Continuous DC-CIK Infusions Restore CD8⁺ Cellular Immunity, Physical Activity and Improve Clinical Efficacy in Advanced Cancer Patients Unresponsive to Conventional Treatments

Zhao, Yan-Jie,Jiang, Ni,Song, Qing-Kun,Wu, Jiang-Ping,Song, Yu-Guang,Zhang, Hong-Mei,Chen, Feng,Zhou, Lei,Wang, Xiao-Li,Zhou, Xin-Na,Yang, Hua-Bing,Ren, Jun,Lyerly, Herbert Kim Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.6

Background: There are few choices for treatment of advanced cancer patients who do not respond to or tolerate conventional anti-cancer treatments. Therefore this study aimed to deploy the benefits and clinical efficacy of continuous dendritic cell-cytokine induced killer cell infusions in such patients. Materials and Methods: A total of 381 infusions (from 67 advanced cases recruited) were included in this study. All patients underwent peripheral blood mononuclear cell apheresis for the following cellular therapy and dendritic cells-cytokine induced killer cells were expanded in vitro. Peripheral blood T lymphocyte subsets were quantified through flow cytometry to address the cellular immunity status. Clinical efficacy and physical activities were evaluated by RECIST criteria and Eastern Cooperative Oncology Group scores respectively. Logistic regression model was used to estimate the association between cellular infusions and clinical benefits. Results: An average of $5.7{\pm}2.94{\times}10^9$ induced cells were infused each time and patients were exposed to 6 infusions. Cellular immunity was improved in that cytotoxic $CD8^+CD28^+$ T lymphocytes were increased by 74% and suppressive $CD8^+CD28^-$ T lymphocytes were elevated by 16% (p<0.05). Continuous infusion of dendritic cells-cytokine induced killer cells was associated with improvement of both patient status and cellular immunity. A median of six infusions were capable of reducing risk of progression by 70% (95%CI 0.10-0.91). Every elevation of one ECOG score corresponded to a 3.90-fold higher progression risk (p<0.05) and 1% increase of $CD8^+CD28^-$ T cell proportion reflecting a 5% higher risk of progression (p<0.05). Conclusions: In advanced cancer patients, continuous dendritic cell-cytokine induced killer cell infusions are capable of recovering cellular immunity, improving patient status and quality of life in those who are unresponsive to conventional cancer treatment.

Clinical Value of Real Time Elastography in Patients with Unexplained Cervical Lymphadenopathy: Quantitative Evaluation

Fu, Ying,Shi, Yun-Fei,Yan, Kun,Wang, Yan-Jie,Yang, Wei,Feng, Guo-Shuang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Ultrasonography is non-invasive and can give useful clues in the diagnosis of cervical lymphadenopathy, However, differential diagnosis is difficult in some situations even combined with color Doppler imaging. The present study was conducted to evaluate the clinical value of real time elastography in patients with unexplained cervical lymphadenopathy using a quantitative method. From May 2011 to February 2012, 39 enlarged lymph nodes from 39 patients with unexplained cervical lymphadenopathy were assessed. All the patients were examined by both B-mode ultrasound, color Doppler flow imaging and elastography. The method of analyzing elasto-graphic data was the calculation of the 10 parametres ("mean", "sd", "area%", "com", "kur", "ske", "con", "ent", "idm", "asm") offered by the software integrated into the Hitachi system. The findings were then correlated with the definitive tissue diagnosis obtained by lymph node dissection or biopsy. Final histology revealed 10 cases of metastatic lymph nodes, 11 cases of lymphoma, 12 cases of tuberculosis and 6 cases of nonspecific lymphadenitis. The significant distinguishing features for conventional ultrasound were the maximum short diameter (p=0.007) and absent of echogenic hilum (p=0.0293). The diagnostic accuracy was 43.6% (17/39 cases) and there were 17 patients with equivocal diagnosis. For elastography, "mean" (p=0.003), "area%" (p=0.009), "kurt" (p=0.0291), "skew" (p=0.014) and "cont" (p=0.012) demonstrated significant differences between groups. With 9 of the 17 patients with previous equivocal diagnoses (52.9%) definite and correct diagnoses could be obtained. The diagnostic accuracy for conventional ultrasound combined elastography was 69.2% (27/39 cases). There were differences in the diagnostic sensitivity of the two methods (p=0.0224). Ultrasound combined with elastography demonstrated higher rates of conclusive and accurate diagnoses in patients with unexplained cervical lymphadenopathy than conventional ultrasound. The quantitative program showed good correlation with the pathology of different lymph node diseases.

