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G Canti

Publications and source records attributed to G Canti.

At least 19 recordsLinked to original sources
PubMed2001

Rapamycin increases the cellular concentration of the BCL-2 protein and exerts an anti-apoptotic effect.

The immunosuppressant rapamycin, an immunophilin-binding antibiotic, has been studied in follicular B-cell lymphoma lines that express the highest level of the BCL-2 protein. The growth rate of human follicular B-cell lymphoma lines was slowed more efficiently than that of other human B-cell lines or non-B-cell lines. This effect was dependent on the arrest of cells in the G(1) phase; the number of apoptotic cells was not increased. Rapamycin inhibited apoptosis or caspase activation induced by cytotoxic drugs, whereas caspase activation by doxorubicin was not inhibited. The increase in the cellular concentration of BCL-2 protein was related to its concentration in the steady state and was unrelated to the amount of bcl-2 mRNA. The increase of BCL-2 level in the cells rather than its level in the steady state may be important for drug resistance. The biochemical target of rapamycin, the mTOR kinase, may be a candidate sensitising agent for chemotherapy. This effect of rapamycin shows that G(1) arrest and protection from apoptosis are combined events susceptible to regulation by pharmacological means.

Antibiotics, Antineoplastic↗
PubMed2001

Effects of photodynamic therapy on the absorption properties of disulphonated aluminum phthalocyanine in tumor-bearing mice.

Time-resolved reflectance spectroscopy was performed on tumor-bearing mice, administered with disulphonated aluminum phthalocyanine (AlS(2)Pc, 5 mg/kg body weight), before, during and after photodynamic therapy. This allowed us to evaluate the absorption spectrum of AlS(2)Pc in vivo from 610 to 700 nm, and to investigate how the therapeutic irradiation affects it. Two tumor locations (intraderma on the back and intramuscular in the leg), and two uptake times (3 and 12 h) were considered. As already observed previously, the absorption spectrum of AlS(2)Pc in vivo is centered at 680-685 nm. The irradiation causes a blue-shift of the measured line shape, more or less marked depending on the experimental conditions. A reduction in absorption is also often observed upon illumination with therapeutic light doses.

Absorption↗
PubMed2000

Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin.

BACKGROUND AND OBJECTIVE: Fluorescence techniques can provide powerful noninvasive means for medical diagnosis, based on the detection of either endogenous or exogenous fluorophores. The fluorescence of delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has already shown promise for the diagnosis of tumors. The aim of the study was to investigate the localization of skin tumors after the topical application of ALA, by detecting the PpIX fluorescence either in the spectral or in the time domain. STUDY DESIGN/MATERIALS N AND METHODS: Two fluorescence imaging systems were used to identify basal cell carcinomas of the skin in humans, after topical application of 20% ALA ointment. Both systems rely on the comparison between the exogenous and the endogenous fluorescence, performed either in the spectral domain or in the time domain. The first system works by using three images acquired through different spectral filters, whereas the second one measures the spatial map of the average fluorescence lifetime of the sample. RESULTS: A clear demarcation of skin malignancies was successfully performed in vivo noninvasively with both fluorescence imaging systems. CONCLUSION: The two complementary approaches considered in the present study show promise for skin tumor detection and delineation based on specific fluorescence features.

Adult↗
PubMed2000

Fluorescence imaging during photodynamic therapy of experimental tumors in mice sensitized with disulfonated aluminum phthalocyanine.

