Postoperative C-reactive Protein Is a Predictive Biomarker for Survival After Non-small Cell Lung Cancer Resection.

BACKGROUND/AIM: Preoperative C-reactive protein (CRP) is well recognized as a prognostic factor of non-small cell lung cancer (NSCLC). The present study aimed to elucidate the prognostic impact of postoperative CRP in patients with NSCLC following lung resection. PATIENTS AND METHODS: We retrospectively reviewed 336 patients with NSCLC treated with lung resection. CRP levels were measured at postoperative week 6 (CRP6w; range: 4-8 weeks). Patients were divided into two groups based on CRP6w median value (5.0 mg/l); the 5-year overall survival (OS) as well as the recurrence-free survival (RFS) was evaluated in both groups. RESULTS: Five-year OS and RFS were worse in the high-CRP6w group than in the low-CRP6w group (62.9% vs. 82.9%; p<0.001, 48.4% vs. 76.1%; p<0.001, respectively). Subgroup analysis for pathological stage I and ≥II also revealed worse OS in the high-CRP6w group. Multivariate analysis revealed an association between high CRP6w and worse OS (hazard ratio, 2.23; p<0.001). CONCLUSION: CRP6w may serve as a prognostic biomarker in patients with resected NSCLC.

Impact of the favorable prognosis of patients with lung cancer adjoining bullae.

BACKGROUND: Lung cancer adjoining bullae (LC-AB) is an uncommon manifestation. The clinical characteristics and prognosis of LC-AB remain unclear. The aim of this study is to investigate the clinical features and overall survival (OS) of patients with LC-AB following lung resection compared to non-LC-AB group. METHODS: We retrospectively investigated 291 consecutive patients with lung cancer who underwent curative resection in a single institution between April 2007 and March 2015. A total of LC-AB was 52 patients. LC-AB was determined using thin slice computed tomography (CT) imaging and pathological findings. Survival analysis was calculated using the Kaplan-Meier method. We used a Cox proportional hazards model for the univariate and multivariate analysis to identify prognostic factors. RESULTS: The LC-AB group showed a higher frequency of younger patients (P=0.017), former or current smokers (P=0.011), men (P=0.021), tumor location in the upper lobe (P=0.031), moderately or poorly differentiated tumor histology (P<0.001), pleural indentation (P=0.007), and non-adenocarcinoma histology (P=0.016) than the non-LC-AB group. The 5-year survival and recurrence-free survival (RFS) rates were significantly higher in the LC-AB group than the non-LC-AB group (88.5% vs. 74.9%, P=0.010, 75.4% vs. 61.3%, P=0.030, respectively). Multivariate analysis using a Cox proportional hazard model of OS showed that LC-AB was an independent prognostic factor [hazard ratio (HR): 0.30, 95% confidence interval (CI): 0.12-0.77, P=0.012]. CONCLUSIONS: Patients with LC-AB had better OS than those with non-LC-AB. Thus, LC-AB may be an independent favorable prognostic factor following curative resection.

Impact of Postoperative Pneumonia Developing After Discharge on Long-Term Follow-up for Resected Lung Cancer.

BACKGROUND: Postoperative nosocomial pneumonia is a common immediate complication following lung resection. However, the incidence and mortality of pneumonia developing after discharge (PDAD) for lung-resected patients during long-term observation remain unclear. The aim of this study was to investigate the clinical features of PDAD in patients with resected lung cancer. METHODS: We conducted a retrospective cohort study of 357 consecutive patients with lung cancer who had undergone lung resection at a single institution, between April 2007 and December 2016. The clinical characteristics, pathological features, and overall survival were analyzed. Propensity score matched analysis was used for the evaluation of overall survival between PDAD and non-PDAD groups with adjusted relevant confounding factors. RESULTS: PDAD was observed in 66 patients (18.5%). The cumulative incidence of PDAD was 14.9% at 3 years and 21.6% at 5 years. Mortality of PDAD was 30.3%. Multivariate analysis demonstrated that the risk factors for PDAD were age (OR 1.07; P = 0.005), oral steroid use (OR 5.62; P = 0.046), and lower-lobe resection (OR 1.87; P = 0.034). After propensity score matching, 52 patients with PDAD and 52 patients without it were compared. The incidence of PDAD resulted in a worse 5-year overall survival (56.1 vs. 69.3%; P = 0.024). The Cox proportional hazards model indicated that PDAD was associated with poor overall survival (HR 1.99, P = 0.027). CONCLUSIONS: Our findings revealed a high incidence and mortality of PDAD among patients who had undergone lung resection with long-term follow-up. Therefore, PDAD could be associated with poorer overall survival.

