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Ahmed Elhassanny Rene Escobedo Daniel Ladin Colin Burns Rukiyah Van Dross 《Oncotarget》2020,11(52):4788
Metastatic melanoma is the most deadly skin neoplasm in the United States. Outcomes for this lethal disease have improved dramatically due to the use of both targeted and immunostimulatory drugs. Immunogenic cell death (ICD) has emerged as another approach for initiating antitumor immunity. ICD is triggered by tumor cells that display damage-associated molecular patterns (DAMPs). These DAMP molecules recruit and activate dendritic cells (DCs) that present tumor-specific antigens to T cells which eliminate neoplastic cells. Interestingly, the expression of DAMP molecules occurs in an endoplasmic reticulum (ER) stress-dependent manner. We have previously shown that ER stress was required for the cytotoxic activity of the endocannabinoid metabolite, 15-deoxy, Δ12,14 prostamide J2 (15dPMJ2). As such, the current study investigates whether 15dPMJ2 induces DAMP signaling in melanoma. In B16F10 cells, 15dPMJ2 caused a significant increase in the cell surface expression of calreticulin (CRT), the release of ATP and the secretion of high-mobility group box 1 (HMGB1), three molecules that serve as surrogate markers of ICD. 15dPMJ2 also stimulated the cell surface expression of the DAMP molecules, heat shock protein 70 (Hsp70) and Hsp90. In addition, the display of CRT and ATP was increased by 15dPMJ2 to a greater extent in tumorigenic compared to non-tumorigenic melanocytes. Consistent with this finding, the activation of bone marrow-derived DCs was upregulated in co-cultures with 15dPMJ2-treated tumor compared to non-tumor melanocytes. Moreover, 15dPMJ2-mediated DAMP exposure and DC activation required the electrophilic cyclopentenone double bond within the structure of 15dPMJ2 and the ER stress pathway. These results demonstrate that 15dPMJ2 is a tumor-selective inducer of DAMP signaling in melanoma. 相似文献
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Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery 总被引:5,自引:0,他引:5
Arthur M. Carlin M.D. D. Sudhaker Rao MB B.S. F.A.C.P. F.A.C.E. Ali M. Meslemani M.D. Jeffrey A. Genaw M.D. Nayana J. Parikh Shiri Levy M.D. Arti Bhan M.D. Gary B. Talpos M.D. 《Surgery for obesity and related diseases》2006,2(2):696-103
BACKGROUND: Abnormalities in calcium and vitamin D metabolism have been reported after bariatric surgery. The purpose of this study was to evaluate vitamin D nutritional status among morbidly obese patients before gastric bypass surgery. METHODS: We prospectively studied 279 morbidly obese patients seeking gastric bypass surgery for vitamin D nutritional status as assessed by serum 25-hydroxyvitamin D level. In addition, serum samples were analyzed for calcium, alkaline phosphatase (AP), intact parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D. RESULTS: Mean patient age was 43 +/- 9 years; 87% of the study patients were women, and 72% were white. Serum calcium and AP levels were normal in 88% and 89% of the patients, respectively. Vitamin D depletion, defined as serum 25-hydroxyvitamin D level 相似文献
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LESLEY BOULTON MB CHB FRACO DO Ophthalmologist 《Clinical & experimental ophthalmology》1986,14(4):365-371
The Low Vision Clinic at the Palmerston North Hospital has now been oerating for 70 years. Over the course of these ten years a number of factors have emerged which can be as readily applied to general ophthalmological practice as to low vision practice. The philosophy of low vision care is one of which all ophthalmologists should be aware and includes factors to be taken into account when dealing with children, people in the workplace, and everyday factors involved in daily living activities, all of which are equally relevant in routine ophthalmological practice. This paper endeavours to share some thoughts on these factors and also discusses means by which the visually handicapped can be helped in areas where specialist low vision services are not readily available. 相似文献
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Comparison of trichloroethylene and enflurane as adjuncts to nitrous oxide and relaxant anaesthesia 总被引:1,自引:0,他引:1
Forty women who underwent gynaecological surgery were randomly allocated to receive trichloroethylene, enflurane, or enflurane plus fentanyl as adjuncts to nitrous oxide/relaxant anaesthesia with controlled ventilation. No serious cardiac dysrhythmias were seen in any group. Each patient was observed postoperatively for 4 hours by a nurse blind to the technique used, and questioned at 24 hours by a similarly blinded anaesthetist. Recovery after trichloroethylene was not significantly prolonged although postoperative analgesia by visual analogue was better, opiate analgesia was required less frequently and there was less nausea and vomiting than in either of the enflurane groups. We argue for the continued use of trichloroethylene by this technique, because it costs one hundred times less than enflurane and because of the potential morbidity of the postoperative opiate dosage required after enflurane. 相似文献
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E.Paul Kirk MB BS J. Santa MD T. Heckler MBA M. Collins MD 《American journal of obstetrics and gynecology》1998,178(6):1222-1228
OBJECTIVE: Our purpose was to assess whether legislative action influenced the role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An observational study was performed on the basis of a questionnaire sent to 410 obstetrician-gynecologists and 27 medical directors of managed-care organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical directors who responded, there was agreement as to the content of primary care, but a minority (38%) of obstetrician-gynecologists identified themselves as primary care providers. A minority of medical directors (35%) felt that obstetrician-gynecologists should serve in that role. Both obstetrician-gynecologists and medical directors felt that legislation had little impact. CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in primary care appears to be the result of an uneasiness with accepting a more comprehensive role in patient management and gatekeeping. They appear comfortable with the more traditional roles but feel that training and experience has not prepared them well for the management of more complex medical problems. (Am J Obstet Gynecol 1998;178:1222-8.) 相似文献
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Patients'attitudes to rectal drug administration 总被引:2,自引:0,他引:2
One hundred adult patients attending for day case surgery were surveyed by anonymous questionnaire in order to determine their attitudes to rectal drug administration. Fifty four patients did not want an analgesic drug (diclofenac sodium) administered rectally whilst under anaesthesia, all preferring to take it orally if available. Ninety eight patients thought that drugs administered per rectum should always be discussed with them beforehand and a few had very strong feelings about this route of administration. We suggest that prescribers of rectal diclofenac should always discuss it with patients pre-operatively. Whilst many are happy to have suppositories, some young patients are sensitive about this and prefer to take such medication by mouth. 相似文献