In Vivo Efficacy of an Injectable Human Acellular Dermal Matrix.

BACKGROUND: Human acellular dermal matrix (hADM) has found applications in a variety of settings, particularly in breast surgery. The most common hADM is a sheet. Recently, an injectable hADM has been introduced; we compared the biocompatibility and long-term structural integrity of, an injectable hADM and a sheet-type hADM in mice. METHODS: An injectable hADM (experimental group) and a sheet-type hADM (control group) were implanted into sub-panniculus pockets on the backs of 50 mice. The animals were sacrificed 2, 4, 8, 12, or 24 weeks later and the hADMs and surrounding tissues were recovered and stained for histopathological analyses. The microscopic endpoints included the thickness of the hADM and capsule around the hADM, and the extents of fibroblast proliferation and neovascularization. RESULTS: No animal developed a complication or infection. The capsule was significantly thinner in the experimental than the control group. There were no significant differences between groups in the hADM thickness. Microscopically, the fibroblast density inside the hADM was significantly higher in the experimental group. The fibroblasts inside of the hADM lay significantly deeper in the experimental group. Similarly, the experimental group exhibited significantly deeper microvessels inside the hADM. CONCLUSIONS: The injectable hADM had a thinner capsule thickness (more biocompatible), than the sheet-type hADM. It maintained its thickness as well as the sheet-type hADM and had a more fibroblast proliferation and neovascularization. This means the tissue incorporation and long-term structural integrity of the injectable hADM may be as good as or better than that of the sheet-type hADM. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Single Cell Analysis of Human Thyroid Reveals the Transcriptional Signatures of Aging.

The thyroid gland plays a critical role in the maintenance of whole-body metabolism. However, aging frequently impairs homeostatic maintenance by thyroid hormones due to increased prevalence of subclinical hypothyroidism associated with mitochondrial dysfunction, inflammation, and fibrosis. To understand the specific aging-related changes of endocrine function in thyroid epithelial cells, we performed single-cell RNA sequencing (RNA-seq) of 54 726 cells derived from pathologically normal thyroid tissues from 7 patients who underwent thyroidectomy. Thyroid endocrine epithelial cells were clustered into 5 distinct subpopulations, and a subset of cells was found to be particularly vulnerable with aging, showing functional deterioration associated with the expression of metallothionein (MT) and major histocompatibility complex class II genes. We further validated that increased expression of MT family genes are highly correlated with thyroid gland aging in bulk RNAseq datasets. This study provides evidence that aging induces specific transcriptomic changes across multiple cell populations in the human thyroid gland.

Age-Dependent Clinicopathological Characteristics of Patients with T1b Papillary Thyroid Carcinoma: Implications for the Possibility of Active Surveillance.

BACKGROUND: Active surveillance (AS) of low-risk T1a papillary thyroid carcinoma (PTC) is generally accepted as an alternative to immediate surgery. The cut-off in the size criterion for AS has recently been extended in select individuals, especially older patients. We evaluated the clinicopathological differences of T1b PTC according to age to investigate the possibility of AS in older patients. PATIENTS AND METHODS: From a cohort study of 1269 patients undergoing lobectomy for PTC, 1223 PTC patients with T1 stage disease (tumor ≤ 2 cm) were enrolled. The clinicopathological characteristics between T1a and T1b patients according to age were analyzed. RESULTS: Among the 1223 T1 cases, 918 (75.1%) were T1a (≤ 1 cm) and 305 (34.9%) T1b (> 1 and ≤ 2 cm). T1b PTC was associated with male sex, minimal extrathyroidal extension, lymphovascular invasion, occult central lymph node (LN) metastasis, and a higher number of metastatic LNs than T1a. However, in patients over 55 years of age, the clinicopathological features of the patients with T1a and T1b PTC were not significantly different except for minimal extrathyroidal extension, although many clinicopathological differences were observed in patients under 55 years of age. CONCLUSION: The clinicopathological features of patients with T1b PTC over 55 years of age are similar to those with T1a PTC and less aggressive than those with T1b PTC under 55 years of age. These findings suggest that AS may be possible in patients with T1b PTC over 55 years of age without high-risk features on preoperative examinations.

Eribulin Mesylate Improves Cisplatin-Induced Cytotoxicity of Triple-Negative Breast Cancer by Extracellular Signal-Regulated Kinase 1/2 Activation.

Background and Objectives; Triple-negative breast cancer (TNBC) is associated with poor patient prognosis because of its multiple molecular features. Thus, more effective treatment for TNBC is urgently needed. This study determined the possible involvement of ERK1/2 activation in cisplatin-induced cytotoxicity in TNBC by providing additional eribulin treatment. Materials and Methods; We investigated cell viability and apoptosis caused by eribulin, cisplatin, or co-treatment in HCC38, MDA-MB-231, and SKBR3 human breast cancer cells. Results; Cisplatin significantly lowered cell viability and caused high apoptotic cell death in all breast cancer cell lines. The viability of TNBC cells was significantly lower in the group co-treated with cisplatin and eribulin than in the cisplatin-only treatment group. Additional eribulin treatment significantly enhanced PARP cleavage and caspase-3 activity in cisplatin-treated TNBC cells. Moreover, cisplatin treatment activated ERK1/2 in all breast cancer cell lines. The cisplatin and eribulin combination synergistically activated ERK1/2 in TNBC cells compared with the cisplatin-only treatment. Administration of the ERK1/2 inhibitor PD98059 increased the viability of TNBC cells treated with cisplatin plus eribulin. Conclusions; Eribulin could synergize the cytotoxic and apoptotic activities of cisplatin and increase ERK1/2 activation, thus enhancing anti-cancer effects against TNBC cells.