Prognostic Impact of Postoperative C-reactive Protein for Non-small Cell Lung Cancer Following Lobectomy.

BACKGROUND/AIM: C-reactive protein (CRP) is associated with cancer progression; however, the prognostic impact of postoperative CRP remains controversial. The aim of this study was to investigate the prognostic significance of postoperative CRP in patients with resected non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 198 consecutive patients with NSCLC that had undergone lobectomy were retrospectively reviewed. CRP was measured on postoperative days 1, 3, and 5. Patients were divided into two groups according to the median of CRP on postoperative day 3 (CRP3); the high and low CRP3 groups (n=99, respectively). RESULTS: Five-year overall survival was significantly higher in the high CRP3 group than the low CRP3 (75.3% vs. 86.5%; p=0.016), as was the 5-year recurrence-free survival (62.7% vs. 73.0%; p=0.016). Multivariate analysis revealed that high CRP3 was associated with a favorable prognosis (hazard ratio(HR)=0.36; p<0.001). CONCLUSION: High CRP3 may be a favorable prognostic predictor in patients with NSCLC following lobectomy.

Characterization of in vivo tumorigenicity tests using severe immunodeficient NOD/Shi-scid IL2Rγnull mice for detection of tumorigenic cellular impurities in human cell-processed therapeutic products.

The contamination of human cell-processed therapeutic products (hCTPs) with tumorigenic cells is one of the major concerns in the manufacturing and quality control of hCTPs. However, no quantitative method for detecting the tumorigenic cellular impurities is currently standardized. NOD/Shi-scid IL2Rγnull (NOG) mice have shown high xeno-engraftment potential compared with other well-known immunodeficient strains, e.g. nude mice. Hypothesizing that tumorigenicity test using NOG mice could be a sensitive and quantitative method to detect a small amount of tumorigenic cells in hCTPs, we examined tumor formation after subcutaneous transplantation of HeLa cells, as a model of tumorigenic cells, in NOG mice and nude mice. Sixteen weeks after inoculation, the 50% tumor-producing dose (TPD50) values of HeLa cells were stable at 1.3 × 104 and 4.0 × 105 cells in NOG and nude mice, respectively, indicating a 30-fold higher sensitivity of NOG mice compared to that of nude mice. Transplanting HeLa cells embedded with Matrigel in NOG mice further decreased the TPD50 value to 7.9 × 10 cells, leading to a 5000-fold higher sensitivity, compared with that of nude mice. Additionally, when HeLa cells were mixed with 106 or 107 human mesenchymal stem cells as well as Matrigel, the TPD50 values in NOG mice were comparable to those of HeLa cells alone with Matrigel. These results suggest that the in vivo tumorigenicity test using NOG mice with Matrigel is a highly sensitive and quantitative method to detect a trace amount of tumorigenic cellular impurities in human somatic cells, which can be useful in the quality assessment of hCTPs.

Carcinogenicity evaluation for the application of carbon nanotubes as biomaterials in rasH2 mice.

