Aneurysmal fibrous histiocytoma (AFH) is a rare variant of cutaneous fibrous histiocytoma, with low malignant potential and infrequent metastatic progression. We present the case of a 19-year-old female with a large AFH of the neck metastatic to soft tissue and treated with radiation therapy and molecularly targeted therapy. To our knowledge, this is the first report describing either radiation therapy and palliation or the use of targeted therapy in this uncommon malignancy and can provide insight into future therapeutic strategies.

As a potential protein kinase C inhibitor, the fungus metabolite balanol has become more attractive in recent decades. In our previous work, we revealed its biosynthetic pathway through overexpression of the cluster-situated regulator gene blnR in Chinese herb fungus Tolypocladium ophioglossoides. However, information on the regulation of blnR is still largely unknown. In this study, we further investigated the regulation of balanol biosynthesis by BlnR through the analysis of affinity binding using EMSA and RNA-seq analysis. The results showed that BlnR positively regulates balanol biosynthesis through binding to all promoters of bln gene members, including its own promoter. Microscopic observation revealed blnR overexpression also affected spore development and hypha growth. Furthermore, RNA-seq analysis suggested that BlnR can regulate other genes outside of the balanol biosynthetic gene cluster, including those involved in conidiospore development. Finally, balanol production was further improved to 2187.39 mg/L using the optimized medium through statistical optimization based on response surface methodology.

Limited treatment options and development of resistance to targeted therapy within few months pose significant challenges in the treatment of BRAF-mutated malignant melanoma. Moreover, extensive angiogenesis and vasculogenic mimicry promote the rapid progression of disease. The purpose of this study was to develop a protein kinase C inhibitor anchored BRD4 PROTAC (ARV) loaded PEGylated nanoliposomes (LARPC). Palmitoyl-dl-carnitine chloride (PC) was used as a protein kinase C inhibitor to provide a cationic surface charge to LARPC. The formulation was characterized for particle size, zeta potential, drug release and various cell culture assays using HUVEC and vemurafenib resistant melanoma cells. The particle size of LARPC was found to be 105.25 ± 2.76 nm with a zeta potential of +26.6 ± 6.25 mV. Inhibition of angiogenesis was demonstrated by ARV and LARPC using human umbilical vein endothelial cells (HUVEC)-based matrigel basement membrane model. Additionally, LARPC demonstrated very low IC50 with promising inhibition of vasculogenic mimicry channel formation, cell migration as well as colony formation in vemurafenib-resistant melanoma cell lines. Hence, the outcome of this combination therapy indicated the suitability of LARPC as a potential and novel approach for eradicating vemurafenib-resistant melanoma.

Nowadays many drugs with improved therapeutic efficacy are discovered but cannot be utilized due to their low solubility and insufficient bioavailability. An example of such a drug molecule is a protein kinase C inhibitor that influences an enzyme which plays an important role in several signal transduction cascades. The aim of this study was to formulate a stable nanoparticle dispersion of the PKC inhibitor encapsulated into PLGA nanoparticles (NPs). Encapsulation of the PKC inhibitor into PLGA NPs of 100-200 nm diameter should provide a targeted delivery to the inflammation sites. The NPs were prepared via nanoprecipitation and different surfactants were investigated: Fully and partially hydrolyzed poly(vinyl alcohol) (PVA, Mowiol X-88 and X-98), poloxamers (Pluronic F68 and F127) and polysorbates (Tween 20 and 80). From all surfactants tested, only NPs prepared with partially hydrolyzed PVA (Mowiol X-88) provided the desired stability throughout the downstream processes. These NPs were subsequently analyzed regarding their particle size, polydispersity, encapsulation efficiency and loading capacity. Dynamic light scattering results revealed that monodisperse NPs of 150-220 nm were formed, a size range that favors targeted delivery. The drug encapsulation efficiency varied from 31 to 75% with a drug loading of 1.3-2%. Moreover, the long-term stability was studied and the residual amount of PVA of the NP solutions was quantified via nuclear magnetic resonance (NMR) measurements. The shell-less hen\'s egg model was used to test toxic effects (hemorrhage, vascular lysis, thrombosis, hemolysis and lethality) of the NPs in a more complex biological system under dynamic flow conditions.

