Tumor immune checkpoint therapy is a clinical treatment strategy developed based on the new principle of the inhibition of negative immune regulation. In this article, the tumor immune checkpoint therapy and the drug delivery strategies were reviewed, mainly including immunity and tumor therapy, tumor immune checkpoint therapy and its mechanism of action, clinical application of tumor immune checkpoint therapy and therapeutic drugs, immune resistance of programmed cell death protein 1 (PD1)/programmed cell death ligand 1 (PDL1) treatment and countermeasures, drug delivery strategies for tumor immune checkpoint therapeutic agents, etc. As a revolutionary new immunotherapy strategy, tumor immune checkpoint therapy has shown obvious superior therapeutic efficacy in a variety types of tumor. However, tumor immune checkpoint therapy is also faced with a big challenge, namely, immunotherapy resistance. With the discovery of new mechanism, the continuous development of new therapeutic drugs and delivery strategies, tumor immune checkpoint therapy is expected to further improve the clinical efficacy of tumor.

OBJECTIVETo evaluate the effect of transcatheter arterial chemoembolization (TACE) with high-dose iodized oil on hepatic tumor growth and metastasis in rabbits.

METHODSForty-eight rabbits with implanted VX2 tumor were randomly divided into control group, routine dose iodized oil TACE group and high-dose iodized oil TACE group to receive perfusion through the hepatic artery with 0.9% saline, 5 mg adriamycin with routine-dose iodized oil, and 5 mg adriamycin with high-dose iodized oil, respectively. The tumor volume, tumor necrosis, intrahepatic and lung metastasis were examined 2 weeks after TACE.

RESULTSNo significant difference was found in the tumor volume between the 3 groups before TACE (P>0.05). The rabbits receiving TACE with iodized oil, especially at the high dose, showed significantly reduced tumor volume as compared with the control group (P<0.01). TACE with high-dose iodized oil resulted in significantly increased tumor necrosis rate in comparison with the control group and TACE with a routine dose of iodized oil (P<0.05); high-dose iodized oil TACE was also associated with reduced intrahepatic and lung metastasis as compared routine dose iodized oil TACE (P<0.05).

CONCLUSIONTACE with high-dose iodized oil can obviously inhibit the growth and intrahepatic and lung metastasis of transplanted VX2 liver tumor in rabbits .

Animals ; Catheterization, Peripheral ; Chemoembolization, Therapeutic ; methods ; Contrast Media ; administration & dosage ; Dose-Response Relationship, Drug ; Drug Carriers ; administration & dosage ; Female ; Hepatic Artery ; Iodized Oil ; administration & dosage ; Liver Neoplasms, Experimental ; therapy ; Male ; Rabbits

OBJECTIVETo investigate the effects of Echinococcus multilocularis on host liver cell proliferation in vivo using a BALB/c mouse alveolar hydatid infection model.

METHODSSixty-five 8-10-week-old female BALB/c mice were randomly divided into an experimental group (n = 40) and a control group (n = 25) and administered an abdominal injection into the left liver lobe of E. multilocularis protoscolices in saline solution or saline solution alone, respectively. At post-injection day 2, 8, 30, 60, and 90, liver samples were collected for analysis of lesions and lesion-adjacent tissue by hematoxylin-eosin staining and differential expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin A, and cyclin B1 by immunohistochemical staining. The significance of intergroup differences was assessed by Student's t-test.

