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Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation

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World Journal of Gastrointestinal Oncology 2014年第3期6卷 74-82页

作者： Caitlin A Schonewolf Monal Mehta Devora Schiff Hao Wu Bruce G Haffty Vassiliki Karantza Salma K Jabbour Departments of Radiation Oncology Robert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyThe Cancer Institute of New JerseyNew BrunswickNJ 08903United States Departments of medicine Robert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyThe Cancer Institute of New JerseyNew BrunswickNJ 08903United States

AIM:To investigate whether the inhibition of autophagy by chloroquine(CQ)sensitizes rectal tumors to radiation therapy(RT)or concurrent chemoradiation(chemoRT).METHODS:In vitro,HCT-116 and HT-29 colorectal cancer(CRC)cell lines were treated as following:(1)PBS;(2)CQ;(3)5-fluorouracil(5-FU);(4)RT;(5)CQ and RT;(6)5-FU and RT;(7)CQ and 5-FU;and(8)5-FU and CQ and *** group was then exposed to various doses of radiation(0-8 Gy)depending on the *** viability and proliferative capacity were measured by3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)and clonogenic *** survivalcurves were constructed and compared across treatment *** status was determined by assessing the LC3-Ⅱto LC3-Ⅰratio on western blot analysis,autophagosome formation on electron microscopy and identification of a perinuclear punctate pattern with GFPlabeled LC3 on fluorescence *** cycle arrest and cell death were evaluated by FACS and AnnexinⅤ*** experiments were performed in triplicate and statistical analysis was performed by the student’s t test to compare means between treatment ***:RT(2-8 Gy)induced autophagy in HCT-116and HT-29 CRC cell lines at 4 and 6 h post-radiation,respectively,as measured by increasing LC3-Ⅱto LC3-Ⅰratio on western ***,electron microscopy demonstrated autophagy induction in HT-29 cells24 h following irradiation at a dose of 8 *** treatment with 5-FU(25μmol/L)induced autophagy and the combination of 5-FU and RT demonstrated synergism in autophagy ***(10μmol/L)alone and in combination with RT effectively inhibited autophagy and sensitized both HCT-116 and HT-29 cells to treatment with radiation(8 Gy;P<0.001 and 0.00001,respectively).Significant decrease in clonogenic survival was seen only in the HT-29 cell line,when CQ was combined with RT at doses of 2 and 8 Gy(P<0.5 and P=0.05,respectively).There were no differences in cell cycle progression or Annexin V st

关键词： Autophagy Chloroquine Radiosensitization Colorectal cancer

Genomic instability and cancer:an introduction

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分子细胞生物学报:英文版 2011年第1期3卷 1-3页

作者： Zhiyuan Shen The Cancer Institute of New jersey and Department of Radiation OncologyRobert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New Jersey195 Little Albany StreetNew BrunswickNJ 08903USA

Genomic instability refers to an increased tendency of alterations in the genome during the life cycle of *** is a major driving force for *** a cell division,genomic instability is minimized by four major mechanisms:high-fidelity DNA replication in S-phase,precise chromosome segregation in mitosis,error free repair of sporadic DNA damage,and a coordinated cell cycle *** introduction summarizes the major molecular processes that contribute to these mechanisms in the context of prevention of genomic instability and tumorigenesis.

关键词： alterations damage precise

Immunosuppressive properties of cloned bone marrow mesenchymal stem cells

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Cell Research 2007年第3期17卷 240-248页

作者： robert C Zhao Department of Molecular Genetics Microbiology and Immunology robert wood johnson medical school-university of medicine and dentistry of New jersey 661 Hoes Lane Piscataway NJ 08854 USA

Mesenchymal stem cells(MSCs),derived from adult tissues,are multipotent progenitor cells,which hold greatpromise for regenerative *** studies have shown that MSCs are immunosuppressive in vivo and in vitro inboth animals and ***,the mechanisms that govern these immune modulatory functions of MSCs remainlargely *** studies with bulk populations of MSCs indicated that soluble factors such as PGE2 and TGFβ areimportant,while others support a role for cell-cell *** this study,we intended to clarify these issues by examin-ing immunosuppressive effects of cloned *** derived MSC clones from mouse bone marrow and showed thatthe majority of these clones were able to differentiate into adipocytes and osteoblast-like ***,cells fromthese clones exhibited strong inhibitory effects on TCR activation-induced T cell proliferation in vitro,and injection ofa small number of these cells promoted the survival of allogeneic skin grafts in *** medium from MSCcultures showed some inhibitory effect on anti-CD3 induced lymphocyte proliferation independent of PGE2 and TGFβ.In comparison,direct co-culture of MSCs with stimulated lymphocytes resulted in much stronger ***,the suppression was bi-directional,as MSC proliferation was also reduced in the presence of *** together,our findings with cloned MSCs demonstrate that these cells exert their immunosuppressiveeffects through both soluble factor(s)and cell-cell contact,and that lymphocytes and MSCs are mutually inhibitory ontheir respective proliferation.

