Therapeutic applications of carbon nanomaterials in renal cancer.

Carbon nanomaterials (CNMs), including carbon nanotubes (CNTs), graphene, and nanodiamonds (NDs), have shown great promise in detecting and treating numerous cancers, including kidney cancer. CNMs can increase the sensitivity of diagnostic techniques for better kidney cancer identification and surveillance. They enable targeted medicine delivery specifically to tumour locations, with little effect on healthy tissue. Because of their unique chemical and physical characteristics, they can avoid the body's defence mechanisms, making it easier to accumulate where tumours exist. Consequently, CNMs provide more effective drug delivery to kidney cancer cells. It also helps in improving the efficacy of treatment. This review explores the potential of several CNMs in improving therapeutic strategies for kidney cancer. We briefly covered the physicochemical properties and therapeutic applications of CNMs. Additionally, we discussed how structural modifications in CNMs enhance their precision in treating renal cancer. A thorough overview of CNM-based gene, peptide, and drug delivery strategies for the treatment of renal cancer is presented in this review. It covers information on other CNM-based therapeutic approaches, such as hyperthermia, photodynamic therapy, and photoacoustic therapy. Also, the interactions of CNMs with the tumour microenvironment (TME) are explored, including modulation of the immune response, regulation of tumour hypoxia, interactions between CNMs and TME cells, effects of TME pH on CNMs, and more. Finally, potential side effects of CNMs, such as toxicity, bio corona formation, enzymatic degradation, and biocompatibility, are also discussed.

Stage-specific coexpression network analysis of Myc in cohorts of renal cancer.

The present study investigates the molecular dynamics of Myc in normal precursors and in different stages (I/II/III/IV) of cohorts of renal cancer using two distinct yet complementary approaches: gene expression and gene coexpression. We also analysed the variation of coexpression networks of Myc through the stage-wise progression of renal cancer cohorts. Myc expression is significantly higher in stage I compared to normal tissue but changed inconsistently across stages of renal cancer. We identified that Myc consistently coexpressed with fourteen genes in the KIPAN [Pan-kidney cohort (KICH + KIRC + KIRP)] and eight in the KIRC (Kidney renal clear cell carcinoma) across all stages, providing potential prognostic and diagnostic biomarkers. Coexpression network complexity decreased from normal precursor tissues to associated tumour stage I in KIPAN and KIRC but was inconsistent after that. In the process of cancer development, there is generally lower cross-tissue cancer network homology observed among coexpressed genes with Myc during the normal to the stage I compared to the stage-wise progression of cancer. Overall, this research provides novel perceptions of the molecular causes of kidney cancer. It also highlights potential genes and pathways crucial for diagnosing and treating this disease.

Computational Gene Expression and Network Analysis of Myc Reveal Insights into Its Diagnostic and Prognostic Role in Subtypes of Renal Cancer.

In this study, we analysed the Myc expression in the pan-kidney cohort (KIPAN) and kidney renal clear cell carcinoma (KIRC) in human tumour tissues compared to normal tissues. Myc is overexpressed and associated with poor overall survival (OS) in the KIPAN and KIRC. It shows that Myc plays a crucial role in the growth and maintenance of these malignancies. Additionally, we explored coexpressed genes, gene-set enrichment analysis of coexpressed genes, proteins and regulatory partners directly linked with Myc in KIPAN and KIRC and their role in cancer-specific events. Pathway enrichment analysis concluded that Myc-related genes are involved in many cancer-related pathways. Furthermore, we studied that among KIPAN, mutant forms of tumour suppressor genes have a poor prognosis and are associated with higher Myc expression but not in KIRC. This paper also investigates the correlation between Myc expression and promoter methylation, tumour-infiltrating lymphocytes, and the interaction of Myc with drugs. Our study indicates that Myc can be used as a diagnostic and prognostic biomarker in patients with KIPAN and KIRC with diverse clinical and pathological characteristics.

Integrative Analysis of Potential Biomarkers Involved in the Progression of Papillary Thyroid Cancer.

