Biomedical subjects

Sergio Bernardini

Publications and source records attributed to Sergio Bernardini.

At least 19 recordsLinked to original sources

PubMed2007

Valproic acid induces apoptosis, p16INK4A upregulation and sensitization to chemotherapy in human melanoma cells.

It is known that melanoma develops as a consequence of multifactorial alterations. To date several studies indicate the effective implication of p16 as a tumor suppressor gene with a major role in either the development or progression of human melanoma. Deregulation of melanoma cell growth has been widely associated with mutations in the p16-cyclin D/cdk4-pRb pathway. Recently anticancer therapies are focused on restoration of p16 CDK inhibitory function and other proteins unregulated in melanoma cell cycle pathway (e.g., c-myc, p27). A combined strategy for restoration of normal homeostasis in the melanoma skin with targeted delivery of apoptosis-inducing agents does not seems to be far obtained. New class of antitumoral agents are emerging: histone deacetylase (HDAC) inhibitors have attracted much interest because of their ability to arrest cell growth, induce cell differentiation, and in some cases, induce apoptosis of cancer cells. Recently, attention has been focused on the ability of HDAC inhibitors to induce perturbation in cell cycle regulatory protein (e.g., p21(CIP1)) and down-regulation of survival signalling pathway. In the present study, we have examined the effect of valproic acid (VPA) on M14 human melanoma cell line. Here we observed that VPA induces cell cycle arrest and apoptosis sensitising melanoma cells to cis-platin and etoposide treatment. IC(50) dose (2.99 mM) of VPA was able to induce G(1) arrest (up to 75%) in association with upregulation of p16, p21 and cyclin-D1 related to Rb ipo-phosphorilation. In addition VPA activated apoptosis (50%) in M14 cells, when given alone or in combination with antitumoral agents. The ability of valproic acid to reestablished the G(1) pathway in melanoma cells suggests a potential application of VPA in melanoma therapeutic protocols.

Antineoplastic Agents↗

PubMed2007

Cleavage of cystatin C is not associated with multiple sclerosis.

Recently, Irani and colleagues proposed a C-terminal cleaved isoform cystatin C (12.5 kDa) in cerebrospinal fluid as a marker of multiple sclerosis. In this study, we demonstrate that the 12.5 kDa product of cystatin C is formed by degradation of the first eight N-terminal residues. Moreover, such a degradation is not specific in the cerebrospinal fluid of multiple sclerosis, but rather is given by an inappropriate sample storage at -20 degrees C. We conclude that the use of the 12.5 kDa product of cystatin C in cerebrospinal fluid might lead to a fallacious diagnosis of multiple sclerosis. Preanalytical validation procedure is mandatory for proteomics investigations.

Artifacts↗

PubMed2006

CSF markers in Alzheimer disease patients are not related to the different degree of cognitive impairment.

Standard markers in cerebrospinal fluid (CSF), as soluble amyloid beta 1-42 (Abeta1-42) and total tau protein (t-tau), may contribute to dementia subtypes diagnostic accuracy. Yet, their sensitivity to assess the different degree of cognitive deficit is not fully clarified. Our study analyses Abeta1-42 and t-tau CSF levels in different cohorts of Alzheimer's disease (AD) patients, distinguished as early AD (mild cognitively impaired subjects recently converted to AD), mild AD (MMSE<23; > or =18), and moderately advanced AD (MMSE<18). The control group was represented by age-matched patients affected by depressive pseudo-dementia. Reduced Abeta1-42 and increased t-tau CSF levels were confirmed as hallmarks of AD at any disease stage. In early AD patients, Abeta1-42 levels were already significantly low, if compared to the control group (336 vs 867 ng/L; p<0.0001). On the contrary, Abeta1-42 levels did not differ between AD subgroups, and in particular between mild to moderate AD. A significant progressive increase of t-tau concentration was found when comparing early AD (269 ng/L) to more advanced AD stages (468 ng/L and 495 ng/L for mild and moderate AD, respectively). Our findings confirm that the impairment of amyloidogenic cascade is an early, even pre-clinical process, but suggest that soluble Abeta1-42 concentration has a negligible correlation with the clinical progression. Conversely, t-tau concentration correlates with the transition towards marked cognitive impairment.

Aged↗

PubMed2006

Experimental analysis of lens-forming capacity in Xenopus borealis larvae.