The application of carbon nanotubes (CNTs) as biomaterials is of wide interest, and studies examining their application in medicine have had considerable significance. Biological safety is the most important factor when considering the clinical application of CNTs as biomaterials, and various toxicity evaluations are required. Among these evaluations, carcinogenicity should be examined with the highest priority; however, no report using transgenic mice to evaluate the carcinogenicity of CNTs has been published to date. Here, we performed a carcinogenicity test by implanting multi-walled CNTs (MWCNTs) into the subcutaneous tissue of rasH2 mice, using the carbon black present in black tattoo ink as a reference material for safety. The rasH2 mice did not develop neoplasms after being injected with MWCNTs; instead, MWCNTs showed lower carcinogenicity than carbon black. Such evaluations should facilitate the clinical application and development of CNTs for use in important medical fields.

Detection of the onset of ischemia and carcinogenesis by hypoxia-inducible transcription factor-based in vivo bioluminescence imaging.

An animal model for the early detection of common fatal diseases such as ischemic diseases and cancer is desirable for the development of new drugs and treatment strategies. Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates oxygen homeostasis and plays key roles in a number of diseases, including cancer. Here, we established transgenic (Tg) mice that carry HRE/ODD-luciferase (HOL) gene, which generates bioluminescence in an HIF-1-dependent manner and was successfully used in this study to monitor HIF-1 activity in ischemic tissues. To monitor carcinogenesis in vivo, we mated HOL mice with rasH2 Tg mice, which are highly sensitive to carcinogens and are used for short-term carcinogenicity assessments. After rasH2-HOL Tg mice were treated with N-methyl-N-nitrosourea, bioluminescence was detected noninvasively as early as 9 weeks in tissues that contained papillomas and malignant lesions. These results suggest that the Tg mouse lines we established hold significant potential for monitoring the early onset of both ischemia and carcinogenesis and that these lines will be useful for screening chemicals for carcinogenic potential.

[Effect of lifestyle and health behavior on neutrophil function].

OBJECTIVE: In this study, we investigated the relationships of neutrophil functions with lifestyle factors (namely, subjective stress, exercise habits, smoking habits, alcohol-drinking habits, and self-perceived status health) and health behavior in the Chinese urban elderly. METHODS: We performed a health survey of the elderly aged 65 years or older living in Tianjin. The subjects were 42 males (69.1 ± 4.1 years old) and 41 females (69.1 ± 4.1 years old). Investigations of subjective stress, exercise habits, smoking habits, alcohol-drinking habits, and self-perceived health status were performed. The phagocytosis and superoxide productivity of neutrophils were measured by the nitroblue tetrazolium (NBT) reduction method. In addition, leukocyte count and serum total protein (TP) level were examined. RESULTS: The investigations revealed the associations of health behavior (p<0.05) and self-perceived health (p<0.10) with the balance between phagocytosis and subsequent superoxide production. CONCLUSIONS: The present study revealed that there were correlations of neutrophil functions with lifestyle factors (subjective stress, exercise habits, smoking habits, alcohol-drinking habits, and self-perceived status health) and health behavior in the Chinese urban elderly.

Higher susceptibility of NOG mice to xenotransplanted tumors.

The purpose of tumorigenicity testing, as applied not only to cell substrates used for viral vaccine manufacture but also stem cells used for cell-based therapy, is to discriminate between cells that have the capacity to form tumors and cells that do not. Therefore, tumorigenicity testing is essential in assessing the safety of these biological materials. Recently developed NOD/Shi-scid IL2Rg(null) (NOG) mice have been shown to be superior to NOD/Shi-scid (SCID) mice for xenotransplantation of both normal and cancerous cells. To select a suitable mouse strain as a xenogenic host for tumorigenicity testing, we compared the susceptibility of NOG (T, B, and NK cell-defective), SCID (T and B cell-defective), and the traditionally used nude (T cell-defective) mice to tumor formation from xenotransplanted HeLa S3 cells. When 10(4) HeLa S3 cells were subcutaneously inoculated into the flanks of these mice, the tumor incidence on day 22 was 10/10 (100%) in NOG, 2/10 (20%) in SCID, and 0/10 (0%) in nude mice. The subcutaneous tumors formed reproducibly and semiquantitatively in a dose-dependent manner. Unexpectedly, half of the NOG mice (5/10) that had been inoculated with a mere 10(1) HeLa S3 cells formed progressively growing subcutaneous tumors on day 78. We confirmed that the engrafted tumors originated from inoculated HeLa S3 cells by immunohistochemical staining with anti-HLA antibodies. These data suggest that NOG mice may be the best choice as a suitable strain for testing tumorigenicity.

