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C Balbi

Publications and source records attributed to C Balbi.

At least 19 recordsLinked to original sources
PubMed2005

Sequence specific peptidomimetic molecules inhibitors of a protein-protein interaction at the helix 1 level of c-Myc.

Our work is focused in the broad area of strategies and efforts to inhibit protein-protein interactions. The possible strategies in this field are definitely much more varied than in the case of ATP-pocket inhibitors. In our previous work (10), we reported that a retro-inverso (RI) form of Helix1 (H1) of c-Myc, linked to an RI-internalization sequence arising from the third alpha-helix of Antennapedia (Int) was endowed with an antiproliferative and proapoptotic activity toward the cancer cell lines MCF-7 and HCT-116. The activity apparently was dependent upon the presence of the Myc motif. In this work, by ala-scan mapping of the H1 portion of our molecules with D-aa, we found two amino acids necessary for antiproliferative activity: D-Lys in 4 and D-Arg in 5 (numbers refer to L-forms). In the natural hetero-dimer, these two side chains project to the outside of the four alpha-helix bundle. Moreover, we were able to obtain three peptides more active than the original lead. They strongly reduced cell proliferation and survival (RI-Int-VV-H1-E2A,S6A,F8A; RI-Int-VV-H1-S6A,F8A,R11A; RI-Int-VV-H1-S6A,F8A,Q13A): after 8 days at 10 muM total cell number was approximately 1% of the number of cells initially seeded. In these more potent molecules, the ablated side chains project to the inside in the corresponding natural four alpha-helix bundle. In the present work, we also investigated the behavior of our molecules at the biochemical level. Using both a circular dichroism (CD) and a fluorescence anisotropy approach, we noted that side chains projecting at the interior of the four alpha-helix bundle are needed for inducing the partial unfolding of Myc-H2, without an opening of the leucine zipper. Side chains projecting at the outside are not required for this biochemical effect. However, antiproliferative activity had the opposite requirements: side chains projecting at the outside of the bundle were essential, and, on the contrary, ablation of one side chain at a time projecting at the inside increased rather than decreased biological activity. We conclude that our active molecules probably interfere at the level of a protein-protein interaction between Myc-Max and a third protein of the transcription complex. Finally, CD and nuclear magnetic resonance (NMR) data, plus dynamic simulations, suggest a prevalent random coil conformation of the H1 portion of our molecules, at least in diluted solutions. The introduction of a kink (substitution with proline in positions 5 or 7) led to an important reduction of biological activity. We have also synthesized a longer peptido-mimetic molecule (RI-Int-H1-S6A,F8A-loop-H2) with the intent of obtaining a wider zone of interaction and a stronger interference at the level of the higher-order structure (enhanceosome). RI-Int-H1-S6A,F8A-loop-H2 was less active rather than more active in respect to RI-Int-VV-H1-S6A,F8A, apparently because it has a clear bent to form a beta-sheet (CD and NMR data).

Amino Acid Sequence↗
PubMed2002

Second-line with paclitaxel and carboplatin for recurrent disease following first paclitaxel and platinum compounds in ovarian carcinoma.

OBJECTIVE: The combination of paclitaxel and platinum compounds is considered the best first-line regimen for advanced ovarian carcinoma. The purpose of this study was to evaluate a paclitaxel and carboplatin combination in pretreated patients who recurred within 24 months after a complete clinical response with the same regimen used as first-line chemotherapy. METHODS: 18 patients were included in this study. Second-line chemotherapy consisted of paclitaxel, 175 mg/m2 as a 3-hour infusion, and carboplatin AUC 6 every 21 days. RESULTS: Among 15 evaluable patients, eight (53%) complete and five (34%) partial responses were observed, while two (13%) patients had stable disease (SD). The response rate was 67% among patients with measurable disease and 52% for evaluable disease. The median progression-free interval after second-line chemotherapy was 8.3 months. The median progression-free interval for patients with measurable disease was 8.6 months and for evaluable disease it was 7.9 months. Seven (46%) of 15 patients have developed recurrence after second-line chemotherapy with paclitaxel and carboplatin with a median time to recurrence of 9.8 months. CONCLUSION: Paclitaxel 175 mg/m2 and carboplatin AUC 6 as second-line chemotherapy in this sensitive population is effective in terms of response rate and progression-free interval.