Previously, the only anuran amphibians known to have the capacity to regenerate a lens after lentectomy were Xenopus laevis and Xenopus tropicalis. This regeneration process occurs during the larval life through transdifferentiation of the outer cornea promoted by inductive factors produced by the retina and accumulated inside the vitreous chamber. However, the capacity of X. tropicalis to regenerate a lens is much lower than that of X. laevis. This study demonstrates that Xenopus borealis, a species more closely related to X. laevis than to X. tropicalis, is not able to regenerate a lens after lentectomy. Nevertheless, some morphological modifications corresponding to the first stages of lens regeneration in X. laevis were observed in the outer cornea of X. borealis. This suggested that in X borealis the regeneration process was blocked at early stages. Results from histological analysis of X. borealis and X. laevis lentectomized eyes and from implantation of outer cornea fragments into the vitreous and anterior chambers demonstrated that: (i) in X. borealis eye, the lens-forming competence in the outer cornea and inductive factors in the vitreous chamber are both present, (ii) no inhibiting factors are present in the anterior chamber, the environment where lens regeneration begins, (iii) the inability of X. borealis to regenerate a lens after lentectomy is due to an inhibiting action exerted by the inner cornea on the spreading of the retinal factor from the vitreous chamber towards the outer cornea. This mechanical inhibition is assured by two distinctive features of X. borealis eye in comparison with X. laevis eye: (i) a weaker and slower response to the retinal inducer by the outer cornea; (ii) a stronger and faster healing of the inner cornea. Unlike X. tropicalis and similar to X. laevis, in X. borealis the competence to respond to the retinal factor is not restricted to the corneal epithelium but also extends to the pericorneal epidermis.

Animals↗

PubMed2006

Role of GSTP1-1 in mediating the effect of As2O3 in the Acute Promyelocytic Leukemia cell line NB4.

Arsenic trioxide (As2O3) is a highly effective agent in the treatment of acute promyelocytic leukemia (APL), whereas other hematopoietic tumors are less responsive to this agent and mechanisms underlying As2O3,-resistance are poorly understood. To better understand the complex network of GSH-related pathways in As2O3 sensitivity, we investigated the role of GSH and GSH-relevant enzymes in an APL cell line sensitive to As2O3 (NB4) and in a resistant subclone (AsR). Cell proliferation, viability, and apoptosis were investigated in NB4 cells before and after treatment with 1 muM As2O3 and in AsR cells. In these experimental cell models, GSTP1-1, JNK1 and JNK2 proteins were analyzed by immunoblotting, and a kinase assay for JNK1 was performed. GSH levels as well as the activities of the enzymes glutathione peroxidase, glutathione transferase, gamma-Glutamylcysteynilsinthetase and superoxide dismutase were measured. NB4 cells treated with As2O3 showed a high level of oxidative stress and an increase of GSH levels. GSTP1-1 polymerization and JNK1 activation were detectable after 24 h and were followed by an increase of the apoptotic rate starting at 72 h. Neither GSTP1-1 polymerization nor JNK activation was found in AsR cells that showed a very low apoptotic rate. Our results suggest that APL sensitivity to As2O3 might be, at least in part, mediated by the balance between association and dissociation of JNK from GSTP1-1, depending on the redox status of the cell. Further investigation is warranted to find a way to interfere with this balance, whenever it might represent a mechanism of drug resistance.

Antineoplastic Agents↗

PubMed2006

Acridine Orange based platinum(II) complexes inducing cytotoxicity and cell cycle perturbation in spite of GSTP1 up-regulation.

A series of new ionic Pt(II) complexes of general formula [Pt(II)(A)n(Cl)(AO)]X (A=en, NH3; n=1, 2; X-=BF4-, NO3-, PF6-, CF3SO3-), 1-5, containing Acridine Orange (AO) bound to the metal atom through the endocyclic N atom, have been tested in human melanoma cells (M14, JR8 and PLF2), human neuroblastoma cell line SH-SY5Y and its cis-platin resistant subline SH-SY5Yres. The Pt(II) compounds, and in particular complexes 1 and 4, exhibit higher cytotoxic activity at lower concentration compared to cis-DDP in melanoma cells, affecting cell growth behavior and causing cell cycle perturbation. Moreover, M14 and JR8 cell lines were not able to rescue the impairment due to the new Pt(II) complexes since perturbation of cell cycle phases and cell proliferation inhibition were found after 72 h of recovery time. In order to evaluate whether GSTP1 may play a role in chemo-resistance of our melanoma model, we investigated the effect of the treatment with these Pt(II) compounds on GSTP1 gene expression. Up-regulation of GSTP1, evaluated by Qreal-time PCR was observed after treatment with complexes 1 and 4, showing that the effect of these Pt(II) compounds is GSTP1 indipendent. The lack of resistance of the new Pt(II)-AO complexes and their cytotoxicity, cell growth and cell cycle recovery in melanoma cells provide the basis for the development of new platinum anticancer compounds, directed to those tumors that over express GSTs enzymes.

