Adenoid cystic carcinoma of the peripheral lung: a case report

Adenoid cystic carcinoma of the peripheral lung is a rare entity. We recently encountered a patient with adenoid cystic carcinoma. A 75-year-old woman showed a nodular lesion with 10 mm in diameter in the right upper lung field on chest radiography. The diagnosis was unclear, but lung cancer could not be ruled out. Thoracoscopic biopsy was performed, and intraoperative pathological diagnosis revealed the carcinoma of the lung. We enforced upper lobectomy and mediastinal lymph node dissection to the patient. Histopathological examination revealed adenoid cystic carcinoma with a characteristic cribriform structure. Immunohistochemical examination revealed that the tumor cells were positive for thyroid transcription factor 1 (TTF-1), this tumor was diagnosed primary ACC of the lung

Infrequent RAS mutation is not associated with specific histological phenotype in gliomas

BACKGROUND: Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. METHODS: This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. RESULTS: RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. CONCLUSION: RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma

Analysis of DOC and Ram for NSCLC

Background: Current clinical trials demonstrated that combination regimens comprising chemotherapy and immunotherapy lead to better patient outcomes compared to chemotherapy alone as the first line of treatment for non-small cell lung cancer (NSCLC). In addition, the combination therapy of docetaxel (Doc) and ramucirumab (Ram) was considered one of the standard treatments for advanced or relapsed NSCLC patients. However, little is known about the therapeutic responders of this combination therapy among previously treated NSCLC patients. In the present study, we aimed to identify predictive factors for therapeutic response, including programmed death-ligand 1 (PD-L1) expression in tumors, for Doc treatment in combination with Ram. Methods: We retrospectively analyzed a total of 135 advanced or relapsed NSCLC patients who were refractory to platinum-based chemotherapy at eleven institutions in Japan between July 2016 and November 2018. Results: Our observations showed that PD-L1 expression in tumors is not associated with the efficacy of combined therapy of Doc and Ram in previously treated NSCLC patients. Analysis of the patient clinical profiles indicated that prior treatment with immune checkpoint inhibitors (ICIs) is a reliable predictor for the good progression-free survival (PFS) to this combination therapy (P=0.041). Conclusions: Our retrospective study indicated that combination regimens comprising chemotherapy and ICIs followed by Doc and Ram could be an optimal therapeutic option for NSCLC patients regardless of the PD-L1 status of tumors. Further investigations are required to strengthen clinical evidence demonstrating the effectiveness of the combination therapy of Doc plus Ram in previously treated NSCLC patients

Investigation of the outpatient chemotherapy for lung cancer patients in Tokushima University Hospital

Platinum-doublet regimens and docetaxel as first- and second-line chemotherapy, respectively, are shown to prolong the survival of lung cancer patients in various randomized phase III studies. However, the evidence for the efficacy of chemotherapy for lung cancer in the clinical practice is still insufficient. In the present study, we investigated the effectiveness and safety of outpatient chemotherapy for lung cancer in the clinical practice. Ninety-four lung cancer cases were retrospectively analyzed. Among these cases, 67 (71.3%) were non-small cell lung cancer (NSCLC) and 27 (28.7%) were small cell lung cancer (SCLC). The response rates in SCLC and NSCLC patients were 55.6% (15/27) and 16.9% (11/65), respectively. Objective tumor response rates for the patients were found to decrease substantially with each line of treatment as described previously. All adverse events were well tolerated and no treatment-related death was observed. Median time to treatment failures (TTFs) of first-line treatment were 10.1 months and 4.8 months in SCLC and NSCLC, respectively. These findings indicate that even in the setting of clinical practice, the efficacy and safety of chemotherapy is strictly insured by the appropriate therapeutic management

A multicenter, open‐label, phase II trial of pemetrexed plus bevacizumab in elderly patients with previously untreated advanced or recurrent nonsquamous non‐small cell lung cancer

Abstract Background Although the incidence of lung cancer in elderly individuals has been increasing in recent years, the number of clinical trials designed specifically for elderly patients with advanced non‐small cell lung cancer (NSCLC) is still limited. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of pemetrexed (PEM) plus bevacizumab (Bev) combination chemotherapy in elderly patients with nonsquamous NSCLC. Methods A total of 29 elderly patients (≥75 years old) with nonsquamous NSCLC were enrolled in this multicenter, open‐label, phase II study, and 27 patients were finally analyzed. PEM at 500 mg/m2 on day 1 plus Bev at 15 mg/kg on day 1 were administered triweekly. The primary endpoint was the investigator‐assessed objective response rate. Results The median age at initiating chemotherapy was 80 years old. Almost all patients (92.6%) had adenocarcinoma histology. The median number of cycles administered was 6, and the objective response rate was 40.7%. The median progression‐free survival, overall survival and 1‐year survival were 8.8 months, 27.2 months and 79%, respectively. The treatment was well‐tolerated, and no treatment‐related death was observed. Conclusion Combination chemotherapy with PEM plus Bev in elderly patients with previously untreated advanced non‐squamous NSCLC exhibited favorable antitumor activity and tolerability, suggesting that a combination of PEM plus Bev might be a promising treatment option for this population

Table1_miR-1260b inhibits periodontal bone loss by targeting ATF6β mediated regulation of ER stress.docx

The expression profiles of exosomal microRNAs (miRNAs) are regulated by the microenvironment, and appropriate priming with mesenchymal stem cells (MSCs) is one of the strategies to enhance the paracrine potency of MSCs. Our previous work demonstrated that exosomes from tumor necrosis factor (TNF)-α-primed human gingiva-derived MSCs (GMSCs) could be a therapeutic tool against periodontitis, and that TNFα-inducible exosomal miR-1260b is essential for the inhibition of alveolar bone loss. However, the precise molecular mechanism underlying miR-1260b-mediated inhibition of osteoclastogenesis is not yet fully understood. Here, we found that the activating transcription factor (ATF)-6β, a novel miR-1260b-targeting gene, is critical for the regulation of osteoclastogenesis under endoplasmic reticulum (ER) stress. An experimental periodontal mouse model demonstrated that induction of ER stress was accompanied by enhanced ATF6β expression, and local administration of miR-1260b and ATF6β siRNA using polyethylenimine nanoparticles (PEI-NPs) significantly suppressed the periodontal bone resorption. In periodontal ligament (PDL) cells, the ER stress inducer, tunicamycin, enhanced the expression of the receptor activator of NF-κB ligand (RANKL), while miR-1260b-mediated downregulation of ATF6β caused RANKL inhibition. Furthermore, the secretome from miR-1260b/ATF6β-axis-activated PDL cells inhibited osteoclastogenesis in human CD14+ peripheral blood-derived monocytes. These results indicate that the miR-1260b/ATF6β axis mediates the regulation of ER stress, which may be used as a novel therapeutic strategy to treat periodontal disease.</p