A new furoquinolinone derivative, 1-(3'-hydroxypropyl)-4,6,8-trimethylfuro[2,3-h]quinolin-2(1H)-one (HPFQ, 4), was prepared, in which the nitrogen atom in position 1 carries a hydroxypropyl chain. The antiproliferative activity of HPFQ was studied in comparison with its analogue 1,4,6,8-tetramethylfuro[2,3-h]quinolin-2(1H)-one (FQ) and 8-methoxypsoralen (8-MOP). By incubation in the dark, HPFQ, although retaining antitopoisomerase II activity, appeared less effective than FQ. Upon UVA irradiation, HPFQ produced little amounts of singlet oxygen, but detectable levels of superoxide anion; like FQ, HPFQ induced numbers of DNA-protein cross-links, but no interstrand cross-links in mammalian cells. The HPFQ phototoxicity was comparable to that of FQ and 8-MOP, while mutagenic activity, scored in two Escherichia coli strains, seemed much less remarkable.

Cell Division↗

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Can a mixed damage interfere with DNA-protein cross-links repair?

Some photochemical and photobiological properties of 4,5',8-trimethylpsoralen (TMP) have been studied in comparison with 1,4,6,8-tetramethyl-2H-furo[2,3-h]quinolin-2 one (FQ) and 8-methoxypsoralen (8-MOP). TMP and FQ can photobind to mammalian cell DNA in vivo, by UVA irradiation, forming DNA-protein cross-links (DPC), but only TMP shows a strong capacity of inducing interstrand cross-links (ISC). The mechanism of DPC formation was studied using the double irradiation method in Chinese hamster ovary (CHO) cells, and DPC were detected by alkaline elution. Both TMP and FQ induce covalent diadducts linking together DNA and proteins. Studying the formation of double strand breaks (DSB) in CHO cells we observed that TMP induced a low amount of DSB, similar to 8-MOP. TMP and 8-MOP induced chromosomal aberrations in CHO cells to the same extent, while FQ appeared to be more active. Our data suggest that the ISC induced by TMP could trap enzymes involved in DPC repair.

Animals↗

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Concurrent chemoimmunotherapy in metastatic clear cell sarcoma: a case report.

Clear cell sarcoma is a rare tumor with a poor prognosis. The therapeutic approach in the metastatic disease stage is controversial: to the authors' knowledge the use of concurrent chemoimmunotherapy has not been previously reported. We present a case of a 57-year-old male with metastatic clear cell sarcoma treated simultaneously with subcutaneous interferon-a 2b and six courses of chemotherapy according to the CyVEDIC regimen. Disease stabilization lasting 17 months was achieved.

Antineoplastic Combined Chemotherapy Protocols↗

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The furocoumarin photosensitizing effect on the virus-producing Graffi leukaemia cells.

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Age Factors↗

PubMedDate not supplied

Contribution of monofunctional adducts formed by furocoumarins with DNA to the inhibition of nucleic acids synthesis.

In addition to the bifunctional adducts (cross-linkages), that furocoumarins on radiation at 365 nm form in DNA, monofunctional adducts also proved able to inhibit the nucleic acid synthesis in Ehrlich ascites tumor cells.

Cell Line↗

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Psoralen photosensitization of L 1210 leukaemia cells: an approach to a new combined therapy.

Psoralen photosensitization of L 1210 cells has a strong effect on DNA and RNA syntheses and this result appears connected with the psoralen photobinding to DNA. Protein synthesis is less sensitive and its inhibition seems due to a different photochemical interaction, very likely to the psoralen photobinding to RNA. A combined therapy using cyclophosphamide and L 1210 cells psoralen-photoinactivated was performed after the leukaemia transplant, showing a significant decrease in mortality, even in comparison with the simple treatment with the alkilating drug.

Animals↗

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T2 phage sensitization by linear and angular furocoumarins.

T2 bacteriophage sensitization has been studied using two furocoumarins capable of linking covalently to DNA to the same extent but producing different damages, psoralen and 4,5'-dimethylangelicin. Psoralen is a well-known linear furocoumarin capable of inducing in DNA both monoadducts and cross-links; 4,5'-dimethylangelicin is a new angular compound known as a pure monofunctional reagent. In the sensitization of T2 mature virions both drugs proved very active, yielding survival curves practically superimposable; on the contrary, in the experiments with the T2 vegetative form, i. e. its DNA inside the host, 4,5'-dimethylangelicin resulted much less effective, resembling the picture observed in the inactivation of the host bacteria. This result did not appear related to an enhancement of DNA repair by a Weigle effect. The different killing activity of 4,5'-dimethylangelicin can be explained supposing that this drug is capable of inducing cross-links in T2 DNA inside the virus core, in which it exists in a very folded form, but not in the same DNA after injection into the host bacteria.

DNA, Viral↗

PubMedDate not supplied

Comparison of CEA, MCA, CA 15-3 and CA 27-29 in follow-up and monitoring therapeutic response in breast cancer patients.

