Endoplasmic reticulum (ER), a multifunctional organelle in eukaryotic cells, is responsible for protein synthesis and intracellular signal transduction, which dominates cell function, survival, and apoptosis. Disequilibrium of ER homeostasis may induce ER stress, which closely intertwines with tumor occurrence and progress. A few clinical-used drugs (such as anthraquinones and oxaliplatin) can mediate the immunogenic cell death of tumor cells through excessive ER stress, and sequentially stimulate anti-tumor immune responses as well as long-term immune memory. However, these drugs often exhibit poor targeting ability and extremely low ER accumulation in tumor cells, limiting their clinical efficacy. Therefore, the researches of ER-targeted delivery of these drugs will significantly benefit the efficient and precise anti-tumor immunotherapy. In this review, we introduce the relationship between ER and tumor immunity, and summarize the ER targeting strategies for anti-tumor immunotherapy in recent years. Furthermore, we discuss the problems of existing ER targeting strategies and look into its broad prospects of application.

Objective To detect the sperm apoptosis rate and level of reactive oxygen species (ROS) in seminal plasma and explore their correlation among infertile males. Methods Ninety-two inferitile males were divided into varicocele (VC) group (n=32), leukocytospermia group(n=30) and the other cause group (n=30), and another 24 in vitro fertilization sperm samples were sereved as controls. The routine sperm parameters including seminal pH, sperm viability and sperm density were examined by computer assisted sperm analysis, the sperm apoptosis rate was asseseed using Annexin V/PI staining, and the ROS level in seminal plasma was detected by TBA method. The differences in seminal parameters between three infertile groups and control group were compared, and the correlation of sperm apoptosis rate with level of ROS in seminal plasma was explored in each group. Results The sperm viability of three infertile groups was significantly lower than that of control group (P<0.01). The sperm apoptosis rates and levels of ROS in seminal plasma in VC group and leukocytospermia group were significantly higher than those in control group (P < 0.05 or P < 0.01). The sperm apoptosis rate was positively correlated with the level of ROS in seminal plasma in leukocytospermia group(r=0. 573, P < 0.05). Conclusion The increased sperm apoptosis rate and level of seminal plasma ROS may be related to the infertility of patients with VC and leukocytospermia. The increased level of seminal plasma ROS may be one of the causes of increased sperm apoptosis rate in patients with leukocytospermia.

Objective:To investigate the expression of serum human phosphatidylethanolamine-binding protein 4 (hPEBP4) in patients with multiple myeloma (MM) and its clinical significance.Methods:A total of 59 symptomatic MM patients admitted to West Branch of Beijing Chaoyang Hospital from September 2016 to September 2018 were selected as the research objects. According to the CRAB symptoms [elevated serum calcium (C), kidney injury (R), anemia (A), bone lesions (B)], all patients were divided into 2 groups, including the active group of 44 patients with CRAB symptoms, and the response group of 15 patients who achieved at least partial remission after chemotherapy and symptom relief of CRAB. According to the degree of bone lesions (BL), 30 patients with severe bone-related events were grouped as the severe bone lesions (SBL) group, and 14 patients were grouped as the non-severe bone lesions (NSBL) group. According to the revised international prognostic staging system (R-ISS), patients in the active group were divided into three subgroups: stage Ⅰ, stage Ⅱ, and stage Ⅲ, including 26, 11 and 7 patients, respectively. A total of 15 healthy examination people whose gender and age matched those of the patients were treated as the healthy control group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of hPEBP4, tumor necrosis factor ligand superfamily member 14 (LIGHT/TNFSF14) and activin A of patients in different groups. Pearson was used to analyze the relationship of the expressions of multiple factors in the active group. The optimal cut-off value of multiple factors diagnosing MM was determined by using receiver operating characteristic (ROC) curve, and according to the cut-off value, the differences in overall survival (OS) of patients with different stratification were compared.Results:In the active group, the respond group, the healthy control group, the level of hPEBP4 was (1.48±0.64) μg/L, (1.49±0.75) μg/L, (0.31±0.10) μg/L, respectively; the level of LIGHT/TNFSF14 was (169±112) ng/L, (256±132) ng/L, (44±27) ng/L,respectively; the level of activin A was (383±266) ng/L, (223±79) ng/L, (234±85) ng/L, respectively; and the differences were statistically significant (all P<0.05). In the active group, the level of hPEBP4 was (1.06±0.60) μg/L, (1.15±0.50) μg/L, (1.73±0.68) μg/L, respectively in patients with stage R-ISSⅠ, R-ISSⅡ and R-ISS Ⅲ, and the difference was statistically significant ( F=3.287, P=0.032). The level of activin A was (219±55) ng/L, (247±117) ng/L, (450±215) ng/L, respectively among patients in stage R-ISSⅠ, R-ISSⅡ, R-ISS Ⅲ, and the level of activin A in stage R-ISS Ⅲ was higher than that in stage R-ISSⅠand R-ISSⅡ (all P < 0.05). The levels of LIGHT/TNFSF14 and activin A of SBL patients were higher than those of NSBL patients [(174±101) ng/L vs. (98±53) ng/L; (467±238) ng/L vs. (189±71) ng/L, all P < 0.05]. The level of hPEBP4 was positively correlated with the levels of M protein ( r=0.694, P < 0.01) and activin A ( r=0.252, P < 0.01) of IgG patients in the active group. ROC curve analysis showed that the optimal cut-off value of hPEBP4, LIGHT/TNFSF14, activin A diagnosing MM was 1.04 μg/L, 97.0 μg/L, 156.2 ng/L. The median overall survival (OS) time of patients with hPEBP4 >1.04 μg/L and hPEBP4 ≤ 1.04 μg/L was 57 months (95% CI 22-92 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05); while the median OS time of patients with activin A ≥ 156.2 ng/L and activin A < 156.2 ng/L was 61 months (95% CI 24-98 months) and not reached, respectively, and the difference was statistically significant ( P < 0.05). Conclusions:High expression level of hPEBP4 is related with the progression of MM. It is positively related with the level of M protein and negatively with the OS of MM patients. It is suggested that hPEBP4 may be used as an important marker to judge disease progression and tumor burden in MM. LIGHT/TNFSF14 and activin A cooperate with hPEBP4 to participate in the pathological processes of tumor microenvironment of MM.

