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Biomedical subjects

R Sarmiento

Publications and source records attributed to R Sarmiento.

14 recordsLinked to original sources
PubMed2005

Gefitinib (ZD1839) combined with weekly epirubicin in patients with metastatic breast cancer: a phase I study with biological correlate.

PURPOSE: Epidermal growth factor receptor (EGFR) is overexpressed in approximately 50% of invasive breast carcinomas and it is correlated with hormone resistance and poor prognosis. EGFR suppression by gefitinib, a quinazoline derivative that inhibits phosphorylation of the specific receptor, represents a novel therapeutic strategy. A dose-finding study was performed to evaluate the combination of gefitinib with weekly epirubicin in patients with pretreated metastatic breast cancer. METHODS: Fifteen patients were enrolled at four sequential dose levels. Gefitinib was administered orally, at the fixed daily dose of 250 mg. The starting dose of epirubicin was 20 mg/m2. Escalating dose levels of epirubicin were planned by increments of 5 mg/m2 per level, up to the maximum tolerated dose (MTD). Pharmacodynamic studies were performed by determining serum and tissue ERBB2 and EGFR. RESULTS: At the first three dose levels tested no patient experienced a dose-limiting toxicity (DLT). In cohort 4, two patients experienced DLTs (grade 4 dyspnea and asthenia, grade 3 diarrhea and thrombocytopenia) identifying the MTD of epirubicin as 35 mg/m2. Of the 14 cases assessable for response, partial response was documented in two patients, and stable disease in seven, giving an overall disease control rate of 64.2%. The comparison of pre- and post-therapy ERBB2 and EGFR values was not statistically significant between the subgroups of patients regarding responsiveness to treatment. CONCLUSIONS: The recommended dose of epirubicin for phase II studies is 30 mg/m2 in combination with gefitinib at the daily dose of 250 mg. Pharmacodynamic studies did not identify any biomarker predictive of response.

Adult↗
PubMed2002

Anti-angiogenic therapy: rationale, challenges and clinical studies.

Physiological angiogenesis occurs during embryogenesis, wound healing and reproductive functions in adults. Abnormal angiogenesis takes place in certain chronic diseases (diabetes, psoriasis, rheumatoid arthritis, etc.) and tumours. Genetic changes and local stresses including hypoxia, glucose deprivation and oxidative stress play a pivotal role in angiogenesis switch, which is necessary for tumour development and is rate-limiting for tumour progression. Angiogenesis is tightly regulated by pro- and anti-angiogenic growth factors with a series of complex and interrelated steps. Activated endothelial cells (ECs) migrate as a solid cord and, subsequently, form lumina; the sprout tips then anastomose to form vessel loops or networks. One of the final events is the laying down of a basement membrane and the structural support of pericytes. The molecular alterations that sustain angiogenesis represent novel targets for rationally designed anti-cancer treatment strategies. Inhibition of angiogenesis presents certain advantages on conventional therapies, such as the direct accessibility from the circulation, and the potential low rate of drug resistance related to the genetic stability of ECs. Certain anti-angiogenic compounds were found to have potent anticancer property in in vivo experimental studies. Nevertheless, in contrast to preclinical studies, the first generation of anti-angiogenic drugs tested in clinical trials have shown a moderate activity in advanced disease partly due to suboptimal schedules of therapy or biases in study design.

Angiogenesis Inhibitors↗
PubMed1999

[A uterine pecoma: a case report].

The authors describe the first ever reported case of a malignant pecoma of the uterus infiltrating the ovary, the tube and two bowel loops. This extremely rare tumour usually shows a benign behaviour and seems to arise from the perivascular epithelioid cells (PEC).

Epithelioid Cells↗
PubMed1998

[Role of the oncologist in prevention, diagnosis and treatment of neoplasms].

