Tumor antigen-loaded dendritic cells combined with cytokine-induced killer (CIK) enhance the killing activity of human esophageal cancer cells by promoting ASK1 activation / 细胞与分子免疫学杂志

Objective To clarify the effect and mechanism of tumor antigen-loaded dendritic cells (Ag-DCs) combined with cytokine-induced killers (CIKs) on the killing of esophageal cancer tumor cells. Methods Peripheral blood DCs and CIKs were induced and cultured, and the DCs were loaded with tumor antigen to obtain Ag-DCs, and Ag-DCs were co-cultured with CIKs. The experiment was divided into CIK group, DC combined with CIK group, Ag-DC combined with CIK group. Flow cytometry was used to detect the phenotype of cells. MTT assay was employed to determine the killing activity against EC9706 cells. Annexin V-FITC/PI double staining was used to detect the apoptosis rate of cells, immunofluorescence staining to detect the expression of phosphorylated apoptotic signal-regulated kinase 1 (p-ASK1) and Western blot analysis to detect the expression of ASK1 pathway related proteins. A nude mouse model of esophageal cancer transplantation tumor was constructed and divided into control group, DC combined with CIK group and Ag-DC combined with CIK group. The corresponding immune cells were injected into the tail vein for treatment and the tumor volume was measured every 2 days. After 21 days, all nude mice were sacrificed with the tumors taken out. HE staining was used to observe the tumor pathological changes and immunohistochemical staining was performed to detect the expression of ki67 and ASK1 in the tumor tissue. Results Comparedwith the CIK group alone and the DC combined with CIK group, the ratio of CD3+ CD8+ and CD3+ CD56+ in the cells significantly increased after Ag-DCs and CIKs co-culture, along with the increased killing rate of EC9706 cells, increased apoptosis rate of EC9706 cells, and the improved activation level of ASK1. Compared with the CIK group and the DC combined with CIK group, the growth of the transplanted tumor in nude mice treated with Ag-DCs combined with CIKs was significantly inhibited, and after 21 days, it was observed that the tumor tissue mass in this group was relatively smaller, with sparsely arranged cells in the tumor tissue and a decline in the positive rate of ki67 in tumor tissue, while the positive rate of ASK1 was significantly increased. Conclusion Co-cultivation of tumor antigen-loaded DCs with CIKs can significantly increase the killing activity of esophageal cancer tumor cells. The mechanism of action may be related to the activation of the ASK1 pathway.

Research progress in effects of MAGE-A family on gastric cancer / 中南大学学报(医学版)

Gastric cancer (GC) is one of the most common malignant tumors worldwide, and most of the patients are diagnosed at the advanced stage. Most of the treating options are comprehensive treatment, in which immunotherapy plays more and more important role. Melanoma antigen-associated gene-A (MAGE-A) family is a kind of cancer testis antigens. Except in germ cells of testis and trophoblast cells of placenta, MAGE-A family is highly expressed in cancerous tissues and participates in a variety of biological processes, such as cancer cell proliferation, differentiation and metastasis. In addition, cancer testis antigen also possesses good immunogenicity, which can induce humoral and cellular immune responses, is a good target for immunotherapy, and has good application value in the diagnosis, treatment and prognosis of GC. A variety of targeted therapeutic drugs based on MAGE-A are in phase I or II clinical trials, it has good safety and potential clinical application value. With the continuous progress of clinical trials and basic research on MAGE-A targets in GC, it is expected to provide a theoretical basis for clinical transformation and immunotherapy of MAGE-A in the future.

Recent Progress of Nano-drug Combined with Chimeric Antigen Receptor T Cell Therapy in the Treatment of Soild Tumors / 中国肺癌杂志

Chimeric antigen receptor T cell (CAR-T) therapy has shown remarkable success in treating hematological malignancies. However, CAR-T therapy for solid tumors is still limited due to the unique solid-tumor microenvironment and heterogeneous target antigen expression, which leads to an urgent need of combining other therapies. At present, nano delivery system has become one of the most promising directions for the development of anti-tumor drugs. Based on the background of CAR-T and tumor treatment, we focus on the research progress of nanomedicine combined with CAR-T therapy, and systematically review the strategies and examples in recent years in the aspects of in vivo delivery of mRNA, regulation of tumor microenvironment, combination with photothermal therapy. And we also look forward to the future direction of this filed.
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Expression Levels of the CA9, WT1, and PRAME genes and genotyping-associated antigens for the diagnosis and prognosis of colorectal cancer