A fluorescence imaging system was used to monitor the emission of disulfonated aluminum phthalocyanine (AlS2Pc) during the photodynamic therapy (PDT) of murine tumors. Cells of the MS-2 fibrosarcoma were injected in mice in two compartments in order to cause the development of tumors in different host tissues. Two drug doses and two uptake times were considered. Moreover, the fluorescence of the AlS2Pc was excited using two wavelengths on the opposite sides of the absorption peak to detect a possible change in the absorption spectrum of the sensitizer induced by the PDT. In the tumors, the treatment induces a variation of the fluorescence intensity: in some mice a mild photobleaching takes place, in others a fluorescence enhancement occurs. Which effect predominates depends on the experimental conditions, even though a large spread of data was found amongst mice of the same group. In all mice, independently of the drug dose, uptake time or tumor compartment, a marked increase in the fluorescence signal takes place at the borders of the irradiated area. To quantify this effect we evaluated the ratio between the fluorescence intensities in the peritumoral area and in the tumor itself. This ratio increases monotonically during the PDT, showing a different behavior with the two excitation wavelengths. This indicates that the AlS2Pc absorption spectrum shifts toward shorter wavelengths as a result of the irradiation.

Animals↗
PubMed1998

Antitumor efficacy of the combination of photodynamic therapy and chemotherapy in murine tumors.

Photodynamic therapy (PDT) is based on the administration of tumor-localizing photosensitizers followed by light exposure of the tumor mass. The photocytotoxic effects are mainly caused by the generation of singlet oxygen. Recently, PDT has been proposed for use in combination with anticancer chemotherapy with a view to exploiting any additive antitumor effect. We investigated the effect of PDT with photoactivated aluminum disulfonated phthalocyanine (AlS2Pc) combined with the antiblastic drugs Adriamycin (ADR) and cisplatinum (CDDP) on murine tumors. Mice bearing L1210 leukemia and P388 lymphoma were treated with ADR or CDDP and subsequently treated with PDT. Low chemotherapy doses were ineffective, but the combination of antiblastic drugs + PDT had a significantly additive antitumor effect. In conclusion, with this combined therapy we were able to greatly reduce the effective doses of antiblastic drugs, thus lowering their toxic effects on normal host tissues.

Animals↗
PubMed1997

Fluorescence lifetime imaging of experimental tumors in hematoporphyrin derivative-sensitized mice.

Tumor detection has been carried out in mice sensitized with hematoporphyrin derivative (HpD) by measuring the spatial distribution of the fluorescence lifetime of the exogenous compound. This result has been achieved using a time-gated video camera and a suitable mathematical processing that led to the so-called "lifetime images." Extensive experimental tests have been performed on mice bearing the MS-2 fibrosarcoma or the L1210 leukemia. Lifetime images of mice show that the fluorescence decay of HpD is appreciably slower in the tumor than in healthy tissues nearby, allowing a reliable detection of the neoplasia. The lengthening of the lifetime in tumors depends little on the drug dose, which in our experiments could be lowered down to 0.1 mg/kg body weight, still allowing a definite tumor detection. In order to ascertain the results achieved with the imaging apparatus, high-resolution spectroscopy, based on a time-correlated single photon counting system, has also been performed to measure the fluorescence lifetime of the drug inside the tumor and outside. The outcomes obtained with two techniques are in good agreement.

Animals↗
PubMed1996

A bcl-2/IgH antisense transcript deregulates bcl-2 gene expression in human follicular lymphoma t(14;18) cell lines.

The 14;18 chromosome translocation, characteristic of most human follicular B-cell lymphomas, juxtaposes the bcl-2 gene with the IgH locus, creating a bcl-2/IgH hybrid gene. By mechanisms that are still under investigation, this event increases the cellular levels of the bcl-2 mRNA and thereby induces an overproduction of the antiapoptotic BCL-2 protein which is likely responsible for neoplastic transformation. In an effort to identify potential upregulators of bcl-2 activity in t(14;18) cells, we found, by strand-specific RT-PCR, a bcl-2 antisense transcript that is present in the t(14;18) DOHH2 and SU-DHL-4 but not in the t(14;18)-negative Raji and Jurkat lymphoid cell lines, and thus appears to be dependent on the bcl-2/IgH fusion. This antisense transcript is a hybrid bc1-2/IgH RNA, that originates in the IgH locus, encompasses the t(14;18) fusion site and spans at least the complete 3' UTR region of the bcl-2 mRNA. To achieve some insight into its biological function, we treated the t(14;18) DOHH2 cell line with oligonucleotides (ODNs) by specifically targeting the bc1-2/IgH antisense strand. These ODNs lowered bcl-2 gene expression, inhibited neoplastic cell growth by inducing apoptosis. We would like to propose the hypothesis that the bc1-2/IgH antisense transcript may contribute, by an unknown mechanism, to upregulation of bcl-2 gene expression in t(14;18) cells. The possibility has been considered that the hybrid antisense transcript mask AU-rich motifs present in the 3' UTR of the bcl-2 mRNA characterized in other genes as mRNA destabilizing elements.

