Breast cancer poses a significant threat to women's health. Early diagnosis using pathological images is crucial for effective treatment planning. However, the low resolution of pathological images poses significant challenges for the extraction of valid information, while their high complexity greatly increases the difficulty of image analysis. To address these challenges, this paper introduces an innovative classification method for breast cancer histopathological images, combining enhanced nuclear information with an Enhanced Vision Transformer (EVT) model using wavelet position embedding. The quintessence of the proposed method resides in its capacity to efficiently extract both biological and foundational image features from pathological images. This is accomplished by initially enhancing nuclear information through the application of segmentation models and sophisticated image processing techniques. Subsequently, wavelet positional embedding within the EVT model is leveraged to precisely capture key information embedded within the images. Experimental outcomes have demonstrated that our method attains an accuracy rate of 94.61% and an AUC value of 99.07% on the BreaKHis dataset, significantly outperforming other baseline network models in terms of classification efficacy. Furthermore, through visual representation, this study underscores the significance of nuclear information enhancement and wavelet position transformation in the EVT model, thereby further confirming the effectiveness and effectiveness of the method we proposed.

Electrical impedance spectroscopy (EIS) is a powerful tool used to investigate the properties of materials and biological tissues. This study presents one of the first applications of EIS for the detection and classification of oral potentially malignant disorders (OPMDs) and oral cancer. We aimed to apply EIS in conjunction with deep learning to assist the clinical diagnosis of OPMD and oral cancer as a non-invasive diagnostic technology. Currently, the diagnosis of OPMD and oral cancer relies on clinical examination and histopathological analysis of invasive scalpel tissue biopsies, which is stressful for patients, time-consuming for clinicians and subject to histopathological interobserver variation in diagnosis, although recent advances in artificial intelligence may circumvent discrepancy. Here we developed a novel deep learning convolutional neural network (CNN)-based method to automatically differentiate normal, OPMD and malignant oral tissues using EIS measurements. EIS readings were initially taken from untreated or glacial acetic acid-treated porcine oral mucosa and analyzed via CNN to determine if this method could discriminate between normal and damaged oral epithelium. CNN models achieved area under the curve (AUC) values of 0.92 ± 0.03, with specificity 0.95 and sensitivity 0.84, showing good discrimination. EIS data from ventral tongue and floor-of-the-mouth were collected from 51 healthy humans and 11 patients with OPMD and oral cancer. When a binary classification (low or high risk of malignancy) was applied, the best CNN model achieved an AUC 0.91 ± 0.1, with accuracy 0.91 ± 0.05, specificity 0.97 and sensitivity 0.74. These results demonstrate the considerable potential of EIS in combination with CNN models as an adjunctive non-invasive diagnostic tool for OPMD and oral cancer.

Diffuse large B-cell lymphoma (DLBCL) is a neoplasm affecting adults and children, with different clinical behaviors between age groups. To shed light on those differences, gene expression profiling was evaluated in 48 formalin-fixed paraffin-embedded biopsies of patients with DLBCL. Sixteen differentially expressed genes in pediatric DLBCL compared to adults were demonstrated, involving lymphocyte differentiation, oncogenic signaling and chemotaxis. Pathway analysis confirmed the enrichment in proliferation-related pathways. In addition, the increased presence of NKCD56dim cells in pediatric patients suggests a cytotoxic immune response in this group, perhaps explaining their better outcome. Exclusion of Epstein Barr virus (EBV) + DLBCL, NOS, showed, in pediatric cases, additional downregulated genes associated with immune regulators and checkpoint genes. This suggested EBV infection may have on the modulation of immune response in pediatric lymphomas. Survival analysis showed associations between genes such as MYC, NT5E and CD34, and event-free survival in pediatric patients. Furthermore, higher expression of MYC in children displayed higher risk of death or relapse, while lower expression of NT5E and CD34 was associated with lower risk. This study identifies distinct immune response and proliferation gene expression patterns in pediatric DLBCL compared to adults, and the interaction with tumor microenvironment, with potential implications for disease pathogenesis.

