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Biomedical subjects

G Giannini

Publications and source records attributed to G Giannini.

At least 37 records · Page 2Linked to original sources
PubMed2001

The early growth response gene EGR-1 behaves as a suppressor gene that is down-regulated independent of ARF/Mdm2 but not p53 alterations in fresh human gliomas.

PURPOSE: EGR-1 is an immediate early gene with diverse functions that include the suppression of growth. EGR-1 is down-regulated many cancer cell types, suggesting a tumor suppressor role, and may critically involve the p53 pathway. The aim of this work was to measure the expression of EGR-1 and the p16/INK4a/ARF-Mdm2-p53 pathway status in fresh human gliomas. EXPERIMENTAL DESIGN: Thirty-one human gliomas with different grades of malignancy were investigated for Egr-1 mRNA and the protein expression, frequency, and spectrum of p53 gene mutations, mdm2 gene amplification, and p16/INK4a/ARF allele loss. RESULTS: The amplification of Mdm2 and the deletion of the p16/INK4a gene was found in 3 and 5 cases, respectively, whereas mutations of p53, including two novel mutations, were observed in 10 other cases. The three types of changes occurred strictly mutually exclusively, emphasizing that these genes operate in a common pathway critical to glioma progression. EGR-1 mRNA was significantly down-regulated in astrocytomas (14.7 +/- 5.1%) and in glioblastomas (33.6 +/- 10.0%) versus normal brain. Overall, EGR-1 mRNA was strongly suppressed (average, 15.2 +/- 13.9%) in 27 of 31 cases (87%), independent of changes in p16/INK4a/ARF and Mdm2; whereas 4 of 31 cases with residual EGR-1 expression as well as the highest EGR-1 variance segregated with p53 mutations. Immunohistochemical analyses confirmed the suppression of EGR-1 protein. CONCLUSIONS: These results indicate that EGR-1 is commonly suppressed in gliomas independent of p16/INK4a/ARF and Mdm2 and that suppression is less crucial in tumors bearing p53 mutations, and these results implicate an EGR-1 growth regulatory mechanism as a target of inactivation during tumor progression.

Blotting, Northern↗
PubMed2001

High dose of idarubicin-based regimen for diffuse large cell AIDS-related non-Hodgkin's lymphoma patients: a pilot study.

BACKGROUND AND OBJECTIVES: Intensive chemotherapy (CHT) in AIDS-related non-Hodgkin's lymphoma (AIDS-NHL patients) is a vexing problem. Our purpose was to evaluate the feasibility of a high dose idarubicin (HD-IDA)-based regimen in diffuse large cell (DLC) AIDS-NHL patients. DESIGN AND METHODS: Fourteen stage I-IV untreated DLC AIDS-NHL patients with a performance status <3 and no prior AIDS-related diseases received CIOD: cyclophosphamide, HD-IDA (25 mg/m2 in 8 patients, 20 mg/m2 in 6 patients) vincristine and dexamethasone plus granulocyte colony-stimulating factor (G-CSF) and prophylaxis against infections. The outcomes measured were: rate of response, disease-free survival (DFS), overall survival (OS) and the impact of chemotherapy on immunologic and virological parameters. RESULTS: Complete response was achieved in 13/14 cases (response rate: 93%). The median time of response and survival was 33 (range 5-79) and 35.5 (range 6-84) months, respectively. At 60 months the DFS and OS were 71% and 44%, respectively. CIOD with idarubicin 20 mg/m2 was better tolerated than that with 25 mg/m2 and was administered with a higher mean average-relative-dose-intensity (95.38+/-7% vs 83.35+/-15.59%, p=0.0001). Opportunistic infections were more frequent in patients with a baseline CD4 <100 than those with >100 cells/microL (4/5 vs 1/9: p=0.0229). After 3 CIOD courses the mean CD4 cells/microL was significantly lower (p=0.001) and the mean HIV.1 RNA load was significantly higher (p=0.045) than at baseline. INTERPRETATION AND CONCLUSIONS: The proposed chemotherapeutic regimen for AIDS-related non-Hodgkin's lymphoma is feasible in an outpatient setting in selected patients with relatively well-preserved immune function.

Adult↗
PubMed2000

A randomized trial comparing the introduction of ritonavir or indinavir in 1251 nucleoside-experienced patients with advanced HIV infection.

