Hydrazone-Functionalized -AB-Corroles: Effective Synergy in Photodynamic Therapy of Lung Cancer.

A synthetic route to -AB-corroles combining the macrocyclic core with a hydrazone moiety, based on the reactivity of azoalkenes toward dipyrromethanes, has been established with the aim of developing a new class of photosensitizers for photodynamic therapy of lung cancer. The study of the photophysical properties of the novel macrocycles allowed the identification of photosensitizers with absorption within the phototherapeutic window and high singlet oxygen quantum yield. Relevant structure-photodynamic activity correlations were established by studying the new corroles-based photodynamic therapy (PDT) in human lung cancer cell lines (A549 and H1299).

Differential response of hepatocellular carcinoma glycolytic metabolism and oxidative stress markers after exposure to human amniotic membrane proteins.

Background: The human Amniotic Membrane (hAM) has been studied as a potential therapeutic option in cancer, namely in hepatocellular carcinoma. Previously, our research group evaluated the effect of human Amniotic Membrane Protein Extracts (hAMPE) in cancer therapy, demonstrating that hAMPE inhibit the metabolic activity of human hepatocellular carcinoma cell lines: Hep3B2.1-7, HepG2 and Huh7.

Ring-Fused -Tetraarylchlorins as Auspicious PDT Sensitizers: Synthesis, Structural Characterization, Photophysics, and Biological Evaluation.

Novel 4,5,6,7-tetrahydropyrazolo[1,5-]pyridine-fused -tetraarylchlorins, with different degrees of hydrophilicity (with methyl ester, hydroxymethyl, and carboxylic acid moieties), have been synthesized and their photophysical characterization as well as photocytotoxicity assessment against human melanoma and esophageal and bladder carcinomas was carried out. An integrated analysis of the photosensitizers' performance, considering the singlet oxygen generation data, cell internalization, and intracellular localization, allowed to establish relevant structure-photoactivity relationships and the rationalization of the observed photocytotoxicity. In the diacid and monoalcohol series, chlorins derived from -tetraphenylporphyrin proved to be the most efficient photodynamic therapy agents, showing IC values of 68 and 344 nM against A375 cells, respectively.

Insights into the anticancer activity of chiral alkylidene-β-lactams and alkylidene-γ-lactams: Synthesis and biological investigation.

Chiral alkylidene-β-lactams and alkylidene-γ-lactams were synthesized and screened for their in vitro activity against four human cancer cell lines (melanoma, esophageal, lung and fibrosarcoma carcinoma). Alkylidene-β-lactams were synthesized via Wittig reaction of diverse phosphorus ylides with benzhydryl 6-oxopenicillanate, derived from 6-aminopenicillanic acid. Moreover, novel chiral alkylidene-γ-lactams were synthesized through a multistep strategy starting from a chiral substrate (d-penicillamine).

GLP-1 improves adipose tissue glyoxalase activity and capillarization improving insulin sensitivity in type 2 diabetes.

Methylglyoxal was shown to impair adipose tissue capillarization and insulin sensitivity in obese models. We hypothesized that glyoxalase-1 (GLO-1) activity could be diminished in the adipose tissue of type 2 diabetic obese patients. Moreover, we assessed whether such activity could be increased by GLP-1-based therapies in order to improve adipose tissue capillarization and insulin sensitivity.

Functional Impairment of Circulating FcεRI Monocytes and Myeloid Dendritic Cells in Hepatocellular Carcinoma and Cholangiocarcinoma Patients.

Background: Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response.

Methods: In this study, we have functionally characterized, by flow cytometry, circulating myeloid dendritic cells (mDCs) and FcεRI monocytes in a group of healthy individuals (n = 10) and in a group of patients with HCC (n = 19) and CCA (n = 8), at the time point of the surgical resection (T0) and once the patient had recovered from surgery (T1). Moreover, we proceeded to a more in depth phenotypic characterization of the FcεRI monocyte subpopulation.

Endometrial Cancer Spheres Show Cancer Stem Cells Phenotype and Preference for Oxidative Metabolism.

This study aimed to characterize endometrial cancer regarding cancer stem cells (CSC) markers, regulatory and differentiation pathways, tumorigenicity and glucose metabolism. Endometrial cancer cell line ECC1 was submitted to sphere forming protocols. The first spheres generation (ES1) was cultured in adherent conditions (G1).

Stroma-derived IL-6, G-CSF and Activin-A mediated dedifferentiation of lung carcinoma cells into cancer stem cells.

