Carbonic anhydrase IX: A tumor acidification switch in heterogeneity and chemokine regulation

Article Dermatology

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia-inducible factor-1a and its central downstream factors

F. Toberer et al.

Summary: The study highlights the crucial role of HIF-1α in MCC pathogenesis and suggests significant metabolic differences between McPyV(+) and McPyV(-) tumors.

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY AND VENEREOLOGY (2021)

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Article Peripheral Vascular Disease

A novel lymphatic pattern promotes metastasis of cervical cancer in a hypoxic tumour-associated macrophage-dependent manner

Xiao-Jing Chen et al.

Summary: A novel lymphatic pattern LVEM encapsulating lymphatic vessels by TAMs in the hypoxic TME promotes metastasis of CSCC. IL-10 derived from hypoxic TAMs induces Sp1 upregulation in LECs, facilitating LVEM formation and a positive feedback loop that strengthens LNM. Knockdown of Sp1 or blockage of CCL1 disrupts LVEM formation and attenuates LNM.

ANGIOGENESIS (2021)

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Article Oncology

Tumour acidosis evaluated in vivo by MRI-CEST pH imaging reveals breast cancer metastatic potential

Annasofia Anemone et al.

Summary: This study found that extracellular acidification is associated with metastatic potential, with tumors of higher metastatic potential showing more acidic pH. The marker of CD44(+)CD24(-) is indicative of highly invasive tumors.

BRITISH JOURNAL OF CANCER (2021)

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Editorial Material Oncology

Putting Warburg to work: how imaging of tumour acidosis could help predict metastatic potential in breast cancer

Michala Gylling Rolver et al.

Summary: This study suggests that the degree of acidification of the environment by breast cancer cell lines is correlated with their metastatic potential to the lungs, indicating that measuring tumor extracellular acidosis could be a clinical tool for assessing metastasis risk.

BRITISH JOURNAL OF CANCER (2021)

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Review Oncology

The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment

Asieh Emami Nejad et al.

Summary: Tumor hypoxia, caused by rapid tumor growth and abnormal blood vessel formation, can activate angiogenesis, increase tumor survival, suppress immunity, and requires management through mechanisms such as altering gene expression. The potential use of cancer stem cells in tumor treatment has been highlighted.

CANCER CELL INTERNATIONAL (2021)

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Article Oncology

Tumor microenvironment and metabolic remodeling in gemcitabine-based chemoresistance of pancreatic cancer

Zongting Gu et al.

Summary: PDAC is a solid malignant tumor with a low operative rate and poor prognosis, with gemcitabine chemotherapy being one of the main treatment options. However, the efficacy of gemcitabine therapy is limited due to gemcitabine resistance, which may be influenced by the fibrotic tumor microenvironment and metabolic remodeling in PDAC. Targeting the tumor microenvironment may be a key strategy to overcome gemcitabine resistance and improve patient outcomes.

CANCER LETTERS (2021)

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Review Biochemistry & Molecular Biology

The Effect of Hypoxia on the Expression of CXC Chemokines and CXC Chemokine Receptors-A Review of Literature

Jan Korbecki et al.

Summary: Hypoxia plays a crucial role in the tumor microenvironment, affecting cancer processes. Changes in CXC chemokine expression induced by hypoxia have implications for angiogenesis, lymphangiogenesis, and recruitment of various cells to the tumor niche. Targeting the CXC chemokine system with drugs has potential in cancer therapy.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Chemistry, Medicinal

Binding site comparison for coumarin inhibitors and amine/amino acid activators of human carbonic anhydrases

Andrea Petreni et al.

Summary: This study presents the first structural analysis comparing two opposite classes of modulators binding to the target carbonic anhydrases, showing that coumarin derivatives act as prodrug CA inhibitors while CA activators belonging to the amine and amino acid types enhance CA activity by increasing the efficiency of the rate-determining proton shuttling step in the CA catalytic cycle. The analysis of crystallographic data reveals that both types of CA modulators bind in the same region of the enzyme active site, interacting with superimposable amino acid residues and involving a plethora of water molecules in the formation of adducts. Additionally, the study highlights the importance of certain chemical groups in compound structure to produce an activating rather than inhibitory action, with multiple nitrogen- and oxygen-based moieties capable of shuttling protons or forming extended H-bond networks nearby the proton shuttle residue. This unique finding showcases the significant pharmacological implications of having an identical binding site for both inhibitors and activators in enzymes.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

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Review Urology & Nephrology

Genomic and phenotypic heterogeneity in prostate cancer

Michael C. Haffner et al.

