Modelling the dynamic gas/particle partitioning process of semi-volatile organic compounds emitted from point sources: Quantitative analysis and impact assessment.

The deleterious impact of pollution point sources on the surrounding environment and human has long been a focal point of environmental research. When considering the local atmospheric dispersion of semi-volatile organic compounds (SVOCs) around the emission sites, it is essential to account the dynamic process for the gas/particle (G/P) partitioning, which involves the transition from an initial state to a steady state. In this study, we have developed a model that enables the prediction of the dynamic process for G/P partitioning of SVOCs, particularly considering the influence from emission. It is important to note that the dynamic processes of the concentrations of SVOCs in particle phase (CP) and in gas phase (CG) differ significantly. These differences arise due to the influence of two critical factors: particulate proportion of SVOCs in the emissions (ϕ0) and octanol-air partitioning coefficient (KOA). The validity of our model was assessed by comparing its predictions of the extremum value of the G/P partitioning quotient (KP) with the results obtained from the steady-state model. Remarkably, the characteristic time (tC), used to evaluate the timescale required for SVOCs to reach steady state, demonstrated different variations with KOA for CP and CG. Additionally, the values of tC were quite different for CP and CG, which were markedly influenced by ϕ0. For some SVOCs with high KOA values, it took approximately 35 h to reach steady state. Furthermore, it was found that the time to achieve 95 % of steady state (t95 ≈ 3tC) could reach approximately 105 h. This duration is sufficient for chemicals to disperse from their emission site to the surrounding areas. Therefore, it is crucial to consider the dynamic process of G/P partitioning in local atmospheric transport studies. Moreover, the influence of ϕ0 should be incorporated into future investigations examining the dynamic process of G/P partitioning.

Downregulation of UBB potentiates SP1/VEGFA-dependent angiogenesis in clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) presents a unique profile characterized by high levels of angiogenesis and robust vascularization. Understanding the underlying mechanisms driving this heterogeneity is essential for developing effective therapeutic strategies. This study revealed that ubiquitin B (UBB) is downregulated in ccRCC, which adversely affects the survival of ccRCC patients. UBB exerts regulatory control over vascular endothelial growth factor A (VEGFA) by directly interacting with specificity protein 1 (SP1), consequently exerting significant influence on angiogenic processes. Subsequently, we validated that DNA methyltransferase 3 alpha (DNMT3A) is located in the promoter of UBB to epigenetically inhibit UBB transcription. Additionally, we found that an unharmonious UBB/VEGFA ratio mediates pazopanib resistance in ccRCC. These findings underscore the critical involvement of UBB in antiangiogenic therapy and unveil a novel therapeutic strategy for ccRCC.

The categorizations of vasculogenic mimicry in clear cell renal cell carcinoma unveil inherent connections with clinical and immune features.

Background: Clear cell renal cell carcinoma (ccRCC) stands as the prevailing variant kidney cancer in humans. Unfortunately, patients with disseminated RCC at diagnosis often have a diminished prognosis. Rapid tumor growth necessitates efficient blood supply for oxygen and nutrients, involving the circulation of blood from vessels to tumor tissues, facilitating tumor cell entry into the extracellular matrix. Vasculogenic mimicry (VM) significantly contributes to tumor growth and metastasis. Within this investigation, we identified vasculogenic mimicry-related genes (VMRGs) by analyzing data from 607 cases of kidney renal clear cell carcinoma (KIRC) in The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/). These findings offer insights into ccRCC progression and metastasis. Method: We identified VMRGs-related subtypes using consistent clustering methods. The signature of the VMRGs was created using univariate Cox regression and LASSO Cox regression analyses. To evaluate differences in immune cell infiltration, we employed ssGSEA. Afterwards, we created an innovative risk assessment model, known as the VM index, along with a nomogram to forecast the prognosis of ccRCC. Additionally, we verified the expression of an important gene related to VM, peroxiredoxin 2 (PRDX2), in tissue samples. Furthermore, we assessed the sensitivity to drugs in various groups by utilizing the pRRophetic R package. Results: Significant predictors of survival rates in both high- and low-risk groups of KIRC patients were identified as VMRGs. The independent prognostic factors for RCC were confirmed by both univariate and multivariate Cox regression analyses, validating VMRG risk signatures. Differences were observed in drug sensitivity, immune checkpoint expression, and responses to immune therapy between patients classified into high- and low-VMRG-risk groups. Our nomograms consistently demonstrated precise predictive capabilities. Finally, we experimentally verified PRDX2 expression levels and their impact on prognosis. Conclusion: The signature predicts patient prognosis and therapy response, laying the groundwork for future clinical strategies in treating ccRCC patients.

