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B7-H3 at the crossroads between tumor plasticity and colorectal cancer progression: a potential target for therapeutic intervention

CANCER AND METASTASIS REVIEWS (2023)

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Article Gastroenterology & Hepatology

Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN

Eileen Morgan et al.

Summary: Colorectal cancer is the third most common cancer worldwide, with the highest incidence rates in Australia/New Zealand and Europe, and the lowest rates in Africa and Southern Asia. The burden of colorectal cancer is projected to increase by 2040, with the majority of cases predicted to occur in high HDI countries.

GUT (2023)

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Article Biochemistry & Molecular Biology

Resveratrol Modulates Chemosensitisation to 5-FU via beta 1-Integrin/HIF-1 alpha Axis in CRC Tumor Microenvironment

Aranka Brockmueller et al.

Summary: Resveratrol can enhance the sensitivity of colorectal cancer cells to 5-FU by regulating the beta 1-integrin/HIF-1α signaling axis, leading to suppression of cancer cell growth and invasion, inhibition of inflammation and cancer stem cell production. These findings highlight the potential application of resveratrol in the treatment of colorectal cancer by overcoming chemoresistance to 5-FU.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Review Biochemistry & Molecular Biology

New frontiers in immune checkpoint B7-H3 (CD276) research and drug development

Ayechew Adera Getu et al.

Summary: B7-H3 is a crucial factor in cancer progression, with selective expression in tumor cells and immune cells. It is involved in tumor cell proliferation, metastasis, and therapeutic resistance. Targeting B7-H3 offers cancer-specific toxicity and minimal harm to healthy cells, making it a promising target for cancer therapy.

MOLECULAR CANCER (2023)

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Article Biochemistry & Molecular Biology

Neoadjuvant enoblituzumab in localized prostate cancer: a single-arm, phase 2 trial

Eugene Shenderov et al.

Summary: B7-H3-targeting antibody enoblituzumab has shown potential clinical activity and safety in treating high-risk localized prostate cancer.

NATURE MEDICINE (2023)

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Article Oncology

B7H3 Role in Reshaping Immunosuppressive Landscape in MSI and MSS Colorectal Cancer Tumours

Sylwia Mielcarska et al.

Summary: Colorectal cancer (CRC) is a common malignant tumor with a high mortality rate. This study found that B7H3 is upregulated in CRC tumors and correlated with M2-macrophage polarization and tumor growth-promoting cytokines. Additionally, high B7H3 expression is associated with decreased survival in CRC patients. These findings provide new insights into the role of B7H3 in CRC immunity.

CANCERS (2023)

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Article Medicine, Research & Experimental

B7-H3 immunoregulatory roles in cancer

Keywan Mortezaee

Summary: B7-H3 is a checkpoint that is overexpressed in several human cancers and associated with poor prognosis. It drives immune evasion by impairing T cell infiltration and promoting CD8+ T cell exhaustion. High B7-H3 activity also induces pro-tumor macrophage polarization and aberrant angiogenesis, leading to resistance to immune checkpoint inhibitor therapy. Targeting B7-H3 in cancer immunotherapy holds promise as a desired approach.

BIOMEDICINE & PHARMACOTHERAPY (2023)

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Article Cell Biology

FDW028, a novel FUT8 inhibitor, impels lysosomal proteolysis of B7-H3 via chaperone-mediated autophagy pathway and exhibits potent efficacy against metastatic colorectal cancer

Mengmeng Wang et al.

Summary: Metastatic colorectal cancer (mCRC) lacks effective therapeutics, highlighting the need for new drugs. Fucosyltransferase 8 (FUT8) is highly expressed in CRC and mediates core fucosylation of CD276 (B7-H3), a key immune checkpoint molecule. The small-molecule inhibitor FDW028 targets FUT8 and demonstrates potent anti-tumor activity by defucosylation and lysosomal degradation of B7-H3. FUT8 inhibition destabilizes B7-H3 through chaperone-mediated autophagy, making FDW028 a promising therapeutic candidate for mCRC.

