Diagnostic and economic value of carcinoembryonic antigen, carbohydrate antigen 19-9, and carbohydrate antigen 72-4 in gastrointestinal cancers.

BACKGROUND: The diagnostic and economic value of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9) and CA72-4 for gastrointestinal malignant tumors lacked evaluation in a larger scale. AIM: To reassess the diagnostic and economic value of the three tumor biomarkers. METHODS: A retrospective analysis of all 32857 subjects who underwent CEA, CA19-9, CA72-4, gastroscopy and colonoscopy from October 2006 to May 2018 was conducted. Then, we assessed the discrimination and clinical usefulness. Total cost, cost per capita and cost-effectiveness ratios were used to evaluate the economic value of two schemes (gastrointestinal endoscopy for all people without blood tests vs both gastroscopy and colonoscopy when blood tests were positive). RESULTS: The analysis of 32857 subjects showed that CEA was a qualified biomarker for colorectal cancer (CRC), while the diagnostic efficiencies of CA72-4 were catastrophic for all gastrointestinal cancers (GICs). Regarding early diagnosis, only CEA could be used for early CRC. The combination of biomarkers didn't greatly increase the area under the curve. The economic indicators of CEA were superior to those of CA19-9, CA72-4 and any combination. At the threshold of 1.8 µg/L to 10.4 µg/L, all four indicators of CEA were lower than those in the scheme that conducted gas-trointestinal endoscopy only. Subgroup analysis implied that the health checkup of CEA for people above 65 years old was economically valuable. CONCLUSION: CEA had qualified diagnostic value for CRC and superior economic value for GICs, especially for elderly health checkup subjects. CA72-4 was not suitable as a diagnostic biomarker.

microRNA-106b-5p Promotes Cell Growth and Sensitizes Chemosensitivity to Sorafenib by Targeting the BTG3/Bcl-xL/p27 Signaling Pathway in Hepatocellular Carcinoma.

microRNAs (miRNAs) and miRNA-mediated regulatory networks are promising candidates in the prevention and treatment of cancer, but the role of specific miRNAs involved in hepatocellular carcinoma (HCC) remains to be elusive. Herein, we found that miR-106b-5p is upregulated in both HCC patients' tumor tissues and HCC cell lines. The miR-106b-5p expression level was positively correlated with α-fetoprotein (AFP), hepatitis B surface antigen (HBsAg), and tumor size. Overexpression of miR-106b-5p promoted cell proliferation, migration, cell cycle G1/S transition, and tumor growth, while decreased miR-106b-5p expression had opposite effects. Mechanistic studies showed that B-cell translocation gene 3 (BTG3), a known antiproliferative protein, was a direct target of miR-106b-5p, whose expression level is inversely correlated with miR-106b-5p expression. Moreover, miR-106b-5p positively regulates cell proliferation in a BTG3-dependent manner, resulting in upregulation of Bcl-xL, cyclin E1, and CDK2, as well as downregulation of p27. More importantly, we also demonstrated that miR-106b-5p enhances the resistance to sorafenib treatment in a BTG3-dependent manner. The in vivo findings showed that mice treated with a miR-106b-5p sponge presented a smaller tumor burden than controls, while the mice injected cells treated with miR-106b-5p had more considerable tumor burden than controls. Altogether, these data suggest that miR-106b-5p promotes cell proliferation and cell cycle and increases HCC cells' resistance to sorafenib through the BTG3/Bcl-xL/p27 signaling pathway.

Pre-mRNA processing factor 19 functions in DNA damage repair and radioresistance by modulating cyclin D1 in hepatocellular carcinoma.

Pre-mRNA processing factor 19 (PRP19) is elevated in hepatocellular carcinoma (HCC); however, little is known about its function in DNA damage repair in HCC. In this study, analysis of The Cancer Genome Atlas data and our tumor models after ionizing radiation (IR) treatment indicated that increased expression of PRP19 was positively correlated with DNA damage repair. Gain of PRP19 expression induced by plasmids resulted in decreases in apoptosis and double-strand breaks (DSBs), and an increase in cell survival after IR. Loss of PRP19 expression induced by small interfering RNAs resulted in the accumulation of apoptosis and DSBs, and a decrease in cell survival. Mechanistically, the effect of PRP19 on DNA damage repair was mediated by the modulation of cyclin D1 expression in HCC. PRP19 controlled the translation of cyclin D1 by modulating eukaryotic initiation factor 4E. PRP19 affected the DNA damage repair ability of cyclin D1 by interacting with the WD40 domain. The combination of PRP19 and cyclin D1 was more valuable than each single marker for predicting the prognosis of patients. Taken together, the present results demonstrate that PRP19 promotes DNA damage repair by modulating cyclin D1 expression and function, thereby contributing to the radioresistance in HCC.

