Proteogenomic examination of esophageal squamous cell carcinoma (ESCC): new lines of inquiry.

Introduction: Esophageal squamous cell carcinoma (ESCC), a histopathologic subtype of esophageal cancer is a major cause of cancer-related morbidity and mortality worldwide. This is primarily because patients are diagnosed at an advanced stage by the time symptoms appear. The genomics and mass spectrometry-based proteomics continue to provide important leads toward biomarker discovery for ESCC. However, such leads are yet to be translated into clinical utilities. Areas covered: We gathered information pertaining to proteomics and proteogenomics efforts in ESCC from the literature search until 2020. An overview of omics approaches to discover the candidate biomarkers for ESCC were highlighted. We present a summary of recent investigations of alterations in the level of gene and protein expression observed in biological samples including body fluids, tissue/biopsy and in vitro-based models. Expert opinion: A large number of protein-based biomarkers and therapeutic targets are being used in cancer therapy. Several candidates are being developed as diagnostics and prognostics for the management of cancers. High-resolution proteomic and proteogenomic approaches offer an efficient way to identify additional candidate biomarkers for diagnosis, monitoring of disease progression, prediction of response to chemo and radiotherapy. Some of these biomarkers can also be developed as therapeutic targets.

Delivery of affordable and equitable cancer care in India.

The delivery of affordable and equitable cancer care is one of India's greatest public health challenges. Public expenditure on cancer in India remains below US$10 per person (compared with more than US$100 per person in high-income countries), and overall public expenditure on health care is still only slightly above 1% of gross domestic product. Out-of-pocket payments, which account for more than three-quarters of cancer expenditures in India, are one of the greatest threats to patients and families, and a cancer diagnosis is increasingly responsible for catastrophic expenditures that negatively affect not only the patient but also the welfare and education of several generations of their family. We explore the complex nature of cancer care systems across India, from state to government levels, and address the crucial issues of infrastructure, manpower shortages, and the pressing need to develop cross-state solutions to prevention and early detection of cancer, in addition to governance of the largely unregulated private sector and the cost of new technologies and drugs. We discuss the role of public insurance schemes, the need to develop new political mandates and authority to set priorities, the necessity to greatly improve the quality of care, and the drive to understand and deliver cost-effective cancer care programmes.

Cancer research in India: national priorities, global results.

Over the past 20 years, cancer research in India has grown in size and impact. Clinicians, scientists, and government and state policy makers in India have championed cancer research, from studies to achieve low-tech, large-scale health outcomes to some of the most advanced areas of fundamental cancer science. In this paper, we frame public policy discussions about cancer with use of an in-depth analysis of research publications from India. Cancer research in India is a complex environment that needs to balance public policy across many competing agendas. We identify major needs across these environments such as those for increased research capacity and training and protected time for clinical researchers; for more support from states and enhanced collaborative funding programmes from government; for development of national infrastructures across a range of domains (ie, clinical trials, tissue banking, registries, etc); and for a streamlined and rational regulatory environment. We also discuss improvements that should be made to translate research into improvements in cancer outcomes and public health.

Proteomic analysis of peripheral blood mononuclear cells from OSCC patients reveals potential immune checkpoints to enable personalized treatment.

Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide, with high mortality and prevalence rates. OSCC is defined as an immunogenic tumor with the potential to be recognized and targeted by the immune system. It is characterized by the extensive infiltration of immune cells and plays a vital role in tumorigenesis. Peripheral blood mononuclear cells (PBMC) are a functional subset of immune cells readily accessible through minimally invasive procedures. The molecular characterization of immune cells aids in understanding their functional roles in various pathophysiological conditions. Proteomic analysis of PBMCs from cancer patients provides insight into the mechanism of immunoregulation and the role of immune cells in impeding tumor development and progression. Therefore, the present study investigated the immune cell proteome of a cancer control cohort within OSCC, leveraging data-independent acquisition analysis by mass spectrometry (DIA-MS). Among the differentially abundant proteins in OSCC, we identified promising molecular targets, including LMNB1, CTSB, CD14, CD177, and SPI1. Further exploration of the signaling pathways related to the candidate molecules demonstrated their involvement in cancer immunomodulation. Therefore, this study can serve as a platform for identifying new candidate proteins to further investigate their potential as immunotherapeutic targets and prognostic markers.