Background: Colorectal cancer (CRC) is the third most prevalent type of cancer worldwide, and is one of the major health problems in Asia, Africa, Europe, and America. The tumor antigens recently are of interesting indicators as diagnostic and prognostic tools, The aim of the present study is to detect the expression levels of carbonic anhydrase IX (CA9), the Wilms tumor gene (WT1), and the preferentially expressed antigen in melanoma (PRAME) in the peripheral blood of CRC patients in comparison with healthy controls. Methods: A prospective case-control study of CRC patients was conducted. We included 25 newly-diagnosed CRC eligible patients and obtained peripheral blood samples of them as well as 10 blood samples from the control group. All samples were then submitted to deoxyribonucleic acid (DNA) extraction and a molecular study through real-time polymerase chain reaction (PCR). Results: The CRC group consisted of 15 (60%) female and 10 (40%) male patients with a mean age of 50.52 ± 9.8 years, while the control group included 4 (40%) female and 6 (60%) male patients with a mean age of 47.7 ± 7.9 years. The CRC group, 24 (96%) of patient samples were CA9-positive with strong statistically significant differences (p < 0.00001; sensitivity: 96%; specificity: 90%). Regarding the WT1 gene, there were 11 (44%) positive samples in the CRC group, with no statistically significant differences (p = 0.055; sensitivity: 44%; specificity: 90%). The PRAME gene was positive in 9 (36%) samples in the CRC group, with no statistically significant differences (p = 0.357; sensitivity: 36%; specificity: 80%. Among CA9 (24 patients; 96%) of patients with CRC expressed positive results, in WT1 11(91.6%) CRC patients expressed gene, and in PRAME gene, 9 patients with CRC (81.8%) expressed positive results. Conclusion: Overexpression of the CA9 gene in CRC of high sensitivity and specificity to be used as a tool to discriminate CRC from benign associate with high accuracy compare to WT1 and PRAME genes. (AU)

Diagnostic value of serum tumor markers CEA, CYFRA21-1, SCCAg, NSE and ProGRP for lung cancers of different pathological types / 南方医科大学学报

OBJECTIVE@#To evaluate the diagnostic value of the serum tumor markers carcinoembryonic antigen (CEA), cytokeratin-19-fragment (CYFRA21-1), squamous cell carcinoma associated antigen (SCCAg), neuron-specificenolase (NSE) and pro-gastrin-releasing peptide (ProGRP) for lung cancers of different pathological types.@*METHODS@#This study was conducted among patients with established diagnoses of lung adenocarcinoma (LADC, n=137), lung squamous cell carcinoma (LSCC, n=82), small cell lung carcinoma (SCLC, n=59), and benign chest disease (BCD, n=102). The serum tumor markers were detected for all the patients for comparison of the positivity rates and their serum levels. ROC curve was used for analysis of the diagnostic efficacy of these tumor markers either alone or in different combinations.@*RESULTS@#In patients with LADC, the positivity rate and serum level of CEA were significantly higher than those in the other groups (P < 0.05); the patients with LSCC had the highest positivity rate and serum level of SCCAg among the 4 groups (P < 0.05). The positivity rates and serum levels of ProGRP and NSE were significantly higher in SCLC group than in the other groups (P < 0.05). CYFRA21-1 showed the highest positivity rate and serum level in LADC group and LSCC group. With the patients with BCD as control, CEA showed a diagnostic sensitivity of 62.8% and a specificity of 93.1% for LADC, and the sensitivity and specificity of SCCAg for diagnosing LSCC were 64.6% and 91.2%, respectively. CYFRA21-1 had the highest diagnostic sensitivity for LADC and LSCC. The diagnostic sensitivity and specificity of ProGRP for SCLC were 83.1% and 98.0%, respectively. When combined, CYFRA21-1 and CEA showed a high sensitivity (78.8%) and specificity (86.3%) for diagnosing LADC with an AUC of 0.891; CYFRA21-1 and SCCAg had a high sensitivity (84.1%) and specificity (87.3%) for diagnosing LSCC with an AUC of 0.912. NSE combined with ProGRP was highly sensitive (88.1%) and specific (98.0%) for diagnosis of SCLC, with an AUC of 0.952. For lung cancers of different pathological types, the combination of all the 5 tumor markers showed no significant differences in the diagnostic power from a combined detection with any two of the markers (P>0.05).@*CONCLUSION@#CEA, CYFRA21-1, SCCAg, NSE and ProGRP are all related to the pathological type of lung cancers and can be used in different combinations as useful diagnostic indicators for lung cancers.