Acridine Orange↗

PubMed2006

Differential post-translational modifications of transthyretin in Alzheimer's disease: a study of the cerebral spinal fluid.

Transthyretin (TTR) is a 55 kDa homotetrameric protein. TTR in the cerebral spinal fluid (CSF) is primarily synthesized by the choroid plexus. TTR can bind to the beta-amyloid peptide and a number of familial amyloidosis diseases (familial amyloid polyneuropathy) have been associated with its allele variants. In a transgenic mice model overexpression of TTR was positively correlated with a neuroprotective effect from the pathogenic APPsw mutation. TTR has a free reactive sulphydryl moiety located on the Cys(10) residue which has been implicated to undergo a variety of oxidation reactions. To examine the neuroprotective role of TTR, we investigated the conjugated forms of TTR with cysteine (Cys) and cysteinglycine (CsyGly) in the CSF of 39 probable Alzheimer's disease (AD)-affected subjects and in a cohort of subjects without cognitive impairment (27 subjects). Linear MALDI-TOF MS experiments were employed to obtain high-resolution protein profiling of TTR isoforms. Nano-LC-TANDEM MS combined with reflectron MALDI-TOF-MS was used to unequivocally assign the investigated TTR-conjugate signals. Our results indicate a differential distribution of TTR-Cys and TTR-CysGly adducts. Both oxidized forms of TTR are significantly less abundant in the AD group (p = 0.0001). The investigated population (66 subjects) was then diagnosed using the ratio of conjugated TTR to free TTR in each subject. A sensitivity >90% and a specificity >70% were derived from a receiver operating characteristic curve when the overall cohort is analysed by the TTR-Cys signals. This manuscript is the first report describing the presence of differential post-translational oxidations of TTR in the CSF of AD patients.

Adult↗

PubMed2006

Valproic acid induces apoptosis in prostate carcinoma cell lines by activation of multiple death pathways.

Valproic acid is a well-known antiepileptic drug that was recently discovered to have a wide-spectrum antitumoral action in several tumors. In our work, we tested the proapoptotic activity of valproic acid in prostate cancer. Valproic acid-induced apoptosis was described by several in-vitro assays in three prostate cancer cell lines: two representing the prototype of advanced, clinically untreatable stages of prostate progression, PC3 and DU145, and one resembling a more differentiated androgen-sensitive tumor, LNCaP. We observed that valproic acid was a potent and early apoptotic inducer, mainly in less-differentiated prostate cancer cell lines. The molecular analysis of the apoptotic machinery involved in valproic acid action revealed a central role in Bcl-2 downmodulation. When prostate cancer cells were treated for a longer time with valproic acid, we detected an enhancement of Fas-dependent apoptosis associated with an overexpression in Fas and Fas ligand. Our data indicate that the use of valproic acid may be a suitable therapeutic agent in the control of prostate cancer progression and its action appears particularly relevant in the control of refractory stages of prostate cancer.

Antineoplastic Agents↗

PubMed2005

Pigmented epithelium to retinal transdifferentiation and Pax6 expression in larval Xenopus laevis.

This study examines the retinal transdifferentiation (TD) of retinal pigmented epithelium (RPE) fragments dissected from Xenopus laevis larvae and implanted into the vitreous chamber of non-lentectomized host eyes. In these experimental conditions, most RPE implants transformed into polarized vesicles in which the side adjacent to the lens maintained the RPE phenotype, while the side adjacent to the host retina transformed into a laminar retina with the photoreceptor layer facing the cavity of the vesicle and with the ganglionar cell layer facing the host retina. The formation of a new retina with a laminar organization is the result of depigmentation, proliferation and differentiation of progenitor cells under the influence of inductive factors from the host retina. The phases of the TD process were followed using BrdU labelling as a marker of the proliferation phase and using a monoclonal antibody (mAbHP1) as a definitive indicator of retina formation. Pigmented RPE cells do not express Pax6. In the early phase of RPE to retinal TD, all depigmented and proliferating progenitor cells expressed Pax6. Changes in the Pax6 expression pattern became apparent in the early phase of differentiation, when Pax6 expression decreased in the presumptive outer nuclear layer (ONL) of the new-forming retina. Finally, during the late differentiation phase, the ONL, which contains photoreceptors, no longer expressed Pax6, Pax6 expression being confined to the ganglion cell layer and the inner nuclear layer. These results indicate that Pax6 may have different roles during the different phases of RPE to retinal TD, acting as an early retinal determinant and later directing progenitor cell fate.