RESULTSThe control group showed normal liver histology at all time points. The experimental group developed E. multilocularis lesions that showed increased severity of pathological features, such as inflammatory cell invasion, steatosis and fibrous connective tissue hyperplasia, over time. At post-injection days 2 and 8, enlarged, binuclear and apocyte hepatocytes were observed close to the lesions. At post-injection days 30, 60, and 90, the number of hepatocytes expressing PCNA progressively increased in the experimental group, and the numbers were significantly higher than in the control group (7.01 +/- 1.89 vs. 1.03 +/- 0.52, 8.41 +/- 2.80 vs. 0.93 +/- 0.31, and 13.4 +/- 4.43 vs. 1.07 +/- 0.94; all P < 0.05). The same progressively increasing trend was seen in the number of hepatocytes expressing CyclinD1, but was only significantly different from controls at post-injection days 30 and 60 (6.73 +/- 2.52 vs. 0.48 +/- 0.43 and 8.22 +/- 3.09 vs. 0.55 +/- 0.34; both P < 0.05). In contrast, the number of hepatocytes expressing cyclin A was significantly increased at post-injection day 30 and then showed a decreasing trend at days 60 and 90, although the numbers of expressing cells remained significantly higher than control levels at all time points (7.75 +/- 3.05 vs. 0.69 +/- 0.36, 3.42 +/- 1.80 vs. 1.14 +/- 0.42, and 3.03 +/- 1.50 vs. 0.69 +/- 0.31; all P < 0.05). The number of hepatocytes expressing CyclinB1 in the experimental group was less robust than the other cyclins (with a general temporal trend of increase followed by decrease), but the differential expression was not significantly different from the control levels at any time point.

CONCLUSIONE. multilocularis infection may promote the expression of host factors related to proliferation and anti-apoptosis in liver. This pathogen-mediated modulation of host cell-survival mechanisms may provide a rationale explanation for the clinical observations of hepatomegaly and the unexpected survival of alveolar echinococcosis patients following major hepatic resection.

Animals ; Apoptosis ; Cell Cycle ; Cell Proliferation ; Echinococcosis ; pathology ; Echinococcus multilocularis ; Female ; Hepatocytes ; cytology ; pathology ; Liver ; pathology ; Mice ; Mice, Inbred BALB C

OBJECTIVETo evaluate the association between the polymorphisms of excision repair cross complementation group 1 (ERCC1), X-ray repair cross complementing 1 (XRCC1), glutathione S-transferase Pi 1 (GSTP1) and the survival of advanced gastric cancer patients treated with oxaliplatin-based combination chemotherapy.

METHODSEighty five patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. Peripheral venous blood was taken before chemotherapy. DNA was extracted from peripheral venous blood. The genetic polymorphisms were detected by real-time PCR assay. The association between time to progression, overall survival and the polymorphisms was analyzed.

RESULTSThe median time to progression of the 85 cases was 5.3 months, and the median overall survival was 8.0 months. ERCC1-118 C/C, XRCC1-399 G/G and GSTP1-105 A/G + G/G were favorable genotypes and the number of the favorable genotypes was associated with survival of the patients. The median overall survival was 12.5 months, 10.0 months, 6.5 months and 4.5 months for patients with 3 favorable genotypes, 2 favorable genotypes, 1 favorable genotype and none favorable genotype, respectively, with a significant difference (χ(2) = 35.54, P < 0.01).

CONCLUSIONGenetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with TTP and OS of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based combination chemotherapy as the first-line chemotherapy.

Adenocarcinoma ; drug therapy ; genetics ; pathology ; Adenocarcinoma, Mucinous ; drug therapy ; genetics ; pathology ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; DNA-Binding Proteins ; genetics ; Disease Progression ; Endonucleases ; genetics ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Glutathione S-Transferase pi ; genetics ; Humans ; Male ; Middle Aged ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Polymorphism, Genetic ; Stomach Neoplasms ; drug therapy ; genetics ; pathology ; Survival Rate ; X-ray Repair Cross Complementing Protein 1

OBJECTIVEto investigate the pathologic basis of the difference between clinical response and pathologic response of breast carcinoma after neoadjuvant chemotherapy.

METHODStwo hundred and nine cases of breast cancer with neoadjuvant therapy were analyzed and clinical data were collected from June, 2005 to December, 2007. All patients had core needle biopsy taken before neoadjuvant chemotherapy and were operated within 4 weeks after neoadjuvant chemotherapy. Clinical examination, X-ray of breast and/or B ultrasonography of primary breast focus were taken before and after neoadjuvant chemotherapy. Clinical responses of breast primary focus were evaluated according to RECIST (response evaluation criteria in solid tumors) version 1.1.Pathologic responses of breast primary focus were evaluated according to Miller and Payne (MP) grading system. SPSS 15.0 software was used to statistical analysis.