MiR-93 Inhibits Trophoblast Cell Proliferation and Promotes Cell Apoptosis by Targeting BCL2L2 in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion (RSA) is a common health problem that affects 1-5% of women in reproductive age. Plenty of studies have indicated that microRNAs (miRNAs) are involved in the occurrence of miscarriage. MiR-93 has a wide range of functions in mammalian tissues and plays an important role in many diseases especially for cancers. However, it remains unknown whether miR-93 is associated with human RSA. In this report, clinical samples revealed that miR-93 expression was significantly elevated in the villi tissues of RSA patients. Upregulation of miR-93 inhibited human trophoblast cells HTR-8/SVneo cell proliferation, migration, and invasiveness, but promoted cell apoptosis in vitro. Conversely, the downregulation of miR-93 reversed these effects. Bcl-2 like protein 2 (BCL2L2), a potential target gene of miR-93, was inversely correlated with miR-93 expression in the villi of clinical samples. Furthermore, the luciferase reporter system demonstrated that miR-93 directly downregulated the expression of BCL2L2 by binding a specific sequence of its 3'-untranslated region (3'UTR). Collectively, these data strongly suggest that miR-93 regulates trophoblast cell proliferation, migration, invasive, and apoptosis by targeting BCL2L2 expression and is involved in the pathogenesis of RSA.

[Clinical observation of warm moxibustion therapy to improve quadriceps weakness after total knee arthroplasty].

OBJECTIVE: To evaluate the clinical efficacy of warm moxibustion therapy in the recovery of quadriceps muscle strength in patients undergoing total knee arthroplasty (TKA) with analgesia of the femoral nerve block (FNB). METHODS: A total of 174 patients with KOA were randomized into a warm moxibustion group and a rehabilitation group, 87 cases in each group. In the warm moxibustion group, warm moxibustion combined with conventional quadriceps strength training were used. In the rehabilitation group, conventional quadriceps strength training was given. The warm moxibustion was applied at Liangqiu (ST 34) and Zusanli (ST 36), the treatment was given twice a day, 7 days for one course, with a total of 2 courses.The quadriceps muscle strength of the two groups was recorded and compared at 24 h before FNB, 24, 48, 72 and 96 h after surgery, and the resting and exercise VAS pain scores were also recorded at the same time point. And the first time for standing up and the first straight raising time in the two groups were compared, and the occurrence of adverse reactions in the two groups were observed. RESULTS: At 24, 48, 72 and 96 h after FNB, the quadriceps muscle strength in the warm moxibustion group was better than that in the rehabilitation group (P<0.05, P<0.01). At 72 h and 96 h after FNB, the resting and exercise VAS scores of the warm moxibustion group were lower than those of the rehabilitation group (both P<0.001). The average first straight leg raising time in the warm moxibustion group was postoperative (31.03±10.78) h, and the time in the rehabilitation group was postoperative (47.23±15.78) h. The difference was statistically significant (P<0.001). The average time of the first time for standing up in the warm moxibustion group was postoperative (25.76±7.00) h, and postoperative (33.12±11.18) h in the rehabilitation group. The difference was also statistically significant (P<0.001). No adverse reactions occurred in both groups. CONCLUSION: Warm moxibustion combined with conventional quadriceps strength training can improve the symptoms of quadriceps weakness in patients with femoral nerve block after total knee arthroplasty, and accelerate the recovery of joint function, which is superior to conventional quadriceps strength training.

Hepatoid Adenocarcinoma of Stomach: Emphasis on the Clinical Relationship with Alpha-Fetoprotein-Positive Gastric Cancer.

