The cancer stem cell (CSC) theory features typically rare self‐renewing subpopulations that reconstitute the heterogeneous tumor. Identification of molecules that characterize the features of CSCs is a key imperative for further understanding tumor heterogeneity and for the development of novel therapeutic strategies. However, the use of conventional markers of CSCs is still insufficient for the isolation of bona fide CSCs. We investigated organoids that are miniature forms of tumor tissues by reconstructing cellular diversity to identify specific markers to characterize CSCs in heterogeneous tumors. Here, we report that the receptor for hyaluronan‐mediated motility (RHAMM) expresses in a subpopulation of CD44+ conventional human colorectal CSC fraction. Single‐cell transcriptomics of organoids highlighted RHAMM‐positive proliferative cells that revealed distinct characteristics among the various cell types. Prospectively isolated RHAMM+CD44+ cells from the human colorectal cancer tissues showed highly proliferative characteristics with a self‐renewal ability in comparison with the other cancer cells. Furthermore, inhibition of RHAMM strongly suppressed organoid formation in vitro and inhibited tumor growth in vivo. Our findings suggest that RHAMM is a potential therapeutic target because it is a specific marker of the proliferative subpopulation within the conventional CSC fraction.
Desmoid tumors are clonal fibroblastic neoplasms that arise in soft tissues. Patients with familial adenomatous polyposis (FAP) can develop intra-abdominal desmoid tumors. However, metachronous appearance of intra-abdominal desmoid tumor is rare, and its clinical course is not well known. Here, we report a case of spontaneous regression of metachronous intra-abdominal desmoid tumor in a 36-year-old man with FAP. The patient was diagnosed with FAP and underwent laparoscopic total colorectomy. Intra-abdominal desmoid tumor appeared 2 years later and progressed despite treatment with tamoxifen and sulindac. He received four cycles of combinatory therapy with dacarbazine and adriamycin, resulting in shrinkage and stabilization of the desmoid tumor even after cessation of chemotherapy. A new intra-abdominal desmoid tumor developed 2 years later at a different site from the first lesion and progressed from 65 mm to 70 mm in diameter within a month. The size of the first lesion, however, remained unchanged. We prepared for chemotherapy because the second lesion progressed, but follow-up computed tomography showed spontaneous shrinkage of the second lesion. The patient still has not needed additional therapy as of more than 4 years after the appearance of the second lesion. Immunohistochemical staining showed the presence of macrophages in the second lesion. Although metachronous intra-abdominal desmoid tumor is rare and management protocols have yet to be established, this case suggests that an active surveillance approach may be applicable under careful follow-up in asymptomatic patients.
Rhabdomyosarcoma at para-meningeal regions of the head and neck has a poor prognosis in children. However, there is insufficient data on its outcomes in adults. We retrospectively examined total 10 patients with adult para-meningeal head and neck rhabdomyosarcoma treated at institutions belonging to the Kyushu Medical Oncology Group. Their characteristics were as follows: median age: 39 years (range 25–63 years), histology (alveolar/spindle): 9/1, and risk group (intermediate/high): 6/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 9 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in five patients. The median progression-free survival was 11.4 months (95%CI: 5.2–25.8 months): 14.2 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2–25.8 months) for patients with stage IV. Median overall-survival in all patients was 40.8 months (95%CI: 9.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 3 years after completion of the last therapy. Although the prognosis of adult para-meningeal head and neck rhabdomyosarcoma is poor regarding to progression-free survival, some patients experience prolonged survival with salvage therapy.
Drug-induced immune thrombocytopenia (DITP) is an important cause of thrombocytopenia. A 73-year-old man with relapsed rectal carcinoma received S-1, oxaliplatin and bevacizumab combination therapy (SOX+ Bev). Dexamethasone was administered as an antiemetic prophylaxis. On day 2 of the first cycle, thrombocytopenia (8,000/μL) was observed. We sequentially omitted any drugs suspected to possibly induce thrombocytopenia and confirmed dexamethasone as the cause of thrombocytopenia. DITP induced by synthetic corticosteroids is very rare and this is the first case report of DITP induced by dexamethasone. Although rare, DITP due to synthetic corticosteroids including dexamethasone should be a differential diagnosis among patients receiving synthetic corticosteroids with thrombocytopenia.
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