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Biomedical subjects

Piero Berti

Publications and source records attributed to Piero Berti.

26 records · Page 2Linked to original sources

Regulation of telomerase and its hTERT messenger in colorectal cancer.

Telomeres are the distal ends of human chromosomes composed of tandem repeats of the sequence TTAGGG. In most human somatic cells, telomerase activity is undetectable, and the telomere length is progressively shortened during cell proliferation, leading to cellular senescence. In contrast, telomerase is activated in the vast majority of cancer cells, including colorectal cancer. The human telomerase complex is comprised of multiple components, but telomerase reverse transcriptase (hTERT) is the most important component for the control of telomerase activity. The p53 protein is a transcription factor with multiple biological activities, including cell cycle arrest and/or apoptosis upon DNA damage, hypoxia and oncogene activation; this requires transactivation or repression of specific target genes by wild-type p53. To better understand if a link between hTERT/telomerase regulation and p53 status exists in colorectal carcinogenesis, we analysed 43 cases of colorectal carcinoma for hTERT mRNA expression and telomerase activity. Moreover, a complete analysis of p53 status was performed. Alterations of p53 gene were found in 44.19% of cases and missense point mutations represented a high proportion of p53. Both telomerase activity (p=0.014) and hTERT expression (p=0.03) were significantly associated with p53 mutations, suggesting a role of p53 in the signaling pathway for telomerase control.

Adenocarcinoma↗

Galectin-3 and oncofetal-fibronectin expression in thyroid neoplasia as assessed by reverse transcription-polymerase chain reaction and immunochemistry in cytologic and pathologic specimens.

Oncofetal fibronectin (onfFN) and galectin-3 (Gale-3) have been proposed as possible tools for the preoperative diagnosis of thyroid carcinomas, based on the finding that the expression of both onfFN and Gale-3 are significantly increased in papillary and anaplastic carcinomas, compared to normal thyroid tissues and follicular adenomas. In this study we analyzed the expression of these markers by immunochemical and molecular analysis of benign and malignant thyroid tumors. Sixty-five thyroid nodules, consisting of 20 follicular adenomas (FAs) and 45 papillary thyroid carcinomas (PTCs) at final histology were examined. At the molecular level, among the 45 PTCs, 44 (97.8%) showed a variable level of onfFN mRNA, while 8 of the 20 (40%) adenomas expressed the same marker. Similar results have been found analyzing Gale-3 expression: 97.8% of PTC and 55% of FAs were positive for this marker. Immunohistochemistry (IHC) for Gale-3 was positive in 42 of 45 (93.3%) PTC tissues. Staining was invariably confined to the cytoplasm, with a homogeneous distribution in the large majority of the neoplastic cells. The 3 negative cases (6.7%) were represented by 2 classic variants of PTC and 1 follicular variant of PTC. Eighteen of the 20 (90.0%) adenomas stained negative for Gale-3. A significant association was found between positive staining and malignant phenotype (p < 0.0001). Gale-3 protein expression was also performed on samples obtained by ex vivo fine-needle aspiration (FNA) in 35 PTCs by immunocytochemistry (ICC). Immunoreactivity was present in 32 (91.0%) and negative in 3 (8.8%) cases. With the exception of 1 case (negative by ICC and positive by IHC), ICC and IHC were fully concordant. In conclusion, our results indicate that a search for Gale-3 protein overexpression by IIC or ICC, but not by reverse transcription-polymerase chain reaction (RT-PCR), may yield an additional marker of malignant potential of thyroid nodular lesions, and may be a useful adjunct to the currently available diagnostic tools for the preoperative diagnosis of malignant thyroid tumors.

Adenoma↗

Minimally invasive video-assisted thyroidectomy: multiinstitutional experience.

Minimally invasive video-assisted thyroidectomy (MIVAT) was described in 1998. In this study we collected the experience of four third-level referral centers that adopted this technique. A total of 336 patients (279 females, 57 males) were selected for MIVAT. Selection criteria were thyroid volume <15 ml, nodules not exceeding 3.5 cm of diameter, and an absence of thyroiditis, previous neck surgery, or previous irradiation. The procedure, totally gasless, is carried out through a 15 mm central incision above the sternal notch. Dissection is performed under endoscopic vision using conventional and endoscopic instruments. The mean operating time was 69.4 +/- 30.6 minutes for lobectomy (range 20-150 minutes) and 87.4 +/- 43.5 minutes for total thyroidectomy (range 30-220 minutes). The mean postoperative stay was 1.9 +/- 0.8 days. Postoperative complications were 7 transient and 1 definitive recurrent nerve palsies and 11 cases of hypoparathyroidism (9 transient, 2 definitive). Conversion to open surgery was necessary in 15 patients (4.5%). This study confirms in a large number of cases the safety and feasibility of MIVAT, even in different surgical settings where similar results were achieved. The complication rate was not different from that of standard thyroidectomy. Although the operating time appears longer than with conventional procedures, the learning curve demonstrates a sharp decrease with increasing experience and the introduction of new technologies. The number of patients eligible for this approach remains low, thereby limiting its use, but it should be considered a valid option in selected surgical centers, offering some advantages to patients in terms of cosmetic results and postoperative distress.

