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Fullerene C60 and its malonate derivatives, produced via the Bingel-Hirsch reaction, have displayed promising properties against various diseases. These molecules have great therapeutic potential, but their broad use has been limited due to poor aqueous solubility and toxicity caused by accumulation. In this study, we synthesized new malonates and malonamides attached to first- and second-generation polyester dendrons using click chemistry (CuAAC). These dendrons were then linked at C60 through the Bingel-Hirsch reaction, resulting in an amphiphilic system that retains the hydrophobic nature of C60. The dendronized malonate derivatives showed good reaction yields for the Bingel-Hirsch mono-adducts and were easier to work with than the corresponding malonamides. However, the malonamide derivatives, which were obtained through a multistep reaction sequence, showed moderate yields in the Bingel-Hirsch reaction. Surprisingly, removing acetonide protecting groups from dendritic architectures was more challenging than anticipated, likely due to product decomposition. Only the corresponding free malonate derivatives 25 and 26 were obtained, but in a low yield due to decomposition under the reaction conditions. Meanwhile, it was not possible to obtain the corresponding malonamide derivatives 27 and 28. Currently, efforts are being made to improve the production of the desired molecules and to design new synthesis routes that allow direct access to the desired poly-hydroxylated derivatives. These derivatives will be evaluated as multitarget ligands against Alzheimer's disease, through their use as inhibitors of amyloid ß-peptide aggregation, acetylcholinesterase modulators, and antioxidants.

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Despite of the capacity that several drugs have for specific inhibition of the androgen receptor (AR), in most cases, PCa progresses to an androgen-independent stage. In this context, the development of new targeted therapies for prostate cancer (PCa) has remained as a challenge. To overcome this issue, new tools, based on nucleic acids technology, have been developed. Aptamers are small oligonucleotides with a three-dimensional structure capable of interacting with practically any desired target, even large targets such as mammalian cells or viruses. Recently, aptamers have been studied for treatment and detection of many diseases including cancer. In PCa, numerous works have reported their use in the development of new approaches in diagnostics and treatment strategies. Aptamers have been joined with drugs or other specific molecules such as silencing RNAs (aptamer-siRNA chimeras) to specifically reduce the expression of oncogenes in PCa cells. Even though these studies have shown good results in the early stages, more research is still needed to demonstrate the clinical value of aptamers in PCa. The aim of this review was to compile the existing scientific literature regarding the use of aptamers in PCa in both diagnosis and treatment studies. Since Prostate-Specific Membrane Antigen (PSMA) aptamers are the most studied type of aptamers in this field, special emphasis was given to these aptamers.

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Curcumin and its analogs, chalcones, and C5-monocarbonyl are molecules of great therapeutic potential, but their poor stability and hydrophobicity have hampered their extensive use in clinical trials. Therefore, significant efforts have been made in materials science to improve their physicochemical properties. In this study, we propose dendronization as a synthetic strategy to strengthen some physicochemical properties such as solubility and stability of curcumin and analogs, taking advantage of the click chemistry (CuAAC) to attach second-generation polyester dendrons to the unsaturated cores. The dendronization, with the subsequent formation of aromatic triazole groups as linkers, not only modified the solubility and stability of the molecular systems but also favored the diketo tautomeric form of curcumin, as demonstrated spectroscopically. This result is significant since the diketo tautomer, which preserves the antioxidant properties of curcumin, is the most biologically active form. The hydrophobic/hydrophilic balance, achieved after dendronization, allowed the solubilization of the chromophoric molecules in buffered solutions at relevant pH values (7.4 and 6.4). Furthermore, the stability of all molecules was also upgraded since UV-vis absorption spectra did not exhibit modified profiles after 7 days at physiologic pH. From photochemical stability experiments irradiating at 415 nm, the dendritic derivatives containing triazole linkers were more susceptible to being degraded. All derivatives exhibited emission properties according to the length of each conjugate fragment. Fluorescence experiments evidenced the role of dendrons in preventing emission quenching by aggregation and exhibited differentiated emission behavior depending on the linker type (triazole or ester) between the chromophoric core and the polyester dendrons.

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Prostate cancer (PCa) is a common type of cancer affecting male population. PCa treatments have side effects and are temporarily effective, so new therapeutic options are being investigated. Due to the high demand of energy for cell proliferation, an increase in the expression and activity of lipogenic enzymes such as the stearoyl-CoA desaturase (SCD) have been observed in PCa. Sterculic acid, contained in the seed's oil of Malvales, is a natural inhibitor of SCD. The objective of our investigation was to evaluate the effects of sterculic oil (SO) from Sterculia apetala seeds on proliferation, cell cycle and apoptosis in prostate cancer cells. SO was administered to PC3 and LNCaP cells, and to prostate normal cells; cell viability, cell cycle, apoptosis, SCD gene and protein expression and enzymatic activity were analyzed. SO administration (4 mM sterculic acid) diminished cell viability in LNCaP and PC3 cells, arrested cell cycle in G2 and promoted apoptosis. SO diminished SCD enzymatic activity with no effects on gene nor protein expression. Our results suggest that SO might offer benefits as an adjuvant in hormonal and chemotherapy prostate cancer treatments. This is the first study to analyze the effect of SO on cancer cells.