AIM:To explore the protective effects of exosome secreted by human umbilical mesenchymal stem cells on cardiac fibrosis in diabetic mouse model.METHODS:Male C57BL/6 mice at 6～8 weeks of age were divided in-to 3 groups randomly:control group ,diabetes mellitus(DM)group and DM+exosome group.To develop mouse DM mo-del,the mice were fed with high-fat diet for 5 weeks,followed by intraperitoneal injection of 45 mg/kg streptozocin once a week for 5 weeks.It was considered as a successful DM model that the blood glucose of the mice was ≥16.7 mmol/L.The mice in DM+exosome group were injected with exosome via tail vein.The mice in other 2 groups were injected with saline at the same volume.The heart function was evaluated by color Doppler echocardiography for small animals.The blood sam-ples were collected from abdominal aortas.The blood glucose and non-esterified fatty acids were measured by biochemical colorimetric assay.HE staining was performed to observe the structural changes of myocardial fibers ,and Masson staining was used to observe the cardiac fibrosis.RESULTS:The results of echocardiography showed that left ventricular end-dias-tolic dimension(LVIDd)and left ventricular end-systolic dimension(LVIDs)of diabetic mice were larger than those incontrol mice(P<0.05 and P<0.01,respectively).The ejection fraction(EF)and fractional shortening(FS)decreased in the diabetic mice(P<0.01).Exosome treatment significant decreased the LVIDs(P<0.01),but increased the EF and FS(P<0.01).The blood glucose and non-esterified fatty acids were significantly increased in the diabetic mice.The injection of the stem cell exosome significantly decreased the blood glucose and non -esterified fatty acids(P<0.01).HE staining observation showed that cardiomyocyte hypertrophy and fragmentation of cardiomyocyte in DM group were more se -rious than those in control group.Masson staining showed that the area of fibrosis in DM group was larger than that in con-trol group(P<0.01),but that in DM+exosome group was reduced(P<0.01).CONCLUSION:Exosome secreted by human umbilical mesenchymal stem cells protects the DM model mice from cardiac fibrosis.

OBJECTIVE: To investigate the clinical features,therapy and prognosis of patients with peripheral T cell lymphoma(PTCL), and to find out the prognostic factors of the disease. METHODS: The clinical data of 73 patients with PTCL were reviewed.The median pre-treatment disease course was 3 months.Fifty-five patients were males, and 18 were females, with the median age of 42 years.Five patients received the combined chemo-radio therapy, 65 received chemotherapy alone, and the other 3 patients were treated with auto hematopoietic stem cell transplantation (HSCT). RESULTS: Of all the patients, the overall 3 -year and 5-year survival rates were 38% (28 /73) and 22% ( 16 /73) respectively.The survival rates decreased with the progression of the Ann Arbor stages.The survival rate of the patients with B symptom (fever, night sweat, and weight loss) or the international prognostic factors index ( IPI)>2 was lower than those of the patients without B symptom or IPI<2.The patients with the increased CA125 or D-dimer lever had the worst curative effect. CONCLUSION Peripheral T cell lymphoma is highly aggressive with poor prognosis.The clinical features,Ann Arbor staging, IPI and B symptom are important prognostic factors.CA125 and D-dimer may be also important prognostic factors.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; CA-125 Antigen ; blood ; Female ; Fibrin Fibrinogen Degradation Products ; metabolism ; Humans ; Lymphoma, T-Cell, Peripheral ; diagnosis ; pathology ; therapy ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Survival Rate