The clinical significance, immune infiltration, and tumor mutational burden of angiogenesis-associated lncRNAs in kidney renal clear cell carcinoma.

Background: Poor prognosis of kidney renal clear cell carcinoma (KIRC) is often related to angiogenesis. The lncRNAs that regulate angiogenesis could also affect the prognosis of KIRC. It is meaningful for us to use lncRNAs related to angiogenesis to construct a generic, individualized prognostic signature for patients with KIRC. Methods: We identified eight angiogenesis-associated genes (AAGs) by differential expression analysis and univariate Cox regression from The Cancer Genome Atlas dataset, including 537 KIRC samples and 72 normal samples. In total, 23 prognostic lncRNAs were screened out after Pearson correlation analysis and univariate Cox regression analysis. Then, we performed least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox regression to establish a four-AAG-related lncRNA prognostic signature. Results: The risk score was calculated for each KIRC patients by using a four-AAG-related lncRNA prognostic signature. We divided the KIRC patients into high- and low-risk groups by the median of the risk score. It was confirmed that the AAG-related lncRNA prognostic signature has good prognostic value for KIRC patients by time-dependent receiver operating characteristic and Kaplan-Meier survival analysis. We identified 3,399 differentially expressed genes between the high- and low-risk groups and performed their functional enrichment analyses. The AAG-related lncRNA prognostic signature was an independent prognostic predictor for KIRC patients and was used to perform a combined nomogram. We reevaluated them in terms of survival, clinic characteristics, tumor-infiltrating immune cells and tumor mutation burden. Conclusion: Our research indicates that the AAG-related lncRNA prognostic signature is a promising and potential independent prognostic indicator for KIRC patients. Then, it could offer new insights into the prognosis assessment and potential treatment strategies of KIRC patients.

Tumor-associated macrophage-derived exosomes transmitting miR-193a-5p promote the progression of renal cell carcinoma via TIMP2-dependent vasculogenic mimicry.

Previous studies have investigated whether tumor-associated macrophages (TAMs) play tumorigenic and immunosuppressive roles to encourage cancer development, but the role of TAMs in regulating vasculogenic mimicry (VM) in clear-cell renal cell carcinoma (ccRCC) cells has not been completely clarified. We conducted immunostaining of the tumor-associated macrophage biomarkers CD68/CD163 and double staining for PAS/CD31 in ccRCC human specimens to find that higher TAM infiltration was positively correlated with VM formation. Then we demonstrated that TAM-derived exosomes downregulate TIMP2 expression in RCC cells to promote VM and invasion by shuttling miR-193a-5p. Mechanistic analysis indicated that HIF-1α upregulation in macrophages could transcriptionally increase miR-193a-5p expression. Exosome-shuttled miR-193a-5p then targeted the 3' untranslated region (UTR) of TIMP2 mRNA to suppress its translation. A preclinical study using an in vivo orthotopic xenograft model of ccRCC in mice substantiated that TAM-derived exosomes enhance VM and enable tumor progression, which confirmed our in vitro data. Suppressing TAM-derived exosomal miR-193a-5p successfully inhibited tumor progression and metastasis. Overall, miR-193a-5p from TAM-derived exosomes downregulates the TIMP2 gene to facilitate the development of RCC, which provides a novel perspective for developing therapeutic strategies for RCC.

Efficacy of intravitreal conbercept injection on short- and long-term macular edema in branch retinal vein occlusion.