In order to define the most useful tumor marker panel in breast cancer patients' follow-up and in monitoring treatment response, serological levels of CEA, MCA, Ca 15-3 and Ca 27-29 were evaluated in 220 patients. 180 patients had no evidence of disease (NED) after primary treatment, and 40 had metastases at first diagnosis time; in a 4 years follow-up, 30 of the NED patients relapsed, and were then included in the group of metastatic patients subjected to anticancer treatment. Overall sensitivity in metastatic patients was: CEA 40%, MCA 35%, Ca 15-3 79%, Ca 27-29 70%, with the highest percentages and mean values in liver and bone localizations. Combination of Ca 15-3 and Ca 27-29 improved sensitivity in bone lesion (85% vs 80%), in locoregional relapses only association with CEA increased sensitivity (60% vs 40%). Ca 15-3 and Ca 27-29 values increased on average 3 months before clinical diagnosis. In treated patients there was a better correlation with a clinical course of disease for Ca 15-3 and Ca 27-29 (both 81%) as compared to the other determined markers.

Adult↗

PubMedDate not supplied

Studies on the photosensitizing properties of angelicin, an angular furocoumarin forming only monofunctional adducts with the pyrimidine bases of DNA.

The bioligical photosensitizing properties of furocoumarins are due to the formation of adducts with the pyrimidine bases of DNA under irradiation with long wavelength ultraviolet light. The greatest importance is attributed to the difunctional adducts, which form cross-linkings between the 2 strands of DNA. As angelicin, photoreacting with DNA, forms only monofunctional adducts, and therefore no cross-linkings, its photosensitizing properties have been studied in order to evaluate the ability of monofunctional adducts to produce biological effects. The results obtained studying the inhibition of DNA, RNA and protein synthesis in Ehrlich ascite tumor cells after irradiation in the presence of angelicin and psoralen (for a comparison), and the inhibition of the ability of identically treated cells to transmit the tumor showed a remarkable ability of monofunctional adducts to produce biological effects.

Animals↗

PubMedDate not supplied

[Totally implantable venous access systems. Analysis of complications].

UNLABELLED: Totally implantable central venous access devices (Port-a-Cath, PaC) allow better treatment of cancer patients, with safe administration of chemotherapeutic agents, and are well accepted by the patients. The aim of the present paper is to analyze the complications of the different implant techniques on the basis of a personal experience of 92 central venous access devices. MATERIAL AND METHODS: A total of 92 PaC (Port-a-Cath, Pharmacia: Celsite Braun) have been implanted in 88 patients between August 1992 and June 1995 for cancer treatment. Age ranged between 19 and 79 years (median 52 years), 56 were male and 32 women. PaC have been implanted by percutaneous cannulation of the subclavian vein, with Seldinger technique, in 34 cases; by venous cutdown respectively on the cephalic vein in 46 cases, the jugular vein in 7 cases, the basilar vein in 4 and the saphenous vein in 1 case. Four patients experienced a double implant. In 84 cases the implant was done under local anesthesia, while in 8 required general anesthesia, during operation for the primary neoplasm. RESULTS: A total of 7 complications were experienced (7.6%, 7/92): 4 sepsis and 3 mechanical. No cases of pnx were observed. Sepsis occurred after 29, 45, 64, 401 days of implantation respectively, and culture demonstrated S. aureus in 2 cases, and E. coli and Klebsiella oxytoca in 1 case each. Mechanical complication comprehends 2 cases of catheter dislodgement and 1 case of port rotation. No complications were noticed in case of implant during surgery for primary cancer (8 cases). In 7 cases the procedure has been converted from cephalic vein cutdown to percutaneous cannulation of the subclavian vein due to anatomic reasons (13.2%, 7/53). Five PaC have been explanted for complications. DISCUSSION: On the basis of the personal experience we think that PaC are of easy implant, with few complications and of good acceptance from the patients. We prefer venous cutdown on cephalic vein as implant technique because of avoidance of pnx or bleeding complications. Percutaneous puncture of subclavian vein is useful for implantation during major surgery, because less time consuming, and in case of anatomical anomalies fo the cephalic vein. Basilic vein cutdown has been utilized exclusively for esthetic reason in young people, to avoid the scar in the upper thoracic region. Alternative implant techniques has been employed in special conditions, such as catheter position in the inferior v.cava, or early in our experience (internal jugular vein). A total of 7 complication have been reported (7.6%), 4 sepsis and 3 mechanical (2 dislodgement, 1 rotation). Sepsis were not related to implant technique, presenting on day 29, 45, 64 and 401 respectively; all required the explant of the PaC as a treatment. Mechanical complications are related to surgical technique; all required re-exploration with 1 explant and 2 reposition of the PaC. In PaC positioning during surgery for primary cancer (8 cases) no morbidity has been reported. All but the 5 PaC explanted were functioning until patient's need; maximum length reported is 42 months.

Adult↗