CAR T cells redirected against tumor-specific antigen glycoforms: can low-sugar antigens guarantee a sweet success? / 医学前沿

Immune-based therapies have experienced a pronounced breakthrough in the past decades as they acquired multiple US Food and Drug Administration (FDA) approvals for various indications. To date, six chimeric antigen receptor T cell (CAR-T) therapies have been permitted for the treatment of certain patients with relapsed/refractory hematologic malignancies. However, several clinical trials of solid tumor CAR-T therapies were prematurely terminated, or they reported life-threatening treatment-related damages to healthy tissues. The simultaneous expression of target antigens by healthy organs and tumor cells is partly responsible for such toxicities. Alongside targeting tumor-specific antigens, targeting the aberrantly glycosylated glycoforms of tumor-associated antigens can also minimize the off-tumor effects of CAR-T therapies. Tn, T, and sialyl-Tn antigens have been reported to be involved in tumor progression and metastasis, and their expression results from the dysregulation of a series of glycosyltransferases and the endoplasmic reticulum protein chaperone, Cosmc. Moreover, these glycoforms have been associated with various types of cancers, including prostate, breast, colon, gastric, and lung cancers. Here, we discuss how underglycosylated antigens emerge and then detail the latest advances in the development of CAR-T-based immunotherapies that target some of such antigens.

Clinical features and prognosis of childhood B-lineage acute lymphoblastic leukemia expressing the PRAME gene / 中国当代儿科杂志

OBJECTIVES@#To study the clinical and prognostic significance of the preferentially expressed antigen of melanoma (PRAME) gene in the absence of specific fusion gene expression in children with B-lineage acute lymphoblastic leukemia (B-ALL).@*METHODS@#A total of 167 children newly diagnosed with B-ALL were enrolled, among whom 70 were positive for the PRAME gene and 97 were negative. None of the children were positive for MLL-r, BCR/ABL, E2A/PBX1, or ETV6/RUNX1. The PRAME positive and negative groups were analyzed in terms of clinical features, prognosis, and related prognostic factors.@*RESULTS@#Compared with the PRAME negative group, the PRAME positive group had a significantly higher proportion of children with the liver extending >6 cm below the costal margin (P<0.05). There was a significant reduction in the PRAME copy number after induction chemotherapy (P<0.05). In the minimal residual disease (MRD) positive group after induction chemotherapy, the PRAME copy number was not correlated with the MRD level (P>0.05). In the MRD negative group, there was also no correlation between them (P>0.05). The PRAME positive group had a significantly higher 4-year event-free survival rate than the PRAME negative group (87.5%±4.6% vs 73.5%±4.6%, P<0.05), while there was no significant difference between the two groups in the 4-year overall survival rate (88.0%±4.4% vs 85.3%±3.8%, P>0.05). The Cox proportional-hazards regression model analysis showed that positive PRAME expression was a protective factor for event-free survival rate in children with B-ALL (P<0.05).@*CONCLUSIONS@#Although the PRAME gene cannot be monitored as MRD, overexpression of PRAME suggests a good prognosis in B-ALL.

Immunohistochemical Markers in the Differential Diagnosis of Melanoma and Nevus in Humans

SUMMARY: Immunohistochemistry allows in situ detection of cell and extracellular components through specific antibodies. The objective was to compare the immunohistochemical expression patterns of the S-100, HMB-45 and MART-1 proteins for differential diagnosis of malignant melanoma and melanocytic nevus in human skin biopsies. Thirty-nine biopsies of human tissue were used. They were divided into two groups: 19 in malignant melanoma and 20 in melanocytic nevi. Next, the samples were fixed with paraformaldehyde and processed following the protocol for inclusion. Then, immunohistochemical staining was performed. Finally, the histological and qualitative analysis of the samples was carried out. S-100, HMB-45, and MART-1 markers showed positive immunoreaction in melanoma biopsies. HMB-45 marker was generally present with weaker expression than S-100 and MART-1 in melanocytic nevus biopsies. No expression pattern was observed which specifically associates one or more markers with some types of histopathological diagnosis. Immunohistochemistry is fundamental in differential diagnosis of melanomas and melanocytic nevi. However, there is no antibody or set of antibodies which allows unequivocal diagnosis between melanoma and nevus. It is therefore necessary to analyze with care the expression pattern and location of the lesion using standard morphological characteristics.

