Publications by authors named "Hans Raskov"

Objective: This clinical trial investigated the safety and efficacy of single-cycle pembrolizumab in patients with localized deficient mismatch repair (dMMR) colon cancer.

Background: Neoadjuvant immunotherapy has induced remarkable rates of pathological complete response in patients with dMMR colon cancer. However, the optimal length and type of treatment are yet to be determined.

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In cancer, activation of platelets by tumor cells is critical to disease progression. Development of precise antiplatelet targeting may improve outcomes from anticancer therapy. Alongside a distinct shift in functionality such as pro-metastatic and pro-coagulant properties, platelet production is often accelerated significantly early in carcinogenesis and the cancer-associated thrombocytosis increases the risk of metastasis formation and thromboembolic events.

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Objective: To give surgeons a review of the current and future use of neoadjuvant immunotherapy in patients with localized colorectal cancer (CRC).

Background: Immunotherapy has revolutionized the standard of care in oncology and improved survival outcomes in several cancers. However, the applicability of immunotherapy is still an ongoing challenge.

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Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence hybridization (FISH) and dual-RNA sequencing.

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Background: Evidence suggests that the human gut microbiota modulates the treatment response of immune checkpoint inhibitors (ICI) in cancer. Thus, finding predictive biomarkers in the fecal gut microbiota of patients who are less likely to respond to ICI would be valuable. This systematic review aimed to investigate the association between fecal gut microbiota composition and ICI-treatment response in patients with cancer.

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Article Synopsis
  • The study focused on patients with non-metastasizing sigmoid or rectal cancer to determine if an endoscopic intratumoral influenza vaccine could promote immune response, particularly CD8+ T-cell infiltration, in proficient mismatch repair tumors.
  • Conducting a phase 1/2 trial with 10 patients, the results showed that the vaccine was safe and did not cause any adverse events, allowing all patients to proceed with planned surgeries.
  • Post-treatment analysis indicated a significant increase in CD8+ T-cells within the tumors and changes in gene expression, suggesting the vaccine effectively enhanced local immune activity against the tumors.
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As the core component of all organs, the extracellular matrix (ECM) is an interlocking macromolecular meshwork of proteins, glycoproteins, and proteoglycans that provides mechanical support to cells and tissues. In cancer, the ECM can be remodelled in response to environmental cues, and it controls a plethora of cellular functions, including metabolism, cell polarity, migration, and proliferation, to sustain and support oncogenesis. The biophysical and biochemical properties of the ECM, such as its structural arrangement and being a reservoir for bioactive molecules, control several intra- and intercellular signalling pathways and induce cytoskeletal changes that alter cell shapes, behaviour, and viability.

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Cell metabolism is characterised by the highly coordinated conversion of nutrients into energy and biomass. In solid cancers, hypoxia, nutrient deficiencies, and tumour vasculature are incompatible with accelerated anabolic growth and require a rewiring of cancer cell metabolism. Driver gene mutations direct malignant cells away from oxidation to maximise energy production and biosynthesis while tumour-secreted factors degrade peripheral tissues to fuel disease progression and initiate metastasis.

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The discovery of electroporation in 1968 has led to the development of electrochemotherapy (ECT) and irreversible electroporation (IRE). ECT and IRE have been established as treatments of cutaneous and subcutaneous tumors and locally advanced pancreatic cancer, respectively. Interestingly, the treatment modalities have been shown to elicit immunogenic cell death, which in turn can induce an immune response towards the tumor cells.

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Neutrophils are central mediators of innate and adaptive immunity and first responders to tissue damage. Although vital to our health, their activation, function, and resolution are critical to preventing chronic inflammation that may contribute to carcinogenesis. Cancers are associated with the expansion of the neutrophil compartment with an escalation in the number of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC) in the peripheral circulation and tumor microenvironment.

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Surgical resection is the mainstay in intended curative treatment of colorectal cancer (CRC) and may be accompanied by adjuvant chemotherapy. However, 40% of the patients experience recurrence within five years of treatment, highlighting the importance of improved, personalized treatment options. Monolayer cell cultures and murine models, which are generally used to study the biology of CRC, are associated with certain drawbacks; hence, the use of organoids has been emerging.

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Current evidence suggests that bacteria contribute to the development of certain cancers, such as colorectal cancer (CRC), partly by stimulating chronic inflammation. However, little is known about the bacterial impact on molecular pathways in CRC. Recent studies have demonstrated how specific bacteria can influence the major CRC-related pathways, i.

