Search

To improve a cancer patient’s quality of life, short treatment duration resulting in rapid tumour removal while sparing normal tissue are highly desirable. Photodynamic therapy (PDT) commonly applied in a single treatment, while often effective can be limited at low photosensitizer or light doses. Combination therapies can overcome the efficacy limitations while not increasing treatment-associated morbidity. Here the efficacy of combination therapy comprised of doxorubicin (DOX) or methotrexate (MTX) with Photosens mediated PDT was investigated in three cell lines in vitro, employing multiple incubation sequences. Photosense is a mixture of aluminium phthalocyanines with different sulfonation. The results demonstrated higher synergistic effects when DOX or MTX-mediated chemotherapy preceded PDT light activation by 24 h. MTX is marginally more cytotoxic than DOX, when combined with Photosens (AlPcS2-4) mediated PDT. While MTX and DOX exposure prior to AlPcS2-4 incubation may enhance mitochondrial localisation photosensitizer, the simultaneous targeting of DNA, proteins, and lipids of the combination therapies leads to the observed high cytotoxicity at sub μM drug doses. Keywords: Photodynamic Therapy, Chemotherapy, Cancer, Combination therapy

Summary In 1992–2006 at P.A. Hertsen Moscow Oncology Research Institute photodynamic therapy (PDT) was performed in 48 esophageal cancer patients (total 48 lesions). For PDT we used Russian photosensitizers (Photogem, Photosens, Radachlorin, Alasens), Russian diode lasers (Crystall) and endoscopic equipment. As a result of PDT complete regression was in 77% of esophageal cancer lesions, partial regression was in 23%. The follow-up period was 3–11 years. Median of survival was in 4.59 years of esophageal cancer patient.

We have analyzed the results of photodynamic therapy using light-sensitizing agent "Photogem" in 72 patients - 56 women with pre-cancerous lesions of cervix and 16 women with early cervical cancer (group 1); Photosens in 47 patients - 35 women with pre-cancerous lesions (CIN III), 12 women with non-invasive cervical cancer (carcinoma in situ) (group 2); and Alasens in 22 patients - 8 women with virus-associated pre-cancerous lesions (high-grade CIN III), 14 with virus-associated early cervical cancer (carcinoma in situ, cervical cancer 1A1) (group 3). The results were as follows: group 1 - complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 50 (89.2%) and 11 (68.8%) cases, significant regression was achieved in 2 cases (3.6%) and in 2 cases (12.5%), stabilization was achieved in 2 cases (3.6%) and in 2 cases (12.5%), progression was achieved in 2 cases (3.6%) and in 1 case (6.2%) accordingly. In the group of patients after PDT using Photosens complete regression of CIN III and non-invasive cervical cancer (carcinoma in situ) was achieved in 33 cases (94.2%) and in 10 cases (83.4%) cases, significant regression was achieved in 1 case (2.9%) and in 1 case (8.3%), stabilization was achieved in 1 cases (2.9%) and in 1 cases (8.3%). In the group of women after surgical treatment anti-viral efficacy was assessed. It s necessary to note that not a single relapse was observed. Anti-viral effect was registered in 49 (90.4%) cases The longest HPV-free period that we observed was 5 years. 12 women with CIN III and 4 women with carcinoma in situ became pregnant.

Photodynamic therapy (PDT) and the use of cationic antimicrobial peptides (AMPs) are two very promising strategies to combat antibiotic resistant bacteria. Recently, we demonstrated that the conjugation of a porphyrin photosensitizer with Apidaecin 1b, a small peptide belonging to the Pro-Arg rich AMPs family, provides a potent antimicrobial agent with broad spectrum activity. Porphycenes are structural isomers of porphyrins with 10-fold higher absorption coefficient in the red part of the spectrum, and excellent photochemical and photodynamic properties. Therefore, in an attempt to improve the potential application of the photosensitizer—peptide conjugates, we extended our studies to a porphycene—apidaecin conjugate, in which the porhycene is linked to the N-terminus of Apidaecin. After checking that conjugation is not detrimental of the photophysical properties of the porphycene the antibacterial activity of the conjugate (hereafter G-api) was tested against Gram negative (E. coli) and Gram positive (methicillin resistant S. aureus) bacteria. The phototoxic activity against eukaryotic cells was measured to assess selectivity. In the dark G-api did not exhibit any toxicity against both E. coli and S. aureus. On the contrary, following activation with red light (36 J/cm2), G-api caused a significant (3—4 log10) reduction of both E. coli and S. aureus survival. Under the same experimental conditions porphycene plus Apidaecin, administrated together but not conjugated, did not affect the survival of both E. coli and S. aureus. The G-api conjugate therefore appears a very promising agent for the photoinactivation of both Gram positive and Gram negative bacteria.

required by the Brazilian Registration for clinical experiments (CIEPesquisa/UNIARA 33/2008, 09/12/2008). Main outcome measures: The development of new strategies to treat condyloma by HPV, to trace the infection, to combat its consequences and to guide women with HPV. Results: Aesthetic results were much superior to those obtained by conventional techniques as surgery or cryogenics, with no recurrence reported after two years of treatment. This study discusses how different conditions about lesions and women are important to be considered when choosing PDT as a suitable alternative for each case. Protoporphyrin production and photodegradation were analyzed and pain during the illumination was correlated with the light intensities. Conclusions: The good results are encouraging, evidencing PDT as an alternative to be considered and further studied for the treatment of HPV condyloma.