关键词： suppression T ceils cytokines stem cells transplantation

Contrasting treatment and outcomes of septic shock： presentation on hospital floors versus emergency department

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Chinese medical Journal 2010年第24期123卷 3550-3553页

作者： WANG Zhen Chrism Schorr Krystal Hunter R. Phillip Dellinger Department of Emergency medicine Beijing Shijitan Hospital Beijing 100038 China Department of Critical Care medicine Robert Wood Johnson School of Medicine University of Medicine and Dentistry of New Jersey Cooper University Hospital Camden NJ USA Biostatistics Group Robert Wood Johnson School of Medicine University of Medicine and Dentistry of New Jersey Cooper University Hospital Camden NJ USA

Background Patients with septic shock have a high mortality. This study used the Surviving Sepsis Campaign （SSC）database to compare characteristics, treatments and outcomes of septic shock patients diagnosed in the emergency department （ED） to patients developing septic shock on hospital floors （HF）.Methods The studied population included patients admitted to the intensive care unit （ICU） of an urban tertiary care medical center over an 18-month period. Acute physiology and chronic health evaluation （APACHE Ⅱ） scores, need for mechanical ventilation （MV）, performance on four of the SSC resuscitation bundle indicators, ICU length of stay （LOS）,hospital LOS and in-hospital mortality were *** Sixty-six ED and 27 HF septic shock patients were included in this study. Urinary tract infections （UTI） and pneumonia were the two most common sites of infection in the ED patients. The sources of infection for HF septic shock patients were fairly well distributed across etiologies. The time to achieve superior vena cava oxygen saturation （ScvO2）＞ 70% in HF patients （（10.8±9.1） hours） was longer when compared to the ED patients （（6.6±-6.1） hours）（P ＜0.05）.Hospital mortality for the ED and HF patients were 25.8% and 59.3%, respectively （P ＜0.05）. Use of MV during the first 24 hours of shock was 44% in the ED patients and 70% in the HF patients （P ＜0.05） and was linked to *** When compared to HF patients, ED septic shock patients have lower in-hospital mortality, there was less use of MV during the first 24 hours following onset of septic shock and the HF patients required a longer time to achieve target ScvO2. The need for mechanical ventilation is independently associated with increased mortality.

关键词： septic shock mechanical ventilation mortality

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Unusual colonoscopy finding:Taenia saginata proglottid

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World Journal of Gastroenterology 2007年第41期13卷 5540-5541页

作者： Nayan M Patel Eric L Tatar university of medicine and dentistry of NJ Robert Wood Johnson Medical SchoolDepartment of Internal MedicineNew BrunswickNJ 08901United States

Infection with tapeworms is a major problem in many parts of the world. Patients may be asymptomatic or have a significant morbidity depending on the species. Infection with Taenia species is sometimes found by expulsion of eggs or proglottids in stool. Species specific diagnosis of Taenia is difficult,but possible. We present a case of Taenia saginata incidentally discovered,and risk factors for transmission,diagnosis,symptoms,and treatment.

关键词： Taenia saginata colonoscopy Tapeworm

Effects of metoclopramide on gastric motility measured by short-term bio-impedance

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World Journal of Gastroenterology 2009年第38期15卷 4763-4769页

作者： María-Raquel Huerta-Franco Miguel Vargas-Luna Kathleen M Capaccione Etna Yaez-Roldán Ulises Hernández-Ledezma Ismael Morales-Mata Teodoro Córdova-Fraga Department of Applied Science and Labor Research DCS-Campus LeónUniversity of Guanajuato Department of Physical Engineering DCI-Campus LeónUniversity of Guanajuato robert wood johnson medical school The University of Medicine and Dentistry of New Jersey

