Biomedical subjects

L Frigerio

Publications and source records attributed to L Frigerio.

At least 19 recordsLinked to original sources

PubMed2006

Laparoscopic-assisted vaginal hysterectomy versus abdominal hysterectomy in endometrial cancer.

OBJECTIVE: To see whether laparoscopy provides exact staging and effective treatment of endometrial cancer patients, compared with total abdominal hysterectomy, with shorter hospital stay, prompter recovery, and better quality of life. METHOD: This retrospective study identified 110 patients scheduled for surgery for early-stage endometrial cancer. Fifty-five (50%) were treated by laparoscopic-assisted vaginal hysterectomy (LAVH) and 55 (50%) by total abdominal hysterectomy (TAH). All patients underwent pelvic lymphadenectomy. The majority of patients (79%) had stage I disease. RESULTS: The mean number of lymph nodes removed was 17 for the LAVH group and 18.5 for the TAH group (p = 0.294). Compared with TAH, LAVH required a significantly longer operating time (220 vs. 175 min; p < 0.01); but shorter hospital stay (4 vs. 8.5 days; p < 0.001) and less estimated blood loss (177 cm3 vs. 285 cm3; p = 0.02). Overall, there were fewer post-operative complications in the LAVH group (6 vs. 11 cases; p < 0.001). Three TAH patients (5.4%) had recurrence of disease. No LAVH patients had recurrences and all are currently disease-free. CONCLUSION: These findings suggest LAVH gives correct staging of endometrial disease, like TAH, but with fewer complications and a slightly longer operating time.

Adult↗

PubMed2005

Pathways for protein transport to seed storage vacuoles.

Plant vacuoles have multiple functions: they can act both as digestive organelles and as receptacles for storage proteins. Different types of vacuoles can coexist in the same cell, which adds complexity to the process of targeting to these compartments. A fuller understanding of this process is of evident value when endeavouring to exploit the plant secretory pathway for heterologous protein production. Positive sorting signals are required in order to sort proteins to vacuoles, and these have been split into three groups: ctVSS [C-terminal VSS (vacuolar sorting signals)], ssVSS (sequence-specific VSS) and physical structure VSS. The current working model posits that soluble proteins are delivered from the Golgi apparatus to the lytic vacuoles in clathrin-coated vesicles by virtue of their ssVSS, or to the storage vacuole [PSV (protein-storage vacuole)] in dense vesicles in a manner dependent on ctVSS or physical structure VSS. Although targeting to LV appears to be receptor-mediated, no such receptor has been identified for the recruitment of proteins to the PSV. We have studied the vacuolar targeting of two castor bean (Ricinus communis L.) storage proteins, proricin and pro 2 S albumin, in their native endosperm and in the heterologous system of tobacco protoplasts. We have found that both these proteins contain bona fide ssVSS and bind to sorting receptors in vitro in a similarly sequence-specific manner. The apparent similarities to lytic VSS and possible implications with respect to the working model for transport to storage vacuoles are discussed.

Ricinus communis↗

PubMed2002

Identification of high risk patients with endometrial carcinoma. Prognostic assessment of endometrial cancer.

OBJECTIVES: To verify the importance of DNA ploidy on clinical outcome in endometrial carcinoma and to investigate whether the prognostic information obtained by this variable is independent from other clinical-pathologic features. MATERIALS AND METHODS: Univariate and multivariate analysis of clinical and pathologic prognostic factors obtained from 203 consecutive cases of endometrial cancer, that had been surgically treated in our hospital, were performed. RESULTS: Significant prognostic factors according to the Kaplan-Meier method were age at the time of diagnosis, grade of differentiation, peritoneal cytology, node involvement, vascular invasion, myometrial infiltration and ploidy. At multivariate analysis only DNA ploidy resulted to be an independent variable. CONCLUSIONS: In our analysis DNA content is the only parameter which preserved prognostic significance in multivariate analysis.

Adult↗

PubMed2001

Ricin A chain without its partner B chain is degraded after retrotranslocation from the endoplasmic reticulum to the cytosol in plant cells.