The present study aimed to evaluate the renoprotective effects of chelerythrine (CHE), a protein kinase C inhibitor, on neonatal rats after partial unilateral ureteral obstruction (UUO) surgery. New born Sprague Dawley rats were subjected to partial UUO 48 h after birth and received a daily intraperitoneal injection of 5 mg/kg CHE. At 21-day age, the rats were scarified and the kidneys were collected for analysis. Results showed that CHE treatment significantly increased kidney weight and restored renal function in the obstructed kidney. Histological examination demonstrated that CHE attenuated renal injury by reducing renal parenchymal loss and preventing glomerular and tubular degeneration. In addition, CHE inhibited partial UUO-induced upregulated kidney injury molecule-1 expression and apoptosis and renal fibrosis. Moreover, as a PKC inhibitor, CHE significantly inhibited PKCα and PKCβ membrane translocation. This action may be associated with its effects of anti-apoptosis and anti-fibrosis and contribute to the renoprotection. This short-term study suggests that CHE is beneficial for obstructive nephropathy in neonatal rats and provides foundation for further studies to reveal the long-term effects of CHE on obstructive nephropathy in children and infants.

Tolerogenic dendritic cells (tDCs) are a promising therapeutic tool for specific induction of immunological tolerance. Human tDCs can be generated ex vivo using various compounds. However, the compound(s) most suitable for clinical application remain undefined. We compared the tolerogenic properties of tDCs treated with protein kinase C inhibitor (PKCI), dexamethasone, vitamin D3 (Vit D3), rapamycin (Rapa), interleukin (IL)-10, transforming growth factor (TGF)-β, and a combination of peroxisome proliferator-activated receptor γ agonist and retinoic acid. All tDCs had a semi-mature DC phenotype. PKCI-, TGF-β-, and Rapa-tDCs showed CCR7 expression and migration to CCL19, but other tDCs showed little or none. PKCI- and IL-10-tDCs induced functional regulatory T cells more strongly than other tDCs. The tolerogenic properties of all tDCs were stable against proinflammatory stimuli. Furthermore, PKCI-tDCs were generated from patients with rheumatoid arthritis and primary Sjögren\'s syndrome. Therefore, PKCI-tDCs showed the characteristics best suited for tolerance-inducing therapy.

Protein kinase C (PKC) that transduces signals to modulate a wide range of cellular functions has been shown to regulate a number of viral infections. Herein, we showed that inhibition of PKC with the PKC inhibitor GF109203X significantly impaired porcine reproductive and respiratory syndrome virus (PRRSV) replication. Inhibition of PKC led to virus yield reduction, which was associated with decreased viral RNA synthesis and lowered virus protein expression. And this inhibitory effect by PKC inhibitor was shown to occur at the early stage of PRRSV infection. Subsequently, we found that PRRSV infection activated PKCδ in PAMs and knockdown of PKCδ by small interfering RNA (siRNA) suppressed PRRSV replication, suggesting that novel PKCδ may play an important factor in PRRSV replication. Taken together, these data imply that PKC is involved in PRRSV infection and beneficial to PRRSV replication, extending our understanding of PRRSV replication.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus. Protein kinase C (PKC) inhibitor\'s has been thought to be a potential disease modifying drug\'s in DPN as it slows or reverse neuropathy\'s progression. To assesses the efficacy and safety of ruboxistaurin on the progression of symptoms, signs, or functional disability in DPN.
METHODS: A systematic review of the literature databases like PubMed, ProQuest, EBSCO, EMBASE, and Cochrane Central was performed up to August 2012. We included randomized controlled trials (RCTs) comparing PKC inhibitor ruboxistaurin (RBX) with control and lasting at least 6 months. Our primary outcome measure was change in neurological examination, measured by neurological total symptom score (NTSS) and vibration detection threshold (VDT). Secondary outcome measures were total quality of life (QoL), skin microvascular blood flow and others.
RESULTS: Six RCTs were included in review. Change in neurological function assessed by NTSS was reported in six studies, out of which significant difference between the RBX and placebo group seen in four studies favouring treatment group while remaining two studies reported no significant difference. VDT was assessed in only one study in which no significant difference seen between RBX and placebo group. Two studies reported significant improvement in QoL data. Safety data was reported in only two studies in which none of side effect was related to RBX.
CONCLUSIONS: RBX had effects on DPN in some studies, but the evidence is not enough for meta-analysis and firm conclusion.