PubMed Health⌕ Search

Biomedical subjects

Marco Caricato

Publications and source records attributed to Marco Caricato.

16 recordsLinked to original sources
PubMed2006

Electron transfer in a radical ion pair: quantum calculations of the solvent reorganization energy.

Results are presented for an investigation of intermolecular electron transfer (ET) in solution by means of quantum calculations. The two molecules that are involved in the ET reaction form a solvent-separated radical ion pair. The solvent plays an important role in the ET between the two molecules. In particular, it can give rise to specific solute-solvent interactions with the solutes. An example of specific interactions is the formation of a hydrogen bond between a protic solvent and one of the molecules involved in the ET. We address the study of this system by means of quantum calculations on the solutes immersed in a continuum solvent. However, when the solvent can give rise to hydrogen bond formation with the negatively charged ion after ET, we explicitly consider solvent molecules in the solute cavity, determining the hydrogen bond energetic contribution to the overall interaction energy. Solute-solvent pair distribution functions, showing the different arrangement of solvent molecules before and after ET in the first solvation shell, are reported. We provide results of the solvent reorganization energy from quantum calculations for both the two isolated fragments and the ion pair in solution. Results are in agreement with available experimental data.

Journal Article↗
PubMed2006

Chronomodulated administration of oxaliplatin plus capecitabine (XELOX) as first line chemotherapy in advanced colorectal cancer patients: phase II study.

BACKGROUND: The combination of 5-fluorouracil (5-FU), leucovorin (LV), and oxaliplatin (I-OHP) was shown to be both more active against metastatic colorectal carcinoma and better tolerated if the drug delivery rate was chronomodulated according to circadian rhythms rather than constant. The aim of the present study was to define the feasibility and efficacy of XELOX administered through a new chronomodulated schedule in untreated advanced colorectal cancer (CRC) patients. METHODS: Chemotherapy-naive patients with advanced CRC were considered eligible for the study accrual. TREATMENT: oxaliplatin 70 mg/m(2) continuous infusion (c.i.) for 12 h (8:00 a.m. to 8:00 p.m.) days 1, 8 plus chronomodulated oral capecitabine 1,750 mg/m(2)/die (h 8:00 a.m. 25% of total dose; h 6:00 p.m. 25% of total dose; h 11:00 p.m. 50% of total dose), days 1-14 every 21 days. RESULTS: Forty-six patients were evaluated for safety and efficacy (male/female, 20/26). Median age was 64 years (range 28-77 years). Median Eastern Cooperative Oncology Group performance status (PS) was 0 (range 0-1). A total of 324 cycles have been administered: median per patient 6 (range 3-10 courses). Median number of metastatic sites was 1. Metastatic sites distribution was as follows: liver (65.2%), lung (34.8%), and nodes (32.6%). Median follow-up was 14 months (range 6.0-40.3 months). In an intent-to-treat efficacy analysis, objective response and stable disease were recorded in 27 (58.6%) and in 16 patients (34.9%), respectively. The median response duration was 8.0 months (95% CI; 5.03-10.96 months). The median time to progression (TTP) was 9.0 months (95% CI; 6.47-11.52 months). The overall survival (OS) was not reached, with a median value > 24 months (95% CI; 23.66-36.30 months). The grade 3 toxicities were diarrhea (8.7%), liver toxicity (13.1%), fatigue (8.7%), neurotoxicity (2.2%), neutropenia (8.7%), and thrombocytopenia (2.2%). CONCLUSION: This regimen resulted of particular interest for patients with untreated metastatic CRC.

Adult↗
PubMed2006

Semiempirical (ZINDO-PCM) approach to predict the radiative and nonradiative decay rates of a molecule close to metal particles.

