Clinical manifestations of 102 cases with the Crow- Fukase syndrome (the syndrome of polyneuropathy, anasarca, skin changes, endocrinopathy, dysglobulinemia, and organomegaly), with or without myeloma, were reviewed. Fifty-six cases with myeloma consisted of 31 with osteosclerotic, 17 with mixed osteosclerotic and osteolytic, and 8 with osteolytic. Forty-six cases without myeloma consisted of 2 with extramedullary plasmacytoma, 33 with M protein alone, and 11 with polyclonal protein alone. There was no significant difference in incidence of the major clinical manifestations between the two groups with and without myeloma. They had a common characteristic histologic finding of the lymph node resembling that of Castleman's disease.
Lung cancer treatment is difficult owing to chemoresistance. Hypoxia‐inducible factor 1 (HIF‐1) and HIF‐1‐induced glycolysis are correlated with chemoresistance; however, this is not evident in lung cancer. We investigated the effect of HIF‐1α and carbonic anhydrase IX (CAIX), a transmembrane protein neutralizing intracellular acidosis, on chemoresistance and prognosis of lung cancer patients after induction chemoradiotherapy. Associations of HIF‐1α, glucose transporter 1 (GLUT1), and CAIX with chemoresistance of lung cancer were investigated using A549 lung cancer cells under normoxia or hypoxia in vitro. HIF‐1α‐induced reprogramming of glucose metabolic pathway in A549 cells and the effects of HIF‐1 and CAIX on the cytotoxicity of vinorelbine were investigated. Immunohistochemical analyses were performed to determine HIF‐1α, GLUT1, and CAIX expression levels in cancer specimens from lung cancer patients after induction chemoradiotherapy. Hypoxia induced HIF‐1α expression in A549 cells. Moreover, hypoxia induced GLUT1 and CAIX expression in A549 cells in a HIF‐1‐dependent manner. Glucose metabolic pathway was shifted from oxidative phosphorylation to glycolysis by inducing HIF‐1α in A549 cells. HIF‐1 and CAIX induced chemoresistance under hypoxia, and their inhibition restored the chemosensitivity of A549 cells. The expression levels of HIF‐1α, GLUT1, and CAIX were associated with poor overall survival of lung cancer patients after induction chemoradiotherapy. HIF‐1 and CAIX affected the chemosensitivity of A549 cells and prognosis of lung cancer patients. Therefore, inhibition of HIF‐1 and CAIX might improve prognosis of lung cancer patients after induction chemoradiotherapy. Further analysis might be helpful in developing therapies for lung cancer.
The epithelial‐mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug‐resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E‐cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E‐cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E‐cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.
Electromyography (EMG) of anal sphincter muscles was different in patients with amyotrophic lateral sclerosis (ALS) and Shy-Drager syndome. In 30 patients with ALS, EMG of the external sphincter muscle was essentially normal, with no signs of denervation. In eight cases of Shy-Drager syndrome, however, motor unit potentials of the anal sphincter had highly polyphasic forms of long duration and high amplitude. In the Shy-Drager syndrome, there seems to be specific damage of lower motor neurons that innervate the external sphincter muscle of the anus.
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