Summary: Prostate cancer is heterogeneous, with primary tumors being multifocal and metastatic tumors potentially originating from a single clone but exhibiting subclonal heterogeneity at the genomic, epigenetic, and phenotypic levels. The complex heterogeneous constellation of molecular alterations poses challenges for diagnosis and treatment of prostate cancer.

NATURE REVIEWS UROLOGY (2021)

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Article Biochemistry & Molecular Biology

Inhibition of Carbonic Anhydrase IX Suppresses Breast Cancer Cell Motility at the Single-Cell Level

Agne Janoniene et al.

Summary: Inhibition of CA IX by VD11-4-2 decreases movement speed in breast cancer cells without affecting non-cancerous cells. The inhibitor hinders cells from reaching their maximum speed and reduces cell movement towards growth factors.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Chronic and Cycling Hypoxia: Drivers of Cancer Chronic Inflammation through HIF-1 and NF-κB Activation: A Review of the Molecular Mechanisms

Jan Korbecki et al.

Summary: This paper discusses the mechanisms and effects of chronic low-grade inflammation caused by chronic hypoxia and cycling hypoxia in malignant tumors, as well as their impact on the tumor microenvironment and cell recruitment.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Cell Biology

Carbonic Anhydrases II and IX in Non-ampullary Duodenal Adenomas and Adenocarcinoma

Minna Nortunen et al.

Summary: Non-ampullary duodenal adenocarcinoma (DAC) is a rare malignancy with little information on histopathological prognostic factors. Carbonic anhydrases (CAs) are metalloenzymes associated with prognosis in various cancers. The study found low expression of CAII and comparable expression of CAIX in adenomas and adenocarcinoma, suggesting potential as biomarkers for epithelial dysplasia in the duodenum.

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY (2021)

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Article Genetics & Heredity

The context-specific role of germline pathogenicity in tumorigenesis

Preethi Srinivasan et al.

Summary: The study identified pathogenic germline variants in cancer predisposition genes in 17,152 patients with cancer, revealing different mechanisms of tumorigenesis based on the penetrance and lineage of the gene variants.

NATURE GENETICS (2021)

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Article Pathology

Carbonic anhydrase IX: a regulator of pH and participant in carcinogenesis

Alessandro Pietro Aldera et al.

Summary: Carbonic anhydrase IX (CAIX) is a transmembrane metalloenzyme upregulated in tumor cells under hypoxic conditions. High expression of CAIX is associated with poor prognosis in breast, lung, ovarian, and bladder carcinomas, while low expression indicates poor prognosis in clear cell renal cell carcinoma (CCRCC). CAIX immunohistochemistry is useful for diagnosing metastatic CCRCC and clear cell papillary renal cell carcinoma, and there is interest in targeting it with monoclonal antibodies and small molecule inhibitors.

JOURNAL OF CLINICAL PATHOLOGY (2021)

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Review Gastroenterology & Hepatology

Therapeutic resistance in pancreatic ductal adenocarcinoma: Current challenges and future opportunities

Aditi Jain et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. This review discusses the molecular mechanisms involved in therapy resistance in PDAC, current approaches in targeting these mechanisms, lessons learned from the failure of immunotherapy in PDAC, and ongoing efforts to improve tumor's immunological response.

WORLD JOURNAL OF GASTROENTEROLOGY (2021)

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Article Multidisciplinary Sciences

Deciphering cell lineage specification of human lung adenocarcinoma with single-cell RNA sequencing

Zhoufeng Wang et al.

Summary: This study analyzed the composition and progression of LUAD in patient samples using single-cell RNA-seq and multiplex imaging, revealing a potential transcriptional divergence from alveolar type 2 cells. The research identified a group of cells resembling AT2 cells in LUAD progression and detected upregulated genes related to energy metabolism and ribosome synthesis in early stages of LUAD. Potential biomarkers including MDK and TIMP1 were identified for understanding LUAD pathogenesis, shedding light on the transcriptional signatures of distinct histologic stages of LUAD progression that may facilitate early diagnosis.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Deciphering intratumoral heterogeneity using integrated clonal tracking and single-cell transcriptome analyses

Humberto Contreras-Trujillo et al.

Summary: Cellular heterogeneity is a major obstacle in cancer treatment, making it difficult to relate molecular profiles to cancer-cell activities. The integrated experimental system presented in this study links single-cell gene expression to cancer cell growth, metastasis, and treatment response, providing insights into intratumoral heterogeneity and disease progression. DNA barcoding combined with single-cell RNA sequencing is a promising approach for analyzing genetic and phenotypic heterogeneity in cancer.