Adult↗
PubMed2001

Paclitaxel and carboplatin as outpatient therapy for stage III and IV epithelial ovarian cancer.

BACKGROUND: To determine the toxicity and the response rate of a three-hour paclitaxel infusion and carboplatin administered as outpatient treatment for stage III and IV epithelial ovarian cancer. METHODS: Forty-three patients with stage III/IV epithelial ovarian cancer underwent cytoreductive surgery and then received paclitaxel 175 mg/m2 over 3-hr infusion and carboplatin AUC5 every 21 days for six cycles. Elegible patients had adequate bone marrow, renal and hepatic function; G-CSF was recommended if white cell count fell under 3,000/mm3. RESULTS: No patients had hypersensivity reactions; 15 out of 43 patients (35%) required colony-stimulating factors, 39 patients (91%) had general alopecia, three patients (7%) had severe emesis, 20 patients (46%) had mild emesis, four patients (9%) had severe myalgias, eight patients (18%) had moderate myalgias, one patient (2%) had grade 3 neurotoxicity. Three patients experienced grade 3 thrombocytopenia (7%). At a median follow-up of 29 months, 32 of 43 patients are alive (74%). Median progression-free survival is 14 months. Median overall survival has not been reached. CONCLUSIONS: Three-hour infusion paclitaxel and carboplatin is an effective and safe outpatient therapy for epithelial ovarian cancer.

Adult↗
PubMed2001

Women with a pelvic mass: indicators of malignancy.

OBJECTIVE: To evaluate the efficacy of five methods: pelvic examination (PE), transvaginal ultrasonography (US), Doppler ultrasonography, serum CA125 assay and serum CA72-4 assay, alone or associated, to predict malignancy in patients presenting a pelvic mass originating in the ovary. METHODS: 92 patients underwent a standard protocol for physical examination, CA125, CA72-4, transvaginal ultrasonography and Doppler ultrasonography. RESULTS: Eighteen women were dropped from the study because they had clearly benign masses; two women were dropped from the study because they had clearly malignant lesions. Twenty-two malignant (30%) and 50 benign (70%) pelvic tumors were found. When one method was considered alone the best sensitivity (SENS) was found in physical examination (90%) and the best specificity (SPEC) was found in CA72-4: 88%. If all indicators were positive, the SPEC was 100% but the SENS was 40%. Logistic regression analysis prediction of the character of the pelvic masses was correct in 86%. CONCLUSION: Some additional information to discriminate between malignant and benign pelvic masses can be obtained from the valuation of serum tumor markers, particularly CA72-4. Also Doppler ultrasonography appeared to be useful in the differential diagnosis of pelvic tumors. The prediction of the character of the pelvic masses calculated by a logistic model in which PE, US, CA 125, and CA72-4 are included is very good.

Adult↗
PubMed2000

Changes in the expression of cytokeratins and nuclear matrix proteins are correlated with the level of differentiation in human prostate cancer.

The nuclear matrix-intermediate filament complex (NM-IF) is a protein scaffold which spans the whole cell, and several lines of evidence suggest that this structural frame represents also a functional unit, which could be involved in the epigenetic control of cancer development. Here we report the characterization by high resolution two-dimensional gel electrophoresis and Western blot analysis of the NM-IF complex isolated from prostate cancer (PCa); tumor-associated proteins were identified by comparing the electrophoretic patterns with those of normal human prostate (NHP). Extensive changes in the expression of both the NM and IF proteins occur; they are, however, related in a different way to tumor progression. Poorly differentiated PCa (Gleason score 8-9) shows a strong down regulation of several constitutive cytokeratins (CKs 8, 18, and 19); their expression significantly (P < 0.05) decreases with respect to both NHP and benign prostatic hyperplasia (BPH) and, more interestingly, also with respect to moderately (Gleason score 6-7) and well (Gleason score 4-5) differentiated tumors. Moreover, we have identified a tumor-associated species which is present in all of the tumors examined, systematically absent in NHP and occurs only in a few samples of BPH; this polypeptide, of M(r) 48,000 and pI 6.0, represent a proteolytic fragment of CK8. At variance with these continuing alterations in the expression, the NM proteins undergo stepwise changes correlating with the level of differentiation. The development of less differentiated tumors is characterized by the appearance of several new proteins and by the decrease in the expression of others. Six proteins were found to be expressed with a frequency equal to one in poorly differentiated tumor, namely in all the samples of tumor examined, while in moderately and well differentiated tumors the frequency is less than one, and decreases with increasing the level of differentiation. When tumors of increasing Gleason score are compared with NHP a dramatic increase in the complexity of the protein patterns is observed, indicating that tumor dedifferentiation results in a considerable increase in the phenotypic diversity. These results suggest that tumor progression can be characterized using an appropriate subset of tumor-associated NM proteins.

