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Biomedical subjects

G Colella

Publications and source records attributed to G Colella.

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

Endoscopic surgery for large posterior fossa arachnoid cysts.

The authors report two cases of large arachnoid cysts of the posterior fossa treated by endoscopic surgery. One patient underwent a successful endoscopic cyst fenestration by burr hole approach after several procedures of shunt revision. In another an endoscope-assisted microsurgical intervention was necessary. Lateral (cerebellar or cerebellopontine angle) cysts, as two reported cases, may be treated through a lateral retromastoid approach by fenestration into the prepontine cistern and eventually into the cisterna magna. We advise to start the operation through a burr hole and to try to realize the fenestration by endoscopy only. If this attempt fails, an endoscope-assisted microsurgical technique may be performed by enlarging the craniectomy. In this last instance the endoscope is useful particularly deeply to fenestrate the anterior cyst wall in the prepontine or ambient cisterns, where it provides more illumination and helps to identify the nervous and vascular structures.

Adult↗
PubMed2001

Endoscopic surgery for pineal region tumors.

Endoscopic surgery may play an important role in most patients with pineal region tumors. We report our experience with 5 patients treated by a burr hole endoscopic technique. The procedure included in all cases third ventriculostomy for the correction of hydrocephalus, CSF sample for cytology and tumor markers, and tumor biopsy for histological diagnosis. Endoscopic biopsies showed a pineocytoma in two cases, a germinoma in 2 and a low-grade astrocytoma in one. We agree that endoscopic surgery may allow us to select cases requiring a microsurgical approach (medium-sized or large non-germ-cell tumors) from cases to be treated only by irradiation and chemotherapy (germinomas and other non-germ-cell tumors). Then, in some patients with pineal region tumors the endoscopic procedure remains the only surgical treatment. When a direct microsurgical approach is indicated, it may be performed in a non-emergency situation and after correction of the hydrocephalus by endoscopic third ventriculostomy.

Adolescent↗
PubMed2001

[Circulating biomarkers association in the follow-up of patients with oral cancer].

The goal of this study is to analyze the importance of circulating biomarkers association in the management of patients affected by oral cancer. In this study a survey is made of the international experience from 1980 to 1990 based on the presence of CEA, LASA, SCC Ag, TPA, ferritina, CA-50 and others in patients affected by oral cancer and the sensitivity and specificity of these circulating biomarkers association are assessed. In patients with active disease, the results obtained at the time of diagnosis of oral cancer are not satisfactory due to poor specificity of these circulating biomarkers association. The conclusions is drawn that the circulating biomarkers association (especially CEA, SCC Ag, LASA, ferritin, TPA and CA-50) appears to be useful in the prognosis and staging of oral cancer, while their presence is not significative for the diagnosis.

Biomarkers, Tumor↗
PubMed2000

Inhibition of telomerase activity by a hammerhead ribozyme targeting the RNA component of telomerase in human melanoma cells.

Reactivation of telomerase, an RNA-dependent DNA polymerase that synthesizes new telomeric repeats at the end of chromosomes, is a very common feature in human cancers. Telomerase is thought to be essential in maintaining the proliferative capacity of tumor cells and, as a consequence, it could represent an attractive target for new anti-cancer therapies. In this study, we generated a hammerhead ribozyme composed of a catalytic domain with flanking sequences complementary to the RNA component of human telomerase and designed to cleave specifically a site located at the end of the telomerase template sequence. In vitro the ribozyme induced cleavage of a synthetic RNA substrate obtained by cloning a portion of the RNA component of human telomerase. The extent of cleavage was dependent on the ribozyme/substrate ratio as well as the Mg2+ concentration. Moreover, when added to cell extracts from two human melanoma cell lines (JR8 and M14), or three melanoma surgical specimens, the ribozyme inhibited telomerase activity in a concentration- and time-dependent manner. When the ribozyme was delivered to growing JR8 melanoma cells by (N-(1-(2,3 dioleoxyloxy)propil)-N,N,N trimethylammonium methylsulfate-mediated transfer, a marked inhibition of telomerase activity was observed. Next, the ribozyme sequence was cloned in an expression vector and JR8 cells were transfected with it. The cell clones obtained showed a reduced telomerase activity and telomerase RNA levels and expressed the ribozyme. Moreover, ribozyme transfectants had significantly longer doubling times than control cells and showed a dendritic appearance in monolayer culture. No telomere shortening, however, was observed in these clones. Overall, our results indicate that the hammerhead ribozyme is a potentially useful tool for the inactivation of telomerase in human tumors.

Humans↗
PubMed1999

Endoscopic surgery for intracranial cerebrospinal fluid cyst malformations.