ISS-IP1, a multicenter, randomized, 48-week open trial, was designed to compare the introduction of ritonavir or indinavir in patients with previous nucleoside experience and CD4+ cell counts below 50/mm3. Concomitant antiretroviral treatment with nucleoside analogs was allowed. Primary efficacy measures were survival and time to a new AIDS-defining event or death, analyzed through the whole period of observation by the intention-to-treat approach. Primary toxicity measures were time to treatment discontinuation and adverse events, grade at least 3/serious, analyzed by an on-treatment approach. Evaluation-of efficacy also included CD4+ cell and RNA response. The trial enrolled 1251 patients in 5 months. At baseline, mean CD4+ cell count was about 20 cells/mm3 and mean HIV RNA copy number was 4.9 log10/ml in both groups. Overall, 402 patients in the ritonavir group and 250 patients in the indinavir group permanently discontinued the assigned treatment (relative risk, 1.96; 95% CI, 1.68-2.30; p = 0.0001), with most of this difference dependent on a higher number of discontinuation for adverse events in the ritonavir group. After a mean follow-up of 307 days (ritonavir, 304; indinavir, 309), 124 deaths (ritonavir, 61; indinavir, 63; relative risk, 0.96; 95% CI, 0.67-1.36; p = 0.80) and 330 new AIDS-defining events (ritonavir, 170; indinavir, 160; relative risk, 1.05; 95% CI, 0.85-1.31; p = 0.60) were observed. CD4+ cell counts increased in both groups in patients still receiving treatment, with about 100 cells gained by week 24 and 150 cells gained by week 48. Body weight also increased over time in both groups. Analysis of RNA response showed a decrease of 1.5 log10 or higher in both treatment groups. Overall, 400 patients in the ritonavir group and 338 patients in the indinavir group developed at least one grade 3/serious new adverse event during follow-up (relative risk, 1.48; 95% CI, 1.28-1.72; p = 0.0001). Favorable CD4+ cell and RNA responses at 24 and 48 weeks were observed in both groups of patients remaining on treatment. Indinavir showed slightly better effects in sustaining RNA, CD4+ cell, and body weight responses. Ritonavir and indinavir results were comparable in terms of clinical outcome (survival and AIDS-defining events).

Adult↗
PubMed2000

Quality of life outcomes of combination zidovudine- didanosine-nevirapine and zidovudine-didanosine for antiretroviral-naive advanced HIV-infected patients.

OBJECTIVES: To evaluate the quality of life outcomes in antiretroviral-naive patients randomized to zidovudine plus didanosine versus zidovudine plus didanosine plus nevirapine for treatment of advanced HIV disease (the Istituto Superiore di Sanità 047 trial). DESIGN: A 48-week randomized, double-blind trial. METHODS: Sixty patients were enrolled and evaluated over 24 weeks. Quality of life was assessed using a modified version of the Medical Outcomes Study-HIV Health Survey. For analysis, we calculated two summary scores reflecting the physical (PHS) and the mental (MHS) components of health. RESULTS: Although the three-drug combination was superior at inducing immunologic and virologic responses, the two-drug regimen was superior for both PHS and MHS, especially at week 8 where differences were both statistically and clinically significant (5.8 and 9.2 points, respectively, P< 0.02 for both). Quality of life changes paralleled trends in body weight and Karnofsky performance status score. CONCLUSION: Although a three-drug antiretroviral therapy regimen was superior in terms of short term virologic/immunologic response, the two-drug regimen was better in terms of quality of life. In general, triple therapy remains the most effective treatment option. However, quality of life assessments can yield results that may be discordant with and complementary to those obtained using conventional endpoints. Comparative trials should collect a comprehensive range of outcome measures, including patient-reported quality of life, in order to provide clinicians and patients with additional information that may influence treatment decisions.

Adult↗
PubMed2000

Plasma HIV-1 copy number and in vitro infectivity of plasma prior to and during combination antiretroviral treatment.

