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  • 1
    Online Resource
    Online Resource
    Site-selective photocatalytic functionalization of peptides and proteins at selenocysteine
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-11-12)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-11-12)
    Abstract: The importance of modified peptides and proteins for applications in drug discovery, and for illuminating biological processes at the molecular level, is fueling a demand for efficient methods that facilitate the precise modification of these biomolecules. Herein, we describe the development of a photocatalytic method for the rapid and efficient dimerization and site-specific functionalization of peptide and protein diselenides. This methodology, dubbed the photocatalytic diselenide contraction, involves irradiation at 450 nm in the presence of an iridium photocatalyst and a phosphine and results in rapid and clean conversion of diselenides to reductively stable selenoethers. A mechanism for this photocatalytic transformation is proposed, which is supported by photoluminescence spectroscopy and density functional theory calculations. The utility of the photocatalytic diselenide contraction transformation is highlighted through the dimerization of selenopeptides, and by the generation of two families of protein conjugates via the site-selective modification of calmodulin containing the 21 st amino acid selenocysteine, and the C-terminal modification of a ubiquitin diselenide.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-34530-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 2
    Online Resource
    Online Resource
    Epigenetically defined therapeutic targeting in H3.3G34R/V high-grade gliomas
    American Association for the Advancement of Science (AAAS) ; 2021
    In:  Science Translational Medicine Vol. 13, No. 615 ( 2021-10-13)
    Details
    In: Science Translational Medicine, American Association for the Advancement of Science (AAAS), Vol. 13, No. 615 ( 2021-10-13)
    Abstract: High-grade gliomas with arginine or valine substitutions of the histone H3.3 glycine-34 residue (H3.3G34R/V) carry a dismal prognosis, and current treatments, including radiotherapy and chemotherapy, are not curative. Because H3.3G34R/V mutations reprogram epigenetic modifications, we undertook a comprehensive epigenetic approach using ChIP sequencing and ChromHMM computational analysis to define therapeutic dependencies in H3.3G34R/V gliomas. Our analyses revealed a convergence of epigenetic alterations, including (i) activating epigenetic modifications on histone H3 lysine (K) residues such as H3K36 trimethylation (H3K36me3), H3K27 acetylation (H3K27ac), and H3K4 trimethylation (H3K4me3); (ii) DNA promoter hypomethylation; and (iii) redistribution of repressive histone H3K27 trimethylation (H3K27me3) to intergenic regions at the leukemia inhibitory factor ( LIF ) locus to drive increased LIF abundance and secretion by H3.3G34R/V cells. LIF activated signal transducer and activator of transcription 3 (STAT3) signaling in an autocrine/paracrine manner to promote survival of H3.3G34R/V glioma cells. Moreover, immunohistochemistry and single-cell RNA sequencing from H3.3G34R/V patient tumors revealed high STAT3 protein and RNA expression, respectively, in tumor cells with both inter- and intratumor heterogeneity. We targeted STAT3 using a blood-brain barrier–penetrable small-molecule inhibitor, WP1066, currently in clinical trials for adult gliomas. WP1066 treatment resulted in H3.3G34R/V tumor cell toxicity in vitro and tumor suppression in preclinical mouse models established with KNS42 cells, SJ-HGGx42-c cells, or in utero electroporation techniques. Our studies identify the LIF/STAT3 pathway as a key epigenetically driven and druggable vulnerability in H3.3G34R/V gliomas. This finding could inform development of targeted, combination therapies for these lethal brain tumors.