AIMS: Both hepatoid adenocarcinoma of stomach (HAS) and alpha-fetoprotein-positive gastric cancer (AFPGC) are rare but aggressive subtypes of gastric cancer, but few studies focus on the clinicopathologic differences and prognostic factors between them because of their rarity and histologic overlap. And the significance of AFP level in HAS prognosis was not well studied. METHODS: 41 patients with AFPGC and 52 patients with HAS were included in this study. The clinicopathologic features were compared by Chi-square analysis. Prognostic factors for overall survival (OS) and disease-free survival (DFS) were analyzed with the Kaplan-Meier method. RESULTS: The patients with HAS were of a younger age compared with AFPGC, and nearly 60% of tumor located in the gastric antrum and the gastric fundus of cardia. The OS of AFPGC was shorter than that of HAS, due to a higher rate of metastasis. Furthermore, the survival analysis showed that HAS with high AFP expression (AFPHigh HAS) had a significantly poorer OS compared to HAS with low AFP expression (AFPLow HAS) (P=0.046). CONCLUSIONS: Compared with AFPGC, the patients of HAS were of a younger age and had less rate of liver and other organ metastasis. The serum AFP level was a sensitive prognostic indicator for OS. Therefore, much attention should be paid to AFPHigh HAS in clinical practice.

Haplotype-based association of two SNPs in miR-423 with unexplained recurrent pregnancy loss in a Chinese Han population.

MicroRNAs (miRNAs) regulate diverse cellular processes such as cell differentiation, proliferation and apoptosis. Mutation in miRNAs results in various pathological conditions such as inflammation, viral infections, neurodegeneration, and autoimmunity. We have evaluated the association of miR-423 rs6505162C>A and rs8067576 A>T among patients with recurrent pregnancy loss (RPL) and controls from North China. Our study found that one SNP rs6505162C>A in miR-423 coding region was associated with the increase risk of humanunexplained RPL (URPL), but no differences were found in another SNP rs8067576 A>T. However, in two-locus haplotype analysis, miR-423-CC/TT haplotype was associated with an increased risk of URPL. The level of mature miR-423 was obviously down-regulated in cells transfected with miR-423-CC/TT haplotype. miR-423-CC/TT haplotype inhibited HTR-8/SVneo cells proliferation and migration and promoted cells apoptosis. Further experiments identified that mesoderm development candidate 1 (MESDC1) was a functionally relevant target of miR-423, and its expression was reversely regulated by miR-423. More importantly, dual-luciferase assay indicated miR-423-CC/TT haplotype decreasing miR-423 expression, could up-regulate MESDC1 expression. Collectively, our data suggest that miR-423-CC/TT haplotype in pre-miR-423 may aggravate the risk of developing URPL by influencing the level of mature miR-423 and its target gene MESDC1.

A negative-doughnut distal resection margin less than 5 mm does not affect prognosis in rectal cancer.

AIM: Many issues relating to the distal margin of anterior resection of the rectum still exist. We aimed to investigate whether negative distal resection margin (DRM) and positive DRM in the main specimen with negative doughnut has equivalent prognosis in patients with rectal cancer. METHODS: We included 287 patients with rectal cancer, including 69 cases with positive margins and 218 cases with negative margins, all of whom underwent regular follow-up. Survival rate was calculated using Kaplan-Meier survival analysis, while the log-rank test was used to determine statistical difference. Prognostic factors were found using the Cox regression model. RESULTS: There was no significant difference in clinicopathological features between the two groups with the exception of tumor location. Positive findings in the DRM with negative findings in the doughnut resection do not affect the overall survival, local recurrence, or distant metastasis. Factors relating to resection margin, such as the length of resection, negative, or positive findings, were not found to be prognostic. CONCLUSION: Given postoperative pathology results with positive DRM but negative findings in the doughnut resection, a second surgery was not necessary. Instead, adjuvant radiochemotherapy and close follow-up will suffice.

Diagnostic and Prognostic Value of Circulating MicroRNAs for Esophageal Squamous Cell Carcinoma: a Systematic Review and Meta-analysis.

