Außergewöhnliche Manifestation eines Magenkarzinoms mit Meningeosis carcinomatosa und spinaler Metastase

Zusammenfassung: Hintergrund:: Eine Meningeosis carcinomatosa ist eine seltene Komplikation solider Tumoren, wie Mamma-, Bronchial- oder gastrointestinale Karzinome. Klinisch manifestiert sie sich mit einer äußerst variablen Symptomatik wie z. B. radikulären Schmerzen mit oder ohne neurologische Ausfälle sowie Kopfschmerzen bis hin zu halluzinatorischen Reizsymptomen. Fallbeschreibung:: Berichtet wird über den seltenen Fall eines 57-jährigen Patienten mit neurologischen Reiz- und Ausfallsymptomen, hervorgerufen durch eine Meningeosis carcinomatosa und eine spinale Metastase bei einem asymptomatischen Siegelringzellkarzinom des Magens. Trotz kombinierter Radiochemotherapie verstarb der Patient bereits 4 Wochen nach Entlassung aus dem Spital an einer Hirnblutung. Schlussfolgerung:: Die Prognose der Meningeosis carcinomatosa ist bis heute unabhängig vom Primärtumor mit einer mittleren Überlebenszeit von 3-4 Monaten sehr schlech

Aussergewöhnliche Manifestation eines Magenkarzinoms mit Meningeosis carcinomatosa und spinaler Metastase

BACKGROUND: Leptomeningeal carcinomatosis is a rare complication of solid tumors, e. g., breast, lung and gastrointestinal carcinomas. Clinical manifestations are variable with radicular pains with or without neurologic deficiencies as well as headache and hallucinations. CASE REPORT: The rare case of a 57-year-old patient with neurologic symptoms caused by a leptomeningeal carcinomatosis and a spinal metastasis of an asymptomatic signet-ring cell gastric carcinoma is reported. In spite of combined radiochemotherapy the patient died already 4 weeks after discharge from hospital due to an intracerebral hemorrhage. CONCLUSION: Until today, prognosis of leptomeningeal carcinomatosis is poor with a median survival between 3-4 months independently of the primary tumor

Tumor cell specific expression of MMP-2 correlates with tumor vascularisation in breast cancer.

The metastatic potential of tumors is dependent on the ability of tumor cells to degrade extracellular matrix components by the expression of matrix metalloproteinases (MMPs) and to induce vascularisation of the tumor tissue. Thus, expression of MMPs and the number of blood vessel in tumor tissue may serve as prognostic markers of aggressive and metastasizing tumor growth. We have determined the vascularisation and the expression of MMP-2 by immuno-histochemical staining of 19 benign and 75 malignant breast tissue specimens with CD31- and MMP-2 specific antisera. The degree of vascularisation was expressed by intratumoral microvascular density (IMD), which takes into account all vessels present in a hot spot irrespective of their size. In addition, we have introduced a novel parameter, vascular grading (VG), which describes the percentage of small microvessels of <20 microm in diameter in the total number of blood vessels. IMD tended to indicate an elevated risk for metastasis formation and disease recurrence, while VG did not correlate with metastasis formation. Similarly, MMP-2 expression neither correlated with the clinical outcome of the disease nor with the classical histo-pathological parameters such as stage, grade, lymph node involvement and estrogen receptor status. Tumor cell-specific MMP-2 expression, however, showed a highly significant correlation with VG but not with IMD. These results indicate that MMP-2 expression is rather involved in the formation of small capillaries than in vessel maturation and tumor cell invasion. Thus, MMP-2 expression by tumor cells may serve as indicator of strong angiogenic induction potential of breast tumor cells

PIEZO1 expression at the glio-vascular unit adjusts to neuroinflammation in seizure conditions

Mechanosensors are emerging players responding to hemodynamic and physical inputs. Their significance in the central nervous system remains relatively uncharted. Using human-derived brain specimens or cells and a pre-clinical model of mesio-temporal lobe epilepsy (MTLE), we examined how the mRNA levels of the mechanosensitive channel PIEZO1 adjust to disease-associated pro-inflammatory trajectories. In brain tissue micro-punches obtained from 18 drug-resistant MTLE patients, PIEZO1 expression positively correlated with that of the pro-inflammatory biomarkers TNFα, IL-1β, and NF-kB in the epileptogenic hippocampus compared to the adjacent amygdala and temporal cortex. Using an experimental mouse model of MTLE, we found hippocampal Piezo1 and cytokine expression levels increased post-status epilepticus (SE) and during epileptogenesis. Piezo1 expression positively correlated with Tnfα, Il1β, and Nf-kb expression in the hippocampal foci. Next, by combining RNAscope with immunofluorescence, we identified Piezo1 in glio-vascular cells. Post-SE and during epileptogenesis, ameboid IBA1 microglia, hypertrophic GFAP astrocytes, and damaged NG2DsRed pericytes exhibited time-dependent patterns of increased Piezo1 expression. Digital droplet PCR analysis confirmed the Piezo1 trajectory in isolated hippocampal microvessels in the ipsi and contralateral hippocampi. The examinations performed in this model showed Piezo1 expression returning towards basal levels after the epileptogenesis-associated peak inflammation. From these associations, we next asked whether pro-inflammatory players directly regulate PIEZO1 expression. We used human-derived brain cells and confirmed that endothelium, astrocytes, and pericytes expressed PIEZO1. Exposure to human recombinant TNFα or IL1β upregulated NF-kB in all cells. Furthermore, TNFα induced PIEZO1 expression in a dose and time-dependent manner, primarily in astrocytes. This exploratory study describes a spatiotemporal dialogue between PIEZO1 neuro-mechanobiology and neuro-inflammatory cell remodeling. The precise cellular and functional mechanisms regulating this interplay in disease conditions warrant further investigation