Matrix metalloproteinase-2 promoter and tissue inhibitor of metalloproteinase-2 gene polymorphisms in non-Hodgkin's lymphoma.

Single nucleotide polymorphisms in the promoter regions of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMP) genes are associated with an adverse outcome in some cancers. We examined three polymorphisms: -1306C/T and -735C/T in MMP-2 and -418G/C in the TIMP-2 gene, using chain reaction restriction fragment length polymorphism typing analysis in 575 patients with non-Hodgkin's lymphoma (NHL). We examined the possible correlations between the three polymorphisms (MMP-2 (-1306C/T and -735C/T) and TIMP-2 gene (-418G/C)) and the clinical significance and survival rate in patients with NHL. The incidence of the CT, TT+CT genotypes and T allele of -735C/T was significantly higher in stage III and IV patients compared to stage I and II patients. In cases with bone marrow infiltration, the TT genotypes of the -1306C/T gene were significantly less frequent compared to CC genotypes. The CT, TT and CT+TT genotypes and T allele in patients exhibiting the -1306C/T polymorphism were significantly less frequent in patients with a large tumor size compared to a smaller tumor. The TT genotypes of the -735C/T polymorphism were more common in patients with a large tumor compared to those with a smaller tumor. The frequency of the -1306C/-735T haplotype in patients with a smaller tumor size was significantly higher compared to patients with a large tumor. The -1306T/-735C and -1306C/-735C haplotypes were significantly less frequent in patients with B-symptoms compared to those without. Interestingly, patients with the -735CT genotype exhibited a lower rate of survival. Our results demonstrate that certain MMP-2 and TIMP-2 gene polymorphisms potentially effect the progression or assessment of prognosis for NHL. This research warrants further, larger scale studies.

Development of a Novel Clinical Prognostic Model for Patients With Angioimmunoblastic T-Cell Lymphoma.

In this study we aimed to identify a set of prognostic factors for angioimmunoblastic T-cell lymphoma (AITL) and establish a novel prognostic model. The clinical data of 64 AITL patients enrolled to the Fourth Hospital of Hebei Medical University (from 2012 Jan to 2017 May) were retrospectively analyzed. The estimated 5-year overall survival and progression-free survival of this cohort of patients were 45.8% and 30.8%, respectively. Univariate analysis showed that age > 60 years, performance status ≥2, Ann Arbor stage III/IV, lactate dehydrogenase > 250 U/L, serum albumin (ALB) < 30 g/l, Coombs test positive, and Ki-67 rate ≥ 70% were significantly associated with poor prognosis. Multivariate analysis demonstrated that age > 60 years, ALB < 30 g/l, Ki-67 rate ≥ 70%, and Coombs test positive were independent prognosis factors for AITL. Here a new prognostic model, named as AITLI, was constructed using the top 5 significant prognostic factors for AITL prognostic prediction. The AITL patients were stratified into 3 risk groups: low, intermediate, and high risk groups. The new prognostic model AITLI showed better performance in predicting prognosis than the International Prognostic Index (IPI) and the prognostic index for PTCL, not otherwise specified (PIT) that were wisely used to predict the outcome for patients with other subtypes of lymphoma.

[Correlation of Gemin 3 SNP in the microRNA Biosynthesis Pathway with Risk and Prognosis of Patients with Non-Hodgkin's Lymphoma].

OBJECTIVE: To evaluate the correlation of single nucleotide polymorphisms (SNP) of Gemin 3(rs197412) in the miRNA biosynthesis with NHL cancer risk and overall prognosis. METHODS: miR-SNP were genotyped using PCR-ligase detection reaction(LAR, LCR) in NHL group of 230 non-Hodgkin lymphoma (NHL) patients and in control group of 120 healthy persons. The survival curves were drawn using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed by using a Cox proportional hazards model. RESULTS: The rs197412 genotype distribution difference was not statistically significant, in NHL and control group; the survival time of patients carrying the rs197412 TT genotype was significantly longer than that of the patients carrying the CC+CT genotype (P=0.007). In addition, rs197412 was independent from the survival of NHL patients by multivariate analysis (RR: 2.138,95% CI: 1.303-3.508, P<0.01). CONCLUSION: The single nucleotide polymorphisms of Gemin 3 (rs197412) in the miRNA processing are not related with NHL risk, but that may affect NHL survival.

