Clara Matei

Protein microarray for complex apoptosis monitoring of dysplastic oral keratinocytes in experimental photodynamic therapy.

BackgroundPhotodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential.ResultsThe destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude.ConclusionsUp to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.BACKGROUND Photodynamic therapy is an alternative treatment of muco-cutaneous tumors that uses a light source able to photoactivate a chemical compound that acts as a photosensitizer. The phthalocyanines append to a wide chemical class that encompasses a large range of compounds; out of them aluminium-substituted disulphonated phthalocyanine possesses a good photosensitizing potential. RESULTS The destructive effects of PDT with aluminium-substituted disulphonated phthalocyanine are achieved by induction of apoptosis in tumoral cells as assessed by flow cytometry analysis. Using protein microarray we evaluate the possible molecular pathways by which photodynamic therapy activates apoptosis in dysplastic oral keratinocytes cells, leading to the tumoral cells destruction. Among assessed analytes, Bcl-2, P70S6K kinase, Raf-1 and Bad proteins represent the apoptosis related biomolecules that showed expression variations with the greatest amplitude. CONCLUSIONS Up to date, the intimate molecular apoptotic mechanisms activated by photodynamic therapy with this type of phthalocyanine in dysplastic human oral keratinocytes are not completely elucidated. With protein microarray as high-throughput proteomic approach a better understanding of the manner in which photodynamic therapy leads to tumoral cell destruction can be obtained, by depicting apoptotic molecules that can be potentially triggered in future anti-tumoral therapies.

A case of disseminated cutaneous Kaposi sarcoma in an immunocompetent patient

Background Kaposi’s sarcoma (KS) is a tumor derived from the endothelial cell lineage caused by Kaposi sarcomaassociated virus (KSHV), also known as human herpes virus 8 (HHV-8). Four subtypes of KS have been described: classical KS, African endemic KS, immunosuppression-associated KS and AIDS-associated KS. Over 95% of the lesions have been found to be infected with HHV-8, regardless of the clinical subtype. Classical KS usually occurs in elderly men from the Mediterranean region. It is a chronic, slowly progressing disorder, usually confined to the skin, which only rarely affects other organs.

Toxicological and efficacy assessment of post-transition metal (Indium) phthalocyanine for photodynamic therapy in neuroblastoma.

Metallo-phthalocyanines due to their photophysical characteristics as high yield of triplet state and long lifetimes, appear to be good candidates for photodynamic therapy (PDT). Complexes with diamagnetic metals such as Zn2+, Al3+ Ga3+ and In3+meet such requirements and are recognized as potential PDT agents. Clinically, Photofrin® PDT in neuroblastoma therapy proved in pediatric subjects diagnosed with progressive/recurrent malignant brain tumors increased progression free survival and overall survival outcome. Our study focuses on the dark toxicity testing of a Chloro-Indium-phthalocyanine photosensitizer (In-Pc) upon SH-SY5Y neuroblastoma cell line and its experimental in vitro PDT. Upon testing, In-Pc has shown a relatively high singlet oxygen quantum yield within the cells subjected to PDT (0.553), and 50 μg/mL IC50. Classical toxicological and efficacy assessment were completed with dynamic cellular impedance measurement methodology. Using this technology we have shown that long time incubation of neuroblastoma cell lines in In-Pc (over 5 days) does not significantly hinder cell proliferation when concentration are ≤ 10 μg/mL. When irradiating neuroblastoma cells loaded with non-toxic concentration of In-Pc, 50% of cells entered apoptosis. Transmission electron microscopy has confirmed apoptotic characteristics of cells. Investigating the proliferative capacity of the in vitro treated cells we have shown that cells that “escape” the irradiation protocol, present a reduced proliferative capacity. In conclusion, In-Pc represents another photosensitizer that can display sound PDT properties enhancing neuroblastoma therapy armentarium.

Capsaicin: Friend or Foe in Skin Cancer and Other Related Malignancies?