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The use of already-approved drugs to treat new or alternative diseases has proved to be beneficial in medicine, because it reduces both drug development costs and timelines. Most drugs can be used to treat different illnesses, due their mechanisms of action are not restricted to one molecular target, organ or illness. Diverging from its original intent offers an opportunity to repurpose previously approved drugs to treat other ailments. This is the case of sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor, which was originally designed to treat systemic hypertension and angina but is currently commercialized as erectile dysfunction treatment. Sildenafil, tadalafil, and vardenafil are PDE5 inhibitors and potent vasodilators, that extend the physiological effects of nitric oxide and cyclic guanosine monophosphate (cGMP) signaling. Although most of the biological implications of these signaling regulations remain unknown, they offer a large therapeutic potential for several diseases. In addition, some PDE5 inhibitors' molecular effects seem to play a key role in different illnesses such as kidney disease, diabetes mellitus, and cancer. In this review, we discuss the molecular effects of PDE5 inhibitors and their therapeutic repurposing in different types of cancer.

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Neoplasic transformation is a continuous process that occurs in the body. Even before clinical signs, the immune system is capable of recognizing these aberrant cells and reacting to suppress them. However, transformed cells acquire the ability to evade innate and adaptive immune defenses through the secretion of molecules that inhibit immune effector functions, resulting in tumor progression. Hormones have the ability to modulate the immune system and are involved in the pathogenesis of autoimmune diseases, and cancer. Hormones can control both the innate and adaptive immune systems in men and women. For example androgens reduce immunity through modulating the production of pro-inflammatory and anti-inflammatory mediators. Women are more prone than men to suffer from autoimmune diseases such as systemic lupus erythematosus, psoriasis and others. This is linked to female hormones modulating the immune system. Patients with autoimmune diseases consistently have an increased risk of cancer, either as a result of underlying immune system dysregulation or as a side effect of pharmaceutical treatments. Epidemiological data on cancer incidence emphasize the link between the immune system and cancer. We outline and illustrate the occurrence of hormone-related cancer and its relationship to the immune system or autoimmune diseases in this review. It is obvious that some observations are contentious and require explanation of molecular mechanisms and validation. As a result, future research should clarify the molecular pathways involved, including any causal relationships, in order to eventually allocate information that will aid in the treatment of hormone-sensitive cancer and autoimmune illness.

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Prostate cancer is one of the main causes of cancer and the sixth cause of death among men worldwide. One of the major challenges in prostate cancer research is cell heterogeneity defined as the different genomic and phenotypic characteristics in each individual cell making more difficult to assess the proper prostate cancer diagnosis and therapy. Tumor 3D spatial arrangement allow a strong interaction between the different cellular lineages and components which modulate cell proliferation, differentiation, and morphology. Prostate cancer spheroids are a cellular model which is capable to mimic the mechanical tensions of tumor tissue, providing a more representative pathophysiological model than the use of conventional 2D culture. Here, we describe a protocol to develop a 3D model of spheroids using prostate cancer cell lines (LNCaP, PC3, VCaP) which can be used to improve research considering tumoral heterogeneity role in cancer development, prognosis, and therapy.

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In the treatment of cancer, over the last decade different drugs delivery systems have been developed to increase therapeutic specificity to improve drug's efficacy, and safety by increasing bioavailability. Among these systems, small nucleic acid molecules with a three-dimensional structure, known as aptamers, have shown several advantages. Several approaches to design aptamers require modifications from starting libraries of DNA sequences. Here, we describe cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment), a sophisticated technique based on RNA aptamers as a starting point, that enables design functional aptamers as drug-delivery tools. This variation of the original SELEX technique using RNA aptamers instead DNA aptamers allows to obtain aptamers that are internalized in prostate cancer cells using as a starting point an RNA aptamer library with 76 nucleotides. The major advantage of this technique is that modifications are not required in the initial library, as initial T7 transcription promoter or 2'F nucleotides before sequencing.

