Inhibitory effects of naturally occurring antioxidants on the initiation stage of hepatocarcinogenesis were studied. Group 1 rats were given a diet containing β‐carotene (β8‐CT, 0.02%), α‐tocopherol (α‐TP, 1.5%), glutathione (GLT, 5%), vanillin (VNL, 1%), quercetin (QCT, 1%) or ellagic acid (ELA, 1%), or 3 doses of diallyl sulfide (DAS, 200 mg/kg, i.g) over an 8‐day period. On day 7, the animals received a single dose of 2‐amino‐3‐methylimidazo[4,5‐f]jumoline (IQ, 100 mg/kg, i.g.), 12 h after two‐thirds partial hepatectomy for initiation and 2 weeks thereafter, were placed on promotion regimen comprising phenobarbital (0.05% in diet) and a single dose of D‐galactosamine (100 mg/kg, i.p.). Groups 2 and 3 were treated as described for Group 1, but without test material or IQ, respectively. Survivors were killed at week 11 and antioxidant influence was assessed by comparing values for preneoplastic glutathione S‐transferase placental form‐positive (GST‐P+) foci between Groups 1 and 2. All lesions larger than 70 βm in diameter consisting of approximately 5 cells in cross section were counted. Numbers of GST‐P+ foci/cm2 in Group 1 were: β ‐CT, 7.99; α‐TP, 8.21; GLT, 9.71; DAS, 10.37; VNL, 10.57; QCT, 11.1; ELA, 12.5 (n = 11‐15). All, except ELA, showed a significant decrease as compared with the Group 2 value of 14.54 (n=15). Only β ‐CT showed a significant decrease for the area value. This is the first report to show that β ‐CT, α‐TP, GLT, DAS, VNL, QCT exert inhibitory effects on initiation of hepatocarcinogenesis by the food carcinogen IQ, suggesting that these antioxidants might find application as chemopreventive agents. Furthermore, the current protocol proved practical for the assessment of chemopreventive agents within 11 weeks, a relatively Short period.

To examine the radiofrequency ablation (RFA) reliability in early breast cancer, we performed RFA followed by delayed surgical resection on 41 patients with invasive or non-invasive breast carcinoma less than 2 cm. MRI scans were obtained before ablation and resection. Excised specimens were examined pathologically by haematoxylin-eosin and nicotinamide adenine dinucleotide-diaphorase staining. 40 patients completed 1 RFA session, which was sufficient to achieve complete tumour cell death. Overall complete ablation rate was 87.8% (36/41). There were no treatment-related complications other than that of a superficial burn in 1 case. After RFA, the tumour was no longer enhanced on MRI in 25/26 (96.2%) cases. Residual cancer, which was suspected on MRI in 1 case, was confirmed pathologically. MRI could be an applicable modality to evaluate therapeutic effect. RFA could be an alternate local treatment option to breast-conserving surgery for early breast cancer.

Retinal degeneration induced by a single parenteral dose (40 mg) of N-methyl-N-nitrosourea (MNU) was studied in rats and rabbits. Sequential observations showed that severe pathological changes, that is, complete or widespread destruction of the photoreceptor layer and the outer nuclear layer of the retina, occurred in both animals by 72 hr after the administration ofMNU. At week 5, at the end stage ofthe retinal degeneration induced by MNU, thin remnants remained with the inner nuclear layer in direct contact with the pigment epithelium. An additional immunohistochemistry study using antibodies against 7-methyldeoxyguanosine (7-mdGua), revealed the presence of high levels of 7-mdGua DNA adducts in the nuclei of the outer nuclear layer cells. This finding suggests that the alkylation of the outer nuclear layer by MNU was the direct cause of the retinal degeneration seen in these animals.

Hepatocyte growth factor (HGF), a potent mitogen for adult rat hepatocytes in primary culture, has previously been shown to be primarily expressed in the nonparenchymal cells of the liver. Using polyclonal antisera against human and rat HGFs we studied the tissue distribution of HGF immunohistochemically and found the most intense staining in the pancreas islet cells in both man (autopsy cases) and the rat. Differential localization of 4 pancreas islet hormones, glucagon, insulin, somatostatin and pancreatic polypeptide, revealed HGF to be preferentially expressed within the glucagon‐positive cells. The results indicate that HGF is primarily produced or stored in A‐cells and may act as a growth factor in a paracrine and an endocrine fashion, like various other hormones.

Introduction: Previous studies have suggested that the efficacy of eribulin is influenced by the activity of antitumor immunity of patients. Absolute lymphocyte count (ALC) and the neutrophil/lymphocyte ratio (NLR) are easily available parameters associated with the immunological status of patients. Objective: Here we tried to classify patients' immunological status by using the scatter plot of ALC and NLR, and investigated its utility for predicting survival among patients with metastatic breast cancer receiving eribulin. Methods: The medical records of 125 patients who received eribulin for metastatic breast cancer at our hospital between July 2011 and April 2019 were retrospectively reviewed. Uni-and multivariate analyses were performed to determine the association between baseline ALC/NLR and progression-free survival (PFS)/overall survival (OS). The cutoff values for ALC and NLR were determined using scatter plot analysis. Results: The entire cohort was classified into immunologically favorable (ALC ≥1,500/µL, 30 patients), intermediate (ALC < 1,500/µL, NLR < 5.0, 76 patients), and unfavorable (NLR ≥5.0, 19 patients) groups. Univariate analysis showed significant differences in PFS and OS between the groups, whereas multivariate analysis revealed that ALC ≥1,500/µL and NLR ≥5.0 were independent predictors of PFS, with adjusted hazard ratios (95% CI) of 0.57 (0.33-0.99) and 1.78 (1.00-3.15), respectively. NLR ≥5.0 was also associated with worse OS (adjusted hazard ratio: 0.55; 95% CI 0.35-0.88; p = 0.013). Conclusions: Among patients with metastatic breast cancer receiving eribulin, survival outcomes were well stratified according to baseline peripheral blood ALC and NLR. Accordingly, high ALC and NLR can be used as predictive markers for longer disease control and worse survival, respectively.