Despite the limitations of in vitro models to investigate cancer cell metabolism, their study can provide new insights essential for understanding tumorigenesis and effectively aiding in the development of novel therapies. The innovative tumor-on-chip models offer a more physiologically relevant platform than the traditional 2D cultures. These 3D cultures incorporate cell-cell and cell-matrix interactions, as well as diffusion dynamics through both the matrix and tumor spheroid, modeling in vivo diffusion within the tumor. Therefore, this work focuses on a quantitative comparison between 2D and 3D cultures through a microfluidic chip that allows daily monitoring of cancer cell key metabolites such as glucose, glutamine and lactate, unveiling critical differences. Our analysis reveals reduced proliferation rates in 3D models, likely due to limited diffusion of nutrients and oxygen. Additionally, 3D cultures showed distinct metabolic profiles, including elevated glutamine consumption under glucose restriction and higher lactate production, indicating an enhanced Warburg effect. The microfluidic chip enabled continuous monitoring, revealing increased per-cell glucose consumption in 3D models, highlighting fewer but more metabolically active cells than in 2D cultures. These findings underscore the importance of using microfluidic-based 3D models to provide a more accurate representation of tumor metabolism and progression compared to traditional 2D cultures.

Acute myeloid leukemia (AML) is the most prevalent type of leukemia in adults. Its heterogeneity, both between patients and within the same patient, is often a factor contributing to poor treatment outcomes. Despite advancements in AML biology and medicine in general, the standard AML treatment, the combination of cytarabine and daunorubicin, has remained the same for decades. Combination drug therapies are proven effective in achieving targeted efficacy while minimizing drug dosage and unintended side effects, a common problem for older AML patients. However, a systematic survey of the synergistic potential of drug-drug interactions in the context of AML pathology is lacking. Here, we examine the interactions between 15 commonly used cancer drugs across distinct AML cell lines and demonstrate that synergistic and antagonistic drug-drug interactions are widespread but not conserved across these cell lines. Notably, enasidenib and venetoclax, recently approved anticancer agents, exhibited the highest counts of synergistic interactions and the fewest antagonistic ones. In contrast, 6-Thioguanine, a purine analog, was involved in the highest number of antagonistic interactions. The interactions we report here cannot be attributed solely to the inherent natures of these three drugs, as each drug we examined was involved in several synergistic or antagonistic interactions in the cell lines we tested. Importantly, these drug-drug interactions are not conserved across cell lines, suggesting that the success of combination therapies might vary significantly depending on AML genotypes. For instance, we found that a single mutation in the TF1 cell line could dramatically alter drug-drug interactions, even turning synergistic interactions into antagonistic ones. Our findings provide a preclinical survey of drug-drug interactions, revealing the complexity of the problem.

Targeting macrophage inhibitory receptors like signal regulatory protein α (SIRPα) is a promising avenue in cancer treatment. Whereas the ligand of SIRPα, CD47, is widely expressed on tumor cells, its simultaneous presence on all normal cells raises concerns about toxicity and efficacy. This study identifies CD200R1, which binds CD200 on specific tumor types and limited normal cells, as an alternative inhibitory checkpoint for phagocytosis. Blocking or removing CD200R1 from macrophages or CD200 from tumor cells increases phagocytosis and suppresses tumor growth. In humans, CD200R1 is mainly expressed in immunosuppressive macrophages and is induced by interleukin-4. Unlike SIRPα that utilizes phosphatases Src homology 2 domain phosphatase (SHP)-1 and SHP-2, CD200R1 mediates its inhibitory effect via the kinase Csk. Combined CD200R1-CD200 and SIRPα-CD47 blockade further boosts phagocytosis and reduces tumor growth of CD200-expressing tumors, compared to either blockade alone. Thus, targeting CD200R1-CD200 is a promising strategy for immune checkpoint blockade in macrophages, either alone or alongside blockade of other checkpoints.

Osteosarcoma (OS) is a highly malignant bone tumor that primarily affects children, adolescents, and young adults. Despite significant progress in chemotherapy, surgery, and limb salvage surgery, the prognosis for patients with high-grade or metastatic OS remains poor. This study explores the role of SAC3D1 gene in OS and its potential as a prognostic marker and therapeutic target. Through analysis of public databases and experimental verification, we found that SAC3D1 is significantly upregulated in OS tissues and cell lines and is associated with poor prognosis in patients. Functional enrichment analysis suggests that SAC3D1 may promote the progression of OS by regulating cell cycle, DNA repair, and immune microenvironment pathways. In addition, the expression level of SAC3D1 is associated with the tumor immune microenvironment and immune therapy response. In vitro experiments further confirmed that knocking down SAC3D1 significantly inhibited the proliferation, migration, and invasion ability of OS cells, while its overexpression enhanced these malignant biological behaviors. In summary, SAC3D1 has important prognostic and therapeutic potential in OS, and may serve as a novel independent prognostic marker and therapeutic target for OS.