NATURE COMMUNICATIONS (2021)

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Article Oncology

Granulocyte Colony Stimulating Factor Expression in Breast Cancer and Its Association with Carbonic Anhydrase IX and Immune Checkpoints

Shawn C. Chafe et al.

Summary: The high expression of G-CSF in breast cancer cells is associated with improved survival in a subset of patients who do not respond to hormonal therapy. These tumors are infiltrated by immune cells expressing biomarkers that can be targeted with immune checkpoint inhibitor drugs. On the other hand, the expression of carbonic anhydrase IX is linked to unfavorable outcomes in breast cancer.

CANCERS (2021)

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Article Oncology

Carbonic Anhydrase IX Promotes Human Cervical Cancer Cell Motility by Regulating PFKFB4 Expression

Min-Chieh Hsin et al.

Summary: Our study revealed that overexpression of CAIX increases PFKFB4 expression and promotes EMT, thereby facilitating cervical cancer cell migration. This suggests that CAIX may play a role in cervical cancer metastasis, and targeting it could be a potential treatment strategy for cervical cancer.

CANCERS (2021)

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Article Cell Biology

Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy

Pavan Bachireddy et al.

Summary: Research suggests that responsive tumors in leukemia treatment are characterized by enrichment of late-differentiated T cells, while resistance is defined by heterogeneous T cell dysfunction. Interestingly, early differentiated T cells in responders primarily originate from pre-existing and novel clonotypes recruited to the leukemic microenvironment.

CELL REPORTS (2021)

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Review Oncology

Chemokines orchestrate tumor cells and the microenvironment to achieve metastatic heterogeneity

Sugandha Saxena et al.

Summary: Chemokines play a crucial role in regulating tumor progression and metastasis, with their complex biology involving various factors related to chemotherapy and immunotherapy. Understanding the interplay between chemokine networks provides a novel approach to overcoming the problem of metastatic heterogeneity.

CANCER AND METASTASIS REVIEWS (2021)

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Review Biochemistry & Molecular Biology

Proton Transport in Cancer Cells: The Role of Carbonic Anhydrases

Holger M. Becker et al.

Summary: Intra- and extracellular pH regulation is crucial for cells and tissues, with distorted pH regulation in tumor tissues creating a hostile environment for cancer cells. Cancer cells manipulate a variety of transporters and carbonic anhydrases to alter pH values, promoting tumor progression. Transport metabolons formed by these components play a key role in tumor pH regulation and potential therapeutic interventions for cancer.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Oncology

Tumor Heterogeneity and Consequences for Bladder Cancer Treatment

Etienne Lavallee et al.

Summary: Bladder cancer is a heterogeneous disease composed of epithelia with varying signatures, which can undergo changes in response to treatment stresses and cues from the tumor microenvironment. Changes in epithelial tumor heterogeneity occur due to natural selection processes, including Darwinian and Lamarckian-like mechanisms. Understanding and managing epithelial tumor heterogeneity is crucial for sustained and durable clinical therapies.

CANCERS (2021)

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Article Cell Biology

Identification of a Hypoxia-Related Gene Signature for Predicting Systemic Metastasis in Prostate Cancer

Haoran Xia et al.

Summary: The study established a hypoxia-related gene signature and a nomogram to predict high-risk prostate cancer metastasis patients. High-risk patients exhibited therapeutic resistance and immunosuppression, with the nomogram showing the strongest predictive power.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Oncology

Phenotypic Heterogeneity of Triple-Negative Breast Cancer Mediated by Epithelial-Mesenchymal Plasticity

Barbora Kvokackova et al.

Summary: Epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) play critical roles in the development of TNBC, shaping aggressive and heterogeneous biological features, but may also contribute to the progression of metastatic disease.

CANCERS (2021)

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Article Cell Biology

Gene Families With Stochastic Exclusive Gene Choice Underlie Cell Adhesion in Mammalian Cells

Mikhail Iakovlev et al.

Summary: Exclusive stochastic gene choice provides a balance between precision and diversity, allowing most T cells to express one receptor isoform while some express two, revealing the stochastic nature of the process. Analyses of single-cell RNA-seq data show that many gene families are expressed exclusively, particularly those involved in ion transport and cell adhesion, suggesting coordinated functions. While chromosomal segments and gene families tend to express genes concurrently rather than exclusively, this may be influenced by evolutionary and biophysical aspects of shared regulation.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Biochemistry & Molecular Biology

Overcoming chemoresistance by targeting reprogrammed metabolism: the Achilles' heel of pancreatic ductal adenocarcinoma

Abudureyimu Tuerhong et al.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is characterized by late diagnosis and metabolic reprogramming related to glucose, lipid, and amino acid metabolism, which lead to resistance to chemotherapy. Targeting critical enzymes and/or transporters involved in metabolism may be a promising approach to overcome chemoresistance in PDAC.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Article Biochemistry & Molecular Biology

Inhibition of Carbonic Anhydrase IX Promotes Apoptosis through Intracellular pH Level Alterations in Cervical Cancer Cells

Ebru Temiz et al.

