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Search results for: IHC

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#36484761   2022/12/09 To Up

Prognostic significance of p16, p21, and Ki67 expression at the invasive front of colorectal cancers.

Cancer cells at the invasive front are believed to be responsible for invasion/metastasis. This has led to examining various morphological features and protein expressions at the invasive front. However, accurate assessment of the pathological section requires long-time training, and inter-observer disagreement is problematic. Immunohistochemistry and digital imaging analysis may mitigate these problems; however, the choice of which proteins to stain and the best analysis method remains controversial. We used the "go-or-grow" hypothesis to select markers with the greatest prognostic relevance. Importantly, nonproliferating cells can migrate. We used Ki67 as a proliferation marker, with p16 and p21 designating nonproliferating cells. We established a semi-automated quantification workflow to study protein expression in serial pathological sections. A total of 51 patients with completely resected colorectal cancer (stages I-IV) were analyzed, and 44 patients were followed up. Patients with cancer cells with p16-high/p21-low or p21-low/Ki67-low at the deepest invasive front demonstrated a significantly worse prognosis than those who did not display these characteristics. These results suggest that the nonproliferating cancer cells at the invasion front possess invasion/metastatic property with heterogeneity of senescence.
Ryosuke Kin, Daisuke Hoshi, Hideto Fujita, Takeo Kosaka, Hiroyuki Takamura, Etsuko Kiyokawa

2816 related Products with: Prognostic significance of p16, p21, and Ki67 expression at the invasive front of colorectal cancers.

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#36484721   2022/12/09 To Up

HRS regulates small extracellular vesicle PD-L1 secretion and is associated with anti-PD-1 treatment efficacy.

PD-L1 localized to immunosuppressive small extracellular vesicles (sEV PD-L1) contributes to tumor progression and is associated with resistance to immune checkpoint blockade (ICB) therapy. Here, by establishing a screening strategy with a combination of tissue microarray (TMA), IHC staining and measurement of circulating sEV PD-L1, we found the endosomal sorting complex required for transport (ESCRT) member protein hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) was the key regulator of circulating sEV PD-L1 in head and neck squamous cells carcinoma (HNSCC) patients. Increased HRS expression was found in tumor tissues and positively correlated with elevated circulating sEV PD-L1 in patients with HNSCC. The expression of HRS was also negatively correlated to the infiltration of CD8+ T cells. Knockdown of HRS markedly reduced PD-L1 expression in HNSCC cell-derived sEVs, and these sEVs from HRS KD cells showed decreased immunosuppressive effects on CD8+ T cells. Knockout of HRS inhibited tumor growth in immunocompetent mice together with PD-1 blockade. Moreover, a higher HRS expression was associated with a lower response rate to anti-PD-1 therapy in patients with HNSCC. In summary, our study reveals HRS, the core component of ESCRT-0, regulates sEV PD-L1 secretion and is associated with the response to ICB therapy in patients with HNSCC, suggesting HRS is a promising target to improve cancer immunotherapy.
Bo-Lin Xiao, Xiao-Le Wang, Hou-Fu Xia, Lin-Zhou Zhang, Kui-Ming Wang, Zhuo-Kun Chen, Ya-Hua Zhong, Huan-Gang Jiang, Fu-Xiang Zhou, Wei Wang, Gai-Li Chen, Gang Chen

2956 related Products with: HRS regulates small extracellular vesicle PD-L1 secretion and is associated with anti-PD-1 treatment efficacy.

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#36484062   2022/11/29 To Up

Topical Application of Chinese Formula Yeliangen Promotes Wound Healing in Streptozotocin-Induced Diabetic Rats.

