Photodynamic therapy combined with a cysteine proteinase inhibitor synergistically decrease VEGF production and promote tumour necrosis in a rat mammary carcinoma.

OBJECTIVES: Photodynamic therapy (PDT) and inhibition of cathepsin B proteases by cystatin (cysteine proteinase inhibitor, CPI) are potential new tumour treatment modalities. We have investigated the efficacy of PDT and CPI alone and in combination on a solid mammary carcinoma transplanted into Wistar rats. MATERIALS AND METHODS: Intraperitoneally injected single doses of chlorine e6 or HpD as photosensitizers were excited at 630 nm (90 J/cm(2)). CPI (500 micro g per animal) was injected around the tumour daily during the 8-day treatment. Inoculation of tumour was either on day 1 of the protocol, or 8 days before. On day 8, tumour size was measured, tumour necrosis and vascularization were determined based on haematoxylin and eosin (H&E)-stained sections and serum vascular endothelial growth factor (VEGF) levels measured using an enzyme-linked immunosorbent assay kit. RESULTS: No differences (two-way anova) were found for treatments started with various time lags. At doses where CPI or PDT alone had no or negligible effect, their combination caused a marked (P < 0.001) decrease in serum VEGF, paralleled by a significant decrease in tumour size and number of capillary vessels, and a significant increase in necrosis (up to 80% of the tumour tissue). CONCLUSIONS: The combination of PDT and CPI could be a useful approach in tumour therapy as the two agents appear to be synergistic and probably decrease VEGF production by the tumour tissue.

Argyrophilic proteins of nucleolar organizer regions (AgNORs) in fallopian tube carcinomas.

Forty-four patients diagnosed with primary cancer of the fallopian tube (PFTC) were analyzed with regard to AgNORs expression, morphological classification, clinical stage and survival rate. Twenty-seven patients were FIGO stage I, 7 FIGO II and 10 FIGO III. Histological classification of PFTC revealed 18 endometrioid types, 9 serous, 7 undifferentiated, 6 urothelial, 2 clear cell and 2 another type of (intestinal, squamous cell) cancer. Histological grading revealed 11 G1, 16 G2 and 17 G3 tumors. The number of AgNORs per nucleus ranged from 1 to 7, mean 2.54+/-0.77. The smallest number of silver stained NORs was observed in the endometrioid type (mean 2.32+/-0.62) and the biggest number of AgNORs in undifferentiated carcinoma (mean 3.05+/-0.82). There was no correlation between number of AgNORs and AgNOR area/nuclear area ratio and survival (p=0.71), histological stage or histological type of PFTC. There was a correlation between the number of AgNORs among tumors with histological grade 1 and grade 3 (p=0.023), and grade 2 and grade 3 (p=0.045). However, there was no correlation between AgNOR number and survival rate in these groups.

Study on ganglioside composition in brain tumours supra- and infratentorial.

The composition of gangliosides in primary tumors depends on their histological origin and differentiation grade (biological malignancy). The aim of the present study was the comparison of gangliosides in various types of brain tumours. The studies were performed on specimens from 20 high grade gliomas, 5 low grade gliomas, 8 meningiomas and 9 metastatic tumours. The isolated gangliosides were separated on silica 60 HPTLC plates and their mobilities were compared with glycolipids standards. The following observations were made: 1. high and low grade gliomas had similar ganglioside profiles comprising 7 different species; 2. the profiles of gangliosides isolated from metastatic neoplasms differ considerably from those of gliomas as well as menigiomas.

[Familial occurrence of hemangioblastoma]. / Rodzinne wystepowanie naczyniaka plodowego.

Haemangioblastoma is a benign vascular neoplasm accounting for approximately 1-2% of all intracranial tumours. Patients with haemangioblastoma are aged usually about 40 years, the tumour is situated mostly in the cerebellum, more frequently in males. The tumour is a component of the Hippel-Lindau syndrome with familial-hereditary dominant aetiology, often associated with retinal angiomatosis, cysts of the pancreas and kidneys, renal carcinoma and phaeochromocytoma. A familial haemangioblastoma is reported in father and son. The father had the tumour in cerebellar vermis but the son had multiple tumours in cerebellum and medulla.

Disseminated nocardiosis as a complication of Evans' syndrome.

Nocardiosis is an opportunistic infection caused by gram-positive, weakly acid-fast filamentous aerobic organisms. Three species cause infection in man: N. asteroides, N. brasiliensis, and N. caviae, the first one being the most common. With increased use of immunosuppressive therapy for various autoimmune diseases, opportunistic infection by Nocardia has increasingly been reported. N. asteroides infections manifest in various ways; the lungs, skin, and brain are the organs most frequently involved. We describe a patient with Evans' syndrome, a disease requiring long-term immunosuppression, who acquired systemic nocardiosis. The infection was primarily pulmonary, misdiagnosed as tuberculosis, with subsequent hematogenous dissemination to the skin and central nervous system. The diagnosis of cerebral involvement was difficult to prove, as the patient presented with stroke-like episodes. After a positive blood culture was obtained, antibiotic therapy was introduced. The patient's condition deteriorated and the brain with infiltration of the meninges, lungs, skin, and kidneys. Nocardia is an important but often overlooked opportunistic infectious agent in immunocompromised hosts, causing diagnostic and therapeutic problems. As the mortality of cerebral nocardiosis is greater than 80%, early diagnosis and appropriate therapy are crucial.

[Clinical applications of photodynamic therapy in the treatment of laryngeal lesions]. / Kliniczne zastosowanie fotodynamicznej terapii w leczeniu schorzen krtani.

Photodynamic therapy (PDT) has been used in the treatment of laryngeal lesions. The disorders comprised primary dysplasia and leukoplakia of the vocal cords. The patients after diagnosis were subjected to the therapy. Six hours prior to the light irradiation the patients received 4% solution of delta-aminolevulinic acid (ALA) during 30 minutes inhalation. After 6 hours all the changes were irradiated using 400 nm wavelength light from 300 W halogen lamp (range: 380-420 nm) in order to visualize them. Next, the wavelength was tuned to 650 nm (range 620-680 nm) and the total dose 120 J/cm2 for all cases. Control examinations in patients revealed complete response of the lesions within 2-3 months after PDT.

A case of severe anti-neutrophil cytoplasmic antibody (ANCA)-positive crescentic glomerulonephritis and asymptomatic gastric cancer.

A 64-year-old man presented with symptoms of systemic immune disease dominated by rapidly progressive glomerular injury with highly positive ANCA of cytoplasmic distribution. The clinical course was characterized by dependence upon the intensity of immunosuppression, which has finally led to development of fungal septicaemia and death. The post mortem examination revealed occult gastric cancer with regional lymphatic involvement and crescentic glomerulonephritis, while failing to substantiate clinical findings of systemic vasculitis. This is, to our knowledge, the first case of ANCA-positive glomerulonephritis accompanying visceral malignancy and as such raises the question of whether it results from a simple coincidence or a causal relationship.