Background and Aim: MicroRNAs, dysregulated in the circulation of esophageal squamous cell carcinoma (ESCC) patient, have been assumed to be with great potential in the diagnosis and prognosis of esophageal cancer. We aimed to review previous articles on ESCC. Methods: A search of electronic databases was performed before Nov 12, 2017. We summarized the identification of microRNA imbalance in the blood of ESCC compared with the healthy controls, with the objective to evaluate the efficiency of microRNAs in diagnosing and forecasting ESCC. Results: A total of 35 studies investigating plasma or serum microRNAs were included in the meta-analysis. Based on the consequences of the quality assessment of each study, the articles involved were appropriate for quantitative synthesis. For diagnostic meta-analysis. The overall pooled sensitivity, specificity, and area under the curve of circulating microRNA is 0.794 (95% CI: 0.765 - 0.820), 0.779 (95%CI: 0.746 - 0.808), 0.86 (95%CI: 0.82 - 0.88). The diagnostic value of each microRNA was calculated respectively. For prognostic meta-analysis, the overall pooled hazard ratios of higher microRNA expression in circulation was 1.34 (95% CI: 1.14-1.58), which could significantly predict poorer survival in ESCC. Conclusions: Circulating microRNAs distinguish patients with ESCC from healthy controls with high sensitivity and specificity, compared to other invasive currently used screening methods. Simultaneously, there was prognostic value for the prognosis of ESCC.

Circulating miR-338-5p is a potential diagnostic biomarker in colorectal cancer.

OBJECTIVE: The expression of miR-338-5p has been reported to be upregulated in colorectal cancer (CRC) tissues. Clinicopathological features indicate that miR-338-5p overexpression correlates with the metastatic status of CRC. This study was aimed to investigate the diagnostic value of serum miR-338-5p for CRC. METHODS: Peripheral blood samples were collected from 210 participants, including 80 patients with CRC, 50 with colorectal polyps and 80 healthy controls. Serum miR-338-5p was quantified by quantitative reverse-transcription polymerase chain reaction. The area under the receiver operating characteristic curve (AUROC) was used to estimate the diagnostic value of miR-338-5p, carcinoembryonic antigen (CEA) and the combination of these two biomarkers. RESULTS: Serum miR-338-5p levels (fold change) in patients with CRC and colorectal polyps, and controls were 4.94 ± 1.13, 4.12 ± 0.75 and 3.07 ± 0.75, respectively. Significant differences were observed between the groups (P < 0.001). The AUROC of miR-338-5p was 0.923 (95% CI 0.882-0.964) and 0.845 (95% CI 0.792-0.898), respectively, for distinguishing CRC from healthy controls or from those without CRC. The AUROC of the combination of miR-338-5p and CEA was 0.932 (95% CI 0.882-0.964), with a sensitivity of 85%, a specificity of 88.8% at a cut-off value of 8.16. CONCLUSIONS: Circulating miR-338-5p may serve as a potential noninvasive diagnostic biomarker for detecting CRC. The combination of miR-338-5p and CEA exhibits the highest diagnostic value in our study.

Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer.

BACKGROUND: Many novel diagnostic biomarkers have been developed for gastric cancer (GC) recently. We chose two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models. METHODS: We reviewed the diagnostic accuracies of all microRNAs identified by previous diagnostic tests. Then appropriate microRNAs and their combinations were validated the diagnostic value. We included 80 patients with GC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was conducted, and we used three multivariate statistical analyses to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models. RESULTS: Sixty-seven published studies and 70 microRNAs were finally included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a and miR-421 were chosen to further validate their diagnostic efficiencies. Five of those microRNAs in GC patients had significantly different expression. The combination of miR-19a and miR-92a had the highest area under the curve (AUC) at 0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis performed an excellent diagnostic value and the AUC reached 1.0. CONCLUSION: There is a good potential for microRNAs and GC/MS analysis as new diagnostic methods in view of their high diagnostic value compared with traditional biomarkers.

Serum microRNA signatures and metabolomics have high diagnostic value in colorectal cancer using two novel methods.

Recently, many new diagnostic biomarkers have been developed for colorectal cancer. We chose 2 methods with high diagnostic efficiency, the detection of serum microRNA and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models. We reviewed the diagnostic value of all microRNA identified by previous diagnostic tests. We selected appropriate microRNA to validate their diagnostic efficiency, and determined the optimal combination. We included 85 patients with colorectal cancer (CRC) and 78 healthy controls (HC) and detected the expression of the microRNA. GC/MS analysis was conducted, and we used 3 multivariate statistical methods to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models. Ultimately, 62 published studies and 63 microRNA were included in this review. MiR-21, miR-29a, miR-92a, miR-125b and miR-223 were selected to further validate their diagnostic value. The serum levels of the 5 microRNA in CRC patients were significantly higher than those in the HC. The combination of miR-21, miR-29a, miR-92a and miR-125b had the highest area under the curve (AUC) at 0.952, with a sensitivity of 84.7% and a specificity of 98.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. With regard to traditional biomarkers, the AUC of CEA and CA19-9 were 0.808 and 0.705, respectively. The application prospects are good for microRNA and metabolomics as new diagnostic methods because of their high diagnostic value compared with traditional biomarkers.