    Type of Medium: Online Resource
    ISSN: 1946-6234 , 1946-6242
    URL: Article
    DOI: 10.1126/scitranslmed.abf7860
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2021
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  • 3
    Online Resource
    Online Resource
    Effect of pretreatment clinical factors on overall survival in glioblastoma multiforme: a Surveillance Epidemiology and End Results (SEER) population analysis
    Springer Science and Business Media LLC ; 2012
    In:  World Journal of Surgical Oncology Vol. 10, No. 1 ( 2012-12)
    Details
    In: World Journal of Surgical Oncology, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2012-12)
    Abstract: Glioblastoma Multiforme (GBM) is one of the most aggressive primary brain tumors and is associated with a dismal prognosis. The median survival after the primary diagnosis remains poor, even after multimodal treatment approaches. However, a few patients have been reported to have long term survival greater than three years. A number of studies have attempted to define factors capable of predicting long term outcomes in specific patient groups. This article reports the outcomes of a very large group of patients diagnosed with GBM, and analyzes specific prognostic factors known to influence survival in these patients. Methods We used the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute (NCI) to investigate various patient-related and treatment- related factors that could influence the long term survival in patients diagnosed with glioblastoma. A total of 34,664 patients aged 20 years or older with a diagnosis of GBM during the years 1973 to 2008 were studied. Overall survival outcomes were examined with Kaplan-Meier survival analysis and Cox hazard models. Results Asian/Pacific Islanders had a better survival compared to the white population ( P  =  〈 0.001). Patients diagnosed with GBM during the years 2000 to 2008 had a superior survival rate when compared with earlier decades ( P  =  〈 0 .001). Statistically significant improvements in overall survival were also found for patients who received surgical resections, and adjuvant radiation treatment versus no radiation ( P -values 〈 0.001). Young age was also found to be highly predictive of improved overall survival rates when separated into age groups as well as when studied as a continuous variable. Conclusions Clinical pretreatment and treatment factors, including young age at diagnosis, Asian/Pacific Islander ethnicity, recent year of diagnosis, surgical resection and the use of adjuvant radiation therapy favorably influence survival in patients diagnosed with glioblastoma. Trial Registration All data were obtained from the United States Surveillance Epidemiology and End Results (SEER) database.
    Type of Medium: Online Resource
    ISSN: 1477-7819
    URL: Article
    DOI: 10.1186/1477-7819-10-75
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2118383-1
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  • 4
    Online Resource
    Online Resource
    Gamma knife radiosurgery for essential tremor: A Case report and review of the literature
    Springer Science and Business Media LLC ; 2010
    In:  World Journal of Surgical Oncology Vol. 8, No. 1 ( 2010-12)
    Details
    In: World Journal of Surgical Oncology, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2010-12)
    Abstract: Approximately 5 million people in America are affected by essential tremors (ET), which are classified as a type of benign movement disorder. This disease manifests as tremors that usually occur in the hands, but they may also be present in the head, face, tongue, and lower limbs. Radiofrequency thalamotomy (RF) and deep brain stimulation (DBS) are common invasive procedures with proven track records that are used to treat ET. Although these procedures have high success rates, they still put patients at risk of potential side effects and are invasive by nature. Thalamotomy using the gamma knife (GK) also produces favorable outcomes in treating tremors, without the complications associated with invasive neurosurgery procedures. This report describes the presenting symptoms and extended treatment outcome for a patient with an advanced case of ET, who received GK thalamotomy treatment six years ago. Because of this non-invasive treatment, she regained the ability to paint and live with an improved quality of life. We also discuss and review the relevant literature regarding the risks and benefits of this treatment modality. GK thalamotomy is one effective option for the treatment of ET, and due to its noninvasive nature, it has a different risk profile than neurosurgery. We suggest that GK thalamotomy should be presented as one viable treatment option to all ET patients, and should be recommended to those who would be best served by less invasive treatment techniques.