Summary: This study investigated how a synthetic CAIX inhibitor induces apoptosis in the HeLa cell line, revealing that CAIX inhibition alters cell morphology, increases apoptotic cell ratio, disrupts intracellular homeostasis of pHi, MMP and ROS levels, ultimately triggering apoptosis and autophagy in HeLa cells. These findings support the potential therapeutic strategy of CAIX inhibitors in various cancer types.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Review Oncology

Therapeutic targeting of the hypoxic tumour microenvironment

Dean C. Singleton et al.

Summary: The article discusses the relationship between two different tumor microenvironment research fields: physicochemical gradients and cellular interactions, with a focus on translational therapeutic opportunities. Hypoxia is a common feature of tumors, influencing various cancer characteristics and responses to anticancer therapies.

NATURE REVIEWS CLINICAL ONCOLOGY (2021)

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Article Pharmacology & Pharmacy

Lenvatinib enhances T cell immunity and the efficacy of adoptive chimeric antigen receptor-modified T cells by decreasing myeloid-derived suppressor cells in cancer

Mengmeng Lu et al.

PHARMACOLOGICAL RESEARCH (2021)

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Article Oncology

Characterization of hypoxia response patterns identified prognosis and immunotherapy response in bladder cancer

Rui Cao et al.

Summary: This study identified different hypoxia response patterns in bladder cancer patients, showing that the low HPXscore group had immune activation and high DNA damage repair, highlighting an immune-inflamed phenotype, while the high HPXscore group exhibited stromal-related pathway activation, indicating a T cell suppressive and immune-excluded phenotype. The HPXscore was also found to be an independent prognostic factor and a good predictor for immunotherapeutic outcomes in bladder cancer.

MOLECULAR THERAPY-ONCOLYTICS (2021)

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Article Multidisciplinary Sciences

Genome-wide synthetic lethal screen unveils novel CAIX-NFS1/xCT axis as a targetable vulnerability in hypoxic solid tumors

Shawn C. Chafe et al.

Summary: The study identified a redox homeostasis network involving the iron-sulfur cluster enzyme NFS1 in the survival mechanisms governed by the tumor hypoxia-induced pH regulator CAIX. Targeting CAIX while depleting NFS1 or blocking cyst(e)ine availability enhanced ferroptosis and inhibited tumor growth significantly. Altering intracellular pH and iron homeostasis through inhibiting CAIX activity may lead to the development of innovative therapeutic strategies for solid tumors to overcome hypoxia- and acidosis-mediated tumor progression and therapeutic resistance.

SCIENCE ADVANCES (2021)

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Review Oncology

Cancer metabolism: looking forward

Inmaculada Martinez-Reyes et al.

Summary: This Perspective discusses the main themes in cancer metabolism research, focusing on the relationship between tumour initiation and progression with metabolic reprogramming, as well as the importance of tumor microenvironment and metabolic regulation.

NATURE REVIEWS CANCER (2021)

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Review Medicine, Research & Experimental

Emerging role of carbonic anhydrase inhibitors

Claudiu T. Supuran

Summary: Inhibition of carbonic anhydrase has been used clinically for various applications including treating glaucoma, epilepsy, obesity, and cancer. Recent studies have discovered new roles of CA isoforms in areas like pain management, Alzheimer's disease, and oxidative stress, leading to potential novel clinical applications. Additionally, inhibition of CA in pathogenic microorganisms is being explored for new anti-infective drugs.

CLINICAL SCIENCE (2021)

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Article Oncology

Hypoxia-Related Radiomics and Immunotherapy Response: A Multicohort Study of Non-Small Cell Lung Cancer

Ilke Tunali et al.

Summary: This study developed a concise model using radiomics and clinical data to predict survival outcomes in NSCLC patients undergoing immunotherapy. The high-risk group had significantly lower survival rates compared to the low-risk group in validation cohorts. The most informative radiomic feature, GLCM inverse difference, was associated with hypoxia-related carbonic anhydrase 9.

JNCI CANCER SPECTRUM (2021)

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Review Oncology

Group Behavior and Emergence of Cancer Drug Resistance

Supriyo Bhattacharya et al.

