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- Ahlgren, Sara, et al.
(författare)
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Evaluation of maleimide derivative of DOTA for site-specific labeling of recombinant affibody molecules
- 2008
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Ingår i: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 19:1, s. 235-243
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Tidskriftsartikel (refereegranskat)abstract
- Affibody molecules are a new class of small (7 kDa) scaffold affinity proteins, which demonstrate promising properties as agents for in vivo radionuclide targeting. The Affibody scaffold is cysteine-free and therefore independent of disulfide bonds. Thus, a single thiol group can be engineered into the protein by introduction of one cysteine. Coupling of thiol-reactive bifunctional chelators can enable site-specific labeling of recombinantly produced Affibody molecules. In this study, the use of 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid-10-maleimidoethylacetamide (MMA-DOTA) for 111 In-labeling of anti-HER2 Affibody molecules His 6-Z HER2:342-Cys and Z HER2:2395-Cys has been evaluated. The introduction of a cysteine residue did not affect the affinity of the proteins, which was 29 pM for His 6-Z HER2:342-Cys and 27 pM for Z HER2:2395-Cys, comparable with 22 pM for the parental Z HER2:342. MMA-DOTA was conjugated to DTT-reduced Affibody molecules with a coupling efficiency of 93% using a 1:1 molar ratio of chelator to protein. The conjugates were labeled with 111 In to a specific radioactivity of up to 7 GBq/mmol, with preserved binding for the target HER2. In vivo, the non-His-tagged variant 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys demonstrated appreciably lower liver uptake than its His-tag-containing counterpart. In mice bearing HER2-expressing LS174T xenografts, 111 In-[MMA-DOTA-Cys61]-Z HER2:2395-Cys showed specific and rapid tumor localization, and rapid clearance from blood and nonspecific compartments, leading to a tumor-to-blood-ratio of 18 +/- 8 already 1 h p.i. Four hours p.i., the tumor-to-blood ratio was 138 +/- 8. Xenografts were clearly visualized already 1 h p.i.
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- Galván, Ignacio Fdez., et al.
(författare)
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OpenMolcas : From Source Code to Insight
- 2019
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Ingår i: Journal of Chemical Theory and Computation. - : American Chemical Society (ACS). - 1549-9618 .- 1549-9626. ; 15:11, s. 5925-5964
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Tidskriftsartikel (refereegranskat)abstract
- In this Article we describe the OpenMolcas environment and invite the computational chemistry community to collaborate. The open-source project already includes a large number of new developments realized during the transition from the commercial MOLCAS product to the open-source platform. The paper initially describes the technical details of the new software development platform. This is followed by brief presentations of many new methods, implementations, and features of the OpenMolcas program suite. These developments include novel wave function methods such as stochastic complete active space self-consistent field, density matrix renormalization group (DMRG) methods, and hybrid multiconfigurational wave function and density functional theory models. Some of these implementations include an array of additional options and functionalities. The paper proceeds and describes developments related to explorations of potential energy surfaces. Here we present methods for the optimization of conical intersections, the simulation of adiabatic and nonadiabatic molecular dynamics, and interfaces to tools for semiclassical and quantum mechanical nuclear dynamics. Furthermore, the Article describes features unique to simulations of spectroscopic and magnetic phenomena such as the exact semiclassical description of the interaction between light and matter, various X-ray processes, magnetic circular dichroism, and properties. Finally, the paper describes a number of built-in and add-on features to support the OpenMolcas platform with postcalculation analysis and visualization, a multiscale simulation option using frozen-density embedding theory, and new electronic and muonic basis sets.
