A novel liquid biopsy assay for detection of (HER2) amplification in circulating tumor cells (CTCs).

Purpose: Circulating tumor cell (CTC)-based (HER2) assay is a laboratory test developed by Epic Sciences using single-cell genomics to detect (HER2) amplification in CTCs found in the peripheral blood of metastatic breast cancer (MBC) patients.

Patients And Methods: Peripheral blood was collected in Streck tubes and centrifugation was used to remove plasma and red blood cells. The remaining nucleated cells were deposited on glass slides, immunofluorescent-stained with proprietary antibodies, scanned by a high-definition digital scanner, and analyzed by a proprietary algorithm.

Fructose stimulated de novo lipogenesis is promoted by inflammation.

Benign hepatosteatosis, affected by lipid uptake, de novo lipogenesis and fatty acid (FA) oxidation, progresses to non-alcoholic steatohepatitis (NASH) on stress and inflammation. A key macronutrient proposed to increase hepatosteatosis and NASH risk is fructose. Excessive intake of fructose causes intestinal-barrier deterioration and endotoxaemia.

Tumor-associated macrophages and response to 5-fluorouracil adjuvant therapy in stage III colorectal cancer.

Tumor-associated macrophages (TAMs) play a role in tumor development and progression. We hypothesized that abundance of TAMs might modify efficacy of 5-fluorouracil chemotherapy in colorectal cancer. We measured the density of CD68+ TAMs at the invasive front of primary tumor of colorectal carcinoma (PT-TAMs; n = 208), at available matched metastatic lymph node (LN-TAMs; n = 149), and in an independent set of primary colorectal cancers (PT-TAMs, n = 111).

Stress-Activated NRF2-MDM2 Cascade Controls Neoplastic Progression in Pancreas.

Despite expression of oncogenic KRAS, premalignant pancreatic intraepithelial neoplasia 1 (PanIN1) lesions rarely become fully malignant pancreatic ductal adenocarcinoma (PDAC). The molecular mechanisms through which established risk factors, such as chronic pancreatitis, acinar cell damage, and/or defective autophagy increase the likelihood of PDAC development are poorly understood. We show that accumulation of the autophagy substrate p62/SQSTM1 in stressed Kras acinar cells is associated with PDAC development and maintenance of malignancy in human cells and mice.

YAP-IL-6ST autoregulatory loop activated on APC loss controls colonic tumorigenesis.

Loss of tumor suppressor adenomatous polyposis coli (APC) activates β-catenin to initiate colorectal tumorigenesis. However, β-catenin () activating mutations rarely occur in human colorectal cancer (CRC). We found that APC loss also results in up-regulation of IL-6 signal transducer (IL-6ST/gp130), thereby activating Src family kinases (SFKs), YAP, and STAT3, which are simultaneously up-regulated in the majority of human CRC.

Mast cells are not associated with systemic insulin resistance.

Background: Infiltration of white adipose tissue (WAT) by inflammatory cells in obesity is considered to be a key event in the development of insulin resistance. Recently, mast cells (MCs) have been identified as new players in the pathogenesis of obesity. We aimed to investigate the relationship between MCs and various inflammatory markers in serum and WAT and to determine the role of MCs in the aetiology of insulin resistance.

Correction: Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer.

[This corrects the article DOI: 10.1371/journal.pone.

Occurrence and significance of tumor-associated neutrophils in patients with colorectal cancer.

Inflammatory cells are an essential component of the tumor microenvironment. Neutrophils have emerged as important players in the orchestration and effector phase of innate and adaptive immunity. The significance of tumor-associated neutrophils (TAN) in colorectal cancer (CRC) has been the subject of conflicting reports and the present study was designed to set up a reliable methodology to assess TAN infiltration in CRC and to evaluate their clinical significance.

Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer.

Background: Cytokines and chemokines in the tumor microenvironment drive metastatic development and their serum levels might mirror the ongoing inflammatory reaction at the tumor site. Novel highly sensitive tools are needed to identify colorectal cancer patients at high risk of recurrence that should be more closely monitored during post-surgical follow up. Here we study whether circulating inflammatory markers might be used to predict recurrence in CRC patients.

Dual prognostic significance of tumour-associated macrophages in human pancreatic adenocarcinoma treated or untreated with chemotherapy.

Objective: Tumour-associated macrophages (TAMs) play key roles in tumour progression. Recent evidence suggests that TAMs critically modulate the efficacy of anticancer therapies, raising the prospect of their targeting in human cancer.

Design: In a large retrospective cohort study involving 110 patients with pancreatic ductal adenocarcinoma (PDAC), we assessed the density of CD68-TAM immune reactive area (%IRA) at the tumour-stroma interface and addressed their prognostic relevance in relation to postsurgical adjuvant chemotherapy (CTX).

Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy.

Cancer-associated genetic alterations induce expression of tumour antigens that can activate CD8(+) cytotoxic T cells (CTLs), but the microenvironment of established tumours promotes immune tolerance through poorly understood mechanisms. Recently developed therapeutics that overcome tolerogenic mechanisms activate tumour-directed CTLs and are effective in some human cancers. Immune mechanisms also affect treatment outcome, and certain chemotherapeutic drugs stimulate cancer-specific immune responses by inducing immunogenic cell death and other effector mechanisms.

Tertiary lymphoid tissue in the tumor microenvironment: from its occurrence to immunotherapeutic implications.

Recruitment of immune and inflammatory cells in the microenvironment of solid tumors is highly heterogeneous and follows patterns, varying according to the organ of origin and stage of disease, with critical roles in the process of cancer onset and progression. While adaptive cells are endowed with anti-tumor activities, inflammatory components of the immune infiltrate orchestrate an immunosuppressive microenvironment that reveals ambivalent functions of the immune contexture in the tumor milieu. The balance between opposing pro-tumoral and anti-tumoral immune pathways, which occur concomitantly in the tumor microenvironment, and the regulatory networks of these phenomena have been the target of several immunotherapeutic strategies.

