Metabolic Health Summit’s Post

📃Scientific paper: Trajectories of immune-related serum proteins and quality of life in patients with pancreatic and other periampullary cancer: the CHAMP study Abstract: BACKGROUND: There is still a profound lack of efficient therapeutic strategies against pancreatic and other periampullary adenocarcinoma. Surgery is seldom possible, leaving palliative chemotherapy the only option for most patients. Chemotherapy treatment is however often accompanied by serious side-effects, and the identification of biomarkers for early prediction of disease and treatment-associated symptoms could help alleviate patient suffering. This study investigated the dynamic interrelationship between immune-related serum proteins, routine biomarkers, and health-related quality of life (HRQoL) factors during chemotherapy treatment of patients enrolled in the prospective, observational study Chemotherapy, Host response And Molecular dynamics in Periampullary cancer (CHAMP). METHODS: Proximity extension assay was applied to analyse 92 immune-associated proteins in longitudinal serum samples from 75 patients, 18 treated with curative and 57 with palliative intent. HRQoL data were available from all patients at baseline (BL), from 41 patients at three months, and from 23 patients at six months. Information on routine laboratory parameters albumin, CA19-9, CEA and CRP were collected from medical charts. RESULTS: In total nine proteins; chemokine (C–C motif) ligand 23 (CCL23), cluster of differentiation 4 (CD4), cluster of differentiation 28 (CD28), decorin (DCN), galectin-1 (Gal-1), granzyme B (GZMB), granzyme H (GZMH), matrix metallopeptidase 7 (MMP7), and monocy... Continued on ES/IODE ➡️ https://etcse.fr/ZCk5f ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer. Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B(+) natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B(+) NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection. Source: Nat Med https://lnkd.in/eek8MtFP

🟨🟥 𝙈𝙖𝙘𝙧𝙤𝙥𝙝𝙖𝙜𝙚𝙨 𝙖𝙣𝙙 𝙗𝙤𝙣𝙚 𝙢𝙚𝙩𝙖𝙨𝙩𝙖𝙨𝙞𝙨 #MD_Immunol   Learn more online ⬇️ https://lnkd.in/dQYv43jZ 🟥 #Macrophages are involved in various aspects of the metastatic process, including: 1️⃣ Tumor-associated macrophages (TAMs) 2️⃣ Bone marrow-derived macrophages (BMDMs) 3️⃣ #Metastasis-associated macrophages (MAMs) 4️⃣ #Bone metastasis–associated macrophages (BoMAMs) 🟥 #Macrophages contribute to the development of bone metastasis by: 1️⃣ Promoting a pro-inflammatory environment in the metastatic niche 2️⃣ Releasing chemokines that recruit a distinctive tumor associated macrophages (TAMs) polarization towards the immunosuppressive and pro-tumorigenic M2 phenotype . 3️⃣ Interacting with cancer cells during the metastatic cascade to bone, impacting macrophages and their profiles. 🟥 Androgen dependency is a feature of prostate cancer (PC), and hormone deprivation is the mainstay therapy to treat advanced tumors. 🟥 In the prostate bone metastasis microenvironment, macrophages have been found to activate a cascade involving Activin A, the extracellular matrix, and SRC kinase, which drives resistance to anti-androgen therapy 🟥 Anti-androgen therapies, which include surgical intervention and administration of gonadotropin inhibitory factor and antagonists of the androgen receptor, show a robust clinical efficacy in the initial phases of the disease. 🟥 TAMs are an essential component of the TME and contribute to PC tumor progression by paracrine signaling 🟥 Indeed, TAMs transfer cholesterol to tumor cells, thus contributing to androgen synthesis. Accordingly, TAM depletion reduces androgen levels within prostate tumors, and combinatorial administration of TAM-depleting agents and androgen deprivation shows strong preclinical efficacy. 🟥 Bones are a major site of PC metastasis, TAM abundance in bone metastasis was associated with poor overall survival in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC ) that underwent anti-androgen therapies. 🟥 Investigation of primary tumors and metastatic sites revealed that TAM-derived Activin A induced an extracellular matrix (ECM)-related transcription program in cancer cells, resulting in resistance to enzalutamide therapy 👉 (Fig. 1). 🟥 Activin A induced Fibronectin 1 (FN1) that sustained the activation of an SRC-mediated signaling pathway in tumor cells, promoting cancer cell proliferation and finally it inhibited patient resistance to enzalutamide. 👉 (Fig.1) 🟥 Researchers have shown activation of the androgen receptor has been reported to impair T cell anti-cancer activity and to confer pro-tumoral functions to TAMs in preclinical 👉(Fig.2) 🟥 These components of metastasis responsiveness to hormonal and immunological therapies may pave the way to better therapeutic exploitation. #immunology #Bone #macrophages #metastasis #enzalutamide