RESUMEN: La inmunohistoquímica permite la detección in situ de componentes celulares y extracelulares a través de anticuerpos específicos. El objetivo de nuestro estudio fue comparar los patrones de expresión inmunohistoquímica de las proteínas S-100, HMB-45 y MART-1 para el diagnóstico diferencial de melanoma maligno y nevo melanocítico en biopsias de piel humana. Se utilizaron treinta y nueve biopsias de tejido humano, las que fueron divididas en dos grupos: 19 en melanoma maligno y 20 en nevos melanocíticos. A continuación, las muestras se fijaron con paraformaldehído y se procesaron siguiendo el protocolo convencional para su inclusión. Luego, se realizó la tinción inmunohistoquímica. Finalmente, se realizó el análisis histológico y cualitativo de las muestras. Los marcadores S-100, HMB- 45 y MART-1 mostraron inmunorreacción positiva en biopsias de melanoma. El marcador HMB-45 estuvo generalmente presente con una expresión más débil que S-100 y MART-1 en biopsias de nevo melanocítico. No se observó ningún patrón de expresión que asocie específicamente uno o más marcadores con algunos tipos de diagnóstico histopatológico. La inmunohistoquímica es fundamental en el diagnóstico diferencial de melanomas y nevos melanocíticos. Sin embargo, no existe ningún anticuerpo o panel de anticuerpos que permita un diagnóstico inequívoco entre el melanoma y el nevo. Por tanto, es necesario analizar con cuidado el patrón de expresión y la localización de la lesión utilizando características morfológicas estándar.

Spontaneous remission of follicular bronchiolitis with nonspecific interstitial pneumonia: A case report and literature review / 北京大学学报(医学版)

A 41-year-old female patient was admitted in Department of Respiratory and Critical Care Medicine, Peking University Third Hospital because of having cough for a year. Multiple subpleural ground grass and solid nodules could be seen on her CT scan. Four months before admission, she began to experience dry mouth and eyes, blurred vision, finger joints pain, muscle pain and weakness in both lower limbs and weight loss. At the time of admission, the patient's vital signs were normal, no skin rash was seen, breath sounds in both lungs were clear, no rales or wheeze, no deformities in her hands, no redness, swelling, or tenderness in the joints. There was no edema in both lower limbs. Some lab examinations were performed. Tumor markers including squamous cell carcinoma (SCC) antigen, neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), Cyfra21-1, pro-gastrin-releasing peptide (proGRP), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were all normal. The antinuclear antibody, rheumatoid factor, antineutrophil cytoplasmic antibody, anti-dsDNA antibody, anti-Sm antibody, anti-SSA/SSB antibody, anti-ribonucleoprotein (RNP) antibody, anti-Jo-1 antibody, anti-SCL-70 antibody and anti-ribosomal antibody were all negative. The blood IgG level was normal. The blood fungal β-1.3-D glucose, aspergillus galactomannan antigen, sputum bacterial and fungal culture, and sputum smear test for acid-fast staining were all negative. Lung function was normal. Bronchoscopy showed the airways and mucosa were normal. To clarify the diagnosis, she underwent thoracoscopic lung biopsy, the histopathology revealed follicular bronchiolitis (FB) with nonspecific interstitial pneumonia (NSIP). She did not receive any treatment and after 7 months, the lung opacities were spontaneously resolved. After 7 years of follow-up, the opacities in her lung did not relapse. To improve the understanding of FB, a literature research was performed with "follicular bronchiolitis" as the key word in Wanfang, PubMed and Ovid Database. The time interval was from January 2000 to December 2018. Relative articles were retrieved and clinical treatments and prognosis of FB were analyzed. Eighteen articles concerning FB with complete records were included in the literature review. A total of 51 adult patients with FB were reported, including 18 primary FB and 33 secondary FB, and autoimmune disease was the most common underlying cause. Forty-one (80.4%) patients were prescribed with corticosteroids and/or immunosuppressive agents, 6 (11.8%) patients were treated with anti-infective, 5 (9.8%) patients did not receive any treatment. The longest follow-up period was 107 months. Among the 5 patients without any treatment, 1 patients died of metastatic melanoma, the lung opacities were unchanged in 1 patient and getting severe in 3 patients. In conclusion, FB is a rare disease, the treatment and prognosis are controversial. Corticosteroid and immunosuppressive agents could be effective. This case report suggests the possibility of spontaneous remission of FB.