This study aims to explore key prognostic and diagnostic biomarkers involved in the pathogenesis of papillary thyroid cancer (PTC) which is one of the most common endocrine cancers and whose occurrence is rapidly increasing. Papillary thyroid cancer datasets containing normal and tumor samples were collected from Gene Expression Omnibus. Protein-protein interaction (PPI) network for common upregulated differentially expressed genes (DEGs) was constructed, and hub genes were studied. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed to identify the vital biological behaviors and pathways involved in PTC. PPI network analysis demonstrated the interaction between 134 common upregulated DEGs, and top 15 pivotal genes with highest degree of connectivity were retrieved. Three of the hub genes (DPP4, ITGA2, FN1) were linked to the prognosis of PTC patients and considered clinically relevant core genes via survival analysis. We suggest that the identification of key genes associated with PTC development help us in understanding molecular mechanisms related to disease. These genes could also be considered the diagnostic biomarkers or as therapeutic targets in the future treatment for PTC.

Antibody-based biosensor to detect oncogenic splicing factor Sam68 for the diagnosis of lung cancer.

OBJECTIVE: The present work aimed to investigate the potential utility of Sam68 protein as a prognostic marker in lung cancer. Then an electrochemical immunosensor is fabricated that is sufficiently sensitive to detect Sam68. RESULTS: Analysis of stage-specific Lung cancer microarray data shows that differential expression of Sam68 is associated with cancer stage and monotonically increases from early tumor stage to advanced metastatic stage. Moreover, the higher expression of Sam68 results in reduced survival of lung cancer patients. Based on these observations, an electrochemical immunosensor was developed for the quantification of Sam68 protein. The target protein was captured by the Anti-Sam68 antibody that was immobilized on the modified Glassy carbon electrode. The stepwise assembly process was characterized by cyclic voltammetry and electrochemical impedance spectroscopy. This fabricated immunosensor displayed good analytical performance in comparison to commercial ELISA kit with good sensitivity, lower detection limit (LOD) of 10.5 pg mL-1, and wide linear detection range from 1 to 5 µg mL-1. This method was validated with satisfactory detection of Sam68 protein in lung adenocarcinoma cell line, NCI-H23. Besides, spike and recovery assay reconfirm that the sensor can precisely quantify Sam68 protein in a complex physiological sample. CONCLUSION: We conclude Sam68 as a valuable prognostic biomarker for early detection of lung cancer. Moreover, we report the first study on the development of an electrochemical immunosensor for the detection of Sam68. The fabricated immunosensor exhibit excellent analytical performance, which can accurately predict the lung cancer patient pathological state.

Grade-specific diagnostic and prognostic biomarkers in breast cancer.

An integrative approach is presented to identify grade-specific biomarkers for breast cancer. Grade-specific molecular interaction networks were constructed with differentially expressed genes (DEGs) of cancer grade 1, 2, and 3. We observed that the molecular network of grade3 is predominantly associated with cancer-specific processes. Among the top ten connected DEGs in the grade3, the increase in the expression of UBE2C and CCNB2 genes was statistically significant across different grades. Along with UBE2C and CCNB2 genes, the CDK1, KIF2C, NDC80, and CCNB2 genes are also profoundly expressed in different grades and reduce the patient's survival. Gene set enrichment analysis of these six genes reconfirms their role in metastatic phenotype. Moreover, the coexpression network shows a strong association of these six genes promotes cancer specific biological processes and possibly drives cancer from lower to a higher grade. Collectively the identified genes can act as potential biomarkers for breast cancer diagnosis and prognosis.

A comprehensive study on genome-wide coexpression network of KHDRBS1/Sam68 reveals its cancer and patient-specific association.

Human KHDRBS1/Sam68 is an oncogenic splicing factor involved in signal transduction and pre-mRNA splicing. We explored the molecular mechanism of KHDRBS1 to be a prognostic marker in four different cancers. Within specific cancer, including kidney renal papillary cell carcinoma (KIRP), lung adenocarcinoma (LUAD), acute myeloid leukemia (LAML), and ovarian cancer (OV), KHDRBS1 expression is heterogeneous and patient specific. In KIRP and LUAD, higher expression of KHDRBS1 affects the patient survival, but not in LAML and OV. Genome-wide coexpression analysis reveals genes and transcripts which are coexpressed with KHDRBS1 in KIRP and LUAD, form the functional modules which are majorly involved in cancer-specific events. However, in case of LAML and OV, such modules are absent. Irrespective of the higher expression of KHDRBS1, the significant divergence of its biological roles and prognostic value is due to its cancer-specific interaction partners and correlation networks. We conclude that rewiring of KHDRBS1 interactions in cancer is directly associated with patient prognosis.

Fabrication of an immunosensor for quantitative detection of breast cancer biomarker UBE2C.

