P Pani

Università degli studi di Cagliari, Cagliari, Sardinia, Italy

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Publications (95)390.53 Total impact

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    ABSTRACT: Many human solid cancers arise from focal proliferative lesions that long precede the overt clinical appearance of the disease. The available evidence supports the notion that cancer precursor lesions are clonal in origin, and this notion forms the basis for most of the current theories on the pathogenesis of neoplastic disease. In contrast, far less attention has been devoted to the analysis of the phenotypic property that serves to define these focal lesions, i.e. their altered growth pattern. In fact, the latter is often considered a mere morphological by-product of clonal growth, with no specific relevance in the process. In the following study, evidence will be presented to support the concept that focal growth pattern is an inherent property of altered cells, independent of clonal growth; furthermore, it will be discussed how such a property, far from being merely descriptive, might indeed play a fundamental role in the sequence of events leading to the development of cancer. Within this paradigm, the earliest steps of neoplasia should be considered and analysed as defects in the mechanisms of tissue pattern formation.
    No preview · Article · Feb 2009 · Histology and histopathology
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    ABSTRACT: The retrorsine (RS)-based model for massive liver repopulation was laid on the hypothesis that transplanted cells can proliferate in the recipient liver if the growth capacity of endogenous hepatocytes is persistently impaired. In order to directly test this hypothesis, we examined the long-term response to 2/3 partial hepatectomy (PH) in rats pretreated with RS, according to the protocol for liver repopulation. Rats were given RS or saline and 4 weeks later they underwent PH; they were killed up to 16 weeks thereafter. Liver weights, liver DNA, and protein content were significantly lower in the RS group throughout the experimental time considered (e.g., at 16 weeks post-PH relative liver weight was 1.99 +/- 0.30% in RS group vs. 3.06 +/- 0.5% in controls). Regenerative nodules were present in RS-treated livers; they occupied about 3% of the liver at 2 weeks post-PH and this value increased to nearly 50% at 8 weeks and to > 95% at 16 weeks. In conclusion, RS-treated rat liver is unable to recover its original mass for several months following PH, despite the development of regenerative nodules. This long-lasting effect is likely to contribute to the growth of transplanted hepatocytes, leading to massive liver repopulation.
    No preview · Article · Dec 2008 · Cell Transplantation
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    ABSTRACT: Liver repopulation by transplanted normal hepatocytes has been described in a number of experimental settings. Extensive repopulation can also occur from the selective proliferation of endogenous normal hepatocytes, both in experimental animals and in the human liver. This review highlights the intriguing association between clinical and experimental conditions related to liver repopulation and an increased risk for development of hepatocellular carcinoma. It is suggested that any microenvironment that is able to sustain the clonal growth of normal transplanted (or endogenous) hepatocytes is also geared to select for the emergence of rare resistant cells with an altered phenotype. Whereas the first pathway leads to liver repopulation with normal histology, the latter results in the growth of focal proliferative lesions and carries an increased risk of neoplastic disease. The implications of this association are discussed, both in terms of pathogenetic significance and possible therapeutic exploitation.
    Full-text · Article · May 2008 · American Journal Of Pathology
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    ABSTRACT: Transplantation of isolated hepatocytes in rats treated with retrorsine (RS) results in massive repopulation of the host liver. In this study, the long-term fate of hepatocytes transplanted into RS-treated recipients was followed for up to two years. Dipeptidyl-peptidase type IV-deficient (DPPIV) Fischer 344 rats were given two injections of RS (30 mg/kg), followed by transplantation of 2 million hepatocytes, isolated from a syngenic, DPPIV donor. Extensive (91+/-7%) liver replacement by transplanted hepatocytes was observed in animals sacrificed 18 months posttransplantation. Similar levels of repopulation persisted at two years (87+/-5%). No evidence of preneoplastic and/or neoplastic evolution of the transplanted cell population was present in the RS-treated and repopulated livers at any time point considered. Furthermore, serum parameters related to hepatocyte function and integrity were in the normal range. In control groups given cell transplantation in the absence of prior treatment with RS, only small clusters of donor-derived, DPPIV hepatocytes were discerned. These results indicate that liver repopulation in this model is largely stable, persisting for up to two years and allowing for a normal liver function. In addition, no increased risk of neoplastic transformation appears to be associated with the process of liver repopulation for as long as over two thirds of the life span of the recipient animal.
