Waxy wheat (Triticum aestivum L.) lacks the waxy protein, which is also known as granule-bound starch synthase I (GBSSI). The starch granules of waxy wheat endosperm and pollen do not contain amylose and therefore stain red-brown with iodine. However, we observed that starch from pericarp tissue of waxy wheat stained blue-black and contained amylose. Significantly higher starch synthase activity was detected in pericarp starch granules than in endosperm starch granules. A granule-bound protein that differed from GBSSI in molecular mass and isoelectric point was detected in the pericarp starch granules but not in granules from endosperm. This protein was designated GBSSII. The N-terminal amino acid sequence of GBSSII, although not identical to wheat GBSSI, showed strong homology to waxy proteins or GBSSIs of cereals and potato, and contained the motif KTGGL, which is the putative substratebinding site of GBSSI of plants and of glycogen synthase of Escherichia coli. GBSSII cross-reacted specifically with antisera raised against potato and maize GBSSI. This study indicates that GBSSI and GBSSII are expressed in a tissue-specific manner in different organs, with GBSSII having an important function in amylose synthesis in the pericarp.
BackgroundClear cell renal cell carcinoma (ccRCC) displays heterogeneity in appearance—a distinctive pale clear to eosinophilic cytoplasm; however, little is known about the underlying mechanisms and clinical implications. We investigated the role of these eosinophilic features in ccRCC on oncological outcomes and response to tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs).MethodsOne-hundred and thirty-eight ccRCC cases undergoing radical surgery (cohort 1) and 54 metastatic ccRCC cases receiving either TKIs or ICIs (cohort 2) were included. After histological evaluation, all cases were divided into three phenotypes based on the eosinophilic features at the highest-grade area: clear, mixed, or eosinophilic type. Gene expression and immunohistochemical analyses were performed to explore the potential mechanisms of these phenotypes in cohort 1. Further, the association of the three phenotypes with the best objective response to TKI or ICI, clinical benefit (complete/partial response or stable disease), and overall survival (OS) was assessed in cohort 2.ResultsThe clear type was significantly associated with increased hypoxia as well as angiogenesis gene signatures compared with the eosinophilic type. Gene signatures and protein expression related to effector T cell and immune checkpoint molecules were elevated to a greater extent in the eosinophilic type, followed by the mixed and clear types. The mixed and eosinophilic types exhibited greater PBRM1-negativity and increased prevalence of the epithelial-mesenchymal transition gene signature than the clear type. In the mixed/eosinophilic types of cohort 2, significant clinical benefit was observed in the ICI therapy group versus the TKI therapy group (p=0.035), and TKI therapy vs ICI therapy was an independent factor for worse prognosis of OS (HR 3.236; p=0.012).ConclusionThe histological phenotype based on the eosinophilic features, which are linked to major immunological mechanisms of ccRCC, was significantly correlated with therapeutic efficacy.
Molecular assessments of muscle‐invasive bladder cancer (MIBC) have yielded several molecular categorizations associated with basal and luminal subtypes or tumor‐associated immune cell status (TAICs). However, the histological relationships among histological subtypes, molecular subtypes, and TAICs and their clinical implications remain unclear. Thus, we aimed to evaluate the histological associations among these factors and their clinicopathological outcomes. We retrospectively analyzed 106 patients with MIBC who underwent radical cystectomy. The histological subtypes and TAICs were evaluated with hematoxylin and eosin staining, while the basal and luminal molecular subtypes were determined by immunohistochemical expression of cytokeratin (CK) 5/6, CK14, CK20, GATA3 and uroplakin II. Urothelial carcinoma with squamous differentiation and the sarcomatoid variant were highly associated with the basal subtype (P < 0.001 and P = 0.04, respectively). Additionally, high TAICs were significantly correlated with the basal subtype (P < 0.001). Although there was no significant difference in the cancer‐specific survival (CSS) rate between molecular subtypes (P = 0.295), TAICs significantly discriminated CSS rates (P < 0.001). Furthermore, the combination of molecular subtypes and TAICs significantly stratified cancer‐specific mortality rates. In conclusion, a comprehensive pathological evaluation of histological subtypes, molecular subtypes, and TAICs is feasible and can influence the oncological outcome.
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