Diabetic wound is one of the most severe complications of diabetes mellitus (DM). Despite the associated risks of wound healing impairment in diabetes, treatment strategies remain limited. Yeliangen (YLG) is a Chinese formulation mainly composed of the rhizome of , the root of , and the leaf of . We investigated the wound healing effects of YLG in type 2 diabetic (T2DM) rats, which were induced by intraperitoneal administration of streptozotocin after a high-fat diet for four weeks. 3 × 3 cm full-thickness excisional wounds were created on the dorsal surface of rats and then divided to control (DC), negative (DPJ), positive (DPC), and YLG-treated (DYLG) groups. Rat's wounds were treated twice daily for 21 days. Wound area and wound contraction were detected on days 0, 3, 7, 14, and 21. Histopathological examinations were performed by H&E staining and immunohistochemistry (IHC). The biochemical parameters, mRNAs, and protein expressions were analyzed through enzyme-linked immunoassays (ELISA), qPCR, and western blot, respectively. Compared with other groups, the histological changes of wound tissue in the DYLG group were improved, and the expressions of CD31, eNOS, and PCNA were significantly upregulated. Besides, YLG significantly reduced the inflammatory factors' expressions of TNF-, NF-B, MMP-9, and IL-1B on days 7, 14, and 21 postwounding. Moreover, YLG induced angiogenesis and neovascularization by significantly increasing the levels of VEGF, TGF-1, EGF, PDGF, and SDF-1 on days 3, 7, and 14. In conclusion, YLG improved wound healing by reducing inflammation and increasing angiogenesis which may provide an alternative and effective approach for diabetic wound therapy.
Abdulbaset Al-Romaima, Xiong Guan, Xihui Qin, Yinan Liao, Guiming Qin, Shixiong Tang, Jie Feng

1928 related Products with: Topical Application of Chinese Formula Yeliangen Promotes Wound Healing in Streptozotocin-Induced Diabetic Rats.

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#36483974   // To Up

Folate receptor-targeted near-infrared photodynamic therapy for folate receptor-overexpressing tumors.

Photodynamic therapy (PDT) is a minimally invasive form of cancer therapy, and the development of a novel photosensitizer (PS) with optimal properties is important for enhancing PDT efficacy. Folate receptor (FR) membrane protein is frequently overexpressed in 40% of human cancer and a good candidate for tumor-specific targeting. Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety. A folate-linked, near-infrared (NIR)-sensitive probe, folate-Si-rhodamine-1 (FolateSiR-1), was previously developed and is expected to be applicable to NIR-PDT.
Winn Aung, Atsushi B Tsuji, Kenjiro Hanaoka, Tatsuya Higashi

1744 related Products with: Folate receptor-targeted near-infrared photodynamic therapy for folate receptor-overexpressing tumors.

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#36483015   2022/11/22 To Up

The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses.

Hearing depends on fast and sustained calcium-dependent synaptic vesicle fusion at the ribbon synapses of cochlear inner hair cells (IHCs). The implication of the canonical neuronal SNARE complex in this exocytotic process has so far remained controversial. We investigated the role of SNAP-25, a key component of this complex, in hearing, by generating and analyzing a conditional knockout mouse model allowing a targeted postnatal deletion of in IHCs. Mice subjected to IHC inactivation after hearing onset developed severe to profound deafness because of defective IHC exocytosis followed by ribbon degeneration and IHC loss. Viral transfer of in these mutant mice rescued their hearing function by restoring IHC exocytosis and preventing synapses and hair cells from degeneration. These results demonstrate that SNAP-25 is essential for normal hearing function, most likely by ensuring IHC exocytosis and ribbon synapse maintenance.
Charlotte Calvet, Thibault Peineau, Najate Benamer, Maxence Cornille, Andrea Lelli, Baptiste Plion, Ghizlène Lahlou, Julia Fanchette, Sylvie Nouaille, Jacques Boutet de Monvel, Amrit Estivalet, Philippe Jean, Vincent Michel, Martin Sachse, Nicolas Michalski, Paul Avan, Christine Petit, Didier Dulon, Saaid Safieddine

1185 related Products with: The SNARE protein SNAP-25 is required for normal exocytosis at auditory hair cell ribbon synapses.

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#36482538   // To Up

A case report of anterior mediastinal signet ring cell carcinoma.

