Several studies have emphasized the importance of immune composition of the melanoma microenvironment for clinical outcome. The contribution of IL4I1, a phenylalanine oxidase with immunoregulatory functions, has not been yet explored. Here we studied a primary cutaneous melanoma series from stage I-III patients to investigate the association between in situ IL4I1 expression and clinical parameters or tumor-infiltrating T-cell subsets.
View Article and Find Full Text PDFToll-like receptors (TLRs) belong to the group of pathogen recognition receptors known to play a crucial role in the innate immune system. In cancer, TLR expression is still debated controversially due to contradictory results reporting that both induction of apoptosis as well as tumor progression could depend on TLR signaling, whereby recent data rather indicate a pro-tumorigenic effect. The biological phenomenon of cell fusion has been associated with cancer progression due to findings revealing that fusion-derived hybrid cells could exhibit properties like an increased metastatogenic capacity and an increased drug resistance.
View Article and Find Full Text PDFInflamm Allergy Drug Targets
September 2016
Aneuploidy, metastasis formation, and drug resistance are major issues to overcome in most cancers. If there exists common underlying proceedings for the formation of these phenomena is still unknown. The searching and thereby better understanding of causal mechanisms could promote the generation of drugs targeting the ultimate cause of these cancer promoting events.
View Article and Find Full Text PDFInflamm Allergy Drug Targets
December 2012
Inflamm Allergy Drug Targets
February 2012
Inflamm Allergy Drug Targets
October 2011
At the symposium, approaches to individualized cancer medicine were considered, from basic sciences (genetics, epigenetics, biological tumor signatures) to clinical investigations, including strategies about how best to undertake the clinical development of targeted agents.
View Article and Find Full Text PDFInflamm Allergy Drug Targets
August 2011
The dendritic cell (DC) immunoreceptors (DCIR) and DC-immunoactivating receptors (DCAR) represent a subfamily of cell surface C-type lectin receptors (CLR), whose multifunctional capacities range from classical Ag uptake and immunoregulatory mechanisms to the involvement in DC ontogeny. On the basis of the generation of specific mAbs, we functionally characterized mouse DCAR1 (mDCAR1) as a member of the DCIR/DCAR family. Expression of mDCAR1 was strongly tissue dependent.
View Article and Find Full Text PDFTumor infiltrating neutrophil granulocytes do not only exhibit tumor eliminating functions but also promote tumor progression. We have recently shown that neutrophil granulocytes can serve as linking cells for the adhesion of MDA-MB-468 breast carcinoma cells to pulmonary endothelium. Neutrophil granulocytes but not MDA-MB-468 cells express beta(2)-integrins, the ligands of the intercellular adhesion molecule (ICAM)-1, whereas ICAM-1 is strongly expressed on MDA-MB-468 cells.
View Article and Find Full Text PDFLow productivity and the escalating costs of drug development have been well documented over the past years. A fraction of new pre-clinical compounds successfully pass experimental test batteries, and less than 10% of these compounds that enter clinical trials ultimately make it to the market. These challenges in the "critical path" of drug development will be discussed for drugs in the field of oncology, regarding the i) the impact of FDA and EMEA guidelines, and ii) microdosing studies/phase 0 trials before a drug enters phase I to III, to inform drug development, compressing drug development timelines and decision-making for continuation into clinical trials.
View Article and Find Full Text PDFOur previous studies have shown that norepinephrine induces the migratory activity of human PC-3 prostate, SW 480 colon and MDA-MB-468 breast carcinoma cells. In contrast to these results, we show here that human ES-2 ovarian carcinoma cells have a reduced migratory activity after norepinephrine treatment. This inhibitory effect is possibly mediated by a cAMP-dependent activation of the small GTPase Rap1 via Epac.
View Article and Find Full Text PDFHuman plasmacytoid dendritic cells (PDC) are believed to link innate and adaptive immunity by producing type I interferon (IFN-I) and triggering adaptive T cell-mediated immunity. However, it remains elusive to which degree both PDC functions are linked. Here we show that CMV antigen targeted to PDC using a CD303 (blood dendritic cell antigen 2, BDCA-2) mAb is rapidly endocytosed and traffics via early sorting endosomes to emerging MHC-enriched compartments.
View Article and Find Full Text PDFPurpose: After apparently successful excision of breast cancer, risk of local recurrence remains high mainly in the area surrounding the original tumor, indicating that wound healing processes may be implicated. The proportional reduction of this risk by radiotherapy does not depend on the extent of surgery, suggesting that radiotherapy, in addition to killing tumor cells, may influence the tumor microenvironment.
Experimental Design: We studied how normal and mammary carcinoma cell growth and motility are affected by surgical wound fluids (WF), collected over 24 h following breast-conserving surgery in 45 patients, 20 of whom had received additional TARGeted Intraoperative radioTherapy (TARGIT), immediately after the surgical excision.
The nervous system is a superordinate organ in the body that controls the function of virtually all other organs and tissues. In the past, the role of the nervous system in cancer development and progression has largely been ascribed to an immunosuppressive function, which saps the immune system's ability to respond to a tumor. However, it is now clear that direct interactions of tumor cells with nerve cells occur, too.
View Article and Find Full Text PDFA leading cause of death, cancer remains the bane of modern society and one of the most challenging research fields. Cancer is initially a localized disease that can be often treated well at a very early stage. However the vast majority of cancer deaths result from a pernicious progression of the disease, the development of distant metastases.
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