High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone.

We tested the feasibility and toxicity of high activities Rhenium-186 hydroxyethylidene diphosphonate, with peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. Twenty-five patients received between 2500 and 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate followed 14 days later by the return of peripheral blood peripheral blood stem cells. Activity limiting toxicity was defined as grade III haematological toxicity, lasting at least 7 days, or grade IV haematological toxicity of any duration or any serious unexpected toxicity. Activity limiting toxicity occurred in two of six who received activities of 5000 MBq and maximum tolerated activity was defined at this activity level. Prostate specific antigen reductions of 50% or more lasting at least 4 weeks were seen in five of the 25 patients (20%) all of whom received more than 3500 MBq of Rhenium-186 hydroxyethylidene diphosphonate. The actuarial survival at 1 year is 54%. Administered activities of 5000 MBq of Rhenium-186 hydroxyethylidene diphosphonate are feasible using autologous peripheral blood peripheral blood stem cell rescue in patients with progressive hormone refractory prostate cancer metastatic to bone. The main toxicity is thrombocytopaenia, which is short lasting. A statistically significant activity/prostate specific antigen response was seen. We have now commenced a Phase II trial to further evaluate response rates.

Studies on the nematode; Moaciria icosiensis (Seurat, 1917) from Chalcides ocellatus (Forsk.) in Egypt.

With the aid of scanning electron microscopy certain morphological features (e.g.lateral alae, posterior end of male and cuticular surface) are used as principal pilars in the description of the nematode Moaciria icosiensis (Seurat, 1917) from Chalcides ocellatus (Forsk). Cuticular surface is distinguished by minute striations. Lateral alae are smooth and showing undulation. The posterior end of the male is curved and carries specific papillae. These morphological features are specific and aid in proper identification of Moaciria icosiensis.

Ecology of some sympatric reptilian species from Egypt with special reference to helminthic parasites: Ptyodactylus guttatus and Tarentola annularis.

Ptyodactylus guttatus and Tarentola annularis are sympatric throughout most of their geographical distribution in Egypt. Their temporal activities, feeding habits, food items, feeding strategy are almost similar. These species have been harboured 6 species of nematodes, one species of trematodes in addition to helminthic cysts of cestodes in the liver of each specific host.

Purification of DNA-derived deoxynucleotides from leukocytes involving nuclease elution of an ion-exchange column.

A method has been developed in which the DNA of leukocytes (as the buffy coat from blood) is isolated in the form of its constituent deoxynucleotides. The steps in this method are as follows: (1) lyse the leukocytes with sodium dodecyl sulfate (SDS) and enzymatically digest the proteins and RNA, (2) remove the SDS on a non-polar adsorbent (Bio-Beads SM-4) and then trap the DNA on a quaternary amine silica cartridge, (3) wash the column with 1 M NaCl-buffer, (4) digest the DNA on the column with staphylococcal nuclease and (5) elute the digested DNA with 0.5 M NaCl-buffer and digest it further with bovine spleen phosphodiesterase II to deoxynucleotide-3'-monophosphates. From a 40-microliters sample of butty coat was obtained 126 +/- 14 micrograms (two experiments, eight sample total) of deoxynucleotides. Reversed-phase high-performance liquid chromatography, which removed the added enzymes, showed only peaks for deoxynucleotides. For comparison, the amount of deoxynucleotides obtained from the leukocytes by an automated phenol extraction procedure was 101 +/- 5.4 micrograms (one experiment in triplicate).

Acrylonitrile interaction with testicular DNA in rats.

In the present study we report the in vivo interaction of acrylonitrile (VCN) with testicular tissue in rats. Covalent binding of radioactivity to testicular tissue DNA was examined for a period of 72 hr after a single oral dose (46.5 mg/kg) of [2,3-14C] VCN. Maximal covalent binding was observed at 0.5 hr (8.9 mumol VCN equivalent/mol nucleotide). Binding decreased gradually thereafter but was still detected (2.5 mumol VCN equivalent/mol nucleotide) at 72 hr following VCN administration. Further, we examined the effects of VCN on DNA synthesis and repair in the testes of rats following a single oral dose (46.5 mg/kg) of VCN to clarify the impact of the covalent binding observed on the testicular genetic material. A significant decrease in DNA synthesis (80% of control) was observed at 0.5 hr after treatment. At 24 hr following acrylonitrile administration, testicular DNA synthesis was severely inhibited (38% of control). Testicular DNA repair was increased 1.5-fold at 0.5 hr and more than 3.3-fold at 24 hr following treatment with VCN. These results suggest that VCN can act as a multipotent genotoxic agent by alkylating DNA in testicular tissue and may affect the male reproductive function by interfering with testicular DNA synthesis and repair processes.

Preparation of ethylenediaminephosphoramidates of nucleotides and derivatization with fluorescein isothiocyanate.

Fluorescence post-labeling of nucleotides is a potentially useful technique for the detection of trace amounts of damaged DNA (DNA adducts). Towards this goal, we have studied a derivatization procedure starting with the four major 5'-deoxynucleotides as model compounds. The 5'-phosphate group was first labeled with ethylenediamine via a phosphorimidazolide intermediate in methanol with an organic-soluble carbodiimide. The resulting ethylenediaminephosphoramidate products were reacted in turn with fluorescein isothiocyanate. The reaction sequence has been characterised at all stages by high-performance liquid chromatography.

Serial determinations of serum CEA in monitoring management of patients with colorectal carcinoma.

Serum concentrations were determined serially in two groups of patients with colorectal carcinoma: in 123 after curative resection and in 34 with residual cancer. Of the first group, in 98 serum CEA fluctuated within the normal range or with a 2-fold larger amplitude evidencing effective surgery because only 9 had recurrence; in 25 serum CEA rose persistently from a postoperative nadir indicating relapse, mostly liver metastases. Of the 34 patients with relapse, 3 had clinically and 7 CEA-directed second-look laparotomy; although 7 had operation with curative intent, only 3 remained disease-free. In the second group, there were 26 patients after palliative surgery and 8 during nonsurgical treatment. Serum CEA fluctuated within the normal range in 2 patients in remission and in 3 with progressive cancer, and rose in parallel to cancer progression in 29. Thus, serum CEA within or slightly above the normal range was 88% predictive that the patient might be free of disease or in remission; whereas elevated or rising level indicated disease progression. Accordance between serum CEA and clinical status occurred in 145 of 157 (92%) patients.