own self-reported choices. However, little research has investigated the more long-term effects of choice blindness. We examined whether people would detect alterations to their own memory reports, and whether such alterations could influence participants' memories. Participants viewed slideshows depicting crimes, and then either reported their memories for episodic details of the event (Exp. 1) or identified a suspect from a lineup (Exp. 2). Then we exposed participants to manipulated versions of their memory reports, and later tested their memories a second time. The results indicated that the majority of participants failed to detect the misinformation, and that exposing witnesses to misleading versions of their own memory reports caused their memories to change to be consistent with those reports. These experiments have implications for eyewitness memory.
          Cover page: Memory blindness: Altered memory reports lead to distortion in eyewitness memory
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2019)
          How people remember feeling in the past informs future decisions; however, memory for past emotion is subject to a number of biases. Previous research on choice blindness has shown that people often fail to notice when they are exposed to misinformation about their own decisions, preferences, and memories. This type of misinformation can influence how they later remember past events. In the present study, we examined the memory blindness effect in a new domain: memory for pain. Participants (N = 269) underwent a cold-pressor task and rated how much pain, distress, and positive and negative affect they had experienced. Later, participants were shown their pain ratings and asked to explain them. Some of the participants were shown lower pain ratings than they had actually made. In a second session, participants recalled how painful the task had been and how much distress and positive and negative affect they remembered experiencing. The results indicated that the majority of participants who were exposed to misinformation failed to detect the manipulation, and subsequently remembered the task as being less painful. The participants in the misinformation condition were not overall more willing to repeat the study tasks, but the participants who recalled less distress, less negative affect, and more positive affect were more willing to repeat the study tasks again in a future experiment. These results demonstrate the malleability of memory for painful experiences and that willingness to repeat aversive experiences may depend more on memory for affective reactions to the original experience than on memory for the physical pain itself.
            Cover page: Misremembering pain: A memory blindness approach to adding a better end.
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2021)
            Wound healing is a multi-step process to rapidly restore the barrier function. This process is often impaired in diabetic patients resulting in chronic wounds and amputation. We previously found that paradoxical activation of the mitogen-activated protein kinase (MAPK) pathway via topical administration of the BRAF inhibitor vemurafenib accelerates wound healing by activating keratinocyte proliferation and reepithelialization pathways in healthy mice. Herein, we investigated whether this wound healing acceleration also occurs in impaired diabetic wounds and found that topical vemurafenib not only improves wound healing in a murine diabetic wound model but unexpectedly promotes hair follicle regeneration. Hair follicles expressing Sox-9 and K15 surrounded by CD34+ stroma were found in wounds of diabetic and non-diabetic mice, and their formation can be prevented by blocking downstream MEK signaling. Thus, topically applied BRAF inhibitors may accelerate wound healing, and promote the restoration of improved skin architecture in both normal and impaired wounds.
              Cover page: Wound healing with topical BRAF inhibitor therapy in a diabetic model suggests tissue regenerative effects
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2018)
              A promising arsenal of targeted and immunotherapy treatments for metastatic melanoma has emerged over the last decade. With these therapies, we now face new mechanisms of tumor-acquired resistance. We report here a patient whose metastatic melanoma underwent dedifferentiation as a resistance mechanism to adoptive T-cell transfer therapy (ACT) to the MART1 antigen, a phenomenon that had been observed only in mouse studies to date. After an initial period of tumor regression, the patient presented in relapse with tumors lacking melanocytic antigens (MART1, gp100) and expressing an inflammation-induced neural crest marker (NGFR). We demonstrate using human melanoma cell lines that this resistance phenotype can be induced in vitro by treatment with MART1 T cell receptor-expressing T cells or with TNFα, and that the phenotype is reversible with withdrawal of inflammatory stimuli. This supports the hypothesis that acquired resistance to cancer immunotherapy can be mediated by inflammation-induced cancer dedifferentiation.Significance: We report a patient whose metastatic melanoma underwent inflammation-induced dedifferentiation as a resistance mechanism to ACT to the MART1 antigen. Our results suggest that future melanoma ACT protocols may benefit from the simultaneous targeting of multiple tumor antigens, modulating the inflammatory response, and inhibition of inflammatory dedifferentiation-inducing signals. Cancer Discov; 8(8); 935-43. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 899.
                Cover page: Immunotherapy resistance by inflammation-induced dedifferentiation
                • Article
                • Peer Reviewed
                ICTS Publications (2014)
                  Cover page: A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma PathobiologyCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2014)

                  Purpose

                  To evaluate the immunomodulatory effects of cytotoxic T-lymphocyte-associated protein 4 (CTLA4) blockade with tremelimumab in peripheral blood mononuclear cells (PBMC).

                  Experimental design

                  We used next-generation sequencing to study the complementarity-determining region 3 (CDR3) from the rearranged T-cell receptor (TCR) variable beta (V-beta) in PBMCs of 21 patients, at baseline and 30 to 60 days after receiving tremelimumab.

                  Results

                  After receiving tremelimumab, there was a median of 30% increase in unique productive sequences of TCR V-beta CDR3 in 19 out of 21 patients, and a median decrease of 30% in only 2 out of 21 patients. These changes were significant for richness (P = 0.01) and for Shannon index diversity (P = 0.04). In comparison, serially collected PBMCs from four healthy donors did not show a significant change in TCR V-beta CDR3 diversity over 1 year. There was a significant difference in the total unique productive TCR V-beta CDR3 sequences between patients experiencing toxicity with tremelimumab compared with patients without toxicity (P = 0.05). No relevant differences were noted between clinical responders and nonresponders.

                  Conclusions

                  CTLA4 blockade with tremelimumab diversifies the peripheral T-cell pool, representing a pharmacodynamic effect of how this class of antibodies modulates the human immune system.
                    Cover page: CTLA4 Blockade Broadens the Peripheral T-Cell Receptor Repertoire
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2014)
                    On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed. ©2014 AACR.
                      Cover page: A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology
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