Crystallization of polypropylene near the surface in injection-molded plaques: A comparison of morphology and a numerical analysis

Skin morphology formation on injection-molded isotactic polypropylene (PP) was investigated using micro-beam synchrotron wide-angle X-ray diffraction and numerical simulation. The 1-20 Î?m depth range was characterized with an X-ray beam of 0.273 Î?m Ï? 0.389 Î?m in size. From an evaluation of doping nucleating agents (NA) in PP, the NAs did not work at a depth of 1 Î?m. α-specified NA affected crystallization within a 5-Î?m depth. β-specified PP showed α-form crystallinity at the 5-20 Î?m depth. The mesomorphic crystal near the surface showed extremely high orientation. From viscoelastic flow simulation, PP molecules near the surface were oriented in the flow direction by extensional flow in the flow front, but freezing occurred faster than flow-induced crystallization. It was estimated that the delay of crystallization occurred during the transient temperature. The deformation rate did not cause a difference in crystal morphology near the surface, but the cooling rate did. Copyright © 2009 Society of Plastics Engineers

Recent trend of research on the nongenotoxic mechanisms of chemical carcinogenesis

本総説は,筆者らが進めている｢低線量放射線の健康への影響と医療への応用｣に関する研究に資するために調査した,化学発がんの非遺伝毒性的メカニズムの解明に関する最近の動向の概要についてまとめたものである｡即ち,非遺伝毒性的発がんにおける細胞増殖,シトクロムP450誘導,酸化的ストレス,および遺伝子発現のそれぞれの役割,並びに量的な応答性について言及した｡また,後成的発がんにおけるアポトーシス,およびギャップ結合による情報伝達のそれぞれの役割についても触れた｡その結果,非遺伝毒性的な発がん物質の作用の様式とメカニズムやこれによる後成的な影響などについては解明さ れつつあり,特に,これらの発がん物質がゲノムDNAに対し直接的な相互作用,突然変異,修飾などを行う発がん物質とは機能的に異なった作用をすることが明らかになった｡また,これらは放射線発がんなど低線量放射線の健康への影響などについて研究する上で,重要な知見となっていることもわかった。To elucidate the health effects by low dose radiation, we reviewed the recent trend of research on the epigenetic mechanisms of chemical carcinogenesis. The following view were obtained. It has become apparent that chemical and physical agents that induce cancer may do so through different cellular and molecular mechanisms. Investigators, recognizing the apparent differences in the ways compounds participate in the carcinogenesis process, coined the phrases "genotoxic" and "epigenetic" in describing activities of chemicals and physical agents that induced cancer. The term "nongenotoxic" has to some extent replaced "epigenetic" and thus, classification of chemical carcinogens has been frequently delegated to either the genotoxic or nongenotoxic categories. Moreover, while much work remains in the understanding of the modes and mechanisms of action of nongenotoxic carcinogens and the epigenetic effects of these agents, it is apparent that this category of chemicals are functionally different than those compounds which directly interact, mutate, and modify genomic DNA

Monocyte or white blood cell counts and β₂ microglobulin predict the durable efficacy of daratumumab with lenalidomide

BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts

〈Originals〉Trib1 and Trib2 inhibit granulocytic differentiation by suppressing Akt pathway

[Abstract] Background :Overexpression of Tribbles homolog 1 (Tribl) and Tribbles homolog 2 (Trib2) in hematopoietic stem/progenitor cells evokes acute myeloid leukemia (AML) in murine transplantation models. Degradation of CCAAT-enhancer-binding-protein α (C/EBPα) plays a crucial role in Trib1 or Trib2-induced AML. However, because C/EBPα knockout mice do not develop AML, it is likely that Trib1 and Trib2 influence other signaling pathways besides C/EBPα. Elevated Akt phosphorylation is considered to contribute to the development of AML. In contrast, two groups recently reported that reduced Akt activity is involved in the pathogenesis of leukemia. We performed this study to reveal the role of Akt signaling in Trib family-induced AML.Methods : G-CSF-induced granulocytic differentiation of 32D cells was assessed morphologically and phenotypically. G-CSF-induced signaling wasassessed by Westernblotting. Results : Overexpression of Trib1 or Trib2 inhibited GCSF-induced granulocytic differentiation of 32D cells, which was accompanied by reduced Akt phosphorylation. Also, an Akt inhibitor API-2 blocked G-CSF-induced granulocytic differentiation independently of C/EBPα degradation.　Furthermore, retroviral C/EBPα restoration did not completely abolish the differentiation block caused by Trib1 and Trib2. Conclusion :Trib1 and Trib2 block granulocytic differentiation, at least partially, by suppressing Akt phosphorylation

Efficacy of elotuzumab for multiple myeloma in reference to lymphocyte counts and kappa/lambda ratio or B2 microglobulin

Abstract Novel therapeutic drugs have dramatically improved the overall survival of patients with multiple myeloma. We sought to identify the characteristics of patients likely to exhibit a durable response to one such drug, elotuzumab, by analyzing a real-world database in Japan. We analyzed 179 patients who underwent 201 elotuzumab treatments. The median time to next treatment (TTNT) with the 95% confidence interval was 6.29 months (5.18–9.20) in this cohort. Univariate analysis showed that patients with any of the following had longer TTNT: no high risk cytogenic abnormalities, more white blood cells, more lymphocytes, non-deviated κ/λ ratio, lower β2 microglobulin levels (B2MG), fewer prior drug regimens, no prior daratumumab use and better response after elotuzumab treatment. A multivariate analysis showed that TTNT was longer in patients with more lymphocytes (≥ 1400/μL), non-deviated κ/λ ratio (0.1–10), lower B2MG (< 5.5 mg/L) and no prior daratumumab use. We proposed a simple scoring system to predict the durability of the elotuzumab treatment effect by classifying the patients into three categories based on their lymphocyte counts (0 points for ≥ 1400/μL and 1 point for < 1400/μL) and κ/λ ratio (0 points for 0.1–10 and 1 point for < 0.1 or ≥ 10) or B2MG (0 points for < 5.5 mg/L and 1 point for ≥ 5.5 mg/L). The patients with a score of 0 showed significantly longer TTNT (p < 0.001) and better survival (p < 0.001) compared to those with a score of 1 or 2. Prospective cohort studies of elotuzumab treatment may be needed to validate the usefulness of our new scoring system

Impact of cytogenetic abnormalities in symptomatic multiple myeloma; a Japanese real-world analysis from Kansai Myeloma Forum

To evaluate the specific prognostic value of CAs, we conducted an analysis of 923 symptomatic multiple myeloma patients. Among this cohort, 480 patients had complete data set of high-risk CAs by interphase fluorescent in situ hybridization at diagnosis. In the high-risk group analysis, the median OS of patients without CAs (n = 338, 72 %) was 6.5 years, patients with del(17p) (n = 42, 9 %) was 4.4 years, patients with t(4;14) or t(14;16) (n = 72, 15 %) was 4.4 years, and patients with double-positive CAs(del(17p) and t(4;14) or t(14;16)) (n = 18, 4 %) was 2.1 years (p = 0.032). Patients with double-positive CAs had a significantly worse prognosis