1.Reduction of β-catenin expression in hepatocellular carcinoma inhibited the enhanced metastatic potential of hypoxia
Liang LIU ; Xianjun YU ; Chuntao WU ; Jiang LONG ; Chen LIU ; Jin XU ; Quanxing NI ; Zhaoyou TANG
Chinese Journal of Hepatobiliary Surgery 2012;18(1):58-62
ObjectiveTo explore the role of β-catenin in the proinvasive consequences of hypoxia in hepatocellular carcinoma (HCC).MethodsWe established in vitro and in vivo hypoxic models using the highly metastatic MHCC97 and the stable red fluorescent protein-expressing MHCC97-R cells.The role of β-catenin in hypoxia-mediated aggressiveness was investigated by β-catenin knockdown.ResultsHypoxia caused a pronounced arrest of proliferation in MHCC97 cells,suppressed tumor growth in MHCC97-R xenografts,but promoted in vitro invasiveness and in vivo metastasis.β-Catenin-silencing by short hairpin significantly inhibited the enhanced invasiveness of MHCC97 cells due to hypoxia,reduced the increase in distant metastasis by hepatic arterial ligation,but failed to further restrain cell proliferation.Conclusionβ-Catenin in HCC cells plays an essential role in the hypoxia-induced metastatic potential.A reduction of βcatenin expression inhibited the proinvasive consequences of hypoxia in HCC.
2.Gemcitabine or gemcitabine plus cisplatin for in 42 patients with locally advanced or metastatic pancreatic cancer.
Xingyuan WANG ; Quanxing NI ; Maolin JIN ; Zhaoshen LI ; Yuxin WU ; Yupei ZHAO ; Fengyi FENG
Chinese Journal of Oncology 2002;24(4):404-407
OBJECTIVEA multi-center randomized phase III clinical trial was designed to evaluate the efficacy, clinical benefit response (CBR) and toxicity profile of germcitabine (GEM) or GEM plus cisplatin (CDDP) for locally advanced (LAPC) or metastatic pancreatic cancer (MPC).
METHODSFrom July 2000 to May 2001, 42 untreated patients with LAPC or MPC were collected and randomized into two groups: Arm A-GEM 20 patients and Arm B-GEM + CDDP 22 patients. Eligibility criteria were: cytologically and pathologically proven pancreatic carcinoma, Karnosky performance status (KPS) 60 - 80, age 18 - 75 yrs, adequate hematological, renal and liver function, measurable disease, and controllable pain. For Arm A patients, weekly dose of GEM 1 000 mg/m(2)/w for 7 times followed by a week rest. Then weekly GEM at the same dose for 3 times every 4 weeks. Arm B patients were given weekly dose of GEM 1 000 mg/m(2)/w for 3 times every 4 weeks combined with CDDP 60 mg/m(2) on D15 for 3 cycles.
RESULTSThirty-four patients were available for objective response (Arm A 16 and Arm B 18) and 36 (Arm A 16 and Arm B 20) for CBR evaluation. In Arm A and Arm B, PR 1 (6.3%) and 2 (11%), MR 4 (25%) and 3 (16.7%), SD 7 (43.8%) and 8 (44.4%), PD 4 (25%) and 5 (27.8%), PR + MR 31.3% and 27.8%, PR + MR + SD 75% and 72.2% were observed. Positive CBR was 14/16 (87.5%) in Arm A and 14/20 (70.0%) in Arm B. The negative results was 2/16 (12.5%) in Arm A and 6/20 (30.0%) in Arm B. The median time of disease progression was not yet available at present. The 3-month survival rate of both Arm A and B was 100%, the 6-month survival rates of Arm A and B were 81.3% and 61.6% and the 12-month survival rates of Arm A and B was 31.3% and 11.1%, with median survivals of 273 and 217 days. The incidence of hematological and non-hematological toxicity of Arm A was lower than that of Arm B without statistical significance. The toxicity ranging from being mild to moderate was manageable.
CONCLUSIONGEM or GEM plus CDDP is able to lead to a moderate objective response rate, also significantly improve the quality of life in patients with locally advanced or metastatic pancreatic cancer patients, prolonging the survival time with tolerable toxicity.
Adult ; Aged ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; CA-19-9 Antigen ; analysis ; Cisplatin ; adverse effects ; therapeutic use ; Deoxycytidine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Pancreatic Neoplasms ; drug therapy ; mortality ; Survival Rate ; Treatment Outcome
3.Research progress of histone lactylation in immunomodulation after traumatic brain injury
Quanxing WU ; Axiang ZHOU ; Zaiyun LONG ; Yongtang WANG ; Ying YU ; Ce YANG
Chinese Journal of Trauma 2023;39(7):659-664
Traumatic brain injury (TBI) is a major reason for temporary or permanent dyskinesia and cognitive impairment of the organism. Generally, TBI induces subsequent neuroinflammation to assist cell debris removal and tissue repair and regeneration after injury. However, overactivation or long-term activation of immune cells will exacerbate nerve damage or death, cause cognitive dysfunction, and ultimately lead to neurodegenerative diseases. Therefore, secondary damage caused by persistent inflammation is a key component of TBI pathological process. As the main metabolite of anaerobic glycolysis, lactate is increased after TBI and participates in brain inflammation as an important immune regulatory molecule rather than a metabolic waste. Importantly, histone lysine lactylation as a novel type of histone post-translational modifications (HPTM) derived from lactate allows lactate to participate in the regulation of complex immunopathophysiological processes of the central nervous system after TBI. Further study on the process of histone lactylation and its immune regulation mechanism during TBI may provide new insights for early intervention and improvement of TBI prognosis. Thus, the authors reviewed the role of histone lactylation in the immune regulation of TBI, so as to further elucidate the mechanism of TBI and the explore new warning and prevention measures from the perspective of HPTM.