Small-cell lung cancer with a rare epidermal growth factor receptor gene mutation showing “wax-and-wane” transformation

BACKGROUND: Small-cell lung cancer with epidermal growth factor receptor (EGFR) gene mutation typically manifests as a transformation occurring after EGFR tyrosine kinase inhibitor therapy for adenocarcinoma with EGFR mutation, whereas primary small-cell lung cancer showing EGFR mutation is extremely rare. Second biopsy of EGFR-mutated tumor has been broadly recognized as necessary, but is not always performed in daily practice, mainly due to the imbalance between the potential risk of the diagnostic procedure and the therapeutic impact of the biopsy result. CASE PRESENTATION: A 70-year-old woman who had never smoked was referred to our hospital with chief complaints of cough and back pain. Transbronchial lung biopsy from the primary tumor of the left upper lobe revealed combined small-cell lung cancer and adenocarcinoma, a subtype of small-cell lung cancer. EGFR L861Q mutation was detected in both small-cell lung cancer and adenocarcinoma components. Given the staging of cT2aN3M1b (Stage IV) and histological diagnosis, first-line chemotherapy with cisplatin plus irinotecan was initiated, and partial response was achieved. Seven months after initial diagnosis, the primary tumor enlarged again, and a second biopsy from the enlarged lesion detected only adenocarcinoma with the L861Q mutation. Erlotinib was started, but multiple brain metastases and enlarged mediastinal lymph nodes subsequently appeared. Whole-brain radiation therapy was performed, and endobronchial ultrasonography-guided transbronchial biopsy from the lymph node revealed reverse transformation to small-cell lung cancer with the L861Q mutation. Amrubicin therapy achieved partial response after two cycles, with the shrinkage lasting for eight months. Serum sialyl Lewis X antigen level increased when the adenocarcinoma component was dominant, whereas plasma pro-gastrin-releasing peptide level increased when the small-cell lung cancer component became dominant. CONCLUSIONS: Transformation of the tumor correlates with the difference between small-cell lung cancer and adenocarcinoma in sensitivity to therapies, so repeated biopsies are beneficial for choosing appropriate treatments. Noninvasively obtainable parameters such as tumor markers can support the need for biopsy

第768回千葉医学会例会・第3回磯野外科例会 83.

Chest computed tomography of DMM lesions of Case 4. Figure-path-case-4 (a) Low-power image of case 4. (b) High-power image of case 4. (ZIP 7796 kb

グアー起泡性アルブミンの起泡特性

From guar meal we recently isolated an albumin fraction with a high foaming ability, named guar foaming albumin (GFA) . Here, we further characterized the foaming activity, foam stability and surface tension of GFA solutions. Foaming activity and foam stability were estimated by measuring the conductivity of foam using a glass column with a conductivity cell. Surface tension was measured by the drop weight method using a stalagmometer. GFA showed higher foaming activity than casein at any protein concentrations compared. Foam stability of GFA was comparable to that of casein. The reduction of disulfide bonds of GFA did not significantly affect its foaming properties at higher concentrations ( ＞ 3 mg/ml) of GFA. The ability of GFA to reduce surface tension was substantially affected by the ionic strength of solutions, suggesting the importance of the electrostatic interaction of GFA in its foaming activity. These results indicated a potential usefulness of GFA as a foaming agent in food processing【目的】我々はグアー豆からグアーガムを精製する際に廃棄されるグアーミールから,起泡性の高いタンパク質画分を単離し,グアー起泡性アルブミンGFA(Guar　Foaming　Albumin)と命名した。本研究ではGFAの起泡性及び泡沫安定性を導電率によって定量的に測定し,さらに,起泡性の第一要件である表面張力の低下減少能を滴重法により測定することで,GFAの起泡特性を詳細に調べることとした。　【方法】タンパク質試料溶液に窒素ガスを通し,発生した泡の導電率を測定した。発生した泡がガラス管の上端に達するまでの時間を起泡時間とし,起泡性の評価として用いた。また,導電率の値の低下から,泡沫安定性を評価した。表面張力の測定には滴重法を用いた。　【結果・考察】GFAは,オボアルブミンやβ-カゼインと比べて,起泡性,泡沫安定性ともに優れていることがわかった。またGFAは,ジスルフィド結合を切断するメルカプトエタノールを加えても,影響を受けにくいことが示された。GFA溶液の表面張力は低タンパク質濃度で急激な減少を示したが,β-カゼインよりも低下可能は低かった。また塩の添加により表面張力低下能は促進された。pHによる影響を調べたところpH　7.0で表面張力は最低の値を示した。これらの結果,起泡性を利用する食品で,GFAは卵白などの代替タンパク質として使用できることが示唆された