Some studies on untreated patients have shown a general correlation between plasma HIV copy number and plasma infectivity in in vitro models. Recent observations also indicate that HIV-RNA level is an important predictor of perinatal transmission and may also have a role in heterosexual transmission. To further analyse the correlation between HIV viral load and plasma infectivity, we studied the relationship between HIV-1 plasma copy number and plasma infectivity prior to and during treatment with antiretroviral combination regimens in HIV-1 infected adults. Plasma infectivity was assessed in vitro by coculture of plasma from HIV-positive patients with PHA-stimulated fresh PBMC from uninfected donors. A positive plasma isolation, in almost all cases (43/45) and irrespective of treatment status, was associated with an HIV viral load higher than 100000 copies per ml, with higher plasma HIV-1 RNA values in isolation-positive samples compared with isolation-negative samples (median values, 710000 vs. 37500 copies per ml, respectively). SI and NSI strains had similarly high viral load values (470000 vs. 790000 copies per ml), but CD4 counts were lower in the SI phenotype group. Our data indicate that low levels of viral load are only exceptionally associated with isolation from plasma in the in vitro model we used. This observation confirms indirectly the presence of an association between viral load and infectivity. The requisite of a high plasma viral load in order to obtain infectivity (i.e. positivity of HIV isolation from plasma) also seems maintained under antiretroviral treatment, adding confidence in the conclusion that reductions in viral load translate into reduction of plasma infectivity. Due to the extreme complexity of factors determining transmission, a very prudent interpretation of the results is essential when information from experimental studies has to be transferred to clinical situations requiring assessment of risks or clinical decisions.

Adult↗
PubMed2000

PCR testing for HCV in anti-HCV negative blood donors involved in the so called HCV +ve post-transfusion hepatitis.

UNLABELLED: Although it is infrequent, post-transfusion HCV infection may occur if the donors blood is collected in the window period between exposure and anti-HCV detectability by ELISA testing. STUDY DESIGN: In these last years, despite of routine application of anti-HCV testing, our blood transfusion center has been involved in 53 cases of alleged post-transfusion HCV hepatitis and look-back programs were set up with the goal of finding out the donors possibly involved in viral transmission. Most of these patients were hematological cases with multiple transfusions given because of aplastic anemia (3 cases), leukemia with or without bone marrow transplantation (5/4 cases) but necessitating long-term platelet support, leukemia and solid cancer patients undergoing autologous PBSC transplantation (3/4 cases) and TTP (2 cases). Only 32 patients were of the simple medical or surgical type, 9 transfused because of cardiac or vascular surgery, 8 because of spine surgery, 5 for different diseases and 5 for different types of cancer surgery. Donor's infectivity was determined by ELISA anti-HCV testing, by recombinant immunoblotting assay, and by nucleic acid testing. RESULTS AND CONCLUSION: No donors out of 267 traced of a total of 359 involved was found with anti-HCV seroconversion, or positive on PCR testing. This suggests that the responsibility for HCV transmission can only hypothetically be related to blood or blood components and that other transmission routes should be found out.

Blood Donors↗
PubMed2000

Expression of the HMGI(Y) gene products in human neuroblastic tumours correlates with differentiation status.

HMGI and HMGY are splicing variants of the HMGI(Y) gene and together with HMGI-C, belong to a family of DNA binding proteins involved in maintaining active chromatin conformation and in the regulation of gene transcription. The expression of the HMGI(Y) gene is maximal during embryonic development, declines in adult differentiated tissues and is reactivated in most transformed cells in vitro and in many human cancers in vivo. The HMGI(Y) genomic locus is frequently rearranged in mesenchymal tumours, suggesting a biological role for HMGI(Y) gene products in tumour biology. HMGIs are both target and modulators of retinoic acid activity. In fact, HMGI(Y) gene expression is differentially regulated by retinoic acid in retinoid-sensitive and -resistant neuroblastoma cells, while HMGI-C participates in conferring retinoic acid resistance in some neuroblastoma cells. In this paper we show that HMGI and HMGY isoforms are equally regulated by retinoic acid in neuroblastoma cell lines at both RNA and protein levels. More importantly our immunohistochemical analysis shows that, although HMGI(Y) is expressed in all neuroblastic tumours, consistently higher levels are observed in less differentiated neuroblastomas compared to more differentiated ganglioneuromas, indicating that HMGI(Y) expression should be evaluated as a potential diagnostic and prognostic marker in neuroblastic tumours.

Antineoplastic Agents↗
PubMed2000

[Preoperative autologous blood donation and transfusion in gynecology].