Adenocarcinoma↗
PubMed2000

Influence of menstrual factors and dietary habits on menstrual pain in adolescence age.

OBJECTIVES: The aim of this study was to determine the frequency of the primary dysmenorrhea in adolescence age and investigate correlation between menstrual factors, dietary habits and this pathology. STUDY DESIGN: The sample was constituted from 356 students that were subjected to questionnaire, abdominal ultrasound, and in some cases, hormonal dosing. RESULTS: The frequency of the primary dysmenorrhea was 85%. Early menarche was related to an increase of its prevalence and its severity. A long and heavy menstrual flow was related to an increase of its severity. As far as dietary habits, it was noted that a higher consumption of fish, eggs, fruit and a lower consumption of wine is correlated with a lower frequency. CONCLUSION: Primary dysmenorrhea is very common in young women. The risk factors for this pathology are early menarche, long and heavy menstrual flow, and lower consumption of fish, eggs, and fruit.

Adolescent↗
PubMed2000

[Changes of the pulsatile index in ovarian and uterine arteries of infertile women. Case-control study].

BACKGROUND: This study was performed to evaluate the frequency of female pathology that cause infertility and to appraise the difference of pulsatility index in the ovarian and uterine arteries in infertile women and in a control group of healthy women. METHODS: In the period between January 1997 and March 1999 52 infertile couples were examined carrying out an accuracy anamnesis and objective examination. The dosing of FSH, LH, estrogens, progesterone, and an ultrasound examination for each woman was required. The pulsatility index in the ovarian and uterine vases was calculated with the color Doppler technique. RESULTS: A female pathology caused infertility in 24 couples, where only in nine couples the cause was masculine. In 14 couples there was a pathology in both the partners. In 5 couples any pathology was identified. The median of pulsatility index in healthy women was 1.8. Variations were observed in all the women with ovarian or uterine pathology unless in those with uterine malformations. An increase of the pulsatility index was observed also in 3 couples in which any cause of infertility was identified. CONCLUSIONS: Female pathology is a very common cause of infertility. The evaluation of the pulsatility index in ovarian and uterine arteries can be useful diagnosing the cause of infertility and in to explain an infertility due to unknown cause.

Adult↗
PubMed2000

Fetuses with cystic hygroma. A retrospective study.

BACKGROUND: The aim of this study is to analyse several theories of pathogenesis of cystic hygroma, its correlation with chromosomal abnormalities and the indicators of poor or good prognosis. METHODS EXPERIMENTAL DESIGN: This is a retrospective study that evaluates all cases of cystic hygroma seen during the four-year period from January 1994 to December 1997. SETTING: This study was performed in the center of prenatal diagnosis of institutional hospital in Caserta. PATIENTS: All cases of fetuses with cystic hygroma were examined in 2100 pregnant female who visited the ambulatory. INTERVENTIONS: The modality of diagnosis of this pathology and the presence of abnormal maternal serum levels of alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol were evaluated. Moreover, the presence of karyotype abnormalities or other non chromosomal abnormalities were also evaluated. Prognostic indicators such as the presence of septae seen by sonography were examined. RESULTS: Nine fetuses with cystic hygroma were diagnosed sonographically. Septae were identified in six cases. Chromosomal abnormalities were found in five cases. Two cases presented Turner's syndrome and one case Downs' syndrome. There were two cases with associated anomalies. The amniotic fluid alpha-fetoprotein (AFP) levels were high in all cases. CONCLUSIONS: Cystic hygroma is a malformation of the lymphatic system that is diagnosed by ultrasound very well from the first quarter of pregnancy. It is frequently associated with chromosomal and non chromosomal abnormalities. The presence of septae in it and amniotic fluid AFP levels are prognostic indicators.

