Human Skin Cancer Research Articles

Conditional Knockout of N-WASP Enhanced the Formation of Keratinizing Squamous Cell Carcinoma Induced by KRasG12D.

Squamous cell carcinoma (SCC) is one of the most common forms of skin cancer in humans, and Neural Wiskott-Aldrich Syndrome Protein (N-WASP) plays a crucial role in epidermal homeostasis. To elucidate the role of N-WASP in skin cancer, we generated mice which expressed constitutively active KRas (KRasG12D) in keratinocytes with either homozygous (N-WASPKOG12D) or heterozygous (N-WASPHetG12D) N-WASP knockout upon Tamoxifen (TAM) injection. Both the N-WASPKOG12D and N-WASPHetG12D mice had similar body weights and no congenital malformations prior to the injection of TAM. Within 2 weeks of the injections, the N-WASPKOG12D mice exhibited significant reductions in weight coupled with visible tumors at numerous sites, unlike the N-WASPHetG12D mice, which had no visible tumors. We found that both sets of mice had oily, sticky skin and wet eyes 3 weeks after their exposure to TAM, indicating the overproduction of sebum/meibum. At 37 days post TAM injection, several notable observations were made. Tumors collected from the N-WASPKOG12D mice had small- to large-sized keratin pearls that were not observed in the N-WASPHetG12D mice. A Western blot and immunostaining analysis both highlighted significantly higher levels of expression of SCC markers, such as the cytokeratins 8, 17, 18, and 19 and TP63, in the tumors of the N-WASPKOG12D mice compared to those of the latter group. Furthermore, we noted increases in the expression levels of EGFR, P-ERK, GLUT1, P-mTOR, and P-4EBP in the N-WASPKOG12D mice, suggesting that the deletion of N-WASP in the keratinocytes enhanced KRas signaling and glucose uptake, resulting in aggressive tumor formation. Interestingly, a thickening of the epidermal layer within the esophagus and tongue was only observed in the N-WASPKOG12D mice. Immunostaining for PCNA emphasized a significantly higher number of PCNA-positive cells in the skin of the N-WASPKOG12D mice compared to their counterparts, implying that epidermal thickening and enhanced tumorigenesis are due to an increased proliferation of keratinocytes. Through our results, we have established that N-WASP plays a tumor-suppressive role in skin cancer.

Formulation and evaluation of nanosized hippadine-loaded niosome: Extraction and isolation, physicochemical properties, and in vitro cytotoxicity against human ovarian and skin cancer cell lines

Formulation and evaluation of nanosized hippadine-loaded niosome: Extraction and isolation, physicochemical properties, and in vitro cytotoxicity against human ovarian and skin cancer cell lines

Topical Drug Delivery of Concentrated Cabazitaxel in an α-Tocopherol and DMSO Solution.

Topical chemotherapy approaches are relevant for certain skin cancer treatments. This study observes that cabazitaxel (CTX), a broad-spectrum second-generation taxane cytotoxic agent, can be dissolved in α-tocopherol at high concentrations exceeding 100mgmL-1 . 2D nuclear magnetic resonance (NMR) analysis and molecular dynamics (MD) are used to study this phenomenon. The addition of 30% dimethyl sulfoxide (DMSO) to the α-tocopherol/CTX solution improves its working viscosity and enhances CTX permeation through human skin in vitro (over 5µgcm-2 within 24h), while no detectable drug permeates when CTX is dissolved in α-tocopherol alone. In a transepidermal water loss assay, the barrier impairment induced by CTX in 30% DMSO in α-tocopherol, but not in pure DMSO, is reversible 8h after the formulation removal from the skin surface. Antitumor efficacy of the topical CTX formulation is evaluated in nude mice bearing A431 human squamous carcinoma skin cancer xenografts. With topical application of concentrated CTX solutions (75mgmL-1 ), tumor growth is significantly suppressed compared to lower concentration groups (0, 25, or 50mgmL-1 CTX). Taken together, these findings show that topical delivery of CTX using a DMSO and α-tocopherol solvent warrants further study as a treatment for skin malignancies.