Adolescent↗

Establishment of a non-tumorigenic papillary thyroid cell line (FB-2) carrying the RET/PTC1 rearrangement.

A novel human thyroid papillary carcinoma cell line (FB-2) has been established and characterized. FB-2 cells harbor the RET/PTC1 chimeric oncogene in which the RET kinase domain is fused to the H4 gene. FB-2 cells neither formed colonies in semisolid media nor induced tumors after heterotransplant into severe combined immunodeficient mice. However, HMGI(Y), HMGI-C and c-myc genes, which are associated to thyroid cell transformation, were abundantly expressed in FB-2 cells but not in normal thyroid cells. FB-2 cells only partially retained the differentiated thyroid phenotype. In fact, the PAX-8 gene, which codes for a transcriptional factor required for thyroid cell differentiation, was expressed, while thyroglobulin, TSH-receptor and thyroperoxidase genes were not. Moreover, FB-2 cells produced high levels of interleukin (IL)-6 and IL-8.

Adult↗

Preparation with iopanoic acid rapidly controls thyrotoxicosis in patients with amiodarone-induced thyrotoxicosis before thyroidectomy.

BACKGROUND: Amiodarone-induced thyrotoxicosis (AIT) may develop either in apparently normal glands (type II AIT) or in the presence of thyroid abnormalities (type I AIT). Sometimes AIT is resistant to conventional treatment. Thyroidectomy was used in patients with AIT, but in patients who are thyrotoxic it may be hazardous. METHODS; Seven patients with AIT (6 type I and 1 type II, 5 men, 2 women, mean age 70 years [range, 60-82 years]) were prepared for total thyroidectomy with a short course of iopanoic acid (1 g/day orally for a mean of 13 days), an oral iodinated cholecystographic agent inhibiting 5'-deiodinase and causing a reduction in the peripheral conversion of thyroxine to triiodothyronine. Mean thyroid volume was 64 mL (range, 10-145 mL). RESULTS: Mean serum-free triiodothyronine levels decreased from 20 +/- 16.7 pmol/L to 6 +/- 2 pmol/L (P =.0004), whereas serum-free thyroxine values remained unchanged. Euthyroidism was rapidly (7-20 days) restored, allowing an uncomplicated total thyroidectomy in all patients and the ability to continue amiodarone therapy in 6 patients. None had increased surgical bleeding, recurrent nerve palsy, or hypoparathyroidism. No cardiovascular complications occurred. CONCLUSIONS: Iopanoic acid is an effective drug allowing rapid control of hyperthyroidism in AIT.

Aged↗

Minimally invasive video-assisted thyroidectomy for papillary carcinoma: a prospective study of its completeness.

BACKGROUND: The effectiveness of minimally invasive video-assisted thyroidectomy (MIVAT) in papillary thyroid carcinoma is still debated. Some are concerned about this procedure in patients with thyroid cancer. This prospective study aimed to demonstrate that near-total thyroidectomy can be performed by MIVAT with similar results compared with open thyroidectomy. METHODS: A total of 33 patients with a thyroid nodule proven to be a papillary thyroid carcinoma underwent a near-total thyroidectomy. They were randomly assigned to group A (n = 16) or group B (n = 17) who were treated either by MIVAT or conventional near-total thyroidectomy, respectively. Iodine-131 thyroid bed uptake and serum thyroglobulin were measured 1 month after operation. Data were analyzed by unpaired t test and Mann-Whitney statistic methods. RESULTS: . Mean iodine-131 uptake was 5.1 +/- 4.9% in group A and 4.6 +/- 6.7% in group B. Mean thyroglobulin serum levels were 5.3 +/- 5.8 ng/mL in group A and 7.6 +/- 21.7 ng/mL in group B. The differences were not statistically significant. CONCLUSIONS: The results of this study showed that the completeness obtained with MIVAT is similar to that obtained with open thyroidectomy, with the great advantage of a minimal neck wound. No conclusions can be drawn in terms of influence of MIVAT on the outcome of the patients with small papillary thyroid carcinoma.

Adult↗