Evaluation of squamous cell carcinoma antigen 1 expression in oral squamous cell carcinoma (tumor cells and peritumoral T-lymphocytes) and verrucous carcinoma and comparison with normal oral mucosa

Abstract Background: Squamous cell carcinoma antigen (SCCA) is used as a prognostic marker for recurrence of squamous cell carcinoma in various sites, including head and neck. Studies suggest that its high serum levels are correlated to some clinical features, such as nodal metastasis. However, it is still unknown if high SCCA in patients with SCCA tissue expression in tumor cells are related to peripheral T-lymphocytes. Therefore, we did this study to evaluate SCCA expression in squamous cell carcinoma and verrucous carcinoma and to compare it with normal oral mucosa, also investigating the correlation between serum-based and tissue-based antigen levels. Methodology: In this study, the immunohistochemistry (IHC) technique was used to determine the SCCA1 expression pattern in 81 specimens divided into 3 groups, including oral squamous cell carcinoma, verrucous carcinoma, and normal oral mucosa. Serum-based and tissue-based antigen levels of 20 oral squamous cell carcinoma cases were compared by the western blot assay. SCCA expression was also evaluated and compared in both tumor cells and peripheral T-lymphocytes by the immunofluorescence assay. Results: Our results showed that the SCCA levels in SCC specimens were significantly lower than in verrucous carcinoma and normal and hyperplastic oral mucosa specimens. We found no correlation between the IHC expression of SCCA and serum levels. SCCA was well expressed in both tumor cells and peripheral T-lymphocytes. Conclusion: Decreasing SCCA in SCC specimens suggested that SCC tumor cells may affect more than the serum levels of SCCA in some patients. In addition, expression of SCCA in peripheral T-lymphocytes showed that both tumor cells and T-lymphocytes may cause serum SCCA.

Association of RAGE gene polymorphisms with MHR ratio and heart rate variability among patients with coronary heart disease / 中华医学遗传学杂志

OBJECTIVE@#To assess the association of polymorphisms of receptor of advanced glycation end products (RAGE) gene, monocyte to high-density lipoprotein cholesterol ratio (MHR) and variability of heart rate among patients with coronary heart disease (CHD).@*METHODS@#120 patients with CHD and 120 healthy individuals were respectively selected as the observation group and the control group. Allelic and genotypic differences of -429T>C, 1704G>T, 82G>S, MHR ratio and heart rate variability between the two groups and patients with different severity were analyzed. The correlation between their genotypes and MHR ratio and heart rate variability was analyzed.@*RESULTS@#The 82G>S polymorphism of the RAGE gene and the allelic difference between the two groups and patients with different severity were statistically significant (P< 0.05). Compared with the control group and patients with mild to moderate phenotype, monocyte, total cholesterol, triglyceride, low density lipoprotein, MHR, low frequency in the observation group and patients with severe symptoms were significantly higher, while their high density lipoprotein, standard deviation of NN intervals (SDNN), standard deviation average of NN intervals (SDANN), root mean square successive differences, percentage of differences exceeding 50ms between adjacent normal number of intervals (PMN50), high frequency (HF) were significantly lower. The gene frequencies of G-Gly-T, T-Gly-T, G-Ser-T and G-Gly-C were correlated with SDNN, SDANN, rMSSD, PMN50, HF and MHR, but negatively correlated with low frequency.@*CONCLUSION@#Polymorphisms of the RAGE gene in patients with coronary heart disease are associated with the MHR ratio and heart rate variability, which can be used as markers for the diagnosis and efficacy evaluation.

Diagnosis accuracy of PCA3 level in patients with prostate cancer: a systematic review with meta-analysis

