Therapeutic Effect of Mirogabalin on Peripheral Neuropathic Pain due to Lumbar Spine Disease

Study Design Retrospective study. Purpose This study aims to evaluate the effectiveness of mirogabalin in treatment of peripheral neuropathic pain due to lumbar spine disease. Overview of Literature Mirogabalin is a novel selective ligand for the α2δ subunit of voltage-gated Ca channels. Methods Between April and December 2019, we used mirogabalin to treat 60 consecutive patients (mean age, 67.6 years) with leg symptoms due to lumbar disease. The treatment outcome after 8 weeks of mirogabalin therapy was evaluated by comparing the preand post-administration Numerical Rating Scale (NRS) for leg symptoms and sleep disturbance, the NRS and Roland–Morris Disability Questionnaire for low back pain (LBP), and the quality of life (QOL) score (based on EuroQol five-dimension five-level scale). Results Mirogabalin treatment was stopped at less than eight weeks in eight patients. The remaining 52 patients for evaluation were divided as group 1 (17 patients who presented with leg symptoms that lasted for less than 3 months) and group 2 (35 patients with leg symptoms that lasted longer than 3 months). The leg symptoms and LBP in both groups significantly improved at 4 and 8 weeks of treatment, and sleep disturbance and QOL were improved at 8 weeks as well. Compared to group 2, the pretreatment leg symptoms and QOL were significantly worse in group 1, and their improvement after 8 weeks of mirogabalin treatment was significantly better (p<0.05). Of the 60 original patients, 17 suffered adverse effects, which were mild in 16 patients and required treatment cessation due to excessive weight gain in one patient. Conclusions We have validated the effect of mirogabalin on neuropathic pain due to lumbar spine disease, which has effectively addressed the associated leg symptoms, LBP, and sleep disturbance

Breast cancer cell lines carry cell line-specific genomic alterations that are distinct from aberrations in breast cancer tissues: Comparison of the CGH profiles between cancer cell lines and primary cancer tissues

<p>Abstract</p> <p>Background</p> <p>Cell lines are commonly used in various kinds of biomedical research in the world. However, it remains uncertain whether genomic alterations existing in primary tumor tissues are represented in cell lines and whether cell lines carry cell line-specific genomic alterations. This study was performed to answer these questions.</p> <p>Methods</p> <p>Array-based comparative genomic hybridization (CGH) was employed with 4030 bacterial artificial chromosomes (BACs) that cover the genome at 1.0 megabase resolution to analyze DNA copy number aberrations (DCNAs) in 35 primary breast tumors and 24 breast cancer cell lines. DCNAs were compared between these two groups. A tissue microdissection technique was applied to primary tumor tissues to reduce the contamination of samples by normal tissue components.</p> <p>Results</p> <p>The average number of BAC clones with DCNAs was 1832 (45.3% of spotted clones) and 971 (24.9%) for cell lines and primary tumor tissues, respectively. Gains of 1q and 8q and losses of 8p, 11q, 16q and 17p were detected in >50% of primary cancer tissues. These aberrations were also frequently detected in cell lines. In addition to these alterations, the cell lines showed recurrent genomic alterations including gains of 5p14-15, 20q11 and 20q13 and losses of 4p13-p16, 18q12, 18q21, Xq21.1 and Xq26-q28 that were barely detected in tumor tissue specimens. These are considered to be cell line-specific DCNAs. The frequency of the HER2 amplification was high in both cell lines and tumor tissues, but it was statistically different between cell lines and primary tumors (P = 0.012); 41.3 ± 29.9% for the cell lines and 15.9 ± 18.6% for the tissue specimens.</p> <p>Conclusions</p> <p>Established cell lines carry cell lines-specific DCNAs together with recurrent aberrations detected in primary tumor tissues. It must therefore be emphasized that cell lines do not always represent the genotypes of parental tumor tissues.</p

Luminal A and luminal B (HER2 negative) subtypes of breast cancer consist of a mixture of tumors with different genotype

<p>Abstract</p> <p>Background</p> <p>The St Gallen International Expert Consensus 2011 has proposed a new classification system for breast cancer. The purpose of this study was to elucidate the relationship between the breast cancer subtypes determined by the new classification system and genomic characteristics.</p> <p>Methods</p> <p>Invasive breast cancers (n = 363) were immunohistochemically classified as follows: 111 (30.6%) as luminal A, 95 (26.2%) as luminal B (HER2 negative), 69 (19.0%) as luminal B (HER2 positive), 41 (11.3%) as HER2, and 47 (12.9%) as basal-like subtypes.</p> <p>Results</p> <p>The high expression of Ki-67 antigen was detected in 236 tumors; no cases of luminal A subtype showed high expression of the Ki-67 antigen, but more than 85% of tumors of the other subtypes showed high expression. In addition, DNA ploidy and chromosomal instability (CIN) were assessed using imaging cytometry and FISH, respectively. In this series, 336 (92.6%) tumors consisted of 129 diploid/CIN- and 207 aneuploid/CIN + tumors. Diploid/CIN- and aneuploid/CIN+ features were detected in 64.9% and 27.9% of luminal A, 41.1% and 49.5% of luminal B (HER2-), 11.6% and 81.2% of luminal B (HER2+), 4.9% and 90.2% of HER2, and 17.0% and 76.6% of basal-like subtypes, respectively. Unlike the luminal B (HER2+), HER2 and basal-like subtypes, the luminal A and luminal B (HER2-) subtypes were heterogeneous in terms of DNA ploidy and CIN.</p> <p>Conclusions</p> <p>It is reasonable to propose that the luminal A and luminal B (HER2-) subtypes should be further divided into two subgroups, diploid/CIN- and aneuploid/CIN+, based on their underlying genomic status.</p