Acute downregulation of emerin alters actomyosin cytoskeleton connectivity and function.

Fetal lung fibroblasts contribute dynamic infrastructure for the developing lung. These cells undergo dynamic mechanical transitions, including cyclic stretch and spreading, which are integral to lung growth in utero. We investigated the role of the nuclear envelope protein emerin in cellular responses to these dynamic mechanical transitions. In contrast to control cells, which briskly realigned their nuclei, actin cytoskeleton, and extracellular matrices in response to cyclic stretch, fibroblasts that were acutely downregulated for emerin showed incomplete reorientation of both nuclei and actin cytoskeleton. Emerin-downregulated fibroblasts were also aberrantly circular in contrast to the spindle-shaped controls and exhibited an altered pattern of filamentous actin organization that was disconnected from the nucleus. Emerin knockdown was also associated with reduced myosin light chain phosphorylation during cell spreading. Interestingly, emerin-downregulated fibroblasts also demonstrated reduced fibronectin fibrillogenesis and production. These findings indicate that nuclear-cytoskeletal coupling serves a role in the dynamic regulation of cytoskeletal structure and function and may also impact the transmission of traction force to the extracellular matrix microenvironment.

Sensitizing drug-resistant cancer cells from blood using microfluidic electroporator.

Direct assessment of patient samples holds unprecedented potential in the treatment of cancer. Circulating tumor cells (CTCs) in liquid biopsies are a rapidly evolving source of primary cells in the clinic and are ideal candidates for functional assays to uncover real-time tumor information in real-time. However, a lack of routines allowing direct and active interrogation of CTCs directly from liquid biopsy samples represents a bottleneck for the translational use of liquid biopsies in clinical settings. To address this, we present a workflow for using a microfluidic vortex-assisted electroporation system designed for the functional assessment of CTCs purified from blood. Validation of this approach was assessed through drug response assays on wild-type (HCC827 wt) and gefitinib-resistant (HCC827 GR6) non-small cell lung cancer (NSCLC) cells. HCC827 cells trapped within microscale vortices were electroporated to sequentially deliver drug agents into the cytosol. Electroporation conditions facilitating multi-agent delivery were characterized for both cell lines using an automatic single-cell image fluorescence intensity algorithm. HCC827 GR6 cells spiked into the blood to emulate drug-resistant CTCs were able to be collected with high purity, demonstrating the ability of the device to minimize background cell impact for downstream sensitive cell assays. Using our proposed workflow, drug agent combinations to restore gefitinib sensitivity reflected the anticipated cytotoxic response. Taken together, these results represent a microfluidics multi-drug screening panel workflow that can enable functional interrogation of patient CTCs in situ, thereby accelerating the clinical standardization of liquid biopsies.

Inertial Microfluidics Enabling Clinical Research.

Fast and accurate interrogation of complex samples containing diseased cells or pathogens is important to make informed decisions on clinical and public health issues. Inertial microfluidics has been increasingly employed for such investigations to isolate target bioparticles from liquid samples with size and/or deformability-based manipulation. This phenomenon is especially useful for the clinic, owing to its rapid, label-free nature of target enrichment that enables further downstream assays. Inertial microfluidics leverages the principle of inertial focusing, which relies on the balance of inertial and viscous forces on particles to align them into size-dependent laminar streamlines. Several distinct microfluidic channel geometries (e.g., straight, curved, spiral, contraction-expansion array) have been optimized to achieve inertial focusing for a variety of purposes, including particle purification and enrichment, solution exchange, and particle alignment for on-chip assays. In this review, we will discuss how inertial microfluidics technology has contributed to improving accuracy of various assays to provide clinically relevant information. This comprehensive review expands upon studies examining both endogenous and exogenous targets from real-world samples, highlights notable hybrid devices with dual functions, and comments on the evolving outlook of the field.

A case of pachydermodactyly.