In this work, we present an extension of a model previously proposed (Andreussi et al. J. Chem. Phys. 2004, 121, 10190) to treat the effect of a metal particle on the optical properties of a molecule in solution (close to such a particle) in the framework of the polarizable continuum model (PCM). This extension concerns the combination of such a model with the semiempirical method Zerner's intermediate neglect of differential overlap (ZINDO), which allows us to treat large size molecular systems, as the ones normally used in the experiments. A refinement of the model is also introduced to take into account the effect of the metal specimen on the absorption process of the molecular system, which affects the probability that a molecule reaches the excited state. Numerical tests are presented to validate the reliability of the ZINDO results with respect to quantum-mechanical DFT methods. Comparisons with experimental results on two different large molecular systems are reported, and the effect of the metal on the absorption process is discussed.

Journal Article↗
PubMed2006

Cerebellar metastasis from pancreatic adenocarcinoma. A case report.

The first discovery of a cerebellar metastasis of pancreatic carcinoma in a living patient is described. Two years earlier the patient had undergone a pancreaticoduodenectomy for an adenocarcinoma of the head of the pancreas with a lymph node metastasis. After complete surgical removal of the tumor, he underwent adjuvant chemoradiation. Two years later the patient presented with intractable vomiting, which was attributed to peritoneal carcinomatosis. Clinical evaluation revealed an intracranial tumor without signs of pancreatic recurrence. The tumor was surgically removed. One year later the patient developed multiple brain metastases and he is currently undergoing gemcitabine-based chemotherapy.

Adenocarcinoma↗
PubMed2006

Formation and relaxation of excited states in solution: a new time dependent polarizable continuum model based on time dependent density functional theory.

In this paper a novel approach to study the formation and relaxation of excited states in solution is presented within the integral equation formalism version of the polarizable continuum model. Such an approach uses the excited state relaxed density matrix to correct the time dependent density functional theory excitation energies and it introduces a state-specific solvent response, which can be further generalized within a time dependent formalism. This generalization is based on the use of a complex dielectric permittivity as a function of the frequency, epsilonomega. The approach is here presented in its theoretical formulation and applied to the various steps involved in the formation and relaxation of electronic excited states in solvated molecules. In particular, vertical excitations (and emissions), as well as time dependent Stokes shift and complete relaxation from vertical excited states back to ground state, can be obtained as different applications of the same theory. Numerical results on two molecular systems are reported to better illustrate the features of the model.

Journal Article↗
PubMed2005

DNA end binding activity and Ku70/80 heterodimer expression in human colorectal tumor.

AIM: To determine the DNA binding activity and protein levels of the Ku70/80 heterodimer, the functional mediator of the NHEJ activity, in human colorectal carcinogenesis. METHODS: The Ku70/80 DNA-binding activity was determined by electrophoretic mobility shift assays in 20 colon adenoma and 15 colorectal cancer samples as well as matched normal colonic tissues. Nuclear and cytoplasmic protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS: A statistically significant difference was found in both adenomas and carcinomas as compared to matched normal colonic mucosa (P<0.00). However, changes in binding activity were not homogenous with approximately 50% of the tumors showing a clear increase in the binding activity, 30% displaying a modest increase and 15% showing a decrease of the activity. Tumors, with increased DNA-binding activity, also showed a statistically significant increase in Ku70 and Ku86 nuclear expression, as determined by Western blot and immunohistochemical analyses (P<0.001). Cytoplasmic protein expression was found in pathological samples, but not in normal tissues either from tumor patients or from healthy subjects. CONCLUSION: Overall, our DNA-binding activity and protein level are consistent with a substantial activation of the NHEJ pathway in colorectal tumors. Since the NHEJ is an error prone mechanism, its abnormal activation can result in chromosomal instability and ultimately lead to tumorigenesis.

Adenoma↗
PubMed2005

Continuous infusion of oxaliplatin plus chronomodulated capecitabine in 5-fluorouracil- and irinotecan-resistant advanced colorectal cancer patients.

