Profiling DNA mutation patterns for cancer classification plays an essential role in precision and personalized medicine. Conventional PCR-based mutation assay is limited by the extensive labour on ...target amplification. We herein create an amplification-free surface enhanced Raman spectroscopy (SERS) biochip which enables direct and simultaneous identification of multiple point mutations in tumor cells. Without pre-amplifying the target sequences, the SERS assay reads out the presence of cellular mutations through the interpretation of Raman fingerprints. The SERS sensor is integrated into a microfluidic chip, achieving one-step multiplex analysis within 40 min. Importantly, by combining SERS spectra encoding technique with supervised learning algorithm, a panel of nucleotide mixtures can be well distinguished according to their mutation profiles. We initially demonstrate an excellent levels of classification in samples from colorectal cancer and melanoma cell lines. For final clinical validation, the system performance is verified by classifying cancer patient samples, which shows an accuracy above 90%. Due to the simplicity and rapidness, the SERS biosensor is expected to become a promising tool for clinical point-of-care diagnosis towards precision medicine.
•A SERS biochip for analyzing cellular DNA mutation is developed.•Amplification-free detection of multiple cellular point mutations is achieved.•Supervised learning algorithm is employed for cancer classification.•The chip is capable to analyse real clinical samples from colorectal cancer patients.
Background
Perioperative complications can affect outcomes after gastrectomy for cancer, with high mortality and morbidity rates ranging between 10 and 40%. The absence of a standardized system for ...recording complications generates wide variation in evaluating their impacts on outcomes and hinders proposals of quality-improvement projects. The aim of this study was to provide a list of defined gastrectomy complications approved through international consensus.
Methods
The Gastrectomy Complications Consensus Group consists of 34 European gastric cancer experts who are members of the International Gastric Cancer Association. A group meeting established the work plan for study implementation through Delphi surveys. A consensus was reached regarding a set of standardized methods to define gastrectomy complications.
Results
A standardized list of 27 defined complications (grouped into 3 intraoperative, 14 postoperative general, and 10 postoperative surgical complications) was created to provide a simple but accurate template for recording individual gastrectomy complications. A consensus was reached for both the list of complications that should be considered major adverse events after gastrectomy for cancer and their specific definitions. The study group also agreed that an assessment of each surgical case should be completed at patient discharge and 90 days postoperatively using a Complication Recording Sheet.
Conclusion
The list of defined complications (soon to be validated in an international multicenter study) and the ongoing development of an electronic datasheet app to record them provide the basic infrastructure to reach the ultimate goals of standardized international data collection, establishment of benchmark results, and fostering of quality-improvement projects.
Decades of research have disclosed a plethora of alterations in protein glycosylation that decisively impact in all stages of disease and ultimately contribute to more aggressive cell phenotypes. The ...biosynthesis of cancer-associated glycans and its reflection in the glycoproteome is driven by microenvironmental cues and these events act synergistically toward disease evolution. Such intricate crosstalk provides the molecular foundations for the activation of relevant oncogenic pathways and leads to functional alterations driving invasion and disease dissemination. However, it also provides an important source of relevant glyco(neo)epitopes holding tremendous potential for clinical intervention. Therefore, we highlight the transversal nature of glycans throughout the currently accepted cancer hallmarks, with emphasis on the crosstalk between glycans and the tumor microenvironment stromal components. Focus is also set on the pressing need to include glycans and glycoconjugates in comprehensive panomics models envisaging molecular-based precision medicine capable of improving patient care. We foresee that this may provide the necessary rationale for more comprehensive studies and molecular-based intervention.
Saliva has gained increasing attention in the quest for disease biomarkers. Because it is a biological fluid that can be collected is an easy, painless, and safe way, it has been increasingly studied ...for the identification of oral cancer biomarkers. This is particularly important because oral cancer is often diagnosed at late stages with a poor prognosis.
The review addresses the evolution of the experimental approaches used in salivary proteomics studies of oral cancer over the years and outlines advantages and pitfalls related to each one. In addition, examines the current landscape of oral cancer biomarker discovery and translation focusing on salivary proteomic studies. This discussion is based on an extensive literature search (PubMed, Scopus and Google Scholar).
The introduction of mass spectrometry has revolutionized the study of salivary proteomics. In the future, the focus will be on refining existing methods and introducing powerful experimental techniques such as mass spectrometry with selected reaction monitoring, which, despite their effectiveness, are still underutilized due to their high cost. In addition, conducting studies with larger cohorts and establishing standardized protocols for salivary proteomics are key challenges that need to be addressed in the coming years.
The study of the microbiome has significantly contributed to our understanding of complex diseases including cancer, with a profound influence of the microbiota on clinical prognosis and the efficacy ...of cancer treatments. Oesophageal cancer is positioned amongst the most aggressive malignant diseases, resulting from a complex interaction between anthropometric, genetic, immune response, and environmental factors. Oesophageal squamous cell carcinoma (OSCC) is the most common type of oesophageal cancer and is a serious burden in Eastern Africa, in the area known as the African oesophageal cancer corridor (AOCC). OSCC is often diagnosed at a late stage, with patients already suffering from severe malnutrition and dehydration due to swallowing difficulties, leading to high mortality rates. So far, aetiological factors have been individually analysed with an inappropriate contextualisation. The upper digestive tract microbiome has been proposed to contribute to the onset and progression of OSCC but with limited understanding of the mechanisms behind this interaction. Data on African populations are limited, and the aetiology of AOCC is still poorly understood. This review discusses the current knowledge of the aetiology of OSCC in Africa, with special focus on the probable influence of the upper digestive tract microbiota.
