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Somatostatin is a peptide with a potent and broad antisecretory action, which makes it an invaluable drug target for the pharmacological management of pituitary adenomas and neuroendocrine tumors. Somatostatin receptors (SSTR1, 2A and B, 3, 4 and 5) belong to the G protein coupled receptor family and have a wide expression pattern in both normal tissues and solid tumors. Investigating the function of each SSTR in several tumor types has provided a wealth of information about the common but also distinct signaling cascades that suppress tumor cell proliferation, survival and angiogenesis. This provided the rationale for developing multireceptor-targeted somatostatin analogs and combination therapies with signaling-targeted agents such as inhibitors of the mammalian (or mechanistic) target of rapamycin (mTOR). The ability of SSTR to internalize and the development of rabiolabeled somatostatin analogs have improved the diagnosis and treatment of neuroendocrine tumors. 相似文献
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《Vaccine》2018,36(5):698-706
BackgroundTo support vaccination programs in developing countries, a 4-dose vial presentation of pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) was developed. This study assessed immunologic non-inferiority and safety of the investigational PHiD-CV 4-dose versus licensed 1-dose vial presentation in infants.MethodsIn this phase III, mono-center, observer-blind study in Bangladesh, 6–10-week-old infants were randomized 1:1 to receive PHiD-CV primary vaccination (at ages 6, 10, 18 weeks) and a booster dose (at age 9 months) with a 4-dose vial (with preservative, 4DV group) or 1-dose vial (preservative-free, 1DV group). DTPw-HBV/Hib was (co)-administered per study protocol and polio, measles and rubella vaccines as part of the national immunization program. Non-inferiority of PHiD-CV 4-dose versus 1-dose vial for each vaccine pneumococcal serotype (VT) and vaccine-related serotype 19A in terms of antibody geometric mean concentration (GMC) was assessed (criterion: upper limit of 2-sided 95% confidence interval of antibody GMC ratios [1DV/4DV] <2-fold). Immune responses were measured. Solicited, unsolicited and serious adverse events (AEs) were evaluated.ResultsOf 320 infants (160 per group) vaccinated during the primary vaccination phase, 297 received a booster. Non-inferiority was demonstrated for each VT and 19A. One month post-primary vaccination, for most VT, ≥97.9% of infants in each group had antibody concentrations ≥0.2 μg/mL; for 19A ≥ 80.1% reached this threshold. Pneumococcal antibody responses and opsonophagocytic activity for each VT and 19A were within similar ranges between groups after primary and booster vaccination, as were anti-protein D responses. Booster immune responses were observed in both groups. Reported AEs were within similar ranges for both presentations.ConclusionImmunologic non-inferiority of PHiD-CV 4-dose vial (with preservative) versus PHiD-CV 1-dose vial (preservative-free) was demonstrated. Immune responses and reactogenicity following primary/booster vaccination were within similar ranges for both presentations. PHiD-CV 4-dose vial would help improve access and coverage in resource-limited countries.Clinical Trial Registry: NCT02447432. 相似文献
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目的 调查估算江苏省乳腺X射线摄影的频度,进而估算乳腺摄影对江苏省女性人口的剂量负担,并评估乳腺摄影对江苏省各年龄组女性人口诱发乳腺癌的风险。方法 采用分层随机抽样调查的方法,通过调查30台乳腺摄影设备年检查人数和受检者年龄分布,估算全省乳腺摄影的频度,并计算乳腺摄影对女性人口的剂量负担。使用美国科学院电离辐射生物效应报告BEIR-Ⅶ中的超额归因风险(EAR)模型估算乳腺摄影检查对3个年龄组诱发乳腺癌的风险。结果 江苏省乳腺摄影检查的频度为3.77次/千人口;乳腺摄影对江苏省女性人口剂量负担为0.02 mGy/人。每次乳腺摄影检查对0~15岁组、16~40岁和>40岁3个年龄组的乳腺癌终生归因风险(LAR)分别为138/10万人、14.7/10万人和1.0/10万人。结论 乳腺摄影对人群乳腺癌诱发风险较小,但低年龄组的风险较大,提示针对低年龄乳腺摄影检查仍应慎重。 相似文献
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Sergio Huerta Bryce Murray Craig Olson Prapti Patel Thomas Anthony 《The Indian journal of surgery》2009,71(6):356-362
The management of rectal cancer has drastically evolved over the past two decades as a result of implementation of circular
stapling devices and the introduction of neoadjuvant chemoradiation. In spite of current aggressive multimodality treatments,
the recurrence rate remains unacceptably high and the expected 5-year survival in patients who develop recurrent disease is
dismal. The management of rectal cancer must involve a multidisciplinary approach. An understanding of the biology of rectal
tumours may allow for selection of patients who may have an aggressive phenotype allowing for alterations in the operative
and neoadjuvant planning. Efforts to improve local control and survival in rectal cancer are the focus of multiple current
clinical and preclinical research efforts. Preoperative chemoradiation for and surgical management of rectal cancer, including
the laparoscopic approach are areas of dynamic progression. In the present report, we review the current evidence in the new
strategies pertaining to the multimodality approach in the management of rectal cancer. 相似文献
6.