    No preview · Article · Dec 2006 · Transplantation
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    ABSTRACT: Cancer increases with age and often arises from the selective clonal growth of altered cells. Thus, any environment favoring clonal growth per se poses a higher risk for cancer development. Using a genetically tagged animal model, we investigated whether aging is associated with increased clonogenic potential. Groups of 4-, 12-, 18-, and 24-month-old Fischer 344 rats were infused (via the portal vein) with 2x10(6) hepatocytes isolated from a normal syngenic 2-month-old donor. Animals deficient in dipeptidyl-peptidase type IV (DPP-IV-) enzyme were used as recipients, allowing for the histochemical detection of injected DPP-IV+ cells. Groups of animals were sacrificed at various times thereafter. No growth of DPP-IV+ transplanted hepatocytes was present after either 2 or 6 months in the liver of rats transplanted at young age, as expected. In striking contrast, significant expansion of donor-derived cells was seen in animals transplanted at the age of 18 months: clusters comprising 7-10 DPP-IV+ hepatocytes/cross-section were present after 2 months and were markedly enlarged after 6 months (mean of 88+/-35 cells/cluster/cross-section). These results indicate that the microenvironment of the aged liver supports the clonal expansion of transplanted normal hepatocytes. Such clonogenic environments can foster the selective growth of pre-existing altered cells, thereby increasing the overall risk for cancer development associated with aging.
    Preview · Article · Nov 2006 · Aging Cell
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    Mariano Cadoni · Paolo Pani
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    ABSTRACT: We investigate the formation of acoustic horizons for an inviscid fluid moving in a pipe in the case of stationary and axi-symmetric flow. We show that, differently from what is generally believed, the acoustic horizon forms in correspondence of either a local minimum or maximum of the flux tube cross-section. Similarly, the external potential is required to have either a maximum or a minimum at the horizon, so that the external force has to vanish there. Choosing a power-law equation of state for the fluid, $P\propto \rho^{n}$, we solve the equations of the fluid dynamics and show that the two possibilities are realized respectively for $n>-1$ and $n<-1$. These results are extended also to the case of spherically symmetric flow.
    Preview · Article · Nov 2005 · Classical and Quantum Gravity
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    ABSTRACT: We reported massive liver repopulation by transplanted hepatocytes in rats given retrorsine (RS), a pyrrolizidine alkaloid which blocks proliferation of resident cells. In these studies, molecular alterations induced by RS on hepatocyte cell cycle were investigated. Animals were treated according to the protocol for liver repopulation, i.e. two injections of RS (30 mg/kg) followed by two-thirds partial hepatectomy (PH) and were sacrificed at various time points thereafter. Livers were analyzed for the expression of cell cycle-related genes. Prior to PH, increased cyclin D1 mRNA and protein levels were found in livers of RS-treated rats. Expression of PCNA was also increased; however, DNA synthesis was not significantly changed. Other cyclins, including cyclin B and cyclin E, were not induced. Cyclin D1 expression increased in controls post-PH and then declined by 48 h, as expected. By contrast, no such modulation of cyclin D1 levels was seen in RS group receiving PH and expression remained high at 48 h, without mitotic division. Exposure to RS is able to block cell cycle progression after cyclin D1 and PCNA induction, but prior to S phase. Such persistent block outside the resting phase may contribute to the selective replacement of resident cells during liver repopulation.
    No preview · Article · Oct 2005 · Journal of Hepatology
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    ABSTRACT: This study describes a nonisotopic polymerase chain reaction-reverse hybridization-based method (PCR-RH) for the one-step detection and genotyping of anogenital human papillomavirus (HPV) in a microwell format. HPV DNA was amplified and labeled by PCR using GP5+/GP6+ primers. Labeled amplicons were hybridized to 20 HPV type-specific capture probes anchored to the surface of plastic microwells and detected by an immunoenzymatic assay. Assay sensitivity was <50 pg labeled amplicon, and no cross-reactivity was observed, as determined by hybridizing serial dilutions of labeled PCR products to either matched or mismatched capture probes. The assay was tested on 66 clinical samples (23 specimens with normal histology, I fibropapilloma, 26 cervical intraepithelial neoplasia grade 1 [CIN1], 9 CIN2, and 7 CIN3) and compared with a method based on restriction fragment length polymorphism (RFLP) of PCR products. PCR-RH and PCR-RFLP performed equally well on clinical samples. The overall HPV detection rate was similar: 65.1% (43/66) for PCR-RH and 57.6% (38/66) for PCR-RFLP. HPV DNA was found in all CIN2 and CIN3 samples by both methods; however, PCR-RH detected more positives among normal biopsy samples and CINI cases. Overall, there was good agreement between the two genotyping methods, but RH yielded fewer cases with undetermined HPV genotype.