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- Hedestig, Oliver, 1943-
(författare)
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Att leva med lokaliserad prostatacancer : "oss män emellan"
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The purpose of this thesis is to explore how men experience living with localized prostate cancer. It includes four substudies carried out between 1997 and 2005. To gather data, the men were interviewed at home and the interviews were recorded. The men (n=27; ages 60-70) who participated in the substudies had a PSA ≤10 ng/ml at the time of diagnosis, and had what is known as low-risk prostate cancer. Seven of the men chose to “wait and see” how the disease would progress after receiving the diagnosis. Twenty men chose curative treatment (10 men external radiation therapy, 10 men radical surgery). The interviews were analyzed using a phenomenological hermeneutical method inspired by the philosophy of Paul Ricoeur, and qualitative content analysis. Men who live with localized prostate cancer perceive the disease as life-threatening, unpredictable, and without early symptoms, which creates a sense of uncertainty, worry, anxiety, despair, and fear of death. Men primarily share perceptions of the disease and treatment with their wives and relatives, as well as with other men in the same situation. They avoid talking about their illness, and keep their innermost thoughts about their disease, prognosis, and the future to themselves. The choice to share their thoughts and feelings only sparingly with others is related in part to the perceived stigmatization of the diagnosis, as well as to consideration for friends and family. The men report that external radiation therapy and radical surgery have negative side effects such as erectile dysfunction, urinary incontinence, and intestinal leakage. They describe the side effects as socially isolating; for example, urinary leakage can require a change of incontinence pads and clothing, and they feel that they smell bad. Men with erectile dysfunction describe themselves as maimed, and their sex lives have changed or disappeared. They report a change in their self-esteem and identity as men and they long for life as it was before the diagnosis, when they felt they had control over their bodily functions. A few men describe a sense of being literally and figuratively “exposed” when they are undressed for examinations or participate in discussions with female doctors and nurses about their erectile dysfunction. They do not describe this perception in the same way with respect to contact with male personnel. In the new situation after treatment, men try to regain a perceived sense of control in their daily lives, over the disease and the effects of treatment. They experience a sense of control over the disease through regular PSA tests; the implications of regular PSA tests can be interpreted as a life preserver in an uncertain world, considering that at the time they were diagnosed they had no symptoms and only had a PSA elevation. The PSA is important for this sense of control, and each PSA test is preceded by tense expectation. The PSA level is described as a reliable expression of the medical condition. The men cannot trust that their own perception of feeling healthy means that the disease is under control. Low and stable PSA levels over a long period of time give a sense of safety, security, and control over the situation. If the PSA climbs, the men feel that despite everything, they have caught it in time for further treatment. Discussions with other men with prostate cancer are also described as a way of having control over the situation. The men's endeavor to reconcile themselves to the new situation can be understood as a process, where they describe various strategies which can be used to forget the “cancer perspective” and achieve a perception of safety and security. Reconciliation with a new situation can be interpreted as a reorientation after the trauma of the cancer diagnosis. The study results show that the men are restrained in communicating their needs to others, which can be interpreted as their having a greater need for support and information than indicated by their signals. Having an internal image of what a man should be like can be an obstacle to showing these needs.
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| 10. |
- Hedestig, Oliver, et al.
(författare)
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Meanings of prostate-specific antigen testing as narrated by men with localized prostate cancer after primary treatment
- 2008
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Ingår i: Scandinavian Journal of Urology and Nephrology. - Stockholm : Taylor & Francis. - 0036-5599 .- 1651-2065. ; 42:2, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To illuminate the meanings of prostate-specific antigen (PSA) testing as narrated by men with localized prostate cancer (LPC) after primary treatment. Material and methods: Fifteen men were interviewed in their homes. The narrative interview text was analyzed using a phenomenological hermeneutic method inspired by the philosophy of Paul Ricoeur. Results: Life after treatment for LPC means feeling unsafe because of being affected by a life-threatening and unpredictable disease, characterized by a lack of early signs of progression. In this situation, PSA testing is ascribed as providing a sense of control to enable one to achieve a feeling of safety. Thus one meaning of PSA testing is receiving a message about the status of the body; another is a tense waiting related to fear of the results. A low, stable PSA value is interpreted as a sense of being safe based on confidence in the PSA tests and a sense of having control over the LPC via regular PSA testing. A rising value of the PSA blood test is understood as an indication of progression of the disease, but confidence in PSA testing also means that when the PSA value rises there is a sense of catching the cancer in good time. Conclusions: The comprehensive understanding of the meaning of PSA testing can be understood in terms of a lifeline to cling to when wondering whether the cancer is still in progress in the body or whether the treatment has been curative. This lifeline creates a feeling of security in a post-treatment life situation which is experienced as being unsafe.
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