Calcitonin gene-related peptide stimulates proliferation of alveolar epithelial cells.

BACKGROUND: Alveolar epithelial cells are known as progenitor cells for the restoration from the damage in the lung. Calcitonin gene-related peptide (CGRP) has been reported to play an important role in the proliferation of various types of epithelial and endothelial cells. We investigated the effects of CGRP on the proliferation of alveolar epithelial cells in vitro and in vivo. METHODS: A549 cells were cultured in Dulbecco Modified Eagle Medium with 5% fatal bovin serum for 24 hours, then CGRP was added in vitro. The proliferation of DNA synthesis was measured using 5-bromo-2-deoxyuridine, an analog of thymidine, by enzyme-linked immunosorbent assay.As one intracellular response to CGRP, we examined activation of p44/42- extracellular signal-regulated kinase (ERK) pathway by adding CGRP, using western blotting method.Recombinant adenovirus encoding nuclear-targeted-human beta-CGRP (rhCGRP) was administered into Male Wister rat (n = 5, 10 weeks old) lungs by intratracheal instillation in vivo. 7 days after the administration of CGRP, rat lungs were harvested and histological findings and immunohistochemical staining of proliferating cell nuclear antigen (PCNA) were evaluated to examine cell proliferation. RESULTS: In vitro study, CGRP increased the proliferation of A549 cells in a dose and time dependent manner. CGRP8-37 (inhibitor of CGRP receptor) decreased CGRP induced proliferation of DNA synthesis. Phosphorylation of ERK pathway was observed within 15 minutes and peaked in one hour. U0126 (inhibitor of ERK pathway) decreased CGRP induced proliferation of DNA synthesis.In vivo study, histological examination of the lung indicated proliferation of alveolar epithelial cells in the rhCGRP-treated group and the nuclei of alveolar epithelial cells were positive for PCNA immunostaining. CONCLUSION: In this study, we conclude that CGRP stimulates proliferation of human alveolar epithelial cells in vivo and in vitro.

Carcinogenic comparative study on rasH2 mice produced by two breeding facilities.

CByB6F1-Tg(HRAS)2Jic mice (brand name: rasH2 mouse) are produced by two breeding facilities, CLEA Japan, Inc. (Fuji, Shizuoka, Japan) and Taconic (Germantown, NY, USA), and supplied world wide. To confirm carcinogenic conformity of both mice, a 26-week carcinogenicity test was performed on a total of 120 mice obtained from both facilities under the same protocol and same timing in our facility. All mice were divided into a vehicle (citrate buffer at pH 4.5, 10 ml/kg, single intraperitoneal injection) group and a MNU (N-methyl-N-nitrosourea, 75 mg/kg, single intraperitoneal injection) group. Fifteen mice of each sex were assigned to each group. The survival rate of the vehicle group was maintained at 100% for mice from both facilities at completion of the test. In the MNU group, MNU-induced tumor death occurred from 9 to 12 weeks after administration, and the final survival rate for both facilities was 6.7%. In the pathological examination, only benign tumors of lungs, spleen, forestomach and skin were observed in a few mice in the vehicle group of both facilities. In the MNU group, the incidence of forestomach papilloma/squamous cell carcinoma in mice from both facilities was 100%. The incidences of malignant lymphoma in CLEA Japan mice and Taconic mice were 86.7% and 93.3%, respectively, and no significant difference was observed (Fisher's exact probability test). Although lung adenoma and skin papilloma/keratoacanthoma, which are major MNU induced tumors in this strain, were observed in several mice from both facilities, no significant differences were found. Consequently, carcinogenic conformity of rasH2 mice derived from two breeding facilities was confirmed by the present study.

