Harnessing Cationic Bilosomes to Create a Green Light-Triggered Nanoplatform for Skin Melanoma Treatment

Melanoma is a serious form of skin cancer that begins in cells known as melanocytes. While it is less common than the other forms of skin cancer, melanoma is more dangerous because of its ability to spread to other organs more rapidly if it is not treated at an early stage. The number of people diagnosed with melanoma has increased over the last few decades. The most widely used treatments include surgery, chemotherapy, and radiation therapy. The search for new drugs to treat various cancers is one of the most important challenges of modern scientific research. Some isoquinoline alkaloids found in different plant species have strong cytotoxic effects on various cancer cells. We tested the effect of isoquinoline alkaloids and extracts obtained from various parts of Mahonia aquifolium collected in various vegetation seasons on human melanoma cancer cells and our data indicated that investigated extract induced significant reduction in cell viability of Human malignant melanoma cells (A375), human Caucasian malignant melanoma cell line (G361), and human malignant melanoma cell line (SKMEL3 cancer cell lines in a dose- and time-dependent manner. Differences in cytotoxic activity were observed for extracts obtained from various parts of Mahonia aquifolium. Significant differences were also obtained in the alkaloids content and cytotoxic activity of the extracts depending on the season of collection of plant material. Our investigations exhibit that these plant extracts can be recommended for further in vivo experiments in order to confirm the possibility of their use in the treatment of human melanomas.

Histidine Decarboxylase Expression in Human Melanoma

RhoA controls changes in cell morphology and invasion associated with cancer phenotypes. Cell lines derived from melanoma tumors at varying stages revealed that RhoA is selectively activated in cells of metastatic origin. We describe a functional proteomics strategy to identify proteins regulated by RhoA and report a previously uncharacterized human protein, named “mediator of RhoA-dependent invasion (MRDI),” that is induced in metastatic cells by constitutive RhoA activation and promotes cell invasion. In human melanomas, MRDI localization correlated with stage, showing nuclear localization in nevi and early stage tumors and cytoplasmic localization with plasma membrane accentuation in late stage tumors. Consistent with its role in promoting cell invasion, MRDI localized to cell protrusions and leading edge membranes in cultured cells and was required for cell motility, tyrosine phosphorylation of focal adhesion kinase, and modulation of actin stress fibers. Unexpectedly MRDI had enzymatic function as an isomerase that converts the S-adenosylmethionine catabolite 5-methylribose 1-phosphate into 5-methylribulose 1-phosphate. The enzymatic function of MRDI was required for methionine salvage from S-adenosylmethionine but distinct from its function in cell invasion. Thus, mechanisms used by signal transduction pathways to control cell movement have evolved from proteins with ancient function in amino acid metabolism.

BackgroundCAN-3110 is a first-in-class, replication-competent herpes simplex virus-1 (HSV-1) oncolytic viral immunotherapy candidate designed with dual activity for oncolysis and immune activation under development in recurrent high-grade glioma. CAN-3110 is...

Since telomerase plays a role in cellular resistance to apoptosis, which is the primary mode of cell death induced by several drugs, telomerase could be involved in determining the chemosensitivity profile of tumor cells. Thus, we investigated the relationship between telomerase activity, telomere length and chemosensitivity to effective antitumor agents in a panel of human melanoma and ovarian cancer cell lines. Telomerase activity, as detected by the telomeric repeat amplification protocol, ranged from 0.58 to 1.10 arbitrary units in individual cell lines, with similar median values for melanoma and ovarian carcinoma cell lines (0.80 vs. 0.90). Telomeres were generally longer in melanoma than in ovarian carcinoma cell lines, with a more than 2-fold median telomere restriction fragment length (7.74 vs. 3.82 kb). No significant correlation was evidenced between the two telomere-related parameters and cell population doubling time, DNA index or TP53 gene status. No precise relation was found between telomerase activity and cellular sensitivity to different DNA damaging agents including doxorubicin, cisplatin and the multinuclear platinum compound BBR 3464. In contrast, longer telomeres were associated to resistance to the drugs, even though the association reached statistical significance only for cisplatin. Since platinum compounds may have affinity for telomere sequences, it is conceivable that the interaction is relevant for drug sensitivity/resistance status depending on telomere length.

DNMT targets MiRacle torching TORCh.

