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  • 1
    Online Resource
    Online Resource
    Low-Energy X-Ray Intraoperative Radiation Therapy (Lex-IORT) for Resected Brain Metastases: A Single-Institution Experience
    MDPI AG ; 2022
    In:  Cancers Vol. 15, No. 1 ( 2022-12-20), p. 14-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 1 ( 2022-12-20), p. 14-
    Abstract: Background: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. Method: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16–30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan–Meyer analysis were applied. Results: The mean follow-up time was 10.8 months (range, 0–39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3–100%), 71.4% (95%-CI 50.2–92.6%) and 58.0% (95%-CI 34.1–81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. Conclusion: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15010014
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Image Analysis Reveals Microstructural and Volumetric Differences in Glioblastoma Patients with and without Preoperative Seizures
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 4 ( 2020-04-17), p. 994-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 4 ( 2020-04-17), p. 994-
    Abstract: Purpose: Seizures related to tumor growth are common in glioma patients, especially in low-grade glioma patients this is often the first tumor manifestation. We hypothesize that there are associations between preoperative seizures and morphologic features (e.g., tumor size, location) and histogram features in patients with glioblastoma (GB). Methods: Retrospectively, 160 consecutive patients with initial diagnosis and surgery of GB (WHO IV) and preoperative MRI were analyzed. Preoperative MRI sequences were co-registered (T2-FLAIR, T1-contrast, DTI) and tumors were segmented by a neuroradiologist using the software ITK-snap blinded to the clinical data. Tumor volume (FLAIR, T1-contrast) and histogram analyses of ADC- and FA-maps were recorded in the contrast enhancing tumor part (CET) and the non-enhancing peritumoral edema (FLAIR). Location was determined after co-registration of the data with an atlas. Permutation-based multiple-testing adjusted t statistics were calculated to compare imaging variables between patients with and without seizures. Results: Patients with seizures showed significantly smaller tumors (CET, adj. p = 0.029) than patients without preoperative seizures. Less seizures were observed in patients with tumor location in the right cingulate gyrus (adj. p = 0.048) and in the right caudate nucleus (adj. p = 0.009). Significant differences of histogram analyses of FA in the contrast enhancing tumor part were observed between patients with and without seizures considering also tumor location and size. Conclusion: Preoperative seizures in GB patients are associated with lower preoperative tumor volume. The different histogram analyses suggest that there might be microstructural differences in the contrast enhancing tumor part of patients with seizures measured by fractional anisotropy. Higher variance of GB presenting without seizures might indicate a more aggressive growth of these tumors.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12040994
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 3
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    Online Resource
    Effects of a Change from an Indoor-Based Total Mixed Ration to a Rotational Pasture System Combined With a Moderate Concentrate Feed Supply on Rumen Fermentation of Dairy Cows
    MDPI AG ; 2018
    In:  Animals Vol. 8, No. 11 ( 2018-11-10), p. 205-
    Details
    In: Animals, MDPI AG, Vol. 8, No. 11 ( 2018-11-10), p. 205-
    Abstract: In spring, transition from a total mixed ration (TMR) to pasture requires rumen adaptions for the cow. It had been shown that transition period does not necessarily mean an increased risk for subacute ruminal acidosis (SARA). After adaption to pasture, however, supplying low amounts of concentrate did indicate increased risk, but caused no adverse effects on rumen morphology and absorption capacity. The present study aimed to investigate the effect of transition, and how a supply of 4.5 kg dry matter concentrate·cow−1 · day−1 during fulltime grazing influenced different rumen parameters. During a 12-week trial eleven rumen-cannulated dairy cows were observed during transition from confinement to pasture (PG; n = 6) and compared to cows fed TMR indoors (CG; n = 5). The CG stayed on a TMR based ration (35% corn silage, 35% grass silage, 30% concentrate; dry matter basis), whereas the PG slowly switched to a pasture-based ration (week 0 and 1 = TMR, week 2 = TMR and 3 h pasture·day−1, week 3 and 4 = TMR and 12 h pasture·day−1, and week 5 to 11 = pasture combined with 4.5 kg DM concentrate · cow−1·day−1). Papillae surface area decreased during transition and increased again during fulltime grazing, while the fractional absorption rate of volatile fatty acids (VFA) was not influenced. This suggests only a limited effect of papillae surface area on VFA absorption rate. Feeding changes resulted in different fermentation profiles of VFA. Changing ratio of starch to sugar during transition to fulltime grazing plus concentrate supply did not lead to lower rumen pH. In conclusion, the concentrate supply combined with high fermentable grass during fulltime grazing increased papillae surface area but did not affect absorption rate or rumen pH, so that risk for SARA was not increased.
