RASSF8 regulates progression of cutaneous melanoma through nuclear factor-κb

Our group previously demonstrated that the RASSF1 gene has a significant tumor suppressor role in cutaneous melanoma. The RASSF8 gene is a member of the N-terminal RASSF gene family. Previously, we identified RASSF8 (HOJ1, NCBI Gene ID:11228) expression in cutaneous melanoma; however the functional role of RASSF8 in melanoma is not known. RASSF8 expression was assessed in melanoma cell lines and tumors of different AJCC stages. Results indicated that RASSF8 expression was low in metastatic melanoma lines and decreased with melanoma progression. We then explored the mechanism of RASSF8 downregulation in melanoma by assessing methylation of RASSF8 and demonstrated that methylation of RASSF8 gene promoter was higher in advanced than in early stages melanomas. Functional activity of RASSF8 in melanoma lines by knockdown and overexpression of RASSF8 demonstrated that RASSF8 expression significantly inhibited cell growth, cell migration and invasion, whereas knockdown of RASSF8 expression significantly increased cell growth, cell migration and invasion of melanoma cells by increasing expression of P65 and its downstream target IL-6. Moreover RASSF8 was found to induce apoptosis in melanoma cells by activating the P53-P21 pathway, and also in vivo studies demonstrated that inhibiting RASSF8 increases the tumorigenic properties of human melanoma xenografts. These results suggest that RASSF8 plays a significant role in suppressing the progression of cutaneous melanoma.     

The relationship between the soluble Klotho protein and the residual renal function among peritoneal dialysis patients

Background

Klotho has been investigated as an anti-aging protein that is predominantly expressed in the distal convoluted tubules in the kidneys and in the choroid plexus of the brain. The purpose of the present study was to determine the relationship between the soluble form of Klotho and renal function in chronic peritoneal dialysis (PD) patients, a relationship which remains poorly understood.

Methods

The soluble Klotho levels in the serum, urine, and peritoneal dialysate obtained from thirty-six PD patients were determined by a sandwich enzyme-linked immunosorbent assay system.

Results

The amount of urinary excreted soluble Klotho over 24?h ranged from 1.54 to 1774.4?ng/day (median 303.2?ng/day; interquartile range [IR] 84.1–498.5), while the serum soluble Klotho concentration ranged from 194.4 to 990.4?pg/ml (mean 553.7?±?210.4?pg/ml). The amount of urinary Klotho excretion was significantly correlated with residual renal function. However, there was no apparent correlation between the serum soluble Klotho levels and the residual renal function. Klotho was also detected in the 24-h dialysate collections. There was a significant correlation between the peritoneal Klotho excretion and the amount of albumin contained in the dialysate collections (r?=?0.798, p?Conclusions The total amount of urinary excreted Klotho, but not the serum level of soluble Klotho, may be a potential biomarker for assessing the residual renal function among PD patients. Whether our findings are also valid for chronic kidney disease patients overall should therefore be evaluated in greater detail.     

Progressive systemic sclerosis associated with primary small cell carcinoma of the stomach

A 64-year-old man with a 5-year history of progressive systemic sclerosis (PSS) was hospitalized because of melena. Radiological and endoscopic examinations showed an ulcerative lesion with sharply demarcated and raised margins in the fornix of the stomach. Tumor markers—serum carcinoembryonic antigen (CEA, 11.3 ng/ml) and neuron-specific enolase (NSE, 38.9 ng/ml) were elevated. Histological examination of endoscopic biopsy specimens (and of necropsy specimens) showed proliferation of atypical small round cells. Immunohistological examination of these cells showed they were positive for epithelial membranous antigen (EMA), and neuron-specific enolase (NSE), but negative for UCHL1, leukocyte common antigen (LCA), anti-leukocyte B-cell (MB1), and antileukocyte T-cell (MT1) antigens. Based on these histological and immunohistological tests, a definite diagnosis of small cell carcinoma of the stomach with PSS was established. Our case is a rare combination of PSS and gastric small cell carcinoma. We also reviewed the literature for the association between PSS and gastric cancer in Japanese patients.     

Brain natriuretic peptide is a predictor of anthracycline-induced cardiotoxicity

Anthracyclines are effective antineoplastic drugs, but they frequently cause dose-related cardiotoxicity. The cardiotoxicity of conventional anthracycline therapy highlights a need to search for methods that are highly sensitive and capable of predicting cardiac dysfunction. We measured the plasma level of brain natriuretic peptide (BNP) to determine whether BNP might serve as a simple diagnostic indicator of anthracycline-induced cardiotoxicity in patients with acute leukemia treated with a daunorubicin (DNR)-containing regimen. Thirteen patients with acute leukemia were treated with a DNR-containing regimen. Cardiac functions were evaluated with radionuclide angiography before chemotherapies. The plasma levels of atrial natriuretic peptide (ANP) and BNP were measured at the time of radionuclide angiography. Three patients developed congestive heart failure after the completion of chemotherapy. Five patients were diagnosed as having subclinical heart failure after the completion of chemotherapy. The plasma levels of BNP in all the patients with clinical and subclinical heart failure increased above the normal limit (40 pg/ml) before the detection of clinical or subclinical heart failure by radionuclide angiography. On the other hand, BNP did not increase in the patients without heart failure given DNR, even at more than 700 mg/m(2). The plasma level of ANP did not always increase in all the patients with clinical and subclinical heart failure. These preliminary results suggest that BNP may be useful as an early and sensitive indicator of anthracycline-induced cardiotoxicity.     

Two cases of tuberculous peritonitis and clinical significance of serum CA-125

We had recently experienced two cases of tuberculous peritonitis. One was suspected of ovarian cancer but finally diagnosed as tuberculosis by the exploratory laparotomy. The other was found out casually at the operation of benign ovarian tumor. Both cases accompanied with pulmonary tuberculosis. Tuberculous peritonitis should be considered in the differential diagnosis in patients with abdominal disorders. Remarkable elevation of serum CA-125 related to ovarian cancer was found in both cases. It was suggested that level of serum CA-125 might be useful for diagnosis and monitoring of the disease.     

Hepatic resection for colorectal metastases in the caudate lobe of the liver

Although hepatic resections for colorectal metastases have become established procedures, there is still only a small number of reports of hepatic resections for such metastases in the caudate lobe. From 1993 to 2001, seven patients underwent eight hepatic resections for colorectal metastases in the caudate lobe at our department. The patients were five men and two women, and their ages were from 53 to 73 years. The ratio of synchronous to metachronous liver metastases was 2?:?5. Solitary metastasis was observed in one patient. One patient with a metastasis in the Spiegel lobe and three patients with metastasis in the caudate process underwent partial resection of the site. The other patients underwent resection of the Spiegel lobe (two times), resection of the right-sided caudate lobe, and total caudate lobe resection. The mean (±SE) operative time was 315.9 ± 30.6?min. Mean intraoperative blood loss was 1325.9 ± 421.1?ml, and mean postoperative hospital stay was 21 ± 3.7 days. One patient, who underwent sigmoidectomy and hepatectomy as an emergency operation due to ileus, experienced wound infection. No patient died within 12 months after the surgery. Five patients were alive at 24 months, and three at 36 months. The outcome of these patients encourages us to continue performing hepatic resection for colorectal metastases in the caudate lobe, as it is assumed to be a safe and effective procedure.