Background: Although many authors have reported that the median survival time of surgically resected non-small cell lung cancer (NSCLC) was shorter in aneuploid than in diploid determined by flow cytometry, there are few reports about DNA ploidy using bronchial brushing material in all types of lung cancer. Method: The DNA ploidy test results of 109 consecutive patients with lung cancer were analyzed to find the relationship of DNA ploidy and anatomic or physiologic stage. And the differences of the response to various therapeutic modalities according to DNA ploidy were evaluated at least 8 weeks after the begining of the therapy. Results: Numbers of patients with DNA aneuploid pattern or high proliferative activity (S+G2M>22%) were not different among the various cell types of lung cancer. The relationship of DNA ploidy and anatomic or physiologic stage was not significant. However, NSCLC patients with high proliferative activity showed more advanced anatomic stage than those without that (p<0.05). The short-term response rate to therapy depended on the anatomic (p<0.005) or physiologic stages (p<0.05) in patients with NSCLC, and not on DNA ploidy or proliferative activity. Conclusion: DNA ploidy test using bronchial brushing material revealed that high proliferative activity means advanced anatomic stage, but it was not useful to predict the therapeutic response.
The maintenance of a viable pregnancy has long been viewed as an immunological paradox. The deveolping embryo and trophoblast are immunologically foreign to the maternal immune system due to their maternally inherited genes products and tissue-specific differentiation antigens (Hill & Anderson, 1988). Therefore, speculation has arisen that spontaneous abortion may be caused by impaired maternal immune tolerance to the semiallogenic conceptus (Hill, 1990). Loss of recall antigen has been reported in immunosuppressed transplant recipients and is associated with graft survival (Muluk et al., 1991; Schulik et al., 1994). Progesterone $(10^{-5}M)$ has immunosuppressive capabilities (Szekeres-Bartho et al., 1985). Previous study showed that fertile women, but not women with unexplained recurrent abortion (URA), lose their immune response to recall antigens when pregnant (Bermas & Hill, 1997). Therefore, we hypothesized that immunosuppressive doses of progesterone may affect proliferative response of lymphocytes to trophoblast antigen and alloantigen. Proliferative responses using $^3H$-thymidine ($^3H$-TdR) incorporation of peripheral blood mononuclear cells (PBMCs) to the irradiated allogeneic periperal blood mononuclear cells as alloantigen, trophoblast extract and Flu as recall antigen, and PHA as mitogen were serially checked in 9 women who had experienced unexplained recurrent miscarriage. Progesterone vaginal suppositories (100mg b.i.d; Utrogestan, Organon) beginning 3 days after ovulation were given to 9 women with unexplained RSA who had prior evidence of Th1 immunity to trophoblast. We checked proliferation responses to conception cycle before and after progesterone supplementation once a week through the first 7 weeks of pregnancy. All patients of alloantigen and PHA had a positive proliferation response that occmed in the baseline phase. But 4 out of 9 patients (44.4%) of trophoblast antigen and Flu antigen had a positive proliferative response. The suppression of proliferation response to each antigen were started after proliferative phase and during pregnancy cycles. Our data demonstrated that since in vivo progesterone treated PBMCs suppressed more T-lymphocyte activation and $^3H$-TdR incorporation compare to PBMCs, which are not influenced by progesterone. This data suggested that it might be influenced by immunosuppressive effect of progesterone. In conclusion, progesterone may play an important immunological role in regulating local immune response in the fetal-placental unit. Furthermore, in the 9 women given progesterone during a conception cycle, Only two (22%) repeat pregnancy losses occured in these 9 women despite loss of antigen responsiveness (one chemical pregnancy loss and one loss at 8 weeks of growth which was karyotyped as a Trisomy 4). These finding suggested that pregnancy loss due to fetal aneuploidy is not associated with immunological phenomena.
The purpose of the study was to determine the effect of vitamin B complex on stress-induced immune alteration. 21 medical students participated in the study 4 weeks before an academic examination period(baseline), 2 weeks before the exam period and during the exam period. Among them, 10 subjects were given vitamin B complex for 4 weeks, and 11 were not given vitamin B during the whole period. Cell-mediated immune function was measured by lymphocyte proliferative response to phytohemagglutinin(PHA) and interleukin-2(IL-2) production. Global assessment of recent stress(GARS) scale and symptom checklist-90-revised(SCL-90-R) were used to measure the level of subjective stress and psychopathology. Vitamin group had significantly lower scores of anxiety scale on SCL-90-R than non-vitamin group. No significant differences were found in lymphocyte proliferative response to PHA and IL-2 production between vitamin and non-vitamin groups during each period. There were no significant differences in change of of each of the two immune parameters over time as well as between vitamin and non-vitamin groups. However, lymphocyte proliferative response to PHA was significantly increased over time. In conclusion, it was suggested that vitamin B complex is likely to decrease anxiety level, and that exam stress might enhance lymphocyte proliferation regardless of vitamin B.