ΔM4: Membrane-Active Peptide with Antitumoral Potential against Human Skin Cancer Cells.

Peptides have become attractive potential agents due to their affinity to cancer cells. In this work, the biological activity of the peptide ΔM4 against melanoma cancer cell line A375, epidermoid carcinoma cell line A431, and non-tumoral HaCaT cells was evaluated. The cytotoxic MTT assay demonstrates that ΔM4 show five times more activity against cancer than non-cancer cells. The potential membrane effect of ΔM4 was evaluated through lactate dehydrogenase release and Sytox uptake experiments. The results show a higher membrane activity of ΔM4 against A431 in comparison with the A375 cell line at a level of 12.5 µM. The Sytox experiments show that ΔM4 has a direct effect on the permeability of cancer cells in comparison with control cells. Infrared spectroscopy was used to study the affinity of the peptide to membranes resembling the composition of tumoral and non-tumoral cells. The results show that ΔM4 induces a fluidization effect on the tumoral lipid system over 5% molar concentration. Finally, to determine the appearance of phosphatidylserine on the surface of the cell, flow cytometry analyses were performed employing an annexin V-PE conjugate. The results suggest that 12.5 µM of ΔM4 induces phosphatidylserine translocation in A375 and A431 cancer cells. The findings of this study support the potential of ΔM4 as a selective agent for targeting cancer cells. Its mechanism of action demonstrated selectivity, membrane-disrupting effects, and induction of phosphatidylserine translocation.

Encapsulation of Diosgenin in chitosan nanoparticles with enhanced invitro and invivo anticancer activity in Female Sprague Dawley rats

The main purpose of this study was to optimize the conditions for synthesizing diosgenin-encapsulated chitosan nanoparticles (DIO@CS NPs) and anticancer activity. Nanoparticles encapsulating diosgenin were synthesized using ionic gelation utilizing three different chitosan weight percentages and polyanion STPP (Sodium tripolyphosphate) as the cross-linking agent. The synthesis depended on ionic interaction between positively charged chitosan and negatively charged STPP. The incorporation of diosgenin into the chitosan nanoparticles was verified by Fourier transform infrared spectroscopy (FTIR). Chitosan nanoparticle entrapment effectiveness (EE%) was between 76% to 94% and increased with diosgenin concentration. Invitro diosgenin drug release from nanoparticles was decelerated when employing greater molecular weight chitosan. Chitosan nanoparticles released diosgenin diffusion-controlled in drug release study. DIO@CS nanoparticles evaluated on A431 human skin cancer cells demonstrated significant anticancer activity. These results suggest that DIO@CS NPs could be a novel skin cancer therapy. Each rat received 25 mg/kg DMBA subcutaneously. Tumor-bearing animals were lighter. DMBA-induced mice gained less weight than DIO@CS NPs. Oral DIO@CS NPs (2.5 mg/kg b.wt) recovered cellular antioxidants and mitigated histopathological staining of hematoxylin and eosin on breast carcinoma. Based on the foregoing results, Diosgenin nanoformulations provide a novel breast cancer treatment.

Computational formulation of a multiepitope vaccine unveils an exceptional prophylactic candidate against Merkel cell polyomavirus.

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy caused by human Merkel cell polyomavirus (MCV), leading to the most aggressive skin cancer in humans. MCV has been identified in approximately 43%-100% of MCC cases, contributing to the highly aggressive nature of primary cutaneous carcinoma and leading to a notable mortality rate. Currently, no existing vaccines or drug candidates have shown efficacy in addressing the ailment caused by this specific pathogen. Therefore, this study aimed to design a novel multiepitope vaccine candidate against the virus using integrated immunoinformatics and vaccinomics approaches. Initially, the highest antigenic, immunogenic, and non-allergenic epitopes of cytotoxic T lymphocytes, helper T lymphocytes, and linear B lymphocytes corresponding to the virus whole protein sequences were identified and retrieved for vaccine construction. Subsequently, the selected epitopes were linked with appropriate linkers and added an adjuvant in front of the construct to enhance the immunogenicity of the vaccine candidates. Additionally, molecular docking and dynamics simulations identified strong and stable binding interactions between vaccine candidates and human Toll-like receptor 4. Furthermore, computer-aided immune simulation found the real-life-like immune response of vaccine candidates upon administration to the human body. Finally, codon optimization was conducted on the vaccine candidates to facilitate the in silico cloning of the vaccine into the pET28+(a) cloning vector. In conclusion, the vaccine candidate developed in this study is anticipated to augment the immune response in humans and effectively combat the virus. Nevertheless, it is imperative to conduct in vitro and in vivo assays to evaluate the efficacy of these vaccine candidates thoroughly. These evaluations will provide critical insights into the vaccine's effectiveness and potential for further development.