Single nucleotide polymorphisms of microRNA processing genes and outcome of non-Hodgkin's lymphoma.

OBJECTIVE: microRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) in miRNA-processing machinery genes can affect cancer risk, treatment efficacy, and patients' prognosis by mediating the expression of targeted genes. Five miR-SNPs in miRNA processing machinery genes, including XPO5 (rs11077), RAN (rs14035), TNRC6B (rs9623117), GEMIN3 (rs197412), and GEMIN4 (rs2740348), in 168 non-Hodgkin's lymphoma (NHL) patients were evaluated for their association with the cancer risk and outcomes associated with NHL. MATERIALS AND METHODS: miR-SNPs were genotyped using polymerase chain reaction-ligase detection reaction. The survival curves were calculated using the Kaplan-Meier method, and comparisons between the curves were made using the log-rank test. Multivariate survival analysis was performed using a Cox proportional hazards model. RESULTS: Among the five SNPs, only rs197412 located in the coding region of the GEMIN3 gene was identified; it was independently associated with overall survival in NHL patients, as determined by multivariate analysis (relative risk: 1.649; 95% confidence interval: 1.110-2.449; P=0.013). The prognostic value of this miR-SNP in patient outcomes was also observed in the diffuse large B-cell lymphoma and T-cell lymphoma NHL subtypes. CONCLUSION: Our results suggested that the specific genetic variants observed in the miRNA machinery genes may affect NHL survival.

Sequence polymorphisms in the D-loop region of mitochondrial DNA and outcome of non-Hodgkin lymphoma.

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) might be associated with cancer risk and disease outcome. We have identified 140 SNPs including 26 SNPs with frequency distribution of minor allele greater than 5% in a case-control study for non-Hodgkin lymphoma patients previously. In this study, we assessed the predictive power of D-loop SNPs in NHL patients. Five SNP sites were identified by log-rank test for statistically significant prediction of NHL survival in a univariate analysis. In an overall multivariate analysis, allele 16304 was identified as an independent predictor of NHL outcome. The survival time of NHL patients with 16304C was significantly shorter than that of patients with 16304T (relative risk, 0.513; 95% CI, 0.266-0.989; p = 0.046). The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of a poor disease outcome.

Identification of sequence polymorphisms in the D-loop region of mitochondrial DNA as a risk factor for non-Hodgkin lymphoma.

Accumulation of single nucleotide polymorphisms (SNPs) in the displacement loop (D-loop) of mitochondrial DNA (mtDNA) may be associated with an increased cancer risk. We investigated the non-Hodgkin lymphoma (NHL) risk profile of D-loop SNPs in a case-control study. The minor alleles of nucleotides 73A/G, 263A/G, 315C/C insert were associated with a decreased risk for NHL. The minor alleles of the nucleotides 200G/A were specifically associated with the risk of diffuse large B-cell lymphoma, whereas the minor allele of nucleotides 16362C/T and 249Del/A was specifically associated with the decreased risk of T-cell lymphoma. In conclusion, SNPs in mtDNA are potential modifiers of NHL risk. The analysis of genetic polymorphisms in the mitochondrial D-loop can help identify subgroups of patients who are at a high risk of developing NHL.

A polymorphism at the microRNA binding site in the 3' untranslated region of C14orf101 is associated with non-Hodgkin lymphoma overall survival.

