Objectives Multiple studies show orthopedic health problems for medical staff due to wearing radiation protection aprons. The aim of this study was to evaluate the weight pressure on the shoulder as ...a marker of physical strain caused by different radiation-protection devices. Methods For the weight pressure measurement, a pressure sensor (OMD-30-SE-100N, OptoForce, Budapest, Hungary) placed on the left and right shoulder was used. Wearing different radiation protection systems the force measurement system was used to quantify the weight pressure. Measurements were acquired in still standing position and during various movements. Results A mean significant decreasing weight pressure on the shoulder between 74% and 84% (p<0.001) was measured, when the free-hanging radiation protection system was used in comparison to one-piece and two-piece radiation protection aprons and coats. Using two-piece radiation protection aprons, the weight pressure was significantly lower than that of one-piece radiation protection coats. If a belt was used for the one-piece radiation protection coat, the weight pressure on the shoulder was reduced by 32.5% (p = 0.003). For a two-piece radiation protection apron and a one-piece radiation protection coat (with and without belt) a significant different weight pressure distribution between the right and left shoulder could be measured. Conclusions The free-hanging radiation protection system showed a significant lower weight pressure in comparison to the other radiation protection devices. Apart from this, use of a two-piece radiation protection apron or addition of a belt to a radiation protection coat proved to be further effective options to reduce weight pressure.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The Arp2/3-activator Wiskott-Aldrich syndrome protein and Scar homologue (WASH) is suggested to regulate actin-dependent membrane scission during endosomal sorting, but its cellular roles have not ...been fully elucidated. To investigate WASH function, we generated tamoxifen-inducible WASH-knockout mouse embryonic fibroblasts (WASHout MEFs). Of interest, although EEA1(+) endosomes were enlarged, collapsed, and devoid of filamentous-actin and Arp2/3 in WASHout MEFs, we did not observe elongated membrane tubules emanating from these disorganized endomembranes. However, collapsed WASHout endosomes harbored segregated subdomains, containing either retromer cargo recognition complex-associated proteins or EEA1. In addition, we observed global collapse of LAMP1(+) lysosomes, with some lysosomal membrane domains associated with endosomes. Both epidermal growth factor receptor (EGFR) and transferrin receptor (TfnR) exhibited changes in steady-state cellular localization. EGFR was directed to the lysosomal compartment and exhibited reduced basal levels in WASHout MEFs. However, although TfnR was accumulated with collapsed endosomes, it recycled normally. Moreover, EGF stimulation led to efficient EGFR degradation within enlarged lysosomal structures. These results are consistent with the idea that discrete receptors differentially traffic via WASH-dependent and WASH-independent mechanisms and demonstrate that WASH-mediated F-actin is requisite for the integrity of both endosomal and lysosomal networks in mammalian cells.
Brain metastases in gastroesophageal cancers—an underestimated complication Brunner, Marius; Soll, Dominik; Adler, Kathrin ...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association,
01/2022, Letnik:
25, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Background
Brain metastases represent a severe complication in many gastrointestinal malignancies especially those arising from the upper gastrointestinal tract, including cancer of the esophagus, ...gastroesophageal junction, and stomach (GEC). However, there is little knowledge about the onset or potential risk factors for brain metastases (BRMs) in upper gastrointestinal cancers resulting in a lack of screening guidelines for BRMs.
Methods
We analyzed 827 patients from our cancer registry suffering from gastroesophageal cancer (GEC) and treated at the University Medical Center Göttingen between January 2013 and December 2019 for the presence of BRMs.
Results
From 827 patients with GEC we found 54 patients with BRMs, resulting in an incidence of 6.5%. BRMs are more frequent in male patients (90.74% vs 9.26%,
p
= 0.0051) and in adenocarcinomas (90.74% vs 9.26%,
p
= 0.0117). Mean duration for the onset of BRMs from initial cancer diagnoses was 20.9 months in limited disease (curative approach) and 9.3 months in advanced disease (palliative approach) (
p
= 0.0026). However, early detection of BRMs is a prognostic factor since patients with successful resection of BRMs have a better prognosis compared to those with unresectable BRMs (5.93 vs 2.07 months,
p
= 0.0091).