Anterior mediastinal signet ring cell carcinoma (SRCC) is a rare tumor that has only been reported in two cases of thymic cancer. Positive immunohistochemistry (IHC) staining for caudal-type homeobox (CDX) 2, cytokeratin (CK) 20 and special AT-rich binding protein (SATB) 2 usually indicate gastrointestinal tumors but begin to appear in thymic cancers with enteric differentiation. Here, we describe a case of the anterior mediastinal SRCC with enteric differentiation who was correctly treated with surgery and chemo-radiation and was alive after four months.
Simin Liu, Anbang Zhao, Ming Mao

1285 related Products with: A case report of anterior mediastinal signet ring cell carcinoma.



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#36482448   2022/12/08 To Up

Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment.

Neuromedin U (NMU) was identified as one of the hub genes closely related to colorectal cancer (CRC) progression and was recently shown to be a motility inducer in CRC cells. Its autocrine signalling through specific receptors increases cancer cell migration and invasiveness. Because of insufficient knowledge concerning NMU accessibility and action in the tumour microenvironment, its role in CRC remains poorly understood and its potential as a therapeutic target is still difficult to define.
Patrycja Przygodzka, Kamila Soboska, Ewelina Sochacka, Marcin Pacholczyk, Marcin Braun, Hassan Kassassir, Izabela Papiewska-Pająk, Michal Kielbik, Joanna Boncela

2011 related Products with: Neuromedin U secreted by colorectal cancer cells promotes a tumour-supporting microenvironment.

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#36482313   2022/12/08 To Up

Patterns and prognostic predictive value of perineural invasion in esophageal squamous cell carcinoma.

The pathological phenotype of perineural invasion (PNI) in squamous cell carcinoma (ESCC) is prevalent but highly heterogeneous.
Yu Ma, Jie Chen, Xi Yao, Zhenzhen Li, Wensheng Li, Hongtao Wang, Jianfei Zhu

1637 related Products with: Patterns and prognostic predictive value of perineural invasion in esophageal squamous cell carcinoma.



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#36482310   2022/12/08 To Up

Tissue microarrey: a potential cost-effective approach for mismatch repair testing in colorectal cancer.

Deficiencies in Mismatch Repair (MMR) proteins are one of the major pathways in the development of colorectal cancer (CRC). MMR status evaluation is recommended in every new CRC patient. However, this is not fully implemented due to high costs. Tissue microarray (TMA) enables allocating tissue cores from few specimens to a single paraffin block. The primary objective of this study was to evaluate the accuracy of TMA MMR immunohistochemistry (IHC) compared to whole slide. The secondary objective was to evaluate and validate automatic digital image analysis software in differentiating pathological and normal TMA cores.
Shai Farkash, Naama Schwartz, Natalia Edison, Sophia Greenberg, Hila Belhanes Peled, Wail Sindiany, Judit Krausz

2122 related Products with: Tissue microarrey: a potential cost-effective approach for mismatch repair testing in colorectal cancer.



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#36482276   // To Up

Pitfalls in breast pathology.

Accurate pathological diagnosis is the cornerstone of optimal clinical management for patients with breast disease. As non-operative diagnosis has now become the standard of care, histopathologists encounter the daily challenge of making definitive diagnoses on limited breast core needle biopsy (CNB) material. CNB samples are carefully evaluated using microscopic examination of haematoxylin and eosin (H&E)-stained slides and supportive immunohistochemistry (IHC), providing the necessary information to inform the next steps in the patient care pathway. Some entities may be difficult to distinguish on small tissue samples, and if there is uncertainty a diagnostic excision biopsy should be recommended. This review discusses (1) benign breast lesions that may mimic malignancy, (2) malignant conditions that may be misinterpreted as benign, (3) malignant conditions that may be incorrectly diagnosed as primary breast carcinoma, and (4) some IHC pitfalls. The aim of the review is to raise awareness of potential pitfalls in the interpretation of breast lesions that may lead to underdiagnosis, overdiagnosis, or incorrect classification of malignancy with potential adverse outcomes for individual patients.
Cecily Quinn, Aoife Maguire, Emad Rakha

2175 related Products with: Pitfalls in breast pathology.



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