REMEMProt: a resource of membrane-enriched proteome profiles, their disease associations, and biomarker status.

The differential expression of plasma membrane proteins is integrally analyzed for their diagnosis, prognosis, and therapeutic applications in diverse clinical manifestations. Necessarily, distinct membrane protein enrichment methods and mass spectrometry platforms are employed for their global and relative quantitation. First of its kind to explore, we compiled membrane-associated proteomes in human and mouse systems into a database named, Resource of Experimental Membrane-Enriched Mass spectrometry-derived Proteome (REMEMProt). It currently hosts 14,626 proteins (9,507 proteins in Homo sapiens; 5,119 proteins in Mus musculus) with information on their membrane-protein enrichment methods, experimental/physiological context of detection in cells or tissues, transmembrane domain analysis, and their current attribution as biomarkers. Based on these annotations and the transmembrane domain analysis in proteins or their binary/complex protein-protein interactors, REMEMProt facilitates the assessment of the plasma membrane localization potential of proteins through batch query. A cross-study enrichment analysis platform is enabled in REMEMProt for comparative analysis of proteomes using novel/modified membrane enrichment methods and evaluation of methods for targeted enrichment of membrane proteins. REMEMProt data are made freely accessible to explore and download at https://rememprot.ciods.in/.

A review of global cancer burden: trends, challenges, strategies, and a role for surgeons.

Cancer is one of the leading causes of death worldwide. The global cancer burden (GCB) is expected to rise significantly and will disproportionately affect the less developed world (LDW). The aim of this review is to analyze the trends in GCB and describe the types, estimates, and causes of new cancer cases. The challenges and strategies associated with tackling this rising GCB are described in which surgeons can play a vital role.

Novel Insight into the Concept of Favorable Combination of Electrodes in High Voltage Supercapacitors: Toward Ultrahigh Volumetric Energy Density and Outstanding Rate Capability.

Most of the biomass-derived carbon-based supercapacitors using organic electrolytes exhibit very low energy density due to their low operating potential range between 2.7 and 3.0 V. A novel insight into the concept of the different porous architecture of electrode materials that is employed to extend a device's operating potential up to 3.4 V using TEABF4 in acetonitrile, is reported. The combination of two high surface area activated carbons derived from abundant natural resources such as industrial waste cotton and wheat flour as sustainable and green carbon precursors is explored as an economical and efficient supercapacitor carbon electrode. Benefitting from the simultaneous achievement of the higher potential window (3.4 V) with higher volumetric capacitance (101 F cm-3), the supercapacitor electrodes exhibit higher volumetric energy density (42.85 Wh L-1). Bimodal pore size distribution of carbon with a tuned pore size and high specific surface area of the electrode can promote the fast transport of cations and anions. Hence, it exhibits a high rate capability even at 30 A g-1. In addition, the electrodes remain stable during operation cell voltage at 3.4 V upon 15 000 charging-discharging cycles with 90% capacitance retention.

Multiple G-quadruplex binding ligand induced transcriptomic map of cancer cell lines.

The G-quadruplexes (G4s) are a class of DNA secondary structures with guanine rich DNA sequences that can fold into four stranded non-canonical structures. At the genomic level, their pivotal role is well established in DNA replication, telomerase functions, constitution of topologically associating domains, and the regulation of gene expression. Genome instability mediated by altered G4 formation and assembly has been associated with multiple disorders including cancers and neurodegenerative disorders. Multiple tools have also been developed to predict the potential G4 regions in genomes and the whole genome G4 maps are also being derived through sequencing approaches. Enrichment of G4s in the cis-regulatory elements of genes associated with tumorigenesis has accelerated the quest for identification of G4-DNA binding ligands (G4DBLs) that can selectively bind and regulate the expression of such specific genes. In this context, the analysis of G4DBL responsive transcriptome in diverse cancer cell lines is inevitable for assessment of the specificity of novel G4DBLs. Towards this, we assembled the transcripts differentially regulated by different G4DBLs and have also identified a core set of genes regulated in diverse cancer cell lines in response to 3 or more of these ligands. With the mode of action of G4DBLs towards topology shifts, folding, or disruption of G4 structure being currently visualized, we believe that this dataset will serve as a platform for assembly of G4DBL responsive transcriptome for comparative analysis of G4DBLs in multiple cancer cells based on the expression of specific cis-regulatory G4 associated genes in the future.