Serum microRNA signatures and metabolomics have high diagnostic value in hepatocellular carcinoma.

BACKGROUND: Many new diagnostic biomarkers have been developed for hepatocellular carcinoma (HCC). We selected two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and attempted to establish appropriate models. METHODS: We reviewed the diagnostic efficiencies of all microRNAs identified by previous diagnostic tests. Then we chose appropriate microRNAs to validate the diagnostic efficiencies, and determined the optimal combination. We included 66 patients with HCC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was performed, and we used three multivariate statistical methods to establish diagnostic models. The concentration of alpha feto-protein (AFP) was determined for comparison with the novel models. RESULTS: 82 published studies and 92 microRNAs were ultimately included in this systematic review. Seven microRNAs were selected for further validation of their diagnostic efficiencies. Among which, miR-21, miR-106b, miR-125b, miR-182 and miR-224 had a significantly different expression in HCC patients. The combination of miR-21, miR-106b and miR-224 had the highest area under the curve (AUC) at 0.950 with a sensitivity of 80.3% and a specificity of 92.7%. The GC/MS analysis exhibited an excellent diagnostic value and the AUC reached 1.0. In comparison, the AUC of the traditional biomarker, AFP, was 0.755. CONCLUSION: MicroRNAs and metabolomics shows promising potential as new diagnostic methods due to their high diagnostic value compared with traditional biomarkers.

RNA binding protein Nova1 promotes tumor growth in vivo and its potential mechanism as an oncogene may due to its interaction with GABAA Receptor-γ2.

BACKGROUND: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAA receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1. METHODS: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma. In vivo tumorigenticity test was conducted in nude mice by regulation the expression of Nova1. Later, western blot and co-immunoprecipitation were carried out to verify the interaction between Nova1 and GABAARγ2 in HCC tissue. RESULTS: Immunohistochemical staining showed GABAARγ2 expression in HCC. Survival analysis showed intratumoral GABAARγ2 was an independent prognostic factor for overall survival (OS) and disease free survival (DFS). Up-regulation of Nova1 expression promotes subcutaneous HCC growth in nude mice and western blot showed the ectopic expression of Nova-1 restro-regulates the expression of GABAARγ2 and GABA. Protein level interaction of GABAARγ2 and Nova-1 was evidenced by co-immunoprecipitation. CONCLUSIONS: Nova1 interacts with GABAARγ2 not only in CNS but also in HCC. Nova1's potential mechanism as an oncogene may due to its interaction with GABAA Rγ2. A better understanding of the mechanism of Nova1 for HCC progression provides a novel target for an optimal immunotherapy against this fatal malignancy.

[Long-term follow-up for 39 newly diagnosed diffused large B-cell lymphoma patients treated by (R)-EPOCH].

The purpose of this study was to evaluate the efficacy and safety of (R)-EPOCH protocol on patients with diffuse large B-cell lymphoma(DLBCL). From February 2004 to April 2009, a total of 39 patients who suffered from DLBCL and received (R)-EPOCH protocol were enrolled in the study. The median age of patients was 52 years old. 24 patients were on stage I/II, and 15 cases were on stage III/IV. Patients with stage I/II were administered with 4-6 cycles of (R)-EPOCH, while other patients with stage III/IV received 6-8 cycles of (R)-EPOCH. DLBCL patients with bulky disease received radiotherapy after completion of chemotherapy. 39 patients received a total of 209 cycles of chemotherapy and the median chemotherapy cycles was 6 (range, 2-8 cycles). The results showed that the overall response rate of 39 assessable patients was 87.2%, including 28 patients (71.8%) in complete remission (CR) and 6 patients (15.4%) in partial remission(PR). With a median follow-up of 57.7 months, the 1-year overall survival rate was 81.8%, while 70.9% for 3-year and 58.8% for 5-year. The major toxicity of (R)-EPOCH protocol was hematologic toxicity and the incidence of grade III-IV neutropenia and anemia were 29.2% and 14.4%, respectively. Other toxicities were mild, no treatment-related deaths occurred. At the end of follow-up,no secondary tumors occurred. It is concluded that (R)-EPOCH protocol is a effective and safe protocol for the patients with DLBCL.