    Type of Medium: Online Resource
    ISSN: 1477-7819
    URL: Article
    DOI: 10.1186/1477-7819-8-20
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2118383-1
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  • 5
    Online Resource
    Online Resource
    Gamma knife radiosurgery for movement disorders: a concise review of the literature
    Springer Science and Business Media LLC ; 2010
    In:  World Journal of Surgical Oncology Vol. 8, No. 1 ( 2010-12)
    Details
    In: World Journal of Surgical Oncology, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2010-12)
    Abstract: Medication is the predominant method for the management of patients with movement disorders. However, there is a fraction of patients who experience limited relief from pharmaceuticals or experience bothersome side-effects of the drugs. Deep brain stimulation (DBS) and surgical lesioning of the thalamus and basal ganglia are respected neurosurgical procedures, with valued success rates and a very low incidence of complications. Despite these positive outcomes, DBS and surgical lesioning procedures are contraindicated for some patients. Stereotactic radiosurgery with the Gamma Knife (GK) has been used as a lesioning technique for patients seeking a non-invasive treatment alternative and for medication-intolerable patients, who are unable to undergo DBS or lesioning due to comorbid medical conditions. Tremors of various etiologies are treated using GK thalamotomy, which targets the ventralis intermedius nucleus. GK thalamotomy produces favorable outcomes when treating tremors, with success rates ranging from 80-100%. In contrast, GK pallidotomy targets the internal globus pallidus, and is used in treating bradykinesia, rigidity, and dyskinesia. Although radiosurgery has proven beneficial for tremors, radiosurgical pallidotomy for bradykinesia, rigidity, and dyskinesia remains questionable, with mixed success rates in the literature that ranges from 0-87%. We suggest that GK thalamotomy be offered along with other neurosurgical approaches as a feasible treatment option to patients who prefer the non-invasive nature of radiosurgery and to those who are unqualified candidates for the neurosurgical alternatives. Also, we advise that patients with bradykinesia, rigidity, and dyskinesia be educated about the variability in the literature pertaining to GK pallidotomy before proceeding with treatment.
    Type of Medium: Online Resource
    ISSN: 1477-7819
    URL: Article
    DOI: 10.1186/1477-7819-8-61
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2118383-1
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  • 6
    Online Resource
    Online Resource
    Long-Term Survival after Gamma Knife Radiosurgery in a Case of Recurrent Glioblastoma Multiforme: A Case Report and Review of the Literature
    Hindawi Limited ; 2012
    In:  Case Reports in Medicine Vol. 2012 ( 2012), p. 1-6
    Details
    In: Case Reports in Medicine, Hindawi Limited, Vol. 2012 ( 2012), p. 1-6
    Abstract: The management of recurrent glioblastoma is highly challenging, and treatment outcomes remain uniformly poor. Glioblastoma is a highly infiltrative tumor, and complete surgical resection of all microscopic extensions cannot be achieved at the time of initial diagnosis, and hence local recurrence is observed in most patients. Gamma Knife radiosurgery has been used to treat these tumor recurrences for select cases and has been successful in prolonging the median survival by 8–12 months on average for select cases. We present the unique case of a 63-year-old male with multiple sequential recurrences of glioblastoma after initial standard treatment with surgery followed by concomitant external beam radiation therapy and chemotherapy (temozolomide). The patient was followed clinically as well as with surveillance MRI scans at every 2-3-month intervals. The patient underwent Gamma Knife radiosurgery three times for 3 separate tumor recurrences, and the patient survived for seven years following the initial diagnosis with this aggressive treatment. The median survival in patients with recurrent glioblastoma is usually 8–12 months after recurrence, and this unique case illustrates that aggressive local therapy can lead to long-term survivors in select situations. We advocate that each patient treatment at the time of recurrence should be tailored to each clinical situation and desire for quality of life and improved longevity.
