| 1. |
- Lundgren Mortensen, Anja Charlotte, et al.
(författare)
-
Combination therapy of tyrosine kinase inhibitor sorafenib with the HSP90 inhibitor onalespib as a novel treatment regimen for thyroid cancer
- 2023
-
Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Thyroid cancer is the most common endocrine malignancy, affecting nearly 600,000 new patients worldwide. Treatment with the BRAF inhibitor sorafenib partially prolongs progression-free survival in thyroid cancer patients, but fails to improve overall survival. This study examines enhancing sorafenib efficacy by combination therapy with the novel HSP90 inhibitor onalespib. In vitro efficacy of sorafenib and onalespib monotherapy as well as in combination was assessed in papillary (PTC) and anaplastic (ATC) thyroid cancer cells using cell viability and colony formation assays. Migration potential was studied in wound healing assays. The in vivo efficacy of sorafenib and onalespib therapy was evaluated in mice bearing BHT-101 xenografts. Sorafenib in combination with onalespib significantly inhibited PTC and ATC cell proliferation, decreased metabolic activity and cancer cell migration. In addition, the drug combination approach significantly inhibited tumor growth in the xenograft model and prolonged the median survival. Our results suggest that combination therapy with sorafenib and onalespib could be used as a new therapeutic approach in the treatment of thyroid cancer, significantly improving the results obtained with sorafenib as monotherapy. This approach has the potential to reduce treatment adaptation while at the same time providing therapeutic anti-cancer benefits such as reducing tumor growth and metastatic potential.
|
|
| 2. |
- Mahendar, Senthil Krishnan, 1988-
(författare)
-
Mitigating Knock in Heavy Duty Spark Ignition Engines : Experiments and simulations of diluted ethanol and methanol combustion
- 2021
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- To effectively reduce fossil fuel dependence in the transport sector, an unprecedented increase in renewable fuel production is required. Short chain alcohols, such as ethanol and methanol, are well placed as they can be produced in a variety of renewable pathways from most carbon sources. Due to its high autoignition resistance, ethanol and methanol cannot be used as drop-in fuels in compression ignition engines that are prevalent in the heavy duty (HD) transport sector but can be an immense advantage when used in HD spark ignition (SI) engines.One crucial disadvantage experienced by HD SI engines is the end gas autoignition or knock which limits engine load, compression ratio and efficiency. It was not established if ethanol and methanol can in fact achieve the required load range in HD SI engines and if so, how efficient they would be. Diluting the air-fuel mixture with excess air or exhaust gas recirculation can add knock resistance by lowering in-cylinder temperature. Though dilution increases load and efficiency, it also increases instability and ultimately causes misfires. In this thesis, diluted combustion, knock limit and performance of ethanol and methanol was studied using a single cylinder heavy duty research engine. The required load was achieved with relatively good efficiency at lean operation and potential for improving efficiency further was investigated using 1D simulations. The modifications needed to utilize a semi-predictive combustion model in diluted operation were presented. Using simulations, the impact of turbulence on the performance of Miller valve timing and the effect of squish area on piston shapes to improve turbulence was discussed. With Miller timing and fast combustion using high squish pistons, lean burn ethanol and methanol can offer high efficiency, on par with compression ignition engines. If ethanol or methanol production can be scaled up, HD SI engines can provide good performance, low capital and operating cost for future transport.
|
|
| 3. |
- Spiegelberg, Diana, 1982-, et al.
(författare)
-
Higher Risk of Recurrence in Patients Treated for Head and Neck Cancer with Low BMI and Elevated Levels of C-Reactive Protein
- 2022
-
Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:20
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Head and neck cancer (HNC) treatment poses several challenges in clinical practice, and treatment side effects can be debilitating due to the close proximity of important anatomical structures. Cancer recurrence post-treatment presents some of the most challenging HNC management issues. This prospective study identifies high-risk groups for recurrence of head and neck cancer, based on commonly accessible clinical parameters. In this study with 272 HNC patients, elevated pre- and post-treatment CRP levels, low BMI and advanced stage at admission indicate higher risk for recurrence of disease. Using these parameters, a risk model is proposed which may be useful for estimating the probability of cancer recurrence and allow the identification of high and low-risk patients. This prospective study identifies high-risk groups for recurrence of head and neck cancer by BMI and circulating inflammatory response markers. Head and neck cancer patients from three Swedish hospitals were included (n = 272). Leukocyte and thrombocyte counts, CRP levels, and BMI were measured pre-treatment and post-treatment. Associations between the four factors and treatment failure (residual tumor, loco-regional failure, general failure/distant metastasis) were assessed using a Cox proportional hazards model adjusted for sex, age at the initial visit, smoking status, cancer stage, and hemoglobin count. CRP level was the only significant single variable, with an average increase in risk of recurrence of 74% (p = 0.018) for every doubling. The predictive power of a combined model using all variables was highest during the initial months after treatment, with AUC under the ROC curve 0.75 at the 0-3 month timepoints. Patients with elevated pre- and post-treatment CRP levels are at higher risk for recurrence of disease. Male patients with low post-treatment BMI, advanced stage, and high CRP at any time post treatment are at high risk for recurrence. The combined model may be useful for stratifying post-treatment patients into low and high-risk groups, to enable more detailed follow-up or additional treatment regimens.
|
|