    No preview · Article · Sep 2001 · Diagnostic Molecular Pathology
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    ABSTRACT: We recently have shown that selective growth of transplanted normal hepatocytes can be achieved in a setting of cell cycle block of endogenous parenchymal cells. Thus, massive proliferation of donor-derived normal hepatocytes was observed in the liver of rats previously given retrorsine (RS), a naturally occurring alkaloid that blocks proliferation of resident liver cells. In the present study, the fate of nodular hepatocytes transplanted into RS-treated or normal syngeneic recipients was followed. The dipeptidyl peptidase type IV-deficient (DPPIV(-)) rat model for hepatocyte transplantation was used to distinguish donor-derived cells from recipient cells. Hepatocyte nodules were chemically induced in Fischer 344, DPPIV(+) rats; livers were then perfused and larger (>5 mm) nodules were separated from surrounding tissue. Cells isolated from either tissue were then injected into normal or RS-treated DPPIV(-) recipients. One month after transplantation, grossly visible nodules (2--3 mm) were seen in RS-treated recipients transplanted with nodular cells. They grew rapidly, occupying 80--90% of the host liver at 2 months, and progressed to hepatocellular carcinoma within 4 months. By contrast, no liver nodules developed within 6 months when nodular hepatocytes were injected into the liver of recipients not exposed to RS, although small clusters of donor-derived cells were present in these animals. Taken together, these results directly point to a fundamental role played by the host environment in modulating the growth and the progression rate of altered cells during carcinogenesis. In particular, they indicate that conditions associated with growth constraint of the host tissue can drive tumor progression in vivo.
    Preview · Article · Jul 2001 · Proceedings of the National Academy of Sciences
  • S. Laconi · P. Pani · E. Laconi

    No preview · Article · Apr 2001 · European Journal of Cancer
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    ABSTRACT: A strategy for hepatocyte transplantation was recently developed whereby massive replacement of the recipient liver is achieved after a combined treatment with retrorsine, a pyrrolizidine alkaloid, and partial hepatectomy. We now investigated whether liver repopulation could occur in this animal model in the absence of any exogenous growth stimuli (eg, partial hepatectomy) for the transplanted cells. Dipeptidyl-peptidase type IV-deficient (DPPIV-) rats were used as recipients. Rats were given two injections of retrorsine (30 mg/kg each, 2 weeks apart), followed by transplantation of 2 x 10(6) hepatocytes isolated from a normal, syngeneic, DPPIV+ donor. At 2 weeks after transplantation, clusters of DPPIV+ hepatocytes occupied 3.3 +/- 0.9% of host liver, increasing to 38.2 +/- 6.3% at 2 months, and to 65.9 +/- 8.8% at 5 months. By 1 year, >95% of the original hepatocytes were replaced by donor-derived cells. Serum parameters related both to hepatocyte function and integrity (including glucose, bilirubin, total proteins, cholinesterase, alanine aminotransferase, and alkaline phosphatase) were in the normal range in retrorsine-treated and repopulated animals. These results provide further insights toward developing strategies for effective liver repopulation by transplanted hepatocytes with reduced toxicity for the host and potential clinical applicability.
    Preview · Article · Feb 2001 · American Journal Of Pathology
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    ABSTRACT: Genotyping of Human papillomavirus (HPV) is an important step in the clinical evaluation of the oncogenic risk associated with HPV infection of cervical mucosa. The purpose of this work was to develop a fast PCR-reverse-hybridization assay (PCR-RH) for the simultaneous detection and genotyping of anogenital HPVs. HPV DNA from cervical biopsies was amplified by consensus primer-PCR. Digoxigenin-labeled PCR products were hybridized to type-specific probes anchored to the surface of plastic microwells and revealed by an ELISA system. The method was tested on 115 clinical samples (81 koilocytic atypias, 11 CIN1, 10 CIN2, 12 CIN3 and 1 squamous carcinoma). HPV DNA was found in 56.7% koilocytic atypias, in 90.9% of CIN1 and in 100% of CIN2 and higher-grade lesions. Thus, PCR-RH is sensitive, rapid, easy-to-perform and readily applicable to the routine analysis of a large number of samples.