This work reports the design of a new electrochemical impedimetric immunosensor for the direct determination of ubiquitin-conjugating enzymes 2C (UBE2C), a potential diagnostic biomarker for breast cancer. The immunosensor was fabricated by immobilizing the capture anti-UBE2C antibody onto a polyaniline (PANI) modified glassy carbon electrode (GCE) through glutaraldehyde crosslinking. The assembly process of the immunosensor was examined using scanning electron microscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The fabricated immunosensor enabled the detection of recombinant human UBE2C in the range of 500 pg mL-1 to 5 µg mL-1. The limit of detection and limit of quantification were found to be 7.907 pg mL-1 and 26.356 pg mL-1, respectively. The diagnostic application of the fabricated immunosensor was explored for the analysis of breast cancer cell line MCF-7 cell extract. The immunosensor demonstrated high selectivity for UBE2C. The fabricated immunosensor also exhibited good reproducibility and storage stability.

Recent advances in biosensor development for the detection of cancer biomarkers.

Cancer is the second largest disease throughout the world with an increasing mortality rate over the past few years. The patient's survival rate is uncertain due to the limitations of cancer diagnosis and therapy. Early diagnosis of cancer is decisive for its successful treatment. A biomarker-based cancer diagnosis may significantly improve the early diagnosis and subsequent treatment. Biosensors play a crucial role in the detection of biomarkers as they are easy to use, portable, and can do analysis in real time. This review describes various biosensors designed for detecting nucleic acid and protein-based cancer biomarkers for cancer diagnosis. It mainly lays emphasis on different approaches to use electrochemical, optical, and mass-based transduction systems in cancer biomarker detection. It also highlights the analytical performances of various biosensor designs concerning cancer biomarkers in detail.

Alternative splicing within the Wnt signaling pathway: role in cancer development.

BACKGROUND: The Wnt signaling cascade plays a fundamental role in embryonic development, adult tissue regeneration, homeostasis and stem cell maintenance. Abnormal Wnt signaling has been found to be prevalent in various human cancers. Also, a role of Wnt signaling in the regulation of alternative splicing of several cancer-related genes has been established. In addition, accumulating evidence suggests the existence of multiple splice isoforms of Wnt signaling cascade components, including Wnt ligands, receptors, components of the destruction complex and transcription activators/suppressors. The presence of multiple Wnt signaling-related isoforms may affect the functionality of the Wnt pathway, including its deregulation in cancer. As such, specific Wnt pathway isoform components may serve as therapeutic targets or as biomarkers for certain human cancers. Here, we review the role of alternative splicing of Wnt signaling components during the onset and progression of cancer. CONCLUSIONS: Splice isoforms of components of the Wnt signaling pathway play distinct roles in cancer development. Isoforms of the same component may function in a tissue- and/or cancer-specific manner. Splice isoform expression analyses along with deregulated Wnt signaling pathway analyses may be of help to design efficient diagnostic and therapeutic strategies.

Nanomaterials towards fabrication of cholesterol biosensors: Key roles and design approaches.

Importance of cholesterol biosensors is already recognized in the clinical diagnosis of cardiac and brain vascular diseases as discernible from the enormous amount of research in this field. Nevertheless, the practical application of a majority of the fabricated cholesterol biosensors is ordinarily limited by their inadequate performance in terms of one or more analytical parameters including stability, sensitivity and detection limit. Nanoscale materials offer distinctive size tunable electronic, catalytic and optical properties which opened new opportunities for designing highly efficient biosensor devices. Incorporation of nanomaterials in biosensing devices has found to improve the electroactive surface, electronic conductivity and biocompatibility of the electrode surfaces which then improves the analytical performance of the biosensors. Here we have reviewed recent advances in nanomaterial-based cholesterol biosensors. Foremost, the diverse roles of nanomaterials in these sensor systems have been discussed. Later, we have exhaustively explored the strategies used for engineering cholesterol biosensors with nanotubes, nanoparticles and nanocomposites. Finally, this review concludes with future outlook signifying some challenges of these nanoengineered cholesterol sensors.

Covalent immobilization of cholesterol oxidase on self-assembled gold nanoparticles for highly sensitive amperometric detection of cholesterol in real samples.