Huang Z Dias R Jones T Liu S Styhler A Claveau D Otu F Ng K Laliberte F Zhang L Goetghebeur P Abraham WM Macdonald D Dubé D Gallant M Lacombe P Girard Y Young RN Turner MJ Nicholson DW Mancini JA 《Biochemical pharmacology》2007,73(12):1971-1981
Type 4 phosphodiesterases (PDE4) inhibitors are emerging therapeutics in the treatment of a number of chronic disorders including asthma, chronic obstructive pulmonary disease (COPD) and cognitive disorders. This study delineates the preclinical profile of L-454,560, which is a potent, competitive and preferential inhibitor of PDE4A, 4B, and 4D with IC50 values of 1.6, 0.5 and 1.2 nM, respectively. In contrast to the exclusive binding of cilomilast and the preferential binding of roflumilast to the PDE4 holoenzyme state (Mg2+-bound form), L-454,560 binds to both the apo-(Mg2+-free) and holoenzyme states of PDE4. The intrinsic enzyme potency for PDE4 inhibition by L-454,560 also results in an effective blockade of LPS-induced TNFalpha formation in whole blood (IC50 = 161 nM) and is comparable to the human whole blood potency of roflumilast. The cytokine profile of inhibition of L-454,560 is mainly a Th1 profile with significant inhibition of IFNgamma and no detectable inhibition of IL-13 formation up to 1 microM. L-454,560 was also found to be efficacious in two models of airway hyper-reactivity, the ovalbumin (OVA) sensitized and challenged guinea pig and the ascaris sensitized sheep model. Furthermore, L-454560 was also effective in improving performance in the delayed matching to position (DMTP) version of the Morris watermaze, at a dose removed from that associated with potential emesis. Therefore, L-454,560 is a novel PDE4 inhibitor with an overall in vivo efficacy profile at least comparable to roflumilast and clearly superior to cilomilast. 相似文献
7.
Marie Benoît Olivier Nicolas Jean-Pierre Vronique 《Computerized medical imaging and graphics》2008,32(4):258-269
The joint source–channel coding system proposed in this paper has two aims: lossless compression with a progressive mode and the integrity of medical data, which takes into account the priorities of the image and the properties of a network with no guaranteed quality of service. In this context, the use of scalable coding, locally adapted resolution (LAR) and a discrete and exact Radon transform, known as the Mojette transform, meets this twofold requirement. In this paper, details of this joint coding implementation are provided as well as a performance evaluation with respect to the reference CALIC coding and to unequal error protection using Reed–Solomon codes. 相似文献
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Aberrant astrocytic expression of chondroitin sulfate proteoglycan receptors in a rat model of amyotrophic lateral sclerosis 下载免费PDF全文
Tomomi Shijo Hitoshi Warita Naoki Suzuki Yasuo Kitajima Kensuke Ikeda Tetsuya Akiyama Hiroya Ono Shio Mitsuzawa Ayumi Nishiyama Rumiko Izumi Masashi Aoki 《Journal of neuroscience research》2018,96(2):222-233
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Progressive and systemic loss of motor neurons with gliosis in the central nervous system (CNS) is a neuropathological hallmark of ALS. Chondroitin sulfate proteoglycans (CSPGs) are the major components of the extracellular matrix of the mammalian CNS, and they inhibit axonal regeneration physically by participating to form the glial scar. Recently, protein tyrosine phosphatase sigma (PTPσ) and leukocyte common antigen‐related protein were discovered as CSPG receptors that play roles in inhibiting regeneration. Here we examined the expression of CSPG receptors in transgenic female rats overexpressing an ALS‐linked mutant cytosolic Cu/Zn superoxide dismutase gene (SOD1). In contrast to controls, multiple immunofluorescence analyses revealed aberrant expression of CSPG receptors dominantly in reactive astrocytes, while PTPσ expression in neurons decreased in the spinal ventral horns of ALS transgenic rats. The aberrant and progressive astrocytic expression of CSPG receptors and reactive astrocytes themselves may be therapeutic targets for reconstructing a regeneration‐supportive microenvironment under neurodegenerative conditions such as ALS. 相似文献
10.