When expressed in tobacco cells, the catalytic subunit of the dimeric ribosome inactivating protein, ricin, is first inserted into the endoplasmic reticulum (ER) and then degraded in a manner that can be partially inhibited by the proteasome inhibitor clasto-lactacystin beta-lactone. Consistent with the implication of cytosolic proteasomes, degradation of ricin A chain is brefeldin A-insensitive and the polypeptides that accumulate in the presence of the proteasome inhibitor are not processed in a vacuole-specific fashion. Rather, these stabilized polypeptides are in part deglycosylated by a peptide:N-glycanase-like activity. Taken together, these results indicate that ricin A chain, albeit a structurally native protein, can behave as a substrate for ER to cytosol export, deglycosylation in the cytosol, and proteasomal degradation. Furthermore, retrotranslocation of this protein is not tightly coupled to proteasomal activity. These data are consistent with the hypothesis that ricin A chain can exploit the ER-associated protein degradation pathway to reach the cytosol. Although well characterized in mammalian and yeast cells, the operation of a similar pathway to the cytosol of plant cells has not previously been demonstrated.

Biological Transport, Active↗

PubMed2001

Concomitant radiotherapy and paclitaxel for high-risk endometrial cancer: first feasibility study.

OBJECTIVE: Postoperative radiotherapy (RT) is the most used adjuvant treatment in high risk endometrial cancer (HREC), and it appears to reduce the incidence of pelvic relapses but doesn't seem to improve survival. Paclitaxel (P) has shown in vitro and clinical activity against endometrial cancer, and it is also a potent radiosensitizer by blocking dividing cells in G2/M phase. This is the first study that verifies the feasibility of a treatment with concomitant weekly chemotherapy and RT to potentially reduce the incidence of local and distant relapses in order to improve survival in HREC. PATIENTS AND METHODS: Thirteen patients with HREC have entered the feasibility study at San Raphael Hospital University of Milan. All patients underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and surgical staging. Four patients presented stage IC disease, 2 women had IIB stage tumors, 5 patients revealed IIIA stage disease, and 2 had stage IIIC. The patients received P (60 mg./m(2)) via a continuous 1-h infusion once weekly during the 5 weeks of RT (mean radiation dose of 50.4 Gy). At the end of RT three additional consolidation courses of P (80 mg/m(2)) were subministered. Eleven patients received only pelvic irradiation; in 2 cases radiotherapy was performed on an extended field. RESULTS: Eleven of the 13 enrolled patients have completed the radiochemotherapy regimen. A total of 100 courses of P were performed. All patients completed the RT. Adverse effects were evaluated. Hematological toxicity was mild: four cycles (4%) were delayed 1 week because of grade 1 neutropenia. No severe thrombocytopenia was identified. No hemotrasfusions were performed. One cycle was delayed for fever. Gastrointestinal adverse effects were observed in 2 patients, in which the cycles were delayed 1 week because of diarrhea. One cycle was delayed 1 week because of dermatitis. One patient developed a subocclusion 8 weeks after the end of the treatment, with medical resolution. No patients developed hypersensitivity reactions. CONCLUSIONS: Concomitant P and RT is safe and acceptable treatment in patients with HREC. Prospective clinical studies are necessary to evaluate the benefits of this regimen for the long-term survival rate.

Aged↗

PubMed2001

The internal propeptide of the ricin precursor carries a sequence-specific determinant for vacuolar sorting.

Ricin is a heterodimeric toxin that accumulates in the storage vacuoles of castor bean (Ricinus communis) endosperm. Proricin is synthesized as a single polypeptide precursor comprising the catalytic A chain and the Gal-binding B chain joined by a 12-amino acid linker propeptide. Upon arrival in the vacuole, the linker is removed. Here, we replicate these events in transfected tobacco (Nicotiana tabacum) leaf protoplasts. We show that the internal linker propeptide is responsible for vacuolar sorting and is sufficient to redirect the ricin heterodimer to the vacuole when fused to the A or the B chain. This internal peptide can also target two different secretory protein reporters to the vacuole. Moreover, mutation of the isoleucine residue within an NPIR-like motif of the propeptide affects vacuolar sorting in proricin and in the reconstituted A-B heterodimer. This is the first reported example of a sequence-specific vacuolar sorting signal located within an internal propeptide.

Amino Acid Sequence↗

PubMed2001

Influence of KDEL on the fate of trimeric or assembly-defective phaseolin: selective use of an alternative route to vacuoles.