AIM: To observe the best-corrected visual acuity (BCVA) and central foveal thickness (CFT) repeatedly after the intravitreal injection of conbercept (IVC) for treating cystoid macular edema (CME) in branch retinal vein occlusion (BRVO) and explore the relationship between the duration of CME and visual outcome. METHODS: Subgroup analysis was performed to compare short-term (within 90d of CME onset) and long-term (over 90d of CME onset) macular edema in BRVO. After an initial IVC, a pro re nata (PRN) strategy was performed according to the recurrence of CFT or decrease of BCVA. Analysis of variance using repeated measurements, statistical analysis following indicators including BCVA and CFT collected at baseline and 1, 3, and 6mo after IVC. RESULTS: Among the 60 cases included in this retrospective study, 36 were short-term CME, and 24 were long-term CME. There were statistical significances between and within groups of the BCVAs at different time points (P<0.001). The interaction was found between group and time (P=0.006), indicating the difference in the speed of BCVA improvement between groups. In particular, the improvement speed of BCVA in the short-term CME group was faster than that in the long-term CME group. There were significant differences between and with groups of the CFT at different time points (P<0.001). However, the interaction between group and time in relation to CFT had no significant differences (P=0.59). CONCLUSION: IVC treatment for CME following BRVO is effective and safe. The duration of CME before treatment is a significant predictor of the visual outcomes of patients with BRVO. The improvement of vision might be faster with early IVC treatment than with delayed treatment.

The relationship between endorsing reporting guidelines or trial registration and the impact factor or total citations in surgical journals.

BACKGROUND: A journal's impact factor (IF) and total citations are often used as indicators of its publication quality. Furthermore, journals that require authors to abide by reporting guidelines or conduct trial registration generally have a higher quality of reporting. In this study, we sought to explore the potential associations between the enforcement of reporting guidelines or trial registration and a surgical journal's IF or total citations in order to find new approaches and ideas to improve journal publication quality. METHODS: We examined surgical journals from the 2018 Journal Citation Report's Expanded Scientific Citation Index to quantify the use of reporting guidelines or study registration. We reviewed the "instructions for authors" from each journal and used multivariable linear regression analysis to determine which guidelines were associated with the journal IF and total citations. The dependent variable was the logarithm base 10 of the IF in 2018 or the logarithm base 10 of total citations in 2018 (the results were presented as geometric means, specifically the ratio of the "endorsed group" results to "not endorsed group" results). The independent variable was one of the requirements (endorsed and not endorsed). Models adjust for the publication region, language, start year, publisher and journal size (only used to adjust total citations). RESULTS: We included 188 surgical journals in our study. The results of multivariable linear regression analysis showed that journal IF was associated (P < 0.01) with the following requirements: randomized controlled trial (RCT) registration (geometric means ratio (GR) = 1.422, 95% CI [1.197-1.694]), Consolidated Standards of Reporting Trials (CONSORT) statement (1.318, [1.104-1.578]), Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) statement (1.390, [1.148-1.683]), Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement (1.556, [1.262-1.919]), Standards for Reporting Diagnostic Accuracy (STARD) statement (1.585, [1.216-2.070]), and Meta-analysis of Observational Studies in Epidemiology (MOOSE) statement (2.113, [1.422-3.133]). We found associations between the endorsement of RCT registration (GR = 1.652, 95% CI [1.268-2.153]), CONSORT (1.570, [1.199-2.061]), PRISMA (1.698, [1.271-2.270]), STROBE (2.023, [1.476-2.773]), STARD (2.173, [1.452-3.243]), and MOOSE statements (2.249, [1.219-4.150]) and the number of total citations. CONCLUSION: The presence of reporting guidelines and trial registration was associated with higher IF or more total citations in surgical journals. If more surgical journals incorporate these policies into their submission requirements, this may improve publication quality, thus increasing their IF and total citations.

Requirements for Study Registration and Adherence to Reporting Guidelines in Surgery Journals: A Cross-Sectional Study.