CELL DEATH & DISEASE (2023)

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Article Cell Biology

Exosomal B7-H3 facilitates colorectal cancer angiogenesis and metastasis through AKT1/mTOR/VEGFA pathway

Rendi Wu et al.

Summary: B7-H3 is highly expressed in various types of cancer and plays important roles in tumor immune evasion, carcinogenesis, metastasis, and angiogenesis. This study investigated the effects of cancer cell-derived exosomal B7-H3 on tumor angiogenesis and metastasis. The findings showed that exosomal B7-H3 from colorectal cancer cells was taken up by endothelial cells and activated the AKT1/mTOR/VEGFA signaling pathway, enhancing their migration, invasion, and tube formation abilities. Furthermore, exosomes with reinforced B7-H3 promoted pulmonary angiogenesis and metastasis in mice. High expression of B7-H3 was also observed in urinary exosomes from colorectal cancer patients.

CELLULAR SIGNALLING (2023)

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Article Cell Biology

CircHULC accelerates the growth of human liver cancer stem cells by enhancing chromatin reprogramming and chromosomal instability via autophagy

Shuting Song et al.

Summary: This study reveals that CircHULC promotes the growth of liver cancer stem cells and malignant differentiation of hepatocyte-like cells by regulating PKM2 methylation modification and autophagy. It also affects the expression of chromatin reprogramming factors and oncogenes. Thus, CircHULC may serve as a potential biomarker and therapeutic target for liver cancer.

CELLULAR SIGNALLING (2023)

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Article Oncology

Pediatric medulloblastoma express immune checkpoint B7-H3

S. Li et al.

Summary: This study examined the expression of immune checkpoint B7-H3 in pediatric MB. The results showed that B7-H3 was highly expressed in the majority of cases and that high expression of B7-H3 was associated with reduced infiltration of gamma delta T cells and CD3+ T cells.

CLINICAL & TRANSLATIONAL ONCOLOGY (2022)

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Article Oncology

B7 homolog 3 induces lung metastasis of breast cancer through Raf/MEK/ERK axis

Shuai Wang et al.

Summary: This study discovered elevated levels of B7-H3 in breast cancer, which were associated with poor prognosis. B7-H3 can promote lung metastasis in breast cancer through activation of the Raf/MEK/ERK axis.

BREAST CANCER RESEARCH AND TREATMENT (2022)

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Article Immunology

Microbiota-dependent activation of the myeloid calcineurin-NFAT pathway inhibits B7H3-and B7H4-dependent anti-tumor immunity in colorectal cancer

Kenneth Peuker et al.

Summary: Bacterial sensing by intestinal tumor cells contributes to tumor growth through the calcineurin-NFAT axis, while its inhibition can activate CD8(+) T cell responses and inhibit colorectal cancer growth. This pathway also controls the expression of B7H3 and B7H4 by tumor cells, which inhibits CD8(+) T cell-dependent anti-tumor immunity.

IMMUNITY (2022)

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Article Biochemistry & Molecular Biology

Evidence That beta 1-Integrin Is Required for the Anti-Viability and Anti-Proliferative Effect of Resveratrol in CRC Cells

Aranka Brockmueller et al.

Summary: This study found that resveratrol can exert its suppressive actions on tumor microenvironment (TME)-induced tumorigenesis in colorectal cancer (CRC) cells through the beta 1-integrin receptor. Resveratrol altered the distribution pattern and expression of beta 1-integrin on the surface of CRC cells in TME, leading to decreased cell proliferation and viability, and increased apoptosis. Inhibition of beta 1-integrin or interruption of downstream signaling pathway attenuated the anti-tumor effects of resveratrol. The results highlight the important role of beta 1-integrins as signal carriers for resveratrol in CRC cells.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Multidisciplinary Sciences

The immune checkpoint B7-H3 (CD276) regulates adipocyte progenitor metabolism and obesity development

Elodie Picarda et al.

Summary: The immune checkpoint B7-H3 has been studied in the tumor microenvironment and immunotherapy, but its potential role in metabolism remains largely unknown. This study reveals that B7-H3 is highly expressed in adipose tissue, particularly in adipocyte progenitor cells, and it regulates the glycolytic and mitochondrial activity of these cells. Loss of B7-H3 leads to impaired oxidative metabolism and increased lipid accumulation in derived adipocytes. Knockout of B7-H3 in mice results in spontaneous obesity, metabolic dysfunction, and adipose tissue inflammation.

SCIENCE ADVANCES (2022)

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Article Biotechnology & Applied Microbiology

B7-H3: A Useful Emerging Diagnostic Marker for Colon Cancer

Ozgur Bostanci et al.

Summary: This study found that the preoperative serum B7-H3 levels were significantly higher in colon cancer patients compared to healthy individuals, and it was associated with TNM staging, lymph node status, and distant metastasis. Therefore, B7-H3 could be a potential candidate diagnostic biomarker and therapeutic target in colon cancer.

BIOMED RESEARCH INTERNATIONAL (2022)

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Article Oncology

STRIVE-02: A first-in-human phase 1 trial of systemic B7H3 CAR T cells for children and young adults with relapsed/refractory solid tumors.

Navin R. Pinto et al.

JOURNAL OF CLINICAL ONCOLOGY (2022)

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Review Gastroenterology & Hepatology

Tumor microenvironment involvement in colorectal cancer progression via Wnt/β-catenin pathway: Providing understanding of the complex mechanisms of chemoresistance

Maria Belen Novoa Diaz et al.

Summary: The dysregulation of the Wnt/β-catenin pathway plays a central role in the development and progression of colorectal cancer, and is associated with chemoresistance and aggressiveness. The tumor microenvironment (TME) is crucial in the development and spread of colorectal cancer, as various cell types and biomolecules interact with tumor cells through paracrine factors. Understanding this complex disease in a global context is important for the development of novel and effective therapies.

WORLD JOURNAL OF GASTROENTEROLOGY (2022)

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Review Biochemistry & Molecular Biology

To kill a cancer: Targeting the immune inhibitory checkpoint molecule, B7-H3

Ranjana K. Kanchan et al.

Summary: The prominent deregulation of B7-H3 in various cancers may lead to tumor growth and metastasis, highlighting the importance of understanding its signaling properties for developing efficacious therapies. The article delves into the ways B7-H3 acts as an immunomodulator to promote tumor development and spread, proposing therapeutic strategies to exploit these interactions and associated limitations.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2022)

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Review Oncology

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

Binghao Zhao et al.

Summary: Immunotherapy targeting B7-H3 has shown promising potential for cancer treatment, as B7-H3 is overexpressed in many different cancer types and is associated with poor prognosis. Different approaches are being developed to target B7-H3 in immunotherapy, and ongoing clinical trials are investigating their safety and efficacy. This research suggests that B7-H3 is a valuable target for future immunotherapy, which could improve cancer treatment outcomes and benefit patients.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Oncology

Cellular and molecular mechanisms of plasticity in cancer

Stefan R. Torborg et al.

Summary: Cancer cells have plasticity and can rapidly adapt to their environment and evade therapy. This article provides an overview of the fundamental mechanisms underlying cancer cell plasticity, and highlights the crucial role of high-plasticity cell states in cell state transitions and intra-tumoral heterogeneity.

TRENDS IN CANCER (2022)

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Article Oncology

Soluble B7H3 level in breast cancer and its relationship with clinicopathological variables and T-cell infiltration

Okan Avci et al.

Summary: This study investigated the relationship between sB7H3 and breast cancer and found that sB7H3 may serve as a clinically practical biomarker to differentiate breast cancer from benign breast diseases.

WSPOLCZESNA ONKOLOGIA-CONTEMPORARY ONCOLOGY (2022)

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Article Oncology

miR-34a induces immunosuppression in colorectal carcinoma through modulating a SIRT1/NF-κB/B7-H3/TNF-α axis

Fanyi Meng et al.

