Hepatitis C virus genotype 4 and response to combination therapy with interferon-alpha2b plus ribavirin.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
S Bruno
Publications and source records attributed to S Bruno.
A retro-inverso peptide homologous to helix 1 of c-Myc is a potent and specific inhibitor of proliferation in different cellular systems.
In 1998 we reported that an L-peptide derived from H1 of c-Myc (Int-H1-S6A,F8A), linked to an internalization sequence from the third a-helix of Antennapedia, was endowed with an antiproliferative and proapoptotic activity toward a human mammary cancer cell line: The activity apparently depends upon the presence of the Myc motif. In the present work we have added new dimensions to our original findings. It is known that short retro-inverso (RI-) peptides can assume a 3D conformation very close to their corresponding L-forms and can be recognized by the same monoclonal antibody. We synthesized a RI-peptide form of our original L-peptide: It was much more resistant to serum peptidases than the original molecule (a half life of days rather than hours); in addition, the RI-form of the original Antennapedia internalization sequence was perfectly capable of carrying a D-peptide into human cells. We have studied three different potentially active peptides. L-peptides: Int-H1wt, Int-H1-S6A,F8A. D-peptides: RI-Int -H1-S6A,F8A. We have also studied three presumed control peptides: Int and RI-Int (no H1 motif), H1-S6A,F8A (no internalization sequence). Both 'active' and 'control' peptides have essentially confirmed our expectations, however, in cells treated with the higher concentration (10 mM) of the control peptide RI-Int, non-Myc related side effects could be detected. In order to investigate whether the antiproliferative activities displayed by some of our molecules were indeed related to an interference with the role of c-Myc (and molecules of the family), we chose an iso-amphipathic modified peptide of the H1 motif, with a proximity coefficient >50% and where the major change was at position 7 (F-->A). From a family of 73 H1 motifs belonging to (H1-Loop-H2) hu man sequences, the smallest evolutionary distance from our reference peptide was observed for the H1 of N-Myc, L-Myc, c-Myc, H1-S6A,F8A of c-Myc, and Max, in that order. Our reference peptide was therefore appropriate as a check of whether we were indeed observing activities related to Myc functions. Both Int-H1isoamph and the corresponding RI-Int-H1isoamph peptide were synthesized and studied. In terms of biological targets, we added to the human mammary cancer line of our previous work (MCF-7 cells) a colon cancer line (HCT-116 cells) and also a system of normal cells: human peripheral blood lymphocytes (PBLs) stimulated with phytohemoagglutinin (PHA). Peptides carrying an iso-amphipathic-modified H1 sequence were always very clearly (3-10 times) less active than the corresponding peptides carrying a conserved "H1 of Myc" motif. This finding was noted in five independent situations (all the cellular models considered at the present time): MCF-7 cells treated with L-peptides; MCF-7 cells treated with RI-peptides; HCT-116 cells treated with L-peptides; PBLs treated with L-peptides; PBLs treated with RI-peptides. Modulation of transcription levels of ornithine decarboxylase (ODC), p53, and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), in PBLs treated with our different molecules, was well compatible with an interference by our active peptides at the level of Myc transcriptional activity. We had already reported a similar observation in MCF-7 cells. On a molar basis, RI-peptides were about 5-10 times more potent and 30-35 times more stable in complete culture medium, than their corresponding L-forms. RI-Int can probably internalize longer peptido-mimetic molecules (for instance molecules mimetic of (H1-Loop-H2), or even more. These possibilities open the way to rodent studies and to more potent/selective Myc inhibitors-two steps closer to a potential drug.
Amino Acid Motifs↗
The CD85/LIR-1/ILT2 inhibitory receptor is expressed by all human T lymphocytes and down-regulates their functions.
