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排序方式: 共有53条查询结果,搜索用时 11 毫秒
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Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
3.
Nanoparticles, microparticles, and other biomaterials are advantageous in vaccination because these materials provide opportunities to modulate specific characteristics of immune responses. This idea of “tuning” immune responses has recently been used to combat infectious diseases and cancer, and to induce tolerance during organ transplants or autoimmune disease. Lymph nodes and other secondary lymphoid organs such as the spleen play crucial roles in determining if and how these responses develop following vaccination or immunotherapy. Thus, by manipulating the local microenvironments within these immunological command centers, the nature of systemic immune response can be controlled. This review provides recent examples that harness the interactions between biomaterials and lymph nodes or other secondary lymphoid organs to generate immunity or promote tolerance. These strategies draw on mechanical properties, surface chemistry, stability, and targeting to alter the interactions of cells, signals, and vaccine components in lymph nodes. While there are still many unanswered questions surrounding how best to design biomaterial-based vaccines to promote specific structures or functions in lymph nodes, features such as controlled release and targeting will help pave the way for the next generation of vaccines and immunotherapies that generate immune responses tuned for specific applications.KEY WORDS: autoimmunity and tolerance, biomaterials, immunology, nanoparticles and microparticles, vaccine 相似文献
4.
Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence or absence of predators. Consequently, many organisms have developed corresponding adaptations, which ensure that specific physiological and behavioral events occur at an appropriate time of the day. In mammals, the underlying mechanism responsible for synchronizing internal biochemical processes with circadian environmental cues has been well studied and is thought to comprise three major components: (1) photoreception by the retina and transmission of neural signals along the retinohypothalamic tract, (2) integration of photoperiodic information with an internal reference circadian pacemaker located in the suprachiasmatic nucleus, and (3) dissemination of circadian information to target organs, via the autonomic nervous system and through humoral pathways. Given the importance that neuroendocrine rhythms play in coordinating normal circadian physiology and behavior, it is plausible that their perturbation during aging contributes to the etiology of age-related pathologies. This mini-review highlights some of the most dramatic rhythmic neuroendocrine changes that occur in primates during aging, focusing primarily on data from the male rhesus macaques (Macaca mulatta). In addition to the age-associated attenuation of hormone levels and reduction of humoral circadian signaling, there are also significant age-related changes in intracrine processing enzymes and hormone receptors which may further affect the functional efficacy of these hormones. Rhesus macaques, like humans, are large diurnal primates and show many of the same physiological and behavioral circadian changes during aging. Consequently, they represent an ideal translational animal model in which to study the causes and consequences of age-associated internal circadian disruption and in which to evaluate novel therapies. 相似文献
5.
Ahmed Gabr Joseph Ralph Kallini Vanessa L. Gates Ryan Hickey Laura Kulik Kush Desai Bartley Thornburg Karen Marshall Krystina Salzig Melissa Williams Carlene del Castillo Daniel Ganger Elias Hohlastos Talia Baker Robert J. Lewandowski Riad Salem 《European journal of nuclear medicine and molecular imaging》2016,43(13):2353-2359
Purpose
To assess the feasibility of conducting pretreatment mesenteric angiography, coil embolization, 99mTc macroaggregated albumin (99mTc-MAA) scintigraphy, and 90Y radioembolization treatment in a single, same-day, combined outpatient encounter.Methods
This was a retrospective study of 78 patients treated during the period 2008 – 2015 who were managed in a single outpatient encounter under the guidance of the Interventional Radiology Department and The Nuclear Medicine Department. Pretreatment planning was performed by reviewing baseline imaging and estimated perfused liver volume bearing the tumor. The region of interest was estimated using 3-D software; this value was used for dosimetry planning. Maximum lung shunting fractions of 10 % for hepatocellular carcinoma and 5 % for liver metastases were assumed. Subsequently, hepatic angiography and 99mTc-MAA scintigraphy were performed followed by 90Y treatment in one outpatient encounter. Total in-room procedure time was recorded.Results
All patients underwent same-day angiography, 99mTc-MAA scintigraphy and 90Y radioembolization. Of the 78 patients, 16 received multiple segmental treatments to both lobes, 44 received treatment to the right lobe, and 18 received treatment to the left lobe. The median dose was 106 Gy. The median number of 90Y vials needed was two (range one to six). The median in-room time was 160 min (75 – 250 min). The residential status of the patients was as follows, 18 % (14/78) were local residents, 55 % (43/78) traveled from outside the city limits, 18 % (14/78) were from out-of-state, and 9 % (7/78) were resident abroad. Of the 78 patients, 61 (77 %) had hepatocellular carcinoma, and 17 (22 %) had liver metastases. The median lung dose was 3.5 Gy.Conclusion
This study demonstrated the feasibility of same-day 90Y evaluation and treatment while maintaining the principles of safe and effective 90Y infusion including tumoricidal dosimetry (lobar, segmentectomy), minimization of nontarget flow, and minimization of lung dose. This paradigm translates into expeditious cancer care and significant cost savings.6.
7.
Julia Torabi Juan P. Rocca Krystina Choinski Katherine Lorenzen Camille Yongue Michelle L. Lubetzsky Melvon E. Herbert Attasit Chokechanachaisakul Maria Ajaimy Layla Kamal Enver Akalin Milan Kinkhabwala Jay A. Graham 《Clinical transplantation》2018,32(1)
Background
We analyze our outcomes utilizing imported allografts as a strategy to shorten wait list time for pancreas transplantation.Methods
This is an observational retrospective cohort of 26 recipients who received either a locally procured (n = 16) or an imported pancreas graft (n = 10) at our center between January 2014 and May 2017. Wait list times of this cohort were compared to UNOS Region 9 (New York State and Western Vermont). Hospital financial data were also reviewed to analyze the cost‐effectiveness of this strategy.Results
Imported pancreas grafts had significantly increased cold ischemia times (CIT) and peak lipase (PL) levels compared to locally procured grafts (CIT 827 vs 497 minutes; P = .001, PL 563 vs 157 u/L; P = .023, respectively). There were no differences in graft or patient survival. The median wait time was significantly lower for simultaneous kidney‐pancreas transplants at our center (518 days, n = 21) compared to Region 9 (1001 days, n = 65) P = .038. Despite financial concerns, the cost of transport for imported grafts was offset by lower standard acquisition costs.Conclusions
Imported pancreas grafts may be a cost‐effective strategy to increase organ utilization and shorten wait times in regions with longer waiting times. 相似文献8.
9.
Synthesis of Pyrazino[3,2,1-j,k]carbazole Derivatives The synthesis of the tetrahydrocarbazolones 3a-g from the p-benzoquinones 6a/b and the 2-(aminomethylene)cyclopentanone derivatives 7 is reported as well as the cyclisation of the N-aminoacetonotrile derivative 3d to the title compound 8a. 相似文献
10.
Addition of β-Dicarbonyl Compounds to 2-Acetyl-p-benzoquinone, III1): The reaction of α-hydroxymethylenecyclopentanone 2 with acetylquinone 1 yields the spiro-compound 3 . α-Hydroxymethylenecyclohexanone 7 gives the dibenzopyran 8 and the spiro-compound 9 as by-product. Compounds 3, 8 , and 9 are labile, rearrangement to 6 and 11 is examined by NMR spectroscopy. Acetylation of 6 and 11 yields 5 and 12 . With hydrochloric acid the spiro-compounds 6, 11 are rearranged to 16 and 17 , respectively. 相似文献