A multi-cellular molecular signaling and functional network map of C-C motif chemokine ligand 18 (CCL18): a chemokine with immunosuppressive and pro-tumor functions.

The C-C Motif Chemokine Ligand 18 (CCL18) is a beta-chemokine sub-family member with immunomodulatory functions in primates. CCL18-dependent migration and epithelial-to-mesenchymal transition of oral squamous cell carcinoma, squamous cell carcinoma of head and neck, breast cancer, hepatocellular carcinoma, non-small cell lung carcinoma, ovarian cancer, pancreatic ductal carcinoma and bladder cancer cells are well-established. In the tumor niche, tumor-associated macrophages produce CCL18 and its overexpression is correlated with reduced patient survival in multiple cancers. Although multiple receptors including C-C chemokine receptor type 3 (CCR3), type 6 (CCR6), type 8 (CCR8) and G-protein coupled estrogen receptor (GPER1) are reported for CCL18, the Phosphatidylinositol Transfer Protein, Membrane-Associated 3 (PITPNM3) receptor is currently considered as its predominant receptor. Characterization of the molecular events and check points associated with the immunosuppressive and cancer progression support functions induced by CCL18 for their potential towards therapeutic applications is an area of active research. Hence, in this study, we assembled 917 signaling events reported to be induced by CCL18 through their studied receptors in diverse cell types as an integrated knowledgebase for reference, data integration and gene-set enrichment analysis of global transcriptomic and/or proteomics datasets.

Metal chalcogenide-based core/shell photocatalysts for solar hydrogen production: Recent advances, properties and technology challenges.

Metal chalcogenides play a vital role in the conversion of solar energy into hydrogen fuel. Hydrogen fuel technology can possibly tackle the future energy crises by replacing carbon fuels such as petroleum, diesel and kerosene, owning to zero emission carbon-free gas and eco-friendliness. Metal chalcogenides are classified into narrow band gap (CdS, Cu2S, Bi2S3, MoS2, CdSe and MoSe2) materials and wide band gap materials (ZnS, ZnSe and ZnTe). Composites of these materials are fabricated with different architectures in which core-shell is one of the unique composites that drastically improve the photo-excitons separation, where chalcogenides in the core can be well protected for sustainable uses. Thus,the core-shell structures promote the design and fabrication of composites with the required characteristics. Interestingly, the metal chalcogenides as a core-shell photocatalyst can be classified into type-I, reverse type-I, type-II and S-type nanocomposites, which can effectively influence and significantly enhance the rate of hydrogen production. In this direction, this review is undertaken to provide a comprehensive overview of the advanced preparation processes, properties of metal chalcogenides, and in particular, photocatalytic performance of the metal chalcogenides as a core-shell photocatalysts for solar hydrogen production.

Omics Data Mining for multiPTMs in Oral Cancer: Cellular Proteome and Secretome of Chronic Tobacco-Treated Oral Keratinocytes.

Oral cancer is common worldwide but lacks robust diagnostics and therapeutics. Lifestyle factors, such as tobacco chewing and smoking, are significantly associated with oral cancers. Mapping the changes in the global proteome, secretome and post-translational modifications (PTMs) during tobacco exposure of oral keratinocytes hold great potential for understanding the mechanisms of oral carcinogenesis, not to mention for innovation toward clinical interventions in the future. On the other hand, although advances in mass spectrometry (MS)-based techniques have enabled the deep mining of complex proteomes, a large portion of the mass spectrometric data remains unassigned. These unassigned spectral data can be researched for multiple post-translational modifications (multiPTMs). Using data mining of publicly available proteomics data, we report, in this study, a multiPTM analysis of high-resolution MS-derived datasets on cellular proteome and secretome of chronic tobacco-treated oral keratinocytes. We identified 800 PTM sites in 496 proteins. Among them, 43 PTM sites in 37 proteins were found to be differentially expressed, accounting for their protein-level expression. Enrichment analysis of the proteins with altered phosphosite expression and the known kinases of these phosphosites discovered the overrepresentation of certain biological processes such as splicing and hemidesmosome assembly. These findings contribute to a deeper understanding of omics level changes in chronic tobacco-treated oral keratinocytes, and by extension, pathophysiology of oral cancers.