Conclusion
In this single-center retrospective study, brain metastases (BRMs) occur with a high frequency (6.5%) in gastroesophageal cancer (GEC), significantly more often in male patients and adenocarcinomas. Since survival of these patients considerably correlates with successful BRMs resection, our observations propose further prospective trails to validate our hypothesis and ultimately the implementation of routine screening procedures to detect asymptomatic brain metastases.
Pancreatic cancer is characterized by its invasiveness, early metastasis, and the production of large amounts of extracellular matrix (ECM). We analyzed the influence of type I collagen and ...fibronectin on the regulation of cellular adhesion in pancreatic cancer cell lines to characterize the role of ECM proteins in the development of pancreatic cancer. We show that collagen type I is able to initiate a disruption of the E-cadherin adhesion complex in pancreatic carcinoma cells. This is due to the increased tyrosine phosphorylation of the complex protein beta-catenin, which correlates with collagen type I-dependent activation of the focal adhesion kinase and its association with the E-cadherin complex. The activation and recruitment of focal adhesion kinase to the E-cadherin complex depends on the interaction of type I collagen with beta1-containing integrins and an integrin-mediated activation of the cellular kinase Src. The disassembly of the E-cadherin adhesion complex correlates with the nuclear translocation of beta-catenin, which leads to an increasing expression of the beta-catenin-Lef/Tcf target genes, cyclin D1 and c-myc. In addition to that, cells grown on collagen type I show enhanced cell proliferation. We show that components of the ECM, produced by the tumor, contribute to invasiveness and metastasis by reducing E-cadherin-mediated cell-cell adhesion and enhance proliferation in pancreatic tumor cells.
The side effects of systemic cancer therapy and the lack of clinical data on safety and efficacy of COVID-19 vaccination in cancer patients cause uncertainty among the patients about whether to get ...vaccinated or not. Here, we evaluated attitude towards and effects of COVID-19 vaccination in patients with breast and gynecological cancer undergoing systemic cancer therapy.
Since March 15th, 2021, cancer patients who received one of the approved COVID-19 vaccines were routinely interviewed about immediate and late side effects. Clinical parameters such as current therapy, time interval between therapy administration and vaccination, and changes in the therapy schedule due to vaccination were documented. The collected data were analyzed de-identified as a part of routine quality assurance.
By July 27th, 2021, 218 patients (74.3% breast cancer patients) had received one of two COVID-19 vaccine doses, and 112 patients had received both doses: 77.5% received Conmirnaty (BioNTech/Pfizer), 16.1% Vaxzevria (Astra Zeneca) and 5.9% COVID-19 Vaccine Moderna. The COVID-19 vaccines had an acceptable safety profile with self-limiting local and systemic adverse events, which rarely lasted >48 h post vaccination. Symptoms occurred predominantly after the second dose of the vaccine and less frequently in older patients >55 years. No vaccine-related serious adverse events were reported, and only limited effects of vaccination on the therapy schedule were observed.
Breast and gynecologic cancer patients tolerate the COVID-19 vaccination while undergoing systemic cancer therapy without any additional side effects beyond those reported in the general population.
•COVID-19 vaccine was safe in 218 breast and gynecological cancer patients.•Cancer patients appear to be rather skeptical about COVID-19 vaccination.•vaccine-related adverse events were self-limiting and mostly of short duration.•COVID-19 vaccines had limited effects on the schedule of anti-cancer therapies.
In patients with RAS wild-type metastatic colorectal cancer, depth of response (DpR) has gained importance as a novel end-point in clinical trials. We investigated the overall DpR, as well as the ...prognostic and predictive impact of DpR to induction therapy (six cycles of 5-fluorouracil, leucovorin FU/FA, oxaliplatin FOLFOX and panitumumab Pmab) on consecutive maintenance therapy (FU/FA plus Pmab or FU/FA alone) in patients treated within the PanaMa trial.
Central radiological assessment was performed according to RECIST 1.1. DpR was defined as percentage change in tumour diameter within defined time intervals (induction therapy, maintenance therapy, total course of therapy). For prognostic and predictive analyses, median DpR (</≥) served as threshold.