Utilization and survival outcomes of neoadjuvant chemotherapy for early-stage gastric cancer Abstract Background and Objectives Given increased utilization of neoadjuvant therapy (NAT) for gastric adenocarcinoma, practice patterns deviating from standard of care (upfront resection) remain unknown. We sought to identify factors associated with NAT use and survival outcomes among early-stage gastric cancers. Methods The National Cancer Database identified patients with early-stage (T1N0M0) gastric cancer (2010−2020). Multivariable logistic regression assessed characteristics associated with NAT utilization compared to upfront surgery. After 1:1 propensity score matching, Kaplan−Meier methods and Cox regression assessed overall survival (OS). Results Of 6452 patients with early-stage gastric cancer, 626 (9.7%) received NAT. Patients who received NAT were more likely treated at community hospitals, had moderate to poorly differentiated disease, and tumors located in the cardia (all p < 0.05). After propensity score matching, 1,248 patients remained. Median OS for NAT was 37.1 months (IQR 20.2−64.0) versus 45.6 months (IQR 22.5−72.8) for resection (p < 0.001). Treatment with NAT remained independently predictive of worse OS on Cox regression (hazard ratio 1.19; 95% confidence interval 1.05−1.34). Conclusions Although patients who received NAT had more aggressive prognostic features, NAT was associated with worse OS despite accounting for this selection bias. These results highlight the importance of adhering to guidelines, regardless of differing disease characteristics, which has significant implications on outcomes.

📃Scientific paper: Study of extracorporeal photopheresis mechanisms of action;Etude des mécanismes d'action de la photochimiothérapie extracorporelle Abstract: Extracorporeal photopheresis (ECP) is an autologous immunotherapy based on the reinfusion of photochemical modified mononuclear cells. ECP efficacy is demonstrated in treatment of CTCL, in GvHD and in others T-cell mediated diseases (organ transplant rejection and auto-immune diseases). ECP does not generate generalized immunosuppression. Although it has been used for years, mechanisms of action of ECP are not totally understood. The objective of my thesis was to study these mechanisms of action and set up a murine model to allow an optimization of the clinical protocols. Two hypotheses have been tested to explain the effectiveness of ECP: “Tolerogenic” cell death where the effect would be related to the generation of regulatory T lymphocytes and "immunogenic" death where the effect could be explained by the generation of cytotoxic T lymphocytes.The use of human mononuclear cells obtained from healthy donors enabled us to generate activated alloreactive T cells and to show that the PUVA-treated T-cells emitted a part of the danger molecules (DAMPs), described as immunogenic, such as Calreticulin or HMGB1. These cells are phagocytosed by macrophages and moDCs but do not induce their maturation, which does not therefore generate any stimulation of the immune system.The use of a murine model of rheumatoid arthritis (CIA) allowed us to show the effectiveness of PCE in the treatment of this pathology. Moreover, our results show that the effectiveness of the treatment is b... Continued on ES/IODE ➡️ https://etcse.fr/0YOuX ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