ABSTRACT Background: The diagnostic value and suitability of prostate cancer antigen 3 (PCA3) for the detection of prostate cancer (PCa) have been inconsistent in previous studies. Thus, the aim of the present meta-analysis was performed to systematically evaluate the diagnostic value of PCA3 for PCa. Materials and Methods: A meta-analysis was performed to search relevant studies using online databases EMBASE, PubMed and Web of Science published until February 1st, 2019. Ultimately, 65 studies met the inclusion criteria for this meta-analysis with 8.139 cases and 14.116 controls. The sensitivity, specificity, positive likelihood ratios (LR+), negative likelihood ratios (LR−), and other measures of PCA3 were pooled and determined to evaluate the diagnostic rate of PCa by the random-effect model. Results: With PCA3, the pooled overall diagnostic sensitivity, specificity, LR+, LR−, and 95% confidence intervals (CIs) for predicting significant PCa were 0.68 (0.64-0.72), 0.72 (0.68-0.75), 2.41 (2.16-2.69), 0.44 (0.40-0.49), respectively. Besides, the summary diagnostic odds ratio (DOR) and 95% CIs for PCA3 was 5.44 (4.53-6.53). In addition, the area under summary receiver operating characteristic (sROC) curves and 95% CIs was 0.76 (0.72-0.79). The major design deficiencies of included studies were differential verification bias, and a lack of clear inclusion and exclusion criteria. Conclusions: The results of this meta-analysis suggested that PCA3 was a non-invasive method with the acceptable sensitivity and specificity in the diagnosis of PCa, to distinguish between patients and healthy individuals. To validate the potential applicability of PCA3 in the diagnosis of PCa, more rigorous studies were needed to confirm these conclusions.

Anticuerpos conjugados a fármaco: la nueva generación de terapias biotecnológicas contra el cáncer / Antibody-drug conjugates: the new generation of biotechnological therapies against cancer

Resumen Los anticuerpos terapéuticos son proteínas recombinantes empleadas en el tratamiento del cáncer. Existe una nueva generación de anticuerpos monoclonales con actividad contra las células cancerosas, conocidos como anticuerpos conjugados a fármacos. Estas moléculas están integradas por tres elementos: un anticuerpo monoclonal, un fármaco citotóxico con alta potencia y un enlazador químico que los une. El anticuerpo reconoce antígenos tumorales, por lo que permite la entrega dirigida del agente citotóxico hacia las células cancerosas. Tras el reconocimiento de su antígeno, el anticuerpo conjugado a fármaco es endocitado por las células blanco, donde se induce la degradación lisosomal de la fracción proteica y se libera el fármaco citotóxico. En el presente artículo se revisan las características generales de los anticuerpos conjugados a fármacos y se describe la evidencia clínica de la eficacia y seguridad de los primeros cuatro aprobados por las agencias reguladoras de Estados Unidos y Europa.

Abstract Therapeutic antibodies are recombinant proteins used in the treatment of cancer. There is a new generation of monoclonal antibodies with activity against cancer cells, known as antibody-drug conjugates. These molecules are made up of three elements: a monoclonal antibody, a highly potent cytotoxic drug, and a chemical linker that binds them together. The antibody recognizes tumor antigens, thereby allowing targeted delivery of the cytotoxic agent to cancer cells. After recognizing its antigen, the antibody-drug conjugate is endocytosed by the target cells, where the protein fraction is degradated into lysosomes, releasing the cytotoxic drug. This article reviews antibody-drug conjugates general characteristics and describes the clinical evidence of efficacy and safety of the first four approved by regulatory agencies in the United States and Europe.

Prognostic significance of inflammation-based prognostic scoring in patients with upper urinary tract urothelial carcinoma

ABSTRACT Objectives: To investigate whether Glasgow Prognostic Score has prognostic significance in patients with upper urinary urothelial carcinoma. Patients and methods: We retrospectively reviewed the clinical records of 74 patients with upper urinary urothelial carcinoma. We set the cut-off value for C-reactive protein as 1.0mg/dL, and 3.5mg/dL for albumin as Glasgow Prognostic Score. Their blood data including albumin and C-reactive protein for Glasgow Prognostic Score and cytokeratin 19 fragment 21-1 as a tumor marker were measured before starting treatment. The patients were stratified into three groups with Glasgow Prognostic Score: The Group-1, albumin ≥3.5g/dL and C-reactive protein < 1.0mg/dL; Group-2, albumin < 3.5g/dL or C-reactive protein ≥1.0mg/dL; Group-3, albumin < 3.5g/dL and C-reactive protein ≥1.0mg/dL. Results: The median follow-up for all patients was 26.9 months (range: 10.9-91.1 months), during which 37 (50%) patients died. There was a significant difference in the estimated survival rate among the 3 groups stratified by Glasgow Prognostic Score. The estimated survival rate in the Group-1 was significantly higher than those in Groups 2 and 3. In the univariate analysis C-reactive protein, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were significant predictors of overall survival. On the multivariate analysis, serum cytokeratin 19 fragment 21-1 and Glasgow Prognostic Score were independently associated with shorter overall survival. Conclusion: Our review suggests Glasgow Prognostic Score may play as a prognostic predictor for upper urinary urothelial carcinoma.

