Eric C. Huang

Microfluidic impact printer with interchangeable cartridges for versatile non-contact multiplexed micropatterning

Biopatterning has been increasingly used for well-defined cellular microenvironment, patterned surface topology, and guided biological cues; however, it meets challenges on biocompatibility, thermal and chemical sensitivity, as well as limited availability of reagents. In this paper, we aim at combining the desired features from non-contact inkjet printing and dot-matrix impact printing to establish a versatile multiplexed micropatterning platform, referred to as Microfluidic Impact Printer (MI-Printer), for emerging biomedical applications. Using this platform, we can achieve the distinct features of no cross-contamination, sub-microliter ink loading with a minimal dead volume, high-throughput printing, biocompatible non-contact processing, sequential patterning with self-alignment, wide adaptability for complex media (e.g., cell suspension or colloidal solutions), interchangeable/disposable cartridge design, and simple assembly and configuration, all highly desirable towards laboratory-based research and development. Specifically, the printing resolution of the MI-printer platform has been experimentally characterized and theoretically analysed. Optimal printing resolution of 80 μm has been repeatedly obtained. Furthermore, two useful functions of the MI-printer, multiplexed printing and combinatorial printing, have been experimentally demonstrated with less than 10 μm misalignment. Moreover, molecular and biological patterning, utilizing the multiplexed and combinatorial printing, has been implemented to illustrate the utility of this versatile printing technique for emerging biomedical applications.

Histologic and clinical follow-up of thyroid fine-needle aspirates in pediatric patients

Although fine‐needle aspiration (FNA) has an important role in evaluating thyroid nodules in adults, there is little published information regarding its utility in the pediatric population.

Post‐contrast myocardial T1 and ECV disagree in a longitudinal canine study

Both post‐contrast myocardial T1 and extracellular volume (ECV) measurements have been associated with diffuse interstitial fibrosis. The cardiovascular magnetic resonance (CMR) field is migrating towards ECV, because it is largely insensitive to confounders that affect post‐contrast myocardial T1. Despite the theoretical advantages of myocardial ECV over post‐contrast myocardial T1, systematic experimental studies comparing the two measurements are largely lacking. We sought to measure the temporal changes in post‐contrast myocardial T1 and ECV in an established canine model with chronic atrial fibrillation.

Ferredoxin reductase is critical for p53-dependent tumor suppression via iron regulatory protein 2

Ferredoxin reductase (FDXR), a target of p53, modulates p53-dependent apoptosis and is necessary for steroidogenesis and biogenesis of iron-sulfur clusters. To determine the biological function of FDXR, we generated a Fdxr-deficient mouse model and found that loss of Fdxr led to embryonic lethality potentially due to iron overload in developing embryos. Interestingly, mice heterozygous in Fdxr had a short life span and were prone to spontaneous tumors and liver abnormalities, including steatosis, hepatitis, and hepatocellular carcinoma. We also found that FDXR was necessary for mitochondrial iron homeostasis and proper expression of several master regulators of iron metabolism, including iron regulatory protein 2 (IRP2). Surprisingly, we found that p53 mRNA translation was suppressed by FDXR deficiency via IRP2. Moreover, we found that the signal from FDXR to iron homeostasis and the p53 pathway was transduced by ferredoxin 2, a substrate of FDXR. Finally, we found that p53 played a role in iron homeostasis and was required for FDXR-mediated iron metabolism. Together, we conclude that FDXR and p53 are mutually regulated and that the FDXR-p53 loop is critical for tumor suppression via iron homeostasis.

Giant cell-rich osteosarcoma of the parotid gland: An exceptionally rare entity at an unusual site

Giant cell‐rich osteosarcoma is a rare histologic variant of conventional osteosarcoma that affects mainly the extremities. Extraskeletal giant cell‐rich osteosarcoma is therefore exceedingly rare. Here, we report the first case of this uncommon tumor involving the parotid gland in a 62‐year‐old male who presented with initial right jaw swelling. Radiologic work‐up revealed a 6.2 cm mass involving the right parotid gland. Fine‐needle aspiration cytology showed numerous multinucleated giant cells in a background of dyshesive epithelioid cells and rare clusters of spindle stromal cells, suspicious for malignancy. The subsequent excisional biopsy showed histopathologic features diagnostic for giant cell‐rich osteosarcoma. Diagn. Cytopathol. 2016;44:1107–1111.

