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HighlightsALK-rearranged inflammatory myofibroblastic tumor(IMT) of the bladder is a rare tumor.No standard therapeutic strategy for locally advanced cases has been established.Crizotinib is a promissing treatment for unresectable IMT with ALK rearrangements.Bladder-preserving surgery following neoadjuvant crizotinib is a preferred approach.
Renal cell carcinoma (RCC) is an aggressive genitourinary malignancy which has been associated with a poor prognosis, particularly in patients with metastasis, its major subtypes being clear cell RCC (ccRCC), papillary PCC (pRCC) and chromophobe RCC (chRCC). The presence of intracellular lipid droplets (LDs) is considered to be a hallmark of ccRCC. The importance of an altered lipid metabolism in ccRCC has been widely recognized. The elongation of very-long-chain fatty acid (ELOVL) catalyzes the elongation of fatty acids (FAs), modulating lipid composition, and is required for normal bodily functions. However, the involvement of elongases in RCC remains unclear. In the present study, the expression of ELOVL2 in ccRCC was examined; in particular, high levels of seven ELOVL isozymes were observed in primary tumors. Of note, elevated ELOVL2 expression levels were observed in ccRCC, as well as in pRCC and chRCC. Furthermore, a higher level of ELOVL2 was significantly associated with the increased incidence of a poor prognosis of patients with ccRCC and pRCC. The CRISPR/Cas9-mediated knockdown of ELOVL2 resulted in the suppression of the elongation of long-chain polyunsaturated FAs and increased LD production in renal cancer cells. Moreover, ELOVL2 ablation resulted in the suppression of cellular proliferation via the induction of apoptosis in vitro and the attenuation of tumor growth in vivo. On the whole, the present study provides new insight into the tumor proliferation mechanisms involving lipid metabolism, and suggests that ELOVL2 may be an attractive novel target for RCC therapy.
Objectives
To identify the clinicopathological features of malignant urachal tumor in Japan, and analyze the 5‐year overall survival of malignant urachal tumor patients.
Methods
We used the hospital‐based cancer registry data to extract malignant urachal tumor cases that were diagnosed in 2008–2009 and 2012–2015, histologically confirmed, and received the first course of treatment. We analyzed the 5‐year overall survival using the 2008–2009 cohort’s data.
Results
We identified 456 patients, and malignant urachal tumor accounted for 0.4% of all malignant bladder cancers. The median age was 61 years (range 2–97), and 66% were men. The most common histology was adenocarcinoma (80%), followed by urothelial carcinoma (11%) and squamous cell carcinoma (3%). The proportions of patients were: 19% Ta/Tis/T1N0M0, 55% T2–3N0M0, 13% T4/N+ and 13% M+. Regarding the initial treatment, the proportions of surgery alone were 79% and 33% in cases of T3 or less N0M0 and T4/N+, respectively. The proportion of combination therapy including surgery and chemotherapy were 13% and 44% in T2–3N0M0 and T4/N+, respectively. Radiation therapy was not common at any stage. In the 2008–2009 cohort, the 5‐year overall survival rate in Ta/Tis/T1N0M0, T2–3N0M0, T4/N+ and M+ were 60%, 64%, 63% and 12%, respectively.
Conclusions
Malignant urachal tumors are quite rare in Japan, and most of those without metastasis are likely to be treated by surgery alone, even at advanced stages. A standard of care must be established for malignant urachal tumor patients at advanced stages or with metastasis, as the prognosis of these patients can be poor.
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