The inhibitory molecule CD85/LIR-1/ILT2 has been detected previously on the surface of a small proportion of T lymphocytes. In this study, evidence is provided that, although only a fraction of CD3+ cells are stained by mAb specific for CD85/LIR-1/ILT2 on their surface, this inhibitory receptor is present in the cytoplasm of all T lymphocytes, and that it is detectable on the surface of all T cell clones by the M402 mAb. Biochemical analyses further demonstrate that CD85/LIR-1/ILT2 is present in all T clones analyzed, and that the protein is tyrosine-phosphorylated. Expression of mRNA coding for CD85/LIR-1/ILT2 has been assessed by RT-PCR. Notably, in the NKL cell line and in one T cell clone, amplification of the messenger required 30 cycles only, whereas, in other T cell clones, an amplification product was detected by increasing the number of cycles. CD85/LIR-1/ILT2 inhibits CD3/TCR-mediated activation in both CD4+ and CD8+ clones, and it down-regulates Ag recognition by CD8+ cells in a clonally distributed fashion. Addition of anti-ILT2 HP-F1 mAb in the cytolytic assay enhances target cell lysis mediated by Ag-specific CTL. This could be due to interference of the mAb with receptor/ligand interactions. In contrast, HP-F1 mAb cross-linking triggers inhibitory signals that reduce cytotoxicity. CD85/LIR-1/ILT2 also controls responses to recall Ags and, in low responders, its engagement sharply increases T cell proliferation. The inhibitory function of the molecule is also confirmed by its ability to reduce CD3/TCR-induced intracellular Ca2+ mobilization.
Antibodies, Monoclonal↗
The involvement of human-nuc gene in polyploidization of K562 cell line.
During megakaryocyte differentiation, the immature megakaryocyte increases its ploidy to a 2(x) DNA content by a process called endomitosis. This leads to the formation of a giant cell, the mature megakaryocyte, which gives rise to platelets. We investigated the role of human-nuc (h-nuc), a gene involved in septum formation in karyokynesis in yeast, during megakaryocytic polyploidization. Nocodazole and 12-O-tetradecanoylphorbol-13-acetate (TPA) were used to induce megakaryocytic differentiation in K562 cell line. The ploidy distribution and CD41 expression of treated K562 cells were evaluated by flow cytometry. Using quantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed the h-nuc mRNA expression on treated K562 cells. Mature megakaryocyte-like polyploid cells were detected at day 5-7 of treatment with nocodazole. TPA also had a similar effect on K562 cells, but it was much weaker than that of nocodazole. The analysis of ploidy of nocodazole-treated K562 cells showed that nocodazole preferentially induced polyploidization of K562 cell line with a pronounced increase of the cells 8N at day 7 of culture. Expression of CD41, a differentiation-related phenotype, was significantly induced by TPA after 7 days of treatment, showing that functional maturation was mainly induced by TPA. In contrast, there was no significant increase in CD41 expression in nocodazole-treated K562 cells, suggesting that polyploidization and functional maturation are separately regulated during megakaryocytopoiesis. RT-PCR analysis indicated that h-nuc mRNA increased after 72 hours in the presence of nocodazole, preceding the induction of polyploidization. Our data indicate that h-nuc might play a role in polyploidization during megakaryocytic differentiation via inhibition of septum formation.
Apoptosis↗
Feasibility in needle exchange programme: an evaluation of a pilot programme in Catania, Sicily.
INTRODUCTION: Intravenous drug use (10 V) is a primary transmission route for HIV and other blood borne disease. A criminal approach to illicit drug use leads to aggressive attitudes towards drug users and forces them underground, thus hindering their access to Health Service outlets. A 6-month pilot Needle Exchange Programme was set up in Catania, with the aim of reducing the negative effects and consequences of drug use, preventing the spread of blood borne diseases by encouraging the use of clean needles and reduction of needle sharing. To establish contact with the hidden population of the city's, intravenous drug users (IDUs) and promote condom use and safer sex. METHOD: An equipped camper was parked daily in two of the city's main public squares according to a preset timetable, morning and afternoon. A flexible needle exchange policy, i.e. free clean needles given out regardless of those returned, was adopted as a strategy considered necessary in order to, ensure maximum user-friendliness. Safer shooting information leaflets were given out alongside material for the correct use of the condom and condoms. RESULT: The number of IDUs, contacted who had previously been referred to a National Health Service Drug Unit (Ser.T.) and not, and number of syringes exchanged were low but increased month by month. CONCLUSION: Future projects should be undertaken after building up, a collaborative network between Street Unit and local courts; the city police force; social service outlets; hospitals and other health outlets; Ser.T. units and local pharmacies. In the light of our current experience, the one to one strategy instead to the flexible strategy could lead to stricter adherence to harm reduction strategies amongst IDUs.