BACKGROUND: Reporting guidelines and study registration can minimize bias and improve the reporting quality of biomedical research, but may not be fully utilized. The objective of this study was to investigate the policies of surgery journals as for reporting guidelines and study registration and explore associated journal characteristic variables. METHODS: Study samples were obtained from the Expanded Science Citation Index of the 2018 Journal Citation Reports (surgery category). The online guides for authors were browsed to identify which journals endorsed reporting guidelines and study registration. The predictors related to the endorsement were explored by using Chi-square test and multivariate logistic regression analysis, respectively. RESULTS: One hundred and eighty-eight surgery journals were included in our study. One hundred and sixty-three journals (86.7%) endorsed reporting guidelines and 103 journals (54.8%) endorsed study registration. About reporting guidelines, ICMJE (International Committee of Medical Journal Editors) recommendations were the most frequently endorsed (n = 155, 82.4%) by journals, followed by CONSORT (Consolidated Standards of Reporting Trials) statement (n = 94, 50.0%). About study registration, randomized controlled trial registration was endorsed by 101 (53.7%) journals, whereas the systematic review registration was endorsed by only 9 journals (4.8%). The results of multivariate logistic regression analysis revealed that not North America, higher JCR (Journal Citation Reports) rank journals were more likely to endorse reporting guidelines and study registration. CONCLUSIONS: Surgery journals frequently use reporting guidelines, but nearly half of journals did not require study registration. Implementing these two mechanisms can prevent bias, and their adoption should be strengthened by authors, reviewers and journal editors in surgery.

Tumor Cell-Derived TGFß1 Attenuates Antitumor Immune Activity of T Cells via Regulation of PD-1 mRNA.

Dysfunction in T-cell antitumor activity contributes to the tumorigenesis, progression, and poor outcome of clear cell renal cell carcinoma (ccRCC), with this dysfunction resulting from high expression of programmed cell death-1 (PD-1) in T cells. However, the molecular mechanisms maintaining high PD-1 expression in T cells have not been fully investigated in ccRCC. Here, we describe a mechanism underlying the regulation of PD-1 at the mRNA level and demonstrated its impact on T-cell dysfunction. Transcriptomic analysis identified a correlation between TGFß1 and PD-1 mRNA levels in ccRCC samples. The mechanism underlying the regulation of PD-1 mRNA was then investigated in vitro and in vivo using syngeneic tumor models. We also observed that TGFß1 had prognostic significance in patients with ccRCC, and its expression was associated with PD-1 mRNA expression. CcRCC-derived TGFß1 activated P38 and induced the phosphorylation of Ser10 on H3, which recruited p65 to increase SRSF3 and SRSF5 expression in T cells. As a result, the half-life of PD-1 mRNA in T cells was prolonged. SRSF3 coordinated with NXF1 to induce PD-1 mRNA extranuclear transport in T cells. We then demonstrated that TGFß1 could induce SRSF3 expression to restrict the antitumor activity of T cells, which influenced immunotherapy outcomes in ccRCC mouse models. Our findings highlight that tumor-derived TGFß1 mediates immune evasion and has potential as a prognostic biomarker and therapeutic target in ccRCC.See related Spotlight on p. 1464.

PTRF/CAVIN1, regulated by SHC1 through the EGFR pathway, is found in urine exosomes as a potential biomarker of ccRCC.

Polymerase I and transcript release factor (PTRF)/Cavin1 regulates RNA polymerase I during transcription and plays a critical role in endocytosis. Abnormal expressions of PTRF were detected in multiple cancers according to increasing research. PTRF has been showed to involve in the formation and secretion of exosomes and can be detected in the exosomes, which suggests that PTRF would be a potential biomarker for diagnosis of clear cell renal cell carcinoma (ccRCC) using urine samples. Approximately 50-90% of ccRCC cases suffered abnormal epidermal growth factor receptor (EGFR), which activates a variety of signaling pathways, including the mitogen-activated protein kinase/extracellular signal-regulated kinase and Phosphoinositide 3-Kinase/Akt pathway. According to bioinformatic analysis of gene expression arrays of kidney clear cell carcinoma from The Cancer Genome Atlas, we found SHC1 was significantly overexpressed in high-grade ccRCC and correlated to poor prognosis, and also SHC1 was annotated in extracellular matrix process, which was regulated by EGFR. Further studies showed that the expression of PTRF was regulated by SHC1 through EGFR-Phosphoinositide 3-Kinase/Akt pathway. PTRF was detected in the exosomes isolated from ccRCC patients' urine and ccRCC cancer cells culture medium. It suggested that the abnormal SHC1-increased PTRF, which is detected in exosomes from urine, would be a potential marker for ccRCC diagnose and treatment.

MiR-216a exerts tumor-suppressing functions in renal cell carcinoma by targeting TLR4.