Osteosarcoma of the jaw - experience at the Medical University Vienna and comparative study with international tumor registries

OBJECTIVES: Osteosarcoma of the jaw (OSAJ) is fundamentally different in clinical practice from its peripheral counterparts. Studies are difficult to conduct due to low incidence rates. The primary aim of this study was to provide for the first time a comprehensive retrospective analysis of the treatment concepts and outcome data of OSAJ patients treated at the University Hospital Vienna and to compare these with two recently published studies on OSAJ. The clinical study was accompanied by a biomarker study investigating the prognostic relevance of melanoma-associated antigen-A (MAGE-A) in OSAJ specimens. METHOD: Eighteen patients were included, and their outcomes were compared to published data. Immunohistochemistry was performed with mouse monoclonal antibodies against MAGE-A. Survival rates were estimated by the Kaplan-Meyer method. The log-rank test was used to analyze potential prognostic parameters. Fisher's exact test was performed to define the significant differences between the survival rates of the current study and the DOESAK registry. RESULTS: Disease-specific survival was 93.8% after five and 56.3% after ten years. The development of metastases (p=0.033) or relapse (p=0.037) was associated with worsened outcomes in our group as well as in the comparative group. Despite the different treatment concepts of the study groups, survival rates were comparable. MAGE-A failed to show prognostic relevance for OSAJ patients. CONCLUSIONS: Uncertainties about the optimal treatment strategies of OSAJ patients will currently remain. Thus, prospective studies of OSAJ are needed but are only feasible in a multicenter study setting, conducted over a prolonged time period.

Application Value of Combined Detection of Urinary Amino Acid Metabolite and Tumor Specific Growth Factor in Evaluation of Curative Efficacy for Acute Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the clinical importance of combined detection of urinary amino acid metabolite --urinary tyrosine (UT) and tumor specific growth factor (TSGF) in the disease observation and curative effect evaluation of acute leukemia（AL）.@*METHODS@#In 87 cases of AL, the UT and TSGF levels were detected by using chemical chromogenic method and continuous monitoring method respectively. The 2 indicators of each treatment group were statistically analyzed and compared with that of 50 healthy control group.@*RESULTS@#In 87 AL patients, the levels of UT and TSGF after treatment were significantly lower than those before treatment (P0.05).@*CONCLUSION@#UT and TSGF levels are related with the metabolism of tumor cells in AL patients. UT level can be used to predict the recurrence of patients with CR. The combined dynamical monitoring of these 2 indicators can be used as the indexes for observation of AL status, evaluation of therapeutic efficacy, prediction of prognosis and relapse of AL.

LC-MS/MS-based screening of new protein biomarkers for cervical precancerous lesions and cervical cancer / 南方医科大学学报

OBJECTIVE@#To screen potential plasma protein biomarkers for the progression of cervical precancerous lesions into cervical carcinoma and analyze their functions.@*METHODS@#Plasma samples obtained from healthy control subjects, patients with low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), cervical cancer (CC), and patients with CC after treatment were enriched for low-abundance proteins for liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. The MS data of the samples were analyzed using Discoverer 2.2 software, and the differential proteins (peptide coverage ≥20%, unique peptides≥2) were screened by comparison of LSIL, HSIL and CC groups against the control group followed by verification using target proteomics technology. Protein function enrichment and coexpression analyses were carried out to explore the role of the differentially expressed proteins as potential biomarkers and their pathological mechanisms.@*RESULTS@#Compared with the control group, both LSIL group and HSIL group showed 9 differential proteins; 5 differentially expressed proteins were identified in CC group. The proteins ORM2 and HPR showed obvious differential expressions in LSIL and HSIL groups compared with the control group, and could serve as potential biomarkers for the progression of cervical carcinoma. The expression of F9 increased consistently with the lesion progression from LSIL to HSIL and CC, suggesting its value as a potential biomarker for the progression of cervical cancer. CFI and AFM protein levels were obviously decreased in treated patients with CC compared with the patients before treatment, indicating their predictive value for the therapeutic efficacy. Protein function enrichment analysis showed that all these differentially expressed proteins were associated with the complement system and the coagulation cascades pathway.@*CONCLUSIONS@#We identified 5 new protein biomarkers (F9, CFI, AFM, HPR, and ORM2) for cervical precancerous lesions and for prognostic evaluation of CC, and combined detection of these biomarkers may help in the evaluation of the development and progression of CC and also in improving the diagnostic sensitivity and specificity of cervical lesions.

