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Marijo Bilusic Yu-Ning Wong 《Asian journal of andrology》2014,16(3):372-377
Angiogenesis is a very complex physiological process, which involves multiple pathways that are dependent on the homeostatic balance between the growth factors (stimulators and inhibitors). This tightly controlled process is stimulated by angiogenic factors, which are present within the tumor and surrounding tumor-associated stromal cells. The dependence of tumor propagation, invasion and metastasis on angiogenesis makes the inhibitors of new blood vessel formation attractive drugs for treating the malignancies. Angiogenesis can be disrupted by several distinct mechanisms: by inhibiting endothelial cells, by interrupting the signaling pathways or by inhibiting other activators of angiogenesis. This strategy has shown therapeutic benefit in several types of solid tumors, leading to Food and Drug Administration (FDA) approval of anti-angiogenic agents in the treatment of kidney, non-small cell lung, colon and brain cancers. Although no angiogenesis inhibitors have been approved for patients with metastatic prostate cancer, therapies that target new blood vessel formation are still an emerging and Dromising area of prostate cancer research. 相似文献
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Jason M Redman Yo-Ting Tsai Benjamin A Weinberg Renee N Donahue Shruti Gandhy Margaret E Gatti-Mays Houssein Abdul Sater Marijo Bilusic Lisa
M Cordes Seth M Steinberg Jennifer L Marte Caroline Jochems Sunnie S Kim John L Marshall Sheri McMahon Erica Redmond Jeffrey Schlom James L Gulley Julius Strauss 《The oncologist》2022,27(3):198
BackgroundFOLFOX plus bevacizumab is a standard of care (SOC) for first-line treatment of microsatellite-stable metastatic colorectal cancer (MSS mCRC). This study randomized patients to SOC or SOC plus avelumab (anti-PD-L1) plus CEA-targeted vaccine.MethodsPatients with untreated MSS mCRC enrolled to a lead-in arm assessing safety of SOC + immuno-oncology agents (IO). Next, patients were randomized to SOC or SOC + IO. The primary endpoint was progression-free survival (PFS). Multiple immune parameters were analyzed.ResultsSix patients enrolled to safety lead-in, 10 randomized to SOC, and 10 to SOC + IO. There was no difference in median PFS comparing SOC versus SOC + IO (8.8 months (95% CI: 3.3-17.0 months) versus 10.1 months (95% CI: 3.6-16.1 months), respectively; hazard ratio 1.061 [P = .91; 95% CI: 0.380-2.966]). The objective response rate was 50% in both arms. Of patients analyzed, most (8/11) who received SOC + IO developed multifunctional CD4+/CD8+ T-cell responses to cascade antigens MUC1 and/or brachyury, compared to 1/8 who received SOC alone (P = .020). We detected post-treatment changes in immune parameters that were distinct to the SOC and SOC + IO treatment arms. Accrual closed after an unplanned analysis predicted a low likelihood of meeting the primary endpoint.ConclusionsSOC + IO generated multifunctional MUC1- and brachyury-specific CD4+/CD8+ T cells despite concurrent chemotherapy. Although a tumor-directed immune response is necessary for T-cell–mediated antitumor activity, it was not sufficient to improve PFS. Adding agents that increase the number and function of effector cells may be required for clinical benefit. 相似文献
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Josefine Hirschfeld Mohammed Howait Alexandru Movila Marijo Parčina Isabelle Bekeredjian‐Ding James Deschner Søren Jepsen Toshihisa Kawai 《European journal of oral sciences》2017,125(5):345-354
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter‐regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF–GC regulatory dyad in the expression and release of matrix metalloproteinase‐2 (MMP‐2) during periodontitis, in vivo and in vitro. In a Mif‐knockout (KO) mouse model of ligature‐induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin‐6 (IL‐6), MIF, MMP‐2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL‐6 and MMP‐2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor‐alpha (TNF‐α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild‐type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL‐6 concentrations. Systemic GC levels were reduced in WT and Mif‐KO mice during inflammation, with overall lower concentrations in Mif‐KO mice. In vivo and in vitro, MMP‐2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP‐2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP‐2. Our findings further suggest that MIF may regulate systemic GC levels. 相似文献
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Letizia M Creech S Norton E Shanahan M Hedges L 《Journal of pain and symptom management》2004,27(2):114-124
Barriers to adequate pain management in hospice and palliative care settings are an important area of investigation. In this study, a Caregiver Pain Medicine Questionnaire (CPMQ) was developed and psychometrically tested. The CPMQ is a 22-item self-report instrument that measures concern about reporting pain, concern about administering analgesics, and difficulty administering analgesics. One hundred fifty-one caregivers of patients admitted to three Chicagoland hospice agencies participated; these individuals were family members, hired caregivers in the home, or staff nurses in skilled care facilities. While only a small percentage of the caregivers expressed concern about communicating information about the patient's pain, more than a quarter were concerned about addiction, tolerance, and side effects from medications. A fourth of the caregivers had difficulty administering medications because of fear of doing something wrong and difficulty deciding which or what amount of medications to give. Male caregivers and hired caregivers had greater concerns, both about reporting information about the patient's pain and administering medications. Greater concerns were also evident among less educated caregivers, caregivers who worked in blue-collar jobs, and caregivers who were homemakers or retired. Concerns of caregivers in the home were significantly greater than staff nurse caregivers in skilled care facilities only in the belief that pain could not be controlled and concern about addiction. Caregivers who had greater concern about addiction and tolerance, and more difficulty administering medications, rated the patient's pain as less completely controlled. These findings remind hospice staff members of the importance of assessing specific caregiver concerns about medication administration and devising appropriate strategies to address them. 相似文献
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Ivana Cukovic‐Bagic Jelena Dumancic Mirjana Kujundzic Tiljak Iva Drvaric Biserka Boric Vlatko Kopic Ivana Krupic Danko Bakarcic Marijo Budimir Richard R. Welbury 《International journal of paediatric dentistry / the British Paedodontic Society [and] the International Association of Dentistry for Children》2015,25(6):444-450