BackgroundThe inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1β were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course.MethodsThe expression of CCL2, CCL5, TNFα and IL-1β was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments.ResultsCCL2, CCL5, TNFα and IL-1β were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1β in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1β expression. These results suggest progression-related roles for TNFα and IL-1β in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1β compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1β) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1β acts jointly with other pro-malignancy factors to promote disease relapse.ConclusionsOur findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1β may be important for disease course, and that TNFα & IL-1β may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.
A common complaint of children with auditory processing disorders (APD) is difficulty in understanding speech in the presence of background noise. Evidence from animal and human studies has suggested that the medial olivocochlear bundle (MOCB) may play a role in hearing in noise. The MOCB function can be evaluated by the suppression effect of the transient evoked otoacoustic emissions (TEOAE) in response to contralateral acoustic stimulation (CAS). The present study was conducted to investigate the suppression effect of TEOAE in APD children. The study groups comprised 15 APD children aged 8–13 years associated with learning disabilities and 15 controls matched for gender and age. The suppression effect of TEOAE was evaluated by comparing the TEOAE levels with and without CAS. A significantly reduced suppression effect of TEOAE was demonstrated in the APD group, when compared to the controls. In addition, higher TEOAE levels were found in the APD group, suggesting inherent reduced MOCB activity on the outer hair cells in APD children. These results imply that some APD children present low activity of the MOCB system, which may indicate a reduced auditory inhibitory function and affect their ability to hear in the presence of background noise.
The proposed questionnaire appears to be sufficiently reliable and valid in estimating a patient's QOL after extirpation of anterior skull base tumors. The instrument can be used in face-to-face interviews and via electronic or regular mail.
This study evaluated the cognitive profiles of children with idiopathic generalized epilepsy (IGE), uniformly treated with valproic acid with well-controlled seizures. Twenty-four were neuropsychologically evaluated. They comprised: 14 females, 10 males: 12 with generalized tonic-clonic seizures (GTCS), mean age 14y 4mo, SD ly 7mo, range 12y to 16y 4 mo; 12 with absence seizures (AS]) mean age 14y 5mo, SD ly 10mo, range 11y to 16y 4mo, with intellectual abilities within the normal range and age-appropriate scholastic skills, and 20 healthy controls (12 females, 8 males; mean age 14y 5mo, SD 1y 10mo, range 10y 7mo to 16y 7mo). As a group, children with IGE performed significantly poorer in all tests (non-verbal and verbal attention, verbal learning and memory, word fluency, and controlled sequential fine motor responses) excluding non-verbal memory. Analysis according to type of seizure revealed that both patient groups (AS and GTCS) had an attention deficit, whereas only children with AS showed deficits in verbal learning and memory, word fluency, and controlled fine motor responses. These results suggest a long-term risk of learning impairment for children with IGE, even if they have normal intelligence and their seizures are well controlled.
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