Nasal tau immunotherapy clears intracellular tau pathology and improves cognitive functions in aged tauopathy mice Toxic tau conformation-specific monoclonal antibody 2 (TTCM2) specifically detects and targets disease-relevant tau aggregates. Loaded in micelles, aggregates of water-loving (hydrophilic) and fat-loving (lipophilic) molecules, which are administered intranasally, means that the treatment quickly reaches the brain through the anatomical pathway from the nose to the brain, avoiding by complete the BBB. A single dose of TTCM2 was administered intranasally to old mice that had been genetically modified to express human tau. After three hours, TTCM2 was distributed to several brain regions, including the intracellular compartments of the regions, where it removed "seed-competent" intracellular tau aggregates and tau in synaptic connections between brain neurons. When subjected to behavioral tests, mice treated with TTCM2 performed "markedly better" than other cohorts, suggesting that the treatment alleviated short-term memory loss in mice with advanced tau aggregates. A crucial factor for the therapy was the interaction of TTCM2 with RO52/TRIM21 (Tripartite Motif Containing 21), an intracellular antibody effector in the intracellular antibody-mediated proteolysis pathway (it recognizes Fc domain and binds to IgG, IgA and IgM), which facilitated the removal of antibody-bound tau aggregates. https://lnkd.in/dbyNkMzM PS: The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. TRIM21 is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus

📍 Urine test halves painful procedures in bladder cancer follow up, new trial shows The first time a urine biomarker test has been assessed in a randomised interventional controlled trial A simple urine test can more than halve the number of cystoscopies necessary to follow up high-risk bladder cancer patients, new research has found. Excerpt: Cystoscopies involve inserting a flexible probe through the urethra into the bladder, which allows a clinician to look at the bladder lining for signs of cancer. While they are predominantly safe procedures, cystoscopies do incur some risk of urinary infections and bleeding. They can also cause pain and discomfort. Initial results from a two-year study, presented 6 April 2024 at the European Association of Urology Congress in Paris, suggest that there is also no increased risk of recurrence in patients who had a urine biomarker test rather than a standard flexible cystoscopy. High-risk patients with the most aggressive form of bladder cancer have a 60–70% likelihood of cancer returning within five years post-surgery, which is why follow up for these patients is so intensive. The new research is the first time a urine biomarker test has been assessed in a randomized interventional controlled trial with high-risk patients. This trial design allowed the researchers to assess whether the test could reduce the number of cystoscopies patients had to undergo, as well as picking up any signs of returning cancer. Previous studies have only assessed biomarker tests observationally, adding the biomarker tests to existing standard of care. The researchers, from Aarhus University Hospital in Denmark, recruited 313 patients. Half were randomised to receive the standard three cystoscopies per year. The other half were randomised to receive just one cystoscopy per year, with their remaining two follow up cystoscopies replaced with the #Xpert® #Bladder #Cancer #Monitor test, a #urine #biomarker test. The test monitors for recurrence of bladder cancer by measuring levels of five target #mRNAs, or genetic markers. The researchers chose to trial this particular biomarker test as it had previously shown promising results in high-risk bladder cancer patients. The researchers also found strong evidence that the urine test could pick up cancer recurrence before any disease was visible through the cystoscopy. For more than half of the patients who had a ‘false positive’ test – that is, the biomarker test showed positive but the cystoscopy was clear – the researchers found evidence of recurrence at a later visit. Source : https://lnkd.in/ebenmPAF and https://lnkd.in/epyi3dDF Read ➡ https://lnkd.in/e5qjebmk #urinetest #bladdercancer #cystoscopy

Synergistic immunomodulatory effect of synbiotics pre- and postoperative resection of pancreatic ductal adenocarcinoma: a randomized controlled study https://lnkd.in/gsk2XyqF “`html Benefits of Synbiotics in Pancreatic Ductal Adenocarcinoma Treatment Synbiotics: A New Approach to Improve PDAC Treatment Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a low survival rate. The standard treatment involves surgery, chemotherapy, and radiation, but these treatments have limitations. Synbiotics, a combination of probiotics and prebiotics, have shown promise in improving PDAC treatment outcomes. Synergistic Immunomodulatory Effect of Synbiotics A recent study found that synbiotics can enhance the immune system, leading to a lower incidence of postoperative infections and a shorter hospital stay for PDAC patients. Synbiotics also increased the number of essential immune cells, potentially aiding in the fight against cancer cells. Modulating the Immune System Synbiotics can improve the balance of gut bacteria, leading to a more robust immune response. This is crucial in PDAC treatment, as the immune system plays a critical role in fighting cancer cells. Reducing Side Effects and Direct Anti-Cancer Effects Synbiotics may help alleviate the side effects of chemotherapy and radiation therapy by restoring the balance of gut bacteria. Additionally, certain probiotic strains have been shown to inhibit cancer cell growth, potentially enhancing the effects of traditional cancer treatments. Promising Results and Future Research The study’s findings provide hope for PDAC patients and highlight the potential benefits of incorporating synbiotics into standard treatment protocols. Further research is needed to fully understand the mechanisms of action and determine the optimal use of synbiotics in PDAC treatment. “` #ClinicalTrials #AIinHealthcare #MedicalAI #HealthTech #DigitalHealth #PatientCareAI #AIResearch #MedicalInnovation #BioTech #AIforGood #HealthcareData #AIinMedicine #PharmaAI #ClinicalData #HealthAI #AIHealthSolutions #PrecisionMedicine #AIandHealth #ClinicalAnalytics #AIDiagnostics