Endoscopic surgery represents a new and very useful modality of treatment for intracranial cysts. The authors review the cases of 19 patients with intracranial malformative CSF cysts (seven intraventricular, six paraventricular, and six arachnoid) who underwent endoscopic fenestration by using a burr-hole approach. The various endoscopic approaches and techniques of fenestration, according to the type and location of the cyst, and the causes of unsuccessful outcome are critically discussed. The authors recommend endoscopic fenestration as the treatment of choice for patients with para- and intraventricular cysts, in whom the procedure may help to avoid the microsurgical approach and shunt placement in nearly all patients. In patients with arachnoid cysts, the endoscopic procedure, although associated with a lower rate of successful outcome, may be performed as the primary procedure in most cases because it is a minimally invasive procedure; the traditional surgical treatment may be performed without additional risk in which endoscopic surgery has failed.

Journal Article↗
PubMed1999

Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours.

BACKGROUND: The DNA repair protein O6-alkylguanine-DNA alkyl transferase (AT) mediates resistance to chloroethylnitrosoureas. Agents depleting AT such as DTIC and its new analogue temozolomide (TMZ) can reverse resistance to chloroethylnitrosoureas. We report the results of a dose finding study of TMZ in association with fotemustine. PATIENTS AND METHODS: Twenty-four patients with metastatic melanoma or recurrent glioma were treated with escalating dose of oral or intravenous TMZ ranging from 300 to 700 mg/m2, divided over two days. Fotemustine 100 mg/m2 was given intravenously on day 2, 4 hours after TMZ. AT depletion was measured in peripheral blood mononuclear cells (PBMCs) and in selected cases in melanoma metastases and was compared to TMZ pharmacokinetics. RESULTS: The maximum tolerated dose (MTD) of TMZ was 400 mg/m2 (200 mg/m2/d) when associated with fotemustine the 2nd day with myelosuppression as dose limiting toxicity. The decrease of AT level in PBMCs was progressive and reached 34% of pretreatment values on day 2. There was however wide interindividual variability. AT reduction was neither dose nor route dependent and did not appear to be related to TMZ systemic exposure (AUC). In the same patients, AT depletion in tumour did not correlate with the decrease of AT observed in PBMCs. CONCLUSIONS: PBMCs may not be used as a surrogate of tumour for AT depletion. Further study should concentrate on the pharmacokinetic pharmacodynamic relationship in tumour to provide the basis for individually tailored therapy.

Adult↗
PubMed1999

Mismatch repair deficiency is associated with resistance to DNA minor groove alkylating agents.

Mismatch DNA repair deficiency is associated with resistance to certain major groove alkylating agents including methylating agents and cisplatin. We have now studied the relevance of mismatch repair alterations to the cytotoxicity induced by drugs which alkylate N3 adenines in the minor groove of DNA. We have used the mismatch repair defective human colocarcinoma cell line HCT-116 which has a mutation in the hMLH1 gene, and a subline where hMLH1 expression is restored by chromosome 3 transfer (HCT-116+ch3). We have tested three alkylating minor groove binders (tallimustine, carzelesin and CC1065) and one non-covalent minor groove binder (PNU 151807). The HCT-116+ch3 subline was more sensitive than the parental line to the treatment with the three alkylating minor groove binders, while the non-alkylating compound had a similar activity in both cell lines. Further support for mismatch repair being involved in sensitivity of the minor groove alkylators is that two cisplatin-resistant sublines of the human ovarian adenocarcinoma cell line A2780 (A2780/CP70 and A2780/MCP-1) are defective in hMLH1 expression and are more resistant to these agents than the parental mismatch repair proficient cells. Furthermore, the restoration of hMLH1 activity in the A2780/CP70 cell line, by introduction of chromosome 3, was associated with an increased sensitivity to the three alkylating minor groove binders. Again, the non-covalent minor groove binder was equally effective in mismatch repair deficient and proficient clones. The data indicate that mismatch repair deficiency mediated by loss of hMLH1 expression is associated not only with drug-resistance to major groove binders, but also to minor groove binders. However, loss of mismatch repair does not mediate resistance to the non-covalent minor groove binder PNU 151807.

Adenocarcinoma↗
PubMed1999

Cooperation between p53 and hMLH1 in a human colocarcinoma cell line in response to DNA damage.