    No preview · Article · Jan 2001 · Pathologica
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    ABSTRACT: This study examines the effect of a stress-associated condition on chemical hepatocarcinogenesis in the rat. Rats were given diethylnitrosamine (200 mg/kg. b.w., i.p.), followed, 1 week later, by three cycles of immobilization at room temperature. Two weeks after the last cycle they were treated according to the resistant hepatocyte protocol. At 4 weeks after selection, mean size of glutathione-S-transferase 7-7 positive foci/nodules was increased in the immobilized group (0.82+/-0.22 vs. 0.25+/-0.04 mm(2) in controls). Furthermore, at the end of 1 year 10/13 animals (77%) developed hepatocellular carcinoma in the former group, while only 6/14 (43%) incidence of cancer was found in controls. These results indicate that exposure to restraint stress early during carcinogenesis enhances the development of chemically-induced hepatocellular carcinoma in the rat.
    No preview · Article · Jan 2001 · Cancer Letters
  • Ezio Laconi · Paolo Pani · Emmanuel Farber
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    ABSTRACT: Phenotypic resistance, acquired early in carcinogenesis, has an established role in the pathogenesis of cancer in well-characterised experimental systems, and possibly also has a role in the origin of human cancer. It has been suggested that sunlight, an established risk factor for human skin carcinogenesis, is able to induce rare altered cells resistant to toxicity and to favour their clonal expansion via toxic effects exerted on normal keratinocytes. Other major risk factors for human neoplasia, including smoking and ageing, may also act partly through imposition of a constrained growth environment in the target organ to favour the emergence of altered resistant cells. Strategies aimed at counteracting this constrained environment could be effective in attenuating the force that sustains clonal expansion of altered cells.
    No preview · Article · Jan 2001 · The Lancet Oncology
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    ABSTRACT: Human Papillomavirus (HPV) infection is considered an important risk factor for the development of cervical carcinoma. The aim of this work was to detect and genotype HPV DNA in cervical lesions from our Province. HPV DNA was amplified by polymerase chain reaction (PCR) and genotyped by restriction fragment length polymorphism (RFLP) analysis. A total of 101 biopsies (43 koilocytic atypias, 20 CIN1, 19 CIN2, 17 CIN3 and 2 squamous carcinomas) were analyzed. HPV DNA was found in 41.8% of koilocytic atypias, in 95.0% of CIN1 and 100% of CIN2 and higher grade lesions. Only high risk genotypes were found in CIN2-3 and invasive carcinomas. HPV 16 was the most prevalent type in both CIN1 and CIN2-3 and the only HPV type found in situ and invasive carcinomas. HPV type 51 was found in 21.0% of CIN1 but it was rare in CIN2 and absent in more advanced lesions.
    No preview · Article · Sep 2000 · Pathologica
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    ABSTRACT: We have designed an experimental model in which transplantation of normal hepatocytes into rats previously treated with retrorsine (a naturally-occurring pyrrolizidine alkaloid) results in near-complete replacement of the recipient liver by donor-derived cells. Two/thirds partial hepatectomy was found to be essential for this process to occur. To probe this finding, in the present study we describe the kinetics of liver regeneration in response to partial hepatectomy in rats given retrorsine. Six-weeks-old male Fisher 344 rats received retrorsine (2 injections of 30 mg/kg each, i.p., 2 weeks apart), or the vehicle. Four weeks after the last injection, partial hepatectomy was performed and rats were killed at 1, 2, 3, 6, and 15 days thereafter. At time zero, i.e. prior to partial hepatectomy, liver weight and total liver DNA content were significantly lower in retrorsine-treated animals compared to controls (DNA content: 19.2+/-1.7 vs. 25.7+/-1.1 mg/liver). Diffuse megalocytosis (enlarged hepatocytes) was present in the group exposed to retrorsine. By day 3 post-partial hepatectomy liver DNA content in control animals had more than doubled compared to day 1 values (20.2+/-1.5 vs. 8.8+/-1.2), while very little increase was seen in retrorsine-treated rats at the same time points (7.6+/-0.4 vs. 6.1+/-0.2). At 2 weeks after partial hepatectomy, total DNA content returned close to normal levels in the control group (26.9+/-1.0 mg/liver); however, the value was still very low in animals receiving retrorsine (9.1+/-0.7). Data on BrdU labeling were consistent with this pattern and indicated that DNA synthesis following partial hepatectomy was largely inhibited in the retrorsine group. Similarly, no mitotic response was observed in hepatocytes following partial hepatectomy in animals exposed to retrorsine. These results clearly indicate that retrorsine exerts a strong and persistent cell cycle block on hepatocyte proliferation. Further, these results are in agreement with the hypothesis that selective proliferation of transplanted hepatocytes in retrorsine-treated animals is dependent, at least in part, on the persistent cell cycle block imposed by the alkaloid on endogenous parenchymal cells.
