Effect of Ninjin’yoeito on the Loss of Skeletal Muscle Function in Cancer-Bearing Mice

Ninjin’yoeito (NYT), a traditional Japanese Kampo medicine formula, is used as a remedy for conditions, and physical weakness. Cancer cachexia is seen in advanced cancer patients and is defined by an ongoing loss of skeletal-muscle mass that leads to progressive functional impairment. In the present study, we examined the hypothesis whether NYT improves the functional loss of skeletal muscle cancer cachexia. Male C57/BL 6J mice with B16BF6 melanoma tumor showed decreased expression of myosin heavy chain (MHC) in the gastrocnemius muscle. Moreover, the expression of SOCS3 and phosphorylated STAT3 and AMPK was increased, and the expression of phosphorylated 4E-BP1 was decreased in the gastrocnemius muscle of tumor-bearing mice. These data suggested that amino acid metabolism was altered in tumor-bearing mice, which were normalized by the NYT intervention. The present study showed that NYT might be a novel therapeutic option for the treatment of sarcopenia occurring cancer cachexia

Low-grade B-cell lymphoma presenting primarily in the bone marrow

Cases of low-grade B-cell lymphoma presenting primarily in the bone marrow are rare, and its clinicopathology remains unclear. We retrospectively examined patients with low-grade B-cell lymphoma presenting primarily in the bone marrow. Fourteen patients met the inclusion criteria, including 5 with lymphoplasmacytic lymphoma (LPL), 3 with chronic lymphocytic leukemia/small lymphocytic lymphoma, 2 with follicular lymphoma (FL), and 4 with low-grade B-cell lymphoma not otherwise specified (LGBCL-NOS). The median age was 69.5 years (range, 42-89 years), and a slight male predominance was noted (9 men and 5 women, 1.8: 1). Immunohistochemically, all cases were positive for CD20. One case was positive for CD138. Both cases of FL were positive for CD10 and B-cell lymphoma 2 (BCL-2), and immunoglobulin heavy locus (IgH)/B-cell lymphoma 2 rearrangement was observed by fluorescence in situ hybridization. The myeloid differentiation primary response gene (88) leucine to proline mutation was observed in 3 of 5 LPL, 1 of 2 FL, and 2 of 4 LGBCL-NOS patients. Paraproteinemia was observed in 10 patients; IgM and IgG paraproteinemia were observed in 6 and 3 patients, respectively. In this patient series, 3 patients had died at a median follow-up of 36.5 months; the cause of death of 1 LPL patient was malignant lymphoma itself. Thus, low-grade B-cell lymphoma presenting primarily in the bone marrow has various subtypes, and approximately one-third of the patients had LGBCL-NOS. The immunophenotypic features and myeloid differentiation primary response gene (88) leucine to proline mutation data of LGBCL-NOS suggested that some cases present with characteristics similar to those of LPL or marginal zone lymphoma

Microbe-Specific C3b Deposition in the Horseshoe Crab Complement System in a C2/Factor B-Dependent or -Independent Manner

Complement C3 plays an essential role in the opsonization of pathogens in the mammalian complement system, whereas the molecular mechanism underlying C3 activation in invertebrates remains unknown. To understand the molecular mechanism of C3b deposition on microbes, we characterized two types of C2/factor B homologs (designated TtC2/Bf-1 and TtC2/Bf-2) identified from the horseshoe crab Tachypleus tridentatus. Although the domain architectures of TtC2/Bf-1 and TtC2/Bf-2 were identical to those of mammalian homologs, they contained five-repeated and seven-repeated complement control protein domains at their N-terminal regions, respectively. TtC2/Bf-1 and TtC2/Bf-2 were synthesized and glycosylated in hemocytes and secreted to hemolymph plasma, which existed in a complex with C3 (TtC3), and their activation by microbes was absolutely Mg2+-dependent. Flow cytometric analysis revealed that TtC3b deposition was Mg2+-dependent on Gram-positive bacteria or fungi, but not on Gram-negative bacteria. Moreover, this analysis demonstrated that Ca2+-dependent lectins (C-reactive protein-1 and tachylectin-5A) were required for TtC3b deposition on Gram-positive bacteria, and that a Ca2+-independent lectin (Tachypleus plasma lectin-1) was definitely indispensable for TtC3b deposition on fungi. In contrast, a horseshoe crab lipopolysaccharide-sensitive protease factor C was necessary and sufficient to deposit TtC3b on Gram-negative bacteria. We conclude that plasma lectins and factor C play key roles in microbe-specific TtC3b deposition in a C2/factor B-dependent or -independent manner

Risk factors for CAR-T cell manufacturing failure among DLBCL patients: A nationwide survey in Japan