    Type of Medium: Online Resource
    ISSN: 2076-2615
    URL: Article
    DOI: 10.3390/ani8110205
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2606558-7
    SSG: 23
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  • 4
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    Online Resource
    Effects of a Change from an Indoor-Based Total Mixed Ration to a Rotational Pasture System Combined with a Moderate Concentrate Feed Supply on Immunological Cell and Blood Parameters of Dairy Cows
    MDPI AG ; 2019
    In:  Veterinary Sciences Vol. 6, No. 2 ( 2019-05-24), p. 47-
    Details
    In: Veterinary Sciences, MDPI AG, Vol. 6, No. 2 ( 2019-05-24), p. 47-
    Abstract: In spring, transition from a total mixed ration (TMR) to a full grazing ration with moderate concentrate supply influences cow’s metabolism. It has been shown that feeding moderate amounts of concentrate during fulltime grazing did not prevent energy shortage and lipomobilization, alterations in energy metabolism, decreasing milk production and loss in body weight. As diet change and energy balance are closely related to immune reactivity, in this trial the effect of transition to pasture on specific immune parameters of cows was documented. Over a 12-week trial 43 dairy cows were observed during transition from confinement to pasture (PG; n = 22) and compared to cows fed TMR indoor (CG; n = 21). The CG stayed on a TMR based ration (35% corn silage, 35% grass silage, 30% concentrate; dry matter (DM) basis), whereas the PG slowly switched to a pasture -based ration (week 0 and 1 = TMR, week 2 = TMR and 3 h pasture·day−1, week 3 and 4 = TMR and 12 h pasture·day−1, and week 5 to 11 = pasture combined with 4.5 kg DM concentrate·cow−1·day−1). Inflammatory markers like blood haptoglobin or tryptophan to kynurenine ratio did not indicate acute phase reaction. Proportions of CD4+ (T-helper cells) and CD8+ cells (cytotoxic T-cells) remained uninfluenced as well. White blood cell concentration and its subpopulation of granulocytes increased over time in the PG. Stimulation ability of peripheral blood mononuclear cells to mount an oxidative burst significantly increased during the trial, too. The endogenous antioxidant state as characterized by glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in blood of the PG did not change, whereas the vitamin E concentration reached the highest level at the end of the trial. The 25-CHO metabolites of vitamin D increased as soon as the PG had pasture access, whereas the other metabolite 25-ERG decreased. The results of this study indicate that transition to pasture affects immune related parameters. However, the consequences of the observed effects on health status of the pasture group need to be clarified in further studies with a defined concurrent immune challenge.
    Type of Medium: Online Resource
    ISSN: 2306-7381
    URL: Article
    DOI: 10.3390/vetsci6020047
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2768971-2
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  • 5
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    Setting Priorities to Inform Assessment of Care Homes’ Readiness to Participate in Healthcare Innovation: A Systematic Mapping Review and Consensus Process
    MDPI AG ; 2020
    In:  International Journal of Environmental Research and Public Health Vol. 17, No. 3 ( 2020-02-05), p. 987-
    Details
    In: International Journal of Environmental Research and Public Health, MDPI AG, Vol. 17, No. 3 ( 2020-02-05), p. 987-
    Abstract: Organisational context is known to impact on the successful implementation of healthcare initiatives in care homes. We undertook a systematic mapping review to examine whether researchers have considered organisational context when planning, conducting, and reporting the implementation of healthcare innovations in care homes. Review data were mapped against the Alberta Context Tool, which was designed to assess organizational context in care homes. The review included 56 papers. No studies involved a systematic assessment of organisational context prior to implementation, but many provided post hoc explanations of how organisational context affected the success or otherwise of the innovation. Factors identified to explain a lack of success included poor senior staff engagement, non-alignment with care home culture, limited staff capacity to engage, and low levels of participation from health professionals such as general practitioners (GPs). Thirty-five stakeholders participated in workshops to discuss findings and develop questions for assessing care home readiness to participate in innovations. Ten questions were developed to initiate conversations between innovators and care home staff to support research and implementation. This framework can help researchers initiate discussions about health-related innovation. This will begin to address the gap between implementation theory and practice.