AIM:To analyze the accuracy of short-term bio-impedance as a means of measuring gastric ***: We evaluated differences in the short-term electrical bio-impedance signal from the gastric region in the following conditions: (1) fasting state, (2) after the administration of metoclopramide (a drug that induces an increase in gastric motility) and (3) after food ingestion in 23 healthy volunteers. We record-ed the real component of the electrical impedance signal from the gastric region for 1000 s. We performed a Fast Fourier Transform (FFT) on this data and then compared the signal among the fasting, medicated, and postprandial conditions using the median of the area under the curve, the relative area under the curve and the main peak ***: The median of the area under the curve of the frequency range in the region between 2-8 cycles per minute (cpm) decreased from 4.7 cpm in the fasting condition to 4.0 cpm in the medicated state (t=3.32, P=0.004). This concurred with the decrease seen in the relative area under the FFT curve in the region from 4 to 8 cpm from 38.3% to 26.6% (t=2.81, P=0.012) and the increase in area in the region from 2 to 4 cpm from 22.4% to 27.7%, respectively (t=-2.5, P=0.022). Finally the main peak position also decreased in the region from 2 to 8 cpm. Main peak activity in the fasting state was 4.72 cpm and declined to 3.45 cpm in the medicated state (t=2.47, P=0.025). There was a decrease from the fasting state to the postprandial state at 3.02 cpm (t=4.0, P=0.0013). CONCLUSION: Short-term electrical bio-impedance can assess gastric motility changes in individuals experiencing gastric stress by analyzing the area medians and relative areas under the FFT curve.

关键词： Bio-impedance Fast Fourier Transform Gastric motility Metoclopramide Postprandial

Massive gastrointestinal bleeding: An unusual case of asymptomatic extrarenal, visceral, fibromuscular dysplasia

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World Journal of Gastroenterology 2007年第43期13卷 5771-5774页

作者： Paula Andrea Rodriguez Urrego Mark Flanagan Wilson S Tsai Craig Rezac Nicola Barnard Department of Pathology Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey United States Department of Surgery RWJMS-UMDNJ United States Department of Heart Lung and Esophageal Surgery University of Pittsburgh Medical Center United States

Extrarenal fibromuscular dysplasia causing gastro- intestinal bleeding without other manifestations and especially sparing renal vasculature is uncommon. The diagnosis of this entity is usually made by radiographic appearance and the treatment is controversial. To our knowledge only seven cases of visceral fibromuscular dysplasia as a primary manifestation of the disease have been described, symptoms range from abdominal pain to gangrene. This is the first case of visceral fibromuscular dysplasia presenting with otherwise asymptomatic gastrointestinal bleeding, without bowel necrosis or ischemic changes. We provide a review of the literature.

关键词： Fibromuscular dysplasia Extrarenal Visceral Gastrointestinal bleeding Intimal fibroplasia

Dying T lymphocytes call for the death of tumor cells

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Cell Research 2006年第8期16卷 679-680页

作者： ArthurIroberts Envei Sun Department of Molecular Genetics Microbiology and ImmunologyUniversity of Medicine and Dentistry of New JerseyRobert Wood Johnson Medical SchoolPiscatawayNJ 08854USA Institute of Transplantation Immunology Organ Transplantation DepartmentZhujiang HospitalSouthern Medical UniversityGuangzhou510282China

Immunotherapy that specifically targets tumor cells is the preferred approach to induce tumor *** the pastdecade,significant progress has been made in devising various methods to direct the immune system to respond to *** major hurdle for successful immunotherapy is to overcome immune tolerance in the tumor *** clinical trials with dendritic cell-based vaccination[1,2]and CTLA4 blocking antibodies[3]have shown greatpromise,though complete cancer regression is not always achieved[4].Currently,alternative strategies potentially leadingto cancer eradication or regression in animal or clinical models are being enthusiastically *** this issue of CellResearch,Wang et *** a novel way to induce tumor immunity by the use of irradiated autologous T cells[5].

关键词： Dying T lymphocytes call for the death of tumor cells

A two-hit model of autoimmunity： lymphopenia and unresponsiveness to TGF-β signaling

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Cellular & Molecular Immunology 2012年第5期9卷 369-370页

作者： Andrew L'Huillier Guangwen Ren Yufang Shi Jimin Zhang Dr YF Shi Child Health Institute of New jersey Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey New Brunswick NJ Institute of Health Sciences Shanghai Institutes for Biological Sciences Chinese Academy of Sciences and Shanghai Jiaotong University School of Medicine Shanghai China

he immune system can robustly respond to pathogens, while it is capableor malntaining Itolerance to self and innocu- ous antigens, so that the body is not jeopar- dized by autoimmune reactivity. Under certain circumstances, nonetheless, control of homeostasis of the immune system is sus- pended, and the body subsequently fails to recognize its own constituent parts as self, which contributes to homeostatic peripheral expansion and autoimmune diseases. Although autoimmunity is extensively studied, the ori- gins of this increasing public health challenge remain not well understood.

关键词：自身免疫转化生长因子β 淋巴细胞减少胰岛素免疫系统内环境稳定基因公共卫生