8 research outputs found
Sex (still) Sells: How Sex Trafficking in the United States and Thailand Perpetuates Minority Repression
Human trafficking is the third most profitable illegal international trade behind drug and arms trafficking. Sex trafficking is the second largest subset of this illegal enterprise and soon may equal or surpass labor trafficking as the prominent subset. This research aims to address four integral components of the sex trafficking and forced prostitution trade: (1) to show how sex trafficking in Thailand is being used perpetually to repress minority women and their communities; (2) to show how sex trafficking of minors (ranging in age from 8-17) in Atlanta, Georgia is shockingly similar to sex trafficking practices in Thailand; (3) to find the economic, political and cultural implications which foster the sex trafficking trade in both areas; and 4) to derive from these commonalities a solution to help mitigate and potentially eliminate these atrocities. The prevalence, severity and cruelty of forced prostitution are issues that the globalized world must address and attempt to solve because this practice infiltrates the culture, economics and politics of the countries it affects. If two locations as different as the U.S. and Thailand can show the same commonalities in terms of how and why women and girls are trafficked, then perhaps these same techniques are being used worldwide. By identifying the commonalities behind sex trafficking from the U.S. to Thailand, this paper aims to outline methods and techniques that can eventually lead to the elimination of this harmful practice
Ref-1 redox activity alters cancer cell metabolism in pancreatic cancer: exploiting this novel finding as a potential target
Background: Pancreatic cancer is a complex disease with a desmoplastic stroma, extreme hypoxia, and inherent resistance to therapy. Understanding the signaling and adaptive response of such an aggressive cancer is key to making advances in therapeutic efficacy. Redox factor-1 (Ref-1), a redox signaling protein, regulates the conversion of several transcription factors (TFs), including HIF-1α, STAT3 and NFκB from an oxidized to reduced state leading to enhancement of their DNA binding. In our previously published work, knockdown of Ref-1 under normoxia resulted in altered gene expression patterns on pathways including EIF2, protein kinase A, and mTOR. In this study, single cell RNA sequencing (scRNA-seq) and proteomics were used to explore the effects of Ref-1 on metabolic pathways under hypoxia.
Methods: scRNA-seq comparing pancreatic cancer cells expressing less than 20% of the Ref-1 protein was analyzed using left truncated mixture Gaussian model and validated using proteomics and qRT-PCR. The identified Ref-1's role in mitochondrial function was confirmed using mitochondrial function assays, qRT-PCR, western blotting and NADP assay. Further, the effect of Ref-1 redox function inhibition against pancreatic cancer metabolism was assayed using 3D co-culture in vitro and xenograft studies in vivo.
Results: Distinct transcriptional variation in central metabolism, cell cycle, apoptosis, immune response, and genes downstream of a series of signaling pathways and transcriptional regulatory factors were identified in Ref-1 knockdown vs Scrambled control from the scRNA-seq data. Mitochondrial DEG subsets downregulated with Ref-1 knockdown were significantly reduced following Ref-1 redox inhibition and more dramatically in combination with Devimistat in vitro. Mitochondrial function assays demonstrated that Ref-1 knockdown and Ref-1 redox signaling inhibition decreased utilization of TCA cycle substrates and slowed the growth of pancreatic cancer co-culture spheroids. In Ref-1 knockdown cells, a higher flux rate of NADP + consuming reactions was observed suggesting the less availability of NADP + and a higher level of oxidative stress in these cells. In vivo xenograft studies demonstrated that tumor reduction was potent with Ref-1 redox inhibitor similar to Devimistat.
Conclusion: Ref-1 redox signaling inhibition conclusively alters cancer cell metabolism by causing TCA cycle dysfunction while also reducing the pancreatic tumor growth in vitro as well as in vivo
Exploring transcriptional regulators Ref-1 and STAT3 as therapeutic targets in malignant peripheral nerve sheath tumours
Background
MPNST is a rare soft-tissue sarcoma that can arise from patients with NF1. Existing chemotherapeutic and targeted agents have been unsuccessful in MPNST treatment, and recent findings implicate STAT3 and HIF1-α in driving MPNST. The DNA-binding and transcriptional activity of both STAT3 and HIF1-α is regulated by Redox factor-1 (Ref-1) redox function. A first-generation Ref-1 inhibitor, APX3330, is being tested in cancer clinical trials and could be applied to MPNST.
Methods
We characterised Ref-1 and p-STAT3 expression in various MPNST models. Tumour growth, as well as biomarkers of apoptosis and signalling pathways, were measured by qPCR and western blot following treatment with inhibitors of Ref-1 or STAT3.
Results
MPNSTs from Nf1-Arfflox/floxPostnCre mice exhibit significantly increased positivity of p-STAT3 and Ref-1 expression when malignant transformation occurs. Inhibition of Ref-1 or STAT3 impairs MPNST growth in vitro and in vivo and induces apoptosis. Genes highly expressed in MPNST patients are downregulated following inhibition of Ref-1 or STAT3. Several biomarkers downstream of Ref-1 or STAT3 were also downregulated following Ref-1 or STAT3 inhibition.
Conclusions
Our findings implicate a unique therapeutic approach to target important MPNST signalling nodes in sarcomas using new first-in-class small molecules for potential translation to the clinic
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From the Quadrangle to the River: Revitalizing the Heart of Downtown Springfield
This studio report explores community service learning in the graduate urban design studio taught in the in Department of Landscape Architecture and Regional Planning at the University of Massachusetts Amherst and instructed by Professor Frank Sleegers.
The project will began with a visioning workshop, conducted to engage community members in the shaping of project goals and objectives within the project area of downtown Springfield. These findings were brought to the studio and guided the design process and outcomes.
Five design teams developed five alternative master plans for the core area of downtown Springfield with focus on the revitalization of open space and the connection of the urban axis from the Quadrangle to the Connecticut River. These five design strategies are recommendations to improve the livability of the heart of downtown Springfield for employers, employees, residents, and visitors.
Remarkable for this studio was a simultaneous collaboration with another Landscape Architecture Studio and an Architecture Studio at the University of Massachusetts Amherst. These studios were coordinated through the UMass Amherst Design Center that was launched in the spring of 2010.
The public response to the work of the three studios resulted in the reopening of Pynchon Plaza – a pocket park in the axis of the Quadrangle to the River that had been closed down for 35 years