Kim, Kee Won;Park, Suk Young;Lee, Kyung Bock;Kim, Hyun-su
IMMUNE NETWORK
/
v.4
no.2
/
pp.88-93
/
2004
Background: Bone marrow mesenchymal stem cells (MSC) inhibit the immune response of lymphocytes to specific antigens and dendritic cells (DC) are professional antigenpresenting cells whose function is to present antigen to naive T-lymphocytes with high efficiency and play a central role in the regulation of immune response. We studied the effects of MSC on DC to evaluate the relationship between MSC and DC in transplantation immunology. Methods: MSC were expanded from the bone marrow and DC were cultured from peripheral blood mononuclear cells (PBMNC) of 6 myelogenous leukemia after achieving complete response. Responder cells isolated from PBMNC and lysates of autologous leukemic cells are used as tumor antigen. The effect of MSC on the DC was analyzed by immunophenotype properties of DC and by proliferative capacity and the amount of cytokine production with activated PBMNC against the allogeneic lymphocytes. Also, cytotoxicity tests against leukemic cells studied to evaluate the immunologic effect of MSC on the DC. Results: MSC inhibit the CD83 and HLA-class II molecules of antigen-loaded DC. The proliferative capacity and the amount of INF-$\gamma$ production of lymphocytes to allogeneic lymphocytes were decreased in DC co-cultured with MSC. Also the cytotoxic activity of lymphocytes against leukemic cells was decreased in DC co-cultured with MSC. Conclusion: MSC inhibit the activation and immune response of DC induced by allogeneic or tumor antigen.
Yousef, Amany I;El-Masry, Omar S;Abdel Mohsen, Mohamed A
Asian Pacific Journal of Cancer Prevention
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v.17
no.2
/
pp.743-748
/
2016
Background: $K^-Ras$ activation is an early event in colorectal carcinogenesis and associated mutations have been reported in about 40% of colorectal cancer patients. These mutations have always been responsible for enhancing malignancy and silencing them is associated with attenuation of tumorigenicity. Among downstream effectors are the RAF/MEK/ERK and the PI3K/Akt signaling pathways. PI3K/Akt signaling leads to reduction of apoptosis, stimulated cell growth and enhanced proliferation. Ellagic acid (EA), a naturally occurring antioxidant, has recently emerged as a promising anti-cancer agent. Purpose: To evaluate the impact of cellular genetic makeup of two colon cancer cell lines with different genetic backgrounds, HCT-116 ($K^-Ras^-/p53^+$) and Caco-2 ($K^-Ras^+/p53^-$), on response to potential anti-tumour effects of EA. In addition, the influence of $K^-Ras$ silencing in HCT-116 cells was investigated. Materials and Methods: Cellular proliferation, morphology and cell cycle analysis were carried out in addition to Western blotting for detecting total Akt and p-Akt (at Thr308 and Ser473) in the presence and absence of different concentrations of EA. Cell proliferation was also assessed in cells transfected with different concentrations of $K^-Ras$ siRNA or incubated with ellagic acid following transfection. Results: The results of the present study revealed that EA exerts anti-proliferative and dose-dependent pro-apoptotic effects. Cytostatic and cytotoxic effects were also observed. p-Akt (at Thr308 and Ser473) was downregulated. Moreover, EA treatment was found to (i) reduce $K^-Ras$ protein expression; (ii) in cells transfected with siRNA and co-treated with EA, pronounced anti-proliferative effects as well as depletion of p-Akt (at Thr308) were detected. Conclusions: Cellular genetic makeup ($K^-Ras^-/p53^-$) was not likely to impose limitations on targeting EA in treatment of colon cancer. EA had a multi-disciplinary pro-apoptotic anti-proliferative approach, having inhibited Akt phosphorylation, induced cell cycle arrest and showed an anti-proliferative potential in HCT-116 cells (expressing mutant $K^-Ras$).
We examined the responses of PBMCs to house dust mite (HDM) allergen in atopic and healthy, non-atopic dogs to identify differences in lymphocyte reactivity that might reflect the immunologic status of atopic dermatitis. Thirteen of 20 (65%) atopic dogs showed a positive lymphocyte proliferative response to HDM allergen. The rate of response was significantly higher in the atopic dogs than that in healthy, non-atopic dogs insensitive to the allergen (P = 0.007). The proliferative responses were positively correlated with the level of HDM-specific IgE in serum (P = 0.035), and were thereby confirmed to reflect the activity of lymphocytes competent to promote IgE production. These results suggest that HDM-specific lymphocytes were present in peripheral blood and played a role in the pathogenesis of canine atopic dermatitis.