BACKGROUND: Autologous transfusions reduce the risk of alloimmune and infectious complications of allogenic blood transfusions. We have evaluated preoperative autologous blood donation practice in relation to patients characteristics and surgical technique. METHODS: In the Obstetrics and Gynecology Department of Genoa University, we enrolled 462 patients in an autologous transfusion program during 1997. We did not analyze 105 patients who underwent minor surgery. Patients with hemoglobin lower than 11 g/dl or with other risks related to autotransfusion have been excluded; 284 (79.5%) patients have been able to make preoperative autologous blood donations. Patients who did not undergo predeposit have utilised type screen or cross reaction for a possible who did eterologous transfusion. We have analysed the two groups of patients for kind of pathology, for number of heterologous blood units used, for number of transfused patients and we have considered the mean of the units received by each of them. RESULTS: 44 of the 284 predeposited blood units were reinfused while 10 patients, who did not undergo predeposit, were transfused. Heterologous transfusion was done in 1.06% of the cases that underwent predeposit. Oncologic patients underwent predeposit in 83% of the cases. CONCLUSIONS: We have concluded that autologous blood donation reduces the risk of allogenic blood transfusion especially in oncologic surgery.

Adolescent↗
PubMed1999

HMGI(Y) and HMGI-C genes are expressed in neuroblastoma cell lines and tumors and affect retinoic acid responsiveness.

HMGI-C and HMGI(Y) are architectural DNA-binding proteins that participate in the conformational regulation of active chromatin. Their pattern of expression in embryonal and adult tissues, the analysis of the "pygmy" phenotype induced by the inactivation of the HMGI-C gene, and their frequent qualitative or quantitative alteration in experimental and human tumors indicate their pivotal role in the control of cell growth, differentiation, and tumorigenesis in several tissues representative of the epithelial, mesenchymal, and hematopoietic lineages. In contrast, very little information is available on their expression and function in neural cells. Here, we investigated the expression of the HMGI(Y) and HMGI-C genes in neuroblastoma (NB), a tumor arising from an alteration of the normal differentiation of neural crest-derived cells and in embryonal and adult adrenal tissue. Although HMGI(Y) is constitutively expressed in the embryonal and adult adrenal gland and in all of the NB cell lines and ex vivo tumors examined, its regulation appears to be associated to growth inhibition and differentiation because we observed that HMGI(Y) expression is reduced by retinoic acid (RA) in several NB cell lines that are induced to differentiate into postmitotic neurons, whereas it is up-regulated by RA in cells that fail to differentiate. Furthermore, the decrease of HMGI(Y) expression observed in RA-induced growth arrest and differentiation is abrogated in cells that have been made insensitive to this drug by NMYC overexpression. In contrast, HMGI-C expression is down-regulated during the development of the adrenal gland, completely absent in the adult individual, and only detectable in a subset of ex vivo NB tumors and in RA-resistant NB cell lines. We provide evidence of a causal link between HMGI-C expression and resistance to the growth arrest induced by RA in NB cell lines because exogenous HMGI-C expression in HMGI-C-negative and RA-sensitive cells is sufficient to convert them into RA-resistant cells. Therefore, we suggest that HMGI-C and HMGI(Y) may participate in growth- and differentiation-related tumor progression events of neuroectodermal derivatives.

Adrenal Glands↗
PubMed1999

Thrombospondin-1 is a mediator of the neurotypic differentiation induced by EGF in thymic epithelial cells.

Thymic epithelial cell component originates from cranial neural crest as well as from endoderm and ectoderm of the third pharyngeal pouch and branchial cleft. Epidermal growth factor (EGF) has been previously shown to play a crucial role in directing thymic epithelial cells toward a neural-oriented cell fate. To identify genes that are involved in the EGF-induced neurotypic differentiation of the thymic stroma-derived TC-1S cell line, we studied EGF-treated and untreated cells by RNA fingerprinting PCR-based differential screening. We obtained 23 distinct sequences including 18 known genes and 5 sequences previously unreported, which are currently under characterization. Here, we describe the involvement of one of the isolated genes, the thrombospondin-1, as a mediator of the neurotypic differentiation induced by EGF in TC-1S cells. We show that thrombospondin-1 mRNA and protein levels are increased by EGF. Moreover, exogenous thrombospondin-1 is able to enhance the outgrowth of neurite-like processes as well as the expression of neurofilaments and neural cell adhesion molecule in TC-1S cells. These observations suggest that the up-regulation of thrombospondin-1 synthesis induced by EGF contributes to the differentiation choice of thymic epithelial cells toward a neural fate, reminiscent of their neural crest origin.