Apoptosis↗
PubMed1996

In vivo absorption spectrum of disulphonated aluminium phthalocyanine in a murine tumour model.

The absorption spectrum of aluminum phthalocyanine with an average disulphonation of 2.1 (hereafter called disulphonated aluminum phthalocyanine, A1S2Pc) was measured in vivo in a murine tumour model by means of time-resolved reflectance. Mice bearing the L1210 leukaemia were administered 2.5 or 5 mg/kg body weight (b.w.) of A1S2Pc intraperitoneally. Reflectance measurements were performed in the 650-695 nm range before and 1, 4 and 7 h after the drug administration. Fitting of the data with the diffusion theory allowed us to assess the absorption coefficient in both conditions (i.e. before and after). As a difference between the latter and the former data, the in vivo absorption spectrum of A1S2Pc was evaluated. 1 h after the administration of 2.5 mg/kg b.w. A1S2Pc, the absorption peak was centred at 685 nm, red-shifted about 15 nm with respect to the spectrum in aqueous solution. For the lower dose, the absorption line shapes 4 and 7 h after the administration remained very similar. The red shift of the absorption spectrum is consistent with the therapeutic efficacy of the photodynamic therapy which was measured at 672, 685 and 695 nm, and proved to be maximum at 685 nm for both the L1210 leukaemia and the MS-2 fibrosarcoma. With the higher drug dose, the absorption spectra taken from different animals showed significant differences. In particular, in some mice the line shape was similar to that measured with 2.5 mg/kg b.w., while in other subjects it showed a broadening or a second peak at shorter wavelengths. Measurements on some animals were performed also 18 and 24 h after the injection of 5 mg/kg b.w., leading to no time evolution or to a progressive line shape narrowing.

Animals↗
PubMed1996

Oligonucleotides induce apoptosis restricted to the t(14;18) DHL-4 cell line.

Most human follicular B-cell lymphomas are associated with t(14;18) chromosome translocation that joins the bcl-2 gene with the IgH locus. This hybrid gene causes upregulation of BCL-2 protein expression, endowing cells with survival advantage. Although early BCL-2 overexpression is definitely responsible for immortalization/transformation, its exact role in the overt transformation as well as in the maintenance of the tumor phenotype is not known. The capacity of oligodeoxynucleotides (ODN) to modulate gene expression specifically has been exploited to downregulate the overexpression of BCL-2 protein in the SU-DHL-4 human follicular B-cell lymphoma line by the use of sense ODN or antisense ODN or antisense ODN designed to encompass the unique nucleotide sequence in the fusion region of the hybrid transcript. The specific downregulation of the bcl-2 transcript and of the relevant BCL-2 protein in the treated cells activated programed cell death and inhibited growing cells. The antitumor activity was restricted to the DHL-4 cell line carrying the specific nucleotide sequence at the bcl-2/IgH joining region. Thus, DHL-4 lymphoma cells derived from the acute phase of human follicular B-cell lymphoma, although endowed with additional activated oncogenes, were growth inhibited by bcl-2 downregulation with additional activated oncogenes, were growth inhibited by bcl-2 downregulation in a genetically restricted fashion. The biological activity was exerted exclusively by ODNs synthesized in the sense orientation. The sense ODNs have been proposed to anneal the hybrid bcl-2/IgH antisense RNA as identified in this study.

Amino Acid Sequence↗
PubMed1995

Efficacy of photodynamic therapy against doxorubicin-resistant murine tumors.

