Local-regional staging of endometrial carcinoma: role of MR imaging in surgical planning

PURPOSE: To assess magnetic resonance (MR) imaging in depicting the depth of myometrial infiltration, cervical invasion, and presence of enlarged lymph nodes in patients with endometrial adenocarcinoma compared with surgicopathologic findings. MATERIALS AND METHODS: Thirty-seven consecutive patients with endometrial carcinoma were included in this prospective study. All patients underwent MR imaging and surgery. Qualitative image analysis included the depth of myometrial infiltration, infiltration of the uterine cervix, and presence of enlarged lymph nodes. Quantitative image analysis included tumor and myometrium contrast-to-noise ratios during different phases of dynamic imaging. MR imaging findings were compared with surgicopathologic findings. Sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values of MR imaging in depicting myometrial and cervical infiltration and in lymph node assessment were calculated. RESULTS: Respective sensitivity, specificity, diagnostic accuracy, and positive and negative predictive values in assessing myometrial infiltration were 87%, 91%, 89%, 87%, and 91%; those for cervical infiltration, 80%, 96%, 92%, 89%, and 93%; and those for lymph node assessment, 50%, 95%, 90%, 50%, and 95%. There was significant agreement between MR imaging and surgicopathologic findings in assessment of myometrial invasion (P <.001). Myometrial and cervical invasion and lymph node enlargement were correctly assessed with MR imaging in 28 (76%) of 37 patients. Quantitative analysis showed a significant improvement in tumor and myometrium contrast-to-noise ratios during the equilibrium phase compared with the arterial and precontrast phases (P <.001). CONCLUSION: MR imaging coupled with contrast material-enhanced dynamic MR imaging is highly accurate in local-regional staging of endometrial carcinoma; more challenging is the assessment of pelvic and lumboaortic lymph nodes.     

Potent antiviral activity of amprenavir in primary macrophages infected by human immunodeficiency virus

Objective of the present study was then to assess the antiviral activity of the protease inhibitor amprenavir in macrophages (M/M), and to compare it with its efficacy in peripheral blood lymphocytes (PBL). M/M were obtained from blood of sero-negative healthy donors and infected with M-tropic HIV-1 strain (HIV-1(Ba-L)). The stabilized infection was assessed by monitoring the HIV-1 p24 gag antigen production in the supernatants of M/M cultures. In the setting of acute infection (treatment before HIV-1 challenge), amprenavir showed substantial activity both in M/M and PBL at similar concentrations (EC(50): 0.011 and 0.031 microM, respectively); complete inhibition of HIV-1 replication was achieved in both cell types at concentration of about 2 microM. In the setting of chronical infection (i.e. antiviral treatment several days after established infection), an antiviral effect of amprenavir was achieved in M/M, but at concentrations higher than those active in acutely infected M/M (EC(50): 0.72 microM, EC(90): 18.2 microM). The antiviral effect in chronically infected M/M was sustained for at least 2 weeks of continuous treatment. These findings suggest that amprenavir (at relatively high concentrations) has a clinically relevant antiviral effect in persistently infected reservoirs of HIV.     

PKC-interacting proteins: from function to pharmacology

Protein kinase C (PKC) is a ubiquitously expressed family of kinases that have key roles in regulating multiple cellular activities. The activity of this family is controlled tightly by several molecular mechanisms, including interaction with binding-partner proteins. These PKC-interacting proteins (C-KIPs) confer specificity for individual PKC isoforms by regulating the activity and cellular localization of PKC isoforms and, subsequently, the ability of these isoforms to specifically regulate cellular functional events. Although many C-KIPs have been identified by genome and proteome-mining approaches, it is important to address the specificity and function of the interactions in greater detail because they might form novel drug targets. In this article, we review recent work on C-KIPs and the implications for pharmacological and therapeutic development.     

Non-invasive diagnostic and functional evaluation of cardiac and pulmonary involvement in systemic sclerosis

BACKGROUND: The aim of the present study was to evaluate the role of non-invasive methods in the early detection of pulmonary and cardiac involvement in Systemic sclerosis (SSc) and to identify clinical and/or instrumental patterns of prognostic value. PATIENTS AND METHODS: Twenty female patients affected by SSc (8 with diffuse cutaneous SSc and 12 with limited cutaneous SSc) were enrolled in our study. Cardiac and pulmonary involvement (respiratory function tests and carbon monoxide lung diffusion [DLCO], chest radiography, high resolution computed tomography [HRCT] and lung perfusion magnetic resonance) were evaluated. RESULTS: All 18 patients studied with respiratory function tests showed a significant reduction of DLCO. HRCT was considerably more sensitive than traditional chest radiography (59% versus 28%; p<0.05). Lung perfusion MRI revealed normal findings in 15 patients. Abnormal lung perfusion MRI results were found only in 3 patients. Angina pectoris with electrocardiographic and scintigraphic ischemic changes, severe regional wall motion abnormalities and complex arrhythmias seemed to be associated with poor prognosis. CONCLUSION: Taken together these results indicate that a pulmonary involvement occurs both in limited and in diffuse cutaneous SSc patients and develops, in 83% of the cases, without any regional lung perfusion abnormality. Furthermore, cardiac involvement is detected in 65% of the cases as a consequence of a range of noxious events including myocardial ischemia, fibrosis and pressure overload which may result in ventricular dysfunction and arrhythmias. Lung perfusion MRI should be considered as a complementary diagnostic method for the functional evaluation of these symptoms in systemic sclerosis.     

Primary cultures of microglial cells for testing toxicity of anticancer drugs

Toxicity of anticancer agents on normal neural cells during chemotherapy of primary or secondary brain tumors is a clinical problem of increasing relevance and concern. In this perspective, here we used primary cultures of rat cortical microglia as an in vitro paradigm of normal glia to investigate the neurotoxicity of anticancer agents. The effects of two compounds frequently used for treatment of brain tumors, methotrexate (MTX) and temozolomide (TMZ), were compared to those of a known microglial activator, bacterial lipopolysaccharide (LPS); cell viability and metabolism was assessed by the MTS assay. We found that LPS, in the low-intermediate range of concentrations, strongly activates microglia cells, but a highly significant decrease in viability was observed from 100 ng/ml onward. TMZ has no effect at concentrations of clinical interest, whereas MTX significantly increases cell metabolism at 30 microM, a phenomenon possibly reflecting MTX neurotoxicity observed in patients.     

Adjuvant treatment of colorectal cancer

Colorectal cancer is one of the most frequent causes of cancer deaths. Survival for locoregional colorectal cancer is about 70% overall and 30-60% in stage III patients. Several randomized trials have shown that adjuvant chemotherapy can increase this survival rate. 5-Fluorouracil-based chemotherapy is strongly recommended in this context. There are still some questions about the setting in which patients should be treated as well as the optimal treatment. New data for different schedules and combinations are now available. Physicians have to choose between the different options now available to offer the best treatment to their patients. This Review analyses the current options for adjuvant therapy in colon and rectal cancer.