OBJECTIVES: The aim of the study was to define the feasibility and efficacy of Xelox (capecitabine and oxaliplatin) administered through a new and original schedule in advanced pretreated colorectal cancer (CRC) patients. METHODS: 36 metastatic CRC patients resistant at least to a previous 5-fluorouracil- and irinotecan-based chemotherapy line were included in the study. TREATMENT: Oxaliplatin 70 mg/m2 as continuous infusion for 12 h (8.00 a.m. to 8.00 p.m.) on days 1, 8 plus chronomodulated capecitabine 1,750 mg/m2/day per os (8.00 a.m. 25% of total dose; 6.00 p.m. 25% of total dose; 11.00 p.m. 50% of total dose), on days 1-14 every 21 days. 16 (44.4%) patients had previously received only 1 chemotherapy line for metastatic disease and 20 patients (55.6%) 2 chemotherapy lines. Moreover, 12 patients (33.3%) progressed after a first or second line of oxaliplatin-based regimen as well. RESULTS: Most frequent related G3-4 adverse reactions were diarrhea (11.6%), nausea/vomiting (8.3%), neuropathy (8.3%), mucositis (8.3%), asthenia (16.7%) and hand-foot syndrome (5.5%). G3-4 anemia, leucopenia and liver toxicities were not observed. The overall response rate was 30.6% (11/36 patients). Disease stabilization was observed in 13 patients (36.1%) and progression in 12 patients (34.3%). Between the 12 oxaliplatin-resistant patients, the overall response rate was 25% (3 patients); 6 patients (54.5%) obtained a stable disease, and only 3 patients (25%) progressed. The median overall survival was 11.3 months (95% confidence interval 7.0-15.7 months), the median response duration 2.8 months (95% confidence interval 1.2-5.6 months) and the median time to progression 6.7 months (95% confidence interval 5.7-6.3 months). The 1-year survival rate was 53.8%. CONCLUSIONS: The high overall tumor growth control, the remarkable median time to progression and overall survival and the good safety profile are of particular interest for patients with heavy pretreated metastatic CRC.

Adult↗
PubMed2005

A time-dependent polarizable continuum model: theory and application.

This work presents an extention of the polarizable continuum model to explicitly describe the time-dependent response of the solvent to a change in the solute charge distribution. Starting from an initial situation in which solute and solvent are in equilibrium, we are interested in modeling the time-dependent evolution of the solvent response, and consequently of the solute-solvent interaction, after a perturbation in this equilibrium situation has been switched on. The model introduces an explicit time-dependent treatment of the polarization by means of the linear-response theory. Two strategies are tested to account for this time dependence: the first one employs the Debye model for the dielectric relaxation, which assumes an exponential decay of the solvent polarization; the second one is based on a fitting of the experimental data of the solvent complex dielectric permittivity. The first approach is simpler and possibly less accurate but allows one to write an analytic expression of the equations. By contrast, the second approach is closer to the experimental evidence but it is limited to the availability of experimental data. The model is applied to the ionization process of N,N-dimethyl-aniline in both acetonitrile and water. The nonequilibrium free-energy profile is studied both as a function of the solvent relaxation coordinate and as a function of time. The solvent reorganization energy is evaluated as well.

Journal Article↗
PubMed2005

Retroperitoneal fibrosis and ankylosing spondylitis: which links?

OBJECTIVES: To report a case of retroperitoneal fibrosis (RPF) in a patient with ankylosing spondylitis (AS) and to review the medical literature for similar cases to detect possible links between the 2 diseases. METHODS: The presentation, clinical course, diagnostic work-up, and treatment of our patient are described, and the English and French medical literature from 1960 to 2000 is reviewed using a MEDLINE search for cases with coexisting RPF and spondyloarthritis. RESULTS: Our patient with AS had RPF, which mimicked rectal cancer with retroperitoneal and vertebral metastases. Special attention is paid to the unusual clinical presentation, the multistep diagnostic process, and the therapeutic strategy which was both radiologically and histologically successful. Literature review revealed 18 cases of concomitant RPF and spondyloarthritis, mainly AS. Patients were more frequently male (M/F, 3/1) and developed spondyloarthritis several years before RPF. CONCLUSIONS: RPF may result from a local immune response to products of aortic atheromatous plaques, with subsequent periaortic deposition of fibrous tissue. However, the clinical features and the frequent association with other fibrosing disorders suggest that RPF is a systemic inflammatory condition. The role of AS-associated aortitis in the development of RPF warrants consideration.