CAR-T細胞製造を成功させるためのレシピ --アフェレーシス前の下ごしらえでの工夫--. 京都大学プレスリリース. 2023-04-27.For successful chimeric antigen receptor T (CAR-T) cell therapy, CAR-T cells must be manufactured without failure caused by suboptimal expansion. In order to determine risk factors for CAR-T cell manufacturing failure, we performed a nationwide cohort study in Japan and analysed patients with diffuse large B-cell lymphoma (DLBCL) who underwent tisagenlecleucel production. We compared clinical factors between 30 cases that failed (7.4%) with those that succeeded (n = 378). Among the failures, the proportion of patients previously treated with bendamustine (43.3% vs. 14.8%; p < 0.001) was significantly higher, and their platelet counts (12.0 vs. 17.0 × 10⁴/μL; p = 0.01) and CD4/CD8 T-cell ratio (0.30 vs. 0.56; p < 0.01) in peripheral blood at apheresis were significantly lower than in the successful group. Multivariate analysis revealed that repeated bendamustine use with short washout periods prior to apheresis (odds ratio [OR], 5.52; p = 0.013 for ≥6 cycles with washout period of 3–24 months; OR, 57.09; p = 0.005 for ≥3 cycles with washout period of <3 months), low platelet counts (OR, 0.495 per 105/μL; p = 0.022) or low CD4/CD8 ratios (<one third) (OR, 3.249; p = 0.011) in peripheral blood at apheresis increased the risk of manufacturing failure. Manufacturing failure remains an obstacle to CAR-T cell therapy for DLBCL patients. Avoiding risk factors, such as repeated bendamustine administration without sufficient washout, and risk-adapted strategies may help to optimize CAR-T cell therapy for DLBCL patients

トウカ ニオケル ラジオハ ショウシャク リョウホウ オ モチイタ カンシュヨウ チリョウ : preliminary report

Radiofrequency ablation (RFA) has recently been used to treat liver tumors. RFA is a safe and effective treatment of liver tumors and requires fewer treatment sessions. Between June 2000 and April 2003, hepatocellular carcinoma (77 patients with 106 lesions) and metastatic liver tumors (21 patients with 30 lesions) and cholangiocellular carcinoma (1 patient with 1 lesion) were treated with RFA. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a LeVeen needle (55 lesions) and cool tip RF needle (82 lesions). To evaluate the response, contrast-enhanced CT scans or MRI were obtained. Most patients experienced moderate pain during RFA procedure, especially when the tumor was superficially located. Complete necrosis was achieved in all HCCs with RFA.This result was obtained with an average of 1.12 sessions per HCC. With a median follow-up of 15 months, HCCs have recurred in 6 of 90 treated lesions (6.7%), and metastatic liver tumors have recurred in 2 of 17 treated lesions (11.8%). We are initiating a combining RFA of hepatic malignancies with regional or systemic chemotherapy will reduce hepatic and extrahepatic recurrence rates and enhance long-term survival rates. We believe that RFA will be effective treatment to achieve in patients with unresectable meastatic liver tumors

Influence of environmental temperature and moisture conditions on fatigue resistance of concrete

It is known that the fatigue resistance of concrete decreases when the concrete is saturated with water and that the compressive strength increases with increasing water content at low temperatures below the freezing point of water. However, there have been few systematic studies on the influence of the ambient temperature and moisture content on the fatigue resistance of concrete. In the present study, static loading and fatigue tests were carried out on concrete cylinders to determine their fatigue resistance under compression. The test methods had been conducted to considered environmental temperatures and water contents. The results indicated that at room temperature, the static compressive strength decreases with increasing moisture content. In contrast, at a low temperature, the compressive strength of the samples increased with increasing moisture content. Furthermore, regardless of the temperature, the fatigue resistance decreased as the moisture content increased

Influence of environmental temperature and moisture conditions on fatigue resistance of concrete

It is known that the fatigue resistance of concrete decreases when the concrete is saturated with water and that the compressive strength increases with increasing water content at low temperatures below the freezing point of water. However, there have been few systematic studies on the influence of the ambient temperature and moisture content on the fatigue resistance of concrete. In the present study, static loading and fatigue tests were carried out on concrete cylinders to determine their fatigue resistance under compression. The test methods had been conducted to considered environmental temperatures and water contents. The results indicated that at room temperature, the static compressive strength decreases with increasing moisture content. In contrast, at a low temperature, the compressive strength of the samples increased with increasing moisture content. Furthermore, regardless of the temperature, the fatigue resistance decreased as the moisture content increased

ジシンリョク オ ウケル テッキン コンクリート キョウキャク ノ シンライセイ ニツイテ

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