Summary: This study revealed the mechanism of miR-34a-mediated immune evasion in colorectal cancer through inhibition of SIRT1 and promotion of the NF-kappa B/B7-H3/TNF-alpha axis.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2021)

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Review Biochemistry & Molecular Biology

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

Nadia Bolandi et al.

Summary: Gastric cancer is the third leading cause of death globally, despite a stable reduction in its incidence. Poor response to common treatments and late diagnosis make it a lethal cancer. The emerging use of immunotherapy and immune checkpoint inhibitors has changed the landscape of treatment for gastric cancer patients, with the manipulation of signals from the B7 family showing significant potential in management.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Oncology

B7-H3 and PD-L1 Expression Are Prognostic Biomarkers in a Multi-racial Cohort of Patients with Colorectal Cancer

Wei Zhang et al.

Summary: Low expression of both PD-L1 and B7-H3 in colorectal cancer is associated with better survival outcomes, without significant variation among different racial groups in terms of relevant protein markers for CRC.

CLINICAL COLORECTAL CANCER (2021)

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Article Oncology

Overexpression of B7-H3 Is Associated With Poor Prognosis in Laryngeal Cancer

Yixuan Li et al.

Summary: The study revealed that overexpression of B7-H3 in laryngeal squamous cell carcinoma is associated with clinical and pathological characteristics, serving as a potential biomarker for poor prognosis and a therapeutic target in LSCC.

FRONTIERS IN ONCOLOGY (2021)

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Article Cell Biology

B7-H3 suppresses doxorubicin-induced senescence-like growth arrest in colorectal cancer through the AKT/TM4SF1/SIRT1 pathway

Ruoqin Wang et al.

Summary: The study found that knocking down B7-H3 promoted cellular senescence induced by low-dose doxorubicin, while overexpression of B7-H3 inhibited it. Further analysis revealed that B7-H3 prevented cellular senescence and growth arrest through the AKT/TM4SF1/SIRT1 pathway, and targeting this pathway might be a new strategy for promoting cellular senescence during drug treatment in colorectal cancer.

CELL DEATH & DISEASE (2021)

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Review Biochemistry & Molecular Biology

Metabolic Reprogramming of Colorectal Cancer Cells and the Microenvironment: Implication for Therapy

Miljana Nenkov et al.

Summary: Colorectal carcinoma is a common cancer characterized by metabolic reprogramming that provides tumor cells with energy and nutrients for malignant growth. The metabolic crosstalk between tumor cells, the tumor microenvironment, and gut microbiota facilitates the development and therapy resistance of colorectal carcinoma.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Medicine, Research & Experimental

Molecular subtype identification and prognosis stratification by a metabolism-related gene expression signature in colorectal cancer

Dagui Lin et al.

Summary: Metabolic reprogramming is associated with cancer occurrence and progression in the tumor immune microenvironment. We identified two metabolism-related subtypes of CRC and developed a metabolic risk score (MRS) as a robust prognostic marker for survival prediction in CRC patients.

JOURNAL OF TRANSLATIONAL MEDICINE (2021)

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Article Biochemistry & Molecular Biology

MicroRNA miR-29a Inhibits Colon Cancer Progression by Downregulating B7-H3 Expression: Potential Molecular Targets for Colon Cancer Therapy

Jin Wang et al.

Summary: The research revealed that high expression of B7-H3 protein in colon cancer is associated with tumor staging, lymph node metastasis, and reduced survival. Meanwhile, miR-29a is preferentially expressed in normal tissues and slows down colon cancer progression and metastasis by downregulating B7-H3 expression.

MOLECULAR BIOTECHNOLOGY (2021)

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Article Endocrinology & Metabolism

Immune checkpoint B7-H3 protein expression is associated with poor outcome and androgen receptor status in prostate cancer

Caroline E. Nunes-Xavier et al.

Summary: This study identified distinct clinical relevance of the two immune checkpoint proteins PD-L1 and B7-H3 in prostate cancer, with B7-H3 potentially serving as a significant therapeutic target.