Summary: Drug resistance in cancer is caused by both genetic mutations and non-genetic mechanisms, with intermediate reversible phenotypes playing a crucial role in the emergence of resistant clones. Understanding the complex interplay of clonal groups and the surrounding microenvironment can help in designing more effective treatment strategies to delay or minimize drug resistance.

TRENDS IN CANCER (2021)

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Review Oncology

Hypoxia and its therapeutic possibilities in paediatric cancers

Carolina Bernauer et al.

Summary: Hypoxia in tumors is associated with reduced sensitivity to radiotherapy and chemotherapy, leading to the investigation of strategies to alleviate hypoxia in cancer cells. Prodrugs activated by hypoxic cells and novel imaging techniques such as oxygen-enhanced MRI are being evaluated. Targeting hypoxia in pediatric cancers is supported by preclinical and clinical evidence, emphasizing the need for predictive biomarkers in future clinical trials to improve outcomes for pediatric cancer patients.

BRITISH JOURNAL OF CANCER (2021)

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Review Oncology

Recruitment of stromal cells into tumour microenvironment promote the metastatic spread of breast cancer

Billy Samuel Hill et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Article Biochemistry & Molecular Biology

Design, synthesis, in?vitro inhibition and toxicological evaluation of human carbonic anhydrases I, II and IX inhibitors in 5-nitroimidazole series

Ashok Aspatwar et al.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2020)

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Article Oncology

Carbonic anhydrase 9 (CA9) expression in non-small-cell lung cancer: correlation with regulatory FOXP3+T-cell tumour stroma infiltration

Alexandra Giatromanolaki et al.

BRITISH JOURNAL OF CANCER (2020)

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Review Oncology

Carbonic anhydrase IX and acid transport in cancer

Holger M. Becker

BRITISH JOURNAL OF CANCER (2020)

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Review Biochemistry & Molecular Biology

Carbonic anhydrase IX as a novel candidate in liquid biopsy

Ozen Ozensoy Guler et al.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2020)

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Review Oncology

Integrating tumor hypoxic stress in novel and more adaptable strategies for cancer immunotherapy

Raefa Abou Khouzam et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Review Oncology

Combining epigenetic and immune therapy to overcome cancer resistance

Stephanie Gomez et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Review Oncology

Tumor hypermetabolism confers resistance to immunotherapy

Arthur Liu et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Article Multidisciplinary Sciences

Intratumoral heterogeneity and clonal evolution in liver cancer

Bojan Losic et al.

NATURE COMMUNICATIONS (2020)

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Article Oncology

A Phase 1 Study of SLC-0111, a Novel Inhibitor of Carbonic Anhydrase IX, in Patients With Advanced Solid Tumors

Paul C. McDonald et al.

AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS (2020)

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Article Biochemistry & Molecular Biology

Design, synthesis & biological evaluation of ferulic acid-based small molecule inhibitors against tumor-associated carbonic anhydrase IX

Babita Aneja et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2020)

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Review Immunology

Role of CC Chemokines Subfamily in the Platinum Drugs Resistance Promotion in Cancer

Maria E. Reyes et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Biochemistry & Molecular Biology

Glycolysis, via NADH-dependent dimerisation of CtBPs, regulates hypoxia-induced expression of CAIX and stem-like breast cancer cell survival

Mira Kreuzer et al.

FEBS LETTERS (2020)

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Review Oncology

The Expression of Carbonic Anhydrases II, IX and XII in Brain Tumors

Joonas Haapasalo et al.

CANCERS (2020)

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Review Cell Biology

The roles of carbonic anhydrases IX and XII in cancer cell adhesion, migration, invasion and metastasis

Simonas Daunys et al.

BIOLOGY OF THE CELL (2020)

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Editorial Material Nutrition & Dietetics

Immunotherapy on acid: opportunities and challenges

Sultan Damgaci et al.

EUROPEAN JOURNAL OF CLINICAL NUTRITION (2020)

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Review Biochemistry & Molecular Biology

Carbonic Anhydrase IX in Renal Cell Carcinoma, Implications for Disease Management

Jean Courcier et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Biochemistry & Molecular Biology

Carbonic Anhydrase Inhibitors Targeting Metabolism and Tumor Microenvironment

Andrea Angeli et al.

METABOLITES (2020)

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Review Cell Biology

Interplay of Carbonic Anhydrase IX With Amino Acid and Acid/Base Transporters in the Hypoxic Tumor Microenvironment

Geetha Venkateswaran et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2020)

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Article Oncology

Hypoxia-driven intratumor heterogeneity and immune evasion

Stephane Terry et al.