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BACKGROUND: Prostate cancer (PCa) is the second cause of cancer related death in North American men. Androgens play an important role in its progression by regulating the expression of several genes including fusion ones that results from structural chromosome rearrangements. TMPRSS2-ERG is a fusion gene commonly observed in over 50% of PCa tumors, and its expression can be transcriptionally regulated by the androgen receptor (AR) given its androgen responsive elements. TMPRSS2-ERG could be involved in epithelial-mesenchymal transition (EMT) during tumor development. ERG has been reported as a key transcriptional factor in the AR-ERG-WNT network where five SFRP proteins, structurally similar to WNT ligands and considered to be WNT pathway antagonists, can regulate signaling in the extracellular space  by binding to WNT proteins or Frizzled receptors. It has been shown that over-expression of SFRP1 protein can regulate the transcriptional activity of AR and inhibits the formation of colonies in LNCaP cells. However, the effect of SFRP1 has been controversial since differential effects have been observed depending on its concentration and tissue location. In this study, we explored the role of exogenous SFRP1 protein in cells expressing the TMPRSS2-ERG fusion. METHODS: To evaluate the effect of exogenous SFRP1 protein on PCa cells expressing TMPRSS2-ERG, we performed in silico analysis from TCGA cohort, expression assays by RT-qPCR and Western blot, cell viability and cell cycle measurements by cytometry, migration and invasion assays by xCELLigance system and murine xenografts. RESULTS: We demonstrated that SFRP1 protein increased ERG expression by promoting cellular migration in vitro and increasing tumor growth in vivo in PCa cells with the TMPRSS2-ERG fusion. CONCLUSIONS: These results suggest the possible role of exogenous SFRP1 protein as a modulator of AR-ERG-WNT signaling network in cells positive to TMPRSS2-ERG. Further, investigation is needed to determine if SFRP1 protein could be a target in against this type of PCa.

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BACKGROUND: Blue corn is a cereal rich in phenolic compounds used to make blue tortillas. Tortillas are an important part of the Mexican diet. Blue corn and tortilla represent an important source of the natural antioxidants anthocyanins. However, studies on their biological activity on cancer cell lines are limited. The goal of this study was to evaluate the antioxidant and antiproliferative activity of blue corn and tortilla on different cancer cell lines. METHODS: Total polyphenol content, monomeric anthocyanins, and antioxidant activity by the DPPH and TBARS methods of blue corn and tortilla were determined. The anthocyanin profile of tortilla was obtained by means of HPLC-ESI-MS. The antiproliferative activity of blue corn and tortilla extract on HepG2, H-460, Hela, MCF-7 and PC-3 was evaluated by the MTT assay. RESULTS: Blue corn had higher content of total polyphenols and monomeric anthocyanins as well as lower percentage of polymeric color than tortilla; however, both showed similar antioxidant activity by DPPH. In addition, although a higher degradation of anthocyanins was observed on tortilla extract, both extracts inhibited lipid peroxidation (IC50) at a similar concentration. The anthocyanin profile showed 28 compounds which are primarily derived from cyanidin, including acylated anthocyanins and proanthocyanidins. Blue corn and tortilla extracts showed antiproliferative effects against HepG2, H-460, MCF-7 and PC-3 cells at 1000 µg/mL, however Hela cells were more sensitive at this concentration. CONCLUSION: This is the first report to demonstrate anticancer properties in vitro of tortilla derived from blue corn, suggesting that this product has beneficial health effects. In addition, blue corn could be a potential source of nutraceuticals with anticancer activity.

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Se presenta una técnica como variante de la apendicectomía profiláctica, que consiste en la invaginación del apéndice denudado en el ciego, previa ligadura y sección de la arteria apendicular(AU)

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Se revisan, estadísticamente, los casos de 35 pacientes portadores de pancreatitis aguda, 23 de los cuales fallecieron. Se hace un recuento de la mortalidad actual en los pacientes que padecen esta afección, mencionándose los factores que condicionan un mal pronóstico(AU)

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Se realiza una revisión de la literatura médica relacionada con las indicaciones y tipos de intervenciones quirúrgicas aplicadas en la pancreatitis aguda. Se revisan los hallazgos estadísticos de 35 pacientes que padecen esta afección, destacándose que a diez de ellos se les realizó tratamiento quirúrgico(AU)

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Se revisan los aspectos más importantes del tratamiento médico de la pancreatitis aguda, y se hace énfasis en la reposición de coloides y del equilibrio hidroelectrolítico, la aspiración nasogástrica, el alivio del dolor, la administración de atropina, antitrípticos y antibióticos, como puntos fundamentales del tratamiento médico(AU)

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Se hace un estudio sobre el resultado del tratamiento quirúrgico de la hernia crural con especial referencia a la Técnica de Henry, basado en el tratamiento de ochenta y seis casos en el Servicio de Cirugía del Hospital Nacional "Enrique Cabrera". Se destacan las ventajas de la técnica citada (AU)

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