Capsaicin is the main pungent in chili peppers, one of the most commonly used spices in the world; its analgesic and anti-inflammatory properties have been proven in various cultures for centuries. It is a lipophilic substance belonging to the class of vanilloids and an agonist of the transient receptor potential vanilloid 1 receptor. Taking into consideration the complex neuro-immune impact of capsaicin and the potential link between inflammation and carcinogenesis, the effect of capsaicin on muco-cutaneous cancer has aroused a growing interest. The aim of this review is to look over the most recent data regarding the connection between capsaicin and muco-cutaneous cancers, with emphasis on melanoma and muco-cutaneous squamous cell carcinoma.

New Insights in the Pathogenesis of HPV Infection and the Associated Carcinogenic Processes: The Role of Chronic Inflammation and Oxidative Stress

Human papillomavirus (HPV) is a small double-stranded DNA virus with tropism for epithelial cells. To this date, over 150 genotypes are known and are classified into two major groups, low-risk and high-risk strains, depending on the ability of the virus to induce malignant transformation. The hosts immunity plays a central role in the course of the infection; therefore, it may not be clinically manifest or may produce various benign or malignant lesions. The pathogenic mechanisms are complex and incompletely elucidated. Recent research suggests the role of chronic inflammation and oxidative stress (OS) in the pathogenesis of HPV infection and the associated carcinogenic processes. Chronic inflammation induces OS, which in turn promotes the perpetuation of the inflammatory process resulting in the release of numerous molecules which cause cell damage. Reactive oxygen species exert a harmful effect on proteins, lipids, and nucleic acids. Viral oncogenes E5, E6, and E7 are involved in the development of chronic inflammation through various mechanisms. In addition, HPV may interfere with redox homeostasis of host cells, inducing OS which may be involved in the persistence of the infection and play a certain role in viral integration and promotion of carcinogenesis. Knowledge regarding the interplay between chronic inflammation and OS in the pathogenesis of HPV infection and HPV-induced carcinogenesis has important consequences on the development of new therapeutic strategies.

Kyrle's Disease in a Patient with Delusions of Parasitosis.

Acquired perforating disorders are a group of uncommon skin conditions characterized by transepidermal extrusion of altered dermal material, most often associated with diabetes mellitus and chronic kidney failure. Delusional parasitosis is a primary psychiatric disorder in which affected patients have fixed, false beliefs that their skin is infested by parasites, in the absence of any evidence supporting their statements. A 69 year old malepatient addressed the Dermatology Department for a skin eruption consisting of multiple umbilicated keratotic papules with a generalized distribution. The patient believed that the lesions were produced by small parasites entering and exiting his skin. The histopathological examination confirmed the clinical diagnosis of Kyrle’s disease. The psychiatric examination established the diagnosis of delusions of parasitosis. This is the first reported case of Kyrle’s disease associated with delusions of parasitosis. There is no evidence supporting the hypothesis that delusions of parasitosis might be a predisposing factor for Kyrle’s disease. However, we believe that the pruritic dermatosis might have triggered the delusions of parasitosis due to the associated pruritus. On the other hand the constant excoriations and traumatizing of a skin prone to develop idiopathic Kyrle’s disease in the attempt to remove the parasites prevented the complete resolution of the lesions.

Menstrual synchronizing: myth or reality?

Menstrual synchronizing (MS) represents the temporal correlation of the menstrual cycle debut among women living in spatial proximity. Possible mechanisms underlying some explanations for MS could be the interpolation of various factors of social interaction and/or of some biologic factors (pheromones). The present material aims to review the medical literature in the field. Although seductive as a hypothesis, MS could not be irrefutably proved by any study up until now. Studies attesting MS present important statistical defects which cancel the proof of MS. The analysis of the data obtained by these studies with an adequate statistical apparatus does not allow the demonstration of MS.

Buschke-Löwenstein tumor of the vulva in a patient with a history of squamous cell carcinoma of the cervix

Background Buschke-Lowenstein tumor (BLT) is a very rare sexually-transmitted disease associated with human papillomavirus (HPV) type 6 and 11, but rare cases of oncogenic HPV types including HPV 16 and HPV 18 were also reported. It is characterized by slow, locally invasive growth and clinically presents as exophytic masses with a cauliflower-like morphology. It usually occurs in uncircumcised men and location in sites other than the penis is very rare. It is a premalignant disorder with a low incidence of metastasis but with a considerable risk of malignant transformation to squamous cell carcinoma (SCC).