Reimagining Transitional Justice Cohen, Cynthia E
The international journal of transitional justice,
03/2020, Letnik:
14, Številka:
1
Journal Article
Recenzirano
To recover from periods of mass atrocities, gross abuses of human rights and longstanding systems of oppression, individuals, communities and societies face complex challenges: to understand the ...meaning of what has transpired; to consider reparations for those who were injured; to hold those responsible to account; to transform the underlying systems of power and privilege that contributed to the violence; and to build or rebuild trust in both people and institutions. Sufficient trust allows for the collaborations necessary for solving problems and co-creating a better future. By focusing on the contributions of arts and culture to transitional justice, this Special Issue of the journal enters a debate about whether transitional justice processes should be assessed at least as much by consideration of the quality of lives of ordinary people, especially those who have borne the brunt of violence, as by the number of prosecutions or convictions of criminals.
How can policies align K-12 arts education with urgent needs of students, their communities and our interconnected world? How can they nourish capacities for empathy and moral imagination? ...Inspiration can be found in the oeuvre of the African American music educator, cultural worker, and activist Jane Wilburn Sapp. This article demonstrates how she elicits songs from students, integrates the home cultures of students into the arts curricula of schools, and invites school communities to benefit from their diversity. Sapp's international work is instructive for cultural policy at the level of the municipality: meaningful lifelong learning in a diverse society can take place only when marginalized communities contribute their talents and knowledge to planning processes. Also, researchers should ensure that knowledge generated by communities not be extracted for the exclusive use of the academy; it should rather support communities "to look at what they know...and how to take that knowledge and recognize in it the building blocks for change." Jane Sapp's songs, stories, and reflections are in Let's Make A Better World: Stories and Songs by Jane Sapp, (Jane Sapp, Brandeis University Press, 2018) and a related podcast. These resources, along with a documentary film Someone Sang For Me, can be accessed through
www.janesapp.org
Summary Malignant melanoma patients require BRAF mutation testing prior to initiating BRAF inhibitor therapy. Molecular testing remains the diagnostic gold standard, but recent work suggests that ...BRAF immunohistochemistry (IHC) confers comparable results. Sample attributes and scoring criteria that may affect BRAF IHC interpretation, however, are poorly defined. We investigated formalin-fixed, paraffin-embedded samples with variable challenging interpretative attributes: metastases, core needle biopsies, sample tissues less than 60 mm2 , samples with greater than 50% necrosis, and/or samples with greater than 10% melanin pigmentation. Three pathologists independently scored 122 BRAF V600E IHC-labeled melanoma samples for percentage (0%-100%) of staining intensity (0-3+). Interscorer BRAF IHC discrepancies were resolved by consensus review. Lenient (≥1+, >0%) and stringent (≥2+, ≥10%) IHC scoring criteria were compared to BRAF V600 mutation (cobas) results (n = 118). Specimens with greater than 10% melanin pigmentation and metastatic samples produced the majority of interobserver IHC and IHC/cobas scoring discrepancies. Consensus review using stringent scoring criteria decreased the number of discrepant results, yielded very good interobserver reproducibility, and improved specificity and positive predictive value for BRAF p.V600E detection. BRAF p.V600K mutations accounted for 57.1% of false-negative IHC results when stringent, consensus criteria scoring were used. The cobas test detected 75.0% (8/12) of BRAF IHC-negative BRAF p.V600K mutations confirmed by next-generation sequencing. Molecular BRAF testing is the preferred screening test for BRAF inhibitor therapy eligibility because of superior sensitivity in challenging interpretative melanoma specimens. However, BRAF V600E IHC has excellent specificity and positive predictive value when stringent, consensus scoring criteria are implemented. To decrease IHC scoring discrepancies, pathologists should interpret metastatic and pigmented samples with caution.
Erythroblast transformation specific related gene (ERG), a proto-oncogene member of the erythroblast transformation specific transcription factor family, is a sensitive marker of endothelial ...differentiation and is expressed in vascular tumours, including angiosarcomas (AS). Immunohistochemistry is necessary for the diagnosis of AS in fine needle aspirates where low cellularity and lack of preserved tissue architecture impedes diagnosis. The aim of this study was to assess the utility of an ERG-enriched immunohistochemistry panel in the cytological diagnosis of AS.
25 AS diagnosed on fine needle aspirates were stained for ERG, CD31, CD34, and AE1/AE3. Staining intensity and percentage tumour cell positivity were evaluated. Spearman's correlation was assessed for significant correlations between antibodies.
Sensitivities for ERG, CD31, CD34 and AE1/AE3 were 100%, 100%, 60% and 21%, respectively. Spearman's analysis revealed that ERG and CD31 staining correlated significantly; there was no significant correlation between CD31 and CD34 staining.
With equal sensitivity to, and strong correlation with CD31, ERG staining is highly suitable for the cytological diagnosis of AS. ERG and CD31 are more sensitive vascular markers than CD34. ERG, a nuclear stain, complements the cytoplasmic/membranous staining of CD31. Used in conjunction with CD31, ERG can corroborate the diagnosis of AS.