Animals↗

PubMed2005

Role of gamma-glutamyl cysteine synthetase (gamma-GCS) gene expression as marker of drug sensitivity in acute myeloid leukemias.

BACKGROUND: Elevated levels of glutathione (GSH) have been reported to play an important role in mediating chemoresistance in tumor cells. The regulation of gamma-glutamylcysteine synthetase (gamma-GCS) is one of the major determinants of GSH homeostasis. The aim of our study was to investigate gamma-GCS gene expression in patients affected by acute myeloid leukemia (AML). METHODS: A total of 64 AML samples, including 23 acute promyelocytic leukemia (APL or M3) cases, were included in the study. gamma-GCS mRNA levels were determined by real-time quantitative RT-PCR. All patients were evaluated at diagnosis, whereas post-treatment gamma-GCS mRNA levels were assessed at the end of the consolidation therapy in 16 cases. RESULTS: Our data showed that variable degrees of gamma-GCS expression were detectable in AML, likely reflecting disease heterogeneity; in particular, APL cases, compared to the other AML subsets, showed both significantly lower basal levels of gamma-GCS mRNA at presentation and significantly increased mRNA levels after treatment. CONCLUSIONS: Decreased levels of gamma-GCS leading to reduced GSH may at least in part explain the higher sensitivity of APL to chemotherapy.

Acute Disease↗

PubMed2005

AD with subcortical white matter lesions and vascular dementia: CSF markers for differential diagnosis.

We investigated whether the cerebrospinal fluid (CSF) biomarkers beta-amyloid 1-42 (Abeta1-42), total tau (t-tau) protein and tau protein phosphorylated at threonine 181 (p-tau181) could discriminate Alzheimer's disease (AD) from vascular dementia (VD) patients. CSF samples of Abeta1-42, t-tau, and p-tau181 were collected from probable AD (n=35), probable AD with white matter changes (WMC) indicative of concomitant cerebrovascular disorder (CVD, n=31), VD (n=20), and an age-matched subgroup of patients with other neurological disorders (OND) without cognitive impairment (n=24). AD patients showed very low Abeta1-42 levels (median=393 pg/ml). Abeta1-42, but not t-tau, differentiated AD from VD patients. However, the markers did not discriminate AD vs. AD plus WMC. In particular, both subgroups showed similar CSF biomarkers but they were significantly different from VD. ROC analysis showed that Abeta1-42 could discriminate AD from VD (AUC=0.85). The cutoff of 493 pg/ml gave sensitivity and specificity values of 77% and 80%, respectively. Similar results were obtained when Abeta1-42 was employed to discriminate AD with WMC from VD (95% specificity and 60% sensitivity, but with cutoff of 750 pg/ml). T-tau increased aspecifically in all cognitively impaired patients. P-tau181 performed better than t-tau in discriminating AD (with or without WMC) vs. VD. In conclusion, Abeta1-42 proved to be a valuable tool to discriminate AD vs. VD patients and possibly to improve diagnostic accuracy in clinical forms, improperly classified as "mixed dementia" based on radiological vascular lesions.

Aged↗

PubMed2005

Glutathione S-transferase P1 *C allelic variant increases susceptibility for late-onset Alzheimer disease: association study and relationship with apolipoprotein E epsilon4 allele.