Journal Article↗
Negative influence of IL3 on the expansion of human cord blood in vivo long-term repopulating stem cells.
Identification of culture conditions that support expansion or even long-term maintenance of in vivo repopulating human hematopoietic stem cells is still a major challenge. Using a combination of FLT3 ligand (FL), Stem Cell Factor (SCF), Thrombopoietin (TPO) and Interleukin 6 (IL6), we cultured cord blood (CB) CD34+ cells for up to 12 weeks and transplanted their progeny into sublethally irradiated NOD/SCID mice. Bone marrow engraftment was considered successful when recipients contained measurable numbers of human CD45+, CD71+ and Glycophorin A+(GpA) cells 8 weeks after transplantation. Twelve-week expanded cells with FL+SCF+TPO+IL6 successfully engrafted all of the recipients and human CD45(+)+CD71(+)+GpA(+) cells represented 4.3 to 22.4% of bone marrow. Substitution of IL6 with IL3 led to an even better expansion of cells and a similar clonogenic progenitor output in the first 8 weeks of culture; however, LTC-IC output increased up to week 6 and then decreased and disappeared. By contrast, with FL+SCF+TPO+IL6, LTC-IC kept increasing up to week 12. Four-week cultured cells with FL+SCF+TPO+IL3 less efficiently engrafted NOD/SCID mice, both as measured by frequency of positive recipients (4 out of 10) and percentage of engrafted human cells (< or =2%). Six-week expanded cells failed to engraft. This study provides evidence that many, but not all, of the so-called "early acting" cytokines, can sustain long-term maintenance and even expansion of human primitive in vivo repopulating stem cells. In particular, in the culture conditions used in this study, the presence of IL3 greatly reduces the repopulating potential of expanded CD34+ CB cells.
Animals↗
Cell activation via CD44 occurs in advanced stages of squamous cell carcinogenesis.
Squamous cell carcinoma (SCC) derives from dysplastic or metaplastic stratified epithelia. The process of squamous cell carcinogenesis has been investigated for the potential role of the adhesion molecule CD44, whose standard form (CD44s) and isoforms generated by alternative splicing of variant exons are known to display altered expression during tumorigenesis in other systems. We have utilized an in vitro correlate of squamous cell carcinogenesis, in which progression stages from normal squamous epithelium to dysplastic lesions and to SCC are represented by primary cultures of normal keratinocytes, by human papilloma virus-immortalized keratinocytes (UP) and by HPVimmortalized/v-Ha-ras transfected tumorigenic keratinocytes (UPR). We investigated expression of CD44 and of variant isoforms, from mRNA to intracellular and surface protein levels, and found no relationship between expression of CD44 and stages of squamous cell carcinogenesis. However, when the function of CD44 was analyzed as Ca(2+) mobilization ability upon monoclonal antibody binding and crosslinking, signal transduction via CD44 was found only for the neoplastic stage (UPR cells). Ca(2+) mobilization was completely independent of density of surface CD44. We have performed similar analyses in an in vitro model of SCC in which four squamous tumor cell lines and UPR cells were sorted according to increasing resistance to external cytotoxic stimuli, i.e. starving conditions, treatment with the retinoid N-(4-hydroxyphenyl)retinamide and cytolytic activity of effector lymphokine-activated killer cells. No relationship between expression of CD44 and level of cell resistance against external cell death-inducing stimuli was found, while CD44-mediated Ca(2+) mobilization ability was restricted to the highly resistant tumor cell lines. Our results indicate that the role(s) of CD44 in squamous cell proliferative disorders can be evinced from the functional features of the molecule, rather than from its phenotypic repertoire.
