Hepatocellular carcinoma (HCC) exhibits cellular heterogeneity and embryonic stem‐cell–related genes are preferentially overexpressed in a fraction of cancer cells of poorly differentiated tumors. However, it is not known whether or how these cancer cells contribute to tumor initiation and progression. Here, our data showed that increased expression of pluripotency transcription factor Nanog in cancer cells correlates with a worse clinical outcome in HCC. Using the Nanog promoter as a reporter system, we could successfully isolate a small subpopulation of Nanog‐positive cells. We demonstrate that Nanog‐positive cells exhibited enhanced ability of self‐renewal, clonogenicity, and initiation of tumors, which are consistent with crucial hallmarks in the definition of cancer stem cells (CSCs). NanogPos CSCs could differentiate into mature cancer cells in in vitro and in vivo conditions. In addition, we found that NanogPos CSCs exhibited resistance to therapeutic agents (e.g., sorafenib and cisplatin) and have a high capacity for tumor invasion and metastasis. Knock‐down expression of Nanog in NanogPos CSCs could decrease self‐renewal accompanied with decreased expression of stem‐cell–related genes and increased expression of mature hepatocyte‐related genes. Overexpression of Nanog in NanogNeg cells could restore self‐renewal. Furthermore, we found that insulin‐like growth factor (IGF)2 and IGF receptor (IGF1R) were up‐regulated in NanogPos CSCs. Knock‐down expression of Nanog in NanogPos CSCs inhibited the expression of IGF1R, and overexpression of Nanog in NanogNeg cells increased the expression of IGF1R. A specific inhibitor of IGF1R signaling could significantly inhibit self‐renewal and Nanog expression, indicating that IGF1R signaling participated in Nanog‐mediated self‐renewal. Conclusion: These data indicate that Nanog could be a novel biomarker for CSCs in HCC, and that Nanog could play a crucial role in maintaining the self‐renewal of CSCs through the IGF1R‐signaling pathway. (HEPATOLOGY 2012;56:1004–1014)
Primary adrenal lymphoma is an extremely rare entity. Only 70 cases have been reported in the English literature. Most of the patients are elderly men with bilateral adrenal masses without extraadrenal involvement. The most common presenting symptoms are fever, weight loss, lumbar pain, and/or symptoms of adrenal insufficiency. Of the cases reported, CT, ultrasound, and MRI were the imaging modalities used to describe the lesions. FDG PET has been used successfully to differentiate benign and malignant adrenal masses. The authors report a 67-year-old man diagnosed as having primary bilateral adrenal lymphoma and having no evidence of extraadrenal spread who was evaluated from the time of diagnosis to complete remission with FDG PET scanning. The literature of this unusual neoplasm is reviewed in detail.
Objective To examine the impact of distraction on the retention of rehearsed information in patients with fibromyalgia syndrome (FMS). Methods Data refer to the neurocognitive examination of 134 patients (91 with FMS and 43 control subjects) presenting with memory loss. Four neurocognitive measures free of distraction, along with 2 measures with added distraction, were completed. Differences in the retention of rehearsed and unrehearsed information with a source of distraction present were calculated. Results Patients with FMS showed normal cognitive functioning on verbal memory tests free of distraction. Adding a source of distraction caused unrefreshed information to be lost at a disproportionate rate in patients with FMS. Over 87% of patients with FMS scored in the impaired range on a task of unrehearsed verbal memory. Adding a source of distraction to well‐rehearsed information produced a normal rate of recall in FMS. Conclusion Rehearsal mechanisms are intact in patients with FMS and play beneficial roles in managing interference from a source of distraction. In the absence of rehearsal, a source of distraction added to unrefreshed information signals a remarkable level of cognitive deficit in FMS that goes undetected by conventionally relied‐upon neurocognitive measures. We present a theory to promote understanding of the cognitive deficit of people with FMS based on reduced speed of lexical activation and poor recall after distraction.
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