An electron microscopic and immunohistochemical study of Merkel cell carcinoma

Two cases of Merkel cell carcinoma (MCC) were examined by electron microscopy and immunohistochemistry. Histologically, tumor cells, which extended from the dermis into the subcutis, showed anastomosing bands with partial trabecular pattern. The ultrastructural study showed tumor cells in case 1 with numerous neurosecretory granules. The number of granules in case 2, however, was smaller compared with that in case 1. Perinuclear bundles of filaments were present in case 2, but few bundles were observed in case 1. By immunohistochemistry, cytokeratin (CK)-8, -18, -19, and -20 and epithelial membrane antigen were stained positively within tumor cells in both cases. It was interesting that staining patterns of chromogranin A and of neuron-specific enolase were different in the two cases. These data indicated that CK-20 is a useful marker for diagnosing MCC and that ultrastructural and immunohistochemical differences in both cases were the result of phenotypic variation.     

Spin labeling of a cysteine residue of the Escherichia coli outer membrane lipoprotein in its membrane environment

A method was developed to attach a spin label to a specific site on the structural lipoprotein of the Escherichia coli outer membrane in situ. This method takes advantage of the fact that the outer membrane of wild-type E. coli contains few residues reactive towards sulfhydryl reagents. A mutant E. coli strain has been isolated [Suzuki, H., Nishimura, Y., Iketani, H., Campisi, J., Hirashima, A., Inouye, M. & Hirota, Y. (1976) J. Bacteriol. 127, 1494-1501] in which the second position from the carboxy terminus of the lipoprotein is changed from arginine into a cysteine residue. The membrane fraction of this mutant was treated with N-(1-oxyl-2,2,5,5-tetramethylpyrrolidinyl)maleimide in the presence of EDTA and 2-mercaptoethanol. Spin label was found to be preferentially incorporated into the lipoprotein. The spectrum of the spin-labeled membrane shows two components, both arising from spin label at the same site near the carboxy terminus. The strongly immobilized component has a maximum hyperfine splitting value of 53 G, and the weakly immobilized component, 37 G. A fraction of the lipoprotein is covalently bound to the peptidoglycan layer through its carboxy-terminal lysine; the spectrum of the isolated bound form of the lipoprotein was identical to that of the free form. When the matrix protein, the other major outer membrane protein, was removed by mutation, the spectrum of the lipoprotein was altered, suggesting that these two proteins are closely associated.     

Real-time tumor-tracking radiotherapy for adrenal tumors.

PURPOSE: To investigate the three-dimensional movement of internal fiducial markers near the adrenal tumors using a real-time tumor-tracking radiotherapy (RTRT) system and to examine the feasibility of high-dose hypofractionated radiotherapy for the adrenal tumors. MATERIALS AND METHODS: The subjects considered in this study were 10 markers of the 9 patients treated with RTRT. A total of 72 days in the prone position and 61 treatment days in the supine position for nine of the 10 markers were analyzed. All but one patient were prescribed 48 Gy in eight fractions at the isocenter. RESULTS: The average absolute amplitude of the marker movement in the prone position was 6.1+/-4.4 mm (range 2.3-14.4), 11.1+/-7.1 mm (3.5-25.2), and 7.0+/-3.5 mm (3.9-12.5) in the left-right (LR), craniocaudal (CC), and anterior-posterior (AP) directions, respectively. The average absolute amplitude in the supine position was 3.4+/-2.9 mm (0.6-9.1), 9.9+/-9.8 mm (1.1-27.1), and 5.4+/-5.2 mm (1.7-26.6) in the LR, CC, and AP directions, respectively. Of the eight markers, which were examined in both the prone and supine positions, there was no significant difference in the average absolute amplitude between the two positions. No symptomatic adverse effects were observed within the median follow-up period of 16 months (range 5-21 months). The actuarial freedom-from-local-progression rate was 100% at 12 months. CONCLUSIONS: Three-dimensional motion of a fiducial marker near the adrenal tumors was detected. Hypofractionated RTRT for adrenal tumors was feasible for patients with metastatic tumors.     

Dosimetry of fission neutrons in a 1-W reactor,UTR-KINKI

The energy spectrum of fission neutrons in the biological irradiation field of the Kinki University reactor, UTR-KINKI, has been determined by a multi-foil activation analysis coupled with artificial neural network techniques and a Au-foil activation method. The mean neutron energy was estimated to be 1.26 +/- 0.05 MeV from the experimentally determined spectrum. Based on this energy value and other information, the neutron dose rate was estimated to be 19.7 +/- 1.4 cGy/hr. Since this dose rate agrees with that measured by a pair of ionizing chambers (21.4 cGy/hr), we conclude that the mean neutron energy could be estimated with reasonable accuracy in the irradiation field of UTR-KINKI.     