Oncological pathology represents a topic of particular interest and importance owing to both its rising frequency (151,690 deaths in Italy in 1992) and the continuous progress made in the diagnostic and therapeutic field. The steady growth of this pathology has led to the need to identify a new professional figure: the cancer physician capable of bringing together all the skills required to optimise the diagnosis and treatment of oncological patients. As it is now universally accepted in theory, but not always put into practice, the treatment of oncological pathologies calls for a multidisciplinary approach. The optimal treatment is based on the integration of the roles of all the various specialists: oncologist, surgeon, radiotherapist and expert in pain therapy. In this therapeutic strategy, the cancer physician should manage the starting phase of the disease and subsequently should manage its course together with the surgeon and radiotherapist, returning in the terminal phase to sole management of the cancer patient with the help of other qualified professional figures. In short, the authors feel that it is not exaggerated to state that the cancer physician plays a central role in resolving the needs posed by the problem of cancer, needs which may take the form of diagnosis, therapy and care.

Humans↗
PubMed1995

Coronary stenting decreases restenosis in lesions with early loss in luminal diameter 24 hours after successful PTCA.

BACKGROUND: Early loss of minimal luminal diameter (MLD) after successful percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher incidence of late restenosis. METHODS AND RESULTS: Sixty-six patients (66 lesions) with > 0.3 mm MLD loss at 24-hour on-line quantitative coronary angiography were randomized into two groups: 1, Gianturco-Roubin stent (n = 33) and 2, Control, who received medical therapy only (n = 33). All lesions were suitable for stenting. Baseline demographic, clinical, and angiographic characteristics were similar in the two groups. Restenosis (> or = 50% stenosis) for the overall group occurred in 32 of 66 patients (48.4%) at 3.6 +/- 1-month follow-up angiography. Restenosis was significantly greater in group 2 than in group 1 (75.7% versus 21.2%, P < .001). Vascular complications (21.2% versus 0%) and length of hospital stay (7.3 +/- 1 versus 2.4 +/- 0.5 days, P < .01) were higher for the stent group. Although at follow-up there were no differences in mortality or incidence of acute myocardial infarction between the two groups, patients in the control group had a higher incidence of repeat revascularization procedures (73% versus 21%, P < .001). CONCLUSIONS: In patients with successful PTCA but reduced luminal diameter demonstrated by repeat angiography at 24 hours, the Gianturco-Roubin stent appears to reduce angiographic restenosis at follow-up.

Angioplasty, Balloon, Coronary↗
PubMed1994

Case report: Candida meningitis with an intradural filling defect 1 year after candidemia.

Candida albicans meningitis developed in a 55-year-old diabetic female, 1 year after catheter-associated candidemia. It was characterized by a protracted course, lack of meningeal signs, and the presence of an intradural filling defect within the caudal canal. Complete resolution of this filling defect with antifungal therapy implies that it probably represented an inflammatory mass. The development of meningitis after self-limiting candidemia and similar intradural filling defects have not been reported previously.

Amphotericin B↗
PubMed1993

Group B streptococcal meningitis in adults: case report and review of the literature.

A case of group B streptococcal meningitis in an adult is presented with a review of 42 other cases reported in the English literature since 1940. Their median age was 58 years (72.5% were older than 45 years). Male/female ratio was 0.9:1, with male predominance in patients older than 60 years (76.5%). Predisposing illnesses were common but 13.9% of cases reported had no identifiable risk factor. Encephalopathy and bacteremia were frequent (81.3% and 94.4% respectively) and many patients (30%) had other foci of infection. Gram stain of cerebrospinal fluid was positive in 75% of cases. Mortality was 18.4% and 9.7% of survivors had bilateral hearing loss. Thus, this review illustrates that group B streptococcal meningitis in adults is a rare disease which occurs among high risk individuals. It is characterized by frequent encephalopathy, prevalence of other foci of infection and bacteremia with an outcome similar to other types of purulent meningitides.

Adult↗
PubMed1973

Insect juvenile hormones: highly potent synthetic mimics.

The substitution of a 7-alkoxy group for the 6,7-epoxy moiety in aryl terpenoid ethers having high juvenile hormone activity has produced several compounds exceptionally active against Tenebrio molitor. The most potent compound [7-ethoxy-1-(p-ethylphenoxy)-3,7-dimethyl-2-octene, called JH-25] is active at the level of 10 picograms per insect, or about 100 times more active than other promising juvenile hormone mimics so far reported. Compound JH-25 was also active against Tribolium confusum.

