Interaction of β-lactoglobulin with chaperonin GroEL

Sakai, Kazuko, Hoshino, Masaru and Goto, Yuji "Interaction of β-lactoglobulin with chaperonin GroEL", Proceedings of the Indian National Science Academy, 68, 4A, 341-347, Indian National Science Academy, 200

Multiple Myeloma Presenting Symptoms in the Oral and Maxillofacial Region

Four cases of multiple myeloma presenting symptoms in the oral and maxillofacial region are reported. The main complaints in 2 patients were macroglossia and dysphagia. We doubted these cases were amyloidosis, but examinations performed for possible amyloidosis led us to a diagnosis of multiple myeloma. The other 2 patients presented signs in the mandible. One of them had a mass-type lesion in the gingiva which upon X-ray revealed an osteolytic lesion in the mandible and multiple "punched-out" osteolytic lesions in the cranial bones. The other showed only a diffuse non-homogeneous radiolucent lesion and dental ankylosis. Medical history and biochemical and hematologic findings would be helpful in diagnosing multiple myeloma. Here, we report our summarization of these 4 cases

Nucling Regulates Mammary Gland Involution

Postpartum mammary gland involution is the physiological process by which the lactating gland returns to its pre-pregnant state. In rodent models, the microenvironment of mammary gland involution is sufficient to induce enhanced tumor cell growth, local invasion, and metastasis. Therefore, a deeper understanding of the physiological regulation of involution may provide in-depth information on breast cancer therapy. We herein identified Nucling as an important regulator of involution of the mammary gland. A knock-out mouse model was generated and revealed that postpartum involution were impaired in mice lacking Nucling. Involution is normally associated with an increase in the activation of NF-κB and STAT3, which is required for the organized regulation of involution, and was observed in WT glands, but not in the absence of Nucling. Furthermore, the loss of Nucling led to the suppression of Calpain- 1, IL-6, and C/EBPδ factors, which are known to be essential for normal involution. The number of M2 macrophages, which are crucial for epithelial cell death and adipocyte repopulation after weaning, was also reduced in Nucling-KO glands. Taken together, the results of the present study demonstrated that Nucling played an important role in mammary gland involution by regulating NF-κB and STAT3 signaling pathways

A 6-Year Controlled Gastric Adenocarcinoma Metastasized to the Lung, Cervical Spine and Mandible in a Japanese Male: A Patient Report

Gastric adenocarcinoma metastasized to the lung, cervical vertebrae and mandible 6 years after gastrectomy in a 70-year-old man. When the man visited our clinic, he complained of pain in the left mandible with paralysis in the left lower lip and diffuse swelling with a fluctuation inside the left ramus of the mandible. Medium contrast computed tomography (CT) presented bone loss that looked like a wormhole at the left angle of the mandible. Magnetic resonance imaging (MRI) revealed abscess or osteomyelitis at the site. He showed no response despite treatment with antibiotics, and we suspected a neoplastic lesion. With a mandibular ramus specimen obtained by biopsy and examined histopathologically, adenocarcinoma of the salivary gland was strongly suspected. MRI presented a neoplastic lesion in his cervical vertebrae, and by biopsy he was diagnosed with adenocarcinoma. Thereafter, chest CT presented multiple pulmonary metastases. Considering the patient’s history of gastrectomy due to gastric adenocarcinoma, the stomach, cervical vertebrae or mandible were examined pathologically and immunohistochemically by biopsy: all specimens showed a moderately differentiated type of tubular adenocarcinoma, and the results for cytokeratin-related tumor markers were the same. We finally diagnosed him as having metastases from gastric adenocarcinoma to the lung, cervical vertebrae and mandible. Because the metastases had spread to multiple organs, the mandibular lesion was not treated, and terminal care in another facility was unavoidably selected. In making a differential diagnosis of multiple metastases, pathological and immunohistochemical examinations of metastatic lesions by biopsy were very useful based on the diagnostic imagings by CT and MRI

Ciliated muconodular papillary tumors of the lung with KRAS/BRAF/AKT1 mutation

Background: Ciliated muconodular papillary tumors (CMPTs) are newly recognized rare peripheral lung nodules that are histologically characterized by ciliated columnar, goblet, and basal cells. Although recent studies have shown that CMPTs constitute a neoplastic disease, the complete histogenesis of CMPTs is not fully understood and molecular data are limited. Methods: We reviewed four cases of CMPT and performed immunohistochemical and genomic analyses to establish CMPT profiles. Results: All cases were positive for hepatocyte nuclear factor-4α and mucin 5B and negative for programmed death ligand 1 expression, as determined by immunohistochemistry. The genetic analysis revealed three pathogenic mutations (BRAF V600E, AKT1 E17K, and KRAS G12D), with the KRAS mutation reported here for the first time. Conclusion: Histological and genetic profiles indicate that CMPTs are likely neoplastic and exhibit features similar to mucinous adenocarcinoma. This suggests that some CMPTs may be a precursor lesion of mucinous adenocarcinoma

Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody

Introduction: Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Methods: Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Results: Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells. Discussion/Conclusion: The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI