Melanoma is a cancer that exhibits one of the most aggressive and heterogeneous features. The incidence rate escalates. A high number of clones harboring various mutations contribute to an exceptional level of intratumor heterogeneity of melanoma. It also refers to metastases which may originate from different subclones of primary lesion. Such component of the neoplasm biology is termed intertumor and intratumor heterogeneity. These levels of tumor heterogeneity hinder accurate diagnosis and effective treatment. The increasing number of research on the topic reflects the need for understanding limitation or failure of contemporary therapies. Majority of analyses concentrate on mutations in cancer-related genes. Novel high-throughput techniques reveal even higher degree of variations within a lesion. Consolidation of theories and researches indicates new routes for treatment options such as targets for immunotherapy. The demand for personalized approach in melanoma treatment requires extensive knowledge on intratumor and intertumor heterogeneity on the level of genome, transcriptome/proteome, and epigenome. Thus, achievements in exploration of melanoma variety are described in details. Particularly, the issue of tumor heterogeneity or homogeneity given BRAF mutations is discussed.

Biobanks play an increasing role in contemporary research projects. These units meet all requirements to regard them as a one of the most innovative and up-to-date in the field of biomedical research. They enable conducting wide-scale research by the professional collection of biological specimens and correlated clinical data. Pathology units may be perceived roots of biobanking. The review aims at describing the concept of biobanks, their model of function and scientific potential. It comprises the division of biobanks, sample preservation methods and IT solutions as well as guidelines and recommendations for management of a vast number of biological samples and clinical data. Therefore, appropriate standard operating procedures and protocols are outlined. Constant individualization of diagnostic process and treatment procedures creates the niche for translational units. Thus, the role of biobanks in personalized medicine was also specified. The exceptionality of biobanks poses some new ethical-legal issues which have various solutions, in each legal system, amongst the world. Finally, distribution and activity of European biobanks are mentioned.

PurposeMCM7 (minichromosome maintenance complex component 7), a DNA replication licensing factor, is a host gene for the oncogenic miR-106b~25 cluster. It has been recently revealed as a relevant prognostic biomarker in a variety of cancers, including pituitary adenomas. The purpose of this study was to assess whether miR-106b~25 and MCM7 levels correlate with tumor invasiveness in a cohort of ACTH-immunopositive adenomas.MethodsTissue samples were obtained intraoperatively from 25 patients with pituitary adenoma. Tumor invasiveness was assessed according to the Knosp grading scale. MCM7, Ki-67 and TP53 levels were assessed by immunohistochemical staining, while the expression of miR-106b-5p, miR-93-5p, miR-93-3p and miR-25-3p were measured using quantitative real-time PCR performed on RNA isolated from FFPE tissues.ResultsWe have found a significant increase in MCM7 and Ki-67 labeling indices in invasive ACTHomas. Moreover, MCM7 was ubiquitously overexpressed in Crooke’s cell adenomas. The expression of miR-93-5p was significantly elevated in invasive compared to noninvasive tumors. In addition, all four microRNAs from the miR-106b~25 cluster displayed marked upregulation in Crooke’s cell adenomas. Remarkably, MCM7 and miR-106b-5p both strongly correlated with Knosp grade. A combination of MCM7 LI and miR-106b~25 cluster expression was able to accurately differentiate invasive from noninvasive tumors and had a significant discriminatory ability to predict postoperative tumor recurrence/progression.ConclusionsmiR-106b~25 and its host gene MCM7 are potential novel biomarkers for invasive ACTH-immunopositive pituitary adenomas. Additionally, they are both significantly upregulated in rare Crooke’s cell adenomas and might therefore contribute to their aggressive phenotype.

Peripheral nerve injury is a common posttraumatic complication. The precise surgical repair of nerve lesion does not always guarantee satisfactory motor and sensory function recovery. Therefore, enhancement of the regeneration process is a subject of many research strategies. It is believed that polyethylene glycol (PEG) mediates axolemmal fusion, thus enabling the direct restoration of axon continuity. It also inhibits Wallerian degeneration and recovers nerve conduction. This systemic review, performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, describes and summarizes published studies on PEG treatment efficiency in various nerve injury types and repair techniques. Sixteen original experimental studies in animal models and one in humans were analyzed. PEG treatment superiority was reported in almost all experiments (based on favorable electrophysiological, histological, or behavioral results). To date, only one study attempted to transfer the procedure into the clinical phase. However, some technical aspects, e.g., the maximal delay between trauma and successful treatment, await determination. PEG therapy is a promising prospect that may improve the surgical treatment of peripheral nerve injuries in the clinical practice.