MiR-216a, a tumor-related microRNA (miRNA), has been reported to be implicated in the tumorigenesis and progression of diverse types of human malignancies; however, its role in renal cell carcinoma (RCC) remains unclear. This study aimed to explore the biological role of miR-216a in RCC and clarify the potential mechanisms involved. In the present study, miR-216a was found to be significantly down-regulated in both RCC tissues and cell lines. Functional studies demonstrated that enhanced expression of miR-216a suppressed RCC cell proliferation, migration and invasion in vitro, inhibited tumor growth in vivo, and induced RCC cell cycle arrest and apoptosis. Moreover, the tumor-suppressing effects of miR-216a in RCC were abrogated by the miR-216a inhibitor treatment. Notably, toll-like receptor 4 (TLR4) was downregulated by miR-216a via direct binding to its 3' untranslated region in RCC cells. Furthermore, TLR4 expression was discovered to be markedly up-regulated and inversely correlated with miR-216a expression in RCC tissues. Mechanistic studies revealed that restoring the expression of TLR-4 alleviated miR-216a-induced inhibitory effects on proliferation, migration and invasion of RCC cells. Taken together, these findings suggest that miR-216a functions as a tumor suppressor in RCC by directly targeting TLR4 and that miR-216a might be a novel therapeutic target for RCC.

Oxoglaucine-lanthanide complexes: synthesis, crystal structure and cytotoxicity.

AIM: To evaluate the in vitro cytotoxicity of oxoglaucine (OG) complexes: [Sm(OG)2(NO3)3]•H2O (1), [Eu(OG)2(NO3)3]•1.5CH3OH (2) and [Er(OG)2(NO3)3]•H2O (3) through comparison to oxoglaucine and lanthanide salts. MATERIALS AND METHODS: The reactions of OG with corresponding lanthanide salts gave rise to complexes 1-3. The crystal structures of complexes 1-3 were determined by single-crystal X-ray diffraction analysis. The in vitro cytotoxicity of oxoglaucine and complexes 1-3 against five human cancer cell lines were evaluated by the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium Bromide (MTT) method. RESULTS: Complexes 1-3 have similar mononuclear structures. The 50% inhibitory concentration (IC50) of complex 1 against SGC7901 cells was 32.1 µM; that of complex 2 against MCF-7 cells was 3.2 µM; those of complex 3 on HeLa and MCF-7 cells were 8.3 and 1.4 µM, respectively. CONCLUSION: The three OG-lanthanide complexes exhibited significantly enhanced cytotoxicity vs. OG and corresponding lanthanide salts.

Histotype-specific copy-number alterations in ovarian cancer.

BACKGROUND: Epithelial ovarian cancer is characterized by multiple genomic alterations; most are passenger alterations which do not confer tumor growth. Like many cancers, it is a heterogeneous disease and can be broadly categorized into 4 main histotypes of clear cell, endometrioid, mucinous, and serous. To date, histotype-specific copy number alterations have been difficult to elucidate. The difficulty lies in having sufficient sample size in each histotype for statistical analyses. METHODS: To dissect the heterogeneity of ovarian cancer and identify histotype-specific alterations, we used an in silico hypothesis-driven approach on multiple datasets of epithelial ovarian cancer. RESULTS: In concordance with previous studies on global copy number alterations landscape, the study showed similar alterations. However, when the landscape was de-convoluted into histotypes, distinct alterations were observed. We report here significant histotype-specific copy number alterations in ovarian cancer and showed that there is genomic diversity amongst the histotypes. 76 cancer genes were found to be significantly altered with several as potential copy number drivers, including ERBB2 in mucinous, and TPM3 in endometrioid histotypes. ERBB2 was found to have preferential alterations, where it was amplified in mucinous (28.6%) but deleted in serous tumors (15.1%). Validation of ERBB2 expression showed significant correlation with microarray data (p=0.007). There also appeared to be reciprocal relationship between KRAS mutation and copy number alterations. In mucinous tumors where KRAS mutation is common, the gene was not significantly altered. However, KRAS was significantly amplified in serous tumors where mutations are rare in high grade tumors. CONCLUSIONS: The study demonstrates that the copy number landscape is specific to the histotypes and identification of these alterations can pave the way for targeted drug therapy specific to the histotypes.

Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library.