Skin-Net: a novel deep residual network for skin lesions classification using multilevel feature extraction and cross-channel correlation with detection of outlier

Human Skin cancer is commonly detected visually through clinical screening followed by a dermoscopic examination. However, automated skin lesion classification remains challenging due to the visual similarities between benign and melanoma lesions. In this work, the authors proposed a new Artificial Intelligence-Based method to classify skin lesions. In this method, we used Residual Deep Convolution Neural Network. We implemented several convolution filters for multi-layer feature extraction and cross-channel correlation by sliding dot product filters instead of sliding filters along the horizontal axis. The proposed method overcomes the imbalanced dataset problem by converting the dataset from image and label to vector of image and weight. The proposed method is tested and evaluated using the challenging datasets ISIC-2019 & ISIC-2020. It outperformed the existing deep convolutional networks in the multiclass classification of skin lesions.Graphical

Activin A-Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer.

Cemiplimab is approved for the treatment of locally advanced basal cell carcinomas (BCC), although with mitigated results. We sought to interrogate the cellular and molecular transcriptional reprogramming underlying BCC resistance to immunotherapy. Here, we combined spatial and single-cell transcriptomics to deconvolute the spatial heterogeneity of the tumor microenvironment in regard with response to immunotherapy, in a cohort of both naïve and resistant BCCs. We identified subsets of intermingled cancer-associated fibroblasts (CAF) and macrophages contributing the most to CD8 T-cell exclusion and immunosuppression. Within this spatially resolved peritumoral immunosuppressive niche, CAFs and adjacent macrophages were found to display Activin A-mediated transcriptional reprogramming towards extracellular matrix remodeling, suggesting active participation to CD8 T-cell exclusion. In independent datasets of human skin cancers, Activin A-conditioned CAFs and macrophages were associated with resistance to immune checkpoint inhibitors (ICI). Altogether, our data identify the cellular and molecular plasticity of tumor microenvironment (TME) and the pivotal role of Activin A in polarizing the TME towards immune suppression and ICI resistance.

Bio-Synthesis of zinc oxide nanoparticles and detect its antitumor activity against human skin cancer cell line (A375).

In this study, Lepidium sativum seeds were collected from the local markets in Baghdad. Zinc oxide nanoparticles were manufactured from the aqueous extract of Lepidium sativum by adding zinc acetate in a green, safe and environmentally friendly manner. The formation of zinc oxide nanoparticles was inferred by changing the color of the extract from white to yellow, and for Detection of biosynthetic zinc oxide nanoparticles Examinations were conducted to detect these nanoparticles, including diagnosis using atomic force microscopy (AFM), which showed that the size of the nanoparticles (13) nm and the surface roughness (80.51) nm compared with the aqueous extract, which amounted to (23) nm and (57.22) nm respectively. The diagnosis using UV rays showed a peak absorption of nanoparticles at 350 nm compared with the aqueous extract, which reached 248 nm. As for the scanning electron microscope (SEM) examination, the nanoparticles' size ranged between 46.97 - 81.07 nanometers, compared with the aqueous extract, which reached 676 - 591.8 nanometers. To determine the toxic or inhibitory effect against A375 cancer cells and HdFn normal skin cells, MTT cytotoxicity assay was performed for aqueous extract and zinc oxide nanoparticles. The results showed that the aqueous extract was effective against the cancerous cell line A375, as the viability of the cells decreased with the increase in the concentration of the aqueous extract. The IC50 ratio was equal to 140.0 mg/ml for the A375 cancer cells, and the IC50 ratio was equal to 179.9 mg/ml for the normal HdFn cells. As for zinc oxide nanoparticles, the effectiveness was more substantial than that of the aqueous extract, and the vitality of cells was reduced in the cancerous line A375. The normal line HdFn, the higher the concentration of nanoparticles, and the IC50 ratio was equal to 59.46 mg/ml for the cancerous line. The IC50 ratio was equal to 196.9 mg/ml for the normal line. Keywords: Zinc oxide nanoparticles, Lepidium sativum, antitumor activity or A375 cancer cells.

