Relief of cancer pain in a non small cell lung cancer patient by a polyhedral approach

We report a case of cancer-related pain relieved by a polyhedral approach. A woman in her late 30s with advanced non small cell lung cancer suffered from back pain caused by the cancer invasion to a thoracic vertebra. She could not take a sufficient dose of opioid due to its adverse effects. A supplementary analgesic was not found to be effective. Palliative radiation was considered desirable, but she could not maintain a dorsal position for irradiation due to back pain. Continuous epidural anesthesia was then introduced. Epidural anesthesia allowed her to lie in a spine position for radiation therapy. After completion of radiation therapy, her back pain was relieved with a low dose of transdermal fentanyl without epidural anesthesia

Nano-LC-MS/MS for Quantification of Lyso-Gb3 and Its Analogues Reveals a Useful Biomarker for Fabry Disease.

Biomarkers useful for diagnosis and evaluation of treatment for patients with Fabry disease are urgently needed. Recently, plasma globotriaosylsphingosine (lyso-Gb3) and lyso-Gb3-related analogues have attracted attention as promising biomarkers of Fabry disease. However, the plasma concentrations of lyso-Gb3 and its analogues are extremely low or below the detection limits in some Fabry patients as well as in healthy subjects. In this paper, we introduce the novel application of a nano-liquid chromatography-tandem mass spectrometry (nano-LC-MS/MS) system to the measurement of lyso-Gb3 and its analogues in plasma. Nano-LC-MS/MS requires smaller amounts of samples and is more sensitive than conventional techniques. Using this method, we measured the plasma concentrations of lyso-Gb3 and its analogues in 40 healthy subjects, 5 functional variants (males with E66Q), and various Fabry patients (9 classic Fabry males/9 mutations; 7 later-onset Fabry males/5 mutations; and 10 Fabry females/9 mutations). The results revealed that the mean lyso-Gb3 and lyso-Gb3(-2) concentrations in all the Fabry patient subgroups were statistically higher, especially in the classic Fabry males, than those in the functional variants and healthy subjects. The plasma concentrations of lyso-Gb3 and its analogues in healthy subjects, functional variants, and some Fabry patients with specific mutations (R112H and M296I) that cannot be established by conventional techniques were successfully determined by means of nano-LC-MS/MS. The lyso-Gb3 and lyso-Gb3(-2) concentrations in male patients with these mutations were lower than those in most Fabry patients having other mutations, but higher than those in the functional variants and healthy subjects. This new method is expected to be useful for sensitive determination of the plasma concentrations of lyso-Gb3 and its analogues. This study also revealed that not only lyso-Gb3 but also lyso-Gb3(-2) in plasma is a useful biomarker for the diagnosis of Fabry disease

Mechanical properties of nerve roots and rami radiculares isolated from fresh pig spinal cords

No reports have described experiments designed to determine the strength characteristics of spinal nerve roots and rami radiculares for the purpose of explaining the complexity of symptoms of medullary cone lesions and cauda equina syndrome. In this study, to explain the pathogenesis of cauda equina syndrome, monoaxial tensile tests were performed to determine the strength characteristics of spinal nerve roots and rami radiculares, and analysis was conducted to evaluate the stress-strain relationship and strength characteristics. Using the same tensile test device, the nerve root and ramus radiculares isolated from the spinal cords of pigs were subjected to the tensile test and stress relaxation test at load strain rates of 0.1, 1, 10, and 100 s -1 under identical settings. The tensile strength of the nerve root was not rate dependent, while the ramus radiculares tensile strength tended to decrease as the strain rate increased. These findings provide important insights into cauda equina symptoms, radiculopathy, and clinical symptoms of the medullary cone

Intra-day and inter-day precision and accuracy for controlled plasma samples spiked with lower limit (QCLL, 0.08nM), low (QCL, 0.4nM), medium (QCM, 10nM), and high (QCH, 200nM) concentrations of lyso-Gb3.

<p>Intra-day and inter-day precision and accuracy for controlled plasma samples spiked with lower limit (QCLL, 0.08nM), low (QCL, 0.4nM), medium (QCM, 10nM), and high (QCH, 200nM) concentrations of lyso-Gb3.</p

MS/MS spectra of lyso-Gb3, lyso-Gb3-IS and lyso-Gb3 analogues acquired from a classical Fabry patient with a Q-Exactive.

<p>(A) Lyso-Gb3, (B) Lyso-Gb3-IS, (C) Lyso-Gb3(-28), (D) Lyso-Gb3(-12), (E) Lyso-Gb3(-2), (F) Lyso-Gb3(+14), (G) Lyso-Gb3(+16), (H) Lyso-Gb3(+18), (I) Lyso-Gb3(+34), and (J) Lyso-Gb3(+50). Triangles (▼) indicate the target fragments used for quantification.</p

Genotypes, plasma lyso-Gb3 concentrations, and clinical manifestations in the patients with Fabry disease.

<p>P: Pain in peripheral extremities, A: Angiokeratomas, HH: Hypohidrosis, CO: Corneal opacities, RD: Renal disease, HD: Heart disease, and CV: Cerebrovascular disease. N: Not available. WT: Wild type</p><p>*Ref. 30.</p><p>Genotypes, plasma lyso-Gb3 concentrations, and clinical manifestations in the patients with Fabry disease.</p

Investigation of FOXM1 as a Potential New Target for Melanoma.

Recent studies have shown that immunotherapies and molecular targeted therapies are effective for advanced melanoma. Non-antigen-specific immunotherapies such as immunocheckpoint blockades have been shown to be effective in the treatment of advanced melanoma. However, the response rates remain low. To improve their efficacy, they should be combined with antigen-specific immunotherapy. Elevated expression of the transcription factor, Forkhead box M1 (FOXM1), has been reported in various human cancers, and it has been shown to have potential as a target for immunotherapy. The purpose of this study was to investigate the FOXM1 expression in human melanoma samples and cell lines, to evaluate the relationship between the FOXM1 expression and the clinical features of melanoma patients and to investigate the association between the FOXM1 and MAPK and PI3K/AKT pathways in melanoma cell lines. We conducted the quantitative reverse transcription PCR (qRT-PCR) and Western blotting analyses of melanoma cell lines, and investigated melanoma and nevus tissue samples by qRT-PCR and immunohistochemistry. We performed MEK siRNA and PI3K/AKT inhibitor studies and FOXM1 siRNA studies in melanoma cell lines. We found that FOXM1 was expressed in all of the melanoma cell lines, and was expressed in 49% of primary melanomas, 67% of metastatic melanomas and 10% of nevi by performing immunohistochemical staining. Metastatic melanoma samples exhibited significantly higher mRNA levels of FOXM1 (p = 0.004). Primary melanomas thicker than 2 mm were also more likely to express FOXM1. Patients whose primary melanoma expressed FOXM1 had a significantly poorer overall survival compared to patients without FOXM1 expression (p = 0.024). Downregulation of FOXM1 by siRNA significantly inhibited the proliferation of melanoma cells, and blockade of the MAPK and PI3K/AKT pathways decreased the FOXM1 expression in melanoma cell lines. In conclusion, FOXM1 is considered to be a new therapeutic target for melanoma

The relationship between FOXM1 expression and the overall survival.

<p>A comparison of the overall survival between the patients positive for FOXM1 and those negative for expression, as determined using immunohistochemical staining. The <i>p</i>-values were determined using the log-rank test.</p