Animals↗
PubMed1999

A randomized, double-blind trial on the use of a triple combination including nevirapine, a nonnucleoside reverse transcriptase HIV inhibitor, in antiretroviral-naive patients with advanced disease.

The immunologic and virologic activity of nevirapine in combination with two nucleosides (zidovudine [ZDV] and didanosine [ddI]) was evaluated in antiretroviral-naive patients with a CD4 count <200/mm3 or clinical AIDS. In all, 68 patients were enrolled in a 48-week double-blind, placebo-controlled trial. A group of 32 patients received ZDV + ddI + nevirapine, and 36 patients received ZDV + ddI. Primary efficacy parameters were the activity on HIV-1 RNA and on peripheral blood CD4+ cells, with differences between groups analyzed by the Wilcoxon's nonparametric two-sample test. Baseline RNA was high in both treatment groups (median values, 5.8 and 5.7 log10). RNA and CD4 responses were significantly higher with the triple combination (median RNA reductions, 2.69 versus 1.05 log10 at 24 weeks and 1.97 versus 1.20 log10 at 48 weeks; median CD4 increases, 81 versus 64 cells/mm3 at 24 weeks and 101 versus 27 cells/mm3 at 48 weeks). This study demonstrates that a triple combination of ZDV + ddI + nevirapine used as first-line regimen in antiretroviral-naive patients can induce sustained virologic and immunologic response in patients with low CD4 count or a previous diagnosis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Cascade filtration for TTP: an effective alternative to plasma exchange with cryodepleted plasma.

TTP remains enigmatic both in terms of etiology and management. The most recent approach is aggressive plasma exchange (PE) employing cryopoor plasma for replacement, based on the pathogenetic relevance given to exceedingly large Von Willebrand (VWF) multimers in the determination of the syndrome with normalization during remission. PE with fresh frozen plasma (FFP) is better than FFP infusion as shown by a recent Canadian study, supporting the theory that to treat TTP an offending circulating agent needs to be removed from the patient's plasma in contrast to the hypothesis that a missing factor is to be given along with FFP. A more recent hypothesis is supported by the results of studies published by the end of 1998 [Moake J, Chintagumpala M, Turner N et al. Blood 1994;84:490-97; Moake J, McPherson PD. Am J Med 1989;87: 3-9N] which would show that TTP is mediated by auto-antibodies to VWF-cleaving protease, or is the result of deficiency of the protease ascribed to abnormalities in its production, function or survival. Plasmapheresis without plasma infusion is relatively ineffective perhaps because it does not increase the protease activity. Cascade filtration (CF) is the autologous counterpart of plasmapheresis. It has been used by our group since 1980 to remove from patients plasma macromolecules such as VWF, fibrinogen, LDL and circulatory immune complexes (CIC). After secondary filtration, the autologous plasma has a composition which is very similar to that of allogeneic plasma after cryoprecipitation, a product which used in the management of TTP. Based on this knowledge, in 1994 we began to use CF in the treatment of TTP patients. In the beginning (7 patients) CF was combined with a decreasing number of conventional PEs using allogeneic plasma for substitution. Lately only CF with some plasma supplementation has been used in the last 9 cases. From a clinical point of view our 16 patients achieved remission after a number of treatments (11 +/- 7) that compares sufficiently well with those required by our historical control group of 47 cases (14 +/- 13). Of course the patient's exposure to allogenic plasma was significantly lower for patients in the CF only group (1.4 +/- 1.2 plasma U/session) compared to the PE + CF group (4.4 +/- 2.3 plasma U/session) or for the controls treated by PE only (10.8 +/- 4.6 plasma U/session). There were no deaths in the CF or PE + CF groups and no untoward effect was observed. On the contrary there were 5 deaths (1 on the day of presentation) in the PE group, and 1 HBV and 2 HCV infections as well as 4 severe allergic reactions to plasma proteins (or passive antibody infusion). We conclude that CF is presently the best treatment to offer to patients suffering from sporadic TTP and that CF may contribute to expanding the knowledge of the pathogenetic mechanisms of this uncommon multisystem disorder.

