Pancreatic metastasis of malignant melanoma diagnosed by EUS-guided fine needle aspiration (EUS-FNA)]

Pancreatic metastasis of malignant melanoma is rarely diagnosed while the patient is alive. We report a case of metastatic melanoma of the pancreas in a 35-year-old woman presenting with a solid mass of the pancreas. Her past medical history included a radical hysterectomy 2 years previously for malignant melanoma of the vagina. Twelve months later, lung metastasis was also resected. EUS-guided fine needle aspiration (EUS-FNA) identified that the pancreatic tumor was histologically and immunohistochemically identical to the surgical specimen of her lung neoplasm. Imaging studies including US, CT, and MRI have limited value to distinguish the tumors from primary ductal adenocarcinoma. EUS-FNA can provide tissue diagnosis from pancreatic masses, specifically when other modalities have failed.     

Clinical usefulness of the frontal assessment battery (FAB) for elderly in memory clinic]

To investigate the usefulness of the frontal assessment battery (FAB) as a brief assessment for diagnosis in patients with dementia, we examined cognitive function using the FAB, Mini-mental state examination (MMSE), Kana-hiroi test, and Raven's colored progressive matrices (RCPM). Subjects were 82 senile patients having amnesia as a complaint including 28 Alzheimer's disease (AD), 14 frontotemporal dementia (FTD), 17 vascular dementia (VD), 13 mild cognitive impairment (MCI), and 10 healthy persons. We discussed the difference of scores in different types of dementia. In the FAB, the scores of healthy persons and MCI were much higher compared with the scores of all types of dementia. There were high correlation between FAB and MMSE, Kana-hiroi test, and RCPM. Although some subjects showed normal score in MMSE and/or RCPM, they showed low score in FAB. Based on this, FAB is efficient for the differential diagnosis of dementia as brief screening tool.     

Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress

Pretreatment of cultured hepatocytes with the ferric iron chelator deferoxamine prevents the killing of the cells by tert-butyl hydroperoxide (TBHP). Incubation of the deferoxamine-pretreated hepatocytes in a serum-free medium containing only 0.25 nM iron restored the sensitivity of the cells to TBHP within 4 to 6 hr. An amino acid-free medium accelerated the restoration of sensitivity in parallel with an enhanced rate of degradation of 14C-prelabeled protein. By contrast, inhibitors of the autophagic degradation of protein, including chymostatin, 3-methyladenine, benzyl alcohol, colchicine, oligomycin, and methylamine, inhibited the restoration of sensitivity of deferoxamine-treated hepatocytes to TBHP in parallel with their inhibition of protein degradation. With chymostatin, 3-methyladenine, benzyl alcohol, and colchicine, there was a parallel dose dependency of both the inhibition of protein turnover and the inhibition of the restoration of sensitivity to TBHP. Ascorbic acid, known to specifically retard the autophagic degradation of ferritin, inhibited the restoration of sensitivity to TBHP without effect on the general rate of protein turnover. None of the agents studied had any protective effect on the toxicity of TBHP for hepatocytes that were not pretreated with deferoxamine. These data indicate that the autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by TBHP.     

Antimetastatic Activity of Polymeric RGDT Peptides Conjugated with Poly(ethylene glycol)

Polymeric peptides containing defined repetitive or cyclic structures of RGDT sequence, (RGDT)_n (n = 1 to 11) and cyclo(RGDT)_n (n=2 to 4), at a dose of 500 μg exhibited an inhibitory effect on experimental lung metastasis upon co-injection with tumor cells and the magnitude of the effect increased in parallel with the increase of degree of repetition of the RGDT sequence. The conjugation of (RGDT)_n (n = 1, 5, 11) with poly(ethylene glycol), PEG as a polymeric carrier led to enhanced inhibition of lung metastasis in proportion to the degree of RGDT sequence repetition and in a dose-dependent manner. Multiple i.v. administrations of PEG-(RGDT)₁₁, at 2-day and 3-day intervals before the excision of primary tumors, effectively inhibited spontaneous lung metastasis by s.c. inoculation of tumors, whereas (RGDT)₁₁ exhibited inhibition of lung metastasis only when given at 2-day intervals. This indicates that the conjugation of PEG with (RGDT)_n allowed the prolongation of administration interval, implying a sustained inhibitory effect on tumor metastasis. In support of this supposition, a decrease in the arrest of radiolabeled tumor cells in the lungs was observed when PEG-(RGDT)₁₁ was co-injected i.v. with tumor cells, or injected i.v. one day before tumor inoculation. In contrast, (RGDT)₁₁ significantly inhibited the tumor cell arrest in the lungs only upon co-injection with tumor cells. We also noted that (RGDT)_n, cyclo(RGDT)_n and PEG-(RGDT)₁₁ inhibited tumor cell invasion into Matrigel in a concentration-dependent manner and in proportion to the degree of RGDT sequence repetition, indicating that the peptide-mediated antimetastatic effect is partly associated with the anti-invasive potential. Thus, the conjugation of anti-cell adhesive and antimetastatic RGDT peptide with PEG might provide a therapeutically promising basis for the prevention of cancer metastasis (“anti adhesion therapy”).     

Zebrafish protocadherin 10 is involved in paraxial mesoderm development and somitogenesis.

Here, we present the first report of the molecular cloning of zebrafish protocadherin 10 (Pcdh10, OL-protocadherin) and describe its functional analyses in the development of segmental plate. Epitope-tagged Pcdh10 expressed in embryos was localized on cell peripheries of adjacent cells. In situ hybridization showed that pcdh10 was expressed in the paraxial mesoderm (PAM) and developing somites, and in the pineal body, the diencephalon, and the vicinity of otocysts. Expression in PAM increased in the last few presumptive somites, reached the maximum level in the latest segmenting somites, and decreased thereafter during somite maturation. These expression patterns suggested that Pcdh10 is involved in development of PAM and somites. This was confirmed by morpholino knockdown and dominant-negative inhibition of Pcdh10 in embryos, which disturbed movements of PAM cells and somite segmentation. Comparative studies showed that pcdh10 expression lasted up to approximately three times longer in maturing somites than that of paraxial protocadherin (pcdh8). They also indicated that the adaxial cells expressed pcdh8 but not pcdh10. We propose that Pcdh10 is involved in the morphogenic movements of PAM cells and somite segmentation and that differential adhesion of Pcdh8 and Pcdh10 plays a role in the morphogenic machinery of somites and adaxial cells.