Targeting Hypoxia-inducible Factor-1α With Tf–PEI–shRNA Complex via Transferrin Receptor–mediated Endocytosis Inhibits Melanoma Growth

Uveal melanoma expresses NK-1 receptors and cyclosporin A induces apoptosis in human melanoma cell lines overexpressing the NK-1 receptor

Announcement of the 2022 winners of the Spychala and Women in Science Awards

Dear Sir, Heme oxygenase (HO) is a microsomal enzyme that catalyzes the first, rate-limiting step in the degradation of heme, and plays an important role in its recycling (Maines, 1997). It cleaves the a-meso carbon bridge of heme, yielding equimolar quantities of carbon monoxide, Fe, and biliverdin (Tenhunen et al., 1968). The enzymatic activity of HO results in decreased oxidative stress, an attenuated inflammatory response, and a lower rate of apoptosis. Three distinct mammalian HO isoforms (HO-1, HO-2, and HO-3) have been identified. They are the products of three different genes (Maines, 1988). Heme oxygenase-1, the inducible 32-kDa isoform, also known as heat shock protein 32, is highly expressed in liver and spleen, but can also be detected in many other tissues. It can be induced strongly in response to cellular stress and diverse oxidative stimuli, including its heme substrate, heat shock, ultraviolet (UV) irradiation, reactive oxygen species (ROS), nitric oxide (NO), inflammatory cytokines, prostaglandins, ethanol, heavy metals, and hypoxia (Applegate et al., 1991; Choi and Alam, 1996). Most of the known HO-1 inducers stimulate the production of ROS or lead to the depletion of glutathione levels, suggesting the involvement of HO-1 activity in cellular protection against oxidative stress (Ryter and Choi, 2002). Heme oxygenase-1 is known to play an important role in resistance to apoptosis and in the rapid growth of several solid tumors. It is often up-regulated in tumor tissues, and its expression can be further increased in response to therapy (Jozkowicz et al., 2007). Induction of HO-1 has been recognized as one of the most promising targets for chemoprevention and chemoprotection research (Prawan et al., 2005). Few studies of HO-1 expression in melanoma have been reported. Okamoto et al. (2006) suggested that HO-1 is an important candidate gene in the pathogenesis and growth of melanomas. Was et al. (2006) found that overexpression of HO-1 increased the viability, proliferation, and angiogenic potential of melanoma cells, augmented metastasis, and decreased survival of melanoma-bearing mice. In this study, we examined the expression of HO-1 in melanocytic nevi and melanomas by immunohistochemical staining, and in cultured normal human melanocytes and melanoma cell lines. We enrolled 38 patients, 20 with melanocytic nevi and 18 with melanomas. Patient characteristics are shown in Table S1. The mean age of the patients was 42 ± 23 yr (range 6–80). The diagnoses of the 20 melanocytic nevi were as follows: compound nevi (12; 60%), junctional nevi (4; 20%), intradermal nevus (1; 5%), and Spitz nevi (3; 15%). The histopathological types of the 18 melanomas were superficial spreading type (7; 39%), acral lentiginous type (7; 39%), lentigo maligna type (3; 17%), and metastatic melanoma (1; 6%). Immunohistochemical staining was performed using formalin-fixed, paraffin-embedded tissue specimens from 20 patients with melanocytic nevi and 18 with melanomas, using the LSAB2 System-HRP (DakoCytomation, Carpenteria, CA, USA). The intensity of HO-1 immunoreactivity was graded using the following scale: 0 = negative (no staining of melanocytic cells, but staining of the epidermis); 1 = weakly positive (staining intensity was markedly weaker than that of the epidermis); 2 = moderately positive (staining intensity was mildly weaker than that of the epidermis); and 3 = strongly positive (staining intensity was at least equal to that of the epidermis). The Mann–Whitney test (performed using SPSS version 12.0; SPSS Inc., Chicago, IL, USA) was used to analyze differences in HO-1 staining intensity between melanocytic nevi and melanomas. Additionally, HO-1 expression in melanocytic nevi and melanomas from sun-exposed and sun-protected areas was compared. Expression of HO-1 was detected in 19 of 20 melanocytic nevi (95%) and in 11 of 18 melanomas (61%). Of melanomas, one superficial spreading type, four acral lentiginous type, one lentigo maligna type, and one metastatic type did not express HO-1. Note that the intensity of HO-1 expression was markedly different between melanocytic nevi and melanomas (Figure 1). The mean intensity in melanocytic nevi was 1.82 ± 0.86. There was no difference in staining intensity among the types of melanocytic nevi. The intensity of HO-1 expression in the nearby epidermis in melanocytic nevi was 2.30 ± 0.64 (Figure S1). Only 13 of 20