Immunologic Significance of CD80/CD86 or Major Histocompatibility Complex-II Expression in Thymic Epithelial Tumors

Introduction: Unresectable or recurrent thymic epithelial tumors (TETs) have a poor prognosis, and treatment options are limited. This study aimed to investigate the immunologic significance of CD80/CD86 or major histocompatibility complex class II (MHC-II) expression in TETs, as potential predictive biomarkers for immune checkpoint inhibitors (ICIs). Methods: We analyzed CD80, CD86, MHC class I (MHC-I), and MHC-II expression in TETs using immunohistochemistry and investigated their association with T-cell infiltration or ICI efficacy. In addition, we generated CD80- or MHC-II–expressing mouse tumors, evaluated the effects of ICIs, and analyzed tumor-infiltrating lymphocytes. We also performed tumor-rechallenge experiments in vivo. Results: We found that approximately 50% and 30% of TETs had high expression of CD80/CD86 and MHC-II in tumor cells, respectively, and that this expression was related to T-cell infiltration in clinical samples. In mouse models, both CD80 and MHC-II increase the effects of ICIs. In addition, senescent T cells and long-lived memory precursor effector T cells were significantly decreased and increased, respectively, in tumor-infiltrating lymphocytes from CD80-expressing tumors, and rechallenged tumors were completely rejected after the initial eradication of CD80-expressing tumors by programmed cell death protein 1 blockade. Indeed, patients with CD80-high thymic carcinoma had longer progression-free survival with anti–programmed cell death protein 1 monoclonal antibody. Conclusions: Half of the TETs had high expression of CD80/CD86 or MHC-II with high T-cell infiltration. These molecules could potentially increase the effects of ICIs, particularly inducing a durable response. CD80/CD86 and MHC-II can be predictive biomarkers of ICIs in TETs, promoting the development of drugs for such TETs

Induction of lung lesions in Wistar rats by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone and its inhibition by aspirin and phenethyl isothiocyanate

<p>Abstract</p> <p>Background</p> <p>The development of effective chemopreventive agents against cigarette smoke-induced lung cancer could be greatly facilitated by suitable laboratory animal models, such as animals treated with the tobacco-specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). In the current study, we established a novel lung cancer model in Wistar rats treated with NNK. Using this model, we assessed the effects of two chemopreventive agents, aspirin and phenethyl isothiocyanate (PEITC), on tumor progression.</p> <p>Methods</p> <p>First, rats were treated with a single-dose of NNK by intratracheal instillation; control rats received iodized oil. The animals were then sacrificed on the indicated day after drug administration and examined for tumors in the target organs. PCNA, p63 and COX-2 expression were analyzed in the preneoplastic lung lesions. Second, rats were treated with a single-dose of NNK (25 mg/kg body weight) in the absence or presence of aspirin and/or PEITC in the daily diet. The control group received only the vehicle in the regular diet. The animals were sacrificed on day 91 after bronchial instillation of NNK. Lungs were collected and processed for histopathological and immunohistochemical assays.</p> <p>Results</p> <p>NNK induced preneoplastic lesions in lungs, including 33.3% alveolar hyperplasia and 55.6% alveolar atypical dysplasia. COX-2 expression increased similarly in alveolar hyperplasia and alveolar atypical dysplasia, while PCNA expression increased more significantly in the latter than the former. No p63 expression was detected in the preneoplastic lesions. In the second study, the incidences of alveolar atypical dysplasia were reduced to 10%, 10% and 0%, respectively, in the aspirin, PEITC and aspirin and PEITC groups, compared with 62.5% in the carcinogen-treated control group. COX-2 expression decreased after dietary aspirin or aspirin and PEITC treatment. PCNA expression was significantly reduced in the aspirin and PEITC group.</p> <p>Conclusion</p> <p>(1) A single dose of 25 mg/kg body weight NNK by intratracheal instillation is sufficient to induce preneoplastic lesions in Wistar rat lungs. (2) COX-2 takes part in NNK-induced tumorigenesis but is not involved in proliferation. (3) Aspirin and PEITC have protective effects in the early stages of tumor progression initiated by NNK.</p