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Several systematic reviews and meta-analyses have summarized the association between sedentary behavior (SB) and cancer. However, the level of evidence and the potential for risk of bias remains unclear. This umbrella review summarized the current data on SB in relation to cancer incidence and mortality, with a particular emphasis on assessing the risk of bias. We searched PubMed, Web of Science and Cochrane Database for systematic reviews and meta-analyses on the association between SB and cancer incidence and mortality. We also searched for recent observational studies not yet included in existing meta-analyses. We re-calculated summary risk estimates for cancer incidence and mortality using random effects models. We included 14 meta-analyses covering 17 different cancer sites from 77 original studies. We found that high SB levels increase the risk for developing ovarian, endometrial, colon, breast, prostate, and rectal cancers, with relative risks of 1.29 (95% confidence interval (CI) = 1.08–1.56), 1.29 (95% CI = 1.16–1.45), 1.25 (95% CI = 1.16–1.33), 1.08 (95% CI = 1.04–1.11), 1.08 (95% CI = 1.00–1.17), and 1.07 (95% CI = 1.01–1.12), respectively. Also, we found an increased risk of cancer mortality of 1.18 (95% CI = 1.09–1.26). Most associations between SB and specific cancer sites were supported by a “suggestive” level of evidence. High levels of SB are associated with increased risk of several types of cancer and increased cancer mortality risk.

Diffuse large B-cell lymphoma (DLBCL) is a disease with heterogeneous outcome. Stromal signatures have been correlated to survival in DLBCL. Their use, however, is hampered by the lack of assays for formalin-fixed paraffin-embedded material (FFPE). We constructed a lymphoma-associated macrophage interaction signature (LAMIS) interrogating features of the microenvironment using a NanoString assay applicable to FFPE. The clinical impact of the signature could be validated in a cohort of 466 patients enrolled in prospective clinical trials of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). Patients with high expression of the signature (LAMIShigh) had shorter EFS, PFS, and OS. Multivariate analyses revealed independence from IPI factors in EFS (HR 1.7, 95% CI 1.2–2.4, p-value = 0.001), PFS (HR 1.8, 95% CI 1.2–2.5, p-value = 0.001) and OS (HR 1.8, 95% CI 1.3–2.7, p-value = 0.001). Multivariate analyses adjusted for the IPI factors showed the signature to be independent from COO, MYC rearrangements and double expresser status (DE). LAMIShigh and simultaneous DE status characterized a patient subgroup with dismal prognosis and early relapse. Our data underline the importance of the microenvironment in prognosis. Combined analysis of stromal features, the IPI and DE may provide a new rationale for targeted therapy.

Brain metastases (BMs) are the most frequent malignancy of the central nervous system. Previous research suggested that some metastases show infiltrative behavior rather than sharp demarcation. We hypothesized that three magnetic resonance (MR) imaging parameters—(a) tumor size, (b) extent of peritumoral edema, and (c) presence of multiple BMs—are predictors of cellular invasion beyond the surgically identifiable tumor margins. We performed a post hoc analysis on prospectively collected data of patients with BMs. Biopsies beyond the resection margin and immunohistochemistry were performed to assess infiltration status. The three MR imaging parameters were dichotomized into diameters ≤ 30 mm (“small”) and > 30 mm (“large”), amount of peritumoral edema “extended” and “limited,” and “multiple BMs” and “single BMs,” respectively. The association between infiltration status and imaging parameters was calculated using chi-square test. Biopsy beyond the resection margin was performed in 77 patients; 49 (63.6%) had supramarginal infiltration and 28 patients (36.4%) showed no infiltration. Histological evidence of tumor infiltration was found in 25/41 patients with smaller lesions (61%) and in 24/36 with larger lesions (66.7%, p = 0.64), in 28/44 patients with limited (63.6%) and in 21/33 patients with extended edema (63.6%, p = 1.0), in 28/45 patients (62.2%) with single BM and in 21/32 patients (65.6%) with multiple BMs (p = 0.81). Based on the post hoc analysis of our prospective trial data, we could not confirm the hypothesis that infiltration of brain parenchyma beyond the glial pseudocapsule is associated with the MR imaging parameters tumor size, extent of edema, or multiplicity of metastases.

Gliome stellen in Bezug auf Diagnostik, Einteilung und Therapie eine Besonderheit im Vergleich zu anderen soliden Tumoren dar. Insbesondere die Vulnerabilitat des betroffenen Organs Gehirn erfordert eine sorgfaltige Planung von operativer, strahlentherapeutischer und medikamentoser Therapie sowie die sorgsame Begleitung und Therapieberatung der Betroffenen. Eine selektive Literaturrecherche wurde durchgefuhrt. Ohne integrierte Diagnose von histomorphologischen und molekularen Kriterien ist eine differenzierte Therapie nicht moglich. Aufgrund des meist diffus infiltrierenden Charakters kommt der medikamentosen Therapie ein entscheidender Stellenwert sowohl in der Erstbehandlung als auch beim Rezidiv oder Progress zu. Der rasante Zuwachs der Kenntnis von zugrunde liegenden molekularen und genetischen Veranderungen, die zur Tumorentstehung fuhren, lasst fur die Zukunft eine weitere Diversifizierung in verschiedene Entitaten erwarten, welche die Therapiemoglichkeiten erweitern kann. Dogmen, wie eine immunprivilegierte Stellung des ZNS und fehlende ZNS-Gangigkeit von Medikamenten aufgrund der Besonderheit der Bluthirnschranke rucken im Zusammenhang mit modernen Therapiemoglichkeiten wie „small molecules“, Antikorpern sowie immunonkologischen Therapieverfahren in den Hintergrund. Weitere sowohl klinische als auch praklinische Forschung ist dringend erforderlich, um die fur viele Gliome immer noch schlechte Prognose zu verbessern.