[Significance of low molecular weight urinary protein for assessment of early renal damage in patients with multiple myeloma].

This study was purposed to evaluate the clinical significance of low molecular weight urinary proteins for diagnosis of early renal damage in patients with multiple myeloma (MM). Medical records of 278 patients with MM in Nanjing School of Clinical Medicine from January 2004 to May 2012 were analyzed retrospectively. These patients were divided into 3 groups: glomerular damage group (n = 143), tubular damage group (n = 114) and normal group (n = 21). The clinical and laboratorial data were compared among them. The correlations of urinary retinol-binding protein (RBP) or urinary N-acetyl-ß-D-amino-glucosaminidase (NAG) with blood urea nitrogen (BUN), Scr, blood cystatin-C (Cys-C), clearance of creatinine (Ccr), 24 h protein uria and 24 h urine light chains were further analyzed, and the correlation of renal tubulointerstitial lesion scores with low molecular weight urinary proteins in 61 patients were also analyzed. The area under curve (ROC curve) was used to evaluate and compare the discrimination of urinary RBP and urinary NAG. The results showed that glomerular damage group had higher urinary RBP than tubular damage group. However, glomerular damage group had lower urinary NAG than tubular damage group. The two groups had higher urinary RBP and urinary NAG than that in normal group. Urinary RBP related positively to the level of Scr, BUN, Cys-C, 24 h proteinurias and related negatively to the level of Ccr. Urinary NAG related positively to the level of 24 h proteinurias, Ccr and related negatively to the level of Cys-C. Renal tubulointerstitial lesions were significantly correlated with urinary RBP, but weakly correlated with urinary NAG. It is concluded that urinary RBP significantly correlates with renal tubular damage. Compared with urinary NAG, urinary RBP can better assess the extent of renal damage, and has higher specificity.

Lymphangiogenesis in non-Hodgkin's lymphoma and its correlation with cyclooxygenase-2 and vascular endothelial growth factor-C.

We aimed to investigate the correlations between lymphangiogenesis, cyclooxygenase (COX)-2 and vascular endothelial growth factor-C (VEGF-C) in non-Hodgkin's lymphoma (NHL) and their associations with the clinical parameters of patients. A total of 75 patients diagnosed with NHL were enrolled in this study. Of the 75 patients, 14 (18.7%) had low-grade and 61 (81.3%) had aggressive lymphoma. We examined the immunohistochemical expression of COX-2 and VEGF-C and estimated lymphangiogenesis by counting lymphatic vessels expressing lymph vessel endothelial hyaluronan receptor-1 (LYVE-1). Our results showed that lymphatic vessel density (LVD) was positive in 59.0% of the cases with aggressive morphology, while the LVD positive rate of indolent lymphoma was only 28.6% (P=0.039). Both COX-2 and VEGF-C were correlated with lymphangiogenesis (P=0.030 and 0.000, respectively). The expression levels of COX-2 and VEGF-C were significantly correlated (P=0.015). LVD, COX-2 and VEGF-C were not correlated with the gender, age, lactate dehydrogenase (LDH) levels, ß2 microglobulin (ß2M) levels, extranodal involvement, disease stage, B symptoms or international prognostic index of the patients. In conclusion, lymphangiogenesis was correlated with aggressive histology in NHL. COX-2 and VEGF-C are inducers of lymphangiogenesis and their expression levels were correlated in NHL.

[Relationship between the catalysis of Bence Jones protein and renal impairment in patients with multiple myeloma].

This study was purposed to investigate the relationship between the catalysis of Bence Jones protein (BJP) in urine of patients with multiple myeloma(MM) and toxicity on the renal proximal tubular cells in vitro, and to explore the potential mechanism for the toxicity of BJP to renal impairment in patients with MM. The Michaelis-Menten constant (K(m)) and catalytic constant (k(cat)) of the amidase activity of BJP was calculated by Hanes equation. The LLC-PK1 cells were cultured with different concentration of BJP for 24 h, then proliferation of the cells were determined by MTT method and apoptosis were determined by flow cytometry. The results showed that the BJP from the MM patients with renal impairment significantly inhibited cell proliferation, as compared with that from MM patients without renal impairment. The BJP with higher k(cat) had higher toxicity to LLC-PK1 cells. BJP could induce apoptosis and necrosis of LLC-PK1 cells when reached a certain concentration and this effect enhanced with increase of BJP concentration. It is concluded that the catalysis of BJP and its toxicity to renal tubular epithelial cells has a positive correlation, and toxic effect of BJP on renal tubular epithelial cells results from inhibiting proliferation and inducing apoptosis and necrosis of the cells, which may be one of renal impairment mechanisms in MM patients.

