野口 忠秀

The relapse of tongue cancer (TC) after chemotherapy is caused by minimal residual disease (MRD), which is a few remaining cancer cells after chemotherapy. To understand the mechanism of MRD in TC, we created a library of TC organoids (TCOs) from 28 untreated TC patients at diverse ages and cancer stages. These TCOs reproduced the primary TC tissues both in vitro and in a xenograft model, and several TCO lines survived after cisplatin treatment (chemo-resistant TCOs). Of note, the chemo-resistant TCOs showed "heritable" embryonic diapause-like features before treatment and activation of the autophagy and cholesterol biosynthetic pathways. Importantly, inhibiting these pathways with specific inhibitors converted the chemo-resistant TCOs into chemo-sensitive TCOs. Conversely, autophagy activation with mTOR inhibitors conferred chemo-resistance on the chemo-sensitive TCOs. This unique model provides insights into the mechanism of MRD formation in TCs, leading to effective therapeutic approaches to reduce the recurrence of TC.

ABSTRACT Background Double‐hit lymphoma shows a poor prognosis, necessitating early diagnosis to improve prognosis. Case Presentation A 68‐year‐old Japanese woman presented with pain and a click in the right temporomandibular joint. The right side of her neck was acutely swollen. A biopsy of a mass lesion and lymph node suggested diffuse large B‐cell lymphoma; chromosomal analyses revealed MYC and BCL2 rearrangements. Complete response was achieved with chemotherapy. Peripheral blood stem cell transplantation was performed, but the patient relapsed. She died due to respiratory failure. Conclusion Double‐hit lymphoma is often accompanied by cervical lymphadenopathy. Lymph node biopsy is useful for early diagnosis.