Research progress on the novel glutaminase inhibitor and its antitumor activity / 中国肿瘤临床

Tumor cells use several metabolic pathways to support bioenergetic and biosynthetic demands of proliferation. In addition to glucose, glutamine is an important source of precursor substances and energy for cancer cell growth. Glutaminase (GSL) activity is associated with Ras, c-Myc, and other oncogenes, as well as Rho GTP enzyme. Many preclinical studies have confirmed that glutamin-ase inhibitors not only exhibit anti-tumor activity, but can also remarkably enhance the sensitivity of resistant cancer cells to targeted drugs. At present, the novel GSL inhibitor CB-839 has entered phase I clinical trials and is expected to become a new drug for cancer treatment. This paper reviews the research progress on this novel glutaminase inhibitor and its antitumor activity.

Occurrence, diagnosis and treatment of de novo gastrointestinal malignancies after organ transplantation / 中华胃肠外科杂志

With the continuous use of immunosuppressive agents routinely, the long-term survival rate of organ transplant recipients has been incessantly improved. However, the risk of de novo malignancies is also increasing, which has become the second cause of death after organ transplantation. De novo gastrointestinal malignancies are common after liver or kidney transplantation, mostly with advanced stage when diagnosed and poor prognosis. There is a significant trend in the development of de novo malignancies in transplant recipients, which is probably related to factors, including direct or indirect effects of immunosuppressive agents, precancerosis and survival time of transplanted grafts and recipients. Long-term postoperative use of immunosuppressive agents can keep the recipient's immune system in the inhibitory state, which provides the conditions for tumor cells to escape immune surveillance and to proliferate. In addition, some immunosuppressive agents [such as calcium phosphatase inhibitor (CNI)] are carcinogenic and the use of anti-tumor combined with immunosuppressive drugs can be considered [such as mycophenolate mofetil (MMF), mammalian rapamycin target protein (mTOR) inhibitors]. De novo gastrointestinal malignancy has no specific clinical manifestations. It is suggested that the recipients need to strictly comply with the follow-up time, avoid exposure to carcinogens, treat the precancerosis positively and have a medical examination carefully. At present, there are no literatures and guidelines about a standard treatment for de novo gastrointestinal malignancies after transplantation. The primary treatment of de novo malignancies should be adjusting the dosage of immunosuppressive agents to ensure that their minimum dose can effectively maintain the graft function. For patients with stable postoperative organ function and without acute or chronic rejection, the dosage of immunosuppressive agents can be reduced gradually to avoid an excessive immunosuppressive effect. Thereafter, the incidence of de novo malignancies is reduced to a minimum. Minimization of using CNI as soon as possible after transplantation has been widely recognized, and CNI plus mTOR inhibitor or MMF has become a relatively reasonable method.

Expression relevance of GATA-1 and GATA-2 in bone marrow CD71 +cells of high-altitude polycythemia rat model / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the expression relevance of transcription factors GATA-1 and GATA-2 in the bone marrow CD71 +cells of a high-altitude polycythemia (HAPC) rat model.METHODS:Male SD rats (n=48) were randomly divided into normal control group and HAPC model group .HAPC model was established at an altitude of 4 300 m in the natural environment and verified by the morphology and quantity of the bone marrow cells and hematologic parameters detection .A relative change in the trend of bone marrow CD 71 +cell numbers was detected by flow cytometry analysis .The expression of GATA-1 and GATA-2 at mRNA and protein levels in the CD 71 +cells was examined by RT-qPCR and West-ern blot .CD71 +cells were cultured under hypoxic condition and transfected with the optimal interference sequence of GA -TA-1shRNA1 for 96 h.The expression of GATA-1 and GATA-2 at mRNA and protein levels was detected by RT-qPCR and Western blot .RESULTS:The establishment of the animal model with HAPC was successful as the bone marrow smears and the hematologic parameters showed compared with the control .The quantity of the bone marrow CD 71 +cells of HAPC rats were significantly increased and the expression of GATA-1 at mRNA and protein levels in the CD 71 +cells were higher than those of the control .The expression of GATA-2 at mRNA and protein levels was similar to that of the control .The correla-tion analysis showed that the expression of GATA-1 was negatively correlated with that of GATA-2 in the control, while no obvious correlation between them was observed in the HAPC rats .The expression of GATA-1 at mRNA and protein levels in HAPC group was lower than that in control group after interfered by GATA-1 shRNA1 for 96 h, but no obvious diversity of GATA-2 expression between the 2 groups was observed .CONCLUSION:GATA-1 and GATA-2 are abnormally expressed and their negative correlation is destroyed in HAPC , which may be one of the pathogenesis of HAPC .