    Type of Medium: Online Resource
    ISSN: 1687-9627 , 1687-9635
    URL: Article
    DOI: 10.1155/2012/545492
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2502642-2
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  • 7
    Online Resource
    Online Resource
    A concise review of the efficacy of stereotactic radiosurgery in the management of melanoma and renal cell carcinoma brain metastases
    Springer Science and Business Media LLC ; 2012
    In:  World Journal of Surgical Oncology Vol. 10, No. 1 ( 2012-12)
    Details
    In: World Journal of Surgical Oncology, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2012-12)
    Abstract: Melanoma and renal cell carcinoma have a well-documented tendency to develop metastases to the brain. Treating these lesions has traditionally been problematic, because chemotherapy has difficulty crossing the blood brain barrier and whole brain radiation therapy (WBRT) is a relatively ineffective treatment against these radioresistant tumor histologies. In recent years, stereotactic radiosurgery (SRS) has emerged as an effective and minimally-invasive treatment modality for irradiating either single or multiple intracranial structures in one clinical treatment setting. For this reason, we conducted a review of modern literature analyzing the efficacy of SRS in the management of patients with melanoma and renal cell carcinoma brain metastases. In our analysis we found SRS to be a safe, effective and attractive treatment modality for managing radioresistant brain metastases and highlighted the need for randomized trials comparing WBRT alone vs. SRS alone vs. WBRT plus SRS in treating patients with radioresistant brain metastases.
    Type of Medium: Online Resource
    ISSN: 1477-7819
    URL: Article
    DOI: 10.1186/1477-7819-10-176
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2012
    detail.hit.zdb_id: 2118383-1
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  • 8
    Online Resource
    Online Resource
    Clinical Outcomes of Gamma Knife Radiosurgery in the Treatment of Patients with Trigeminal Neuralgia
    Hindawi Limited ; 2012
    In:  International Journal of Otolaryngology Vol. 2012 ( 2012), p. 1-13
    Details
    In: International Journal of Otolaryngology, Hindawi Limited, Vol. 2012 ( 2012), p. 1-13
    Abstract: Since its introduction by Leksell, Gamma Knife radiosurgery (GKRS) has become increasingly popular as a management approach for patients diagnosed with trigeminal neuralgia (TN). For this reason, we performed a modern review of the literature analyzing the efficacy of GKRS in the treatment of patients who suffer from TN. For patients with medically refractory forms of the condition, GKRS has proven to be an effective initial and repeat treatment option. Cumulative research suggests that patients treated a single time with GKRS exhibit similar levels of facial pain control when compared to patients treated multiple times with GKRS. However, patients treated on multiple occasions with GKRS are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with GKRS. Although numerous articles have reported MVD to be superior to GKRS in achieving facial pain relief, the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and cannot be considered conclusive. Questions remain regarding optimal GKRS dosing and targeting strategies, which warrants further investigation into this controversial matter.
    Type of Medium: Online Resource
    ISSN: 1687-9201 , 1687-921X
    URL: Article
    DOI: 10.1155/2012/919186
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2503281-1
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  • 9
    Online Resource
    Online Resource
    Long-Term Survival in a Patient with Multiple Brain Metastases from Small-Cell Lung Cancer Treated with Gamma Knife Radiosurgery on Four Occasions: A Case Report
    Hindawi Limited ; 2012
    In:  Case Reports in Neurological Medicine Vol. 2012 ( 2012), p. 1-4
    Details
    In: Case Reports in Neurological Medicine, Hindawi Limited, Vol. 2012 ( 2012), p. 1-4
    Abstract: Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient’s primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival.
    Type of Medium: Online Resource
    ISSN: 2090-6668 , 2090-6676
    URL: Article
    DOI: 10.1155/2012/276189
    Language: English
    Publisher: Hindawi Limited
    Publication Date: 2012
    detail.hit.zdb_id: 2629909-4
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  • 10
    Online Resource
    Online Resource
    Clinical Outcomes of Gamma Knife Radiosurgery in the Salvage Treatment of Patients with Recurrent High-Grade Glioma
    Elsevier BV ; 2013
    In:  World Neurosurgery Vol. 80, No. 6 ( 2013-12), p. 872-878
    Details
    In: World Neurosurgery, Elsevier BV, Vol. 80, No. 6 ( 2013-12), p. 872-878
    Type of Medium: Online Resource
    ISSN: 1878-8750
    URL: Article
    DOI: 10.1016/j.wneu.2013.02.030
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2013
    detail.hit.zdb_id: 2530041-6
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