MicroRNAs (miRNAs) can bind to the 3' untranslated regions (UTRs) of messenger RNAs, where they interfere with translation and thereby regulate cell differentiation, apoptosis, and tumorigenesis. Genetic polymorphisms in the 3' UTRs targeted by miRNAs alter the strength of miRNA binding in a manner that affects the behavior of individual miRNAs. In this study, four miRNA binding-site single nucleotide polymorphisms (SNPs) located in the 3' UTR of RYR3 (rs1044129), C14orf101 (rs4901706), KIAA0423 (rs1053667), and GOLGA7 (rs11337) were genotyped in non-Hodgkin lymphoma (NHL) patients to assess their relationships with cancer risk and overall survival. rs4901706, located in the 3' UTR of C14orf101, was shown to be independently related to overall survival in NHL patients by multivariate analysis (relative risk, 1.770; 95% CI, 1.046-2.996; P = 0.033). The prognostic value of this SNP on tumor overall survival was supported in diffuse large B-cell lymphoma patients with a P value of 0.095 and validated in T-cell lymphoma patients with a P value of 0.037.

Prognostic value of microRNA 502 binding site SNP in the 3'-untranslated region of the SET8 gene in patients with non-Hodgkin's lymphoma.

AIMS AND BACKGROUND: A number of important cancer-associated covalent modifications of histone genes can be regulated by microRNAs (miRNAs) that bind to their target sites in the 3'-untranslated regions. We evaluated the effect of single-nucleotide polymorphisms (SNPs) at the miR-502 binding site in the 3'-untranslated region of the SET8 gene on the clinical outcome of non-Hodgkin's lymphomas (NHL). METHODS AND STUDY DESIGN: The miR-502 binding site SNP of rs16917496 in the 3'-untranslated region of SET8 was genotyped with the ligation detection reaction method. The association of rs16917496 with NHL survival was calculated with the log-rank test using the Kaplan-Meier method. Multivariate survival analysis was performed using a Cox proportional hazards model. RESULTS: Patients carrying the rs16917496 CC genotype had a significantly longer survival time than patients carrying the CT genotype (P = 0.043) or TT genotype (P = 0.086). In addition, rs16917496 was associated independently with the survival of NHL patients in multivariate analysis (CC vs TT, 95% CI: 1.021-3.279, RR: 1.829, P = 0.043; CC vs CT, 95% CI: 1.026-3.339, RR: 1.851, P = 0.041). The association of rs16917496 with NHL survival was further identified in the peripheral T cell lymphoma (pTCL) subtype of NHL at borderline statistically significant levels (P = 0.069). CONCLUSION: Our study provides evidence that the SNP in the miRNA binding site of the SET8 3'-untranslated region seems to influence survival of NHL. It may have possible prognostic and survival value in the clinic.

A miR-SNP of the KRT81 gene is associated with the prognosis of non-Hodgkin's lymphoma.

MicroRNA (miRNA), which plays an important role in tumorigenesis, can regulate post-transcriptional gene expression by binding to the 3' untranslated regions (3'-UTRs) of messenger RNAs and repressing its translation. Several single nucleotide polymorphisms (SNPs) are considered to have significant impacts on susceptibility of the role these genetic polymorphisms in development of carcinogenesis through that mechanism. But few of them focus their impact on non-Hodgkin's lymphoma (NHL). Therefore, we conducted this study to investigate the associations between the genetic variants and cancer risk or cancer outcome. MiRNA-related single nucleotide polymorphism (miR-SNP) sites rs3660 of KRT81, rs1044129 of RYR3, rs4901706 of f101, and rs1053667 of KIAA0423 were selected and analyzed in 210 patients in NHL to evaluate their association with cancer risk and prognosis. The results indicated that none of them is associated with the cancer risk in NHL. Otherwise KRT81 rs3660 GG type is associated with a shorter survival time (p=0.012), after being assessed by multivariate Cox analyses, its effect on prognosis was verified (p=0.003). It suggests that KRT81 rs3660 GG type is an independent prognostic marker in NHL.

Primary giant lymphoma of the right thigh: A case report and brief review of the literature.

