Protocol for generating lung and liver metastasis in mice using models that bypass intravasation.

Forced metastasis models, those in which the step of intravasation is bypassed, can be used to investigate the mechanisms underlying metastasis and evaluate potential therapeutic targets. Here, we present a protocol for using three forced models of lung and liver metastasis to generate metastasis within 3-4 weeks in approximately 99% of injected mice. We describe steps for cancer cell preparation, mouse analgesia and anesthesia; injecting through intrasplenic, intraportal, and intravenous techniques; and daily evaluation of metastasis.

Efferocytosis fuels malignant pleural effusion through TIMP1.

Malignant pleural effusion (MPE) results from the capacity of several human cancers to metastasize to the pleural cavity. No effective treatments are currently available, reflecting our insufficient understanding of the basic mechanisms leading to MPE progression. Here, we found that efferocytosis through the receptor tyrosine kinases AXL and MERTK led to the production of interleukin-10 (IL-10) by four distinct pleural cavity macrophage (Mφ) subpopulations characterized by different metabolic states and cell chemotaxis properties.

Loss of p16 and high Ki67 labeling index is associated with poor outcome in esophageal carcinoma.

The p16 tumor suppressor is coded by (9p21) and plays an important role during carcinogenesis and tumor progression in numerous tumor entities. The aim of our study was to evaluate the prognostic role of p16 expression and CDKN2A deletion in esophageal cancer (EC). Therefore, we analyzed p16 and KI67 expression by immunohistochemistry and 9p21 deletion by fluorescence hybridization on a tissue microarray including 398 adenocarcinomas (AC) and 293 squamous cell carcinomas (SCC) with clinical follow up-data.

Prevalence of CD8 cytotoxic lymphocytes in human neoplasms.

Purpose: Immune checkpoint inhibitors have recently been approved by the US FDA as first and/or second line therapy in a subset of cancer types. Recent evidence suggests that the quantity of tumor infiltrating lymphocytes (TILs) influences the likelihood of response to immune checkpoint inhibitors. Here, we set out to assess the density of CD8 lymphocytes in a wide range of different cancer types and subtypes.

Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients.

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry.

High RSF1 protein expression is an independent prognostic feature in prostate cancer.

Remodelling and spacing factor 1 (RSF1) is involved in the regulation of chromatin remodelling and represents a potential therapeutic target. High RSF1 expression has been linked to adverse tumour features in many cancer types, but its role in prostate cancer is uncertain. In this study, RSF1 expression was analysed by immunohistochemistry on a tissue microarray with 17,747 prostate cancers.

Upregulation of SPDEF is associated with poor prognosis in prostate cancer.

SAM pointed domain-containing Ets transcription factor (SPDEF), a member of the ETS transcription factor family, has been associated with prostate cancer development; however, its role in tumour development and progression is controversial. In the present study, SPDEF expression was analysed on a tissue microarray with >12,000 prostate cancer samples. SPDEF expression levels were higher in most prostate cancer samples than in normal prostate epithelium, suggesting SPDEF was upregulated in cancer.

Molecular and functional heterogeneity of IL-10-producing CD4 T cells.

IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4 T cells are phenotypically and functionally heterogeneous.

Improved Risk Stratification by Circulating Tumor Cell Counts in Pancreatic Cancer.

Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3% to 5%. Here, we investigated whether circulating tumor cells (CTC) may predict metastatic spread and survival in pancreatic cancer patients. In a prospective study, we enrolled 69 pancreatic cancer patients.

Her2 expression and gene amplification is rarely detectable in patients with oral squamous cell carcinomas.

Purpose: Her2 (ErbB2) transforms cells when overexpressed and is an important therapeutic target in breast cancer. Contrary to breast cancer, studies on Her2 overexpression and gene amplification in squamous cell carcinomas of the head and neck region described largely different results. This study was undertaken to learn more on the prevalence and clinical significance of HER2 amplification and overexpression in squamous cell carcinomas of the head and neck.

Haeme oxygenase-1 promoter polymorphism is an independent prognostic marker of gastrointestinal stromal tumour.

Aims: Gastrointestinal stromal tumours (GISTs) display genetic alterations on chromosome 22. GTn repeat (GTn) length polymorphism in the promoter of haeme oxygenase-1 gene (HMOX-1) is located on chromosome 22 and associated with malignant growth. The aim was to investigate the role of HMOX-1 promoter polymorphism in GIST patients.

Focal progression in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: a three-center-based study of 38 patients.

Background: This study aimed to investigate the outcome of patients with advanced gastrointestinal stromal tumors (GISTs) exhibiting focal disease progression during imatinib therapy, treated by surgical resection and imatinib continuation.

Methods: A consecutive series of 38 patients with metastatic GISTs who underwent treatment with imatinib at our centers during a defined period of time was evaluated. Patients were evaluated for demographics including tumor-related features, initial response, disease recurrence, and salvage treatment modalities, and were classified as having either focal or generalized progression upon presentation prior to salvage therapy.