Apoptosis↗
Oxygen binding by alpha(Fe2+)2beta(Ni2+)2 hemoglobin crystals.
Oxygen binding by hemoglobin fixed in the T state either by crystallization or by encapsulation in silica gels is apparently noncooperative. However, cooperativity might be masked by different oxygen affinities of alpha and beta subunits. Metal hybrid hemoglobins, where the noniron metal does not bind oxygen, provide the opportunity to determine the oxygen affinities of alpha and beta hemes separately. Previous studies have characterized the oxygen binding by alpha(Ni2+)2beta(Fe2+)2 crystals. Here, we have determined the three-dimensional (3D) structure and oxygen binding of alpha(Fe2+)2beta(Ni2+)2 crystals grown from polyethylene glycol solutions. Polarized absorption spectra were recorded at different oxygen pressures with light polarized parallel either to the b or c crystal axis by single crystal microspectrophotometry. The oxygen pressures at 50% saturation (p50s) are 95 +/- 3 and 87 +/- 4 Torr along the b and c crystal axes, respectively, and the corresponding Hill coefficients are 0.96 +/- 0.06 and 0.90 +/- 0.03. Analysis of the binding curves, taking into account the different projections of the alpha hemes along the optical directions, indicates that the oxygen affinity of alpha1 hemes is 1.3-fold lower than alpha2 hemes. Inspection of the 3D structure suggests that this inequivalence may arise from packing interactions of the Hb tetramer within the monoclinic crystal lattice. A similar inequivalence was found for the beta subunits of alpha(Ni2+)2beta(Fe2+)2 crystals. The average oxygen affinity of the alpha subunits (p50 = 91 Torr) is about 1.2-fold higher than the beta subunits (p50 = 110 Torr). In the absence of cooperativity, this heterogeneity yields an oxygen binding curve of Hb A with a Hill coefficient of 0.999. Since the binding curves of Hb A crystals exhibit a Hill coefficient very close to unity, these findings indicate that oxygen binding by T-state hemoglobin is noncooperative, in keeping with the Monod, Wyman, and Changeux model.
Crystallization↗
Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point.
Retinoids have shown a potential activity in preventing tumor recurrence in superficial bladder cancer. We assessed the activity of the synthetic retinoid fenretinide in superficial bladder cancer using DNA flow cytometry and conventional cytology as surrogate biomarkers. A total of 99 subjects with resected superficial bladder cancer (pTa, pT1) were randomized to either fenretinide (200 mg day p.o. for 24 months) or no intervention. Cystoscopy and bladder washing for DNA flow cytometry end points (proportion of DNA aneuploid histograms, hyperdiploid fraction, and percentage of apoptotic cells) and proportion of abnormal cytological examinations were repeated every 4 months for up to 36 months. The primary study end point was the proportion of DNA aneuploid histograms after 12 months. This figure was 48.9% in the fenretinide arm and 41.9% in the control arm (odds ratio, 1.16; 95% confidence interval, 0.44-3.07). There was no difference in any other response biomarker between the two groups up to 36 months, nor was any biomarker able to predict recurrence risk. Recurrence-free survival was comparable between the arms (27 events in the fenretinide arm versus 21 in the control arm; P = 0.36). Twelve subjects in the fenretinide arm complained of diminished dark adaptability, and nine subjects in the fenretinide arm versus one control subject had mild dermatological alterations. We conclude that fenretinide showed a lack of effect on the DNA content distribution and the morphology of urothelial cells obtained in serial bladder washings. Recurrence-free survival was comparable between groups. Because our data are hampered by the lack of predictivity of the selected biomarkers, additional studies are necessary to assess the activity of fenretinide in preventing bladder cancer.
Aged↗
[Follicular non-Hodgkin lymphomas and minimal residual disease].