RESULTS(1) Clinical responses basing on clinical examination showed complete response, partial response, stable disease and progressive response, in 33, 124, 41 and 11 cases respectively. (2) Eighty-seven cases had X-ray of breast taken before and after neoadjuvant chemotherapy. Clinical response basing on X-ray, showed complete response, partial response and stable disease in 8, 42 and 37 cases respectively. (3) Pathologic responses of breast primary focus were as MP1 (14 cases), MP2 (35 cases), MP3 (106 cases), MP4 (36 cases) and MP5 (18 cases). (4) The clinical response basing on clinical examination were related to the pathologic response (χ(2) = 33.668, P = 0.001); and the clinical response basing on X-ray of breast were also related to the pathologic response (χ(2) = 22.404, P = 0.004). (5) The pathologic basis of the difference between the pathologic response and the clinical response basing on X-ray of breast were: embolism of carcinoma, mucinous carcinoma, intraductal carcinoma with ossifying-type calcification, nodular fibrosis and others.

CONCLUSIONSthe clinical response may be related to the pathologic response. The difference between the two may be caused by pathologic changes. Some benign and malignant pathologic changes may contribute to the under-estimation of clinical response over pathologic response; whereas embolism of carcinoma may contribute to the over-estimation of clinical response over pathologic response.

Adenocarcinoma, Mucinous ; diagnostic imaging ; drug therapy ; pathology ; Adult ; Aged ; Breast Neoplasms ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Ductal, Breast ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; diagnostic imaging ; drug therapy ; pathology ; Carcinoma, Lobular ; diagnostic imaging ; drug therapy ; pathology ; Disease Progression ; Female ; Humans ; Middle Aged ; Neoadjuvant Therapy ; Radiography ; Remission Induction

OBJECTIVETo investigate the expression of annexin I in esophageal squamous cell carcinoma (SCC) and carcinomas of other histological types in order to analyze the correlation between the expression of annexin I and carcinogenesis.

METHODSFirst, a set of tissue microarray was established, which consisted of SCC from the esophagus (208 cases), lung, larynx, cervix, and external genital organs; adenocarcinomas from the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney with 30 cases in each group, meanwhile, the corresponding normal tissue was also obtained for control. Immunohistochemistry was used to detect the expression of annexin I in different types of carcinomas and the corresponding normal controls from different organs. The correlation between the expression of annexin I and the clinicopathological feature was analyzed and compared, which included age, gender, differentiation grade and lymph node metastasis.

RESULTSIt was found that the expression of annexin I was decreased in esophageal SCC, when compared with normal esophageal squamous epithelia (P < 0.001), the similarity was also found in SCC of the lung, larynx and cervix. However, though negative in normal epidermis, annexin I expression was detected in some cases with SCC from external genital organs. Annexin I was found to be overexpressed in adenocarcinomas of the lung, stomach, colon and rectum, liver, pancreas, breast, thyroid and kidney, particularly very strong expression of annexin I was seen in lung adenocarcinoma, uterine endometrioid adenocarcinoma and ovarian serous adenocarcinoma. Interestingly, it was found to be positive in all thyroid papillary carcinomas, but negative in all normal thyroid glands. However, annexin I expression was found to be negative in all hepatocellular carcinoma and normal hepatocytes; and it was only detected in myoepithelium of normal breast tissue, but not in ductal luminal cells, and rarely in infiltrating ductal adenocarcinoma. In SCC, annexin I expression was stronger in well differentiated ones than that in the poorly differentiated ones. However, contrasting with SCC, in the adenocarcinomas from different organs, annexin I expression was much stronger in poorly differentiated ones than that in the well differentiate ones, especially in the adenocarcinomas from stomach, colon and rectum, pancreas, ovarian and kidney.

CONCLUSIONAnnexin I expression is quite different among different types of carcinomas, and is correlated with histopathological type and differentiation grade. Further study is needed to investigate its role in the carcinogenesis.

Adenocarcinoma ; metabolism ; pathology ; Annexin A1 ; metabolism ; Carcinoma, Endometrioid ; metabolism ; pathology ; Carcinoma, Squamous Cell ; metabolism ; pathology ; Cell Differentiation ; Endometrial Neoplasms ; metabolism ; pathology ; Epithelium ; metabolism ; Esophageal Neoplasms ; metabolism ; pathology ; Esophagus ; metabolism ; Female ; Humans ; Immunohistochemistry ; Lung Neoplasms ; metabolism ; pathology ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the bacterial distribution and drug resistance in patients with surgical infections, and provide the basis for the standardization treatment of the surgical infection.