We have studied the possible interactions between the mismatch repair system and p53 in a human colon cancer cell line, HCT-116 (known to have a homozygous mutation in mismatch repair gene hMLH1 on chromosome 3) and in a clone obtained after insertion of a single copy of chromosome 3 (HCT-116+ ch3). Loss of DNA mismatch repair activity resulted in resistance to cisplatin (DDP). p53 accumulated differently in these cell lines after treatment with DDP. Initially at similar high levels after DDP treatment, p53 maintained the increase in HCT-116 cells, even 72-96 h after drug exposure, whereas HCT-116+ch3 mismatch-proficient cell line p53 declined to basal levels after 48 h. The higher levels of p53 in mismatch-deficient HCT-116 cells were accompanied by increased transcriptional activity as assessed by the gel-retardation assay and by activation of a promoter containing a p53 DNA binding site. To better understand the role of p53, if any, in cell sensitivity to DDP, we disrupted p53 in both cell lines by stable transfection with the human papillomavirus type 16 E6 gene. HCT-116/E6 cells were more sensitive to DDP than the parental cell line, whereas HCT-116+ch3/E6 were fairly similar to HCT-116+ch3 with normal p53 function. Although in our system the transfer of the entire chromosome 3 was used (thus not excluding a possible role of other genes localized on this chromosome), our data indicate that p53 can cooperate with the mismatch repair system. In fact, the lack of hLMH1, at least in these cells, enhances the role of p53 in protecting the cells from DDP-induced DNA damage.

Adaptor Proteins, Signal Transducing↗
PubMed1999

[Changes in the mouth mucosa in patients with chronic inflammatory intestinal diseases].

BACKGROUND: Oral mucosa and periodontal lesions occurrence in Inflammatory Bowel Disease (IBD), Ulcerative Colitis (UC) and Crohn Disease (CD). METHODS: This study involved 100 patients examined for 5 years (1990/1995), with a clinical and histopathological diagnosis of CD (21 patients) and UC (79 patients). RESULTS: The analysis of the data obtained, from our sample, showed that 5 patients out of 100 presented aphtha minor lesions; in 3 cases the diagnosis was, respectively, of two neoformations of the genian mucosa--which turned out to be a papilloma and a fibroma--and a retro-commissural leukoplakia, degree OIN I. The 50% of our patients presented parodontal lesions, oral candidosis in 15 out of 67 patients who presented a whitish coating on the back of the tongue. CONCLUSIONS: The results of this investigation, lessen the importance of an association between IBD and oral diseases.

Adolescent↗
PubMed1999

Microsatellite instability and frameshift mutations in genes involved in cell cycle progression or apoptosis in ovarian cancer.

The loss of mismatch repair enzymes increases the mutation rate in microsatellites and coding regions of the genome and appears to be involved in drug resistance. The replication error (RER+) phenotype, associated with microsatellite instability, has been widely described for both familial and sporadic colon cancers and for gastric and endometrial tumors. For ovarian cancer, the incidence of RER+ cases among sporadic tumors is still uncertain. We analyzed epithelial ovarian tumors and ovarian carcinoma cell lines for microsatellite instability and for mutations in the coding regions of different genes, including the recently discovered human CHK-1 gene, which has an important role in controlling cell cycle progression and whose coding region contains a poly(A)9 tract. Microsatellite instability and frameshift mutations in coding regions of BAX, TGFbetaRII, IGFIIR, E2F-4, ICE, and CHK-1 genes were analyzed in ovarian cancer samples and cell lines by polymerase chain reaction (PCR). Approximately 26% of patients showed microsatellite instability in two or more loci. BAT-26 locus showed no alteration in primary tumors. We detected a BAX mutation in one tumor sample and a TGFbetaRII mutation in one cell line. Our findings confirm the presence of the RER+ phenotype in sporadic ovarian cancer. The low rate of mutation in genes previously reported to be altered in colon and gastric cancer suggests that other not yet identified genes might be altered and could play a role in tumor progression and response to treatment in RER+ ovarian tumors.

Adult↗
PubMed1999

[Basaloid squamous carcinoma of the tongue. Clinico-anatomical study of a case].

The basaloid squamous carcinoma was first described in 1986. It is a rare tumor with particular morphologic and biologic features that separate it from the more common squamous cell carcinoma of the head and neck region. A case with histologic diagnosis of basaloid squamous carcinoma of the tongue treated only with radiotherapy, is reported.

Aged↗
PubMed1998

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↗
PubMed1998

Hepatocellular carcinoma: comparison between liver transplantation, resective surgery, ethanol injection, and chemoembolization.