The tetrapeptide KDEL is commonly found at the C terminus of soluble proteins of the endoplasmic reticulum (ER), and it contributes to their localization by interacting with a receptor that recycles between the Golgi complex and the ER. We investigated the effects of the addition of KDEL to phaseolin, a protein normally delivered from the ER to storage vacuoles via the Golgi complex. We show that KDEL prevents acquisition of trans-Golgi-specific glycan modifications and causes interactions with the chaperone BiP that are distinct from the ones between BiP and defective proteins. KDEL markedly increases the stability of phaseolin, but a small proportion of phaseolin-KDEL slowly reaches the vacuole without undergoing Golgi-mediated glycan modifications, in a process that can be inhibited by brefeldin A but not monensin. Our results indicate that KDEL can operate with high efficiency before proteins can reach the late Golgi cisternae but allows or promotes delivery to vacuoles via an alternative mechanism. However, addition of KDEL does not alter the destiny of an assembly-defective form of phaseolin, suggesting that the plant ER quality control mechanism is dominant over KDEL effects.

Carrier Proteins↗

PubMed2001

[Percutaneous implant of Denver peritoneovenous shunt: a new opportunity for the interventional radiologist].

PURPOSE: The study is aimed at presenting our experience in the implant of Denver peritoneovenous shunts. Medical treatment-resistant ascites, either neoplastic or related to hepatic failure, is highly symptomatic and its treatment is indicated in order to improve patients' quality of life. One of the most efficient methods of treatment consists in implanting a peritoneovenous shunt. The availability of this device and its percutaneous implantation provide Interventional Radiologists with the possibility of expanding their repertoire. MATERIAL AND METHODS: Thirteen shunts were implanted in 12 patients, 10 with neoplastic ascites and 2 with hepatic failure-related ascites. In 1 patient a second device had to be implanted. All the procedures were performed in the Interventional Radiology Department, under local anesthesia and mild sedation. The central venous access was by the subclavian vein in 7 cases and the internal jugular vein in 6 cases. The puncture kit is consists of 2 needles, 1 for venous puncture and 1 for peritoneal puncture, 2 angiographic J-guide wires, 2 peel-away introducers, and a chamber containing the double valve-pump connected with both the venous and the peritoneal catheters. The whole device is placed subcutaneously thus allowing fluids to flow from the peritoneum to the vein either spontaneously, if intra-abdominal pressure exceeds 3cm of water, or by manual compression exerted on the pump itself. RESULTS: All implants were successfully performed. One transient complication occurred consisting in a mild inflammatory reaction along the subcutaneous catheter route, which promptly solved by antibiotic therapy. So far a total of 1773 catheter/days have been accumulated. 7/10 of the neoplastic patients died from progressive disease after 915 catheter/days (median 120, range 30-180). In a cirrhotic patient the first shunt occluded after 430 days due to hemoperitoneum caused by hepatic biopsy: it was removed and a new one implanted. Five shunts are in now use, with a follow-up of 30, 48, 70, 120 and 160 days each. DISCUSSION: The implanting technique was well tolerated by all patients and it could be performed under local anesthesia. The central vein puncture was easy for both accesses but the introducer diameter (12F) and the possibility of clavicle pinch-off induced us to use the internal jugular approach in the last six cases, which provided a reduced risk of pneumothorax and a better catheter track. In the patients with neoplastic ascites we observed neither disease dissemination nor changes in the patients' changed related to the shunt. Our results show that the implant of Denver venous-peritoneal shunts is a relatively easy procedure, which can be performed by Interventional Radiologists on a regular basis.

Adult↗

PubMed2000

Glycoprotein degradation: do sugars hold the key?

Secretory glycoproteins that fail to fold or assemble correctly are retained in the endoplasmic reticulum and eventually degraded. Recent evidence shows that trimming of their N-linked oligosaccharide chains plays a key role in targeting glycoproteins for destruction.

Calcium-Binding Proteins↗

PubMed2000

Endoplasmic reticulum-associated protein degradation.

The quality control system in the endoplasmic reticulum of eukaryotic cells ensures that newly synthesized proteins that fail to fold into the correct conformation or unassembled orphan subunits of oligomeric proteins are rapidly eliminated by proteolytic degradation. This entails the export of proteins from the endoplasmic reticulum to the cytosol followed by their destruction by the cytosolic ubiquitin/proteasome pathway. While this mechanism effectively prevents the cellular accumulation of non-functional or unwanted endogenous proteins, it renders the cell vulnerable to certain viruses and toxins that are able to subvert this degradative mechanism for their own advantage.

Autophagy↗

PubMed2000

Diagnosis of persistent ovarian carcinoma with three-step immunoscintigraphy.