Examination of percutaneous application in a 26-week carcinogenicity test in CB6F1-TG rasH2 mice.

We examined the possibility of expanding applications of rasH2 mice, which are genetically manipulated mice for short-term carcinogenicity tests, to percutaneous application. A 26-week short-term carcinogenicity study was performed on a total of 300 mice including 75 male and female rasH2 mice each, and 75 male and female non-Tg mice each from the same litter as the rasH2 mice divided into untreated group, an ethanol group, a white Vaseline group, an acetone group, and a phorbol 12-myristate 13-acetate (TPA) group. Only shaving of dorsal skin was performed on the untreated mice. As a positive control, TPA was administered percutaneously at a dose of 2.5 microg/kg and 3 times/week for 26 weeks based on the protocol for Tg.AC mice in the ILSI/HESI international validation study. In the ethanol, white Vaseline, and acetone groups, no tumorous changes were observed on the skin at the administration site. In the TPA group, nodular changes at the administration site were observed from seven weeks after the start of administration in rasH2 mice, and the incidence in males and females was 50.0% (7/14) and 53.3% (8/15), respectively. In a pathological examination, nodules in 21.4% (3/14) of males and 46.7% (7/15) of females were diagnosed as skin papilloma or keratoacanthoma, and the rest as squamous cell hyperplasia. In the non-Tg mice, no nodules or tumorigenic changes were observed at the administration site. These findings show that percutaneous application in rasH2 mice is possible in 26-week carcinogenicity tests.

[Relationship between lifestyle and oral health in Chinese elderly].

OBJECTIVE: Oral health is very important particularly for elderly to live happily. The purpose of this study is to clarify the relationship between lifestyle and oral health in Chinese elderly. METHODS: The subjects were 96 men (mean +/- SD: 70.1 +/- 4.9) and 92 women (70.7 +/- 5.4). Oral health status was evaluated according to the numbers of remaining, intact, treated, and untreated teeth and score in WHO's CPI code. By carrying out a questionnaire survey, we evaluated lifestyle factors, such as stress (SCL-S), smoking habits, drinking habit, sleeping hours, sports, snack habit, and tooth brushing habit. Logistic regression analysis was used in analyzing the data. RESULTS: By multi-logistic regression analysis, men who smoke were more likely to have a lower CPI score than those who do not {odds ratio (OR) = 4.69, 95% confidence interval (95% CI) = 0.79-27.89, p < .10}. Men who brush their teeth less than once a day are less likely to have a lower CPI score than those who brush their teeth more than twice a day (OR = 0.33, 95% CI = 0.09-1.22, p < .10). On the other hand, women who experience much stress are more likely to have a lower CPI score than women who experience little stress (OR = 5.59, 95% CI = 1.29-24.15, p < .05). CONCLUSIONS: The study indicated that smoking may affect oral health conditions in men, whereas stress may affect oral health conditions in women. The reduction in stress and abstinence from smoking are important in maintaining good oral health in Chinese elderly.

Use of IC tags in short-term carcinogenicity study on CB6F1 TGrasH2 mice.

We studied the effect of IC tags, subcutaneously implanted animal identification tools, on rasH2 mice. A 26-week short-term carcinogenicity study was performed on a total of 299 mice including 75 male and female rasH2 mice each, and 74 male and 75 female non-Tg mice from the same litter as the rasH2 mice divided into a non-IC tag group, the IC-tag group, acetone group, TPA group and MNU group (all of the animals except for those in the non-IC tag group) had IC tags implanted subcutaneously in their backs. The administration methods of the positive control drugs TPA (2.5 micro g/kg, 3 times/week, percutaneously) and MNU (75 mg/kg, single intraperitoneal injection) were based on the protocol of the ILSI/HESI international collaborative study. The results showed no differences in the tumorigenic incidence and organs developing tumors between the IC tag and non-IC tag groups in both rasH2 and non-Tg mice. In the positive control MNU group, the tumorigenic incidence and organs developing tumors were the same as the background data and no promotion of carcinogenesis was observed. In all IC tag groups including the TPA group and MNU group, a fibrous capsule was formed around the IC tags subcutaneously, but no inflammatory changes or neoplastic changes were observed. From these findings, it was concluded that the IC tag has no effect on a 26-week carcinogenicity test of rasH2 mice under the conditions of the present study.

