Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention

Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone protein and is overexpressed in various cancers. However, it is unclear how significance of this molecule play an active role contributing to the oncogenic effect of head and neck cancer (HNC). To investigate the potential function of Grp78, six HNC cell lines were used. We found that Grp78 is highly expressed in all six cell lines and many of the proteins were localized in the periphery regions, implying other function of this molecule aside from endoplasmic reticulum stress response. Knockdown of Grp78 by small interfering RNA significantly reduced cell growth and colony formation to 53% to 12% compared with that of controls in all six HNC cell lines. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 23% to 2% in all these cell lines tested. In vivo xenograft studies showed that administration of Grp78-small interfering RNA plasmid into HNC xenografts significantly inhibited both tumor growth in situ (>60% inhibition at day 34) and liver metastasis (>90% inhibition at day 20). Our study showed that Grp78 actively regulates multiple malignant phenotypes, including cell growth, migration, and invasion. Because knockdown Grp78 expression succeeds in the reduction of tumor growth and metastatic potential, this molecule may serve as a molecular target of therapeutic intervention for HNC. [Mol Cancer Ther 2008;7(9):2788-97].     

Traumatic hyoid bone fracture in patient wearing a helmet: a case report

Fractures of hyoid bone are rare and most of the injuries cause by strangulation. Hyoid bone fractures are usually the result of direct trauma to the neck through manual strangulation or hanging, blunt trauma or from projectiles. But hyoid bone fracture caused by helmet strap has not been reported before. We present a young man wearing a helmet had an isolated hyoid bone fractures after a motorcycle-to-motorcycle accident. So, we should be more aware that helmet wearing riders are prone to have this kind of injury.     

Tardive gait

Tardive dyskinesia (TD) is a hyperkinetic movement disorder induced by dopamine receptor blocking drugs (DRBDs). TD typically presents with stereotypy or dystonia, but may also cause akathisia, myoclonus, or tremor. However, no detailed reports of gait abnormalities have been documented. We report three patients exposed to DRBDs who developed "tardive gait" and conclude that gait dysfunction may be part of the TD spectrum.     

Glucocorticoid signaling and exercise-induced downregulation of the mineralocorticoid receptor in the induction of adult mouse dentate neurogenesis by treadmill running

Physical exercise is known to promote adult neurogenesis, although the underlying mechanisms remain unclear. Glucocorticoid (corticosterone in rodents) is a factor that is known to affect neurogenesis. As physical exercise modulates corticosterone secretion, we hypothesized that corticosterone signaling is involved in exercise-induced adult neurogenesis. We chose treadmill running (TR) to accurately define the intensity and duration of exercise. Our results showed that 5 weeks of TR increased the doublecortin (DCX)-positive neuronal progenitor cells (NPCs) in adult hippocampus and transiently increased the serum corticosterone level at the end of the TR protocol. This protocol reduced the levels of hippocampal mineralocorticoid receptor (MR); however, glucocorticoid receptor levels were unaltered. We then investigated whether reducing corticosterone levels by bilateral adrenalectomy (ADX) attenuated the TR-enhanced adult neurogenesis. Our results showed that ADX not only blocked the TR-induced downregulation of MR, but also reduced the number of TR-enhanced NPCs. In order to examine the role of MR downregulation in TR-induced adult neurogenesis, animals were treated repeatedly with a selective MR antagonist, spironolactone, for 3 weeks. The results revealed that spironolactone increased the number of spontaneously occurring and TR-induced NPC in the dentate area. Further analysis revealed that spironolactone treatment did not alter precursor cell proliferation, but increased the number of DCX-positive NPCs, suggesting that blockage of MR signaling either facilitates the differentiation of progenitor cells towards neurons and/or enhances the survival of NPCs. Taken together, the data indicated that induction of NPCs in the dentate area of adult hippocampus by TR is partly due to the downregulation of glucocorticoid/MR signaling, which subsequently enhances differentiation along a neuronal lineage and/or NPC survival.     

Correlation among subcortical white matter lesions, intelligence and CTG repeat expansion in classic myotonic dystrophy type 1

Objectives –  To analyze the correlation among intelligence, brain magnetic resonance images (MRI) and genotype in classic myotonic dystrophy type 1 (DM1) patients.
Materials and methods –  Seventeen patients with classic DM1 were administered intelligence and neuropsychological tests and brain MRI focusing on a semi-quantitative rating scale of subcortical white matter lesions (WMLs). Statistical analysis was measured to evaluate the correlation among clinical manifestations, intelligence, brain MRI abnormalities, and CTG repeat expansion.
Results –  There were statistically significant correlations between intelligence test and insular WMLs for all DM1 patients and between intelligence quotient and temporal WMLs for those patients with less than 400 of the CTG repeat size. We also documented that temporal WMLs were related to the disease course, and frontal WMLs were correlated with aging in all DM1 patients. However, a poor correlation was found among CTG repeat size and clinical pictures, neuropsychological impairments, and brain MRI abnormalities in all DM1 patients.
Conclusion –  These results suggest that subcortical WMLs are correlated with focal dementia in classic DM1 patients. Temporal and insular WMLs may be responsible for the global intellectual dysfunction of adult DM1 patients.     

Crossreactive B cells are present during a primary but not secondary response in BALB/c mice expressing a bcl-2 transgene.

While it is clear that multiple genetic factors lead to autoimmune diseases such as systemic lupus erythematosus (SLE), it appears that an environmental stimulus is also required to trigger the disease in susceptible individuals. We have previously demonstrated that B cells making crossreactive antibodies that bind to both phosphorylcholine (PC), a component of pneumococcal cell wall polysaccharide, and double stranded DNA (dsDNA) can be found in BALB/c mice immunized with PC coupled to a protein carrier. While these B cells are normally eliminated in vivo by apoptosis, they can be recovered ex vivo by fusion with a cell line overexpressing the anti-apoptotic gene bcl-2. This observation led us to ask whether in vivo expression of bcl-2 might abrogate immunologic tolerance during an ongoing immune response. In the present study, we have examined BALB/c mice that constitutively express a bcl-2 transgene in the B cell compartment. Bcl-2 transgenic BALB/c mice have an expanded B cell number, but display no evidence of anti-dsDNA antibodies in the serum even following immunization with PC coupled to a protein carrier. Crossreactive anti-DNA, anti-PC B cells can be recovered by hybridoma technology late in the primary response, but do not appear in the memory B cell compartment. Thus, in vivo expression of bcl-2 can rescue B cell autoreactivity in the primary immune response, but is not sufficient for activation of these B cells or for their maintenance in the memory compartment.     

Limited hepatic resection by laparoscopy-assisted mini-laparotomy for the treatment of hepatocellular carcinoma in cirrhotic patients

Surgical resection is standard treatment for hepatocellular carcinoma but is often not possible in the presence of cirrhosis or poor liver function. We present a method of performing limited hepatectomy in patients with hepatocellular carcinoma and cirrhosis. We call this method laparoscopy-assisted mini-laparotomy (LAML). The site of the tumor is localized by ultrasound through a laparoscope, and a small skin incision is made over that site to facilitate removal of the portion of liver containing the tumor. Eleven patients underwent limited hepatic resection by LAML. The tumors were on the margin of the liver. There was no hospital mortality or serious complications. The average length of hospital stay was 6.4 days. LAML can be safely performed for hepatocellular carcinoma in cirrhotic patients. It decreases operating time, length of hospital stay, and blood loss.