Chromosome Aberrations↗
PubMed1999

Chromatin condensation is confined to the loop and involves an all-or-none structural change.

Using differential scanning calorimetry in combination with pulsed field gel electrophoresis, we relate here the changes in the thermal profile of rat liver nuclei induced by very mild digestion of chromatin by endogenous nuclease with the chain length distribution of the DNA fragments. The enthalpy of the endotherm at 106 degrees C, which reflects the denaturation of the heterochromatic domains, decreases dramatically after the induction of a very small number of double-strand breaks per chromosome; the thermal transition disappears when the loops have undergone on average one DNA chain scission event. Quantitative analysis of the experimental data shows that the loop behaves like a topologically isolated domain. Also discussed is the process of heterochromatin formation, which occurs according to an all-or-none mechanism. In the presence of spermine, a strong condensation agent, only the loops that have undergone one break are able to refold, in confirmation of the extremely cooperative nature of the transition. Furthermore, our results suggest a relationship between the states that give rise to the endotherms at 90 degrees C and 106 degrees C and the morphologies referred to as class II and class III in a previous physicochemical study of the folding of chromatin fragments (Widom, 1986. J. Mol. Biol. 190:411-424) and support the view that the overall process of condensation follows a sequential (two-step) pathway.

Animals↗
PubMed1999

[Climacteric and quality of life].

BACKGROUND: Menopause is for women a critical period of their life, in which organic troubles and psychological problems cherish themselves. With particular reference to hot flushes and impaired sleep (the frequently found troubles), the benefits of physical exercise in women of this age have been evaluated. METHODS: A study based on a questionnaire has been carried out on 79 women of age between 51 and 58 (who practised regular physical activity, selected at sporting centers), and 481 women of age between 52 and 58, selected between patients who came to the University Hospital for reasons not ascribed to menopause. All the women selected in the study underwent to natural menopause, and didn't use hormonal therapy. The questionnaire evaluated symptomatology and its level of severity. RESULTS: In the first group 57% of the women didn't report symptoms, 30% light symptoms, 12% medium, 1% severe. In the second group 52% didn't report symptoms, 15% light symptoms, 22% medium, 11% severe. CONCLUSIONS: Besides verifying a bigger well-being among women who practice physical activity, the interesting result is that 52% of the second group didn't refer symptomatology. The advantages of a balanced diet, with particular attention to food with phytoestrogens, is discussed and the psychosocial problems of woman in menopause, covering a fundamental role to explain a great part of the symptomatology, are underlined. Finally, the guide lines for a right preparation to menopause are presented.

Climacteric↗
PubMed1998

[Heparin-like factors in pregnancy. Report of a clinical case].

Some authors have described the presence of circulating heparin-like anticoagulants; these substances are frequently associated with neoplastic pathology. Personal experience proves that this pathology of coagulation may be present also in pregnancy. The clinical case of a primipara, nullipara pregnant woman twenty-eight years aged is described; the case history showed that the patient presented circulating heparin-like substances. During this study, routine biochemical examinations were within normal limits as well as the coagulation tests. In the course of this experience, coagulation anomalies and hemorrhagic episodes in the intraoperative and postoperative period were not observed.

Adult↗
PubMed1997

The condensation of chromatin in apoptotic thymocytes shows a specific structural change.

Chromatin condensation and DNA cleavage at internucleosomal sites have been recognized early as hallmarks of apoptosis, and it has been suggested that extensive DNA chain scission could directly result in the formation of dense chromatin bodies. Here we have shown that no causal relationship exists between DNA degradation and chromatin condensation in glucocorticoid-induced thymocyte apoptosis. The chromatin rearrangement occurred independent of as well as prior to DNA cleavage and involved a specific conformational change at the nucleosome level. In the early stages of the process, the core particles appeared to be tightly packed face-to-face in smooth 11-nm filaments that progressively folded to generate a closely woven network. The network finally collapsed, producing dense apoptotic bodies. Since trypsin digestion relaxed condensed chromatin and histone H4 underwent appreciable deacetylation in the apoptotic cell, we suggest that changes in the DNA-histone interactions represented a major modulating factor of condensation.