Aortitis↗
PubMed2004

Liver harvesting surgical technique for the treatment of retro-hepatic caval thrombosis concomitant to renal cell carcinoma: perioperative and long-term results in 15 patients without mortality.

OBJECTIVE: Radical surgical treatment improves the prognosis of patients affected by Inferior Vena Cava (IVC) thrombosis concomitant to renal carcinoma. However, thrombus extension above the infrahepatic IVC represents a major technical topic for surgeons because of the possible occurrence of uncontrollable haemorrhages and tumor fragmentation. We report the results of an innovative surgical approach to caval thrombosis including the isolation of the IVC from the liver as routinely performed during liver harvesting. In the presence of retro-hepatic IVC thrombosis, this technique improves vascular control and allows to perform a large cavotomy with an en-bloc removal of the thrombus and the tumor. METHODS: From January 1995 through June 2003, 15 patients with renal cancer and caval thrombosis were treated at our Institution. Four, ten and one patients were respectively affected by an infrahepatic (Level I), retro-hepatic (Level II) and atrial (Level III) IVC thrombosis. RESULTS: All patients underwent radical surgical treatment. In presence of Level II caval thrombosis, the patients underwent the above reported surgical technique. Perioperative mortality was absent; major morbidity occurred in one patient (6.7%). The thrombus was radically removed in all cases. After a mean follow-up of 53.9 months (5-100 months) all patients but one are still alive. One patient died 9 months after surgery with multiple bilateral pulmonary metastases. CONCLUSIONS: Isolation of the retro-hepatic IVC is a safe and effective manoeuvre to significantly reduce perioperative mortality and morbidity in patients affected by Level II caval thrombosis concomitant to renal carcinoma.

Aged↗
PubMed2004

Thymidylate synthase expression in normal colonic mucosa: a predictive marker of toxicity in colorectal cancer patients receiving 5-fluorouracil-based adjuvant chemotherapy.

OBJECTIVES: We retrospectively evaluated the relevance of thymidylate synthase (TS) expression in normal colonic mucosa as a predictive factor of toxicity in colorectal cancer patients receiving adjuvant fluorouracil (5-FU)-based chemotherapy. METHODS: TS expression was immunohistochemically assessed on normal colonic mucosa from 50 patients with colorectal cancer Dukes' stages B (15 patients) and C (35 patients) treated with 5-FU-based adjuvant chemotherapy. RESULTS: The incidence of grade 2-3 diarrhea and stomatitis (according to WHO) was demonstrated to be significantly higher in patients with low nuclear TS expression in normal mucosa than in those with high TS expression (p < 0.0001). Moreover, patients with low TS expression in normal colonic mucosa developed weight loss and worsening of the performance status (according to ECOG score) more commonly than patients with high TS expression (p = 0.005 and p = 0.02, respectively). Furthermore, low TS expression in normal colonic mucosa significantly correlated with a higher rate of a delay of chemotherapy courses, dose reduction and treatment discontinuation. CONCLUSIONS: Immunohistochemical TS expression in normal colonic mucosa may represent an important predictive parameter for identifying a subset of patients with a high risk of developing severe 5-FU-related toxicities.

Adult↗
PubMed2002

Rectal perforation, retropneumoperitoneum, and pneumomediastinum after stapling procedure for prolapsed hemorrhoids: report of a case and subsequent considerations.

