Combining ZnPc-liposomes and chitosan on a hybrid matrix for enhanced photodynamic therapy.

Photodynamic therapy is an alternative treatment for several pathologies, including cancer. This therapy uses a photosensitizer capable of producing reactive oxygen species through irradiation, promoting cellular death. A limitation of photosensitizers is their low solubility in aqueous media.

Adjusting the Molecular Clock: The Importance of Circadian Rhythms in the Development of Glioblastomas and Its Intervention as a Therapeutic Strategy.

Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I-IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV.

Antitumor Effects of Freeze-Dried Robusta Coffee () Extracts on Breast Cancer Cell Lines.

Coffee consumption is believed to have chemopreventive and chemotherapeutic effects and to contribute to preventing the development and progression of cancer. However, there is still controversy around these claims. As indicated in our previous works, diet can influence the risk of breast cancer.

Current Phthalocyanines Delivery Systems in Photodynamic Therapy: An Updated Review.

Photodynamic therapy has emerged as an effective therapeutic alternative to treat oncological, cardiovascular, dermatological, infectious, and ophthalmic diseases. Photodynamic therapy combines the action of a photosensitizer with light in the presence of oxygen to generate reactive oxygen species, capable of reacting with cellular components, resulting in injury and, consequently, inducing cellular death. Phthalocyanines are considered good photosensitizers, although most of them are lipophilic, difficulting their administration for clinical use.

Temporal regulation of tumor growth in nocturnal mammals: In vivo studies and chemotherapeutical potential.

Tumors of the nervous system including glioblastoma multiforme (GBM) are the most frequent and aggressive form of brain tumors; however, little is known about the impact of the circadian timing system on the formation, growth, and treatment of these tumors. We investigated day/night differences in tumor growth after injection of A530 glioma cells isolated from malignant peripheral nerve sheath tumor (MPNSTs) of NPcis (Trp53 ; Nf1 ) mice. Synchronized A530 cell cultures expressing typical glial markers were injected at the beginning of the day or night into the sciatic nerve zone of C57BL/6 mice subject to a 12:12 hours light/dark (LD) cycle or after being released to constant darkness (DD).

Isolation and initial characterization of human glioblastoma cells resistant to photodynamic therapy.

Glioblastoma is the most severe form of brain cancer. Despite multimodal therapy combining surgery, radiotherapy and chemotherapy, prognosis of patients is dismal. It has been observed that the surgical resection guided by photosensitizer fluorescence followed by photodynamic therapy (PDT) prolongs the average survival in patients with glioblastoma.

Impairing activation of phospholipid synthesis by c-Fos interferes with glioblastoma cell proliferation.

Glioblastoma multiforme is the most aggressive type of tumor of the CNS with an overall survival rate of approximately one year. Since this rate has not changed significantly over the last 20 years, the development of new therapeutic strategies for the treatment of these tumors is peremptory. The over-expression of the proto-oncogene c-Fos has been observed in several CNS tumors including glioblastoma multiforme and is usually associated with a poor prognosis.

The moonlighting protein c-Fos activates lipid synthesis in neurons, an activity that is critical for cellular differentiation and cortical development.

Differentiation of neuronal cells is crucial for the development and function of the nervous system. This process involves high rates of membrane expansion, during which the synthesis of membrane lipids must be tightly regulated. In this work, using a variety of molecular and biochemical assays and approaches, including immunofluorescence microscopy and FRET analyses, we demonstrate that the proto-oncogene c-Fos (c-Fos) activates cytoplasmic lipid synthesis in the central nervous system and thereby supports neuronal differentiation.

Fra-1 and c-Fos N-Terminal Deletion Mutants Impair Breast Tumor Cell Proliferation by Blocking Lipid Synthesis Activation.

Tumor cells require high rates of lipid synthesis to support membrane biogenesis for their exacerbated growth. The only two proteins known that activate phospholipid synthesis are Fra-1 and c-Fos, two members of the AP-1 family of transcription factors. These proteins that are overexpressed in human breast malignant tumors increase the rate of phospholipid synthesis at the endoplasmic reticulum through a mechanism independent of their nuclear function.

Effectiveness of ZnPc and of an amine derivative to inactivate Glioblastoma cells by Photodynamic Therapy: an in vitro comparative study.

Glioblastoma multiforme is considered to be one of the most aggressive types of tumors of the central nervous system, with a poor prognosis and short survival periods of ~ one year. The current protocol for glioblastoma treatment includes the surgical excision of the primary tumor followed by radio and chemotherapy. Photodynamic therapy (PDT) is considered a promising strategy for the treatment of several types of tumors.

Efficient oral vaccination by bioengineering virus-like particles with protozoan surface proteins.

Intestinal and free-living protozoa, such as Giardia lamblia, express a dense coat of variant-specific surface proteins (VSPs) on trophozoites that protects the parasite inside the host's intestine. Here we show that VSPs not only are resistant to proteolytic digestion and extreme pH and temperatures but also stimulate host innate immune responses in a TLR-4 dependent manner. We show that these properties can be exploited to both protect and adjuvant vaccine antigens for oral administration.

Specific histone modifications play critical roles in the control of encystation and antigenic variation in the early-branching eukaryote Giardia lamblia.

During evolution, parasitic microorganisms have faced the challenges of adapting to different environments to colonize a variety of hosts. Giardia lamblia, a common cause of intestinal disease, has developed fascinating strategies to adapt both outside and inside its host's intestine, such as trophozoite differentiation into cyst and the switching of its major surface antigens. How gene expression is regulated during these adaptive processes remains undefined.