SOX2 modulates levels of MITF in normal human melanocytes, and melanoma lines in vitro

<p>Supplementary Figure 4 PDF file - 38K, Identification of human melanoma and colorectal cancer cell lines with coincident B-RAF and NF1 mutations is associated with resistance to PLX4720. Human melanoma and colorectal cancer cell lines from the Cancer Cell Line Encyclopedia with B-RAFV600E and NF1 mutation were identified and compared to NF1 wild-type melanoma cell lines in terms of sensitivity to PLX4720, NF1 mRNA expression, NF1 copy number alterations and NF1 mutation status. In the heat map, blue represents lower values and red represents higher values, whilst NF1 mutation status is represented as wild-type: blue, point mutation: white, potential loss-of-function mutation: red</p>

<p>Supplementary Figure 4 PDF file - 38K, Identification of human melanoma and colorectal cancer cell lines with coincident B-RAF and NF1 mutations is associated with resistance to PLX4720. Human melanoma and colorectal cancer cell lines from the Cancer Cell Line Encyclopedia with B-RAFV600E and NF1 mutation were identified and compared to NF1 wild-type melanoma cell lines in terms of sensitivity to PLX4720, NF1 mRNA expression, NF1 copy number alterations and NF1 mutation status. In the heat map, blue represents lower values and red represents higher values, whilst NF1 mutation status is represented as wild-type: blue, point mutation: white, potential loss-of-function mutation: red</p>

Aim: The study explores glycerosomes as effective vesicular systems for transdermal delivery of atorvastatin (ATO) to overcome drawbacks related to its oral administration.Methodology: The objectives of this study were to formulate, by thin-film hydration method, optimize using definitive screening design and evaluate ATO-loaded glycerosomes (ATOG) which were then incorporated into patch followed by the evaluation of glycerosomes containing different concentration of glycerol.Results & discussion: Vesicle size, Polydispersity index (PDI), zeta potential, entrapment efficiency and loading capacity of spherical ATOG (0-30%w/w) showed 137.3-192d.nm, 0.292-0.403, -3.81 to-6.76mV, 80.03-92.77% and 5.80-6.40%, respectively. In-vitro release study showed sustained release, increased skin permeability and better cell viability than pure drug. ATOG patches showed greater skin permeability than pure drug and ATO-liposomal patches.Conclusion: The study concludes that ATOGs are promising for effective transdermal delivery.

Inhibition of focal adhesion kinase (FAK), a non-receptor tyrosine kinase linked to tumour cell survival, causes cell rounding, loss of adhesion and apoptosis in human cancer cell lines. In this study, we tested antisense oligonucleotide inhibitors of FAK, in combination with 5-fluorouracil (5-FU), to increase its sensitivity in human melanoma cell lines. Antisense oligonucleotides directed to the 5' mRNA sequence of FAK and missense control oligonucleotides were used. In BL melanoma cells, treatment with FAK antisense oligonucleotide was associated with a 2.5-fold increase in cell death compared with treatment with control oligonucleotide (33+/-2% vs. 13+/-3%, P<0.0001). 5-FU alone had no effect on BL cells (4.4% cell death, P=0.15). The addition of 5-FU after antisense oligonucleotide resulted in a significant synergistic increase in cell death equal to 69+/-2% compared with treatments with antisense oligonucleotide alone, 5-FU alone and control oligonucleotide (P<0.0001). Similar results were found in the C8161 melanoma cell line. In both cell lines, reduction in cell viability was accompanied by an increased loss of adhesion and increased apoptosis that was proportional to the decrease in viability. Treatment with antisense oligonucleotide plus 5-FU resulted in significantly decreased p125FAK expression in both C8161 and BL melanoma cell lines, demonstrated by Western blot analyses. These data show that the downregulation of FAK by antisense oligonucleotide combined with 5-FU chemotherapy results in a greater loss of adhesion and greater apoptosis in melanoma cells than treatment with either agent alone, suggesting that the combination may be a potential therapeutic agent for human melanoma in vivo.