Follicular lymphomas constitute 40% of non-Hodgkin lymphomas (NHL). Most of them (85%) present the t14:18 translocation with altered expression of BCL2. The lack of clinical prognostic factors able to separate a group of patients with poor outcome have shifted the interest to the assessment of t14:18 as a molecular marker for clinical response. Moreover, the translocation site is being studied as a prognostic variable. New therapeutic modalities aimed to affect BCL2 such as the antiidiotype vaccines or antisense oligonucleotides against BCL2 have motivated great expectancy.
Antineoplastic Combined Chemotherapy Protocols↗
Varicella immunization practices and the factors that influence them.
OBJECTIVES: To evaluate the varicella immunization practices of physicians in Rochester, NY, and to identify factors that predict whether physicians administer varicella vaccine to children. DESIGN: Evaluation of a 40-item survey addressing varicella immunization practices and opinions about varicella immunization that was sent to 241 pediatricians and family physicians. RESULTS: A total of 172 physicians (71.4%) completed the survey. Sixty-three percent administer the vaccine to some or all varicella-susceptible children aged 1 through 5 years, while 57% administer it to children aged 6 through 11 years, and 74% administer it to adolescents 12 years and older. Physicians who did not offer the immunization were more likely to believe that (1) the vaccine should not be given to preadolescent children because "varicella is a normal part of childhood"; (2) by giving the vaccine, varicella may shift from being primarily a childhood illness to being primarily an adult illness; (3) children get enough immunizations already and should not be given additional immunizations to prevent varicella; (4) it may be preferable to only immunize immunocompromised individuals and their close contacts; and (5) it would cost too much to immunize all American children who have not had varicella. Physicians most likely to offer the vaccine were pediatricians and those whose patients were covered primarily by private insurance plans. After becoming aware of morbidity and mortality rates for varicella-related complications, many physicians who did not administer the vaccine, or administered it only at the request of a parent, indicated that they would be more likely to offer it. CONCLUSIONS: Most physicians in the Rochester area administer varicella vaccine, especially to adolescents 12 years and older. Specialty, predominant insurance type billed, and various opinions characterized those who did not offer the immunization. Providing these physicians with information about varicella-related complications may make them more likely to immunize.
Adolescent↗
Assessment of DNA flow cytometry as a surrogate end point biomarker in a bladder cancer chemoprevention trial.
Although conventional cytology represents the most widely performed cytometric analysis of bladder cancer cells, DNA flow cytometry has, over the past decade, been increasingly used to evaluate cell proliferation and DNA ploidy in cells from bladder washings. We have investigated whether DNA flow cytometry and conventional cytology of epithelial cells obtained from bladder washings provide reliable surrogate endpoint biomarkers in clinical chemoprevention trials. We used cytometric and clinical data from a chemoprevention trial of the synthetic retinoid Fenretinide on 99 patients with superficial bladder cancer. A total of 642 bladder washing specimens obtained from the patients at 4 month intervals was analyzed. Intra-individual agreement and correlation of flow cytometric DNA ploidy (diploid vs. aneuploid), DNA Index, Hyper-Diploid-Fraction (proportion of cells with DNA content higher than 2C), and conventional cytologic examination, as assessed by kappa statistics and Spearman's correlation test, were poor from baseline through 24 months. Moreover, no correlation was found between DNA ploidy and cytology at each time point. The same results were obtained when the analyses were stratified by treatment group. In addition, the association between the results of bladder washing (by either DNA flow cytometry or cytology) and concomitant tumor recurrence was significant only for abnormal cytology, while neither biomarker was predictive of tumor recurrence at the subsequent visit. During the time of this study only four patients progressed to muscle-invasive bladder cancer, indicating the "low-risk" features of the patient population. We conclude that DNA flow cytometry and conventional cytology on epithelial cells obtained from bladder washings do not appear to provide suitable surrogate endpoint biomarkers during the early stages of bladder carcinogenesis.
Antineoplastic Agents↗
Human leukocyte antigen class II and III alleles and severity of hepatitis C virus-related chronic liver disease.