PROSTATE (2021)

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Article Biology

Phenotypic plasticity underlies local invasion and distant metastasis in colon cancer

Andrea Sacchetti et al.

Summary: EpCAM(lo) cells are a subpopulation of colon cancer cells with phenotypic plasticity, exhibiting motility, invasiveness, chemoresistance, and high metastatic potential. These cells show enhanced Wnt/beta-catenin signaling, a spectrum of EMT activation states, and a high correlation with the poor-prognosis CMS4 subtype.

ELIFE (2021)

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Article Pharmacology & Pharmacy

Evidence That Tumor Microenvironment Initiates Epithelial-To-Mesenchymal Transition and Calebin A can Suppress it in Colorectal Cancer Cells

Constanze Buhrmann et al.

Summary: This study showed that Calebin A can inhibit TME-induced EMT in CRC cells by modulating the NF-kappa B/Slug axis, TGF-beta 1, and FAK signaling pathways. This suggests that Calebin A may be a potential agent for the prevention and management of CRC.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Oncology

Combination Strategies to Augment Immune Check Point Inhibitors Efficacy-Implications for Translational Research

Hrishi Varayathu et al.

Summary: Immune checkpoint inhibitor therapy has revolutionized cancer immunotherapy, but not all patients respond to it. Current research is focused on combining immune checkpoint inhibitors with other drugs to explore more effective therapeutic strategies.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

B7-H3 inhibits apoptosis of gastric cancer cell by interacting with Fibronectin

Meiyun Sun et al.

Summary: In this study, it was found that B7-H3 inhibits the apoptosis of gastric cancer cells through the regulation of the FN-mediated PI3K/AKT signaling pathway.

JOURNAL OF CANCER (2021)

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Article Oncology

B7-H3 confers resistance to Vγ9Vδ2 T cell-mediated cytotoxicity in human colon cancer cells via the STAT3/ULBP2 axis

Huimin Lu et al.

Summary: We found that B7-H3 regulates colorectal cancer (CC) cell resistance to the cytotoxicity of Vγ9Vδ2 (Vδ2) T cells through a molecular pathway involving STAT3 activation and reduced ULBP2 expression. Blocking or knocking down ULBP2 can reverse the resistance induced by B7-H3 silencing, suggesting that the B7-H3-mediated STAT3/ULBP2 axis could be a potential target for enhancing gamma delta T cell-based immunotherapy efficiency in CC.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2021)

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LncRNA NEAT1 sponges miR-214 to regulate M2 macrophage polarization by regulation of B7-H3 in multiple myeloma

Yin Gao et al.

MOLECULAR IMMUNOLOGY (2020)

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B7-H3 promotes colorectal cancer angiogenesis through activating the NF-κB pathway to induce VEGFA expression

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MOLECULES (2020)

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Article Cell Biology

B7-H3 regulates KIF15-activated ERK1/2 pathway and contributes to radioresistance in colorectal cancer

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CELL DEATH & DISEASE (2020)

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Clinical and Prognostic Relevance of B7-H3 and Indicators of Glucose Metabolism in Colorectal Cancer

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FRONTIERS IN ONCOLOGY (2020)

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LIFE SCIENCES (2020)

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FRONTIERS IN IMMUNOLOGY (2020)

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INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2020)

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B7-H3 promotes the cell cycle-mediated chemoresistance of colorectal cancer cells by regulating CDC25A

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Antitumor Responses in the Absence of Toxicity in Solid Tumors by Targeting B7-H3 via Chimeric Antigen Receptor T Cells

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EBIOMEDICINE (2019)

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Linda Koch

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B7-H3 promotes aerobic glycolysis and chemoresistance in colorectal cancer cells by regulating HK2

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STEM CELLS INTERNATIONAL (2019)

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Article Cell & Tissue Engineering

CD276 (B7-H3) Maintains Proliferation and Regulates Differentiation in Angiogenic Function in Late Endothelial Progenitor Cells

YeonSung Son et al.