Adult↗
PubMed1999

Multicomponent collection (MCC) with the latest hemapheresis apparatuses.

BACKGROUND: Collection of multiple products including plasma, packed red blood cells (PBRC) and double units of platelets, is increasingly improving donor utilisation and decreasing blood transfusion costs. Total apheresis is the new trend in blood banking and both industry and physicians are progressively expanding their involvement in this field. During 1998, at our hemapheresis unit, we used three new apparatuses for multicomponent collection (MCC). These apparatuses vary in terms of principle, operation and specific capabilities, and thus knowledge of them is essential to match their characteristics with plateletapheresis needs. STUDY DESIGN: We reviewed all MCCs carried out in 1998 with MCS+, Trima and Excel-Pro cell separators. These apparatuses were evaluated in terms of platelet yield, white blood cell (WBC) contamination, efficiency per minute, platelet activation, and PBRC product quality. RESULTS: The three machines are compared in the following table [table in text]. CONCLUSIONS: MCC with the new apparatuses is well accepted by donors and personnel. There are no risks for the donors and, excluding ACD reactions and/or vaso/vagal attacks at the beginning of procedures, no severe reaction was seen. The quality and quantity of platelet products are good. When PRBC or a second platelets unit are collected, the cost of the kit is covered by this double product.

Blood Component Removal↗
PubMed1998

Saquinavir delays the emergence of zidovudine resistance in HIV-1 seropositive patients treated with combination therapy.

During a randomized double-blind study to assess the antiviral activity of saquinavir (SQV) alone or in combination with zidovudine (ZDV), the emergence of phenotypic resistance was evaluated in 44 patients treated with SQV (13 subjects), ZDV (14 subjects), and SQV plus ZDV (17 subjects). A significant (P< 0.05) lower CD4+ cell count and higher HIV RNA copy number at entry were found in six patients who developed resistant viral strain (3 to ZDV and 3 to SQV) during the first 4 months of treatment. After 1 year, drug-resistant strains (12 to ZDV and 14 to SQV) were isolated in 26 out of 37 patients. A significant higher number of patients treated with ZDV alone (10/13) harbored ZDV-resistant strains compared to patients treated by combination therapy (2/13); whereas more than 50% of patients had SQV-resistant strains aside from treatment. Early SQV-resistant strains were isolated in a limited number of patients treated with SQV alone (3/13). The rates of emergence of resistant strains during ZDV or SQV monotherapies are comparable. Combination therapy may delay the emergence of phenotypic resistance to either drugs in the short term and to ZDV, but not to SQV, at least after 1 year.

Anti-HIV Agents↗
PubMed1998

The growth arrest and downregulation of c-myc transcription induced by ceramide are related events dependent on p21 induction, Rb underphosphorylation and E2F sequestering.

Ceramide is an intracellular lipid mediator generated through the sphingomyelin cycle in response to several extracellular signals. Ceramide has been shown to induce growth inhibition, c-myc downmodulation and apoptosis. In this paper we examined the mechanism by which ceramide induces growth suppression and the role of the G1-CDK/pRb/E2F pathway in this process. The addition of exogenous, cell-permeable C2-ceramide to the Hs 27 human diploid fibroblast cell line resulted in a dose-dependent induction of the p21WAF1/CIP1/Sdi1 kinase inhibitor with reduction of cyclin-D1 associated kinase activity. Furthermore, significant dephosphorylation of pRb was observed, with increased association of pRb and the E2F transcription factor into a transcriptionally inactive complex. Ceramide was also capable of inhibiting the transcriptional activity of a CAT reporter vector driven by E2F binding sites containing c-myc promoter transfected into Hs 27 cells. The requirement of the pRb protein for ceramide-induced c-myc downregulation was supported by the failure of ceramide to inhibit promoter activity in HeLa cells, in which pRb function is abrogated by the presence of the E7 Papilloma virus oncoprotein, and in pRb-deleted SAOS2 AT cells. Ceramide-induced downregulation of the c-myc promoter was restored in SAOS2 #1 cells in which a functional Rb gene was reintroduced. Our studies demonstrate that pRb dephosphorylation, induced by ceramide, is at least partly necessary for c-myc downregulation, and therefore the CDK-Rb-E2F pathway appears to be a target for the ceramide-induced modulation of cell cycle regulated gene transcription.

Apoptosis↗