Sind metastasierte, refraktare Krebserkrankungen resistent gegenuber etablierten Tumortherapien, konnte eine biomodulatorische Therapie eine Chance auf anhaltende Remissionen bieten. Dieser palliative Ansatz basiert auf der „kommunikativen Reprogrammierung“ von Tumorsystemen, Anakoinosis genannt. Dabei werden Kommunikationswege der Tumorzellen mit ihrer Umgebung so verandert, dass die entarteten Zellen in den programmierten Zelltod gehen.

Activation of AMPK by the tumor suppressor LKB1 represents an essential gatekeeping step for cells under energetic stress to prevent their growth and proliferation by inhibiting mTOR activation, until the energy supply normalizes. The LKB1/AMPK pathway is frequently downregulated in various types of cancer, thereby uncoupling tumor cell growth and proliferation from energy supply. As yet, little information is available on the role of the LKB1/AMPK pathway in tumors derived from salivary gland tissues. We performed LKB1 protein expression and AMPK and mTOR activation analyses in several salivary gland tumor types and their respective healthy control tissues using immunohistochemistry. No significant downregulation of LKB1 expression or decreased activation of AMPK or mTOR were observed in any of the salivary gland tumors tested. In contrast, we found that the salivary gland tumors exhibited an increased rather than a decreased AMPK activation. Although the PI3K/Akt pathway was found to be activated in most of the analyzed tumor samples, the unchanged robust activity of LKB1/AMPK likely prevents (over)activation of mTOR. In contrast to many other types of cancer, inactivation or downregulation of the LKB1/AMPK pathway does not substantially contribute to the pathogenesis of salivary gland tumors.

Hirnmetastasen systemischer solider Tumoren sollten nur mit einem kompletten systemischen Staging, genauer Beschreibung der lokalen Situation im Hirnparenchym und nach Leitsymptom-orientierter Abklarung einer Meningeosis neoplastica diagnostiziert und behandelt werden. Therapeutisch stehen lokale oder systemische Masnahmen zur Verfugung. Dabei stellt neben einer Lebenszeitverlangerung auch die Symptomlinderung ein relevantes Therapieziel dar.

Liposomes are frequently used in cancer therapy to encapsulate and apply anticancer drugs. Here, we show that a systemic treatment of mice bearing skin tumors with empty phosphatidylcholine liposomes (PCL) resulted in inhibition of tumor growth, which was similar to that observed with the synthetic bacterial lipoprotein and TLR1/2 agonist Pam(3)CSK(4) (BLP). Both compounds led to a substantial decrease of macrophages in spleen and in the tumor-bearing skin. Furthermore, both treatments induced the expression of typical macrophage markers in the tumor-bearing tissue. As expected, BLP induced the expression of the M1 marker genes Cxcl10 and iNOS, whereas PCL, besides inducing iNOS, also increased the M2 marker genes Arg1 and Trem2. In vitro experiments demonstrated that neither PCL nor BLP influenced proliferation or survival of tumor cells, whereas both compounds inhibited proliferation and survival and increased the migratory capacity of bone marrow-derived macrophages (BMDM). However, in contrast to BLP, PCL did not activate cytokine secretion and induced a different BMDM phenotype. Together, the data suggest that similar to BLP, PCL induce an antitumor response by influencing the tumor microenvironment, in particular by functional alterations of macrophages, however, in a distinct manner from those induced by BLP.

Patientenversorgung, Forschung und Lehrtatigkeit im Rahmen der medizinischen Ausbildung stellen die drei Saulen universitarer Medizin dar. Uber die didaktische Ausbildung und Qualifikation der in lehrender Funktion tatigen Arztinnen und Arzte an deutschen medizinischen Hochschulen gibt es jedoch wenige, unzureichende Erhebungen. Im Januar 2009 wurden sowohl Arztinnen und Arzte als auch Studierende der Universitatsmedizin Gottingen in einer Online-Umfrage um Einschatzungen hinsichtlich der didaktischen Qualifikation der klinischen Dozenten gebeten. Zugleich wurde untersucht, ob seitens der in der Lehre tatigen Assistenten Interesse an einem hochschuldidaktischen Fortbildungsprogramm besteht. Wahrend der 12-tagigen Erhebungsperiode beteiligten sich 359 Studierende und 126 Lehrende an der Umfrage. Die in der Lehre tatigen Arztinnen und Arzte fuhlten sich insgesamt schlecht auf ihre didaktischen Aufgaben vorbereitet. Zugleich zeigten sie eine hohe Bereitschaft zur Teilnahme an einer hochschuldidaktischen Fortbildung. Die befragten Studierenden waren der Ansicht, dass Lehrende aller Unterrichtsformen von einer didaktischen Fortbildung profitieren wurden. Im Interesse einer besseren Ausbildung kunftiger Arztinnen und Arzte mussen seitens der Politik und der Verantwortlichen an den einzelnen Fakultaten unbedingt bessere Rahmenbedingungen fur die Implementierung hochschuldidaktischer Fortbildungen in der Medizin geschaffen werden, so wie sie auch in der Ausbildung von Lehrern an Schulen vorgeschrieben sind.