Photodynamic therapy (PDT) is a relatively new cancer treatment modality that employs light excitation of a photosensitizer to yield cytotoxic oxygen-related species. In the present study we explored whether PDT would have therapeutic effect against doxorubicin-resistant murine tumors. We compared the efficacy of PDT with aluminium disulphonated phthalocyanine (A1S2Pc) and laser light on the doxorubicin-sensitive murine tumors, B16 melanoma (B16), L1210 leukemia (L1210), P388 lymphoma (P388) and the corresponding doxorubicin-resistant lines (B16/Dx, L1210/Dx and P388/Dx). Mice bearing L1210-L1210/Dx, P388-P388/Dx and B16-B16/Dx, were treated with 5 mg/kg of A1S2Pc and laser light (100 mW/cm2 x 10 min of exposure) or with doxorubicin (10 or 12 mg/kg i.v.). The results show that PDT is active versus all tumors while doxorubicin is effective only against the three sensitive tumor lines (L1210, P388 and B16). These observations suggest that PDT might be a beneficial alternative treatment for drug-resistant tumors.

Animals↗
PubMed1995

Study of porphyrin fluorescence in tissue samples of tumour-bearing mice.

A time-gated fluorescence-imaging technique was applied to study the distribution of sensitizer in porphyrin-treated tumour-bearing mice. The animals were administered with either haematoporphyrin derivative (HpD) or Photofrin and sacrificed 4 or 12 h later. Fluorescence images were acquired from tumour, skin, muscle, fat, brain, lymph node, bowel and bone of both treated and untreated mice. The results obtained with HpD and Photofrin are similar. In images acquired 30 ns after excitation a bright exogenous fluorescence allows clear detection of the tumour. Nevertheless, the images show that porphyrins localize with different concentrations in all the examined tissues except the brain. Moreover, an appreciable long-living endogenous emission was observed in the bone.

Animals↗
PubMed1995

delta-Aminolevulinic acid induced fluorescence in tumour-bearing mice.

The potential of protoporphyrin IX fluorescence induced by the systemic administration of delta-aminolevulinic acid (ALA) for the detection of tumours was tested in three different murine models (MS-2 fibrosarcoma, L1210 leukaemia, and Lewis lung carcinoma). Time-gated fluorescence images were acquired up to 4 h after the intraperitoneal injection of ALA (200 mg (kg body mass (BM))-1). For comparison images were acquired also after the administration of 25 mg (kg BM)-1 of haematoporphyrin derivative. The latter drug was characterized by better localization in the tumour area, leading to higher fluorescence contrast between neoplastic mass and surrounding healthy tissue, and consequently was preferable for tumour diagnosis in all the models under study.

Aminolevulinic Acid↗
PubMed1994

Antitumor immunity induced by photodynamic therapy with aluminum disulfonated phthalocyanines and laser light.

Photodynamic therapy (PDT) is systemic administration of tumor localizing photosensitizers and subsequent irradiation with light of the appropriate wavelength. The combination of drug uptake in malignant tissues and selective delivery of laser-generated light provides effective therapy, with efficient tumor cytotoxicity and minimal normal tissue damage. There have been few studies of the effects of photoactivated photosensitizers on the host immune response. Since immunity is important in the control of tumor growth and spread, we have examined, in our laboratory, the effects of photoactivated phthalocyanines on the antitumor immune response. Immunosuppressed and normal mice bearing the MS-2 fibrosarcoma treated with 5 mg/kg of aluminum disulfonated phthalocyanine (AIS2Pc) and then the tumor mass exposed to laser light (100 mW/cm2 x 10 min) or treated with surgical excision of the tumor survived indefinitely, with no difference between the different groups. The survivors, tumor-free 100 days after the treatment modalities described above, were rechallenged with the parental MS-2. Some groups of surviving animals were immunosuppressed with cyclophosphamide before the injection of the tumor. Resistance to rechallenge was evidenced only in normal surviving animals cured by PDT, while the immunodepressed surviving animals and animals cured by surgery died of tumor. Finally, mice, cured by PDT and tumor-free, rechallenged with L1210 and P388 murine leukemias did not survive. These results suggest that a potential and specific 'antitumor immunity' is induced by PDT with photoactivated AIS2Pc.