Out of 248 patients receiving maintenance therapy, 211 were evaluable for DpR analyses (FU/FA + Pmab, n = 106; FU/FA alone, n = 105). The overall DpR in all patients was 56.5%. DpR of induction therapy (42.5%) accounted for the largest proportion (75.2%) of the overall DpR. While greater DpR to induction therapy was significantly associated with prolonged PFS (HR 0.70, 95% CI 0.52–0.93, p = 0.013) and OS (HR 0.38, 95% CI 0.28–0.51, p < 0.001), there was no significant correlation of DpR and maintenance treatment arm.
In the PanaMa trial, the overall DpR was similar to DpR achieved by other epidermal growth factor receptor-based regimens. DpR to induction therapy accounted for three quarters of the total tumour shrinkage potentially suggesting that FOLFOX plus Pmab can be de-escalated following induction without substantially compromising efficacy. DpR to induction therapy was prognostic but not predictive for efficacy of consecutive maintenance therapy.
NCT01991873.
Display omitted
•In the PanaMa trial, the median overall DpR was 58.1% versus 54.9%, respectively.•Approximately 75% of the overall DpR was achieved during induction therapy.•Additional DpR achieved by maintenance therapy was numerically greater with Pmab.•DpR to induction was prognostic for PFS and OS of maintenance therapy.
Chromogranin A (CgA) is a well-established marker for diagnosis and follow up of patients with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN). Recently, it has been shown that plasma ...levels of CgA correlate with tumor load and predict survival of patients with NEN of the small bowel. It is assumed that this is as well valid for NEN of the colon and rectum, however, this is not supported by data. To evaluate this assumption, we analyzed 62 patients with NEN of the colon and rectum listed in the Marburg GEP-NEN registry for clinicopathological characteristics, expression and plasma levels of CgA. The present study demonstrates that immunohistochemical CgA and synaptophysin are good markers for histological diagnosis in patients with NEN of the colon and rectum. However, plasma CgA is a poor marker to follow-up these patients because only a minority exhibited increased levels which did not increase significantly during tumor progression. In contrast to NEN of the small bowel, there is no correlation of CgA plasma levels with tumor burden or survival. Patients with NEN of the colon and rectum displayed a relatively good prognosis resulting in a median survival of 8.5 years. However, a subset of patients affected by G3 neoplasms, exhibited a poorer prognosis with a median survival of 2.5 years. Taken together, CgA is a valuable marker for immunohistochemical diagnosis, but CgA plasma concentration is not suitable to mirror tumor burden or prognosis in patients with NEN of the colon and rectum.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Since the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. ...Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources. Methods A monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options. Results All patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs . all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs . 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs . 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time. Conclusion Patients and practitioners prefer oral antitumor therapy—both continuous and 21/7 regimens—over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer.
The debate is ongoing regarding the potential role of preoperative chemoradiotherapy (CRT) for patients with pancreatic ductal adenocarcinoma (PDAC), and whether it should be reserved for borderline ...resectable or unresectable tumors. However, treatment response is heterogeneous, implicating the need to unveil and overcome the underlying mechanisms of resistance. Activation of the transcription factor STAT3 was recently linked to CRT resistance in other gastrointestinal cancers such as rectal and esophageal cancers, but its role in PDAC needs to be clarified. Protein expression and phosphorylation of STAT3 was determined in PDAC cell lines and connected to transcriptional activity measured by dual-luciferase reporter gene assays. Inhibition of STAT3 signaling was achieved by RNAi or the small-molecule inhibitor napabucasin. We observed a positive correlation between STAT3 signaling activity and CRT resistance. Importantly, genetical and pharmacological perturbation of the IL-6/STAT3 pathway resulted in CRT sensitization specifically in those cell lines, in which STAT3 activity was augmented by IL-6. In conclusion, our data underscore the general importance of IL-6/STAT3 signaling for CRT resistance and suggest that pathway inhibition may represents a putative treatment strategy in order to increase the fraction of patients with PDAC who are candidates for surgical approaches.
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