📃Scientific paper: Chronic prednisone, metformin, and nonsteroidal anti-inflammatory drug use and clinical outcome in a cohort of bladder cancer patients undergoing radical cystectomy in Québec, Canada Abstract: Background Studies have suggested a positive association between bladder cancer (BC) outcome and comedication use, including nonsteroidal anti-inflammatory drugs (NSAID), metformin, and prednisone use. To validate these associations, we evaluated whether these medications were associated with clinical outcome in a Canadian cohort of BC patients. Methods This is a retrospective cohort study on BC patients undergoing radical cystectomy (RC) in Québec province in 2000–2015, as registered in the provincial health administration databases. Medication use was considered chronic when prescribed for ≥ 1 year. Overall (OS), disease-specific (DSS) and recurrence-free (RFS) survival were compared using multivariable Cox proportional hazards models. Covariates included age, Charlson’s comorbidity index, region of residence, year of RC, distance to hospital, hospital type, hospital and surgeon annual RC volume, neoadjuvant chemotherapy use, and type of bladder diversion, as well as mutual adjustment for concomitant comedication use (statins, NSAIDs, metformin, and prednisone). Results Of 3742 patients included, 293, 420, and 1503 patients chronically used prednisone, metformin, and NSAIDs before surgery, respectively. In multivariable analyses, preoperative prednisone use was associated with improved OS (HR 0.67, 95%CI 0.55–0.82), DSS (HR 0.58, 95%CI 0.45–0.76), and RFS (HR 0.61, 95%CI 0.47–0.78). Patients who chronically used metformin preoperatively had a worse OS (HR 1.29, 95... Continued on ES/IODE ➡️ https://etcse.fr/lzIC3 ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.

📃Scientific paper: The impact of body weight on the development of peritoneal metastases in colorectal cancer patients: results from a nationwide cohort study Abstract: Background Obesity is a major global health problem and an important risk factor for colorectal cancer (CRC) is increased body weight. Obesity plays a role in the peritoneal dissemination of cancer; however, it is unclear whether this also applies for peritoneal dissemination of CRC. The purpose of this study was to provide insight in the role of obesity on the peritoneal dissemination of colorectal cancer. Methods Of all patients diagnosed with CRC in the Netherlands in the first half of 2015, follow-up data was completed in 2019. Weight at time of primary diagnosis was categorized as underweight, normal weight, overweight, or obese. Logistic regression modelling was used to assess the association between weight and the presence of synchronous colorectal peritoneal metastases (CPM), and Cox regression modelling was used to assess the association between weight and metachronous CPM. Patient and tumor characteristics were taken into account. The analyses were adjusted for tumor stage, nodal stage, tumor location, and tumor histology. Results In total, 6436 patients were included in this study. Two-hundred ninety-three (4.6%) patients presented with synchronous CPM at the time of primary diagnosis, while another 278 (5.1%) patients developed metachronous CPM after a median time of 16.5 months. Univariable and multivariable logistic regression modelling did not identify an effect of weight on the presence of synchronous CPM. Neither underweight (odds ratio [OR] 1.10... Continued on ES/IODE ➡️ https://etcse.fr/npam ------- If you find this interesting, feel free to follow, comment and share. We need your help to enhance our visibility, so that our platform continues to serve you.