Cloning of New Antigen Gene MLAA-34 Promoter and Identification of Core Region in Acute Monocytic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To clone the promoter sequence of acute monocytic leukemia new antigen gene.MLAA-34 and identify its promoter core region.@*METHODS@#The full-length fragment of MLAA-34 gene promoter region was amplified by PCR, then was ligated into pGL3-Basic vector, and the recombinant plasmid was cloned. Constructed a series of MLAA-34 gene promoter 5' flanking region truncated plasmid. These recombinant plasmids were transfected into U937 and HEK293 cells, and the dual luciferase reporter gene was used to detect the promoter activity of each fragment to determine the minimum active region. Transcription factor binding sites were analyzed by bioinformatics methods.@*RESULTS@#The recombinant plasmid containing MLAA-34 promoter sequence and its truncated plasmid were successfully constructed, and the promoter activity was significantly increased as compared with the empty vector (P＜0.001). The minimal active region of MLAA-34 located between 402 bp and 200 bp. It contained multiple transcription factor binding sites such as E2F1, MZF-1, SP1, USF2 and STAT3.@*CONCLUSION@#The promoter of luciferase reporter gene has been successfully constructed with different deletion fragments of MLAA-34, and its core promoter region may contain multiple transcription factor sequence.

A new bioinformatics approach for prediction of potential tumor neoantigens based on the cancer genome atlas dataset / 生物工程学报

Tumor-specific gene mutations might generate suitable neoepitopes for cancer immunotherapy that are highly immunogenic and absent in normal tissues. The high heterogeneity of the tumor genome poses a big challenge for precision cancer immunotherapy. Mutations characteristic of each tumor can help to distinguish it from other tumors. Based on these mutations' characteristic, it is possible to develop immunotherapeutic strategies for specific tumors. In this study, a tumor neoantigen prediction scheme was proposed, in which both the intracellular antigen presentation process and the ability to bind with extracellular MHC molecule were taken into consideration. The overall design is meritorious and may help reduce the cost for validation experiments compared with conventional methods. This strategy was tested with several cancer genome datasets in the TCGA database, and a number of potential tumor neoantigens were predicted for each dataset. These predicted neoantigens showed tumor type specificity and were found in 20% to 70% of cancer patients. This scheme might prove useful clinically in future.

Outcome of complex tibial plateau fractures with Ilizarov external fixation with or without minimal internal fixation / 中华创伤杂志(英文版)

PURPOSE@#To evaluate the clinico-radiological outcome of complex tibial plateau fractures treated with Ilizarov external fixation with or without minimal internal fixation.@*METHODS@#This retrospective review was conducted on all the cases of Schatzker types V and VI tibial plateau fractures treated by Ilizarov external fixation between July 2006 and December 2015 with the minimum follow-up duration of one year. There were 30 patients: 24 males and 6 females, mean age 43.33 years, and mean follow-up 3.6 years. Three of them were open fractures; 15 cases were Schatzkertype V fractures and the other 15 type VI. According to AO/OTA classification, there were 11 type C1, 12 C2 and 7 type C3 fractures. Outcome assessment was made with American Knee Society Score (AKSS) and Rasmussen's Radiological Score (RRS) at final follow-up.@*RESULTS@#Out of the 30 cases, mini-open reduction was performed in 7, bone graft in 4, minimal internal fixation in 10 and knee temporary immobilisation in 11 patients. Mean duration of external fixation was 11.8 weeks. All fractures united. Pin tract infections in 7 and common peroneal neuropathy in 2 patients were self-limiting. Two patients had axial misalignment of less than 10°. At final follow-up, the mean knee range of motion was 114.7, mean AKSS 81.5 and mean RRS 16.7. On statistical analysis, Schatzker type of fractures, use of minimal internal fixation and knee-spanning did not influence the final outcome.@*CONCLUSION@#Ilizarov external fixator with or without minimal internal fixation provides acceptable outcome for complex tibial plateau fractures. Care must be taken to look for minor loss of alignment, especially in Type VI Schatzker fractures after removal of the fixator. However small sample size precludes firm conclusions.