    Type of Medium: Online Resource
    ISSN: 1660-4601
    URL: Article
    DOI: 10.3390/ijerph17030987
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2175195-X
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  • 6
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    Human Glioma Migration and Infiltration Properties as a Target for Personalized Radiation Medicine
    MDPI AG ; 2018
    In:  Cancers Vol. 10, No. 11 ( 2018-11-20), p. 456-
    Details
    In: Cancers, MDPI AG, Vol. 10, No. 11 ( 2018-11-20), p. 456-
    Abstract: Gliomas are primary brain tumors that present the majority of malignant adult brain tumors. Gliomas are subdivided into low- and high-grade tumors. Despite extensive research in recent years, the prognosis of malignant glioma patients remains poor. This is caused by naturally highly infiltrative capacities as well as high levels of radio- and chemoresistance. Additionally, it was shown that low linear energy transfer (LET) irradiation enhances migration and invasion of several glioma entities which might counteract today’s treatment concepts. However, this finding is discussed controversially. In the era of personalized medicine, this controversial data might be attributed to the patient-specific heterogeneity that ultimately could be used for treatment. Thus, current developments in glioma therapy should be seen in the context of intrinsic and radiation-enhanced migration and invasion. Due to the natural heterogeneity of glioma cells and different radiation responses, a personalized radiation treatment concept is suggested and alternative radiation concepts are discussed.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers10110456
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527080-1
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  • 7
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    Online Resource
    Design and Characterization of an “All-in-One” Lentiviral Vector System Combining Constitutive Anti-GD2 CAR Expression and Inducible Cytokines
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 2 ( 2020-02-06), p. 375-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 2 ( 2020-02-06), p. 375-
    Abstract: Genetically modified T cells expressing chimeric antigen receptors (CARs) so far have mostly failed in the treatment of solid tumors owing to a number of limitations, including an immunosuppressive tumor microenvironment and insufficient CAR T cell activation and persistence. Next-generation approaches using CAR T cells that secrete transgenic immunomodulatory cytokines upon CAR signaling, known as TRUCKs (“T cells redirected for universal cytokine-mediated killing”), are currently being explored. As TRUCKs were engineered by the transduction of T cells with two separate vectors, we developed a lentiviral modular “all-in-one” vector system that combines constitutive CAR expression and inducible nuclear factor of activated T cells (NFAT)-driven transgene expression for more efficient production of TRUCKs. Activation of the GD2-specific CAR via GD2+ target cells induced NFAT promoter-driven cytokine release in primary human T cells, and indicated a tight linkage of CAR-specific activation and transgene expression that was further improved by a modified NFATsyn promoter. As proof-of-concept, we showed that T cells containing the “all-in-one” vector system secrete the immunomodulatory cytokines interleukin (IL)12 or IL18 upon co-cultivation with primary human GD2+ tumor cells, resulting in enhanced effector cell properties and increased monocyte recruitment. This highlights the potential of our system to simplify application of TRUCK-modified T cells in solid tumor therapy.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12020375
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 8
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    Online Resource
    Surgical Outcome of Trigeminal Schwannomas
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 6 ( 2021-03-15), p. 1310-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 6 ( 2021-03-15), p. 1310-
    Abstract: (1) Background: As resection of trigeminal schwannomas is challenging, due to anatomical involvement of the anterior, middle and posterior fossa, the appropriate approach is important. We report our experience with surgical resection of trigeminal schwannomas by simple and classic skull-base approaches. (2) Methods: We performed a retrospective single-center study including patients who underwent surgery for trigeminal schwannoma tumors between June 2007 and May 2020, concentrating on surgical technique, extent of resection, postoperative outcome and complications. (3) Results: We included 13 patients (median age 57.5 with range of 36-83 years, 53.8% (7/13) female. The most common preoperative clinical presentations were facial pain in six (46.2%), hypoacusis in four (30.8%), trigeminal nerve hypesthesia in 11 (V1 46.2% (6/13), V2 (61.5% (8/13), V3 46.2% (6/13)) and headache in three (23.1%) patients. In three cases, the tumor was resected in a two-stage technique. The intradural subtemporal approach was performed in six