Inflammation and prostate cancer: friends or foe?

Introduction: Prostate cancer is the most common non-cutaneous malignancy diagnosed in men. Moving from histological observations since a long time, it has been recognized that innate and adaptive immunity actively participates in the pathogenesis, surveillance, and progression of prostate cancer.

Materials And Methods: A PubMed and Web of Science databases search was performed for studies providing evidence on the roles of the innate and adaptive immunity during the development and progression of prostate cancer.

Interleukin-17 receptor a signaling in transformed enterocytes promotes early colorectal tumorigenesis.

Interleukin-17A (IL-17A) is a pro-inflammatory cytokine linked to rapid malignant progression of colorectal cancer (CRC) and therapy resistance. IL-17A exerts its pro-tumorigenic activity through its type A receptor (IL-17RA). However, IL-17RA is expressed in many cell types, including hematopoietic, fibroblastoid, and epithelial cells, in the tumor microenvironment, and how IL-17RA engagement promotes colonic tumorigenesis is unknown.

Immune-based therapies in pancreatic and colorectal cancers and biomarkers of responsiveness.

Immune-based strategies are the most promising treatments to improve cancer disease control. Early clinical trials are ongoing to test the safety and feasibility of immune-based therapies for gastrointestinal cancers. However, to date, immunotherapy has been only an experimental option for these diseases and a better understanding of their molecular, cellular, structural and clinical dissimilarities is crucial in the generation of tailored immunotherapeutic treatments.

Tertiary lymphoid tissue: A gateway for T cells in the tumor microenvironment.

Tumor-infiltrating lymphocytes influence colorectal cancer progression. We have recently documented that tertiary lymphoid tissue in the colorectal cancer microenvironment orchestrates lymphocyte infiltration and that tertiary lymphoid tissue and lymphocytes cooperate in a coordinated antitumor immune response to improve patient outcome. Thus, tertiary lymphoid tissue represents a potential target in the design of tailored immune-based therapeutic approaches.

Immune mediators as potential diagnostic tools for colorectal cancer: from experimental rationale to early clinical evidence.

At the tumor site, solid tumors recruit native and adaptive infiltrating cell subtypes with a unique pattern, varying according to the organ of origin and the stage of the disease, which contributes to the complexity of the cancer microenvironment. The recruitment and activation of immune cells depend on a plethora of soluble immune mediators, including cytokines and chemokines that have a critical role in the process of cancer onset and progression. In colorectal cancer, measurement of soluble immune mediators in the serum seems to reflect the specific inflammatory reaction at the tumor site, and thus they might serve in clinical practice to improve available colorectal cancer detection and screening strategies.

Occurrence of tertiary lymphoid tissue is associated with T-cell infiltration and predicts better prognosis in early-stage colorectal cancers.

Purpose: Tumor-infiltrating T lymphocytes (TIL) play a key role in the clinical outcome of human colorectal cancer; however, the dynamics of their recruitment along colorectal cancer clinical progression have not been fully elucidated. Tertiary lymphoid tissue (TLT) is an ectopic organized lymph node-like structure that typically forms at sites of chronic inflammation and is involved in adaptive immune responses. Its occurrence in cancer is sporadically documented and its role and clinical relevance is largely unknown.

Immune cells: plastic players along colorectal cancer progression.

Inflammatory cells are involved in tumour initiation and progression. In parallel, the adaptive immune response plays a key role in fighting tumour growth and dissemination. The double-edged role of the immune system in solid tumours is well represented in colorectal cancer (CRC).

Presence of Twist1-positive neoplastic cells in the stroma of chromosome-unstable colorectal tumors.

Background & Aims: Cancer cells undergo an epithelial-to-mesenchymal transition (EMT) to become invasive, allowing tumors to progress. However, there is no direct evidence that human cancer cells undergo an EMT. In mouse cancer cells, up-regulation of transcription factor Twist1 was shown to promote an EMT.

Mast cells and the liver aging process.

It has now ascertained that the clinical manifestations of liver disease in the elderly population reflect both the cumulative effects of longevity on the liver and the generalized senescence of the organism ability to adjust to metabolic, infectious, and immunologic insults. Although liver tests are not significantly affected by age, the presentation of liver diseases such as viral hepatitis may be subtler in the elderly population than that of younger patients.Human immunosenescence is a situation in which the immune system, particularly T lymphocyte function, deteriorates with age, while innate immunity is negligibly affected and in some cases almost up-regulated.

Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma.

Background And Aims: Pancreatic cancer risk is increased in Lynch syndrome (LS) patients with mismatch repair gene defects predisposing to colonic and extracolonic cancers with microsatellite instability (MSI). However, the frequency of MSI pancreatic cancers has never been ascertained in consecutive, unselected clinical series, and their contribution to the sporadic and inherited burden of pancreatic cancer remains to be established. Aims of the study were to determine the prevalence of MSI in surgically resected pancreatic cancers in a multicentric, retrospective study, and to assess the occurrence of pancreatic cancer in LS.

MSH3 protein expression and nodal status in MLH1-deficient colorectal cancers.

Purpose: Patients with colorectal cancers (CRC) and high microsatellite instability (MSI) have a better outcome than their chromosome-unstable counterpart. Given the heterogeneity of microsatellite-unstable CRCs, we wanted to see whether any MSI-associated molecular features are specifically associated with prognosis.

Experimental Design: One hundred and nine MSI-high CRCs were typed for primary mismatch repair (MMR) defect and for secondary loss of MMR proteins.