BACKGROUND: While there is strong evidence for phosphatidylinositol 3-kinase (PI3K) involvement in cancer development, there is limited information about the role of PI3K regulatory subunits. PIK3R3, the gene that encodes the PI3K regulatory subunit p55γ, is over-expressed in glioblastoma and ovarian cancers, but its expression in gastric cancer (GC) is not known. We thus used genetic and bioinformatic approaches to examine PIK3R3 expression and function in GC, the second leading cause of cancer mortality world-wide and highly prevalent among Asians. METHODS: Primary GC and matched non-neoplastic mucosa tissue specimens from a unique Asian patient gastric cancer library were comprehensively profiled with platforms that measured genome-wide mRNA expression, DNA copy number variation, and DNA methylation status. Function of PIK3R3 was predicted by IPA pathway analysis of co-regulated genes with PIK3R3, and further investigated by siRNA knockdown studies. Cell proliferation was estimated by crystal violet dye elution and BrdU incorporation assay. Cell cycle distribution was analysed by FACS. RESULTS: PIK3R3 was significantly up-regulated in GC specimens (n = 126, p < 0.05), and 9.5 to 15% tumors showed more than 2 fold increase compare to the paired mucosa tissues. IPA pathway analysis showed that PIK3R3 promoted cellular growth and proliferation. Knockdown of PIK3R3 decreased the growth of GC cells, induced G0/G1 cell cycle arrest, decreased retinoblastoma protein (Rb) phosphorylation, cyclin D1, and PCNA expression. CONCLUSION: Using a combination of genetic, bioinformatic, and molecular biological approaches, we showed that PIK3R3 was up-regulated in GC and promoted cell cycle progression and proliferation; and thus may be a potential new therapeutic target for GC.

TCM active ingredient oxoglaucine metal complexes: crystal structure, cytotoxicity, and interaction with DNA.

The alkaloid oxoglaucine (OG), which is a bioactive component from traditional Chinese medicine (TCM), was synthesized by a two-step reaction and used as the ligand to react with transition metal salts to give four complexes: [OGH][AuCl(4)]·DMSO (1), [Zn(OG)(2)(H(2)O)(2)](NO(3))(2) (2), [Co(OG)(2)(H(2)O)(2)](ClO(4))(2) (3), and [Mn(OG)(2)(H(2)O)(2)](ClO(4))(2) (4). The crystal structures of the metal complexes were confirmed by single crystal X-ray diffraction. Complex 1 is an ionic compound consisting of a charged ligand [OGH](+) and a gold complex [AuCl(4)](-). Complexes 2-4 all have similar structures (inner-spheres), that is, octahedral geometry with two OG coordinating to one metal center and two aqua ligands occupying the two apical positions of the octahedron, and two NO(3)(-) or ClO(4)(-) as counteranions in the outer-sphere. The complexation of OG to metal ion was confirmed by ESI-MS, capillary electrophoresis and fluorescence polarization. The in vitro cytotoxicity of these complexes toward a various tumor cell lines was assayed by the MTT method. The results showed that most of these metal-oxoglaucine complexes exhibited enhanced cytotoxicity compared with oxoglaucine and the corresponding metal salts, with IC(50) values ranging from 1.4 to 32.7 µM for sensitive cancer cells, which clearly implied a positive synergistic effect. Moreover, these complexes appeared to be selectively active against certain cell lines. The interactions of oxoglaucine and its metal complexes with DNA and topoisomerase I were investigated by UV-vis, fluorescence, CD spectroscopy, viscosity, and agarose gel electrophoresis, and the results indicated that these OG-metal complexes interact with DNA mainly via intercalation. Complexes 2-4 are metallointercalators, but complex 1 is not. These metal complexes could effectively inhibit topoisomerase I even at low concentration. Cell cycle analysis revealed that 1-3 caused S-phase cell arrest.

Assessing matched normal and tumor pairs in next-generation sequencing studies.