Dynamic Studies on Physiology and Biochemistry in American Seng Seed During Stratification - Part I. Embryo Ratio, Dry Weight Ratio and respiration Rate

Huang, Yao-Ge,Li, Xiang-Gao,Yang, Ji-Xiang,Kuang, Ya-Lan,Yan, Jie-Kun,Cui, Shu-Yu,Liu, Ren-Song,Kim, Hack-Seang The Korean Society of Ginseng 1996 Journal of Ginseng Research Vol.20 No.3

Dynamic parameters of physiology including embryo ratio (ER), embryo length to endosperm length, dry weight ratio between embryo and endosperm (DWR) and respiration rate (RR) in American send (Panax quinquefolium L.) seed were investigated. According to the changes of ER during seed stratification, the duration of embryo afterripening could be divided into three stages as \circled1 embryo slow growth stage (ESGS), ER increased from 7.31% to 20.48% (0.16% day-1): \circled2 embryo rapid growth stage (ERGS), ER increased to 80.98% (0.61% day-1) (75G5+ ERGS=morphological afterripening stage (MP,5)) and \circled3pysiological afterripening stage (PAS), ER Increased to 88.50% (0.094 day-1) only. DWR Increased slowly from 0.20% to 2.76clp (0.016% day-1) in MAS and rapidly to 8.81% (0.061% day-1) in PAS. The RR correlated significantly with ER as well (r=0.8934 > rot, 0.6610). The steep increment of both DWR and RR in PAS indicated that the PAS was not a static stage although the ER was not changed too much. All of these may provide some information for understanding the dormancy mechanisms of American sting seed.

A unique cytoplasmic localization of retinoic acid receptor-gamma and its regulations.

Han, Young-Hoon,Zhou, Hu,Kim, Jin-Hee,Yan, Ting-dong,Lee, Kee-Ho,Wu, Hua,Lin, Feng,Lu, Na,Liu, Jie,Zeng, Jin-zhang,Zhang, Xiao-kun American Society for Biochemistry and Molecular Bi 2009 The Journal of biological chemistry Vol.284 No.27

<P>Recent evidence suggests that extranuclear action of retinoid receptors is involved in mediating the pleiotropic effects of retinoids. However, whether they reside in the cytoplasm remains elusive. Here, we showed that retinoic acid receptor-gamma (RARgamma) was cytoplasmic in confluent cells, or when cells were released from serum depletion or treated with growth factors. In studying the regulation of RARgamma subcellular localization, we observed that ectopically overexpressed RARgamma was mainly cytoplasmic irrespective of serum concentration and cell density. The cytoplasmic retention of RARgamma was inhibited by ligand retinoic acid (RA). In addition, coexpression of retinoid X receptor-alpha (RXRalpha) resulted in nuclear localization of RARgamma through their heterodimerization. Mutagenesis studies revealed that a C-terminal fragment of RXRalpha potently prevents RA-induced RARgamma nuclear localization and transcriptional function. Furthermore, our results showed that the cytoplasmic retention of RARgamma was due to the presence of its unique N-terminal A/B domain, which was subject to regulation by p38 MAPK-mediated phosphorylation. Deletion or mutation of the N-terminal A/B domain largely impaired its cytoplasmic localization. Together, our data demonstrate that the subcellular localization of RARgamma is regulated by complex interactions among ligand binding, receptor phosphorylation, and receptor dimerizations.</P>

Hepatitis B Virus DNA Negativity Acts as a Favorable Prognostic Factor in Hepatocellular Carcinoma Patients

Li, Xing,Zhong, Xiang,Chen, Zhan-Hong,Xing, Yan-Fang,Wu, Dong-Hao,Chen, Jie,Ma, Xiao-Kun,Lin, Qu,Wen, Jing-Yun,Wei, Li,Wang, Tian-Tian,Ruan, Dan-Yun,Lin, Ze-Xiao,Wu, Xiang-Yuan,Dong, Min Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.22