BACKGROUND: Oxidative stress and neuronal cell death have been implicated in the pathogenesis of Alzheimer disease (AD). Considering that the glutathione transferase (GST) supergene family encodes isoenzymes that appear to be critical in protection against oxidative stress, we aimed at determining the various GSTP1, GSTM1, and GSTT1 polymorphisms and ApoE genotypes to investigate their role as susceptibility genes for late-onset AD (LOAD). METHODS: We included 210 LOAD patients and 228 healthy controls matched for age, sex, and educational level in our case-control genetic association study. GSTM1 and GSTT1 genotypes were studied by conventional PCR, whereas GSTP1 and ApoE genotypes were determined by real-time PCR on the LightCycler. RESULTS: We found a significant association between LOAD and the GSTP1*C allelic variant [odds ratio (OR) = 1.9; P < 0.05], but no association between the GSTM1 and GSTT1 deleted genotypes and LOAD. In addition, a preliminary result suggested that carriers of both the GSTP1*C and ApoE epsilon4 allelic variants were at increased risk of LOAD (OR = 19.98; P < 0.0001). CONCLUSION: The GSTP1*C allelic variant should be considered a candidate for LOAD, particularly in persons having the ApoE epsilon4 allelic variant, because the GSTP1 and ApoE gene products are implicated in oxidative stress and apoptosis processes leading to beta-amyloid-mediated neurodegeneration.

Age of Onset↗

PubMed2005

Idiopathic hypereosinophilic syndrome: a case evolving in B-lymphoblastic lymphoma.

Idiopathic hypereosinophilic syndrome (HES) is a rare disease characterized by tissue involvement and organ dysfunction due to abnormal eosinophil proliferation. Evolution of HES into myeloid or T-cell malignancies has been frequently reported. Here, we describe a case of HES that preceded the occurrence of a high-grade B-lymphoblastic lymphoma in which clonal evolution has been demonstrated at the molecular level.

Humans↗

PubMed2005

A quantitative method for the analysis of glycated and glutathionylated hemoglobin by matrix-assisted laser desorption ionization-time of flight mass spectrometry.

The quantization of glycated isoforms of hemoglobin has been increasingly used in clinical practice in recent years. Glycated hemoglobin is currently considered the most important measurement for long-term control of the glycemic state and it has become a reference tool for the management of diabetes. Glutathionylated hemoglobin is an increasingly clinically relevant covalent adduct of glutathione with beta chain of the globin and its concentration has been correlated with oxidative stress. We have developed an innovative technique based on linear mode matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry for quantitative analysis of hemoglobin species. This method was applied to the quantification of glycated and glutathionylated hemoglobin. A rigorous comparison was pursued to evaluate the analytical performances in quantifying glycated hemoglobin in comparison to an established high-performance liquid chromatography method. Our results indicated a complete equivalence between the two methods. The same analysis enabled the quantitative determination of the glutathionylated hemoglobin fraction. This isoform was investigated in an adult Italian population (184 individuals, 101 males and 83 females), indicating a bimodal distribution of this species. In fact 65.22% of screened individuals had glutathionylated hemoglobin levels lower than 0.50% while 34.78% had glutathionylated hemoglobin levels higher than 0.50%. A semiautomatic robotic procedure was developed for fast analysis of a large number of samples. This is the first report of a quantitative application of linear MALDI-TOF mass spectrometry for the determination of glutathionylated hemoglobin in blood samples. This method allows fast screening of this hemoglobin isoform, therefore opening the route to explore its specificity and sensitivity as a molecular biomarker.

Chromatography, High Pressure Liquid↗

PubMed2005

Lens-forming competence in the epidermis of Xenopus laevis during development.

In larval X. laevis the capacity to regenerate a lens under the influence of inductive factors present in the vitreous chamber is restricted to the outer cornea and pericorneal epidermis (Lentogenic Area, LA). However, in early embryos, the whole ectoderm is capable of responding to inductive factors of the larval eye forming lens cells. In a previous paper, Cannata et al. (2003) demonstrated that the persistence of lens-forming competence in the LA is the result of early signals causing lens-forming bias in the presumptive LA and of late signals from the eye causing cornea development. This paper analyzes 1) the decrease of the lens-forming capacity in ectodermal regions both near LA (head epidermis) and far from LA (flank epidermis) during development, 2) the capacity of the head epidermis and flank epidermis to respond to lens-competence promoting factors released by an eye transplanted below these epidermal regions, and 3) the eye components responsible for the promoting effect of the transplanted eye. Results were obtained by implanting fragments of ectoderm or epidermis into the vitreous chamber of host tadpoles and by evaluating the percentage of implants positive to a monoclonal antibody anti-lens. These results demonstrated that the lens-forming competence in the flank region is lost at the embryonic stage 30/31 and is weakly restored by eye transplantation; however, lens-forming competence in the head region is lost at the larval stage 48 and is strongly restored by eye transplantation. The authors hypothesize that during development the head ectoderm outside the LA is attained by low levels of the same signals that attain the LA and that these signals are responsible for the maintenance of lens-forming competence in the cornea and pericorneal epidermis of the larva. In this hypothesis, low levels of these signals slacken the decrease of the lens-forming competence in the head ectoderm and make the head epidermis much more responsive than the flank epidermis to the effect of promoting factors released by a transplanted eye. Results obtained after transplantation of eyes deprived of some components indicate that the lens and the retina are the main source of these promoting factors. The immunohistochemical detection of the FGFR-2 (bek variant) protein in the epidermis of stage 53 larvae submitted to eye transplantation at stage 46 showed that the eye transplantation increased the level of FGFR-2 protein in the head epidermis but not in the flank epidermis, indicating that the lens-forming competence in X. laevis epidermis could be related to the presence of an activated FGF receptor system in the responding tissue.

