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Supplementary Figure 2 from A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Supplementary Table 3 from A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Supplementary Table 1 from A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Supplementary Table 4 from A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Supplementary Figure 1 from A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Supplementary Table 2 from A Multicenter, Double-Blinded Validation Study of Methylation Biomarkers for Progression Prediction in Barrett's Esophagus

Malignant peripheral nerve sheath tumors (MPNSTs) represent a rare subtype of neural crest cell-derived soft tissue sarcomas (STS). Standard of care therapy comprises surgical resection followed by adjuvant radiation, and most clinical studies have demonstrated finite survival benefit of radiation and chemotherapy. In metastatic disease, palliative chemotherapy provides very limited efficacy. We report a 60-year-old male patient with a primary para vertebral tumor at T7-T8 with lung metastases who recurred after surgical resection and later progressed on epirubicin plus ifosfamide. He was an international patient and referred to the phase 1 clinic. Molecular profiling and immunohistochemistry of the tumor revealed a PD-L1 expression of 70% (2+) and pathogenic genetic alterations by next-generation sequencing in ARID1A, CDKN2A, KMT2A, NF1, and TP53. Immune checkpoint therapy (ICT) with pembrolizumab was commenced, and interval computed tomography revealed a complete remission by cycle 6. Randomized clinical trials illustrate that ICTs such as anti-PD-1 and anti-CTLA4 monoclonal antibodies in STS cohorts display low or modest response rates by variable PD-L1 expression. This and 3 other case reports of disparate PD-L1 expression demonstrate complete responses in PD-L1 positive MPNSTs treated with ICT. These case reports necessitate further study of ICT in neural crest cell subtype of STS.

Chronic liver disease is a worldwide health problem, and hepatic fibrosis (HF) is one of the hallmarks of the disease. The current reference standard for diagnosing HF is biopsy followed by pathologist examination; however, this is limited by sampling error and carries a risk of complications. Pathology diagnosis of HF is based on textural change in the liver as a lobular collagen network that develops within portal triads. The scale of collagen lobules is characteristically in the order of 1 to 5 mm, which approximates the resolution limit of in vivo gadolinium-enhanced magnetic resonance imaging in the delayed phase. We use MRI of formalin-fixed human ex vivo liver samples as phantoms that mimic the textural contrast of in vivo Gd-MRI. We have developed a local texture analysis that is applied to phantom images, and the results are used to train model observers to detect HF. The performance of the observer is assessed with the area-under-the-receiver–operator-characteristic curve (AUROC) as the figure-of-merit. To optimize the MRI pulse sequence, phantoms were scanned with multiple times at a range of flip angles. The flip angle that was associated with the highest AUROC was chosen as optimal for the task of detecting HF.

Cyclooxygenase 2 (COX-2) is an inducible enzyme involved in the production of prostaglandins and thromboxanes during inflammation. There are now several lines of evidence indicating that increased expression of COX-2 plays a functional role in the development and progression of malignant epithelial cancers. However, there is only limited data regarding the role of COX-2 in melanoma pathogenesis. In the present work, we retrospectively examined lesions through out the development of melanoma and metastatic disease (dysplastic nevi n = 10, melanoma in situ n = 4, stage II melanoma n = 10, stage III n = 4, stage IV n = 3, stage V n = 2, melanoma metastasis lymph nodes n = 13 metastasis to other sites n = 3). COX-2 was consistently observed in keratinocytes, dermal fibroblasts, and inflammatory cells in regions adjacent to benign evi and primary cutaneous melanomas. However, no COX-2 staining was detected in the nevi nor in the primary skin melanoma cells. In addition, COX-2 was undetected in all vertical and radial growth phase cases Interestingly, 13 out of 13 of the lymph node metastasis expressed extremely high levels of COX-2 in overlying epithelium and inflammatory cells, and COX-2 was strongly detected in the metastatic cancer cells per se. For additional information on the expression of COX-2 in malignant melanoma, we determined the expression of COX-2 protein in several different melanoma cell lines. We found that 3We found that 5 out of 7 of the melanoma cells over expressed COX-2 compared to normal melanocytes. Collectively, these data suggest that COX-2 may play a functional role in metastases of melanoma, and treatment with COX-2 inhibitors may be efficacious for malignant melanoma.