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#31962011   // Save this To Up

Analysis of Wnt7B and BMP4 expression patterns in congenital pulmonary airway malformation.

Congenital pulmonary airway malformation (CPAM) is a rare disorder characterized by aberrant overgrowth of terminal bronchioles. The objective of this study was to describe wingless-type MMTV integration site family 7B (Wnt7B) and bone morphogenetic protein 4 (BMP4) expression patterns in human CPAM lesions and to explore the possible roles of Wnt7B and BMP4 in the pathogenesis of CPAM.

1870 related Products with: Analysis of Wnt7B and BMP4 expression patterns in congenital pulmonary airway malformation.

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#31961485   // Save this To Up

Resibufogenin (RB) Inhibited Colorectal Cancer Cell Growth and Tumorigenesis through Triggering Ferroptosis and ROS Production Mediated by GPX4 Inactivation.

Resibufogenin (RB) has been used for cancer treatment, but the underlying mechanisms are still unclear. This study aimed to investigate the effects of RB treatment on colorectal cancer (CRC) cells, and to determine the underlying mechanisms.

1902 related Products with: Resibufogenin (RB) Inhibited Colorectal Cancer Cell Growth and Tumorigenesis through Triggering Ferroptosis and ROS Production Mediated by GPX4 Inactivation.

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#31959887   // Save this To Up

Machine learning with autophagy-related proteins for discriminating renal cell carcinoma subtypes.

Machine learning techniques have been previously applied for classification of tumors based largely on morphological features of tumor cells recognized in H&E images. Here, we tested the possibility of using numeric data acquired from software-based quantification of certain marker proteins, i.e. key autophagy proteins (ATGs), obtained from immunohistochemical (IHC) images of renal cell carcinomas (RCC). Using IHC staining and automated image quantification with a tissue microarray (TMA) of RCC, we found ATG1, ATG5 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were significantly reduced, suggesting a reduction in the basal level of autophagy with RCC. Notably, the levels of the ATG proteins expressed did not correspond to the mRNA levels expressed in these tissues. Applying a supervised machine learning algorithm, the K-Nearest Neighbor (KNN), to our quantified numeric data revealed that LC3B provided a strong measure for discriminating clear cell RCC (ccRCC). ATG5 and sequestosome-1 (SQSTM1/p62) could be used for classification of chromophobe RCC (crRCC). The quantitation of particular combinations of ATG1, ATG16L1, ATG5, LC3B and p62, all of which measure the basal level of autophagy, were able to discriminate among normal tissue, crRCC and ccRCC, suggesting that the basal level of autophagy would be a potentially useful parameter for RCC discrimination. In addition to our observation that the basal level of autophagy is reduced in RCC, our workflow from quantitative IHC analysis to machine learning could be considered as a potential complementary tool for the classification of RCC subtypes and also for other types of tumors for which precision medicine requires a characterization.

2541 related Products with: Machine learning with autophagy-related proteins for discriminating renal cell carcinoma subtypes.

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#31959546   // Save this To Up

Comprehensive Assessment of Immuno-oncology Biomarkers in Adenocarcinoma, Urothelial Carcinoma, and Squamous-cell Carcinoma of the Bladder.

In patients with rare histologies of bladder cancer, including adenocarcinoma of the bladder (ACB) and squamous-cell carcinoma (SCC), there are limited standard therapy options, defining an unmet medical need.

2125 related Products with: Comprehensive Assessment of Immuno-oncology Biomarkers in Adenocarcinoma, Urothelial Carcinoma, and Squamous-cell Carcinoma of the Bladder.

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#31959427   // Save this To Up

In-vivo regeneration of bladder muscular wall with whole decellularized bladder matrix: A novel hourglass technique for duplication of bladder volume in rabbit model.

To determine histological aspects of decellularized bladder graft to achieve a double-sized bladder by novel hourglass technique; using rabbit models.

1673 related Products with: In-vivo regeneration of bladder muscular wall with whole decellularized bladder matrix: A novel hourglass technique for duplication of bladder volume in rabbit model.

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#31958674   // Save this To Up

Identification of the JAK-STAT pathway in canine splenic hemangiosarcoma, thyroid carcinoma, mast cell tumor, and anal sac adenocarcinoma.

Dysregulation of the Janus Kinase (JAK) - Signal Transducer and Activator of Transcription (STAT) cellular signaling pathway has been associated with the development and progression of multiple human cancers. STAT3 has been reported to be present and constitutively active in a number of veterinary cancers, and few studies have reported mutations or activation of JAK1 or JAK2. Archived tissue samples from 54 client-owned dogs with histologically-diagnosed HSA, MCT, TC, or AGASACA were evaluated by immunohistochemical scoring of JAK1, JAK2, STAT3, and the phosphorylated counterparts pJAK1, pJAK2, and pSTAT3. IHC scoring was retrospectively analyzed with retrospectively-collected clinical parameters, including patient characteristics, metastasis, and survival. JAK1, pJAK1, JAK2, pJAK2, STAT3, and pSTAT3 were present in all tumor types evaluated. Significant correlations between JAK 1/2 or STAT3 and activated or downstream components were identified in all tumor types. Clinically, pSTAT3 was correlated with development of metastasis in dogs with MCT, while increased JAK1 expression or activation may impact survival in dogs with MCT or HSA. These findings provide a foundation to further investigate the JAK-STAT pathway in canine malignancies for additional therapeutic options.

2985 related Products with: Identification of the JAK-STAT pathway in canine splenic hemangiosarcoma, thyroid carcinoma, mast cell tumor, and anal sac adenocarcinoma.