In this study we investigated effects of supplementation with ethyl acetate extracts of the brown alga Eisenia bicyclis on innate immune cells to evaluate the possibilities as an immunomoulator in exercise stress. Twenty male SD rats were divided into four groups and the treatments were as follows: A, no Eisenia bicyclis extract (EBE) (200 mg/kg) intake and maintained at rest ; B, no EBE intake and undergoing exercise ; C, EBE intake and undergoing exercise ; D, EBE intake and maintained at rest. After 5 weeks of oral supplementation, rats were undergoing intensive swimming exercises for 2 h and sacrificed to assess the effects on peritoneal macrophages, spleen cells and natural killer (NK) cells. We showed increasing effects on nitric oxide-inducible nitric oxide synthase (NO-iNOS) production by macrophages and no effects of NK tumoricidal activity and suppressive effects on spleen cell proliferation in exercise group. However, EBE supplementation suppressed NO-iNOS production by macrophages and increased NK tumoricidal activity and spleen cell proliferative response to mitogen in exercise group. Overall, these results that EBE supplementation has differential effects on innate immune response and could be useful as sports nutrition.
Kim, Hyuck-Joo;Hong, Jong-Tae;Yu, Byeong-Kee;Kim, Giyoung;Kim, Suk
Journal of Biosystems Engineering
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v.38
no.2
/
pp.121-128
/
2013
Purpose: Porcine proliferative enteropathy (PPE), caused by the obligate intracellular bacterium Lawsonia intracellularis, is a widely distributed disease throughout the world causing substantial economic loss. In order to diagnose PPE rapidly, the rapid kit was developed and tested. Methods: In this study, a rapid kit was developed to screen the PPE rapidly at the pig farm. Also, occult blood test with fecal occult blood (FOB) kit was done for detecting the blood in pig feces which might be the evident of hemorrhagic PPE. For developing the kit, we tested fecal samples of PPE infected pigs diagnosed by polymerase chain reaction (PCR) method. Results: With the developed rapid kit, Lawsonia intracellularis was detected in high density emulsion of ileum. On the other hand, the test result of detecting Lawsonia in feces showed too high non-specific response. In addition, nevertheless the FOB test result showed that blood evident could be founded in pig feces, the diagnosing result was not fit to PCR test result, which shows blood in pig feces could be from not only hemorrhagic PPE but also many reasons. Conclusions: To deal with the PPE effectively, it will be better for farmers to screen the PPE in earlier stage with easy and rapid diagnosing tool on farm. This study found out that the rapid kit could detect the Lawsonia intracellularis and hemoglobin in pig feces. However, the non-specific response to negative samples of PPE was too high to use at a pig farm. Further research is needed for lowering the non-specific response with the rapid kit.
Park, Min-Jung;Min, So-Youn;Park, Kyoung-Su;Cho, Mi-La;CHo, Young-Gyu;Min, Jun-Ki;Yoon, Chong-Hyeon;Park, Sung-Hwa;Kim, Ho-Youn
IMMUNE NETWORK
/
v.5
no.4
/
pp.221-231
/
2005
Background: Immune regulatory dendritic cells (DCs) play an important role in maintaining self-tolerance. Recent evidences demonstrate that DCs expressing indoleamine 2,3-dioxygenase (IDO), which is involved in tryptophan catabolism, play an important role in immunoregulation and tolerance and induce T cell apoptosis. This study was devised to examine the role of IDO in the oral tolerance induction in collagen-induced arthritis (CIA) mouse model. Methods: Beginning 2 weeks before immunization, CII was fed six times to DBA/1 mice and the effect on arthritis was assessed. In tolerized mice, $CD11c^+$ DCs were isolated and stimulated with CII, IFN-${\gamma}$, and LPS with or without IDO inhibitor, 1-methyl-DL-tryptophan (1-MT) and IDO expression by $CD11c^+$ DCs was analyzed using FACS and RT-PCR. The expression of IDO, MHC II, CD80, and CD86 by $CD11c^+$ DCs were examined using confocal microscopy. Regulatory effect of $CD11c^+$ DCs on Ag-specific T cell proliferative response to CII was examined by mixed lymphocyte reaction (MLR) with or without 1-MT. Results: The proportion of IDO-expressing $CD11c^+$ DCs was slightly higher in tolerized mice than in CIA mice and significantly increased after stimulation with CII, IFN-${\gamma}$, and LPS in an IDO-dependent manner. On confocal microscopic examination, the expression of IDO was higher and those of MHC II and CD86 were lower in CD11c + DCs from tolerized mice compared to those from CIA mice. On MLR, $CD11c^+$ DCs from tolerized mice inhibited T cell proliferative response to CII in an IDO-dependent manner. Conclusion: Enhanced IDO expression by $CD11c^+$ DCs from tolerized mice may contribute to the regulation of proliferative response of CII-reactive T cells and could be involved in the induction of oral tolerance to CII.
Cellular senescence is defined as a state of stable cell cycle exit in response to various stimuli, which include both cytotoxic stress and physiological cues. In addition to the core non-proliferative aspect, senescence is associated with diverse functionalities, which contribute to the role of senescence in a wide range of pathological and physiological processes. Such functionality is often mediated by the capability of senescent cells to communicate with their surroundings. Emerging evidence suggests that senescence is not a single entity, but a dynamic and heterogeneous collective phenotype. Understanding the diverse nature of senescence should provide insights into the complexity of tissue homeostasis and its disruption, such as in aging and tumorigenesis.
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