Ninjurin 1 has two opposing functions in tumorigenesis in a p53-dependent manner

Significance Nerve injury-induced protein 1 (Ninj1), a p53 target, forms a feedback loop with p53 by repressing p53 translation. Here, we show that cell growth was enhanced by Ninj1 deficiency in cells carrying a mutant p53, but inhibited in cells carrying a WT p53. We also show that in WT p53 background, Ninj1-deficient mice were prone to systemic inflammation, but not to spontaneous tumors. Importantly, loss of Ninj1 altered lifespan and tumor susceptibility in mutant p53 and p53-null mice. Taken together, our results reveal a critical role of Ninj1 in p53-dependent tumor suppression and the Ninj1–p53 loop may be explored as a potential therapeutic target for the treatment of inflammatory diseases and cancers. WT p53 is critical for tumor suppression, whereas mutant p53 promotes tumor progression. Nerve injury-induced protein 1 (Ninj1) is a target of p53 and forms a feedback loop with p53 by repressing p53 mRNA translation. Here, we show that loss of Ninj1 increased mutant p53 expression and, subsequently, enhanced cell growth and migration in cells carrying a mutant p53. In contrast, loss of Ninj1 inhibited cell growth and migration in cells carrying a WT p53. To explore the biological significance of Ninj1, we generated a cohort of Ninj1-deficient mice and found that Ninj1+/− mice were prone to systemic inflammation and insulitis, but not to spontaneous tumors. We also found that loss of Ninj1 altered the tumor susceptibility in both mutant p53 and p53-null background. Specifically, in a mutant p53(R270H) background, Ninj1 deficiency shortened the lifespan, altered the tumor spectrum, and increased tumor burden, likely via enhanced expression of mutant p53. In a p53-null background, Ninj1 deficiency significantly increased the incidence of T-lymphoblastic lymphoma. Taken together, our data suggest that depending on p53 genetic status, Ninj1 has two opposing functions in tumorigenesis and that the Ninj1–p53 loop may be targeted to manage inflammatory diseases and cancer.

Pathology and Molecular Pathology of Uterine and Ovarian Cancers

In this chapter, the embryology and development of the Mullerian tract is first introduced. The chapter is then divided into two major sections: pathology of the uterus and the ovary. In the uterine portion, benign endometrium is first discussed and the dating patterns for cyclic endometrium are described. Other benign, pre-malignant and cancer histology, genetics and genomics are then discussed. For the ovarian portion, in a similar fashion, normal ovarian histology is first introduced, followed by non-neoplastic and neoplastic conditions. The chapter is concluded with genetics and genomics of ovarian cancers. Endometrial carcinoma is the most common malignancy while ovarian carcinoma is one of the deadliest diseases of the Mullerian tract. Thus, understanding the genetic and molecular alterations underlying these cancers is essential in guiding and developing future novel therapeutics.

Synchronous uterine adenocarcinoma and leiomyosarcoma: A rare case report causing a clinical conundrum

Highlights • We present a rare case of concurrent uterine adenocarcinoma and leiomyosarcoma.• Literature review confirms this is a very rare combination of synchronous tumors.• We discuss therapeutic challenges in synchronous gynecologic malignancies.

Pleural fluid metastases of myoepithelial carcinoma: A case report and review of the literature.

Myoepithelial carcinoma (MECA) is one of the rarest salivary gland neoplasms, which may either arise de novo or develop within a preexisting pleomorphic adenoma or benign myoepithelioma. The tumor occurs mainly in the parotid gland followed by minor salivary glands and other body sites. As a result of their morphologic heterogeneity, they can be confused easily with many tumors. Awareness of their unique cytoarchitectural patterns and immunohistochemical profile is crucial for accurate identification. Herein, we report a rare case of a 51-year-old female patient with MECA of the maxillary sinus that metastasized to the pleural fluid. To the best of our knowledge, this is the first case of pleural fluid involvement by MECA reported in the literature.

Sclerosing mucoepidermoid carcinoma with eosinophilia: Cytologic characterization of a rare distinct entity in the thyroid

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is an extremely rare thyroid carcinoma with limited cytologic descriptions in the literature. Here, we present a 52‐year‐old woman with a 3.9 cm thyroid nodule. Fine‐needle aspiration smears consisted of a highly cellular specimen with tumor cells in isolated patterns and solid squamoid nests. Tumor cells had round to oval nuclei, prominent nucleoli, smooth nuclear contours, and moderate amounts of dense cytoplasm. In addition to the polymorphous population of lymphocytes, the background contained a striking abundance of eosinophils. The subsequent right thyroidectomy showed histologic features diagnostic for SMECE.