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Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen—a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection. [ABSTRACT FROM AUTHOR]

Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer. [ABSTRACT FROM AUTHOR]

Bladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application. [ABSTRACT FROM AUTHOR]

The authors present a case involving a 51-year-old male who was diagnosed with a 4-cm mass in the body of the pancreas, initially suspected to be a ductal adenocarcinoma due to an elevated Ca 19.9 during routine analysis. Subsequent imaging studies confirmed a resectable disease without suspicious lymph nodes or distant metastasis, leading to the proposal of surgery. The patient underwent a laparoscopic distal splenopancreatectomy, which was uneventful. The histopathological examination revealed a 3.7-cm pancreatic mixed neuroendocrine neoplasia (MiNEN) with a predominant high-grade ductal adenocarcinoma component and a concurrent high-grade neuroendocrine carcinoma, with negative margins. Two lymph node metastases were identified, each representing metastasis of one of the components. The tumor was classified as pT2N1M0. Currently, the patient is undergoing chemotherapy with FOLFIRINOX. This case prompts reflection on the optimal treatment strategy for pancreatic MiNEN and raises the question of how the preoperative diagnosis could influence the patient's outcome. [ABSTRACT FROM AUTHOR]

(1) Background: Gastric cancer patients are known to be at a high risk of malnutrition, sarcopenia, and cachexia, and the latter impairs the patient's nutritional status during their clinical course and also treatment response. A clearer identification of nutrition-related critical points during neoadjuvant treatment for gastric cancer is relevant to managing patient care and predicting clinical outcomes. The aim of this systematic review was to identify and describe nutrition-related critical domains associated with clinical outcomes. (2) Methods: We performed a systematic review (PROSPERO ID:CRD42021266760); (3) Results: This review included 14 studies compiled into three critical domains: patient-related, clinical-related (disease and treatment), and healthcare-related. Body composition changes during neoadjuvant chemotherapy (NAC) accounted for the early termination of chemotherapy and reduced overall survival. Sarcopenia was confirmed to have an independent prognostic value. The role of nutritional interventions during NAC has not been fully explored. (4) Conclusions: Understanding critical domain exposures affecting nutritional status will enable better clinical approaches to optimize care plans. It may also provide an opportunity for the mitigation of poor nutritional status and sarcopenia and their deleterious clinical consequences. [ABSTRACT FROM AUTHOR]

Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane proteoglycan, is highly expressed in intestinal subtype gastric tumors and that this signature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression. [ABSTRACT FROM AUTHOR]

Paraneoplastic conditions such as cancer cachexia are often exacerbated by chemotherapy, which affects the patient's quality of life as well as the response to therapy. The aim of this narrative review was to overview the body-composition-related changes and molecular effects of different chemotherapy agents used in cancer treatment on skeletal-muscle remodeling. A literature search was performed using the Web of Science, Scopus, and Science Direct databases and a total of 77 papers was retrieved. In general, the literature survey showed that the molecular changes induced by chemotherapy in skeletal muscle have been studied mainly in animal models and mostly in non-tumor-bearing rodents, whereas clinical studies have essentially assessed changes in body composition by computerized tomography. Data from preclinical studies showed that chemotherapy modulates several molecular pathways in skeletal muscle, including the ubiquitin–proteasome pathway, autophagy, IGF-1/PI3K/Akt/mTOR, IL-6/JAK/STAT, and NF-κB pathway; however, the newest chemotherapy agents are underexplored. In conclusion, chemotherapy exacerbates skeletal-muscle wasting in cancer patients; however, the incomplete characterization of the chemotherapy-related molecular effects on skeletal muscle makes the development of new preventive anti-wasting strategies difficult. Therefore, further investigation on molecular mechanisms and clinical studies are necessary. [ABSTRACT FROM AUTHOR]