Neutrophils are the first line of defense in nonspecific immunity (innate immunity) and interact with other immune cells to participate in specific defense mechanisms (adaptive immunity). Studies have shown that the tumor microenvironment (TME) mediates tumor development and recruits neutrophils into tumors to become tumor-associated neutrophils (TANs), an important part of TME, and achieve extended lifespan. TANs can be differentiated into the antitumor or protumor phenotype, and play an important role in tumor occurrence, proliferation and recurrence, invasion and metastasis, angiogenesis, cell necrosis, and so on. Here, we summarize the TAN origin and subtypes found through Single-cell RNA sequencing analysis in different types of tumors in recent literature, and the molecular mechanisms underlying their antitumor and protumor effects on tumors. We focus on the interaction between TANs and immunosuppressive or immunostimulatory TME, as well as signal pathways such as transforming growth factor β (TGF-β) associated with TAN phenotype transition. Based on the summarized mechanisms, we focus on the potential application and latest strategies of TAN-based immunotherapy, chemotherapy, and combination therapy in the preclinical study and clinical trials of tumors. The discussion on promising therapy encompasses five key areas: inhibition of the tumor-promoting effect of TANs, enhancement of the antitumor effect of TANs, targeting the interaction between TANs and the TME, reprogramming of TANs, and drug delivery carriers. Finally, we discuss the potential of TANs and their related markers as emerging biomarkers for predicting the prognosis of cancer patients.

Metastatic risk stratification is critical for uveal melanoma (UM) management, as approximately up to half of patients develop metastatic disease. Current prognostication for patients undergoing eye-preserving therapies relies on tumor staging and molecular analysis of tumor tissue obtained through potentially invasive biopsy, which can be challenging. While liquid biopsy using cell-free DNA (cfDNA) has emerged as a less invasive alternative for other cancers, studies have shown limited utility of blood-derived cfDNA in UM due to low tumor DNA fractions. This study investigates the potential of aqueous humor (AH) and vitreous body (VB) aspirates as alternative sources of tumor DNA for molecular prognostication in UM patients at the time of diagnosis. In this prospective study, AH and/or VB samples were collected from 96 consecutive UM patients undergoing enucleation, transretinal endoresection or transretinal biopsy. DNA was extracted from the ocular fluids and analyzed for the presence of tumor-derived DNA using deep amplicon sequencing targeting mutations in GNAQ and GNA11. This approach achieved an average read depth of 120,000, enabling highly sensitive detection of tumor-specific variants. Tumor DNA was detected in at least one ocular fluid (AH or VB) in 43 of 88 evaluable patients (49%), with variant allele fractions (VAFs) ranging from 0.3 to 50%. Of these positive cases, tumor DNA was identified in VB only in 22 patients, AH only in 5 patients, and both fluids in 16 patients. Importantly, tumor DNA in AH was almost exclusively observed in patients with monosomy 3 UM. No significant correlation was found between the presence of tumor DNA in either ocular fluid and primary tumor size or location. Liquid biopsy of AH and VB offers a promising, minimally invasive strategy for obtaining tumor DNA in nearly half of UM patients at diagnosis. The strong association between detectable tumor DNA in AH and monosomy 3 status warrants further investigation and may offer valuable insights into UM biology and dissemination mechanisms. This approach may improve risk stratification and inform personalized treatment strategies for patients with UM.

Netrin-1 signaling is an essential prototypical neuronal guidance mechanism during embryonic development that also regulates tumor cell survival in a variety of adult cancer entities. In line with these data, a monoclonal netrin-1 blocking antibody (anti-netrin-1 mAb/NP137) has been preclinically developed and netrin-1 blockade has recently been investigated in phase 1 and 2 clinical trials in several adult cancers. Here, we investigate the role of netrin-1 in the most common malignant pediatric brain cancer, Medulloblastoma. Interestingly, we find that netrin-1 is upregulated in medulloblastoma subgroups associated with developmental dysregulation, in particular in medulloblastoma with Sonic Hedgehog (SHH) activation. First, we demonstrate that genetic deletion of netrin-1 or systemic treatment with the clinical-stage anti-netrin-1 blocking antibody significantly reduces tumor growth in vivo in various orthotopic models of SHH medulloblastomas. Second, in vitro and in vivo, we unexpectedly uncover that SHH medulloblastomas treated with an SHH-inhibitor targeting Smoothened (SMO) increase netrin-1 expression, paving the way for combinatorial therapy. In line with that, we next show that netrin-1 blockade potentiates the efficacy of SMO inhibitor therapy in vivo. Together, our data indicate that, netrin-1 blockade, used as monotherapy or in combination with SMO inhibitors, is a promising therapeutic strategy in SHH medulloblastomas.

Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), with a rising incidence worldwide. However, the mechanisms by which ccRCC evades immune surveillance remain incompletely understood. Our findings indicate that fumarate hydratase (FH) expression is significantly downregulated in ccRCC, resulting in fumarate accumulation, which is correlated with a poor prognosis in ccRCC patients. RNA sequencing analysis suggests that dimethyl fumarate (DMF), an FDA-approved fumarate analogue, may impact tumor immunity. Our further investigation reveals that both DMF and the FH inhibitor (FHIN1) can promote immune evasion in ccRCC by upregulating PD-L1. Pre-treatment of tumor cells with DMF notably inhibits the cytotoxic effect of T cells. Mechanistically, fumarate induces PD-L1 expression through succination of HIF-1α at C800, facilitating its interaction with importin α3, p300, and PKM2, which promotes HIF-1α nuclear localization and transcriptional activity. Moreover, combining DMF with PD-L1 blockade therapy significantly enhances the efficacy of immunotherapy and prolongs the survival of tumor-bearing mice. Taken together, our study elucidates a mechanism by which FH downregulation promotes immune evasion through the fumarate-HIF-1α/p300/PKM2-PD-L1 axis, providing a novel target, drug, and strategy to improve immunotherapy for ccRCC.

Neutrophil extracellular traps (NETs) and immunity play critical roles in liver hepatocellular carcinoma (LIHC) progression, but their mechanisms remain unclear. This study explored the potential of NETs-related genes (NETs-RGs) and immune-related genes (IRGs) as prognostic markers for LIHC. LIHC transcriptome data and IRGs were obtained from public databases, and NETs-RGs were derived from prior research. Differentially expressed genes (DEGs) intersecting with key module genes were identified, followed by Cox regression analysis and machine learning to determine prognostic genes. A risk prediction model and nomogram were constructed and validated. Enrichment analysis, immune infiltration, and drug sensitivity studies were conducted to explore underlying mechanisms. Reverse transcription quantitative PCR (RT-qPCR) was used to validate findings. Five prognostic genes-HMOX1, MMP9, TNFRSF4, MMP12, and FLT3-were identified. A risk model and nomogram demonstrated strong predictive ability. Gene set enrichment analysis revealed pathways related to retinol metabolism and cytochrome P450 drug metabolism in different risk groups. Immune infiltration analysis showed regulatory T cells positively correlated with MDSCs, which were directly associated with the five genes. Drug sensitivity analysis identified 74 drugs with differential sensitivity between risk groups; axitinib showed lower sensitivity in high-risk patients, while ABT-888 showed higher sensitivity. RT-qPCR confirmed reduced HMOX1 and FLT3 expression in LIHC tissues, while MMP9 and TNFRSF4 were upregulated. This study developed a robust predictive model for LIHC prognosis, offering valuable insights for clinical management and personalized treatment strategies.

Reactive oxygen species can oxidatively modify enzymes to reroute metabolism according to tumor needs, rendering identification of oxidized proteins important for understanding neoplastic survival mechanisms. Thiol groups are most susceptible to oxidative modifications but challenging to analyze in clinical settings. We here describe the protein and small-molecular thiol oxidation landscape of 70 human lung tumors (and their paired healthy counter parts) and demonstrate that cancer adapts metabolism to increase glutathione synthesis to counteract oxidative stress. Glyoxalases, the key enzymes in the detoxification of methylglyoxal, a byproduct of glycolysis and precursor of advanced glycation end-products, are compromised by oxidation and downregulation. Despite decreased methylglyoxal detoxification capacity, cancers do not accumulate advanced glycation end-products. Since in vitro downregulation or inhibition of GAPDH upregulates glyoxalases, we propose that tumors reduce methylglyoxal by activating GAPDH.

Cystic masses in the abdominal cavity near the vaginal area can have a range of origins, including urothelial cysts, which have never been reported in dogs. This paper reports the first known occurrence of a urothelial cyst in a dog.

Bladder tumors in dogs, particularly urothelial carcinoma (UC), pose a diagnostic challenge due to overlapping imaging features with benign conditions. Accurate diagnosis is crucial for appropriate treatment and prognosis.

This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.