[Volatile organic compounds of the tap water in the Watarase, Tone and Edo River system].

OBJECTIVES: The chlorination of river water in purification plants is known to produce carcinogens such as trihalomethanes (THMs). We studied the river system of the Watarase, Tone, and Edo Rivers in regard to the formation of THMs. This river system starts from the base of the Ashio copper mine and ends at Tokyo Bay. Along the rivers, there are 14 local municipalities in Gunma, Saitama, Ibaragi and Chiba Prefectures, as well as Tokyo. This area is the center of the Kanto plain and includes the main sources of water pollution from human activities. We also analyzed various chemicals in river water and tap water to clarify the status of the water environment, and we outline the problems of the water environment in the research area (Fig. 1). METHODS: Water samples were taken from 18 river sites and 42 water faucets at public facilities in 14 local municipalities. We analyzed samples for volatile organic compounds such as THMs, by gas chromatography mass spectrometry (GC-MS), and evaluations of chemical oxygen demand (COD) were made with reference to Japanese drinking water quality standards. RESULTS: Concentrations of THMs in the downstream tap water samples were higher than those in the samples from the upperstream. This tendency was similar to the COD of the river water samples, but no correlation between the concentration of THMs in tap water and the COD in tap water sources was found. In tap water of local government C, trichloroethylene was detected. CONCLUSIONS: The current findings suggest that the present water filtration plant procedures are not sufficient to remove some hazardous chemicals from the source water. Moreover, it was confirmed that the water filtration produced THMs. Also, trichloroethylene was detected from the water environment in the research area, suggesting that pollution of the water environment continues.

Exhaustive exercise and type-1/type-2 cytokine balance with special focus on interleukin-12 p40/p70.

It is known that interleukin (IL)-12 p70 promotes the differentiation of type-1 helper T (Th1) cells, which produce type-1 cytokines such as IL-2 and interferon (IFN), thereby supporting cellular immunity, whereas IL-12 p40 acts as an antagonist of IL-12 p70. In contrast, IL-4 and IL-6 promote the differentiation of Th2 cells, which produce type-2 cytokines IL-4, IL-6 and IL-10, induce humoral immunity and are involved in allergic reactions. Exhaustive exercise causes the suppression of T lymphocyte activity while asthmatic and allergic diseases are subclinically more prevalent in athletes. One of the mechanisms behind these observations might be a lower type-1 and higher type-2 cytokine balance, which we previously demonstrated to occur after exhaustive exercise. In the present study, we investigated the type-1/type-2 cytokine balance by measuring plasma concentrations of IL-2, IL-4, IL-5, IL-10, tumor necrosis factor (TNF)-alpha and IFN-gamma with microparticle-based flow cytometric technology. IL-5, IL-6 and IL-13 were measured by enzyme-linked immunosorbent assay (ELISA). IL-12 p40 and p70 were measured separately, also by ELISA. Plasma IL-12 p40 concentration rose significantly after maximal exercise and to an even greater extent after a marathon race. Conversely, plasma IL-12 p70 could not be detected even using two different assays. The marathon race caused a marked increase in the plasma concentrations of IL-6 and IL-10. Their responses were correlated (r = 0.78, p < 0.01), indicating that IL-6 is an inducer of IL-10, and may partly induce the type-1 < type-2 cytokine balance. With the exception of one study involving maximal exercise, other studies have failed to show any change in circulating IL-12 concentration with exercise. The present study demonstrated that IL-12 p40 was present in excess of p70 especially after exercise. This may be one of the mechanisms behind several phenomena including cellular immunosuppression, an increase in the relative proportion of type-2 cytokines following exhaustive exercise, and the higher incidence of infections and allergic disorders in regularly exercising endurance athletes.