[The clinical significance of serum free light chain in primary systemic amyloidosis].

OBJECTIVE: To evaluate the diagnostic and therapeutic significance of serum free light chain (sFLC) in primary systemic(AL) amyloidosis. METHODS: Twenty-five patients with AL amyloidosis, including 18 men and 7 women with a mean age of 54 (47 - 77) years old, were enrolled from October, 2005 to May, 2010. sFLC was measured by immunoturbidimetric assay. The type of monoclonal light chain was judged upon sFLC κ/λ and its sensibility was compared with serum immunofixation and immunohistochemical analysis. Four patients were treated with M(T)D (melphalan/thalidomide,and dexamethasone), one with VD (velcade and dexamethasone) and four with high-dose melphalan followed by autologous stem cell support. The changes of sFLC were serially determined before and after treatment. RESULTS: Among the 25 patients with AL amyloidosis, two were κ light chains of precursor protein and 23 were λ light chains. Mean plasma cell in bone marrow was 3.5% (0 - 15%). Nineteen (76%) patients had abnormal elevated sFLC and abnormal κ/λ ratios, and 17(68%) patients with immunofixation positive. The sFLC test had similar sensitivity as serum immunofixation (P = 0.727). Twenty-one (84%) patients were shown to have either κ or λ immunoreactive amyloid deposits on biopsied tissues. The sFLC test combined with serum immunofixation allowed the M protein to be detected in 22 (88%) patients. The positive rates of immunohistochemical analysis combined with sFLC test and/or serum immunofixation were 96%. Four patients with hematologic response showed obvious improvement in visceral organ involvement, but illness of 5 patients without hematologic response kept stable or progressed. CONCLUSIONS: sFLC test is a sensitive qualitative and quantitative method to detect M protein. Preliminary data show the patients with obvious sFLC level decrease and/or κ/λ recovery to normal may have a high percentage of improved organs function. sFLC is critical index in diagnosing AL amyloidosis, which might help efficacy assessment.

[Clinic-pathologic characteristics of autoimmune diseases combined with non-Hodgkin's lymphoma].

This study was aimed to investigate the clinical characteristics and treatment of patients with autoimmune disease combined with non-Hodgkin lymphoma (NHL). The clinical characteristics and pathologic patterns of 6 patients with NHL who concurrently suffered from autoimmune diseases were analysed retrospectively from aspects of clinical course, pathologic features, and therapy. Treatment outcomes for autoimmune diseases and NHL were observed. The results showed that 6 patients included 4 females and 2 males, range in age from 28 to 65 years with a median age of 56 years. The autoimmune diseases are Sjogren's syndrome (SS, 2 cases), rheumatoid arthritis (RA, 2 cases), ulcerative colitis (UC, 1 case) and Crohn's disease (CD, 1 case). The NHL diseases located not only in the lymph node (n = 3) but also in extranodal sites (n = 3). Histologically, 3 cases were diffuse large B cell lymphoma (DLBCL), 2 cases were extranodal nasal NK/T lymphoma (ENKL) and 1 case was peripheral T cell lymphoma, not otherwise specified. Based on CD10, Bcl-6 and MUM1 expression patterns, all 3 DLBCL were classified as non-GC subtype. EBER positive tumor cells were detected in 2 case of ENKL. 5 patients achieved a complete remission (83%) and 1 patient was primary drug-resistant after CHOP chemotherapy or involved radiotherapy. Median survival from the time of lymphoma diagnosis was 3 years. 1 patient showed clinical improvement of the SS symptoms, 2 patients (CD and UC) showed stable state of disease and 2 patients with RA and 1 patient with SS needed continuing treatment for their autoimmune diseases after chemotherapy for NHL. It is concluded that the development of NHL is one of the most serious complications in patients with autoimmune diseases. There is an increased frequency of non-GC subtype DLBCL. CHOP combined with or without radiotherapy proves to be effective for autoimmune disease patients with aggressive NHL but ineffective for concurrent autoimmune diseases.