Background: This retrospective study was aimed to investigate the efficacy of prophylactic agents in hepatocellular carcinoma (HCC) patients receiving TACE and compare the difference between lamivudine and entecavir. Materials and Methods: A consecutive series of 203 HBV-related HCC patients receiving TACE were analyzed including 91 patients given prophylactic agents. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 IU/ml higher than the nadir level, hepatitis flares due to HBV reactivation and progression free survival (PFS) were the main endpoints. Results: Some 48 (69.6%) reached virologic response. Prophylaxis significantly reduced virologic events (8.8% vs 58.0%, p=0.000) and hepatitis flares (1.1% vs 13.4%, p=0.001). Patients presenting undetectable HBV DNA levels displayed a significantly improved PFS as compared to those who never achieved undetectable HBV DNA. Prophylaxis and e-antigen positivity were the only significant variables associated with virologic events. In addition, prophylaxis was the only independent protective factor for hepatitis flares. Liver cirrhosis, more cycles of TACE, HBV DNA negativity, a lower Cancer of the Liver Italian Program score, non-metastasis and no hepatitis flares were protective factors for PFS. Prophylactic lamivudine demonstrated similar efficacy as entecavir. Conclusions: Prophylactic agents are efficacious for prevention of HBV reactivation in HCC patients receiving TACE. Achievement of undetectable HBV DNA levels displayed a significant capability in improving PFS. Moreover, persistent tumor residual lesions, positive HBV DNA and hepatitis B flares might be causes of tumor progression in these patients.

Efficacy of Prophylactic Entecavir for Hepatitis B Virus-Related Hepatocellular Carcinoma Receiving Transcatheter Arterial Chemoembolization

Li, Xing,Zhong, Xiang,Chen, Zhan-Hong,Wang, Tian-Tian,Ma, Xiao-Kun,Xing, Yan-Fang,Wu, Dong-Hao,Dong, Min,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wen, Jing-Yun,Wei, Li,Wu, Xiang-Yuan,Lin, Qu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.18

Background and Aims: Hepatitis B virus (HBV) reactivation was reported to be induced by transcatheter arterial chemoembolization (TACE) in HBV-related hepatocellular carcinonma (HCC) patients with a high incidence. The effective strategy to reduce hepatitis flares due to HBV reactivation in this specific group of patients was limited to lamivudine. This retrospective study was aimed to investigate the efficacy of prophylactic entecavir in HCC patients receiving TACE. Methods: A consecutive series of 191 HBV-related HCC patients receiving TACE were analyzed including 44 patients received prophylactic entecavir. Virologic events, defined as an increase in serum HBV DNA level to more than 1 log10 copies/ml higher than nadir the level, and hepatitis flares due to HBV reactivation were the main endpoints. Results: Patients with or without prophylactic were similar in host factors and the majorities of characteristics regarding to tumor factors, HBV status, liver function and LMR. Notably, cycles of TACE were parallel between the groups. Ten (22.7%) patients receiving prophylactic entecavir reached virologic response. The patients receiving prophylactic entecavir presented significantly reduced virologic events (6.8% vs 54.4%, p=0.000) and hepatitis flares due to HBV reactivation (0.0% vs 11.6%, p=0.039) compared with patients without prophylaxis. Kaplan-Meier analysis illustrated that the patients in the entecavir group presented significantly improved virologic events free survival (p=0.000) and hepatitis flare free survival (p=0.017). Female and Eastern Cooperative Oncology Group (ECOG) performance status 2 was the only significant predictors for virological events in patients without prophylactic antiviral. Rescue antiviral therapy did not reduce the incidence of hepatitis flares due to HBV reactivation. Conclusion: Prophylactic entecavir presented promising efficacy in HBV-related cancer patients receiving TACE. Lower performance status and female gender might be the predictors for HBV reactivation in these patients.