METHODSRetrospectively analyzed from January 2008 to December 2011 surgical infection in our samples bacteria identification and drug sensitivity test results.

RESULTSA total of 3829 nonduplicate isolates from 3257 samples, Gram-negative bacteria accounted for 62.4% (the main microbes were P.aeruginosa, K. pneumonia and E.coli etc) and Gram-positive bacteria accounted for 37.6% (the main microbes were Enterococcus, Staphylococcus and coagulase negative Staphylococcus). Incidence of Staphylococcus aureus and Enterococcus faecalis were on an obvious increase. For the performance of the high level of sensitive to Imipenem, Amikacin, Piperacillin and Tazobactam by E. coli and K. pneumonia. The Pseudomonas aeruginosa and Acinetobacter baumannii to cephalosporins, Carbapenems and Fluoroqinolones were higher resistant with Multidrug resistance. No vancomycin and teicoplanin resistant Enterococcus faecium were found. The prevalence of ESBL E.coli was 45.6%-61.5% and ESBL K.pneumoniae isolates were fluctuated. The methicillin-resistant S.aureus (MRSA) isolates were relatively high (21.1%-55.8%), and methicillin-resistant Staphylococcus epidermidis was higher than the other Gram-positive cocci. Vancomycin for Staphylococcus performance was highly sensitive.

CONCLUSIONSThe main composition of surgical clinical infection pathogens are Gram-negative bacillus, and the emergency of resistance of bacteria to antibacterial drugs is a common phenomenon. The resistant rate shows ascendant trend; Drug resistance is significantly higher in Pseudomonas aeruginosa and Acinetobacter baumannii. Antimicrobial resistance is a serious and challenging issue.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Female ; Humans ; Infant ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Retrospective Studies ; Surgical Wound Infection ; microbiology ; Young Adult

OBJECTIVETo compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT).

METHODSData of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed.

RESULTSIn the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications.

CONCLUSIONSTo compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

Age Factors ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; classification ; methods ; Postoperative Complications ; etiology ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies ; Smoking ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy ; adverse effects ; methods

OBJECTIVETo determine independent factors correlated with clinical effects of DK crush and classical crush technique with drug-eluting stents on bifurcation lesions.

METHODS311 patients with bifurcation lesions were randomized to classical (C, n = 156) or double kissing (DK) crush (n = 155) stent implantation group. The primary endpoints included major adverse cardiac events (MACE).

RESULTSFinal kissing balloon inflation (FKBI) success rate was 76% in C and 100% in DK groups (P < 0.001). DK crush procedure was characterized by lower unsatisfactory FKBI rate (27.6% vs.6.3%, P < 0.01). Clinical follow-up was available in 100% and angiographic follow-up in 82% patients. The overall restenosis rate was 32.3% in C and 20.3% in DK groups (P = 0.01), respectively. Cumulative 8-month MACE was 35.9% in without-FKBI and 19.7% in with-FKBI sub-groups, and 11.4% in DK group (P = 0.02). The incidence of stent thrombosis was 3.2% in C group (5.1% without vs. 1.7% with FKBI) and 1.3% in DK group (P > 0.05). The predictive factors of MACE included minimal side branch stent lumen diameter and lack of DK crush technique.

CONCLUSIONDK crush technique is an alternative of double stenting techniques in terms of improvement of restenosis and clinical outcomes.

Aged ; Angioplasty, Balloon, Coronary ; methods ; Coronary Artery Disease ; therapy ; Coronary Stenosis ; therapy ; Drug-Eluting Stents ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Stents

Parasitic diseases are common infectious diseases closely related to poverty,which are mainly endemic in the trop-ical and subtropical regions.Africa is the major epidemic area of parasitic diseases,and the global burden of malaria and schisto-somiasis is over 85% in Africa.This paper reviews the disease burden,regional distribution and control strategies of the main parasitic diseases in Africa,in order to promote the prevention and control of parasitic diseases in this area.