Cancer stem cells (CSCs) are a small population of resistant cells inhabiting the tumors. Although comprising only nearly 3% of the tumor mass, these cells were demonstrated to orchestrate tumorigenesis and differentiation, underlie tumors' heterogeneity and mediate therapy resistance and tumor relapse. Here we show that CSCs may be formed by dedifferentiation of terminally differentiated tumor cells under stress conditions.

Dental caries and bacterial load in saliva and dental biofilm of type 1 diabetics on continuous subcutaneous insulin infusion.

Objectives: Since most of the studies evaluates diabetics on multiple daily injections therapy and continuous subcutaneous insulin infusion may help gain better metabolic control and prevent complications, the objective of this study was to evaluate the prevalence of dental caries, the unstimulated salivary flow rate and the total bacteria load, Streptococcus spp. levels and Lactobacillus spp. levels in saliva and supragingival dental biofilm of type 1 diabetics on insulin pump.

Intestinal Epithelial Stem Cells: Distinct Behavior After Surgical Injury and Teduglutide Administration.

Background: Previous studies suggest that intestinal epithelial stem cells (IESC), critical drivers of homeostasis and regeneration, include two subpopulations: crypt-based columnar and "position +4" stem cells, identified by Lgr5 and Bmi1 biomarkers, respectively. Teduglutide is an enterotrophic counterpart of glucagon-like peptide 2. This study aimed to investigate the response of putative IESC to surgical injury and teduglutide administration on an animal model of intestinal resection and anastomosis.

Platinum(II) Ring-Fused Chlorins as Near-Infrared Emitting Oxygen Sensors and Photodynamic Agents.

Novel near-infrared luminescent compounds based on platinum(II) 4,5,6,7-tetrahydropyrazolo[1,5-]pyridine-fused chlorins are described. These compounds have high photostability and display light emission, in particular simultaneous fluorescence and phosphorescence emission in solution at room temperature, in the biologically relevant 700-850 nm red and near-infrared (NIR) spectral region, making them excellent materials for biological imaging. The simultaneous presence of fluorescence and phosphorescence emission at room temperature, with the phosphorescence strongly quenched by oxygen whereas fluorescence remains unaffected, allows these compounds to be used as ratiometric oxygen sensors in chemical and biological media.

In vivo biodistribution of antihyperglycemic biopolymer-based nanoparticles for the treatment of type 1 and type 2 diabetes.

This study aimed to assess the biodistribution of antihyperglycemic insulin-loaded alginate/dextran sulfate-based nanoparticles dual coated with chitosan and technetium-99m-albumin (Tc-BSA) after oral administration. The oral administration of 50IU/kg insulin-loaded nanoparticles to type 1 diabetic rats showed prolonged antihyperglycemic effects up to 12h and relative pharmacological availability of 5.04% comparing to the subcutaneous administration.

Novel 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine fused chlorins as very active photodynamic agents for melanoma cells.

The development of new stable 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine-fused chlorins with high absorption properties at 650 nm, and their impressive photosensitizer ability against melanotic and amelanotic cancer cells is described. Comparison between a diester-substituted chlorin with the corresponding dihydroxymethyl derivative demonstrated that the increased hydrophilicity of the latter is crucial to ensure nanomolar activity against melanoma cells. The new photosensitizer leads to death of human melanoma cells being both apoptosis and necrosis in equal parts involved in the treatment response.

Autotransplantation combined with orthodontic treatment: a case involving the maxillary central incisors with root resorption after traumatic injury.

Traumatic dental injury can result in avulsion of anterior teeth. In young patients, it is a challenge to the dental professional because after replantation, late complications such as ankylosis require tooth extraction. Although prosthetic and orthodontic treatment, and implant placement have been described as the options for intervention, autogenous tooth transplantation could be an effective procedure in growing patients if there is a suitable donor tooth available.

Hematogenic Dissemination of Triple-negative Versus Hormonal Receptor-positive Breast Cancer Cells.

The aim of this study was to characterize the hematogeneous spread, in vivo, of breast cancer (BC) cell lines that express hormonal receptors (HR) comparing with triple-negative (TN) BC, particularly considering the lung and liver. Female Balb/c nu nu mice (n=30) were injected with two breast cancer cell lines (MCF7 and HCC1806). Nuclear medicine imaging with Technetium ((99m)Tc)-hydroxymethylene diphosphonate ((99m)Tc-HMDP) and (99m)Tc-Hexakis 2-methoxy-2-methylpropylisonitrile (MIBI) were performed between the 7th and 8th weeks after injection.