Judy-Anne W Chapman Kathleen I Pritchard Paul E Goss James N Ingle Hyman B Muss Susan F Dent Ted A Vandenberg Brian Findlay Karen A Gelmon Carolyn F Wilson Lois E Shepherd Michael N Pollak 《World journal of clinical oncology》2014,5(5):1088-1096
AIM: To show a new paradigm of simultaneously testing whether breast cancer therapies impact other causes of death.METHODS: MA.14 allocated 667 postmenopausal women to 5 years of tamoxifen 20 mg/daily ± 2 years of octreotide 90 mg, given by depot intramuscular injections monthly. Event-free survival was the primary endpoint of MA.14; at median 7.9 years, the tamoxifen+octreotide and tamoxifen arms had similar event-free survival (P = 0.62). Overall survival was a secondary endpoint, and the two trial arms also had similar overall survival (P = 0.86). We used the median 9.8 years follow-up to examine by intention-to-treat, the multivariate time-to-breast cancer-specific (BrCa) and other cause (OC) mortality with log-normal survival analysis adjusted by treatment and stratification factors. We tested whether baseline factors including Insulin-like growth factor 1 (IGF1), IGF binding protein-3, C-peptide, body mass index, and 25-hydroxy vitamin D were associated with (1) all cause mortality, and if so and (2) cause-specific mortality. We also fit step-wise forward cause-specific adjusted models.RESULTS: The analyses were performed on 329 patients allocated tamoxifen and 329 allocated tamoxifen+octreotide. The median age of MA.14 patients was 60.1 years: 447 (82%) < 70 years and 120 (18%) ≥ 70 years. There were 170 deaths: 106 (62.3%) BrCa; 55 (32.4%) OC, of which 24 were other malignancies, 31 other causes of death; 9 (5.3%) patients with unknown cause of death were excluded from competing risk assessments. BrCa and OC deaths were not significantly different by treatment arm (P = 0.40): tamoxifen patients experienced 50 BrCa and 32 OC deaths, while tamoxifen + octreotide patients experienced 56 BrCa and 23 OC deaths. Proportionately more deaths (P = 0.004) were from BrCa for patients < 70 years, where 70% of deaths were due to BrCa, compared to 54% for those ≥ 70 years of age. The proportion of deaths from OC increased with increasing body mass index (BMI) (P = 0.02). Higher pathologic T and N were associated with more BrCa deaths (P < 0.0001 and 0.002, respectively). The cumulative hazard plot for BrCa and OC mortality indicated the concurrent accrual of both types of death throughout follow-up, that is the existence of competing risks of mortality. MA.14 therapy did not impact mortality (P = 0.77). Three baseline patient and tumor characteristics were differentially associated with cause of death: older patients experienced more OC (P = 0.01) mortality; patients with T1 tumors and hormone receptor positive tumors had less BrCa mortality (respectively, P = 0.01, P = 0.06). Additionally, step-wise cause-specific models indicated that patients with node negative disease experienced less BrCa mortality (P = 0.002); there was weak evidence that, lower C-peptide (P = 0.08) was associated with less BrCa mortality, while higher BMI (P = 0.01) was associated with worse OC mortality.CONCLUSION: We demonstrate here a new paradigm of simultaneous testing of therapeutics directed at multiple diseases for which postmenopausal women are concurrently at risk. Octreotide LAR did not significantly impact breast cancer or other cause mortality, although different baseline factors influenced type of death. 相似文献