A complete map of the Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) signaling pathway.

Calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is a serine/threonine-protein kinase belonging to the Ca2+/calmodulin-dependent protein kinase subfamily. CAMKK2 has an autocatalytic site, which gets exposed when Ca2+/calmodulin (CAM) binds to it. This results in autophosphorylation and complete activation of CAMKK2. The three major known downstream targets of CAMKK2 are 5'-adenosine monophosphate (AMP)-activated protein kinase (AMPKα), calcium/calmodulin-dependent protein kinase 1 (CAMK1) and calcium/calmodulin-dependent protein kinase 4 (CAMK4). Activation of these targets by CAMKK2 is important for the maintenance of different cellular and physiological processes within the cell. CAMKK2 is found to be important in neuronal development, bone remodeling, adipogenesis, and systemic glucose homeostasis, osteoclastgensis and postnatal myogensis. CAMKK2 is reported to be involved in pathologies like Duchenne muscular dystrophy, inflammation, osteoporosis and bone remodeling and is also reported to be overexpressed in prostate cancer, hepatic cancer, ovarian and gastric cancer. CAMKK2 is involved in increased cell proliferation and migration through CAMKK2/AMPK pathway in prostate cancer and activation of AKT in ovarian cancer. Although CAMKK2 is a molecule of great importance, a public resource of the CAMKK2 signaling pathway is currently lacking. Therefore, we carried out detailed data mining and documentation of the signaling events associated with CAMKK2 from published literature and developed an integrated reaction map of CAMKK2 signaling. This resulted in the cataloging of 285 reactions belonging to the CAMKK2 signaling pathway, which includes 33 protein-protein interactions, 74 post-translational modifications, 7 protein translocation events, and 22 activation/inhibition events. Besides, 124 gene regulation events and 25 activator/inhibitors involved in CAMKK2 activation were also cataloged. The CAMKK2 signaling pathway map data is made freely accessible through WikiPathway database ( https://www.wikipathways.org/index.php/Pathway:WP4874 ). We expect that data on a signaling map of CAMKK2 will provide the scientific community with an improved platform to facilitate further molecular as well as biomedical investigations on CAMKK2 and its utility in the development of biomarkers and therapeutic targets.

Disparities in cancer care between the United States of America and India and opportunities for surgeons to lead.

The recent report from International Agency for Research in Cancer (IARC) predicted a threefold increase in the global cancer burden by 2030 with a disproportionate rise in cases from the developing world countries such as India. The aim of this study is to compare the cancer care between the developed and developing countries such as the United States of America and India and suggest avenues for surgeons to take a lead in addressing these disparities.

Conversion of Solar Energy into Electrical Energy Storage: Supercapacitor as an Ultrafast Energy-Storage Device Made from Biodegradable Agar-Agar as a Novel and Low-Cost Carbon Precursor.

Solar cells hold promise as energy conversion devices but intermittent sunlight limits their continuous applications. The self-powering integrated solar cells and electrical energy storage devices can be an alternative to resolve this problem. This study demonstrates the integration of solar cell with supercapacitor (SC) device and evaluates its performance for energy conversion and storage for practical validity. SC carbon is derived from agar-agar as low-cost carbon precursor and a high-performance SC electrode is utilized for the first time. The fabricated SC shows an excellent specific capacitance of 170 F g-1 and retains 85% of its original value up to 15 000 charge/discharge cycles at 1 A g-1, and it holds a maximum energy density of 17.7 Wh kg-1. The integration of SCs (three cells in series with 5.4 V) with a commercial solar lantern for a self-sustaining power pack is demonstrated. The SC is charged by solar cells in a few seconds and powers a solar lantern with 40 light-emitting diodes without sunlight, demonstrates its potential for efficient conversion of solar energy into electrical energy storage. This result highlights that solar SC can be considered as an ultrafast next-generation energy-storage device that can mitigate the energy demand in the near future.