    No preview · Article · Jan 2000 · Journal of Hepatology
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    ABSTRACT: Caloric restriction has been associated with a delay in the development of both spontaneous and induced neoplasia. In contrast, cycles of fasting/refeeding were shown by us and others to enhance the incidence of early lesions during chemical carcinogenesis in rat liver. The present, long-term study was undertaken to establish whether such a diffential effect would also extend to the later phases of cancer development, until the overt appearance of neoplasia. Male Fischer 344 rats were initiated with a single dose of diethylnitrosamine (DENA, 200 mg/kg i.p.) and starting 1 week later they were either exposed to three cycles of fasting (3 days) followed by refeeding (11 days) or were fed continuously. Seven weeks after DENA administration the rats were exposed to the resistant hepatocyte model of the liver tumor promotion protocol. All animals were killed 1 year after initiation. Incidence of hepatocellular carcinoma was 2-fold higher in the fasted/refed group compared with the controls (72 versus 36%). In addition, cancers were also larger and of higher histological grade in the former group, with one animal showing metastases to the lungs, while no metastases developed in control animals. Fasting caused a decrease in total liver DNA (from 25.2 +/- 1.1 to 16.5 +/- 1.1 mg after 3 days) which was associated with a decrease in hepatocyte labeling index and mitotic activity and high levels of single cell death (apoptosis). In contrast, a sharp increase in hepatocyte proliferation was observed on day 2 of refeeding and this was more pronounced in glutathione S-transferase 7-7 positive foci compared with surrounding liver (10.2 +/- 2.3 versus 4.6 +/- 0.8%). Such a proliferative wave was associated with a sharp decline in the incidence of cell death. It is concluded that fasting/refeeding performed early after initiation accelerates the development of chemically induced hepatocellular carcinoma in the rat.
    Preview · Article · Nov 1999 · Carcinogenesis
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    ABSTRACT: We have recently developed a new model of extensive liver repopulation by transplanted hepatocytes following exposure to pyrrolizidine alkaloids. In the present study, the effect of 2/3 partial hepatectomy (PH) and that of a potent direct liver mitogen, lead nitrate, were compared in their ability to modulate the kinetics of liver repopulation. Fischer 344 rats deficient in enzymatic activity for dipeptidyl-peptidase IV (DPPIV-) were used as cell transplantation recipients. They were given 2 doses of the pyrrolizidine alkaloid retrorsine (30 mg/kg, i.p.), 2 weeks apart, followed 2 weeks later by transplantation of 2 x 10(6) hepatocytes (via the portal vein), freshly isolated from a normal congeneic DPPIV+ donor. PH was carried out or a single injection of lead nitrate (100 micromol/kg, i.v.) was administered 2 weeks post-transplantation. Liver samples obtained at different time points post-treatment were processed histochemically for DPPIV activity. The percent of liver sections occupied by DPPIV+ hepatocytes was <1% at the time of PH or lead nitrate administration. In animals which underwent PH, it increased to 33.4+/-5.7% at 2 weeks and to 55.6+/-8.5% at 1 month. However, in animals receiving lead nitrate, these percentages were only 3.3+/-1.3% at 2 weeks and 16.2+/-3.9% at 1 month. Repeated injections of lead nitrate had no additional effect. Further experiments indicated that an acute mitogenic response to lead nitrate was present in transplanted cells, while resident hepatocytes were inhibited by retrorsine. These results indicate that direct mitogenic signals (such as those induced by lead nitrate), and compensatory signals (such as those elicited by PH), are not equally effective on kinetics of liver repopulation in this system. The possible reasons for these differential effects are discussed.