Measurement of residual 152Eu activity induced by atomic bomb neutrons in Nagasaki and the contribution of environmental neutrons to this activity

Residual 152Eu activities induced by neutrons from the Nagasaki atomic bomb were measured for nine mineral samples located up to 1,061 m in the slant range and one control sample at 2,850 m from the hypocenter. A chemical separation to prepare europium-enriched samples was performed for all samples, and gamma ray measurements were carried out with a low background well-type germanium detector. In this paper, the measured specific activities of 152Eu are compared with activation calculations based on the DS86 neutron fluence and the 93Rev one. The calculated-to-measured ratios are also compared with those of 60Co and 36Cl. The present results indicate that the measurements agree to the calculation within a factor of three as observed in the nuclear tests at Nevada. The activation level of environmental neutrons and the detection limit for 152Eu are also discussed.     

Phytol is a novel tumor promoter on ICR mouse skin.

Phytol is a branched, long-chain aliphatic alcohol which has various biological effects. In this study, we examined phytol as a tumor promoter in a mouse skin initiation-promotion model, and compared its promotion activity with that of 12-O-tetradecanoyl phorbol-13-acetate (TPA). Female ICR mice, 7 weeks of age, were initiated with 100 microg of 7,12-dimethylbenz(a)anthracene, and were then topically promoted twice a week for 16 weeks with 100 mg of phytol or with 2.5 microg of TPA. In this model 95% of animals treated with phytol developed skin tumors within 16 weeks. The average number of lesions per mouse treated with phytol was significantly lower than that in mice treated with TPA, and this significant difference continued up to 16 weeks after the end of promotion treatment. Characterization of hyperplasia 48 h after topical application of agents showed that epidermal thickness and vertical thickness following topical application of phytol were significantly increased compared with vehicle controls, but were significantly smaller than in animals treated with TPA. Ornithine decarboxylase (ODC) activity following topical application of phytol was increased in a dose-dependent manner and showed a weak, delayed induction (which was maximal 11-12 h after treatment) as compared with the case of TPA. The specific binding of [3H]phorbol-12,13-dibutyrate (PDBU) by JB6 cells was not inhibited by phytol at concentrations up to 1 mM. These results indicate that phytol has a weak tumor promoter activity compared to TPA and is a non-TPA-type tumor promoter in this model of mouse skin carcinogenesis.     

Optimization of fluoroscopy parameters using pattern matching prediction in the real-time tumor-tracking radiotherapy system

In the real-time tumor-tracking radiotherapy system, fluoroscopy is used to determine the real-time position of internal fiducial markers. The pattern recognition score (PRS) ranging from 0 to 100 is computed by a template pattern matching technique in order to determine the marker position on the fluoroscopic image. The PRS depends on the quality of the fluoroscopic image. However, the fluoroscopy parameters such as tube voltage, current and exposure duration are selected manually and empirically in the clinical situation. This may result in an unnecessary imaging dose from the fluoroscopy or loss of the marker because of too much or insufficient x-ray exposure. In this study, a novel optimization method is proposed in order to minimize the fluoroscopic dose while keeping the image quality usable for marker tracking. The PRS can be predicted in a region where the marker appears to move in the fluoroscopic image by the proposed method. The predicted PRS can be utilized to judge whether the marker can be tracked with accuracy. In this paper, experiments were performed to show the feasibility of the PRS prediction method under various conditions. The predicted PRS showed good agreement with the measured PRS. The root mean square error between the predicted PRS and the measured PRS was within 1.44. An experiment using a motion controller and an anthropomorphic chest phantom was also performed in order to imitate a clinical fluoroscopy situation. The result shows that the proposed prediction method is expected to be applicable in a real clinical situation.     

Immunohistochemical expression of cyclooxygenase-2 in skin cancers

BACKGROUND: Cyclooxygenase (COX), also known as prostaglandin endoperoxide synthase, catalyses the conversion of arachidonic acid to prostanoids. There are two different isoforms of COX, referred to as COX-1 and COX-2. Overexpression of COX-2 has been demonstrated in various neoplasms, such as experimentally promoted tumors, gastrointestinal cancers and breast tumors. METHODS: In this study, we used immunohistochemistry to investigate COX-2 expression in a series of basal cell epitheliomas (BCE), Bowen's disease, squamous cell carcinomas (SCC) and metastatic tumors of the skin. RESULTS: Four of 16 BCE showed a positive reaction for COX-2 and the adenoid type of BCE was the most strongly positive. In Bowen's disease, the extent of positive staining for COX-2 was even higher than that in BCE. Eleven of 15 SCC showed a positive reaction for COX-2 and the pattern of staining was heterogeneous with more intense staining in the center of the tumor nests. In metastatic tumors, the percentage of COX-2-positive tumor cells and the intensity of their staining was low compared with Bowen's disease and SCC. CONCLUSIONS: These results indicate that the intensity of COX-2 staining and its heterogeneous distribution are related to the degree of cellular differentiation and the various phenotypes of tumor cells, but the extent of COX-2 staining did not correlate with the degree of malignancy.     

The onset risk of carcinoma in patients continuing tacrolimus topical treatment for oral lichen planus: a case report

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.