In recent years, lipofilling became a popular scar treatment method. Its beneficial outcomes have been partly attributed to the regenerative capacity of adipose-derived stem cells (ADSCs), suspended in an extracellular matrix—the stromal vascular fraction (SVF). The aim of this review was to verify if existing data support the clinical use of ADSC-related interventions in scar treatment. A systematic search of the literature was performed in July 2020 in five databases (Medline, Cochrane, Web of Science, Scopus and Embase). Articles written in English, except for reviews, letters and editorials, were identified and screened for eligibility. We looked for reports of any outcomes in scars treated with ADSCs or SVF. Data from selected articles were extracted and the quality of each study was assessed. Five hundred and fourteen studies were identified in the primary search, of which nineteen were eventually included in the systematic review. Extracted data pointed to beneficial microscopic, functional and aesthetic outcomes in a total of 665 patients. Six studies included comparative interventions—platelet-rich plasma or CO2 fractional laser. Collected data give low-to-average quality evidence for beneficial effects of ADSC-related interventions in scar treatment. Some studies suggest that these interventions are noninferior to PRP or fractional CO2 laser.

Despite significant development of melanoma therapies, death rates remain high. Micro-RNAs, controlling posttranscriptionally gene expression, play role in development of resistance to BRAF inhibitors. The aim of the study was to assess the role of miR-410-3p in response to vemurafenib-BRAF inhibitor. FFPE tissue samples of 12 primary nodular melanomas were analyzed. With the use of Laser Capture Microdissection, parts of tumor, transient tissue, and adjacent healthy tissue were separated. In vitro experiments were conducted on human melanoma cell lines A375, G361, and SK-MEL1. IC50s of vemurafenib were determined using MTT method. Cells were transfected with miR-410-3p mimic, anti-miR-410-3p and their non-targeting controls. ER stress was induced by thapsigargin. Expression of isolated RNA was determined using qRT-PCR. We have found miR-410-3p is downregulated in melanoma tissues. Its expression is induced by vemurafenib in melanoma cells. Upregulation of miR-410-3p level increased melanoma cells resistance to vemurafenib, while its inhibition led to the decrease of resistance. Induction of ER stress increased the level of miR-410-3p. miR-410-3p upregulated the expression of AXL in vitro and correlated with markers of invasive phenotype in starBase. The study shows a novel mechanism of melanoma resistance. miR-410-3p is induced by vemurafenib in melanoma cells via ER stress. It drives switching to the invasive phenotype that leads to the response and resistance to BRAF inhibition.

Background: Because of its subjective character, the term “breast attractiveness” is poorly defined and thus its reliable standardized assessment can be particularly challenging. Because of objective analysis of the observer’s gaze pattern, eye-tracking technology may provide a better insight into the visual perception of breast aesthetics and symmetry. Methods: One hundred observers, 50 women and 50 men, assessed the aesthetics and symmetry of eight types of female breasts displayed as digital images on frontal, lateral, and oblique projections. The gaze pattern of each observer was recorded using eye-tracking technology, and gaze data were subsequently analyzed. Results: Although sex and breast type exerted an effect on attention capturing by some areas of interest, key characteristics of gaze patterns in female and male observers were essentially the same. Irrespective of observers’ sex, the longest fixation duration and the highest fixation number were recorded for lower breast regions, in particular, for the nipple-areola complex. Mean fixation duration in this area corresponded to 58 and 57 percent of overall observation time for female and male observers, respectively, during the assessment of breast aesthetics; and to 56 and 52 percent of overall observation time for female and male observers, respectively, during the assessment of breast symmetry. Conclusions: Nipple-areola complex and lower breast are key focus areas for the assessment of breast aesthetics and symmetry. Gaze data collected during this study may constitute a valuable source of reference values for future eye-tracking research on various patient groups’ visual perception of breast attractiveness and deformities.

The aim was to examine the efficiency of a scaffold made of poly (L-lactic acid)-co-poly(ϵ-caprolactone), collagen (COL), polyaniline (PANI), and enriched with adipose-derived stem cells (ASCs) as a nerve conduit in a rat model. P(LLA-CL)-COL-PANI scaffold was optimized and electrospun into a tubular-shaped structure. Adipose tissue from 10 Lewis rats was harvested for ASCs culture. A total of 28 inbred male Lewis rats underwent sciatic nerve transection and excision of a 10 mm nerve trunk fragment. In Group A, the nerve gap remained untouched; in Group B, an excised trunk was used as an autograft; in Group C, nerve stumps were secured with P(LLA-CL)-COL-PANI conduit; in Group D, P(LLA-CL)-COL-PANI conduit was enriched with ASCs. After 6 months of observation, rats were sacrificed. Gastrocnemius muscles and sciatic nerves were harvested for weight, histology analysis, and nerve fiber count analyses. Group A showed advanced atrophy of the muscle, and each intervention (B, C, D) prevented muscle mass decrease (p < 0.0001); however, ASCs addition decreased efficiency vs. autograft (p < 0.05). Nerve fiber count revealed a superior effect in the nerve fiber density observed in the groups with the use of conduit (D vs. B p < 0.0001, C vs. B p < 0.001). P(LLA-CL)-COL-PANI conduits with ASCs showed promising results in managing nerve gap by decreasing muscle atrophy.