    No preview · Article · Sep 1999 · Journal of Hepatology
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    ABSTRACT: The ascites hepatoma Yoshida AH130 causes in the host a rapid and progressive body weight loss, associated with reduced food intake, and protein and lipid hypercatabolism. Because insulin regulates glucose as well as lipid and protein metabolism, we suggest that the observed alterations are at least in part secondary to hypoinsulinemia and/or to the increase of counterregulatory hormones in AH130-bearing rats. To verify this hypothesis, controls with free access to food (n = 4), controls with free access to food plus insulin (107 micromol. kg body wt-1. d-1) (n = 4), controls pair-fed to the tumor-bearing rats (n = 4), pair-fed controls treated with insulin (n= 4), tumor hosts (n = 9), and tumor hosts treated with insulin (n = 6) were used. The Yoshida ascites hepatoma cells ( approximately 10(8) cells/rat) were inoculated intraperitoneally. Daily food intake and body weight were measured; insulin was injected starting the day of tumor implantation for 6 d. The metabolism of both cholesterol and lipids was investigated in tumor cells, and ascitic fluid and blood serum were investigated at the end of treatment. Insulin prevented the reduction of food intake (19 +/- 0.6 vs. 13 +/- 0.4 g/d, P < 0.01; AH130 hosts treated and not treated with insulin, respectively), the loss of body weight (202 +/- 12 vs. 135 +/- 9 g, P < 0.01), lowered the circulating triglycerides (48.3 +/- 4.9 vs. 84.5 +/- 7.1 mmol/L, P < 0.01), and free fatty acids (561 +/- 47 vs. 989 +/- 54 mmol/L (P < 0.01), while corrected the decrease of adipose lipoprotein lipase activity (1,240 +/- vs. 300 +/- pmol FA, P < 0.01) observed in AH130 hosts. Moreover, insulin prevented the decrease in HDL cholesterol (13.2 +/- 0.8 vs. 9.3. +/- 0.7 mmol/L, P < 0.01) and significantly increased hepatic cholesterol synthesis as evaluated by 14C-acetate incorporation into cholesterol, in both liver (3,337 +/- 245 vs. 830 +/- 115 Bq/g, P < 0.01) and AH130 cells (11,676 +/- 1,693 vs. 4,196 +/- 527 Bq/10(6) cells, P < 0.01). Thus insulin treatment ameliorated many metabolic derangements, with a lengthening of rats survival time (7 +/- 1 vs. 11 +/- 1 d, P < 0.05) without significantly stimulating tumor growth. These data, together with our previous observations on the effectiveness of insulin on protein turnover perturbations, suggest that many metabolic alterations occurring during cancer cachexia can be avoided by the administration of this hormone.
    No preview · Article · Mar 1999 · Journal of Nutrition
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    ABSTRACT: Genetically marked hepatocytes from dipeptidyl peptidase (DPP) IV+ Fischer 344 rats were transplanted into the liver of DPPIV- mutant Fischer 344 rats after a combined treatment with retrorsine, a pyrrolizidine alkaloid that blocks the hepatocyte cell cycle, and two-thirds partial hepatectomy. In female rats, clusters of proliferated DPPIV+ hepatocytes containing 20 to 50 cells/cluster, mostly derived from single transplanted cells, were evident at 2 weeks, increasing in size to hundreds of cells per cluster at 1 month and 1000 to several thousand cells per cluster at 2 months, representing 40 to 60% of total hepatocyte mass. This level of hepatocyte replacement remained constant for up to 1 year, the duration of experiments conducted. In male rats, liver replacement occurred more rapidly and was more extensive, with transplanted hepatocytes representing 10 to 15% of hepatocyte mass at 2 weeks, 40 to 50% at 1 month, 90 to 95% at 2 months, 98% at 4 months, and 99% at 9 months. Transplanted hepatocytes were integrated into the parenchymal plates, exhibited unique hepatic biochemical functions, and fully reconstituted a normal hepatic lobular structure. The extensive proliferation of transplanted cells in this setting of persistent inhibition of resident hepatocytes represents a new general model to study basic aspects of liver repopulation with potential applications in chronic liver disease and ex vivo gene therapy.
    Preview · Article · Aug 1998 · American Journal Of Pathology

Publication Stats

2k Citations
390.53 Total Impact Points


  • 1975-2008
    • Università degli studi di Cagliari
      • • Department of Biomedical Science
      • • Department of Physics
      Cagliari, Sardinia, Italy
  • 1993-2000
    • University of Toronto
      • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
  • 1994
    • Università degli Studi del Sannio
      Benevento, Campania, Italy