Pachydermodactyly (PDD) is a rare, benign form of digital fibromatosis and this is characterized by asymptomatic soft tissue swelling that affects the lateral aspects of the proximal interphalangeal (PIP) joints of the fingers. Although the etiology of PDD is unknown, the possibility of repetitive minor trauma by habitual or compulsive habits of interlacing the fingers or rubbing of the fingers has been suggested as a cause by several authors. We experienced a 14-year-old boy who was diagnosed as having PDD by the clinical manifestations and this was supported by a radiological study and the routine laboratory tests. He also had the habit of repetitively manipulating his hands when feeling emotional distress. PDD sometimes can be misdiagnosed as a rheumatic condition. Although an unusual disorder, PDD should be considered in the differential diagnosis of patients who present with digital bulbous swelling.

Imiquimod as an adjuvant treatment measure for desmoplastic trichoepithelioma.

Desmoplastic trichoepithelioma is a rare benign adnexal tumor. Although it is a benign lesion, patients often want to treat it due to cosmetic concerns when it occurs in an easily visible site. For our two cases, topical 5% imiquimod was an attractive treatment option as it is applied by the patients themselves and it has minimal side effects, including leaving no scar. However, the lesions recurred after clinical remission. To the best of our knowledge, this is the only report on utilizing imiquimod to treat a benign adnexal tumor, and especially desmoplastic trichoepithelioma.

Apocrine Carcinoma of the Groin Possibly Associated with Extramammary Paget's Disease.

Apocrine carcinoma is a rare malignancy with invasive potential. It presents as painless, slow-growing, firm or cystic, red nodules with focal ulcerations. The tumor is capable of hematogenous dissemination to the liver, lungs, and bone as well as lymphatic spread. In addition, apocrine carcinomas cause intra-epidemial pagetoid spread. We report a case of an apocrine carcinoma related with extensive extramammary Paget's disease (EMPD). The relationship between apocrine carcinoma and EMPD remains to be understood. Co-existing cases with apocrine carcinoma and EMPD are discussed to better understand the relationship between these two malignant apocrine tumors.

Pulmonary metastasis of Basal cell carcinoma.

Although basal cell carcinoma is the most common skin cancer, it rarely metastasizes. Metastatic basal cell carcinoma may, therefore, initially elude diagnosis and management. We describe the case of a patient with a metastatic basal cell carcinoma present in the lungs. The differential diagnosis of suspected metastatic lesions should include metastases from a cutaneous basal cell carcinoma, in addition to those from more commonly metastasizing carcinomas, especially in patients with a history of a large basal cell carcinoma that has involved the head and neck regions, and was refractory to treatment.

An open, randomized, comparative clinical and histological study of imiquimod 5% cream versus 10% potassium hydroxide solution in the treatment of molluscum contagiosum.

BACKGROUND: Although molluscum contagiosum (MC) resolves spontaneously, there are several reasons to treat this dermatological disorder. OBJECTIVE: To evaluate the safety and efficacy of 5% imiquimod cream versus 10% potassium hydroxide (KOH) solution in treating MC, and to propose the mechanism of cure by observing the histological findings. METHODS: Imiquimod or KOH were applied by the patient or a parent 3 days per week until all lesions cleared. The number of MC lesions was counted and side effects were evaluated at 5 points during the treatment (the initial visit, week 2, week 4, week 8, and week 12). Histological changes were compared between 2 patients of each group, before and after the 2 weeks of application. RESULTS: In both group, the mean lesion counts decreased all through to week 12, and the reduction in number of lesions were statistically significant in both groups (p <0.005). Over 40% of each group developed local side effects, and no systemic side effects were noted in either group. Before treatment, histological findings showed little or no dermal infiltrates. After treatment, specimens showed dense lymphocytic infiltrates, especially T cells, around the lesions which had resolved. CONCLUSION: Both 10% KOH solution and 5% imiquimod cream are effective and safe treatment of MC.