Esophagectomy for cancer of the esophagus. A regional cancer centre experience.

Surgery is an important component of treatment for patients with resectable cancer of the mid and lower third of the esophagus. There are many controversies associated with esophagectomy. We share our experience with esophagectomy for cancer of the mid and lower third of the esophagus. Between January 2007 and December 2011, 210 patients with cancer of the esophagus underwent surgery. The patients' pre and intra- operative factors, morbidities and mortality were noted and studied. Transhiatal esophagectomy was done in 175 patients and right transthoracic esophagectomy was done in 35 patients. The most common location of the tumor was lower third and most common histopathology was squamous cell carcinoma. There were 5 in-hospital deaths (2.4 %) and the common morbidities encountered were respiratory (30 %), anastomotic leak (5 %) and anastomotic stricture (15 %). The morbidity was higher in the transthoracic group. Our R0 resection rate was 89 %. Esophagectomy can be accomplished with acceptable morbidity in the management of patients with oesophageal cancer. We attribute the favourable results to the high volume at our centre, surgical expertise, good patient selection and performance of the anastomosis in the neck.

Downregulation of cornulin in esophageal squamous cell carcinoma.

Early events in the development of esophageal squamous cell carcinoma (ESCC) are poorly understood and many of the key molecules involved have not yet been identified. We previously used isobaric tags for a relative and absolute quantitation (iTRAQ)-based quantitative proteomics approach to identify differentially expressed proteins in ESCC tissue as compared to the adjacent normal mucosa. Cornulin was identified as one of the major downregulated molecules in ESCC. Cornulin is a member of the S100 fused-type protein family, which has an EF-hand calcium binding motif and multiple tandem repeats of specific peptide motifs. Cornulin was 5-fold downregulated in ESCC as compared to normal epithelium mirroring our previous findings in a gene expression study of ESCC. In the present study, we performed immunohistochemical validation of cornulin (CRNN) in a larger set of patients with ESCC. Downregulation of cornulin was observed in 89% (n=239) of 266 different ESCC tissues arrayed on tissue microarrays (TMAs). Expression of cornulin was observed in the prickle and functional cell layers of normal esophageal mucosa, localized predominantly in the cytoplasm and perinuclear region. The large majority of ESCC cases had little or no expression of cornulin in the carcinoma or stroma. These findings suggest that cornulin is an important molecule in normal esophageal pathology and is likely lost during the conversion of normal to neoplastic epithelium.

To operate or not to operate n0 neck in early cancer of the tongue? A prospective study.

Squamous cell carcinoma (SCC) of the tongue is a common cancer across the globe. These cancers have a high predilection for nodal metastasis and a high incidence of occult metastasis. The management of clinically negative neck nodes (N0) remains controversial. We have undertaken a prospective study to evaluate the rate of occult nodal metastasis, the characteristic of metastasis, and assess the usefulness of tumor depth as a predictor of metastasis and as a guide to treat the neck. Prospective study between January 2000 to December 2005. Patients with SCC of the anterior 2/3rd of tongue with N0 neck were included. Wide excision of the primary and subsequent modified radical neck dissection (in patients with tumor depth > 4 mm) was performed. Postoperative radiotherapy was given in patients with lymph node metastasis. Patients who had no node metastasis (p N -ve) were observed. The total number of eligible patients was 180. Occult lymph node metastasis (p N +ve) was seen in 122 (62.2%) patients (p < 0.001), multiple levels of node involvement in 79 (70.5%) patients and extracapsular spread (ECS) in 38 (33.6%) patients. Patients in the p N +ve group who were disease free was 63.1% as compared to 68.2% in the p N -ve group (p = 0.36). Recurrence was seen in 28 (36.8%) patients of p N +ve group and 14 (31.8%) patients of p N -ve group. Early cancer of tongue with tumor depth >4 mm was associated with predominantly high grade tumors, high incidence of occult nodal metastasis, multiple levels of nodal involvement and ECS. The disease free status of patients with occult metastasis who were treated was similar to that of patients with no nodal metastasis. Elective neck dissection appears essential for early oral tongue cancer with tumor depth >4 mm as there is no investigational modality which can reliably identify patients without occult metastasis.