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

( Jia-yi Dou ),( Yu-chen Jiang ),( Zhong-he Hu ),( Kun-chen Yao ),( Ming-hui Yuan ),( Xiao-xue Bao ),( Mei-jie Zhou ),( Yue Liu ),( Zhao-xu Li ),( Li-hua Lian ),( Ji-xing Nan ),( Yan-ling Wu ) 한국응용약물학회 2022 Biomolecules & Therapeutics(구 응용약물학회지) Vol.30 No.3

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7r-NLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.

Staged Improvement in Awareness of Disease for Elderly Cancer Patients in Southern China

Li, Xing,Dong, Min,Wen, Jing-Yun,Wei, Li,Ma, Xiao-Kun,Xing, Yan-Fang,Deng, Yun,Chen, Zhan-Hong,Chen, Jie,Ruan, Dan-Yun,Lin, Ze-Xiao,Wang, Tian-Tian,Wu, Dong-Hao,Liu, Xu,Hu, Hai-Tao,Lin, Jia-Yu,Li, Zhu Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

Background: In mainland China, awareness of disease of elderly cancer patients largely relies on the patients' families. We developed a staged procedure to improve their awareness of disease. Materials and Methods: Participants were 224 elderly cancer patients from 9 leading hospitals across Southern China. A questionnaire was given to the oncologists in charge of each patient to evaluate the interaction between family and patients, patient awareness of their disease and participation in medical decision-making. After first cycles of treatment, increased information of disease was given to patients with cooperation of the family. Then patient awareness of their disease and participation in medical decision-making was documented. Results: Among the 224 cancer elderly patients, 26 (11.6%) made decisions by themselves and 125 (55.8%) delegated their rights of decision-making to their family. Subordinate family members tended to play a passive role in decision-making significantly. Patients participating more in medical decision-making tended to know more about their disease. However, in contrast to the awareness of disease, patient awareness of violation of medical recommendations was reversely associated with their participation in medical decision-making. Improvement in awareness of diagnosis, stages and prognosis was achieved in about 20% elderly cancer patients. About 5% participated more actively in medical decision-making. Conclusions: Chinese elderly cancer patient awareness of disease and participation in medical decision-making is limited and relies on their family status. The staged procedure we developed to improve patient awareness of disease proved effective.

충적과정 중 미국삼 종자의 생리 및 생화학적 지표에 관한 동태학적 연구 - I . 배아율 , 건조중량비 및 호흡강도 ( Dynamic Studies on Physiology and Biochemistry in American Seng Seed During Stratification - Part 1. Embryo Ratio , Dry Weigh Ratio and Respiration Rate - )

Yao Ge Huang,Xiang Gao Li,Ji Xiang Yang,Ya Lan Kuang,Jie Kun Yan,Shu Yu Cui,Ren Song Liu,김학성 고려인삼학회 1996 Journal of Ginseng Research Vol.20 No.3

충적과정중 미국인삼 종자의 생리 및 생화하적 지표에 관한 동태학적 연구 III

Huang, Yao-Ge,Li, Xiang-Gao,Kuang, Ya-Lan,Yan, Jie-Kun,Cui, Shu-Yu,Yu, Wen-Bo,Yang, Ji-Xiang,Liu, Ren-Song,Kim, Hack-Seang 고려인삼학회 1997 Journal of Ginseng Research Vol.21 No.1

Dynamic parameters of biochemistry including the POD (peroxidase) activity, contents of DNA and RNA, isozymes of POD and ES (esterase) in American send (Panax quinquefolium L.) seed are reported in the present paper. The dynamic changes of POD activity proved that the PAS (physiological afterripening stage) is a stage in which some substances are prepared for seed germination. The POD activity correlated with ER (embryo ratio) significantly DNA content changed little only within 0.0036∼0.013 mg/ml, which did not correlate with ER. RNA content changed from 0.1539 to 1.0313 mg/ml and correlated significantly with RE during all of the embryo afterripening. None of the POD isozyme band was obtained in ESGS (embryo slowly growth stage), but five bands in ERGS (embryo rapidly growth stage) and six bands in PAS. Four bands of ES isozymes were obtained in ESGS, but six bands in ERGS, particularly, the content of ES isozymes increased in PAS. All of these may provide some information for understanding the dormancy mechanisms of American song seed.