Animals↗

PubMed2005

A proteomic investigation into etoposide chemo-resistance of neuroblastoma cell lines.

Neuroblastoma, one of the most common pediatric solid tumors, originates from the peripheral sympathetic nervous system and is responsible for approximately 15% of all childhood cancer deaths. Among the several antineoplastic drugs used in neuroblastoma chemotherapeutic protocols, topoisomerase inhibitors (i.e., etoposide) represent the most commonly used. Several resistance mechanisms limit the clinical success of topoisomerase-targeting drugs, mainly reducing the ability of neoplastic cells to start programmed cell death when exposed to antineoplastic drugs. The aim of this study was to determine, by means of proteomics, potential markers of etoposide resistance in human neuroblastoma cell lines as well as to investigate protein levels and modifications possibly involved in the onset of resistance. The etoposide resistant clone showed overexpression of the following proteins: peroxiredoxin 1, beta-galactoside soluble lectin binding protein, vimentin (three protein spots), heat shock 27 kDa protein (two protein spots) and heterogeneous nuclear ribonucleoprotein K. In addition, we also found down-regulation of dUTP pyrophosphatase. This investigation might represent a first step towards the development of novel prognostic markers of neuroblastoma chemotherapy.

Antineoplastic Agents, Phytogenic↗

PubMed2005

Post-transcriptional regulation of Smad7 in the gut of patients with inflammatory bowel disease.

BACKGROUND & AIMS: Transforming growth factor (TGF)-beta1 is one of the most powerful endogenous negative regulators of inflammation. In patients with inflammatory bowel disease, despite abundant local TGF-beta1, there is a failure of TGF-beta-mediated negative regulation of nuclear factor kappaB activation and proinflammatory cytokine production because of increased intracellular expression of the endogenous inhibitor of TGF-beta1 signaling, Smad7. In this study, we examined the molecular mechanism underlying the induction of Smad7 in the human gut. METHODS: Whole intestinal mucosal and lamina propria mononuclear cell samples were analyzed for Smad7 by real-time polymerase chain reaction and Western blotting. Smad7 ubiquitination and acetylation, and interaction of Smad7 with the intrinsic histone acetyltransferase, p300, were examined by immunoprecipitation and Western blotting. The effect of p300 silencing on Smad7 expression was determined in Crohn's disease lamina propria mononuclear cells. RESULTS: We showed that Smad7 is not transcriptionally regulated in human gut but that its increase in patients with inflammatory bowel disease is due to posttranscriptional acetylation and stabilization by p300, which prevents Smad7 ubiquitination and degradation in the proteasome. Hence, Smad7 protein in cells from normal gut is ubiquitinated and rapidly degraded. In contrast, in inflamed gut, Smad7 is acetylated and not ubiquitinated, is not degraded, and can be decreased by short interfering RNA to p300. CONCLUSIONS: These results identify posttranslational protein modification as of importance in chronic gut inflammation in humans.

Acetylation↗

PubMed2005

Use of proteomics to study chemosensitivity.

Chemoresistance remains an unresolved problem in clinical oncology. Therefore it is important to identify molecular factors that lead to an understanding of the mechanisms of drug resistance in cancer cells. On the protein-expression level, this can be done using proteomics, which has become the focus of significant interest and research over the past decade. We describe an easy and practicable standardized technique that can be used to study global protein expression in chemosensitive and chemoresistant cancer cells to find candidate proteins that are potentially associated with the drug-resistant phenotype. As an example, fractionation of human neuroblastoma cells using two-dimensional polyacrylamide electrophoresis, spot detection, image analysis, and finally protein identification is illustrated.

Antineoplastic Agents↗