Between January 1989 and June 1997, 533 patients (423 male, 110 female, mean age 61 years, range 22-89 years) with hepatocellular carcinoma (HCC) were observed at our center. We report on 419 patients retrospectively compared for different treatments: liver transplantation (LT; 55 patients), resective surgery (RS; 41 patients), transarterial chemoembolization (TACE; 171 patients) and percutaneous ethanol injection (PEI; 152 patients). The 3- and 5-year actuarial survival rates were, respectively, 72% and 68% for LT, 64 and 44% for RS, 54 and 36% for PEI, and 32 and 22% for TACE. Survival curves were compared for sex, age, tumor characteristics, alphafetoprotein level, Child class, and etiology of cirrhosis. All patient-related characteristics examined (sex, age) are not significantly related to patient survival. Tumor-related variables and associated liver disease variables significantly conditioned survival in relation to different treatments. LT seems to be the treatment of choice for monofocal HCC less then 5 cm in diameter and in selected cases of plurifocal HCC.

Actuarial Analysis↗
PubMed1998

Olfactory groove meningioma with paranasal sinus and nasal cavity extension: removal by combined subfrontal and nasal approach.

A very unusual case of olfactory groove meningioma with recurrence extending into the paranasal sinuses and nasal cavities, 15 years after the first transcranial operation, is described. The patient was successfully treated by a combined subfrontal and nasal approach. Large downward extension of an olfactory groove meningioma into the nasal cavities is a rare event, with no or isolated cases reported even in large series of these tumours. The nasal extent of these meningiomas is more often asymptomatic, although signs of sinus obstruction and epistaxis have been described. Although small paranasal sinus extensions of the meningioma may be removed by the transcranial route, a combined subfrontal and nasal approach is necessary in cases with large tumour masses extending into the nasal cavities, as in our own one.

Adult↗
PubMed1998

IFN-beta partially counteracts inhibition of natural killer activity induced by some antitumor agents.

We investigated whether recombinant human (rHu-IFN-beta) (IFN-beta) could counteract the inhibition of natural killer (NK) activity caused by antitumor agents. Peripheral blood lymphocytes (PBL) were incubated with different antitumor agents alone or in combination with IFN-beta for 3 days and then tested in a cytotoxicity assay against the K562 cell line. The following drugs were used, all of which caused a dose-dependent inhibition of NK activity: etoposide, camptothecin, doxorubicin, cis-DDP, tallimustine, and L-PAM. Concomitant treatment with (1000 U/ml) IFN-beta counteracted the inhibitory effect of etoposide and camptothecin but had no consistent effect on the inhibition mediated by the other drugs. Mean values of inhibition of NK activity at 1 microM camptothecin was 48%+/-3.4% and with IFN-beta was 10%+/-4.9%. With 100 microM etoposide, mean value of inhibition was 78%+/-3.3%, and with IFN-beta, it was 18%+/-1.5%. Cell viability, assessed by vital dye exclusion, and drug uptake, assessed with radiolabeled etoposide, were similar in cells treated with or without IFN-beta. The protective effect of IFN-beta on NK function was rather selective, as IFN-beta did not counteract the drug-mediated inhibition of PBL proliferation when stimulated by phytohemagglutinin (PHA). Other cytokines, IFN-alpha, IFN-gamma, and interleukin-2 (IL-2), had similar protective effect, although IFN-beta, was slightly more potent. On the other hand, IL-6, a cytokine sharing some properties with IFNs was ineffective. Camptothecin inhibited the expression of mRNA for granzyme B, a lytic protein involved in lymphoid-mediated cytotoxicity. Combined treatment with IFN-beta restored-at least in part-the transcription of granzyme B mRNA. These results show that the immunosuppressive effect of some antitumor agents could be partly counteracted by treatment with IFN-beta.

Antineoplastic Agents↗
PubMed1998

hMLH1 and hMSH2 expression and BAX frameshift mutations in ovarian cancer cell lines and tumors.

The expression of mismatch repair proteins hMSH2 and hMLH1 was investigated in human ovarian cancer cell lines and in biopsies of ovarian carcinomas obtained from 20 patients undergoing surgical operation. By Western blotting analysis hMSH2 protein was detected in all the tumor samples analyzed and in eight out of nine human ovarian cancer cell lines, while hMLH1 was undetectable in four out of 20 ovarian tumors and in five out of nine human ovarian cancer cell lines analyzed. The possible presence of frameshift mutations in the BAX gene, which contains a sequence of eight contiguous guanines in its third exon, was tested in all the samples. All the cell lines presented the normal alleles for the BAX gene while only in one of the tumor samples a heterozygous frameshift mutation was found. The frameshift mutation was associated to a low, almost undetectable, level of BAX protein which was instead present at much higher levels in all the other samples investigated. The results indicate that frameshift mutations in the BAX gene, possibly arising as a consequence of microsatellite instability (detectable in these tumors), is detectable in human ovarian cancer although quantitatively it does not appear to be a major determinant of the low apoptotic response to chemotherapy observed in ovarian cancer cells.

Adaptor Proteins, Signal Transducing↗