Gastric cancer is one of the most common malignant tumors in the digestive tract, which has the characteristics of high morbidity and mortality. However, gastric cancer is not achieved overnight but is gradually developing through the interaction of many factors. Therefore, actively delaying or blocking the "inflammation-cancer" transformation in gastric mucosa is the key to treatment. Nod-like receptor protein 3(NLRP3) inflammasome is a multi-protein signal complex and one of the important innate immune signal receptors. Inflammation plays an important role in the occurrence and development of gastric cancer, and continuous inflammation mediation will trigger the transformation from inflammation to cancer. Therefore, the significance of NLRP3 inflammasome to gastric mucosa lies in the transformation between inflammation and cancer. Traditional Chinese medicine(TCM) has the functions of multi-components, multi-targets, and few adverse reactions. A large number of studies show that TCM and related monomers have significant effects in treating liver, kidney, and immune diseases through mediating NLRP3 inflammasome, but there is less research on the "inflammation-cancer" transformation in gastric mucosa. By combing the NLRP3-related nuclear factor-κB transcription factor(NF-κB), hypoxia inducible factor-1α(HIF-1α), phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), and other signal pathways, this paper clarified their mechanisms in the "inflammation-cancer" transformation in gastric mucosa, delayed the process of "inflammation-cancer" transformation in gastric mucosa through four aspects: energy metabolism, pyroptosis, immune response, and vascular endothelial growth factor, and prevented and treated "inflammation-cancer" transformation in gastric mucosa from three aspects: TCM monomer, TCM compound prescription, and other therapies, so as to provide ideas for the subsequent treatment of "inflammation-cancer" transformation in gastric mucosa with TCM.

Patients with node-positive breast cancer having primary surgery currently undergo axillary node clearance (ANC) to reduce the risk of breast cancer recurrence. Evidence that this highly morbid procedure improves survival is lacking, but approximately 30% of patients will develop lifelong complications which significantly impact their quality of life.Targeted axillary dissection (TAD) may be a safe, less morbid alternative to ANC and will be evaluated in the upcoming Targeted Axillary Dissection versus axillary node clearance in patients with POsitive axillary Lymph nodes in Early breast cancer (TADPOLE) randomised controlled trial.TAD is not currently routine practice in patients having primary surgery, so it is vital that the procedure is performed in an agreed upon, standardised way within the trial and procedure fidelity monitored to ensure the results are generalisable and will be accepted by the surgical community. Robust surgical quality assurance (SQA) is essential. Here we describe the first phase of the TADPOLE SQA, a consensus process with the breast surgical community to agree upon how (1) surgery should be performed and standardised; (2) procedure fidelity will be monitored and (3) requirements for surgeon credentialling within the trial.

Bronchopulmonary carcinoids are rare neuroendocrine tumors, categorized as either typical (low-grade malignancy) or atypical (intermediate-grade malignancy), with an incidence of approximately 0.5 per 100000 people. One third of patients remain asymptomatic, while others may present with symptoms such as cough, hemoptysis, and recurrent infections, often resulting from bronchial obstruction. Endocrine syndromes, like carcinoid- or Cushing syndrome, are rare in pulmonary carcinoids.The prognosis of these tumors largely depends on histological classification and disease stage at diagnosis. Typical carcinoids, which are less aggressive, show higher 5- and 10-year survival rates compared to atypical carcinoids. Diagnostic factors such as tumor size, chromogranin A (CgA) levels, and clear differentiation from other lung pathologies, including carcinomas and metastases, are essential for accurate diagnosis and therapy planning.Due to the rarity of carcinoids, treatment requires an interdisciplinary approach. Surgical resection remains the preferred therapy for localized carcinoids, offering the potential for prolonged survival. Early detection and complete tumor removal are crucial to optimizing outcomes and minimizing the risk of recurrence.

Kaiso (ZBTB33) is a transcription factor involved in mitotic clonal expansion and tumorigenesis in association with Adenomatous Polyposis Coli (APC) loss of heterozygosity. ENCODE data show strong overlap of the Kaiso promoter-binding site-encode-derived Kaiso-binding site (eKBS) and many other transcription factors, including BRCA1. Here we sought to determine whether BRCA1 is a component of the Kaiso enhanceosome that regulates gene transcription. Using proximal ligation assays, immunoprecipitation followed by mass spectrometry, luciferase assays and ChIP-seq experiments, we evaluated the association between BRCA1 and Kaiso. Kaiso nuclear extract immunoprecipitation experiments revealed that Kaiso associates strongly with genes involved in RNA splicing and processing. When Kaiso was not crosslinked to DNA, BRCA1 was not detected among Kaiso-binding proteins. However, overexpression of BRCA1 increased Kaiso-mediated gene transcription in luciferase assays in a Kaiso-dependent manner. Comparison of BRCA1 ChIP-seq and Kaiso ChIP-seq data from HCT116 cells revealed both BRCA1 and Kaiso commonly bind to the promoters of 379 genes. The most enriched term associated with these genes where BRCA1 and Kaiso bind their promoters is metabolism of RNA. Disease processes associated with these BRCA1/Kaiso gene promoters indicate that BRCA1 is functionally linked to a Kaiso-directed programme of RNAP2-mediated gene transcription and likely associated with colorectal cancer development and maintenance.