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#31958633   // Save this To Up

VDR in Salivary Gland Homeostasis and Cancer.

The vitamin D receptor (VDR) and its ligand 1,25(OH)D (1,25D) impact differentiation and exert anti-tumor effects in many tissues, but its role in salivary gland has yet to be defined. Using immunohistochemistry (IHC), we have detected strong VDR expression in murine and human salivary gland ducts. Compared to normal gland, VDR protein expression was retained in differentiated human pleomorphic adenoma (PA) but was undetectable in undifferentiated PA and in carcinomas, suggesting deregulation of VDR during salivary cancer progression. To gain insight into the potential role of VDR in salivary cancer, we assessed the effects of vitamin D in vivo and in vitro. Despite the presence of VDR in salivary gland, chronic dietary vitamin D restriction did not alter morphology of the salivary epithelium in C57/Bl6 mice. The localization of VDR in ductal epithelium prompted us to examine the effects of 1,25D in an established cell line (mSGc) derived from normal murine submandibular gland (SMG). This previously characterized cell line consists of multiple stem, progenitor and differentiated cell types as determined by mutually exclusive cellular expression of basal, ductal and myoepithelial markers. We demonstrated VDR expression and regulation of VDR target genes Vdr and Postn by 1,25D in mSGc, indicating functional ligand-mediated transcriptional activity. The effect of VDR signaling on epithelial differentiation markers was assessed by qPCR and IHC in mSGc cells treated with 1,25D. We found that 1,25D reduced mRNA expression of the basal cell progenitor marker keratin 5 (K5) and increased expression of the differentiated ductal cell marker keratin 7 (K7). Further, we found that 1,25D significantly decreased the number of proliferating cells, including proliferating K5 cells. Characterization of cell cycle by Muse cytometry indicated 1,25D treatment decreased cells in S, G, and M phase. The inhibition of K5 cell proliferation by 1,25D is of particular interest because K5 basal cells contribute to a wide variety of salivary tumor types. Our studies suggest that 1,25D alters cancer-relevant progenitor and differentiation markers in the salivary gland.

2593 related Products with: VDR in Salivary Gland Homeostasis and Cancer.

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#31957823   // Save this To Up

Fyn stimulates the progression of pancreatic cancer via Fyn-GluN2b-AKT axis.

To assess the expression levels of Fyn in human tissue samples and pancreatic cancer cells and explore the potential mechanisms of Fyn in pancreatic cancer progression.

1474 related Products with: Fyn stimulates the progression of pancreatic cancer via Fyn-GluN2b-AKT axis.

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#31956475   // Save this To Up

Bone decalcification to assess programmed cell death ligand 1 expression in bone metastases of non-small cell lung cancers.

As for molecular alterations of lung adenocarcinoma, it is critical that pathologists are able to give PD-L1 expression status before first-line of treatment. The present study compared PD-L1 expression (clone 22-C3) in decalcified using EDTA or formic acid and non-decalcified lung cancer metastases bone samples. Amongst the 84 bone samples analysed for PD-L1 expression, and independently of decalcification, TPS ≥ 1% was 25.0% and ≥ 50% was 11.4%. There was no significant difference between decalcified samples ( = 45) and non-decalcified samples ( = 39) for both TPS ≥ 1% ( = 0.32) and TPS ≥ 50% ( = 1). To conclude, we confirm decalcified bone metastasis specimens may be used for PD-L1 IHC in routine practice. These results also highlight potentially interesting specificities of the bone microenvironment that should be further studied.

2289 related Products with: Bone decalcification to assess programmed cell death ligand 1 expression in bone metastases of non-small cell lung cancers.

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#31956474   // Save this To Up

The immune landscape of chondrosarcoma reveals an immunosuppressive environment in the dedifferentiated subtypes and exposes CSFR1+ macrophages as a promising therapeutic target.

Survival rate for Chondrosarcoma (CHS) is at a standstill, more effective treatments are urgently needed. Consequently, a better understanding of CHS biology and its immune environment is crucial to identify new prognostic factors and therapeutic targets. Here, we exhaustively describe the immune landscape of conventional and dedifferentiated CHS. Using IHC and molecular analyses (RT-qPCR), we mapped the expression of immune cell markers (CD3, CD8, CD68, CD163) and immune checkpoints (ICPs) from a cohort of 27 conventional and 49 dedifferentiated CHS. The impact of the density of tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and immune checkpoints (ICPs) on clinical outcome were analyzed. We reveal that TAMs are the main immune population in CHS. Focusing on dedifferentiated CHS, we found that immune infiltrate composition is correlated with patient outcome, a high CD68+/CD8+ ratio being an independent poor prognostic factor ( < 0.01), and high CD68+ levels being associated with the presence of metastases at diagnosis ( < 0.05). Among the ICPs evaluated, CSF1R, B7H3, SIRPA, TIM3 and LAG3 were expressed at the mRNA level in both CHS subtypes. Furthermore, PDL1 expression was confirmed by IHC exclusively in dedifferentiated CHS (42.6% of the patients) and CSF1R was expressed by TAMs in 89.7% of dedifferentiated CHS (vs 62.9% in conventional). Our results show that the immune infiltrate of CHS is mainly composed of immunosuppressive actors favoring tumor progression. Our results indicate that dedifferentiated CHS could be eligible for anti-PDL1 therapy and more importantly immunomodulation through CSF1R + macrophages could be a promising therapeutic approach for both CHS subtypes.

1811 related Products with: The immune landscape of chondrosarcoma reveals an immunosuppressive environment in the dedifferentiated subtypes and exposes CSFR1+ macrophages as a promising therapeutic target.

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