Hermanlorentzen2116
To report our dosimetric analysis of the hippocampi (HC) and the incidence of perihippocampal tumor location in patients with ≥25 brain metastases who received stereotactic radiosurgery (SRS) in single or multiple sessions.
Analysis of our prospective registry identified 89 patients treated with SRS for ≥25 brain metastases. Gusacitinib research buy HC avoidance regions (HA-region) were created on treatment planning MRIs by 5mm expansion of HC. Doses from each session were summed to calculate HC dose. The distribution of metastases relative to the HA-region and the HC was analyzed.
Median number of tumors irradiated per patient was 33 (range 25-116) in a median of 3 (range1-12) sessions. Median bilateral HC D
(D
), D
, D
, D
, and D
(Gy) was 1.88, 3.94, 3.62, 16.6, and 3.97 for all patients, and 1.43, 2.99, 2.88, 5.64, and 3.07 for patients with tumors outside the HA-region. Multivariate linear regression showed that the median HC D
, D
, and D
were significantly correlated with the tumor number and tumor volume (p<0.001). Of the total 3059 treated tumors, 83 (2.7%) were located in the HA-region in 57% evaluable patients; 38 tumors (1.2%) abutted or involved the HC itself.
Hippocampal dose is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.
Hippocampal dose is higher in patients with tumors in the HA-region; however, even for patients with a high burden of intracranial disease and tumors located in the HA-regions, SRS affords hippocampal sparing. This is particularly relevant in light of our finding of eventual perihippocampal metastases in more than half of our patients.
We present the first implementation of Adaptive 4D cone beam CT (4DCBCT) that adapts the image hardware (gantry rotation speed and kV projections) in response to the patient's real-time respiratory signal. Adaptive 4DCBCT was applied on lung cancer patients to reduce the scan time and imaging dose in the ADaptive CT Acquisition for Personalised Thoracic imaging (ADAPT) trial.
The ADAPT technology measures the patient's real-time respiratory signal and uses mathematical optimisation and external circuitry attached to the linear accelerator to modulate the gantry rotation speed and kV projection rate to reduce scan times and imaging dose. For each patient, ADAPT scans were acquired on two treatment fractions and reconstructed with a motion compensated reconstruction algorithm and compared to the current state-of-the-art four-minute 4DCBCT acquisition (conventional 4DCBCT). We report on the scan time, imaging dose and image quality for the first four adaptive 4DCBCT patients.
The ADAPT imaging dose was reduced by 85% and scan times were 73±12s representing a 70% reduction compared to the 240s conventional 4DCBCT scan. The contrast-to-noise ratio was improved from 9.2±3.9 with conventional 4DCBCT to 11.7±4.1 with ADAPT.
The ADAPT trial represents the first time that gantry rotation speed and projection acquisition have been adapted and optimised in real-time in response to changes in the patient's breathing. ADAPT demonstrates substantially reduced scan times and imaging dose for clinical 4DCBCT imaging that could enable more efficient and optimised lung cancer radiotherapy.
The ADAPT trial represents the first time that gantry rotation speed and projection acquisition have been adapted and optimised in real-time in response to changes in the patient's breathing. ADAPT demonstrates substantially reduced scan times and imaging dose for clinical 4DCBCT imaging that could enable more efficient and optimised lung cancer radiotherapy.The biosocial data of 90 children with acute lymphoblastic leukemia, were collected along with assessment of gastrointestinal side-effects of chemotherapy using visual analogue scale. Ginger lozenges has more effect than acupressure in alleviating nausea and vomiting. Acupressure alleviate the nausea best in the group aged 13-15 years. Ginger helped more the other two groups (7-12 years, 69 % of the group didn't suffer from nausea), versus 50 % aged 13-15). Both acupressure and ginger affected girls more than boys in alleviating nausea. The acupressure effect on vomiting incidence didn't differ in both males and males, whilst ginger helped the males more.Medical cannabis access has been legalized in more than 30 countries worldwide and popularity among patients is increasing rapidly. Cannabinoid-based treatments have been shown to be beneficial for several symptoms such as chemotherapy-induced nausea and vomiting, spasticity, chronic pain, intractable seizures and insomnia, yet high-quality clinical trials are still limited. As millions of patients now have legal access to medical cannabis, little information is available about the development of best clinical practices and an effective medical cannabis clinic model. A medical cannabis clinic is an innovative and emergent practice model that may be necessary to bridge the gap between patient and healthcare provider interest and existing barriers to the prescription of medical cannabis treatments, such as limited medical education, lack of high-quality clinical research and challenging or evolving regulatory frameworks. In this paper, we describe the model of care and organization of a dedicated medical cannabinic model of care can be adapted to different healthcare settings and regulatory frameworks; it may assist physicians and health care providers in the development of medical cannabis clinics or the implementation of best practices as medical cannabis access continues to evolve.The development of printable filaments has been identified as a critical aspect for the processing of pharmaceutical grade polymers and the fabrication of oral solid dosage forms. In this study a range of plain and drug loaded polymers were