OBJECTIVETo prepare cytochrome (CYP)2E1-silenced hepatocytes by lentivirus-mediated RNA interference technology and to investigate the hepatotoxicity of trichloroethylene (TCE) in CYP2E1-silenced hepatocytes.

METHODSShort hairpin RNA fragments were designed and synthesized and were then ligated into the lentiviral vector; single colonies were screened; the plasmid was extracted after PCR and sequence identification and then transferred into L02 hepatocytes; the CYP2E1-silenced hepatocytes were selected; real-time quantitative PCR and Western blot were used to evaluate the interference effects. The obtained CYP2E1-silenced hepatocytes, as well as normal L02 hepatocytes, were treated with TCE (0, 0.25, 0.50, 1.00, 2.00, and 4.00 mmol/L). The cell viability and half maximal inhibitory concentration (IC50) of TCE were measured; the apoptotic rate of cells was measured by flow cytometry; the mRNA expression levels of apoptosis genes and oncogenes were measured by real-time quantitative PCR.

RESULTSThe IC50s of TCE for L02 hepatocytes and CYP2E1-silenced hepatocytes were 15.1 mmol/L and 23.6 mmol/L, respectively. The apoptotic rate increased as the dose of TCE rose in the two types of cells; the CYP2E1-silenced hepatocytes hada significantly lower apoptotic rate than L02 hepatocytes when they were exposed to 2.0 and 4.0 mmol/L TCE (P < 0.05 or P < 0.01). The mRNA expression level of bcl-2 (anti-apoptosis gene) in CYP2E1-silenced hepatocytes was 15% ∼ 60% higher than that in L02 hepatocytes (P < 0.01), while the mRNA expression levels of caspase-3 and caspase-9 (apoptosis genes) in CYP2E1-silenced hepatocytes were 30% ∼ 60% lower than those in L02 hepatocytes (P < 0.01). The mRNA expression level of p53 (cancer suppressor gene) in CYP2E1-silenced hepatocytes was 81 - 278% higher than that in L02 hepatocytes (P < 0.01), while the mRNA expression levels of c-fos and k-ras (oncogenes) in CYP2E1-silenced hepatocytes were 20-68% lower than those in L02 hepatocytes (P < 0.01).

CONCLUSIONCYP2E1-silenced cells can be successfully prepared by lentivirus-mediated RNA interference technology. Silencing CYP2E1 gene can reduce the hepatotoxicity of TCE and inhibit the expression of some apoptosis genes and oncogenes, suggesting that CYP2E1 gene plays an important role in TCE metabolism and is related to the hepatotoxicity of TCE.

Apoptosis ; drug effects ; genetics ; Cell Line ; Cell Survival ; drug effects ; genetics ; Cytochrome P-450 CYP2E1 ; genetics ; metabolism ; Genetic Vectors ; Hepatocytes ; drug effects ; metabolism ; Humans ; Lentivirus ; genetics ; RNA Interference ; Trichloroethylene ; toxicity

OBJECTIVETo investigate the large germline deletion of the VHL gene in Chinese families with von Hippel-Lindau disease (VHL).

METHODSThe large deletion of the VHL gene in 20 unrelated Chinese VHL families was analyzed by using universal primer quantitative fluorescent multiplex polymerase chain reaction (UPQFM-PCR) and GeneScan analysis.

RESULTSPartial and complete VHL gene deletions were detected in 6 probands, including 3 exon 1 deletions, 1 exon 3 and 2 complete deletions. Of the 2 families with the complete deletions, patients developed multi-centric hemangioblastoma in the retina and central nervous system (CNS), and none developed renal cell carcinoma (RCC).

CONCLUSIONPartial and complete VHL gene deletions could be detected in Chinese kindreds with von Hippel-Lindau disease and the test for large deletion of the VHL gene should be implemented in routine DNA diagnosis for VHL disease. Further investigations are required to confirm that entire VHL deletions may be associated with a high risk of hemangioblastomas in the retina and central nervous system.