A novel scheme for the fabrication of gold nanoparticle modified cholesterol oxidase based bioelectrode is presented and its application potential for cholesterol biosensor is investigated. The fabrication procedure is based on the deposition of gold nanoparticles on the 1,6-hexanedithiol modified gold electrode, functionalization of the surface of deposited gold nanoparticles with carboxyl groups using 11-mercaptoundecanoic acid and then covalent immobilization of cholesterol oxidase on the surface of gold nanoparticle film using the N-ethyl-N'-(3-dimethylaminopropyl carbodimide) and N-hydroxysuccinimide ligand chemistry. The assembly process of the bioelectrode is investigated using atomic force microscopy, cyclic voltammetry and electrochemical impedance spectroscopy. The gold nanoparticle film on the electrode surface provided an environment for the enhanced electrocatalytic activities and thus resulted in enhanced analytical response. The resulting bioelectrode is further applied to the amperometric detection of cholesterol and exhibited a linear response to cholesterol in the range of 0.04-0.22 mM with a detection limit of 34.6 µM, apparent Michaelis-Menten constant (K(m)(app)) of 0.062 mM and a high sensitivity of 9.02 µA mM(-1). The fabricated bioelectrode is successfully used for the selective determination of cholesterol in human serum samples.

Silk mat as bio-matrix for the immobilization of cholesterol oxidase.

Cholesterol oxidase (ChOx) was covalently immobilized onto the woven silk fiber (silk mat) produced by Antheraea assamensis. The immobilization was done using N-ethyl-N'-(3-dimethylaminopropyl) carbodimide and N-hydroxysuccinimide ligand chemistry. The attachment of ChOx to the silk mat was demonstrated by scanning electron microscopy and activity study. The kinetic studies of the immobilized ChOx were performed by using a biological oxygen monitor. The enzyme loading was found to be 0.046 U cm(-2) of silk mat and the enzyme loading efficiency of the silk mat was estimated to be 70%. Remarkably high storage and operational stability (t(1/2) of initial activities) corresponding to 13 months and 25 numbers of assay (for a period of 6 h), respectively, of the fabricated ChOx electrode were demonstrated.

Status of Stat3 in an ovalbumin-induced mouse model of asthma: analysis of the role of Socs3 and IL-6.

BACKGROUND: Stat3, Socs3 and cytokines play an integral role in the coordination and persistence of inflammation. However, a clear understanding of the role played by the Stat3/IL-6 and Socs3 pathway in airway inflammation is lacking. We report the alteration in the status of expression and activation of Stat3 by ovalbumin (OVA), and establish its relationship with Socs3 and IL-6 in the lungs of mice with eosinophilic pulmonary inflammation and airway hyperresponsiveness. METHODS: Alterations in the expression of Stat3, Socs3 and IL-6 were determined in a murine model of asthma, where Balb/c mice were sensitized and challenged with OVA (OVA/OVA) and compared with control mice sensitized and challenged with saline (SAL) (SAL/SAL) mice. The OVA/OVA mice were characterized by a moderate increase in methacholine-induced specific airway resistance, the presence of 150 microg/ml of OVA-specific IgG and 8.93 microg/ml OVA-specific IgE antibody and elevated levels of eosinophils and Th2 cytokines (IL-4 and IL-5) in the bronchoalveolar lavage fluid. In contrast SAL/SAL mice had low eosinophils, IL-4 and IL-5 and no OVA-specific IgG and IgE antibodies in the BALF. Stat3 and Socs3 expression profiles were monitored in OVA/OVA and Stat3- and Socs3-silenced OVA/OVA mice. Furthermore, expression of IL-6 in Stat3- and Socs3-silenced mice and the exogenous effect of IL-6 on Stat3 were studied. RESULTS: The results show that expression and activation of Stat3 mRNA and proteins are significantly low in lung of OVA/OVA mice in comparison to SAL/SAL mice following OVA challenge. An increased pool of Socs3 mRNA is observed in OVA/OVA mice with or without OVA challenge and in SAL/SAL mice 24 h after OVA challenge. Transient in vivo blocking of Socs3 gene by Socs3 siRNA restores the expression of IL-6 mRNA and protein in OVA/OVA mice, and nasal administration of recombinant IL-6 to OVA/OVA mice enhanced Stat3 mRNA expression. CONCLUSIONS: Our data suggest that airway inflammation is associated with low expression of Stat3 and IL-6 and overexpression of Socs3 genes in a mouse model of asthma. Furthermore, IL-6 is under the influence of the Socs3 gene and may contribute to the negative regulation of Stat3 via IL-6 following a challenge with an allergen during the development of asthma.