Clinicopathological analysis of immunohistochemical expression of CD47 and SIRPα in adult T-cell leukemia/lymphoma

The interaction of CD47 and signal-regulatory protein alpha (SIRPα) induces “don't eat me signal”, leading suppression of phagocytosis. This signal can affect the clinical course of malignant disease. Although CD47 and SIRPα expression are associated with clinicopathological features in several neoplasms, the investigation for adult T-cell leukemia/lymphoma (ATLL) has not been well-documented. This study aimed to declare the association between CD47 and SIRPα expression and clinicopathological features in ATLL. We performed immunostaining on 73 biopsy samples and found that CD47 is primarily expressed in tumor cells, while SIRPα is expressed in non-neoplastic stromal cells. CD47 positive cases showed significantly higher FoxP3 (P = .0232) and lower CCR4 (P = .0214). SIRPα positive cases presented significantly better overall survival than SIRPα negative cases (P = .0132). SIRPα positive cases showed significantly HLA class I (P = .0062), HLA class II (P = .0133), microenvironment PD-L1 (miPD-L1) (P = .0032), and FoxP3 (P = .0229) positivity. In univariate analysis, SIRPα expression was significantly related to prognosis (Hazard ratio [HR] 0.470; 95% confidence interval [CI] 0.253-0.870; P = .0167], although multivariate analysis did not show SIPRα as an independent prognostic factor. The expression of SIRPα on stromal cells reflects activated immune surveillance mechanism in tumor microenvironment and induce good prognosis in ATLL. More detailed studies for gene expression or genomic abnormalities will disclose clinical and biological significance of the CD47 and SIRPα in ATLL.     

Risk of second malignancies in patients with gastric marginal zone lymphomas of mucosa associate lymphoid tissue (MALT)

Background

It is controversial whether patients with gastric marginal zone lymphomas of mucosa associated lymphoid tissue (MALT) have higher risk of second malignancies. The aim of this study was to define the risk of second malignancies in these patients.

Methods

We analyzed prospective follow-up data of 146 consecutive patients with gastric MALT lymphoma treated at Aichi Cancer Center Hospital and compared the incidence of second malignancies with that in the general population. We calculated the standardized incidence ratio (SIR), using age- and sex-specific incidence rates from the Aichi Cancer Registry.

Results

The median follow-up period was 74 months. A total of 27 tumors occurred in 22 patients (15.1 %), including 19 solid tumors. Of these, nine tumors were detected concomitantly with, and 18 tumors following, the diagnosis of gastric MALT lymphoma. Four patients had two second malignancies each. For the entire group, the SIR of an additional malignancy was 3.39 (95 % confidence interval [CI] 2.11–4.66). An increased incidence of solid tumors (SIR 2.91 [1.60–4.22]) and hematologic malignancies (SIR 5.54 [1.70–9.38]) were seen. In addition, there was increased risk for development of second malignancies during follow up (SIR 2.26 [1.21–3.30]). Chemotherapy for treatment of MALT was an independent risk factor for second malignancies (age–sex adjusted hazard ratio 3.98 [1.47–10.79].

Conclusions

Compared with the general population, patients with gastric MALT lymphoma are at increased risk for second malignancies, including gastric cancer.     

Anti-ageing effects of dentifrices containing anti-oxidative,anti-inflammatory,and anti-bacterial agents (Tomarina) on gingival collagen degradation in rats

Objective

Previous studies have demonstrated the relationship between ageing and oxidative stress. In this study, we examined the effects of topical application of a dentifrice containing anti-oxidative, anti-inflammatory, and anti-bacterial agents (Tomarina^®) to the gingival surface on gingival collagen degradation in rats.

Design

Fischer 344 male rats (4 or 8 months old) were divided into two groups: experimental group and control group. Tomarina^® (the experimental group) or control dentifrice (the control group) was applied 5 days per week for 2 months.

Results

In the control group, gingival collagen density decreased with ageing. In the experimental group, the collagen density did not change with ageing, and was greater than that in the control group at 10 months of age (p < 0.0083). In addition, the control group showed an increase in serum oxidative stress with ageing. The experimental group also showed increased serum oxidative stress, but the value was lower than the control group at 10 months of age (p < 0.0083). Furthermore, low expressions of protein oxidative damage in the periodontal tissue were observed in the experimental group, compared to the control group at 6 months and 10 months.

