Citations

Abstract Regulator of G-protein signaling–GAIP-interacting protein COOH terminus (GIPC) is involved in protein trafficking, endocytosis, and receptor clustering and is associated with insulin-like growth factor I receptor (IGF-IR), a receptor important for proliferation and anchorage-independent growth. Here, we described GIPC expression in different human pancreatic adenocarcinoma (PCA) cell lines and we examined the role of GIPC in the regulation of IGF-IR protein levels in PCA. Interestingly, inhibition of GIPC expression by RNA interference led to reduced IGF-IR protein levels and a subsequent decrease in proliferation of PCA cells. We also determined that the PDZ domain of GIPC is essential for the post-translational regulation and the binding of IGF-IR. The importance of GIPC in pancreatic cancer development and progression is supported by tissue microarray data of 300 pancreatic cancer specimens where GIPC is highly expressed in PCA. Taken together, our data suggest that GIPC is a central molecule for the stability of IGF-IR and could be a target for future therapy. (Cancer Res 2006; 66(21): 10264-8)

Abstract Context: Most thyroglobulin (Tg) assays have a sensitivity of 0.5–1 ng/ml. A minority of patients with undetectable T4-suppressed Tg levels have a recombinant human TSH (rhTSH)-stimulated Tg above 2 ng/ml and identifiable residual disease. Objective: The objective was to determine whether a Tg assay with improved sensitivity could eliminate the need for rhTSH stimulation when baseline Tg is below 0.1 ng/ml. Design: A retrospective study of two academic endocrine practices was conducted. Population: A total of 194 patients undergoing rhTSH stimulation participated in the study. Results: Of the 80 patients with Tg below 0.1 ng/ml, two (2.5%) had rhTSH-stimulated Tg above 2 ng/ml. One other patient with stimulation to 0.3 ng/ml and negative 123I scan had an ultrasound-detected malignant lymph node resected. None had 131I/123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. If T4-suppressed Tg was 0.1–0.5 or 0.6–2.0 ng/ml, rhTSH Tg was above 2 ng/ml in 24.2 and 82.4%, respectively. Conclusions: Patients with differentiated thyroid carcinoma and a T4-suppressed serum Tg below 0.1 ng/ml rarely have a rhTSH-stimulated Tg above 2 ng/ml, and none of these patients had 131I or 123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. We recommend monitoring such patients with a T4-suppressed Tg level and periodic neck ultrasonography. An increase in T4-suppressed serum Tg to a detectable level or the appearance of abnormal lymph nodes by physical or ultrasound exam should prompt further investigation.

In this article, we have characterized and compared gene expression profiles from laser capture microdissected neurons in six functionally and anatomically distinct regions from clinically and histopathologically normal aged human brains. These regions, which are also known to be differentially vulnerable to the histopathological and metabolic features of Alzheimer’s disease (AD), include the entorhinal cortex and hippocampus (limbic and paralimbic areas vulnerable to early neurofibrillary tangle pathology in AD), posterior cingulate cortex (a paralimbic area vulnerable to early metabolic abnormalities in AD), temporal and prefrontal cortex (unimodal and heteromodal sensory association areas vulnerable to early neuritic plaque pathology in AD), and primary visual cortex (a primary sensory area relatively spared in early AD). These neuronal profiles will provide valuable reference information for future studies of the brain, in normal aging, AD and other neurological and psychiatric disorders.

Sepsis, the systemic inflammatory response to infection, imposes a high demand for bodily adaptation, with the cardiovascular response a key determinant of outcome. The homeostatic elements that secure cardiac tolerance in the setting of the sepsis syndrome are poorly understood. Here, in a model of acute septic shock induced by endotoxin challenge with Escherichia coli lipopolysaccharide (LPS), knockout of the KCNJ8 gene encoding the vascular Kir6.1 K ATP channel pore predisposed to an early and profound survival disadvantage. The exaggerated susceptibility provoked by disruption of this stress‐responsive sensor of cellular metabolism was linked to progressive deterioration in cardiac activity, ischemic myocardial damage, and contractile dysfunction. Deletion of KCNJ8 blunted the responsiveness of coronary vessels to cytokine‐ or metabolic‐mediated vasodilation necessary to support myocardial perfusion in the wild‐type (WT), creating a deficit in adaptive response in the Kir6.1 knockout. Application of a K ATP channel opener drug improved survival in the endotoxic WT but had no effect in the Kir6.1 knockout. Restoration of the dilatory capacity of coronary vessels was required to rescue the Kir6.1 knockout phenotype and reverse survival disadvantage in lethal endotoxemia. Thus, the Kir6.1containing K ATP channel, by coupling vasoreactivity with metabolic demand, provides a vital feedback element for cardiovascular tolerance in endotoxic shock.—Kane, G. C., Lam, C‐F., O'Cochlain, F., Hodgson, D. M., Reyes, S., Liu, X‐K., Miki, T., Seino, S., Katusic, Z. S., Terzic, A. Gene knockout of the KCNJ8encoded Kir6.1 KATP channel imparts fatal susceptibility to endotoxemia. FASEB J. 20, 2271–2280 (2006)

We have investigated the significance of the method of treatment on the oncological and functional outcomes and on the complications in 184 patients with soft-tissue sarcomas of the adductor compartment managed at three international centres. The overall survival at five years was 65% and was related to the grade at diagnosis and the size of the tumour. There was no difference in overall survival between the three centres. There was, however, a significant difference in local control with a rate of 28% in Centre 1 compared with 10% in Centre 2 and 5% in Centre 3. The overall mean functional score using the Toronto Extremity Salvage Score in 70 patients was 77% but was significantly worse in patients with wound complications or high-grade tumours. The scores were not affected by the timing of radiotherapy or the use of muscle flaps. This large series of soft-tissue sarcomas of the adductor compartment has shown that factors influencing survival do not vary across the international boundaries studied, but that methods of treatment affect complications, local recurrence and function.

ObjectiveMicrovascular reconstruction requires postoperative monitoring to prevent vascular occlusion and flap failure. These methods require skilled personnel and can delay diagnosis and treatment of threatened flap failures. The Cook‐Swartz implantable Doppler flow system provides continual feedback on vascular pedicle status, which in turn provides rapid assessment of minute‐to‐minute changes in flap vasculature that may allow intervention before total vascular occlusion and expeditious reexploration for threatened flap failure, possibly improving flap salvage.Study Design and SettingCharts of 24 patients with microvascular free‐flap reconstruction and implantation of Doppler flow system at Mayo Clinic Rochester were retrospectively reviewed. Surgical technique and flap outcomes were evaluated.ResultsMicrovascular reconstruction and implantation of Doppler flow system were successful in all patients. Complications were minimal, and postoperative monitoring system facilitated rapid reexploration when necessary. Flap viability was 96%.ConclusionDoppler flow system is reliable for monitoring minute‐to‐minute changes in microvascular flap vascular status postoperatively, and allows rapid recognition of complications and facilitating reexploration. This is a valuable, easily mastered tool for microvascular reconstructive surgery.SignificanceMay alter postoperative monitoring techniques of microvascular surgeons.