Background & Aims Epidemiological studies have shown that obesity is a risk factor for hepatocellular carcinoma (HCC). Lower adiponectin levels are associated with poor prognosis in obese HCC ...patients, hence it is plausible that adiponectin acts as a negative regulator of HCC. We investigated the effects of adiponectin on HCC development and its molecular mechanisms. Methods Assays with Huh7 and HepG2 HCC cells were used to examine the signal transduction pathways involved in the protective functions of adiponectin in HCC. These studies were followed by in vivo approaches using HCC xenografts and tumor analysis. Results from in vitro and in vivo findings were corroborated using human HCC tissue microarray and analysis of clinicopathological characteristics. Results Adiponectin increased apoptosis of HCC cells through activation of caspase-3. Adiponectin increased phosphorylation of c-Jun-N-terminal kinase (JNK) and inhibition of c-Jun-N-terminal kinase−phosphorylation inhibited adiponectin-induced apoptosis and caspase-3 activation. Adiponectin increased phosphorylation of 5′-adenosine monophosphate−activated protein kinase and tumor suppressor tuberous sclerosis complex 2 and inhibited mammalian target of rapamycin phosphorylation. Inhibition of 5′-adenosine monophosphate−activated protein kinase phosphorylation not only inhibited adiponectin-induced c-Jun-N-terminal kinase phosphorylation, but also blocked biological effects of adiponectin. Adiponectin substantially reduced liver tumorigenesis in nude mice. Importantly, analysis of adiponectin expression levels in tissue microarray of human HCC patients revealed an inverse correlation of adiponectin expression with tumor size. Conclusions Adiponectin protects against liver tumorigenesis; its reduced expression is associated with poor prognosis in obese patients with HCC.
Obesity is rapidly becoming a pandemic and is associated with increased carcinogenesis. Obese populations have higher circulating levels of leptin in contrast to low concentrations of adiponectin. ...Hence, it is important to evaluate the dynamic role between adiponectin and leptin in obesity‐related carcinogenesis. Recently, we reported the oncogenic role of leptin including its potential to increase tumor invasiveness and migration of hepatocellular carcinoma (HCC) cells. In the present study we investigated whether adiponectin could antagonize the oncogenic actions of leptin in HCC. We employed HCC cell lines HepG2 and Huh7, the nude mice‐xenograft model of HCC, and immunohistochemistry data from tissue‐microarray to demonstrate the antagonistic role of adiponectin on the oncogenic actions of leptin. Adiponectin treatment inhibited leptin‐induced cell proliferation of HCC cells. Using scratch‐migration and electric cell‐substrate impedance‐sensing‐based migration assays, we found that adiponectin inhibited leptin‐induced migration of HCC cells. Adiponectin treatment effectively blocked leptin‐induced invasion of HCC cells in Matrigel invasion assays. Although leptin inhibited apoptosis in HCC cells, we found that adiponectin treatment induced apoptosis even in the presence of leptin. Analysis of the underlying molecular mechanisms revealed that adiponectin treatment reduced leptin‐induced Stat3 and Akt phosphorylation. Adiponectin also increased suppressor of cytokine signaling (SOCS3), a physiologic negative regulator of leptin signal transduction. Importantly, adiponectin significantly reduced leptin‐induced tumor burden in nude mice. In HCC samples, leptin expression significantly correlated with HCC proliferation as evaluated by Ki‐67, whereas adiponectin expression correlated significantly with increased disease‐free survival and inversely with tumor size and local recurrence. Conclusion: Collectively, these data demonstrate that adiponectin has the molecular potential to inhibit the oncogenic actions of leptin by blocking downstream effector molecules. (HEPATOLOGY 2010
Summary Expression of GATA-3 in female breast cancers has been linked to estrogen receptor (ER) expression and, in turn, to improved outcomes. However, GATA-3 has not been studied in male breast ...cancers. Nineteen male breast carcinomas (average age: 63 years) and 164 female breast carcinomas (average age: 57 years) were immunostained for GATA-3. Results were compared to age, tumor size, tumor grade, lymph node status, distant metastases, survival, and positivity for ER, progesterone receptor (PR), and HER2/neu. Six of 19 (31.6%) male and 135 of 164 (82.3%) female breast carcinomas were GATA-3 positive ( P < .001). In women, 82.1% of GATA-3-positive cancers were grade 1 or 2, whereas 75.9% of GATA-3-negative cancers were grade 3 ( P < .001); no such significant correlation was seen in men. Unlike female cancers, male cancers showed no correlation between GATA-3 positivity and ER positivity, PR positivity, or distant metastases. Nodal metastasis and HER2 status were not linked to GATA-3 in either sex. Seventeen (89.5%) men were alive at follow-up (average: 61 months); only 1 died of disease. Most women (159/164, 97.0%) were also alive at follow-up (average: 41 months), with a higher proportion of GATA-3-negative women dead than GATA-3-positive women (3/29 10.3% vs. 2/135 1.5%, P = .039). GATA-3 is expressed less often in male than female breast cancers. Male cancers show no correlation between GATA-3 positivity and ER/PR positivity or distant metastases, unlike female cancers. There appears to be no link between GATA-3 positivity and survival in men, whereas in women, GATA-3-positive tumors are typically lower grade with a better prognosis.
Abstract
There is an urgent need to develop new tumor biomarkers for early cancer detection, but the variability of tumor-derived antigens has been a limitation. Here we demonstrate a novel anti-Tn ...antibody microarray platform to detect Tn+ glycoproteins, a near universal antigen in carcinoma-derived glycoproteins, for broad detection of cancer. The platform uses a specific recombinant IgG1 to the Tn antigen (CD175) as a capture reagent and a recombinant IgM to the Tn antigen as a detecting reagent. These reagents were validated by immunohistochemistry in recognizing the Tn antigen using hundreds of human tumor specimens. Using this approach, we could detect Tn+ glycoproteins at subnanogram levels using cell lines and culture media, serum, and stool samples from mice engineered to express the Tn antigen in intestinal epithelial cells. The development of a general cancer detection platform using recombinant antibodies for detection of altered tumor glycoproteins expressing a unique antigen could have a significant impact on cancer detection and monitoring.
We have developed a novel anti-Tn antigen-based immuno-platform to detect Tn+ glycoproteins expressed by tumor cells as a single reagent to promote early universal cancer detection.
Summary GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor ...expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor–positive, Her2/neu–positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor–positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.
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