Cancer cells often overexpress and/or express de novo glycoproteins modified with short-chain sialylated O-glycans, sialyl-Tn (STn), sialyl-3-T (S3T) and sialyl-6-T (S6T) antigens, that hold potential for carbohydrate-based vaccines. However, the generation of glycopeptide libraries composed by structurally defined standards remains a critical step for carbohydrate metrology and vaccine development. A simple and fast multi-enzymatic single-pot method was applied for generating a wide array of STn, S3T and S6T glycopeptides. A 20-mer tandem repeat peptide from the cancer-associated glycoprotein MUC16 was used as a scaffold towards this end. Different glycosyltransferases and nucleotide sugars were combined in a stepwise manner to generate the glycopeptide libraries. TiO2 enrichment was further used to isolate sialoglycopeptides, and the glycopeptide libraries were characterized by nanoLC-MS. Multiple glycopeptides were conjugated with protein immunogens, bovine serum albumin (BSA) and keyhole limpet hemocyanin (KLH), foreseeing multivalent glycoepitopes that may pave the way for immunotherapy. We have synthesized MUC16-Tn antigens containing up to 5 glycosites and mapped the main occupied glycosites. We have also successfully synthesized MUC16-STn, S3T and S6T glycopeptides and hybrid MUC16-Tn/STn, MUC16-Tn/S3T, MUC16-T/S6T and MUC16-Tn/T/S6T glycoproteoforms. As proof-of-concept, we have coupled MUC16-Tn/STn glycopeptides to immunogenic proteins. This sets the molecular background for the future development of multivalent glycan-based vaccines exploiting MUC16 glycoepitopes. [ABSTRACT FROM AUTHOR]

Helminthiases are extremely prevalent in the developing world. In addition, the chronic infection with some parasitic worms are classified as carcinogenic. Therefore, it is utmost importance to understand the parasite-host interactions, the mechanisms underlay carcinogenesis and how they could be counteracted. This knowledge may ultimately guide novel control strategies that include chemotherapy-based approaches targeting these pathogens and associated pathologies caused by their infections. Little is known on how some helminthiases are associated with cancer; however, it has been hypothesized that chemical carcinogenesis may be involved in the process. Here, we summarize the current knowledge on chemical carcinogenesis associated with helminthiases, along with available therapeutic options and potential therapeutic alternatives including chemotherapy and/or immunotherapy. Ideally, the treatment of the carcinogenic helminthiases should target both the parasite and associated pathologies. The success of any chemotherapeutic regimen often depends on the host immune response during the infection and nutritional status among other factors. The close association between chemotherapy and cell-mediated immunity suggests that a dual therapeutic approach would be advantageous. In addition, there is a pressing need for complementary drugs that antagonize the carcinogenesis process associated with the helminth infections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Eastern Africa was recently described as a high-incidence geographic area for esophageal cancer. Mozambique is included in this region. This study aimed to characterize this malignant disease at Maputo Central Hospital (MCH) to develop a global program for esophageal cancer management in Mozambique. Methods: MCH records from between 2012 and 2016 were used to assess the clinical, pathologic, and outcome profiles of esophageal tumors. A descriptive analysis of data collected was performed. Overall survival was evaluated using Kaplan-Meier curves. Results: In the study, 522 consecutive patient cases of esophageal cancer were recorded. The median patient age was 56.1 years (range, 27 to 97 years); 291 (55.7%) patients were women, and 230 (44.1%) were men. Regarding tumor site, 113 patients (21.6%) had a tumor in the lower third, 154 (29.5%) in the middle, and 50 (9.6%) in the upper third of the esophagus; in the remaining 196 (37.5%), tumor site was unknown. Squamous cell carcinoma comprised 94.4% of cases with documented histopathology (74.9% of the sample). Surgical treatment was possible in 32 patients (6.1%). Disease stage was documented only in these 32 surgical patients; 28.1%, 53.1%, and 18.8% had stage I, II, and III disease, respectively. The remaining patient cases seemed to involve clinically advanced tumors. The median follow-up time was of 1.6 months. The median survival time was of 3.5 months for all patients; for patients treated with curative intent, it was of 8.7 months. Conclusion: Esophageal carcinoma is a common malignant tumor at MCH and is diagnosed in the advanced stages resulting in poor prognosis. Therefore, implementation of an Esophageal Cancer Program in Mozambique is essential. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]