The diagnosis of recurrent ovarian carcinoma is usually determined at surgical re-exploration since the main non-invasive diagnostic tests have low accuracy. It would be desirable to have a high accuracy non-invasive diagnostic procedure. With this aim, we have assessed the utility of three-step immunoscintigraphy. Thirty patients were intravenously injected with biotinylated monoclonal antibodies MOv18 and B72.3, followed by avidin-streptavidin injection and finally by 111In-biotin. Tumour recurrences were imaged 2 h post radioactivity injection. All patients underwent surgical re-exploration 3-4 days after immunoscintigraphy; the presence of tumour in the area of immunoscintigraphic uptake was evaluated in the biopsied material. Twenty-one patients studied were true-positive, five were true-negative, four were false-positive and none was false-negative. The diagnostic accuracy, positive predictive value and negative predictive value were 87%, 84% and 100% respectively. If these findings are confirmed in a larger number of patients, we expect immunoscintigraphy to be introduced as a cost-effective procedure in the follow-up of patients who have received surgery for ovarian carcinoma, since it promises to reliably identify patients who do not require surgical re-exploration, and guide biopsies when they are indicated.

Adult↗

PubMed2000

Assembly, secretion, and vacuolar delivery of a hybrid immunoglobulin in plants.

Secretory immunoglobulin (Ig) A is a decameric Ig composed of four alpha-heavy chains, four light chains, a joining (J) chain, and a secretory component (SC). The heavy and light chains form two tetrameric Ig molecules that are joined by the J chain and associate with the SC. Expression of a secretory monoclonal antibody in tobacco (Nicotiana tabacum) has been described: this molecule (secretory IgA/G [SIgA/G]) was modified by having a hybrid heavy chain sequence consisting of IgG gamma-chain domains linked to constant region domains of an IgA alpha-chain. In tobacco, about 70% of the protein assembles to its final, decameric structure. We show here that SIgA/G assembly and secretion are slow, with only approximately 10% of the newly synthesized molecules being secreted after 24 h and the bulk probably remaining in the endoplasmic reticulum. In addition, a proportion of SIgA/G is delivered to the vacuole as at least partially assembled molecules by a process that is blocked by the membrane traffic inhibitor brefeldin A. Neither the SC nor the J chain are responsible for vacuolar delivery, because IgA/G tetramers have the same fate. The parent IgG tetrameric molecule, containing wild-type gamma-heavy chains, is instead secreted rapidly and efficiently. This strongly suggests that intracellular retention and vacuolar delivery of IgA/G is due to the alpha-domains present in the hybrid alpha/gamma-heavy chains and indicates that the plant secretory system may partially deliver to the vacuole recombinant proteins expected to be secreted.

Brefeldin A↗

PubMed1998

Free ricin A chain, proricin, and native toxin have different cellular fates when expressed in tobacco protoplasts.

The catalytic A subunit of ricin can inactivate eukaryotic ribosomes, including those of Ricinus communis where the toxin is naturally produced. How such plant cells avoid intoxication has remained an open question. Here we report the transient expression of a number of ricin A chain-encoding cDNA constructs in tobacco protoplasts. Ricin A chain entered the endoplasmic reticulum lumen, where it was efficiently glycosylated, but it was toxic to the cells and disappeared with time in a brefeldin A-insensitive manner, suggesting reverse translocation to the cytosol and eventual degradation. Proricin (the natural precursor form containing A and B chains joined together by a linker sequence) was glycosylated, transported to the vacuole, and processed to its mature form, but was not toxic. Free ricin A chain and proricin were not secreted, whereas free ricin B chain was found entirely in the extracellular medium. The coexpression of ricin A and B chains resulted in the formation of disulfide-linked, transport-competent heterodimers, which were secreted, with a concomitant reduction in the observed cytotoxicity. These results suggest that the production of ricin as a precursor is essential for its routing to the vacuole and for protection of ricin-producing cells.

Ricinus communis↗

PubMed1998

The level of urokinase-type plasminogen activator receptor is increased in serum of ovarian cancer patients.