Asian Continental Ancestry Group ; genetics ; Exons ; Female ; Gene Deletion ; Germ-Line Mutation ; Humans ; Male ; Pedigree ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; von Hippel-Lindau Disease ; genetics

OBJECTIVETo summarize the experience of radical retropubic prostatectomy (RRP) and the multi-factors which influence on the prognosis and long life quality.

METHODSFrom January 1993 to March 2005, 132 cases radical retropubic prostatectomy were performed. The patients were divided into 2 groups: the early group and recent group. Eleven items in peri-operative time and follow up results were analysed. The erection function of 78 cases were investigated with international index of erectile function 5 score. In these patients, nocturnal electrobioimpedance volumetric assessment (NEVA) were observe in 19 cases.

RESULTSComparing of the 2 groups, the index connected with operative skill changed to optimization. No one died of prostate cancer in 63 follow up patients. Nine cases showed biochemical failure with criterion as prostate specific antigen > 0.4 microg/L. Fifty patients passed urine normal post-operation in 6 months. Eight patients had stress incontinence and 5 had entire incontinence at 6 month. Four patients had vesical neck stricture. Another follow up result shows 33 (58.9%) erection function recovered in 55 bilateral nerve-sparing operation and 7 recovered in 22 of unilateral nerve-sparing operation. NEVA shows 14 cases with artery supply insufficient in whom 4 regained erection function and 5 cases vein leakage in whom no one recovered.

CONCLUSIONSThe radical retropubic prostatectomy remains the procedure of choice for the cure of localized prostatic cancer. The keys for the operation are anatomic dissection, preservation of the neurovascular bundle and good skill. These are also important for a good life quality for the patients.

Aged ; Erectile Dysfunction ; etiology ; prevention & control ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Penile Erection ; Postoperative Complications ; etiology ; prevention & control ; Prostatectomy ; adverse effects ; methods ; Prostatic Neoplasms ; physiopathology ; surgery ; Quality of Life ; Retrospective Studies ; Treatment Outcome ; Urinary Incontinence ; etiology ; prevention & control

OBJECTIVETo evaluate the 5-item version of the international index of erectile function (IIEF-5) as a method to differentiate the causes of vasculogenic erectile dysfunction (ED).

METHODSIn all, 103 ED patients (mean age 46.8 +/- 18.7) were reviewed by IIEF-5. Penile blood flow was also assessed in each patient after an intracavernosal injection (ICI) and audio-visual sex stimulation by duplex Doppler ultrasonography. The 99mTc-(113m)In dual radioisotope test was performed to confirm specific vascular causes in the vasculogenic ED cases. Kruskal-Wallis TEST was employed to compare the scores of IIEF-5 with the results of ICI, duplex Doppler ultrasonography and the 99mTC-(113m)In dual radioisotope test.

RESULTSOf the total number of ED cases, 37 (37/103, 35.9%) were nonvasculogenic, 18 (18/103, 17.5%) arteriogenic, 35 (35/103, 34.0%) venogenic and 13 (13/103, 12.6%) combined vasculogenic. There was no significant difference in the IIEF-5 scores either between the vasculogenic group and the non-vasculogenic one (P = 0.253) or among different groups of the vasculogenic ED patients.

CONCLUSIONIIEF-5 cannot be used as a tool for differential diagnosis of vasculogenic ED, or to compare its specific vascular causes, nor can the scores of IIEF-5 reflect penile vascular conditions.

Adult ; Humans ; Impotence, Vasculogenic ; diagnosis ; diagnostic imaging ; Male ; Middle Aged ; Penis ; diagnostic imaging ; Smoking ; Surveys and Questionnaires ; Ultrasonography

The aim of this study was to clarify whether bortezomib might induce apoptosis in Burkitt's lymphoma Raji cell line and its mechanism. Different concentrations of bortezomib were used to treat Raji cells and its effects of time and dose were observed. Cell morphology was observed under light microscope; flow cytometry was used to analyze cell apoptosis; RT-PCR was used to detect the expressions of NF-kappaB and p53 gene mRNAs. The results showed that the bortezomib could inhibit Raji cell growth within a certain range of treating time and dose. Apoptosis were induced in relation to time and dose. The expression of NF-kappaB mRNA and p53 mRNA decreased after treatment with bortezomib. It is concluded that the bortezomib can induce Raji cell apoptosis, which provides a theoretical basis for clinical treatment. NF-kappaB and p53 gene are supposed to participate in the bortezomib induced apoptosis of Raji cells.
Apoptosis ; drug effects ; Boronic Acids ; pharmacology ; Bortezomib ; Burkitt Lymphoma ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Flow Cytometry ; Humans ; NF-kappa B ; metabolism ; Pyrazines ; pharmacology ; Tumor Suppressor Protein p53 ; metabolism