Animals↗
PubMed1997

[Evaluation of bone loss in patient treated with Gn-Rh analogs].

BACKGROUND: The increasing use of analogs of Gn-RH during treatment of some benign gynaecological diseases, has induced the authors to investigate the principal collateral effects, fixing one's attention on the loss of bony mass. METHODS: This perspective research has considered 38 patients selected for two diseases "endometriosis" and "uterine fibromyomatosis". The therapy has been effected with triptorelin intramuscularly in a dose of 3.75 mg every 28 days for six months, in all six phials. RESULTS: After a half-yearly cycle of therapy, the loss of bony mass was valued about 3% medium. CONCLUSIONS: In the light of other studies too, it was decided to confirm the necessity of associating other medicines able to prevent the side effects caused by their analogs of Gn-RH.

Adult↗
PubMed1996

Differential nuclear matrix-intermediate filament expression in human prostate cancer in respect to benign prostatic hyperplasia.

We have characterized the changes in composition of the nuclear matrix-intermediate filament complex (NM-IF) isolated from prostate cancer (PCa), compared with benign prostatic hyperplasia (BPH). We prepared the NM-IF from ten patients undergoing radical retropubic prostectomy; the benign hyperplastic tissue was obtained from the prostate lobe contralateral to the cancer zone. Several quantitative and qualitative changes have been identified. Three new proteins of molecular weight 48, 47 and 29 kDa and isoelectric point 6.0, 4.9 and 6.4, respectively, were detected in PCa, referred to here as P8, P5 and NM-1, P8 was present in all ten of the tumors examined, P5 was expressed in 9/10 PCa; conversely, they were present in only one and two BPH, respectively; NM-1 was found in eight tumors out of nine and never in BPH. These proteins are expressed in moderately differentiated malignant cells, suggesting that the proteins of the NM-IF complex can be interesting biomarkers for prostate cancer. Immunoblot analysis shows that P8 and P5 proteins belong to the IF superfamily. This observation, taken together with previous data obtained by our and other groups, suggests that the characterization of NM-IF protein changes could also shed light on mechanistic aspects of cancer progression.

Aged↗
PubMed1996

Changes in the cytoskeletal and nuclear matrix proteins in rat hepatocyte neoplastic nodules in their relation to the process of transformation.

In a previous paper (Barboro et al., 1993, Biophys. J. 65, 1690-1699) we have shown that cancer development in the resistant hepatocyte model of Solt and Farber is characterized by the progressive unfolding of the higher-order structure of chromatin. A possible functional role of decondensation phenomena in cell transformation cannot be ruled out. Genetic activation involves the relaxation of the superstructure of chromatin, which may be, at least in part, modulated by its interaction with the nuclear matrix. Moreover, recent observations suggest that gene expression can be stimulated by alterations in the organization of the cytoskeleton. Therefore, we have characterized the changes in composition that the nuclear matrix-intermediate filament complex undergoes during the evolution of rat hepatocyte nodules. Dramatic changes in the expression of both the nuclear matrix and intermediate filament proteins occur during transformation; they are, however, related in a different way to the stages of carcinogenesis. Several new nuclear matrix proteins appear in early nodules, isolated 9 weeks after initiation. The subsequent evolution of persistent nodules is also characterized by discrete changes in the composition. Thus, the new synthesis of nuclear matrix proteins reflects the emergence of successive cellular populations, in line with the recent finding that a subset of components of the nuclear matrix is cell type-specific. In contrast, intermediate filament proteins undergo continuing changes. A new keratin with apparent molecular weight of 39 kDa, analogous to human keratin 19, appears in early nodules, and its expression steadily increases up to the 32nd week from initiation; at the same time, the amount of the proteolytic fragments of keratins A and D increases sharply. These findings suggest that the inappropriate expression of keratin 19 may be involved in the epigenetic activation of new cellular programs, through the rearrangement of the cytoskeleton which in turn may perturb nuclear matrix function.

Animals↗