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The detection and killing of neoplastic cells require coordination of a variety of antitumor effector cells. Natural killer (NK) cells of the innate immune system are at the forefront of the body's defense systems and evidence suggests that the infiltration and cytotoxicity of NK cells in the cancer tissue influence treatment efficacy and survival. As powerful effectors in the anticancer immune response, NK cells rapidly recognize and kill transformed cells with little reactivity against healthy self-tissues, which highlights their potential role in cancer immunotherapy.

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Our understanding of the tumor microenvironment (TME), including the interplay between tumor cells, stromal cells, immune cells, and extracellular matrix components, is mandatory for the innovation of new therapeutic approaches in cancer. The cell-cell communication within the TME plays a pivotal role in the evolution and progression of cancer. Cancer-associated fibroblasts (CAF) and tumor-associated macrophages (TAM) are major cell populations in the stroma of all solid tumors and often exert protumorigenic functions; however, the origin and precise functions of CAF and TAM are still incompletely understood.

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The functions of, and interactions between, the innate and adaptive immune systems are vital for anticancer immunity. Cytotoxic T cells expressing cell-surface CD8 are the most powerful effectors in the anticancer immune response and form the backbone of current successful cancer immunotherapies. Immune-checkpoint inhibitors are designed to target immune-inhibitory receptors that function to regulate the immune response, whereas adoptive cell-transfer therapies use CD8 T cells with genetically modified receptors-chimaeric antigen receptors-to specify and enhance CD8 T-cell functionality.

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Importance: Tumour-infiltrating lymphocytes (TILs) have previously been found to influence patient prognosis in other gastrointestinal cancers, for instance in colorectal cancer. An immunosuppressive phenotype often characterizes pancreatic cancer with a low degree of immune cell infiltration. Cytotoxic CD8 T cell infiltration in tumours is found to be the best predictive variable for response to immune checkpoint inhibitor therapy, emphasizing the importance of investigating TILs in pancreatic cancer, especially focussing on CD8 T cells.

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The aim of this study was to conduct a systematic review of the association between gut microbiota and prognosis after colorectal cancer surgery. The review was conducted according to the PRISMA guidelines. A systematic literature search was conducted in PubMed, Embase, and Scopus.

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The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and growth of residual cancer. Human and animal studies show that cancer surgery can increase survival, migration and proliferation of residual tumor cells.

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Objective: The majority of patients with colorectal cancer are diagnosed with locally advanced and/or disseminated disease, and treatment options include surgery in combination with cytotoxic chemotherapy regimens, biologics, and/or radiotherapy. Thus, colorectal cancer remains a heavy burden on society and health care systems.Mounting evidence show that driver gene mutations play only part of the role in carcinogenesis.

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In vivo- and in vitro research accumulate mounting evidence, that the interaction between the colorectal microbiota and the immune system plays an important role in the development and progression of colorectal cancer and for the treatment outcomes. In future, modulation of the microbiota and immune system will, by all accounts, become important targets for prevention and treatment of colorectal cancer. In this review, we summarise current knowledge on bacterial drivers, biofilm formation, colon cancer sidedness and oncological treatment of colorectal cancer including the use of checkpoint inhibitors.

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Background: Research in the field of relation between microbes and colorectal carcinogenesis has gained increasing interest in past years. Recently, link between microbial biofilm and carcinogenesis in colon was demonstrated by several authors indicating that biofilm not only is a key player in carcinogenesis, but also may contribute to the understanding of side-specific colon cancer-right sided colon cancer versus left sided. In this article, we briefly highlight the major findings of the research of biofilm and carcinogenesis and demonstrate our findings of colonic cancer tissue and colonic polyp examined for biofilm.

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Pre-clinical and clinical data produce mounting evidence that the microbiota is strongly associated with colorectal carcinogenesis. Dysbiosis may change the course of carcinogenesis as microbial actions seem to impact genetic and epigenetic alterations leading to dysplasia, clonal expansion and malignant transformation. Initiation and promotion of colorectal cancer may result from direct bacterial actions, bacterial metabolites and inflammatory pathways.

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Purpose: Evidence supports an association between certain colorectal adenoma characteristics and predisposition to cancer. The association between anatomical location of colorectal adenoma, age and advanced adenomas needs attention. The objective of this study was to evaluate the possible association between occurrence of sporadic advanced adenomas with location and age.

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Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role.

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Background & Aims: Chemopreventive strategies might be used to reduce the recurrence of colorectal adenomas and the incidence of colorectal cancer. We performed a randomized, double-blind, placebo-controlled trial to determine whether a combination of acetylsalicylic acid (aspirin), calcitriol, and calcium carbonate could prevent colorectal adenoma recurrence.

Methods: We included 1107 patients with 1 or more sporadic adenoma(s) removed from the colon or rectum at centers in Europe, Russia, or the United States, from 2004 through 2010.

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