Ascites and serum of patients with ovarian carcinoma contain a soluble form of urokinase-type plasminogen activator receptor (uPAR). We now report that pro-uPA-Sepharose-purified uPAR from ascites of patients with ovarian carcinoma is the full-length molecule missing the glycosyl-phosphatidylinositol anchor, as determined by its amino acid composition. We next examined the significance of determining serum soluble uPAR (suPAR) levels in ovarian cancer patients using a specific ELISA and compared the results with serum concentrations of CA-125, an established diagnostic marker. Serum from pre- and postoperative ovarian cancer patients was assayed for suPAR and CA-125. The majority of the patients with ovarian cancer had enhanced preoperative serum levels of suPAR compared with healthy controls, but suPAR concentrations decreased after operation. Although uPAR was associated with most ovarian carcinomas, it appeared to be a less specific indicator for ovarian cancer than CA-125. On the other hand, suPAR was more specific for other types of solid tumors. Moreover, we have observed some cases of ovarian cancer that showed increase of suPAR but not of CA-125. The prognostic significance of serum suPAR assay for survival of ovarian carcinoma patients was evaluated using Cox's proportional hazards analysis. Our preliminary data show that high preoperative levels of suPAR were associated with worse survival of the patients, whereas CA-125 had no prognostic implications. This is the first report evaluating the assay of serum suPAR levels in ovarian cancer and analyzing its value as a tumor or prognostic marker.

Amino Acids↗

PubMed1998

Sclerosing stromal tumor of the ovary. Report of eight cases and review of the literature.

In this article, we describe eight cases of sclerosing stromal tumors (SST) of the ovary and review the literature. We could not demonstrate unequivocal hormonal activity in any of the cases, although suggestive evidence for it has been reported in the literature in the form of clinical, histologic, electron microscopic and immunohistochemical findings.

Adolescent↗

PubMed1998

Sorting of phaseolin to the vacuole is saturable and requires a short C-terminal peptide.

Phaseolin, one of the major legume proteins for human nutrition, is a trimeric glycoprotein of the 7S class that accumulates in the protein storage vacuoles of common bean. Phaseolin is cotranslationally introduced into the lumen of the endoplasmic reticulum; from there, it is transported through the Golgi complex to the storage vacuoles. Phaseolin is also transported to the vacuole in vegetative tissues of transgenic plants. By transient and permanent expression in tobacco leaf cells, we show here that vacuolar sorting of phaseolin is saturable and that saturation leads to Golgi-mediated secretion from the cell. A mutated phaseolin, in which the four C-terminal residues (Ala, Phe, Val, and Tyr) were deleted, efficiently formed trimers but was secreted entirely outside of the cells in transgenic tobacco leaves, indicating that the deleted sequence contains information necessary for interactions with the saturable vacuolar sorting machinery. In the apoplast, the secreted phaseolin remained intact; this is similar to what occurs to wild-type phaseolin in bean storage vacuoles, whereas in vegetative vacuoles of transgenic plants, the storage protein is fragmented.

Amino Acid Sequence↗

PubMed1998

Hashimoto's disease in a papillary carcinoma of the thyroid originating in a teratoma of the ovary (malignant struma ovarii).

Adenocarcinomas represent a relatively rare complication of a cystic teratoma of the ovary. Those of thyroid origin have been reported in only a few cases. In this paper we report a case of papillary carcinoma of the thyroid arising from a cystic teratoma. The patient had no thyroid symptoms, but because of the presence of antimicrosomal and antithyroglobulin antibodies the diagnosis of Hashimoto's disease was made.

Autoantibodies↗

PubMed1997

The triangular vaginal patch sling for stress urinary incontinence and hypermobile urethra.

OBJECTIVE: We describe an alternative sling procedure that permits concomitant correction of urethral hypermobility and urinary incontinence through a single surgical exposure. STUDY DESIGN: Fifteen women with severe urinary stress incontinence and urethral hypermobility underwent a sling procedure by creation of a simple triangular patch from the anterior vaginal wall. RESULTS: The mean operative time for the vaginal sling procedure was 38 minutes (range 29 to 65 minutes) in addition to other operations. The mean postoperative hospital stay was 7.7 days (range 5 to 13 days) and all patients were routinely discharged with an indwelling Foley catheter. Spontaneous micturition occurred in 12 patients after a mean period of 25 days (range 13 to 36 days). In three cases long-term catheterization was necessary. By subjective and objective evaluations, all the patients were cured of their stress incontinence. CONCLUSION: The triangular vaginal patch with the single sutures on each side provides an alternative approach for bladder neck stabilization that may permit a more anatomic suspension of a hypermobile urethra.

Aged↗