Hepatitis C outcome is likely related both to viral factors and host's immune responses. We correlated the severity of liver disease with human leukocyte antigen (HLA) genes (C4A, C4B, TNFA, TNFB, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, TAP1, and TAP2) in three groups of subjects: 99 patients with chronic hepatitis, 41 asymptomatic carriers, and 179 uninfected controls. Patients with grade/stage 3 to 4 hepatitis significantly differentiated for their low frequency of alleles TNFB*1, DRB1*1104, and DRB3*03, which had a protective role, and high frequency of allele DRB1*1001, which was associated with disease severity. HLA-DRB*11 subtypes were differentially distributed: DRB1*1104 was most frequent in carriers, whereas DRB1*1101 was more frequent in patients. The TAP1C,2A haplotype was also underrepresented in patients with respect to controls. Finally, a decrease of heterozygous subjects was observed in patients with respect to carriers at the DQB1 locus. Multivariate analysis by correspondence analysis and multiple logistic regression indicated that age, sex, and hepatitis C virus (HCV) type were the strongest risk factors; however, some immunogenetic variables (TNFB*1, DRB1*1104, and DRB3*03) showed an independent contribution, especially in comparing patients with extreme manifestations of disease. The involvement of different genes in various HLA subregions suggests that anti-HCV responses are modulated by a complex gene interplay rather than by single alleles.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
High prevalence of multinodular hepatocellular carcinoma in patients with cirrhosis attributable to multiple risk factors.
To see whether or not there is an association between the cause of cirrhosis and the number of hepatocellular carcinoma (HCC) nodules, we analyzed 178 consecutive patients in whom HCC was detected during a prospective screening by abdominal ultrasound (US). The relevant information was obtained from the database of the screening programs operating at four hospitals in the Milan area. One hundred twenty-nine (72%) patients had a single tumor nodule detected by US and 49 (28%) patients had multinodular disease. Ninety-eight (55%) patients had normal serum values of alpha-fetoprotein (AFP). Tumor staging with biphasic computed tomography (CT) scan or hepatic arteriography with lipiodol revealed that 101 (57%) patients had single tumor nodules and 77 (43%) patients had more than one HCC nodule. After staging, multinodular HCC was more common in patients with multiple risk factors than in the hepatitis C virus (HCV) carriers (56% vs. 38%, P =.05). Interestingly, single tumors were as common in the 126 patients undergoing 6-month interval screening as in the 52 patients who were studied at yearly intervals. The former patients, however, had more small tumors than the latter ones (91% vs. 74%, P =.04). The 22 patients who were alcohol abusers had normal levels of serum AFP more often than the hepatitis B virus (HBV) or HCV carriers or those with multiple risk factors (86% vs. 57%, P <.04; vs. 47%, P <.002; vs. 52%, P <.006, respectively). We concluded that multinodular HCC was underdetected by real time US; it prevailed among patients with multiple risk factors. In these patients, screening with US exams every 6 months may be inadequate for early detection of liver cancer.
Alcoholism↗
Takayasu's arteritis: a cell-mediated large-vessel vasculitis.
Takayasu's arteritis is an idiopathic, systemic inflammatory disease, typically involving the aorta and its main branches. Cell-mediated autoimmunity has been strongly implicated in its pathogenesis. Early or active-stage pathology consists of continuous or patchy granulomatous inflammation, which progresses to intimal and adventitial fibrosis and scarring of the media. Multiple focal or segmental stenoses result and aneurysms may occasionally occur. Clinical presentation is heterogeneous, ranging from asymptomatic to catastrophic. In some patients, constitutional signs and symptoms indicating a systemic inflammatory response are observed, usually in the early stages. Specific features reflect arterial involvement, and result from end-organ or limb ischemia; they include vascular, neurological, cardiac, and pulmonary manifestations. The course of Takayasu's arteritis usually extends for many years with varying degrees of activity. Takayasu's arteritis has a worldwide distribution, with the greatest prevalence in eastern countries. Women of reproductive age are preferentially affected, but the illness is being recognized with increasing frequency in males. Variable phenotypes are recently emerging in different ethnic groups. Diagnosis is based on clinical features and vascular imaging studies that document typical patterns of stenoses or aneurysms of the aorta and its primary branches. Assessment of the activity of Takayasu's arteritis is imprecise, in that clinical features and acute-phase reactants do not accurately reflect active blood vessel inflammation. High-dose corticosteroids alone or a cytotoxic agent in addition to a corticosteroid may be effective in treating active disease. Critical lesions may require correction by surgery or interventional radiology.