Conclusion

These findings indicate that Tomarina^® might suppress the effects of ageing on gingival collagen degradation, by decreasing oxidative stress in the rat model.     

Perioperative Oral Administration of Cystine and Theanine Enhances Recovery After Distal Gastrectomy

Background: It has been reported that cystine and theanine, amino acids related to glutathione synthesis, have immunomodulatory effects, such as suppressing inflammation after strenuous exercise. In this study, we examined the effects of oral administration of cystine and theanine during the perioperative period as a pilot study. Methods: Forty‐three cases of distal gastrectomy for cancer conducted in our department were assigned to the cystine and theanine group (CT group) or to the placebo control group (P group), and a randomized, single‐blind, parallel‐group study was then performed. Cystine (700 mg) and theanine (280 mg) or a placebo was administered to participants for 10 continuous days (4 days before to 5 days after surgery). Changes in pre‐ and postoperative interleukin (IL)–6, C‐reactive protein (CRP), albumin, white blood cell (WBC) count, neutrophil count, total lymphocyte count, resting energy expenditure (REE), and body temperature were compared and examined. Results: Ten patients were excluded, leaving 33 patients in the study. The CT group had significantly lower IL‐6 values (postoperative day [POD] 4), CRP levels (POD 7), neutrophil counts (POD 4), and body temperatures (POD 5) than the P group (P < .05). In addition, REE in the P group peaked on day 1 (1.14 ± 0.16 [pre‐ and postoperative ratio]), whereas the CT group did not show any increase on POD 1 (0.99 ± 0.21, P < .05 vs P group). Conclusions: This study suggests that oral administration of cystine and theanine during the perioperative period may alleviate postgastrectomy inflammation and promote recovery after surgery.     

Increased Serum Levels of Epidermal Growth Factor in Children with Autism

The etiology of autism is unclear, however autism is considered as a multifactorial disorder that is influenced by neurological, environmental, immunological and genetic factors. Growth factors, including epidermal growth factor (EGF), play an important role in the celluler proliferation and the differentiation of the central and peripheral nervous system. In this study we hypothesized that EGF may play a role in the pathophysiology of autism and examined serum EGF levels in children with autism. We measured serum levels of EGF in the 27 autistic children and 28 age- matched normal controls. The serum levels of EGF in the subjects with autism were significantly higher than those of normal control subjects. However, there were no correlations between serum EGF levels and clinical variables in the subjects with autism. This is the first report demonstrating the increased serum levels of EGF in children with autism. This study suggests that increased levels of EGF might have an importance in the pathophysiology of autism.     

IL12RB2 and ABCA1 genes are associated with susceptibility to radiation dermatitis

PURPOSE: Severe acute radiation dermatitis is observed in approximately 5% to 10% of patients who receive whole-breast radiotherapy. Several factors, including treatment-related and patient-oriented factors, are involved in susceptibility to severe dermatitis. Genetic factors are also thought to be related to a patient's susceptibility to severe dermatitis. To elucidate genetic polymorphisms associated with a susceptibility to radiation-induced dermatitis, a large-scale single-nucleotide polymorphism (SNP) analysis using DNA samples from 156 patients with breast cancer was conducted. EXPERIMENTAL DESIGN: Patients were selected from more than 3,000 female patients with early breast cancer who received radiotherapy after undergoing breast-conserving surgery. The dermatitis group was defined as patients who developed dermatitis at a National Cancer Institute Common Toxicity Criteria grade of > or =2. For the SNP analysis, DNA samples from each patient were subjected to the genotyping of 3,144 SNPs covering 494 genes. RESULTS: SNPs that mapped to two genes, ABCA1 and IL12RB2, were associated with radiation-induced dermatitis. In the ABCA1 gene, one of these SNPs was a nonsynonymous coding SNP causing R219K (P = 0.0065). As for the IL12RB2 gene, the strongest association was observed at SNP-K (rs3790568; P = 0.0013). Using polymorphisms of both genes, the probability of severe dermatitis was estimated for each combination of genotypes. These analyses showed that individuals carrying a combination of genotypes accounting for 14.7% of the Japanese population have the highest probability of developing radiation-induced dermatitis. CONCLUSION: Our results shed light on the mechanisms responsible for radiation-induced dermatitis. These results may also contribute to the individualization of radiotherapy.