STEM CELLS (2019)

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Inhibition of phosphoenolpyruvate carboxykinase blocks lactate utilization and impairs tumor growth in colorectal cancer

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Clinical significance of serum soluble B7-H3 in patients with osteosarcoma

Ling Wang et al.

CANCER CELL INTERNATIONAL (2018)

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Expression and clinical significance of negative costimulatory molecules B7-H1, B7-H3 and B7-H4 in the process of colorectal cancer's evolution

Zhichao Qiu et al.

TRANSLATIONAL CANCER RESEARCH (2018)

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Tumor Heterogeneity in Primary Colorectal Cancer and Corresponding Metastases. Does the Apple Fall Far From the Tree?

Annika Blank et al.

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Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer

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Cancer cell-expressed B7-H3 regulates the differentiation of tumor-associated macrophages in human colorectal carcinoma

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ONCOLOGY LETTERS (2017)

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Involvement of soluble B7-H3 in combination with the serum inflammatory cytokines interleukin-17,-8 and-6 in the diagnosis of hepatocellular carcinoma

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ONCOLOGY LETTERS (2017)

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2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications

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B7-H3 combats apoptosis induced by chemotherapy by delivering signals to pancreatic cancer

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Prognostic value of B7-H3 expression in patients with solid tumors: a meta-analysis

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Inhibition of B7-H3 reverses oxaliplatin resistance in human colorectal cancer cells

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Epithelial calcineurin controls microbiota-dependent intestinal tumor development

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TGF-β1 promotes colorectal cancer immune escape by elevating B7-H3 and B7-H4 via the miR-155/miR-143 axis

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B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

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B7-H3 promotes cell migration and invasion through the Jak2/Stat3/MMP9 signaling pathway in colorectal cancer

Fen Liu et al.

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Article Gastroenterology & Hepatology

Overexpression of B7-H3 augments anti-apoptosis of colorectal cancer cells by Jak2-STAT3

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Article Oncology

B7-H3 expression in colorectal cancer: associations with clinicopathological parameters and patient outcome

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Curcumin Suppresses Crosstalk between Colon Cancer Stem Cells and Stromal Fibroblasts in the Tumor Microenvironment: Potential Role of EMT

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JOURNAL OF IMMUNOLOGY RESEARCH (2014)

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Functional Analysis of B7-H3 in Colonic Carcinoma Cells

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ASIAN PACIFIC JOURNAL OF CANCER PREVENTION (2012)

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Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment

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CANCER CELL (2012)

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B7-H3 expression in colorectal cancer: Nuclear localization strongly predicts poor outcome in colon cancer

Vibeke Anett Ingebrigtsen et al.

INTERNATIONAL JOURNAL OF CANCER (2012)

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Accuracy of monitoring serum carcinoembryonic antigen levels in postoperative stage III colorectal cancer patients is limited to only the first postoperative year

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STAT3-mediated metabolic switch is involved in tumour transformation and STAT3 addiction

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Clinical significance and regulation of the costimulatory molecule B7-H3 in human colorectal carcinoma

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CANCER IMMUNOLOGY IMMUNOTHERAPY (2010)

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Peripheral blood gene expression of B7 and CD28 family members associated with tumor progression and microscopic lymphovascular invasion in colon cancer patients

Hyunji Lee et al.

JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY (2010)

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Tumor associated endothelial expression of B7-H3 predicts survival in ovarian carcinomas

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MODERN PATHOLOGY (2010)

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Expression of the costimulatory molecule B7-H3 is associated with prolonged survival in human pancreatic cancer

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BMC CANCER (2009)

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Review Oncology

The Epithelial-to-Mesenchymal Transition and Cancer Stem Cells: A Coalition Against Cancer Therapies

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JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA (2009)

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Inhibitory B7-family molecules in the tumour microenvironment

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NATURE REVIEWS IMMUNOLOGY (2008)

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Identification and expansion of human colon-cancer-initiating cells

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B7-H3 and B7-H4 expression in non-small-cell lung cancer

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The B7 family of immune-regulatory ligands

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B7-H3:: A costimulatory molecule for T cell activation and IFN-γ production

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