Nonmelanoma Skin Cancer

En el manejo del carcinoma basocelular (CBC) es fundamental conocer los factores de riesgo que predicen un comportamiento más agresivo. Estos factores de riesgo se dividen esencialmente en factores clínicos y en factores histopatológicos. En este trabajo revisamos e ilustramos los hallazgos histopatológicos predictivos de agresividad en el CBC. Dichos factores histopatológicos predictivos de agresividad incluyen las variedades histológicas clásicas de CBC «agresivas»: la morfeiforme, la infiltrativa, la micronodular, la metatípica, la basoescamosa y el CBC con diferenciación sarcomatoide. Pero, aparte de las variedades referidas, existen también 2 hallazgos histopatológicos asociados a CBC agresivos, uno bien conocido y reflejado en la literatura, que es la infiltración perineural de filetes nerviosos de más de 0,1 mm de diámetro o subdérmicos, y el otro es la extensión subgaleal. La infiltración galeal no está bien reconocida como tal en literatura, pero es un factor predictivo de agresividad importante en el CBC y queremos llamar la atención sobre él.

Familiarity with predictors of more aggressive behavior is crucial to the management of basal cell carcinoma (BCC). Risk factors for aggressive BCC are essentially divided into clinical and histopathologic factors. In this review we examine histopathologic features predictive of aggressiveness in BCC. The morpheaform, infiltrative, micronodular, metatypical, and basosquamous subtypes and BCC with sarcomatoid differentiation are classically considered predictive of aggressive behavior. However, 2 other features associated with aggressive BCC are perineural invasion (invasion of nerves below the dermis or nerves larger than 0.1 mm in caliber) and subgaleal extension. While the former is well known and widely described in the literature, the latter is not generally recognized as a risk factor, even though it is predictive of highly aggressive behavior. In this review, we draw attention to its importance.

The pharmacological characteristics of phytochemicals have prompted a lot of interest in their application in disease management. Due to the high incidence of cancer related mortality and morbidity throughout the world; experiments have concentrated on identifying the anticancer potential of natural substances. Many phytochemicals such as flavonoids and their derivatives produced from food offer a variety of new anti-cancer agents which prevent the cancer progression. Taxifolin, a unique bioactive flavonoid, is a dietary component that has grabbed the interest of dietitians and medicinal chemists due to its wide range of health benefits. It is a powerful antioxidant with a well-documented effect in the prevention of several malignancies in humans. Taxifolin has shown promising inhibitory activity against inflammation, malignancies, microbial infection, oxidative stress, cardiovascular disease, and liver disease. Anti-cancer activity has been shown to be relatively significant than other activities investigated in vitro and in vivo with a little or no side effects to the normal healthy cells. In summary this review offers the synopsis of recent breakthroughs in the use of taxifolin as a cancer treatment, as well as mechanisms of action. However, to develop a medicine for human usage, more study on pharmacokinetic profile, profound molecular mechanisms, and drug safety criteria should be conducted utilizing well-designed randomized clinical trials.

Alterations in the amide (1500–1700 cm⁻¹) spectral region probed by Fourier-transform infrared spectroscopy (FTIR) have been reported comparing tumor and normal tissues. Usually, bands in this range are assigned to the so-called Amide I, II, and III vibrations which provide pieces of information concerning peptide bonds and secondary structure (α-helix, β-sheet) of proteins. Proteins folding changes due to tumoral process are usually considered to qualitatively explain the observed differences between tumor and normal tissues. In this paper, the observed changes in the FTIR spectra of squamous cell carcinoma compared to normal tissues were analyzed by First-Principles Density Functional Theory vibrational calculations. Computational models for skin and prototype β-sheet model were employed. Our findings shown that predominates conjugated Amide I + Amide II, Amide V, methylene torsions, and ring side chains torsions and swings vibrations in this region. We also notice the lack of evidence concerning changes in the secondary structure of the β-sheet peptidic model to explain the spectral differences. In fact, we concluded that the proline amino acid has the main rule to explain the data in this region being it responsible for the strong coupling between vibrations instead of water.

Increasing incidence rates (IRs) of nonmelanoma skin cancer (NMSC) in white populations have been described worldwide. Cancer registry data from the Saarland and Schleswig-Holstein federal states were used to analyze incidence and mortality trends in Germany. Age-standardized rates were compared with crude rates to assess disease burden. Joinpoint regression models were used to estimate annual percentage changes and 95% confidence intervals, allowing us to assess temporal trends between 1970 and 2012. Incidence predictions until 2030 were based on age-period-cohort models and linear extrapolation techniques. In the Saarland federal state, between 1970 and 2012, NMSC age-standardized and crude IRs increased 10- to 22-fold, respectively. In Schleswig-Holstein, between 1999 and 2012 crude IRs doubled, reaching 250 cases/100,000 persons per year in 2012, with age-standardized IRs increasing 1.5-fold. During this period, NMSC mortality remained stable or decreased. For 2030, the predicted age-standardized IRs are as follows: males, 230 cases; females, 180–200 cases. The predicted crude IRs for the same year are males, 450–500 cases; females, 380–430 cases. There is a continuous long-term increase of NMSC incidence with no tendency for leveling off. By 2030, the current NMSC IR in Germany is expected to double.

High mobility group box 1 (HMGB1) plays an important role as a pro-inflammatory cytokine that regulates inflammation in various diseases. We hypothesized that hemin might reduce HMGB1 release through the induction of HO-1 in UVB-induced HaCaTs.

The effects of hemin on the release of HMGB1 in UVB exposure were evaluated. The mechanisms were investigated using various signal inhibitors and small interfering RNA techniques.

Treatment with hemin inhibited reactive oxygen species (ROS) in UVB-induced HaCaTs in a dose-dependent manner. HMGB1 release by UVB was significantly reduced by hemin, N-acetyl-cysteine and DPI (NADPH oxidase inhibitor). Hemin increased HO-1 induction followed by phosphorylation of AMPK in a time- and dose-dependent manner. Additionally, hemin significantly increased the NAD⁺/NADH ratio in HaCaTs. The inhibitory effects of UVB-induced HMGB1 release by hemin were significantly reversed not only with pharmacological inhibitors of AMPK (compound c) or HO-1 (ZnPPIX) but also through transfection of small interfering RNAs (siRNAs) for AMPK or HO-1. Interestingly, hemin decreased phosphor-AMPK expression by HO-1 siRNA transfection, but it failed to induce HO-1 in AMPK siRNA-transfected cells, which suggested that HO-1 was involved in AMPK activation by hemin in HaCaT. Moreover, recombinant HMGB1 induced Snail and inhibited E-Cadherin in HaCaTs, whereas hemin reversed those effects through rHMGB1.

It is concluded that the increased activity of HO-1/AMPK and scavenging ROS are, at least in part, responsible for the inhibition of UVB-induced HMGB1 release in keratinocyte HaCaTs. Therefore, hemin may be a useful agent for preventing UVB-induced skin cancer.