investigated and assessed for their printability in comparison to commercial filaments. Physicochemical characterizations of the polymers included differential scanning calorimetry (DSC) thermogravimetric analysis (TGA) and rheology were studied prior to Hot Melt Extrusion processing for the filament fabrication. A texture analyser was used to study the filament mechanical properties in order to derive the maximum tensile strength, Young's Modulus and elongation at break. Principal component analysis was used to compare the printability of the polymer and to identify the contribution of each mechanical property. The analysis showed that maximum tensile strength with a threshold between 15 and 20 MPa is the most critical property for the prediction of the printability. Furthermore, printable filaments were processed using Fusion Deposition Modelling technology and optimal printing parameters were identified. The study demonstrated that the prediction of filament printability is feasible by evaluating the mechanical properties.Obesity and diabetes cumulatively create a distinct systemic metabolic pathophysiological syndrome that predisposes patients to several diseases including breast cancer. Moreover, diabetic and obese women with breast cancer show a significant increase in mortality compared to non-obese and/or non-diabetic women. We hypothesized that these metabolic conditions incite an aggressive tumor phenotype by way of impacting tumor cell-autonomous and tumor cell non-autonomous events. In this study, we established a type 2 diabetic mouse model of triple-negative mammary carcinoma and investigated the effect of a glucose lowering therapy, metformin, on the overall tumor characteristics and immune/metabolic microenvironment. Diabetic mice exhibited larger mammary tumors that had increased adiposity with high levels of O-GlcNAc protein post-translational modification. These tumors also presented with a distinct stromal profile characterized by altered collagen architecture, increased infiltration by tumor-permissive M2 macrophages, and early metastatic seeding compared to non-diabetic/lean mice. Metformin treatment of the diabetic/obese mice effectively normalized glucose levels, reconfigured the mammary tumor milieu, and decreased metastatic seeding. Our results highlight the impact of two metabolic complications of obesity and diabetes on tumor cell attributes and showcase metformin's ability to revert tumor cell and stromal changes induced by an obese and diabetic host environment.Dietary fiber intake helps to maintain gut homeostasis. Fiber deficiency causes commensals to utilize mucins as an energy source to destroy mucus layer, thus promoting susceptibility to inflammatory bowel disease. Here, we reported that oroxylin A, a natural flavonoid, ameliorated low-grade colonic inflammation caused by fiber deficiency, alleviated colitis, and further prevented colitis-associated colon cancer in mice. The anti-inflammatory effect of oroxylin A was due to its alteration of gut microbiota. We found that the levels of Eubacterium coprostanoligenes was significantly increased by oroxylin A and the colonized Eubacterium coprostanoligenes significantly protected against colitis and carcinogenesis in colon of mice. Together, our results in this study suggest that oroxylin A may reduce the susceptibility to intestinal diseases by increasing the level of Eubacterium coprostanoligenes which could provide a therapeutic alternation for the treatment of intestinal diseases.Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia, usually driven by cancer-associated fibroblasts (CAFs), influencing patient prognosis. CAFs are a group of plastic cells responsible for tumor growth and metastasis. Fibroblasts have been reported to directly contribute to angiogenesis by undergoing mesenchymal-endothelial transition (MEndoT) after ischemic injury in the heart, brain, and hindlimbs. However, whether CAFs can undergo similar transdifferentiation in the hostile tumor microenvironment and directly contribute to tumor angiogenesis remains unclear. Herein, we provide evidence that CAFs can adopt an endothelial cell-like phenotype and directly contribute to tumor angiogenesis in vitro and in vivo. Furthermore, this program is regulated by the PERK-eIF2α-ERK1/2 axis. Pharmacological inhibition of PERK with GSK2606414 limited the phenotypic transition of CAFs. In conclusion, our results suggest that CAFs contribute to tumor angiogenesis by undergoing the MEndoT, thus representing therapeutic targets for improving PDAC prognosis.Upregulated expression of immune checkpoint molecules correlates with exhausted phenotype and impaired function of cytotoxic T cells to evade host immunity. By disrupting the interaction of PD-L1 and PD1, immune checkpoint inhibitors can restore immune system function against cancer cells. Growing evidence have demonstrated apigenin and luteolin, which are flavonoids abundant in common fruits and vegetables, can suppress growth and induce apoptosis of multiple types of cancer cells with their potent anti-inflammatory, antioxidant and anticancer properties. In this study, the effects and underlying mechanisms of luteolin, apigenin, and anti-PD-1 antibody combined with luteolin or apigenin on the PD-L1 expression and anti-tumorigenesis in KRAS-mutant lung cancer were investigated. Luteolin and apigenin significantly inhibited lung cancer cell growth, induced cell apoptosis, and down-regulated the IFN-γ-induced PD-L1 expression by suppressing the phosphorylation of STAT3. Both luteolin and apigenin showed potent anti-cancer activities in the H358 xenograft and Lewis lung carcinoma model in vivo, and the treatment with monoclonal PD1 antibody enhanced the infiltration of T cells into tumor tissues.
