PURPOSE: The MammaPrint™ gene signature, currently used in clinical practice, provides prognostic information regarding the recurrence and potential metastasis in breast cancer patients. However, the prognostic information of the 70 genes included can only be estimated at the RNA expression level. In this study, we investigated whether copy number information of MammaPrint™ genes at the DNA level can be used as a prognostic tool for breast cancer, as copy number variations (CNVs) are major contributors to cancer progression. METHODS: We performed CNV profiling of MammaPrint™ genes in 59 breast cancer cell lines and 650 breast cancer patients, using publicly available data in The Cancer Genome Atlas (TCGA) database. Statistical analyses including Fisher exact test, chi-square test, and Kaplan-Meier survival analyses were performed. RESULTS: All MammaPrint™ genes showed recurrent CNVs, particularly in TCGA cohort. CNVs of 32 and 36 genes showed significant associations with progesterone receptor and estrogen rector, respectively. No genes showed a significant association with human epidermal growth factor receptor 2 status and lymph node status. In addition, only six genes were associated with tumor stages. RFC4, HRASLS, NMU, GPR126, SCUBE2, C20orf46, and EBF4 were associated with reduced survival and RASSF7 and ESM1 were associated with reduced disease-free survival. CONCLUSION: Based on these findings, a concordance of CNV-based genomic rearrangement with expression profiling of these genes and their putative roles in disease tumorigenesis was established. The results suggested that the CNV profiles of the MammaPrint™ genes can be used to predict the prognosis of breast cancer patients. In addition, this approach may lead to the development of new cancer biomarkers at the DNA level.
Biomarkers ; Biomarkers, Tumor ; Breast Neoplasms* ; Breast* ; Carcinogenesis ; Cell Line ; Cohort Studies ; Disease-Free Survival ; DNA ; DNA Copy Number Variations ; Estrogens ; Genome ; Humans ; Lymph Nodes ; Neoplasm Metastasis ; Prognosis* ; Receptor, Epidermal Growth Factor ; Receptors, Progesterone ; Recurrence ; RNA

OBJECTIVE: The offset connector can allow medial and lateral variability and facilitate intralaminar screw incorporation into the construct. The aim of this study was to compare the biomechanical characteristics of C7 intralaminar screw constructs with and without offset connector using a three dimensional finite element model of a C6-7 cervical spine segment. METHODS: Finite element models representing C7 intralaminar screw constructs with and without the offset connector were developed. Range of motion (ROM) and maximum von Mises stresses in the vertebra for the two techniques were compared under pure moments in flexion, extension, lateral bending and axial rotation. RESULTS: ROM for intralaminar screw construct with offset connector was less than the construct without the offset connector in the three principal directions. The maximum von Misses stress was observed in the C7 vertebra around the pedicle in both constructs. Maximum von Mises stress in the construct without offset connector was found to be 12-30% higher than the corresponding stresses in the construct with offset connector in the three principal directions. CONCLUSION: This study demonstrated that the intralaminar screw fixation with offset connector is better than the construct without offset connector in terms of biomechanical stability. Construct with the offset connector reduces the ROM of C6-7 segment more significantly compared to the construct without the offset connector and causes lower stresses around the C7 pedicle-vertebral body complex.
Biomechanics ; Immobilization ; Range of Motion, Articular ; Spine

Arsenic compounds are widely used for the therapeutic intervention of multiple diseases.Ancient pharmacologists discovered the medicinal utility of these highly toxic substances,and modern phar-macologists have further recognized the specific active ingredients in human diseases.In particular,Arsenic trioxide(ATO),as a main component,has therapeutic effects on various tumors(including leukemia,hepatocellular carcinoma,lung cancer,etc.).However,its toxicity limits its efficacy,and con-trolling the toxicity has been an important issue.Interestingly,recent evidence has pointed out the pivotal roles of arsenic compounds in phase separation and membraneless organelles formation,which may determine their toxicity and therapeutic efficacy.Here,we summarize the arsenic compounds-regulating phase separation and membraneless organelles formation.We further hypothesize their potential involvement in the therapy and toxicity of arsenic compounds,highlighting potential mecha-nisms underlying the clinical application of arsenic compounds.

Objective To report presence of Leishmania major in Khyber Pakhtunkhwa of Pakistan, where cutaneous leishmaniasis (CL) is endemic and was thought to be caused by Leishmania tropica only. Methods Biopsy samples from 432 CL suspected patients were collected from 3 southern districts of Khyber Pakhtunkhwa during years 2011–2016. Microscopy on Giemsa stained slides were done followed by amplification of the ribosomal internal transcribed spacer 1 gene. Results Leishmania amastigotes were detected by microscopy in 308 of 432 samples (71.3%) while 374 out of 432 samples (86.6%) were positive by ribosomal internal transcribed spacer 1 PCR. Subsequent restriction fragment length polymorphism confirmed L. tropica in 351 and L. major in 6 biopsy samples. Conclusions This study is the first molecular characterization of Leishmania species in southern Khyber Pakhtunkhwa. It confirmed the previous assumptions that anthroponotic CL is the major CL form present in Khyber Pakhtunkhwa province. Furthermore, this is the first report of L. major from a classical anthroponotic CL endemic focus identified in rural areas of Kohat district in southern Khyber Pakhtunkhwa.