Biological Assay↗
PubMedDate not supplied

Effect of endothelial dysfunction on regional perfusion in myocardial territories supplied by normal and diseased vessels in patients with coronary artery disease.

BACKGROUND: Endothelium-dependent regulation of coronary tone affects both conduit and resistance coronary arteries. However, little is known about the usefulness of myocardial perfusion imaging in evaluating coronary endothelial function. We evaluated the relation between invasive angiographic measurements of coronary vasomotion in response to intracoronary acetylcholine and the presence of regional perfusion abnormalities assessed by technetium 99m sestamibi imaging. METHODS AND RESULTS: We studied 11 patients (9 men and 2 women) with suspected coronary artery disease (48 +/- 8 years, mean +/- standard deviation). We used quantitative coronary angiography to delineate the vasomotor response to increasing doses of acetylcholine given intracoronary. Regional myocardial perfusion was assessed by planar Tc-99m sestamibi imaging during and after the administration of acetylcholine. In the 11 patients, 23 coronary artery territories were analyzed: 13 were angiographically normal, and 10 showed varying degrees of luminal narrowing. Four (31%) of 13 angiographically normal coronary arteries had a positive vasomotor response to acetylcholine (> or =20% reduction in luminal diameter) that was associated with a regional perfusion defect. Acetylcholine induced a positive vasomotor response, which was also associated with a regional perfusion defect in 1 of 3 coronary arteries with stenoses of intermediate severity (50% to 69%). Likewise, acetylcholine induced a positive vasomotor response in 6 of 7 coronary arteries with significant luminal narrowing (> or =70%), 5 of which showed a corresponding regional perfusion defect. CONCLUSIONS: In patients with coronary artery disease, noninvasive measurements of regional myocardial perfusion by Tc-99m sestamibi correlate well with invasive measurements of coronary endothelial function. These findings may have implications for monitoring the effects of interventions designed to improve endothelial function and microvascular function in patients with coronary artery disease.

Acetylcholine↗
PubMedDate not supplied

Fulminant hepatic failure caused by diffuse intrasinusoidal metastatic liver disease: a case report.

A 53-year-old woman experienced rapidly progressing liver failure four years after a quadrantectomy for a breast carcinoma. She had received adjuvant chemotherapy and radiotherapy, and second-line chemotherapy for bone metastasis one year earlier. The hepatic failure manifested with ascites, jaundice, elevation of serum bilirubin and hepatic enzyme levels and hypoalbuminemia. Imaging studies showed an enlarged liver without metastatic lesions. The patient died of hepatic decompensation within two weeks. Liver examination at autopsy revealed massive neoplastic infiltration consistent with a primary breast carcinoma. It is important to realize that this unusual pattern of liver metastasis cannot be demonstrated even with the most advanced techniques of instrumental diagnosis (CT scan, ultrasonography and magnetic resonance imaging), and should be taken into account in the differential diagnosis of rapidly progressing liver failure.

Autopsy↗
PubMedDate not supplied

Therapeutic strategies to improve the efficacy of oxaliplatin in gastrointestinal tumors.

The pharmacological characteristics of oxaliplatin make it one of the better chemotherapeutics to be combined with novel molecular-targeted anticancer treatments for the therapy of gastrointestinal tumors. The purposes of this review article are to report the preliminary data of combined therapy of oxaliplatin with inhibitors of angiogenesis or epidermal growth factor receptor and to suggest novel oxaliplatin-based therapeutic strategies. It is hypothesized that well designed, personalized, molecular-based treatments may improve the efficacy of oxaliplatin for the treatment of colorectal, gastric and pancreatic cancer. It is mandatory to rationalize such an approach by adequate determination of predictive surrogate biomarkers of response related to the targets in each single tumor against which therapy is aimed, using standardized assays and quality control.

Animals↗