cases, the extradural technique in two cases, the retrosigmoid approach in five cases, a Kawase approach in two cases and the transnasal endoscopic approach in one case. The gross total resection rate was 76.9% (10/13) and the median follow-up time 24.0 (0–136) months. Three (23.1%) patients developed postoperative anesthesia in at least one branch of the trigeminal nerve. Trigeminal motor function was preserved in 11 (84.6%) patients. Ten of the 11 patients (76.9%) who reported decreased gustation, cerebellar ataxia, visual impairment, or headache improved postoperatively. Two (15.4%) patients exhibited minimal facial palsy (House and Brackmann II–III), which resolved during the follow-up. The total adverse event rate requiring surgical intervention during follow-up was 7.7%. Surgery-related mortality was 0%. (4) Conclusions: Trigeminal schwannomas are rare benign lesions with intra- and extracranial extension. Considering the low operative morbidity and satisfying functional outcome, gross total resection of trigeminal schwannomas is achievable by classic, but also individually tailored approaches. More invasive or combined techniques were not needed with meticulous surgical planning.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13061310
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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  • 9
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    Online Resource
    Midline Meningiomas of the Anterior Skull Base: Surgical Outcomes and a Decision-Making Algorithm for Classic Skull Base Approaches
    MDPI AG ; 2020
    In:  Cancers Vol. 12, No. 11 ( 2020-11-03), p. 3243-
    Details
    In: Cancers, MDPI AG, Vol. 12, No. 11 ( 2020-11-03), p. 3243-
    Abstract: (1) Background: Midline meningiomas such as olfactory groove (OGMs), planum sphenoidale (PSMs), or tuberculum sellae meningiomas (TSMs) are challenging, and determining the appropriate approach is important. We propose a decision algorithm for choosing suitable transcranial approaches. (2) Methods: A retrospective chart review between 06/2007 and 01/2020. Clinical outcomes, radiographic findings, and postoperative complication rates were analyzed with respect to operative approaches. (3) Results: We included 88 patients in the analysis. Of these, 18.2% (16/88) underwent an interhemispheric approach, 72.7% (64/88) underwent a pterional/frontolateral/supraorbital approach, 2.3% (2/88) underwent a unilateral subfrontal approach, and 6.8% (6/88) underwent a bifrontal approach. All OGMs underwent median approaches, along with one PSM. All of the other PSMs and TSMs were resected via lateral approaches. The preoperative tumor volume was ∅20.2 ± 27.1 cm3. Median approaches had significantly higher tumor volume but also higher rates of Simpson I resection (75.0% vs. 34.4%). An improvement of visual deficits was observed in 34.1% (30/88). The adverse event rate was 17.0%. Median follow-up was 15.5 months (range 0–112 months). (4) Conclusions: Median approaches provides satisfying results for OGMs, lateral approaches enable sufficient exposure of the visual apparatus for PSMs and TSMs. In proposing a simple decision-making algorithm, the authors found that satisfactory outcomes can be achieved for midline meningiomas.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers12113243
    Language: English
    Publisher: MDPI AG
    Publication Date: 2020
    detail.hit.zdb_id: 2527080-1
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  • 10
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    NOTCH Activation via gp130/STAT3 Signaling Confers Resistance to Chemoradiotherapy
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 3 ( 2021-01-26), p. 455-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 3 ( 2021-01-26), p. 455-
    Abstract: Resistance of tumor cells to chemoradiotherapy represents a fundamental problem in clinical oncology. The underlying mechanisms are actively debated. Here we show that blocking inflammatory cytokine receptor signaling via STAT3 re-sensitized treatment-refractory cancer cells and abolished tumor growth in a xenograft mouse model when applied together with chemoradiotherapy. STAT3 executed treatment resistance by triggering the expression of RBPJ, the key transcriptional regulator of the NOTCH pathway. The mandatory RBPJ interaction partner, NOTCH intracellular domain, was provided by tumor cell-intrinsic expression of NOTCH ligands that caused tonic NOTCH proteolysis. In fact, NOTCH inhibition phenocopied the effect of blocking STAT3 signaling. Moreover, genetic profiling of rectal cancer patients revealed the importance of the STAT3/NOTCH axis as NOTCH expression correlated with clinical outcome. Our data uncovered an unprecedented signal alliance between inflammation and cellular development that orchestrated resistance to chemoradiotherapy. Clinically, our findings allow for biomarker-driven patient stratification and offer novel treatment options.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13030455
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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