Animals↗
PubMed1994

Absorption spectrum of hematoporphyrin derivative in vivo in a murine tumor model.

Time-resolved reflectance was used to measure the absorption spectrum of hematoporphyrin derivative (HpD) in vivo in a murine tumor model. Reflectance measurements were performed in the 600-640 nm range on mice bearing the L1210 leukemia. Then the animals were administered 25 mg/kg body weight of HpD intraperitoneally. One hour later the reflectance measurements were repeated. Fitting of the data using the diffusion theory allowed assessment of the absorption coefficient before and after the administration. As a difference between the latter and the former data, the in vivo absorption spectrum of HpD was evaluated. Maximum absorption was measured at 620-625 nm. Similar spectral behavior was obtained for HpD in solution in the presence of low-density lipoproteins.

Animals↗
PubMed1993

Time-gated fluorescence imaging for the diagnosis of tumors in a murine model.

A system for time-gated fluorescence imaging was used to perform measurements on tumor-bearing mice treated with hematoporphyrin derivative (HpD). The aim of the study was to define the potential of this technique in the diagnosis of tumors by taking advantage of the long fluorescence lifetime of the exogenous dye with respect to the decay times of the natural fluorescence. After the administration of three different drug doses (5, 10 and 25 mg/kg body weight), fluorescence images were acquired at various uptake times (from 2 h to 10 d), to determine the best instrumental conditions and experimental procedure for the detection of tumors in the murine model considered. The optimal fluorescence contrast between the tumor area and the surrounding healthy tissue was found at 12 h after the administration of either 5 or 10 mg/kg HpD and was anticipated at 8 h for the highest drug dose. In this optimum condition, the tumor region could be identified even after the injection of 5 mg/kg HpD. A better fluorescence contrast was always obtained in 15 ns-delayed images with respect to synchronous ones.

Animals↗
PubMed1992

Action spectrum of photoactivated phthalocyanine AIS2Pc in tumor bearing mice.

The action spectrum of disulfonated aluminum phthalocyanine (AIS2-Pc) as a photosensitizer for photodynamic therapy (PDT) was evaluated in vivo from 640 to 710 nm on two murine tumors with different biological properties. Mice bearing MS-2 fibrosarcoma and mice bearing the pigmented tumor B16 melanoma were injected with 5 mg/kg of AIS2Pc and irradiated with a light dose of 50 mW for 10 min for the MS-2 fibrosarcoma and of 100 mW for 10 min for the B16 melanoma. The action spectrum for both tumors presents a red shift with respect to the absorption spectrum of AIS2Pc in saline. The effectiveness is limited for short wavelengths (less than or equal to 655 nm for MS-2 and less than or equal to 660 for B16), whereas it increases at longer wavelengths and reaches its maximum at a peak (672 nm). For wavelengths beyond 672 nm the photodynamic activity remains up to 710 nm despite the significant decrease in absorption. The results obtained for both murine tumors seem therefore to indicate that an appreciable modification of the absorption spectrum takes place when AIS2Pc is incorporated into tissues following systematic administration.

Animals↗
PubMed1991

B16 melanoma response in vivo to photochemotherapy with mitoxantrone and red light.

The cytocidal activity of light-activated mitoxantrone in mice bearing B16 melanoma was investigated. Mice inoculated with 10(6) tumor cells on day 0 were i.p. injected with 1 mg/kg body weight of mitoxantrone on days 1, 5 and 9 and exposed to 108 J/cm2 of suitably filtered red light from a halogen lamp on days 2, 6 and 10. The treatment significantly prolonged the median survival time compared to both therapy with mitoxantrone and with red light alone.

Animals↗