Adult↗
[Gastric solitary plasmacytoma associated with +Helicobacter pylori infection].
Solitary gastric plasmacitomas are infrequent tumors. They account for 5% of the extramedullary plasmacitomas. We report an unusual case in a 14 years old boy. The patient has had gastric symptoms for 2 years prior to an endoscopic examination. A fungating, ulcerated lesion was observed in the antrum. The biopsies showed a monoclonal, Lambda positive, diffuse, plasmocitic proliferation infiltrating the mucosa. Also a moderate number of Helicobacter pylori were identified in the gastric pits and numerous lymphoid follicules were observed in the deep portion of the mucosa. In view of the presence of HP infection the patient was treated with Orneprazole and Clarithromycin. Endoscopic examination and biopsies performed 3 and 5 months later showed a complete remission of the gastric lesion. At the time of this report the patient is in good physical condition, has recovered his weight and has grown 5 cm. Differential diagnosis with plasmo limpho in chronic gastritis and with lympheicitic lymphoma with plasmocitoid features had to be done. The macroscopic appearance of the gastric lesion, the absence of other inflammatory cells and monoclonality of the plasmocitic infiltration ruled out chronic gastritis. The negative staining for CD 20 as well as the abscence of lymphoid cells in the mucosal infiltrate give support: to the diagnosis of plasmocitoma. The close association between gastric MALT lymphoma and HP infection has been reported as well as its regression after antibiotic treatment for its erradication. In our review of the literature we failed to find any references to the association of HP with gastric plasmocitoma nor to its regression after antibiotic therapy.
Adolescent↗
Inhibition of cancer cell growth and c-Myc transcriptional activity by a c-Myc helix 1-type peptide fused to an internalization sequence.
c-Myc is a nuclear protein with important roles in cell transformation, cell proliferation, and gene transcription. It has been previously shown that a 14-amino acid (aa) modified peptide (H1-S6A,F8A) derived from the helix 1 (H1) carboxylic region of c-Myc can interfere in vitro with specific c-Myc DNA binding. Here, we have linked the above Myc-derived 14-aa peptide to a 16-aa sequence from the third helix of Antennapedia (Int). It has been repeatedly reported that this 16-aa Antennapedia peptide is able to cross mammalian cell membranes and to work as a vector for short peptides. Using fluorescent (dansylated or rhodaminated) peptides, we have shown that the fusion peptide with the Antennapedia fragment (Int-H1-S6A,F8A) but not the c-Myc derived fragment alone (H1-S6A,F8A) was capable of internalization inside MCF-7 human breast cancer cells. Int-H1-S6A,F8A and H1-S6A,F8A were the only two peptides capable of inhibiting coimmunoprecipitation of the c-Myc/Max heterodimer in vitro. We have treated (continuously for 10-11 days) MCF-7 cells with four different peptides: Int, H1-S6A,F8A, Int-H1-S6A,F8A, and Int-H1wt [a peptide differing from Int-H1-S6A,F8A by 2 aa (S6 and F8) in the H1 region]. In intact MCF-7 cells, Int-H1-S6A,F8A was the only active peptide capable of inducing the following biological effects: (a) inhibition of cloning efficiency on plates; (b) inhibition of cell growth and induction of apoptosis in subconfluent/confluent cells; and (c) inhibition of transcription of two c-Myc-regulated genes (ODC and p53). Int-H1-S6A,F8A was active in the 1-10 microM range. Int-H1-S6A,F8A may represent a lead molecule for peptidomimetic compounds that have a similar three-dimensional structure but are more resistant to peptidases and, therefore, suitable for in vivo treatment of experimentally induced tumors.
Amino Acid Sequence↗