CANCER LETTERS (2020)

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Review Biochemistry & Molecular Biology

Coumarin carbonic anhydrase inhibitors from natural sources

Claudiu T. Supuran

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2020)

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Article Biochemistry & Molecular Biology

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

Mikhail Krasavin et al.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2020)

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Article Oncology

Hypoxia-induced cancer stemness acquisition is associated with CXCR4 activation by its aberrant promoter demethylation

Nahyeon Kang et al.

BMC CANCER (2019)

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Article Oncology

Acidification of Tumor at Stromal Boundaries Drives Transcriptome Alterations Associated with Aggressive Phenotypes

Nazanin Rohani et al.

CANCER RESEARCH (2019)

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Article Chemistry, Medicinal

Continued exploration of 1,2,4-oxadiazole periphery for carbonic anhydrase-targeting primary arene sulfonamides: Discovery of subnanomolar inhibitors of membrane-bound hCA IX isoform that selectively kill cancer cells in hypoxic environment

Mikhail Krasavin et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Review Biology

The Warburg effect: essential part of metabolic reprogramming and central contributor to cancer progression

Peter Vaupel et al.

INTERNATIONAL JOURNAL OF RADIATION BIOLOGY (2019)

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Review Oncology

The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond

Silvia Pastorekova et al.

CANCER AND METASTASIS REVIEWS (2019)

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Article Chemistry, Medicinal

Pyridazinone-substituted benzenesulfonamides display potent inhibition of membrane-bound human carbonic anhydrase IX and promising antiproliferative activity against cancer cell lines

Mikhail Krasavin et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Article Gastroenterology & Hepatology

Regulation of pH by Carbonic Anhydrase 9 Mediates Survival of Pancreatic Cancer Cells With Activated KRAS in Response to Hypoxia

Paul C. McDonald et al.

GASTROENTEROLOGY (2019)

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Article Oncology

Targeting Hypoxia-Induced Carbonic Anhydrase IX Enhances Immune-Checkpoint Blockade Locally and Systemically

Shawn C. Chafe et al.

CANCER IMMUNOLOGY RESEARCH (2019)

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Article Oncology

Antibody-Based Delivery of Cytokine Payloads to Carbonic Anhydrase IX Leads to Cancer Cures in Immunocompetent Tumor-Bearing Mice

Barbara Ziffels et al.

MOLECULAR CANCER THERAPEUTICS (2019)

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Article Multidisciplinary Sciences

A GPX4-dependent cancer cell state underlies the clear-cell morphology and confers sensitivity to ferroptosis

Yilong Zou et al.

NATURE COMMUNICATIONS (2019)

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Article Multidisciplinary Sciences

Clockophagy is a novel selective autophagy process favoring ferroptosis

Minghua Yang et al.

SCIENCE ADVANCES (2019)

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Review Pharmacology & Pharmacy

Advances in the structural annotation of human carbonic anhydrases and impact on future drug discovery

Alessio Nocentini et al.

EXPERT OPINION ON DRUG DISCOVERY (2019)

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Article Clinical Neurology

Distinct Expression Patterns of Carbonic Anhydrase IX in Clear Cell, Microcystic, and Angiomatous Meningiomas

Rati Chkheidze et al.

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY (2019)

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Article Chemistry, Medicinal

Carbonic anhydrase inhibitors based on sorafenib scaffold: Design, synthesis, crystallographic investigation and effects on primary breast cancer cells

Murat Bozdag et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2019)

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Article Biochemistry & Molecular Biology

The carbonic anhydrase IX inhibitor SLC-0111 sensitises cancer cells to conventional chemotherapy

Elena Andreucci et al.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2019)

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Article Oncology

Hypoxia-activated prodrugs and (lack of) clinical progress: The need for hypoxia-based biomarker patient selection in phase III clinical trials

Linda Spiegelberg et al.

CLINICAL AND TRANSLATIONAL RADIATION ONCOLOGY (2019)

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Review Oncology

Tumour heterogeneity and resistance to cancer therapies

Ibiayi Dagogo-Jack et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2018)

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Article Oncology

Enhanced Therapeutic Activity of Non-Internalizing Small-Molecule-Drug Conjugates Targeting Carbonic Anhydrase IX in Combination with Targeted Interleukin-2

Samuele Cazzamalli et al.

CLINICAL CANCER RESEARCH (2018)

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Review Biochemistry & Molecular Biology

Understanding the Role and Mechanism of Carbonic Anhydrase V in Obesity and its Therapeutic Implications

Aarfa Queen et al.

CURRENT PROTEIN & PEPTIDE SCIENCE (2018)

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Article Cell Biology

A peek into cancer-associated fibroblasts: origins, functions and translational impact

Valerie S. LeBleu et al.