Next generation sequencing technology has revolutionized the study of cancers. Through matched normal-tumor pairs, it is now possible to identify genome-wide germline and somatic mutations. The generation and analysis of the data requires rigorous quality checks and filtering, and the current analytical pipeline is constantly undergoing improvements. We noted however that in analyzing matched pairs, there is an implicit assumption that the sequenced data are matched, without any quality check such as those implemented in association studies. There are serious implications in this assumption as identification of germline and rare somatic variants depend on the normal sample being the matched pair. Using a genetics concept on measuring relatedness between individuals, we demonstrate that the matchedness of tumor pairs can be quantified and should be included as part of a quality protocol in analysis of sequenced data. Despite the mutation changes in cancer samples, matched tumor-normal pairs are still relatively similar in sequence compared to non-matched pairs. We demonstrate that the approach can be used to assess the mutation landscape between individuals.

catena-Poly[[triaqua-(pyridine-κN)nickel(II)]-µ-sulfato-κO:O'].

The title compound, [Ni(SO(4))(C(5)H(5)N)(H(2)O)(3)](n), was synthesized by the hydro-thermal reaction of NiSO(4)·6H(2)O, pyridine and water. The central Ni(II) atom is coordinated in a distorted octa-hedral environment by a pyridine N atom, three aqua O atoms and two O atoms of bridging sulfate anions, yielding a zigzag chain. A three-dimensional network is generated via complex hydrogen bonds involving the sulfate and aqua ligands and a pyridine C-H group.

[Effect of interferon alfa therapy on malignant melanoma of oral mucosa].

PURPOSE: To evaluate the effect of two adjuvant therapy in patients with resected maxillary mucosal melanoma. METHODS: Survival analysis, retrospective study. There were 165 patients with resected maxillary mucosal malignant melanoma in the study, which were divided into three group: control group (50), interferon-alpha2b group (78) and interferon-alpha2b+dacarbazine group (37). All patients had stage II or III lesions according to AJCC(2000) staying system. Cox proportional hazards model was used to analyze the statistically significant prognostic factors. Kaplan-Meire method was used to calculate the cumulated survival rate with 3 different treatments and Log-rank method for comparison of the distribution of the different survival rates in 3 groups. RESULTS: The overall 3-year survival rate was 4%, with 3.0% in the control group, 4.5% in interferon-<2b group and 5.7% in interferon-alpha2b+dacarbazine group, respectively. The significant prognostic factors included thickness(P<0.001, RR=2.696), ulceration(P<0.001, RR=2.068), lymph node metastasis(P<0.001, RR=1.710) and the treatment method(P<0.001, RR=0.395). A beneficial effect in overall survival was observed in two experimental groups. But the effect appeared to become weakening after 2 years. The difference between the two experimental groups was not significant statistically. CONCLUSIONS: The two conjunctive methods used in this study can improve the overall survival in patients with resected maxillary mucosal melanoma. But the beneficial effect would descend and disappear after 2 years. The effect of using interferon-alpha2b+dacarbazine was not better than that of using interferon-alpha2b alone.

[Study on proliferation inhibiting and apoptosis inducing effects of cerulenin on multiple myeloma cells].

OBJECTIVE: To determine whether fatty acid synthase (FAS) is expressed in human multiple myeloma( MM) cells and investigate the proliferation inhibition effect of fatty acid synthase inhibitor cerulenin on multiple myeloma cell line U266 and its mechanism. METHODS: FAS mRNA expression in human MM cell line U266, RPMI8226 cell was assayed by RT-PCR. The proliferation inhibition rate of U266 cells was assayed by MTr analysis. Cell apoptosis and cycle distribution were evaluated by flow cytometry (FCM). RESULTS: FAS mRNA was highly expressed in human multiple myeloma cell lines as compared with healthy donor PBMNCs. After U266 cells were treated with cerulenin (the concentrations from 5 microg/ml to 640 microg/ ml) for 24 h, the cell proliferation was markedly inhibited with a dose related manner, while the inhibition rate of human skin fibroblast cells were all lower than 30%. When U266 cells were treated with 20 pjg/ml cerulenin for 12 h and 24 h, the early apoptosis rate revealed by Annexin V/PI were 56. 9% and 69. 3% respectively, being higher than that of the blank controls (4. 3% and 1.8%, P < 0. 01). Cell cycle analysis showed it was blocked in S phase. Conclusion FAS is highly expressed in human MM. Cerulenin could induce apoptosis and inhibit proliferation of U266 cells. FAS might be a new potential target for multiple myeloma treatment.