Meta-analysis of efficacies of dasatinib and imatinib for patients with chronic myeloid leukemia-chronic phase / 白血病·淋巴瘤

Objective To compare the efficiencies of imatinib and dasatinib in patients with chronic myeloid leukemia-chronic phase (CML-CP).Methods The databases were retrieved,including Cochrane Library,OVID,Embase,PubMed,China National Knowledge Infrastructure (CNKI),WanFang database and VIP database,besides,references of articles were further to search.The quality of randomized controlled trials (RCTs) was assessed by the Cochrane collaboration' s risk tool.Meta-analysis was performed by RevMan 5.1 software.Results A total of 5 articles involved 2 031 patients with CML-CP were included.Meta-analysis showed that the rate of complete cytogenetic response (CCyR) at the 12th month in dasatinib group was higher than that in imatinib group [83.6 ％ (478/572) vs 70.6 ％ (406/575),OR =2.11,95 ％ CI 1.59-2.80,P＜ 0.05],and the rate of major molecular response (MMR) at the 12th month in dasatinib group was higher than that in imatinib group [49.3 ％ (296/600) vs 30.6 ％ (185/605),OR =2.22,95 ％ CI 1.75-2.82,P ＜ 0.05].Conclusion Dasatinib can improve CCyR and MMR rate at the 12th month in CML-CP patients.

Clinical application of Voriconazole treatment in invasive fungal infection for malignant hematology patients: a meta analysis / 实用医学杂志

Objective To estimate the efficacy and safety of Voriconazole as antifungal prophylaxis of invasive fungal infection ( IFI) for malignant hematology patients. Methods The randomized controlled trials of Voriconazole treatment in invasive fungal infection for malignant hematology patients (ended in September 2014) were searched from Cochrane library, Medline, Embase, Pubmed, CBM, CNKI, Blood database. The meta analysis were performed by RevMan5.0. Results Ten literatures reported in 1 773 cases, in which there was significantly difference in effective rate between Voriconazole and other antifungal agents such as Amphotericin-B, Itraconazole, Micafungin and Fluconazole(P < 0.000 01); Four literatures indicated that there was significantly difference in adverse event rate between Voriconazole and amphotericin-B (P < 0.00 001); no significantly difference in adverse event rate between Voriconazole and amphotericin-B(P = 0.57); no significantly difference in adverse event rate between Voriconazole and Micafungin (P = 0.69); no significantly difference in adverse event rate between Voriconazole and Fluconazole (P = 0.70); Subgroup analysis indicated that adverse event rate between Voriconazole and Itraconazole is P=0.001, P = 0.17 respectively. Conclusion Voriconazole showed relative high efficient and low toxicity characteristics in treatment of malignant hematology accompanied by invasive fungal infection. But with its widely clinical application, the clinical value of Voriconazole needs to be further tested.