The Catalytic Efficiency of Lipin 1β Increases by Physically Interacting with the Proto-oncoprotein c-Fos.

Phosphatidic acid (PA) is a central precursor for membrane phospholipid biosynthesis. The lipin family is a magnesium-dependent type I PA phosphatase involved in de novo synthesis of neutral lipids and phospholipids. The regulation of lipin activity may govern the pathways by which these lipids are synthesized and control the cellular levels of important signaling lipids.

Brain development is impaired in c-fos -/- mice.

c-Fos is a proto-oncogene involved in diverse cellular functions. Its deregulation has been associated to abnormal development and oncogenic progression. c-fos-/- mice are viable but present a reduction in their body weight and brain size.

The ubiquitin-activating enzyme (E1) of the early-branching eukaryote Giardia intestinalis shows unusual proteolytic modifications and play important roles during encystation.

Giardia intestinalis is considered an early-branching eukaryote and is therefore a valuable model for studying primordial cellular processes. This work reports the characterization of the ubiquitin-activating enzyme (E1) during growth and different stages of trophozoite differentiation into cysts. We found that in Giardia E1 expression (both at mRNA and protein levels) is regulated during encystation.

Regulation of antigenic variation in Giardia lamblia.

Antigenic variation, a clonal phenotypic variation developed by microorganisms, involves the permanent switching of homologous, antigenically different cell surface molecules. In pathogenic microorganisms, antigenic variation is often described as a mechanism to evade the host immune system and therefore is responsible for the generation of chronic and/or recurrent infections. However, antigenic variation has also been involved in expanding host diversity and differential courses of the diseases.

Disruption of antigenic variation is crucial for effective parasite vaccine.

Giardia lamblia is a human intestinal pathogen. Like many protozoan microorganisms, Giardia undergoes antigenic variation, a mechanism assumed to allow parasites to evade the host's immune response, producing chronic and/or recurrent infections. Recently, we found that the mechanism controlling variant-specific surface protein (VSP) switching in Giardia involves components of the RNA interference machinery and that disruption of this pathway generates trophozoites simultaneously expressing many VSPs.

Antigenic variation in Giardia lamblia.

Giardia lamblia undergoes antigenic variation, both in vitro and within the intestines of infected individuals. Variant-specific surface proteins (VSPs) cover the entire surface of the trophozoites and are the main antigens recognized by the host. Only 1 of about 200 VSP genes encoded by the Giardia genome is expressed on the surface of individual Giardia cells at any time; however, VSP antigen switching occurs spontaneously.

Biodistribution and phototherapeutic properties of Zinc (II) 2,9,16,23-tetrakis (methoxy) phthalocyanine in vivo.

Photodynamic therapy (PDT) was investigated using the phthalocyanine photosensitizer Zinc (II) 2,9,16,23-tetrakis (methoxy) phthalocyanine (ZnPc(OCH(3))(4)) on BALB/c mice. Animals bearing tumor were treated with 0.2mg/kg body weight (bw) ZnPc(OCH(3))(4) and 24h later were irradiated with 70, 140 and 210 J/cm(2) of visible light from a source delivering 39 mW/cm(2).

Antigenic variation in Giardia lamblia is regulated by RNA interference.

Giardia lamblia (also called Giardia intestinalis) is one of the most common intestinal parasites of humans. To evade the host's immune response, Giardia undergoes antigenic variation-a process that allows the parasite to develop chronic and recurrent infections. From a repertoire of approximately 190 variant-specific surface protein (VSP)-coding genes, Giardia expresses only one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by unknown mechanisms.

ORF-C4 from the early branching eukaryote Giardia lamblia displays characteristics of alpha-crystallin small heat-shock proteins.

Giardia lamblia is a medically important protozoan parasite with a basal position in the eukaryotic lineage and is an interesting model to explain the evolution of biochemical events in eukaryotic cells. G. lamblia trophozoites undergo significant changes in order to survive outside the intestine of their host by differentiating into infective cysts.

Cellular inactivation and antitumor efficacy of a new zinc phthalocyanine with potential use in photodynamic therapy.

The aim of the present study was to evaluate the photodynamic efficacy of a novel phthalocyanine derivate 2,3,9,10,16,17,23,24-octakis[(N,N-dimethylamino) ethylsulfanyl]phthalocyaninatozinc(II) (referred here as S1) using MCF-7c3 human breast cancer cells and the LM2 adenocarcinoma subcutaneously implanted in Balb/c mice as experimental models. The S1-l-alpha-dimyristoyl-phosphatidylcholine liposome was selected as the best delivery system because it showed greater internalization into cells (35 nmol/10(6) cells), relative to other liposomes. After 3 h incubation S1 was partially localized in lysosomes, the compartment that represented its primary photodamage site.

Photodynamic activity of a new sensitizer derived from porphyrin-C60 dyad and its biological consequences in a human carcinoma cell line.

The photokilling activity of a porphyrin-C(60) (P-C(60)) dyad was evaluated on a Hep-2 human larynx-carcinoma cell line. This study represents the first evaluation of a dyad, with high capacity to form a photoinduced charge-separated state, to act as agent to inactivate cells by photodynamic therapy (PDT). Cell treatment was carried out with 1 microM P-C(60) incorporated into liposomal vesicles.