Advanced head and neck squamous cell carcinoma, after locoregional treatment and multiple lines of systemic therapies, represents a great challenge to overcome acquired resistance. The present ...clinical case illustrates a successful treatment option and is the first to describe the use of photodynamic therapy (PDT) with Redaporfin, followed by immune checkpoint inhibition with an anti-PD1 antibody. This patient presented an extensive tumor in the mouth pavement progressing after surgery, radiotherapy, and multiple lines of systemic treatment. PDT with Redaporfin achieved the destruction of all visible tumor, and the sequential use of an immune checkpoint inhibitor allowed a sustained complete response. This case is an example of the effect of this therapeutic combination and may provide the basis for a new treatment modality.
Globally, gastric cancer is the 4(th) most frequently diagnosed cancer and the 2(nd) leading cause of death from cancer, with an estimated 990000 new cases and 738000 deaths registered in 2008. In ...the advanced setting, standard chemotherapies protocols acquired an important role since last decades in prolong survival. Moreover, recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2 (HER2) therapies. Trastuzumab, an anti-HER2 monoclonal antibody, was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based chemotherapy. Further, HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this field. Thus, we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer, providing a comprehensive overview of molecular mechanisms and novel trials involved.
Cancer remains a leading cause of death worldwide due to the lack of safer and more effective therapies. Cancer vaccines developed from neoantigens are an emerging strategy to promote protective and ...therapeutic anti-cancer immune responses. Advances in glycomics and glycoproteomics have unveiled several cancer-specific glycosignatures, holding tremendous potential to foster effective cancer glycovaccines. However, the immunosuppressive nature of tumours poses a major obstacle to vaccine-based immunotherapy. Chemical modification of tumour associated glycans, conjugation with immunogenic carriers and administration in combination with potent immune adjuvants constitute emerging strategies to address this bottleneck. Moreover, novel vaccine vehicles have been optimized to enhance immune responses against otherwise poorly immunogenic cancer epitopes. Nanovehicles have shown increased affinity for antigen presenting cells (APCs) in lymph nodes and tumours, while reducing treatment toxicity. Designs exploiting glycans recognized by APCs have further enhanced the delivery of antigenic payloads, improving glycovaccine's capacity to elicit innate and acquired immune responses. These solutions show potential to reduce tumour burden, while generating immunological memory. Building on this rationale, we provide a comprehensive overview on emerging cancer glycovaccines, emphasizing the potential of nanotechnology in this context. A roadmap towards clinical implementation is also delivered foreseeing advances in glycan-based immunomodulatory cancer medicine.
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•Glycans can be explored in anti-cancer vaccines and/or to target APCs.•Glycans conjugation to immunogens is required for effective immune responses.•Glycovaccine co-administration with immune adjuvants is required for anti-cancer efficacy.•Glycoengineering set foregrounds for glycovaccines but clinical translation is still needed.•A roadmap towards glycovaccines' clinical implementation is provided.
Abstract Cisplatin-based chemotherapeutic regimens are the most frequently used (neo)adjuvant treatments for the majority of solid tumors. While platinum-based chemotherapeutic regimens have proven ...effective against highly proliferative malignant tumors, significant relapse and progression rates as well as decreased overall survival are still observed. Currently, it is known that sub-populations of chemoresistant cells share biological properties with cancer stem cells (CSC), which are believed to be responsible for tumor relapse, invasion and ultimately disease dissemination through acquisition of mesenchymal cell traits. In spite of concentrated efforts devoted to decipher the mechanisms underlying CSC chemoresistance and to design targeted therapeutics to these cells, proteomics has failed to unveil molecular signatures capable of distinguishing between malignant and non-malignant stem cells. This has hampered substantial developments in this complex field. Envisaging a novel rationale for an effective therapy, the current review summarizes the main cellular and molecular mechanisms underlying cisplatin resistance and the impact of chemotherapy challenge in CSC selection and clinical outcome. It further emphasizes the growing amount of data supporting a role for protein glycosylation in drug resistance. The dynamic and context-dependent nature of protein glycosylation is also comprehensively discussed, hence highlighting its potentially important role as a biomarker of CSC. As the paradigm of cancer therapeutics shifts towards precision medicine and patient-tailored therapeutics, we bring into focus the need to introduce glycomics and glycoproteomics in holistic pan-omics models, in order to integrate diverse, multimodal and clinically relevant information towards more effective cancer therapeutics.
Bladder cancer is the most common malignancy of the urinary tract, presents the highest recurrence rate among solid tumors and is the second leading cause of death in genitourinary cancers. Despite ...recent advances in understanding of pathophysiology of the disease, the management of bladder cancer patients remains a clinically challenging problem. Particularly, bladder tumors invading the muscularis propria and disseminated disease are often not responsive to currently available therapeutic approaches, which include surgery and conventional chemotherapy. Antibody-based therapeutic strategies have become an established treatment option for over a decade in several types of cancer. However, bladder cancer has remained mostly an “orphan disease” regarding the introduction of these novel therapeutics, which has been translated in few improvements in patients overall survival. In order to shift this paradigm, several clinical studies involving antibody-based therapeutic strategies targeting the most prominent bladder cancer-related biomolecular pathways and immunological mediators are ongoing. This systematic review explores antibody-based therapeutics for bladder cancer undergoing clinical trial and discusses the future perspectives in this field, envisaging the development of more effective guided therapeutics.
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