In this study, we assessed the therapeutic potential of propolis from Poland and performed chemical analysis by GC–MS, as well as determined its botanical origin. Chemical constituents typical for bud exudates of Populus nigra (section Aigeiros) were determined, however, glycerol esters of phenolic acids, as well as unusually high amounts of p-coumaric and ferulic acid and their benzyl esters, were also detected. These constituents are characteristic for buds of Populus tremula (section Leuce). We also evaluated the antiproliferative effect of propolis extracts against nine human cancer cell lines. Additionally, promising antibacterial activity of the dichloromethane extract (Minimal Inhibitory Concentration MIC values of 0.95–1.24 mg/mL), as well as a moderate antifungal activity (MIC values of 1.25–1.40 mg/mL), was noticed. Propolis from Poland appeared as a rich source of antibacterial and antiproliferative compounds and this confirmed that it is a valuable natural product with the potential to improve human health.

Twenty-four patients with persistent epithelial ovarian cancer after chemotherapy with or without external beam irradiation, were treated with intraperitoneally administered 131I-labeled monoclonal antibodies HMFG1, HMFG2, AUA1, H17E2, directed against tumor-associated antigens. Acute side effects were mild abdominal pain, pyrexia, diarrhea, and moderate reversible pancytopenia. One patient developed a subphrenic abscess requiring surgical drainage. Eight patients with large volume disease, ie, greater than 2 cm tumor diameter, did not respond to antibody-guided irradiation and died of progressive disease within 9 months of treatment. Sixteen patients had small-volume (less than 2 cm) disease at the time of treatment with radiolabeled antibody. Seven patients failed to respond, and of nine initial responders, four patients remain alive and free from disease 6 months to 3 years from treatment. Analysis of the data on relapse indicated that doses greater than 140 mCi were more effective than lower doses. We conclude that the intraperitoneal administration of 140 mCi or more of 131I-labeled tumor-associated monoclonal antibodies represents a new and potentially effective form of therapy for patients with small-volume stage III ovarian cancer.

Integrins are cell-surface glycoproteins found in different forms on all cells except erythrocytes. Integrins bind to cell adhesion molecules and to proteins found in the extracellular matrix. A tripeptidic sequence Arg-Gly-Asp (RGD) is often the primary site of recognition by integrins which are expressed on tumour cells and are responsible for tumour invasion and metastasis. A synthetic decapeptide designated alpha P2 containing two RGD sequences radiolabelled with technetium-99m was used to image malignant melanoma in vivo. Fourteen patients previously diagnosed with metastatic melanoma underwent gamma camera imaging 20-180 min following intravenous administration of the radiolabelled synthetic decapeptide alpha P2. Six out of eight (6/8) of the lymph node metastases (75%) and all other neoplastic sites (11 sites) were successfully imaged, with the exception of three sites in the mediastinal area which were not positively imaged. In two cases there was false positive uptake in the rounded pigmented areolar/nipple area. In three cases (seven sites) the peptide scan confirmed the absence of disease in suspected lesions (true-negative). The synthetic peptide was rapidly removed from the circulation by filtration through the kidneys and excretion in the urine. No toxicity or adverse events were recorded. Radiolabelled alpha P2 peptide, which binds specifically to adhesion molecules on tumours, can be used for the in vivo detection of neoplastic metastases.

Purpose To characterize the population pharmacokinetics of bevacizumab, its binding properties to VEGF165 and the effect of demographic data and VEGF-A polymorphisms on the interplay between bevacizumab serum pharmacokinetics and VEGF165 serum concentrations in patients with colorectal cancer stage IV.MethodsBevacizumab and VEGF165 data were collected from 19 adult patients with metastatic colorectal cancer enrolled in an observational clinical study. Bevacizumab was administered with one of the following combinations: 5-FU/Leucovorin/Irinotecan, 5-FU/Leucovorin/Oxaliplatin, Capecitabine/Irinotecan at doses ranging from 5 to 10 mg/kg every 2 or 3 weeks. Data analysis was performed using nonlinear mixed-effects modeling implemented in NONMEM 7.3.ResultsA target-mediated drug disposition model adequately described bevacizumab concentration changes over time and its binding characteristics to VEGF165. The estimated clearance of bevacizumab was 0.18 L/day, the free VEGF165 levels at baseline were 212 ng/L, and the elimination rate constant of free VEGF165 was 0.401 day−1. Body weight was allometrically included in all PK parameters.ConclusionThe final model adequately described the pre- and post-dose concentrations of total bevacizumab and free VEGF165 in patients with colorectal cancer. Model parameters were consistent with those previously reported for patients with solid tumors. Correlations between the binding affinity of bevacizumab and the VEGF-2578C/A and VEGF-634G/C polymorphisms were noticed.Electronic supplementary materialThe online version of this article (doi:10.1007/s00280-015-2701-3) contains supplementary material, which is available to authorized users.

From March 1987 to March 1988, a phase I to II study was carried out in 25 patients with ovarian cancer. They received escalating doses of intraperitoneally (IP) administered yttrium-90 (Y-90)-labeled monoclonal antibody, HMFG1, against a tumor cell-surface antigen. Myelosuppression prevented an escalation of the administered Y-90 activity above 25 mCi. Y-90-labeled antibody was absorbed from the peritoneal cavity into the circulation. Maximum blood Y-90 activity was observed 40 hours after the IP injection with a mean of 21% of the injected activity (range, 14.2% to 26.4%) in the circulation. The radiation dose the bone marrow received from circulating Y-90-labeled antibody (the blood radiation dose) was calculated by applying the Medical Internal Radiation Dose (MIRD) formulation to the measured Y-90 activity in patients blood. Myelosuppression occurred following calculated blood radiation doses to bone marrow of only 10 to 30 cGy. The excessive myelosuppression following such modest radiation doses from circulating Y-90-labeled antibody could be explained by the uptake of Y-90 by bone. In an attempt to reduce bone absorption of Y-90, seven patients received an intravenous (IV) infusion of EDTA (Sinclair Pharmaceuticals Ltd, Godalming, United Kingdom). This increased the urinary excretion of Y-90 from a mean of 11.1% to 32.3% of the injected activity (P = .0001). Fourteen patients had assessable tumor at laparoscopy. Tumor regression was observed in one patient, and palliation of ascites in a further patient.