Stapling procedure is a new technique for the surgical management of third-degree hemorrhoids. Even if long-term experience has not been reported, this new technique is generating a lot of interest and its use is becoming more common in Europe. Some articles have just been published about severe adverse effects of this operation, and in the present article we describe a case of a life-threatening complication that occurred with the use of the stapling technique for hemorrhoidectomy. A patient with perineal descensus and third-degree hemorrhoids underwent a stapling procedure for the treatment of hemorrhoids. Retropneumoperitoneum and pneumomediastinum developed on postoperative Day 2 and a colostomy was performed, allowing a quick recovery of the patient. After six months the colostomy was closed and bowel function restored. Our experience, taken together with some other cases previously published of severe complications after such an operation, suggests caution in the use of this new technique for the treatment of a benign disease.

Female↗
PubMedDate not supplied

Mucinous cystic lesions of the pancreas. Report of a patient submitted to distal pancreatectomy.

Intraductal papillary neoplasm consists a variant of the mucin-producing neoplasms of the pancreas; these are rare diseases that can be divided into mucinous ductal ectasias and intraductal papillary neoplasms. Such neoplasms have a malignant potential, and their prognosis is good if they are early diagnosed and localized surgical resection. This paper describes a case of an intraductal papillary neoplasm localized in the tail of the pancreas and treated by distal splenopancreatectomy. The literature on this rare disease is also reviewed.

Female↗
PubMedDate not supplied

Radiofrequency ablation of hepatic tissue: a new experimental animal model.

BACKGROUND/AIMS: Experimental radiofrequency ablation has already been performed in healthy livers of porcine models, but not in less expensive and easy-to-manage rats, with devices capable of delivering radiofrequency ablation in the 20-30 g liver of such small animals being so far unavailable. METHODOLOGY: We experimented with a modified system of radiofrequency ablation of liver tissue in rat models developing a custom-made needle-microelectrode of very small dimensions (0.3x2 mm) and an electrode-tip cooling technique, based on saline solution infusion. We adjusted duration (seconds) and power (watts) of radiofrequency ablation letting them range between 5-50 seconds and 5-25 W, respectively, to obtain the greatest lesions with the least side effects. After sacrificing the animals, an accurate histological examination of the liver was made. RESULTS: It is possible to establish beforehand the diameter of thermal liver lesion on the basis of joules of applied energy. The greatest increase of liver thermal lesion diameter (8 mm) is obtained with a 250-joule (10 W for 25 seconds) thermal energy cooling the electrode-tissue interface. CONCLUSIONS: Experimental radiofrequency ablation in rat liver is an effective and cheap way to study its effects on healthy hepatic tissues. It might be the first step to treat experimentally caused liver tumors.

Animals↗
PubMedDate not supplied

Persisting perianal ulcer after radiotherapy for anal cancer: recurrence of disease or late radiation-related complication?

We report the case of a 47-year-old HIV-negative male affected by a perianal ulcer which occurred after chemoradiation delivered for anal cancer. In spite of a negative biopsy the lesion was highly suspected to be a disease recurrence. Uncontrollable pain and anal stenosis were also present; abdominoperineal resection with a large excision of perianal tissues and reconstruction with bilateral musculocutaneous gracilis flaps was therefore performed. Histology did not confirm tumor recurrence. Thirteen months after surgery, the patient is still alive and free of disease. The introduction of radiotherapy and concomitant chemotherapy has revolutionized the treatment of anal cancer, avoiding demolitive surgery in a large subset of patients. Radionecrosis is an uncommon but potentially devastating event occurring in up to 10% of patients undergoing radiotherapy for anal cancer. It causes clinical (pain, anal stenosis, mucositis and diarrhea) and diagnostic problems (recurrence vs. benign post-attinic lesion). In the present article we review this uncommon complication, discuss the technical surgical aspects associated with a very large perianal tissue removal, and data of the most recent literature in this field.

Anal Canal↗