Targeting ferroptosis as a cell death pathway in Melanoma: From molecular mechanisms to skin cancer treatment.

Melanoma, the most aggressive form of human skin cancer, has been under investigation to reach the most efficient treatment. Surgical resection for early-diagnosed primary melanoma, targeted therapies, and immune checkpoint inhibitors for advanced/metastatic melanoma is the best clinical approach. Ferroptosis, a newly identified iron-dependent cell death pathway, which is morphologically and biochemically different from apoptosis and necrosis, has been reported to be involved in several cancers. Ferroptosis inducers could provide therapeutic options in case of resistance to conventional therapies for advanced/metastatic melanoma. Recently developed ferroptosis inducers, MEK and BRAF inhibitors, miRNAs such as miR-137 and miR-9, and novel strategies for targeting major histocompatibility complex (MHC) class II in melanoma can provide new opportunities for melanoma treatment. Combining ferroptosis inducers with targeted therapies or immune checkpoint inhibitors increases patient response rates. Here we review the mechanisms of ferroptosis and its environmental triggers. We also discuss the pathogenesis and current treatments of melanoma. Moreover, we aim to elucidate the relationship between ferroptosis and melanoma and ferroptosis implications to develop new therapeutic strategies against melanoma.

Investigating the Toxicity and Edibility of Cocoyam Plant (Colocasia esculenta) in an Arsenic-Contaminated Soil

The exposure of heavy metals such as mercury, cadmium, arsenic, chromium, thallium, and lead, and their interactions with soil and plants are of much concern due to their potential health effect. Phytoremdiation is one method used by plants to clean up soils contaminated with these heavy metals. Arsenic is a carcinogenic substance that thwarts plant growth and causes skin cancer in humans, among other health effects. Although arsenic decontamination by phytoremediation has been reported, the literature is silent about the toxicity and edibility of the plant after arsenic uptake. This study, therefore, assessed the toxicity of the Colocasia esculenta plant after using it as a phyto-sorbent for four weeks in a simulated arsenic-contaminated soil. The Bioaccumulation Factor (BAF) and the Translocation Factor (TF), calculated after the experiment, were 1.43 and 1.60 respectively indicating its hyper-accumulative property and high translocation of arsenic through the various parts. There was a decreasing trend of arsenic concentration in the solution samples across the weeks, and an accumulation of 58%, 28%, and 14% of arsenic in the stem, roots, and leaves of the plant respectively. The results showed that Colocasia esculenta is a good accumulator of arsenic from the soil. A comparison of the different arsenic levels recorded in the plant parts with standards, presents a great concern in consuming this plant exposed to an arsenic-contaminated environment. However, further studies should be conducted to ascertain the bioavailable state of arsenic in the plant parts after its uptake.

Determination of Some Isoquinoline Alkaloids in Extracts Obtained from Selected Plants of the Ranunculaceae, Papaveraceae and Fumarioideae Families by Liquid Chromatography and In Vitro and In Vivo Investigations of Their Cytotoxic Activity.