Analysis of clinical characteristics and prognostic factors of 253 lymphoma cases in Qinghai / 白血病·淋巴瘤

Objective To analyze the clinical features and prognostic factors of lymphoma.Methods The clinical data,pathologic data and survival state of 253 patients with lymphoma in Qinghai were retrospectively studied.The survival differences of patients with different clinical characteristics and laboratory tests were analyzed using Kaplan-Meier method.The prognostic factors of lymphoma were analyzed by Cox proportional hazards regression model.Results Among all of 253 cases of lymphoma,males were in the majority (male∶female =1.56∶1).The median age of patients was 48 years old.There were two peaks of about 40 years old and 60 years old in age of onset.The nodal lymphoma (56.13 ％) was more commonly than the extranodal lymphoma (43.87 ％).The more common extranodal lymphomas were found in the nasopharynx and gastrointestinal tract.Among all cases,40 cases (15.81％) were confirmed to be Hodgkin lymphoma (HL),of which,the commonest subtype was nodular sclerosis (72.5 ％).While 213 of 253 cases (84.19 ％) belonged to non-Hodgkin lymphoma (NHL),of which,B-cell lymphoma was 148 cases (69.48 ％).Overall,three subtypes including diffuse large B-cell lymphoma (39.91％),follicular lymphoma (12.21％) and peripheral T-cell lymphoma (9.39 ％) were the commonest subtypes among all cases.Univariate analysis showed that the clinical stage,B symptoms,Hb concentration,serum LDH level,international prognostic score (IPI) and treatment programs were related to the prognosis of NHL (P ＜ 0.05).However,the Cox regression multivariate analysis showed that only the clinical stage,IPI and treatment programs,not B symptoms,Hb concentration and serum LDH level,were closely related to the prognosis of NHL (P ＜ 0.05).Conclusions In Qinghai area,there are two peaks of about 40 and 60 years old in the age of onset of lymphoma.The nodal lymphoma is more than extranodal lymphoma.B-cell lymphoma is more common.IPI could be as an independent prognostic factor and might be used to estimate the prognosis of NHL.

Typing and staging and treatment of intrahepatic cholangiocarcinoma / 中华消化外科杂志

Objective To investigate the typing, staging and therapeutic outcome of intrahepatic cholan-giocarcinoma (ICC). Methods The clinical data of 60 ICC patients who were admitted to the Renji Hospital of Shanghai Jiaotong University from January 2000 to December 2008 were retrospectively analyzed. ICC was classi-fied according to the type and TNM staging proposed by the Liver Cancer Study Group of Japan (LCSGJ). The relationships between typing, staging, surgical procedures and therapeutic outcome were investigated, as well as the relationship between the LCSGJ staging system and UICC staging system. Results The 1-, 3-, and 5-year survivals of the 60 ICC patients were 44% (23/52), 19% (10/52) and 10% (5/52), respectively. The median survival time for patients with radical resection (n =30) , liver transplantation (n = 10), palliative surgery (n = 11) and exploratory laparotomy (n=9) were 13, 3, 3 and 1 months, respectively. The radical resection rates for mass-forming type, periductal-infiltrating type, intraductal growth type and mixed type were 23/31, 9/15, 5/6 and 3/8, respectively. There were significant relationships between tumor type, degree of differentiation and prog-nosis (χ2 = 8. 308, 10. 009, P < 0. 05), and between tumor type and lymph node metastasis (χ2 = 13. 261, 5.702, P <0.05). There was no significant difference in survival time between patients with different pathological types, but the prognosis of patients with mucinous adenocarcinoma was better than that in the other types, with a median survival time of 20months. The median survival time of patients in LCSGJ stage Ⅳ was 3. 0 months, which was significantly longer than that in UICC stage Ⅳ (χ2 =3. 877, P <0. 05). Tumor staging was intimately related to the macroscopic type χ2 =8.288, P <0. 05). Conclusions The prognosis of ICC is poor. The typing and staging of LCSGJ is concise and practical, which is helpful in guiding treatment and evaluating progno-sis. Surgical treatment should be applied to mucinous ICC, and liver transplantation is not recommended for the treatment of ICC.