The effect of Emdogain gel on periodontal regeneration in autogenous transplanted dog's teeth.

Aim: The aim of this study was to assess the enamel matrix derivative (EMD) as biomaterial used in autogenous tooth transplantation.

Material And Methods: The study consisted of 3 beagle dogs, 5 months old, in which six incisors and six premolars were transplanted to mechanically prepared recipient alveolar sockets. One group of teeth was transplanted to a recipient bed, with EMD in the root surface.

Targeting triple-negative breast cancer cells with 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles.

Further studies on 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles as anticancer agents against breast cancer are reported, allowing to demonstrate the potential of these compounds for the therapy of the triple-negative breast cancer, the most challenging tumors in clinical practice. These compounds were assayed for their in vitro cytotoxicity on several human breast cancer cell lines (MCF7, HCC1954 and HCC1806 cell lines). Particularly interesting were the results obtained for 4-hydroxyphenyl substituted derivative, which proved to be the most promising compound regarding HCC1806 cell line, a triple-negative breast cancer.

2-Bromo-5-hydroxyphenylporphyrins for photodynamic therapy: photosensitization efficiency, subcellular localization and in vivo studies.

Background: Photodynamic therapy (PDT) is a therapeutic modality capable of inducing cell death by oxidative stress through activation of a sensitizer by light. Aryl-porphyrin with hydroxyl groups are good photosensitizers and presence of bromine atoms can enhance the photodynamic activity through heavy atom effect. These facts and our previous work made pertinent to compare the photodynamic capacity of tetraaryl brominated porphyrin (TBr4) with the corresponding diaryl (BBr2) derivative.

Chiral 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles with anti-breast cancer properties.

The synthesis and biological evaluation of 6,7-bis(hydroxymethyl)-1H,3H-pyrrolo[1,2-c]thiazoles as anticancer agents against MCF7 breast cancer cell lines is reported. The design of the new compounds has been guided considering (3R)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole as the lead compound due to its good performance against MCF7 breast cancer cell lines (IC(50) = 1.0 μM).

Synthesis of new 2-galactosylthiazolidine-4-carboxylic acid amides. Antitumor evaluation against melanoma and breast cancer cells.

A set of 2-galactosylthiazolidine-4-carboxylic acid amides was synthesized with different length for the carbon chain amide moiety. The cytotoxicity of the molecules was evaluated against A375 melanoma and MCF7 breast cancer cell lines. For the derivatives tested, the one that contains a C(16) amide carbon chain is the most active with an IC(50) of 17.

Estrogen receptor ligands for targeting breast tumours: a brief outlook on radioiodination strategies.

The design and development of radiolabelled estradiol derivatives has been an important area of research due to their recognized value in breast cancer management. The estrogen receptor (ER) is a relevant biomarker in the diagnosis, prognosis and prediction of the therapeutic response in estrogen receptor positive breast tumours. Hence, many radioligands based on estradiol derivatives have been proposed for targeted functional ER imaging.

Chiral 6-hydroxymethyl-1H,3H-pyrrolo[1,2-c]thiazoles: novel antitumor DNA monoalkylating agents.

New chiral 1H,3H-pyrrolo[1,2-c]thiazoles were synthesized and screened for their in vitro activity as anti-cancer agents in three human tumor cell lines, colorectal adenocarcinoma, melanoma and breast adenocarcinoma. (R)-6-Hydroxymethyl-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole and the corresponding benzylcarbamate showed selectivity for breast cancer cell lines with IC(50) values of 2.4 microM and 2.

Histological evaluation of periodontal regeneration in autogenous tooth transplantation in the dog: a comparison between one and two-stage surgical techniques, a pilot study.

Objective: To compare the periodontal regeneration, associated with autogenous tooth transplantation in dogs, using either one- or two-stage surgical techniques.

Methods: The study group consisted of three Beagles, older than 5 months, in which six incisors and six premolars were transplanted to mechanically prepared recipient sockets. One group was transplanted using a one-stage method to recipient beds prepared immediately before transplantation.

Intermittent pringle maneuver and hepatic function: perioperative monitoring by noninvasive ICG-clearance.

Background: Intermittent Pringle maneuver or selective portal clamping often are used to control inflow during parenchymal liver transection. This study was designed to determinate whether these maneuvers are associated with adverse hepatic function.

Methods: Resection was performed without portal clamping in 17 patients (group 1).