Alkaloids are heterocyclic bases with widespread occurrence in nature. Plants are rich and easily accessible sources of them. Most isoquinoline alkaloids have cytotoxic activity for different types of cancer, including malignant melanoma, the most aggressive type of skin cancer. The morbidity of melanoma has increased worldwide every year. For that reason, developing new candidates for anti-melanoma drugs is highly needed. The aim of this study was to investigate the alkaloid compositions of plant extracts obtained from Macleaya cordata root, stem and leaves, Pseudofumaria lutea root and herb, Lamprocapnos spectabilis root and herb, Fumaria officinalis whole plant, Thalictrum foetidum root and herb, and Meconopsis cambrica root and herb by HPLC-DAD and LC-MS/MS. For determination of cytotoxic properties, human malignant melanoma cell line A375, human Caucasian malignant melanoma cell line G-361, and human malignant melanoma cell line SK-MEL-3 were exposed in vitro to the tested plant extracts. Based on the in vitro experiments, Lamprocapnos spectabilis herb extract was selected for further, in vivo research. The toxicity of the extract obtained from Lamprocapnos spectabilis herb was tested using an animal zebrafish model in the fish embryo toxicity test (FET) for determination of the LC50 value and non-toxic doses. Determination of the influence of the investigated extract on the number of cancer cells in a living organism was performed using a zebrafish xenograft model. Determination of the contents of selected alkaloids in different plant extracts was performed using high performance liquid chromatography (HPLC) in a reverse-phase system (RP) on a Polar RP column with a mobile phase containing acetonitrile, water and ionic liquid. The presence of these alkaloids in plant extracts was confirmed by LC-MS/MS. Preliminary cytotoxic activity of all prepared plant extracts and selected alkaloid standards was examined using human skin cancer cell lines A375, G-361, and SK-MEL-3. The cytotoxicity of the investigated extract was determined in vitro by cell viability assays (MTT). For in vivo determination of investigated extract cytotoxicity, a Danio rerio larvae xenograft model was used. All investigated plant extracts in in vitro experiments exhibited high cytotoxic activity against the tested cancer cell lines. The results obtained using the Danio rerio larvae xenograft model confirmed the anticancer activity of the extract obtained from Lamprocapnos spectabilis herb. The conducted research provides a basis for future investigations of these plant extracts for potential use in the treatment of malignant melanoma.

Design and synthesis of γ‐Fe2O3@Ag‐S‐CH2‐COOH nanocatalyst for one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones and their anti‐skin cancer activity

The ongoing work describes the catalytic evaluation of γ‐Fe2O3@Ag‐S‐CH2‐COOH magnetic nanoparticles utilizing γ‐Fe2O3 obtained from waste iron rust for one‐pot synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones. As‐prepared γ‐Fe2O3@Ag‐S‐CH2‐COOH nanoparticles were characterized by Fourier transform infrared spectroscopy (FT‐IR), X‐ray diffraction (XRD), scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDX), dynamic light scattering (DLS), transmission electron microscopy (TEM), X‐ray photoelectron spectroscopy (XPS), and Brunauer–Emmett–Teller (BET) technique. The catalytic performance of greener γ‐Fe2O3@Ag‐S‐CH2‐COOH nanoparticles was utilized in the synthesis of 2,3‐dihydroquinazolin‐4(1H)‐ones. The excellent catalytic performance was shown by magnetic nanoparticles in addition to its ease of separation by an external magnet and can be recycled for five consecutive turns without significant loss of catalytic activity. Furthermore, the synthesized 2,3‐dihydroquinazolin‐4(1H)‐ones were confirmed by FT‐IR, 1H, 13C nuclear magnetic resonance (NMR), and mass spectrometry. Moreover, the synthesized 2,3‐dihydroquinazolin‐4(1H)‐ones were evaluated for their anticancer efficiency against the human skin cancer cell line B16F10 along with molecular docking investigation.

Synthesis and physicochemical properties of an aromatic chitosan derivative: In vitro antibacterial, antioxidant, and anticancer evaluations, and in silico studies