DISEASE MODELS & MECHANISMS (2018)

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Article Chemistry, Medicinal

Design, synthesis and biological evaluation of novel pyridine-thiazolidinone derivatives as anticancer agents: Targeting human carbonic anhydrase IX

Mohammad Fawad Ansari et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2018)

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Article Chemistry, Medicinal

Synthesis, characterization and biological evaluation of tertiary sulfonamide derivatives of pyridyl-indole based heteroaryl chalcone as potential carbonic anhydrase IX inhibitors and anticancer agents

Mudasir Nabi Peerzada et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2018)

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Article Biochemistry & Molecular Biology

Biological evaluation of p-toluene sulphonylhydrazone as carbonic anhydrase IX inhibitors: An approach to fight hypoxia-induced tumors

Aarfa Queen et al.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2018)

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Article Oncology

The net acid extruders NHE1, NBCn1 and MCT4 promote mammary tumor growth through distinct but overlapping mechanisms

Anne Poder Andersen et al.

INTERNATIONAL JOURNAL OF CANCER (2018)

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Review Immunology

Immunological Approaches Towards Cancer and Inflammation: A Cross Talk

Xinglong Qu et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Article Oncology

Carbonic anhydrase IX is a pH-stat that sets an acidic tumour extracellular pH in vivo

Shen-Han Lee et al.

BRITISH JOURNAL OF CANCER (2018)

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Article Oncology

HIF-2α promotes conversion to a stem cell phenotype and induces chemoresistance in breast cancer cells by activating Wnt and Notch pathways

Yuanyuan Yan et al.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2018)

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Article Multidisciplinary Sciences

Selective inhibition of carbonic anhydrase IX over carbonic anhydrase XII in breast cancer cells using benzene sulfonamides: Disconnect between activity and growth inhibition

Mam Y. Mboge et al.

PLOS ONE (2018)

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Review Oncology

Eco-evolutionary causes and consequences of temporal changes in intratumoural blood flow

Robert J. Gillies et al.

NATURE REVIEWS CANCER (2018)

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Article Chemistry, Medicinal

Structure activity study of carbonic anhydrase IX: Selective inhibition with ureido-substituted benzenesulfonamides

Mam Y. Mboge et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2017)

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Article Oncology

Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406/SARC021): an international, multicentre, open-label, randomised phase 3 trial

William D. Tap et al.

LANCET ONCOLOGY (2017)

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Tracking the Evolution of Non-Small-Cell Lung Cancer

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NEW ENGLAND JOURNAL OF MEDICINE (2017)

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Roles of tumor heterogeneity in the development of drug resistance: A call for precision therapy

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SEMINARS IN CANCER BIOLOGY (2017)

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Overexpression of carbonic anhydrase IX induces cell motility by activating matrix metalloproteinase-9 in human oral squamous cell carcinoma cells

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ONCOTARGET (2017)

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Addition of carbonic anhydrase 9 inhibitor SLC-0111 to temozolomide treatment delays glioblastoma growth in vivo

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JCI INSIGHT (2017)

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Human brain metastatic stroma attracts breast cancer cells via chemokines CXCL16 and CXCL12

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NPJ BREAST CANCER (2017)

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Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

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CANCER CELL (2017)

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Influence of hypoxia-dependent factors on the progression of neuroblastoma

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PEDIATRIC SURGERY INTERNATIONAL (2016)

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Phenotypic and functional heterogeneity of cancer-associated fibroblast within the tumor microenvironment

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ADVANCED DRUG DELIVERY REVIEWS (2016)

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Darwinian Dynamics of Intratumoral Heterogeneity: Not Solely Random Mutations but Also Variable Environmental Selection Forces

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CANCER RESEARCH (2016)

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The Emerging Hallmarks of Cancer Metabolism

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CELL METABOLISM (2016)

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Carbonic anhydrase enzymes II, VII, IX and XII in colorectal carcinomas

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WORLD JOURNAL OF GASTROENTEROLOGY (2016)

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Overcoming Hypoxia-Mediated Tumor Progression:Combinatorial Approaches Targeting pH Regulation,Angiogenesis and Immune Dysfunction

Paul C. McDonald et al.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2016)

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Carbonic Anhydrase IX Promotes Myeloid-Derived Suppressor Cell Mobilization and Establishment of a Metastatic Niche by Stimulating G-CSF Production

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CANCER RESEARCH (2015)

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In a search for selective inhibitors of carbonic anhydrases: coumarin and its bioisosteres - synthesis and derivatization

