The usefulness of mucin-depleted foci (MDF), which have recently been proposed as a new preneoplastic biomarker in rat colon carcinogenesis, was histologically investigated in rat colonic tissues treated with 1,2-dimethylhydrazine dihydrochloride (DMH). The relationship among aberrant crypt foci (ACF), MDF and β β β β-catenin accumulated crypts (BCAC) was examined by comparing the corresponding computer-captured images. Twelve male F344 rats were given DMH s.c. at a dose of 40 mg/kg body weight, once a week for 2 weeks, and randomly divided into two groups. Rats in group 1 were given normal drinking water, while those in group 2 were given drinking water containing indomethacin (IND) at 16 ppm for 6 weeks. All animals were sacrificed 8 weeks after the first DMH treatment. The resected colons were fixed in 10% formalin, and stained with Alcian blue for observation of ACF and MDF. Histological and immunohistochemical analysis revealed that the numbers of ACF, MDF and overlapping lesions in group 2 (treated with IND) were significantly decreased, compared with those in group 1. The number of BCAC in group 2 was also significantly lower than that in group 1. The reduction (61.5%) of MDF by IND was much greater than that (29.3%) of ACF. Analyses of the computer-captured images indicated that MDF had more frequent dysplastic changes and overexpression of β β β β-catenin than did ACF. MDF having over 4 crypts or MDF with the appearance of ACF corresponded well to BCAC. These results suggest that MDF may be useful as an early biomarker in colon carcinogenesis. eliable biomarkers for colon carcinogenesis are needed for screening of chemicals for carcinogenic risk or potential chemopreventive efficacy on colon carcinogenesis. Aberrant crypt foci (ACF), which were originally described by Bird in unsectioned murine colon exposed to a colon-specific carcinogen, azoxymethane (AOM), have been recognized as early preneoplastic lesions. 1) Subsequently, ACF induced by several kinds of chemical carcinogens have been widely used as a biomarker in short-term tests for prediction of colon carcinogenesis. 2) However, some researchers have reported a lack of correlation between ACF induction and tumor development. [3][4][5] Previously, we reported β-catenin accumulated crypts (BCAC) as a new biomarker for rat colon carcinogenesis, strongly predisposing to colon cancer. 6, 7) In addition to the accumulation of oncogenic β-catenin protein, the lesions harbored frequent β-catenin (Ctnnb1) gene mutations that are involved in the development of colon cancer. [8][9][10][11][12] Histological observations of BCAC showed dysplasia, a hallmark of malignant potential, and increasing size with time after the carcinogen exposure. 7) These observations indicate that BCAC are more likely to progress to malignant transformation than are ACF. However, their identification, based on immunohistochemical methods, is difficult in unsectioned colon and the procedure is complicated.Recently, MDF (mucin-depleted foci) have been described to be preneoplastic ...

Brain metastases from gynecological cancers were retrospectively investigated in 18 patients who were treated between 1985 and 2006. Six patients received surgical resection followed by radiotherapy, and 12 patients received only radiotherapy. The median survival for all patients was 4.1 months (range 0.7-48.2 months), and the actuarial survival rates were 11% at both 12 months and 24 months. Univariate analysis showed that treatment modality, extracranial disease status, total radiation dose, number of brain metastases, and Karnofsky performance status (KPS) all had statistically significant impacts on survival. Two patients survived for more than 2 years, and both had single brain metastasis, inactive extracranial disease, 90-100% KPS, and were treated with surgical resection followed by radiotherapy. Improvements in neurological symptoms were observed in 10 of the 12 patients treated with palliative radiotherapy, with median duration of 3.1 months (range 1.5-4.5 months). The prognoses for patients with brain metastases from gynecological cancers were generally poor, although selected patients may survive longer with intensive brain tumor treatment. Palliative radiotherapy was effective in improving the quality of the remaining life for patients with unfavorable prognoses.

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The purpose of this study was to retrospectively analyze the treatment results of boost external beam radiotherapy (EBRT) to clinically positive pelvic nodes in patients with uterine cervical cancer. The study population comprised 174 patients with FIGO stages 1B1–4A cervical cancer who were treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) and high-dose-rate intracavitary brachytherapy (HDR-ICBT). Patients with positive para-aortic or common iliac nodes (≥10 mm in the shortest diameter, as evaluated by CT/MRI) were ineligible for the study. Fifty-seven patients (33%) had clinically positive pelvic nodes. The median maximum diameter of the nodes was 15 mm (range, 10–60 mm) and the median number of positive lymph nodes was two (range, one to four). Fifty-two of 57 patients (91%) with positive nodes were treated with boost EBRT (6–10 Gy in three to five fractions). The median prescribed dose of EBRT for nodes was 56 Gy. The median follow-up time for all patients was 66 months (range, 3–142 months). The 5-year overall survival rate, disease-free survival rate and pelvic control rate for patients with positive and negative nodes were 73% and 92% (P = 0.001), 58% and 84% (P < 0.001), and 83% and 92% (P = 0.082), respectively. Five of 57 node-positive patients (9%) developed pelvic node recurrences. All five patients with nodal failure had concomitant cervical failure and/or distant metastases. No significant difference was observed with respect to the incidence or severity of late complications by application of boost EBRT. The current retrospective study demonstrated that boost EBRT to positive pelvic nodes achieves favorable nodal control without increasing late complications.