This study was designed to synthesize a functionalized chitosan by coupling the amine groups of chitosan with 2,4,6-Trimethoxybenzaldehyde, producing a chitosan Schiff base (Cs-TMB). The development of Cs-TMB was verified employing FT-IR, 1H NMR, the electronic spectrum, and elemental analysis. Antioxidant assays exhibited significant ameliorations of Cs-TMB, reporting scavenging activities of 69.67 ± 3.48 % and 39.65 ± 1.98 % for ABTS•+ and DPPH, respectively, while native chitosan showed scavenging ratios of 22.69 ± 1.13 % and 8.24 ± 0.4.1 % toward ABTS•+ and DPPH, respectively. Besides, Cs-TMB exerted significant antibacterial activity up to 90 % with remarkable bactericidal capacity against virulent gram-negative and gram-positive bacteria compared to the original chitosan. Furthermore, Cs-TMB exhibited a safe profile against normal fibroblast cells (HFB4). Interestingly, flow cytometric analysis showed that Cs-TMB demonstrated prominent anticancer properties of 52.35 ± 2.99 % against human skin cancer cells (A375), compared to 10.66 ± 0.55 % for Cs-treated cells. Moreover, Python and PyMOL in-house scripts were used to predict the interaction of Cs-TMB with the adenosine A1 receptor and visualized as a protein-ligand system submerged in a lipid membrane. Overall, these findings accentuate that Cs-TMB could be a favorable representative for wound dressing formulations and skin cancer treatment.

The impact of technogenic factors on human skin cancer increase in the Odesa region

The impact of technogenic factors on human skin cancer increase in the Odesa region

Terahertz-to-infrared converters for imaging the human skin cancer: challenges and feasibility.

Terahertz (THz) medical imaging is a promising noninvasive technique for monitoring the skin's conditions, early detection of the human skin cancer, and recovery from burns and wounds. It can be applied for visualization of the healing process directly through clinical dressings and restorative ointments, minimizing the frequency of dressing changes. The THz imaging technique is cost effective, as compared to the magnetic resonance method. Our aim was to develop an approach capable of providing better image resolution than the commercially available THz imaging cameras. The terahertz-to-infrared (THz-to-IR) converters can visualize the human skin cancer by converting the latter's specific contrast patterns recognizable in THz radiation range into IR patterns, detectable by a standard IR imaging camera. At the core of suggested THz-to-IR converters are flat matrices transparent both in the THz range to be visualized and in the operating range of the IR camera, these matrices contain embedded metal nanoparticles (NPs), which, when irradiated with THz rays, convert the energy of THz photons into heat and become nanosources of IR radiation detectable by an IR camera. The ways of creating the simplest converter, as well as a more complex converter with wider capabilities, are considered. The first converter is a gelatin matrix with gold 8.5-nm diameter NPs, and the second is a polystyrene matrix with 2-nm diameter NPs from copper-nickel MONEL® alloy 404. An approach with a THz-to-IR converter equipped with an IR camera is promising in that it could provide a better image of oncological pathology than the commercially available THz imaging cameras do.

Effect of Light Emitting Diode and TiO2-decorated Ag Nanoparticles on Skin Cancer A431 Cell Line

Background: Devices based on light-emitting diodes (LEDs) are the newest and safest method for treating a variety of ailments, and dermatologists are now routinely using them. To confirm the effectiveness of this type of treatment, more controlled research are still required. Materials and Methods: A431 Cell line and treatment with blue LED at output light wave intensity 1200-1400 mw/cm. photodynamic therapy (PDT) with TiO2/Ag using human skin cancer cells as experimental model were used. Cell death and a possible mechanism of action were studied. Results: Blue light (wavelength 420–480 nm) exposure caused a rapid and significant decline in viability, which was followed by the death of over half of the cells. The current paper reviews the state of the art in skin LED-based treatment methods. The newest and safest treatment is LED therapy with nanoparticle, the treatment of radioactively irradiated cells with LED causes an increase in cell death. Blue light exposure might open up new possibilities for treating superficial skin cancers in people. Conclusion: The blue light (420–480 nm) of the light-emitting diode had a better anticancer effect on the SCC cell line after 24 hours of incubation. The best results were obtained with a 240-second exposure time in light with a TiO2/Ag concentration of 400 µg/ml.