Raivis Zalubovskis

CHEMISTRY OF HETEROCYCLIC COMPOUNDS (2015)

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Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

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SEMINARS IN CANCER BIOLOGY (2015)

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Evaluation of carbonic anhydrase IX as a therapeutic target for inhibition of breast cancer invasion and metastasis using a series of in vitro breast cancer models

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ONCOTARGET (2015)

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Probing the Surface of Human Carbonic Anhydrase for Clues towards the Design of Isoform Specific Inhibitors

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BIOMED RESEARCH INTERNATIONAL (2015)

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Novel coumarins and benzocoumarins acting as isoform-selective inhibitors against the tumor-associated carbonic anhydrase IX

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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2014)

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BIOORGANIC & MEDICINAL CHEMISTRY (2013)

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Targeting carbonic anhydrase IX depletes breast cancer stem cells within the hypoxic niche

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ONCOGENE (2013)

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Targeting carbonic anhydrase IX by nitroimidazole based sulfamides enhances the therapeutic effect of tumor irradiation: A new concept of dual targeting drugs

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RADIOTHERAPY AND ONCOLOGY (2013)

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SCIENCE (2013)

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FRONTIERS IN PHYSIOLOGY (2013)

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Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms?

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CHEMICAL REVIEWS (2012)

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JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY (2012)

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NATURE (2012)

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Expression of Hypoxic Marker CA IX Is Regulated by Site-Specific DNA Methylation and Is Associated with the Histology of Gastric Cancer

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AMERICAN JOURNAL OF PATHOLOGY (2011)

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Role of hypoxia and EGF on expression, activity, localization and phosphorylation of carbonic anhydrase IX in MDA-MB-231 breast cancer cells

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2011)

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Phosphorylation of Carbonic Anhydrase IX Controls Its Ability to Mediate Extracellular Acidification in Hypoxic Tumors

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CANCER RESEARCH (2011)

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Targeting Tumor Hypoxia: Suppression of Breast Tumor Growth and Metastasis by Novel Carbonic Anhydrase IX Inhibitors

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CANCER RESEARCH (2011)

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JOURNAL OF CELLULAR PHYSIOLOGY (2011)

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Ureido-Substituted Benzenesulfonamides Potently Inhibit Carbonic Anhydrase IX and Show Antimetastatic Activity in a Model of Breast Cancer Metastasis

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NATURE (2011)

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NATURE REVIEWS DRUG DISCOVERY (2011)

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Otto Warburg's contributions to current concepts of cancer metabolism

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BREAST CANCER RESEARCH (2011)

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BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (2010)

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BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (2010)

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2010)

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Selective hydrophobic pocket binding observed within the carbonic anhydrase II active site accommodate different 4-substituted-ureido-benzenesulfonamides and correlate to inhibitor potency

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The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian α-carbonic anhydrase isoforms

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2009)

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The proteoglycan region of the tumor-associated carbonic anhydrase isoform IX acts as anintrinsic buffer optimizing CO2 hydration at acidic pH values characteristic of solid tumors

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2009)

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FEBS LETTERS (2009)

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JOURNAL OF PHYSICAL CHEMISTRY B (2009)

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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RADIOTHERAPY AND ONCOLOGY (2009)

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Crystal structure of human carbonic anhydrase-related protein VIII reveals the basis for catalytic silencing

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Carbonic anhydrase inhibitors: Design of spin-labeled sulfonamides incorporating TEMPO moieties as probes for cytosolic or transmembrane isozymes

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2005)

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Carbonic anhydrase inhibitors. Inhibition of mitochondrial isozyme V with aromatic and heterocyclic sulfonamides

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Carbonic anhydrases: Current state of the art, therapeutic applications and future prospects

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CANCER INVESTIGATION (2004)

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Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozyme IX with aromatic and heterocyclic sulfonamides

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2003)

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GASTROENTEROLOGY (2002)

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)

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Crystal structure of the dimeric extracellular domain of human carbonic anhydrase XII, a bitopic membrane protein overexpressed in certain cancer tumor cells

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)

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Expression of membrane-associated carbonic anhydrase XIV on neurons and axons in mouse and human brain

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2001)

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)

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Carbonic anhydrase inhibitor suppresses invasion of renal cancer cells in vitro

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)

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Carbon dioxide transport and carbonic anhydrase in blood and muscle

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PHYSIOLOGICAL REVIEWS (2000)

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Mitochondrial carbonic anhydrase CA VB: Differences in tissue distribution and pattern of evolution from those of CA VA suggest distinct physiological roles

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)

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Carbonic anhydrase IX: A tumor acidification switch in heterogeneity and chemokine regulation

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