Primary soft tissue non-Hodgkin lymphoma (NHL) of the extremities is very rare. The clinical features of NHL mimic those of other soft tissue tumors, particularly sarcoma; however, they should be differentiated, as the treatment and prognosis are completely different. In this study, the case of a 68-year-old female with a giant mass, movement disorder, numbness and painful sensations in the right thigh is presented. Magnetic resonance (MR) imaging revealed a huge circle-shaped mass. Fine needle aspiration cytology (FNAC) of the tumor demonstrated neoplastic small, round cells. The tentative diagnosis was of a mesenchymal sarcoma. The right thigh was amputated. On histological examination of the amputated extremity, the diagnosis was found to be large B cell lymphoma. Primary soft tissue NHL of the extremities is a systemic malignant disease and is sensitive to chemo-therapy and radiotherapy. The histological diagnosis should be identified as far as possible before the tumor is widely excised.

Association of VEGF genetic polymorphisms with the clinical characteristics of non-Hodgkin's lymphoma.

PURPOSE: Vascular endothelial growth factor (VEGF) plays an important role in tumor angiogenesis and cancer progression. The VEGF genetic polymorphisms were shown to be independently associated with an adverse outcome in various malignancies. We investigated the possible associations of two polymorphisms (-2578C/A and +936C/T) in the VEGF gene with the clinicopathologic parameters for patients with non-Hodgkin's lymphoma (NHL). METHODS: We studied the genotype and allele frequencies of the -2578C/A and +936C/T polymorphism in DNA samples of 431 patients with NHL using restriction fragment length polymorphism typing analysis. RESULTS: The -2578A allele was significantly associated with less frequent clinical staging III, IV and bone marrow involvement (The odds ratio (OR) 0.59; 95% confidence interval (CI) 0.43-0.82; and OR 0.66; 95% CI 0.48-0.91, respectively). The CA and CA + AA genotype of the -2578C/A were significantly associated with less frequent bone marrow involvement than CC genotypes (OR 0.57; 95% CI 0.38-0.86; and OR 0.57; 95% CI 0.39-0.85, respectively). The TT genotype of the +936C/T polymorphism was significantly associated with less frequent T cell histological type, clinical staging III, IV and bone marrow involvement (OR 0.25; 95% CI 0.07-0.89; OR 0.37; 95% CI 0.15-0.89; and OR 0.31; 95% CI 0.10-0.96, respectively). The +936 T allele was marginally associated with less frequent bone marrow involvement and with Clinical staging III, IV (OR 0.71; 95% CI 0.49-1.01; and OR 0.70; 95% CI 0.49-1.00, respectively). None of the evaluated genotypes of -2578C/A was significantly associated with the gender, age, tumor size, B symptoms and immunohistological subtype. No significant associations between the genotype of +936C/T and the clinicopathologic variables, gender, age, tumor size and B symptoms were ascertained. Both of the -2578C/A and +936C/T polymorphisms were not related to the patients' overall survival. CONCLUSION: We present the first data on VEGF gene polymorphisms in NHL. Our findings support the hypothesis that the -2578 CA and CA + AA and +936 TT VEGF genotypes and -2578A and +936T alleles are associated with decreased risk for invasion. But the investigated VEGF gene polymorphisms were not associated with prognosis in patients with NHL.

[Photochemical Effect of the Photosensitizer Hemoporphyrin Derivative on MCF-7 Cell Line and Umbilical Cord Blood Hematopoietic Cells]

To study the effect of hemoporphyrin derivative(HPD) combined with laser irradiation on human breast tumor cell line MCF-7 and normal human umbilical cord blood-derived hematopoietic cells by using MTT assay. The results showed that HPD plus laser irradiation was more efficient for killing MCF-7 cells than normal human umbilical cord blood-derived hematopoietic cells. The photochemical effect with laser irradiation were higher than with light irradiation and it's effect on MCF-7 cells was higher gradually with the increase of HPD concentration.