Anethole suppresses the growth of human skin cancer cells by targeting microRNA498/STAT4 axis

Purpose: To investigate the effects of anethole on human skin cancer cells.
 Methods: Cell viability was determined using CCK-8 and colony formation assay, while AO/EB and Annexin V/PI assays were used to assess apoptosis. The mRNA expressions of genes were assayed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR).
 Results: The growth of skin cancer cells was significantly reduced by anethole (p < 0.05). On the other hand, normal human skin cells were marginally affected by anethole. Furthermore, anethole significantly suppressed the colony formation potential of CRL-6475 skin cancer cells in a concentration-dependent manner (p < 0.05). Results from AO/EB and annexin V/PI staining assays revealed that anethole induced apoptosis in skin cancer cells, while qRT-PCR results indicate that anethole significantly up-regulated microRNA-498 in skin cancer cells (p < 0.05). However, anethole had no effect on the expression levels of miR-7, miR-9, miR-145, miR-31, miR-27, miR-498 miR-1298, miR-1299, 1179, miR-375, miR-508 and miR-23. CCK-8 assay results confirmed that miR-498 up-regulation significantly mimicked the anti-proliferative effects of anethole. Bioinformatics analysis and luciferase reporter assay led to identification of STAT4 as the regulatory target of miR-498. Furthermore, silencing of STAT4 significantly mimicked the effects of anethole administration (p < 0.05).
 Conclusion: These results indicate that anethole inhibits skin cancer cell growth by targeting the miR-498/STAT4 axis, and therefore, has potentials for use in the management of skin cancer.

Toxicokinetic analyses of naphthalene, fluorene, phenanthrene, and pyrene in humans after single oral administration

Polycyclic aromatic hydrocarbons (PAHs) are generated by incomplete combustion of organic matter. They have health effects in multiple organs and can cause lung, skin, and bladder cancers in humans. Although data regarding their toxicity is available, information on the absorption, distribution, metabolism, and excretion of PAHs in humans is very limited. In the present study, deuterium-labeled naphthalene (Nap), fluorene (Flu), phenanthrene (Phe), and pyrene (Pyr) were orally administered as a single dose (0.02–0.04 mg/kg) to eight healthy adults. Both serum and urine samples were monitored for 72 h after the exposure. Parent compounds and PAH metabolites (monohydroxy-PAHs; OH-PAHs) were measured by headspace-solid phase microextraction coupled with gas chromatography–mass spectrometry and high-performance liquid chromatography-tandem mass spectrometry, respectively. Based on the time-concentration profiles in serum and urine, non-compartmental analysis was performed, and two-compartment models were constructed and validated for each PAH. Subsequently, all of the parent compounds were rapidly absorbed (Tmax: 0.25 to 1.50 h) after oral administration and excreted in urine with a biological half-life (T1/2) of 1.01 to 2.99 h. The fractional urinary excretion (Fue) of OH-PAHs ranged from 0.07 % to 11.3 %; their T1/2 values ranged from 3.4 to 11.0 h. The two-compartment models successfully described the toxicokinetic characteristics of each PAH and its metabolites. Fue and the two-compartment models could be useful tools for exposure simulation or dose-reconstruction of PAHs. The results of this study will provide useful information for interpreting biomonitoring data of PAHs.

In Vivo Characterization of Mucin and Amyloid Deposits in Primary Basal Cell Carcinoma through Reflectance Confocal Microscopy: A Correlation with Histopathology.

Basal cell carcinoma (BCC) is the most common keratinocyte carcinoma and the most prevalent skin cancer in humans, worldwide. BCC is histologically characterized by the proliferation of basaloid cells, arranged in globular masses of varying size, often separated from the surrounding stroma by optically empty spaces. Although attributed to tumor retraction during tissue processing for the preparation of pathology slides, these spaces are also seen on cryostat sections. The aim of this study is to in vivo characterize amyloid and mucin deposits in primary BCC lesions through RCM, followed by histopathological correlation. We included twenty-two consecutive subjects totaling thirty-one primary BCCs. Each lesion underwent the same evaluation protocol which included: clinical and dermoscopic images, RCM imaging, excisional biopsy under local anesthesia, and histopathological examination (colloidal iron and cytokeratin 34betaE12 stains). Hypo-reflective peritumoral clefts and hyper-reflective globules were measured on RCM images and compared to mucin and amyloid deposits seen on histology slides. The mean differences between RCM and histology measurements in both mucin and amyloid were not statistically significant. There were medium and strong correlations between RCM and histology regarding mucin and amyloid deposits, respectively.