[The effect of chronic stress on neutrophil function in tumor-inoculated rats].

OBJECTIVES: In order to clarify the relation between stress load and inoculated tumor growth in conjunction with neutrophil functions, several kinds of stress such as physical (Ph) and psychological (Ps) stress were loaded on rats either SST-2 tumor cell inoculated or control, and the functions of their peripheral neutrophils were determined. METHODS: A communication box was used for stress load on rats. SST-2 cells were inoculated in to rats in the tumor-inoculation groups. Two weeks after inoculation, the tumors were removed from the backs of the rats and weighed. The functions of neutrophils in the peripheral blood collected from the tail vein, were determined by the NBT deoxidization method. RESULTS: Tumor growth was enhanced when rats were loaded with either Ph or Ps stresses, but was inhibited when tumor cells were inoculated following either Ph or Ps stresses. These results show that chronological differences of loaded stresses influence immunological functions differently. The O2- production from the neutrophils stimulated by NBT-treated Staphilococcus aureus was suppressed in tumor-inoculated Ph and Ps groups, more markedly in the tumor-inoculated Ph group. It is logically relevant that the size of tumors increased in these groups, predominantly in the tumor-inoculated Ph group. On the other hand, O2- production from the neutrophils was enhanced and tumor growth decreased in tumor-inoculated animals following either Ph or Ps stresses. CONCLUSIONS: Our experiments, it revealed that the function of neutrophils is strongly enhanced by stress load and O2- production is inhibited by the tumor inoculation as shown in stimulation tests. Therefore, our findings suggested that neutrophils may participate in the inhibition of tumor growth.

SST-2 tumor inoculation is a useful model for studying the anti-tumor immune response in SHR rats.

OBJECTIVE: The purpose of the present study was to investigate the relation between the dose of tumor cell inoculation (especially the doses less than minimum required to evoke tumor growth) and the anti-tumor immune system, particularly lymphoblast formation and cytotoxic activity of lymphcytes. METHOD: We inoculated rats with various doses of SST-2 tumor cells and examined natural killer (NK) cell activity and lymphoblast formationin vitro. RESULT: The results showed that the cytotoxicities against SST-2 cells and lymphoblast formation of lymphocytes were enhanced by small dose inoculation of tumor cells that could not induce tumor growth. CONCLUSION: It was suggested that was lymphocutes play an important role as an anti-tumor immune system at small doses of tumor inoculation, which appears to reflect an early stage of tumor growthin vivo. It was also suggested that SST-2 tumor inoculation might be a useful model for studying the anti-tumor immune response in SHR rats.

Relationships between lifestyle factors and neutrophil functions in the elderly.

We investigated the relationships between neutrophil functions and lifestyle factors in the elderly. The subjects (84 males, 73.9+/-5.8 years old; and 63 females, 70.0+/-4.6 years old) belonged to a recreational seniors club in Japan. Investigations of the subjects' stress, exercise habits, smoking habits, and alcohol-drinking habits were performed. The phagocytosis and superoxide productivity of the neutrophils were measured with a nitroblue tetrazolium (NBT) reduction test. In addition, leukocyte counts and serum total protein (TP) levels were determined. The results revealed that aging, high serum levels, and stress-coping factors (e.g., having hobbies, keeping pets, and close links with friends or family) significantly correlated with preferable neutrophil functions. In addition, significant effects of lifestyle factors on the balance between phagocytosis and subsequent superoxide production were observed. Thus, the results of the present study suggest that there are correlations between neutrophil functions and lifestyle factors in the elderly.