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1.
Keith S. Hansen Hila Ghersin Merisa Piper Mehdi Tavakol Brian Lee Laura J. Esserman John P. Roberts Chris Freise Nancy L. Ascher Rita A. Mukhtar 《American journal of transplantation》2021,21(9):3014-3020
Kidney transplantation reduces mortality in patients with end stage renal disease (ESRD). Decisions about performing kidney transplantation in the setting of a prior cancer are challenging, as cancer recurrence in the setting of immunosuppression can result in poor outcomes. For cancer of the breast, rapid advances in molecular characterization have allowed improved prognostication, which is not reflected in current guidelines. We developed a 19-question survey to determine transplant surgeons’ knowledge, practice, and attitudes regarding guidelines for kidney transplantation in women with breast cancer. Of the 129 respondents from 32 states and 14 countries, 74.8% felt that current guidelines are inadequate. Surgeons outside the United States (US) were more likely to consider transplantation in a breast cancer patient without a waiting period (p = .017). Within the US, 29.2% of surgeons in the Western region would consider transplantation without a waiting period, versus 3.6% of surgeons in the East (p = .004). Encouragingly, 90.4% of providers surveyed would consider eliminating wait-times for women with a low risk of cancer recurrence based on the accurate prediction of molecular assays. These findings support the need for new guidelines incorporating individualized recurrence risk to improve care of ESRD patients with breast cancer. 相似文献
2.
Yftach Gepner Nir Goldstein Ilan Shelef Dan Schwarzfuchs Hila Zelicha Anat Yaskolka Meir Gal Tsaban Ehud Grossman 《Journal of general internal medicine》2021,36(8):2300
BackgroundObesity is associated with elevated blood pressure (BP). In patients with obesity and hypertension, weight loss lowers BP, but the long-term effect of weight loss on BP is less clear.ObjectiveWe aimed to assess the effect of long-term weight loss intervention on BP in normotensive and hypertensive subjects.DesignRandomized controlled trial.ParticipantsTwo hundred seventy-eight subjects (mean age 47.9 ± 9.3 years, 89% male, 56% hypertensive) with abdominal obesity or elevated serum triglycerides and low high-density lipoprotein cholesterol were recruited.InterventionEighteen-month weight loss intervention.Main MeasuresBody weight and BP were measured at baseline, after 6 and 18 months.ResultsAfter 6 months of intervention, in the weight loss phase, body mass index (BMI) decreased by an average of −2.2±1.5 kg/m2 (p<0.001) and both diastolic BP (DBP) and systolic BP (SBP) decreased by −2.1±8.8 mmHg and −2.3±12.9 mmHg, respectively (p<0.01 for both). The change in BMI was similar in normotensive and hypertensive subjects (−2.0±1.6 and −2.3±1.5, p = 0.246). However, DBP and SBP decreased significantly (−5.2±7.1 mmHg and −6.2±12.5 mmHg, respectively, p<0.001 for both) in hypertensive subjects, and increased in normotensive subjects (1.8±9.3 mmHg, p = 0.041 and 2.7±11.7 mmHg, p = 0.017, respectively). After 18 months, in the weight maintenance phase, BMI slightly increased (0.9±1.3 kg/m2, p<0.001) but remained significantly lower than at baseline (p<0.0001). Unlike BMI, DBP and SBP increased significantly in hypertensive subjects (p<0.001) and returned almost to baseline levels.ConclusionWeight-loss intervention reduced BP in hypertensive patients, but this was not maintained in the long run.Clinical Trial RegistrationClinicalTrials.gov Identifier: KEY WORDS: NCT01530724blood pressure, weight loss, body mass index, hypertension, randomized controlled trial 相似文献
3.
Anat Klein Hila Schwartz Orit Sagi‐Assif Tsipi Meshel Sivan Izraely Shlomit Ben Menachem Roman Bengaiev Amir Ben‐Shmuel Clara Nahmias Pierre‐Olivier Couraud Isaac P Witz Neta Erez 《The Journal of pathology》2015,236(1):116-127
Melanoma is the leading cause of skin cancer mortality. The major cause of melanoma mortality is metastasis to distant organs, frequently to the brain. The microenvironment plays a critical role in tumourigenesis and metastasis. In order to treat or prevent metastasis, the interactions of disseminated tumour cells with the microenvironment at the metastatic organ have to be elucidated. However, the role of brain stromal cells in facilitating metastatic growth is poorly understood. Astrocytes are glial cells that function in repair and scarring of the brain following injury, in part via mediating neuroinflammation, but the role of astrocytes in melanoma brain metastasis is largely unresolved. Here we show that astrocytes can be reprogrammed by human brain‐metastasizing melanoma cells to express pro‐inflammatory factors, including the cytokine IL‐23, which was highly expressed by metastases‐associated astrocytes in vivo. Moreover, we show that the interactions between astrocytes and melanoma cells are reciprocal: paracrine signalling from astrocytes up‐regulates the secretion of the matrix metalloproteinase MMP2 and enhances the invasiveness of brain‐metastasizing melanoma cells. IL‐23 was sufficient to increase melanoma cell invasion, and neutralizing antibodies to IL‐23 could block this enhanced migration, implying a functional role for astrocyte‐derived IL‐23 in facilitating the progression of melanoma brain metastasis. Knocking down the expression of MMP2 in melanoma cells resulted in inhibition of IL‐23‐induced invasiveness. Thus, our study demonstrates that bidirectional signalling between melanoma cells and astrocytes results in the formation of a pro‐inflammatory milieu in the brain, and in functional enhancement of the metastatic potential of disseminated melanoma cells. Copyright © 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. 相似文献
4.
Yael?C?CohenEmail author Tsila?Zuckerman Moshe?Yeshurun Galit?Perez Hila?Magen Israel?Henig Itai?Levi Liat?Shargian Svetlana?Trestman Uri?Rouvio Elizabeth?Naparstek Eti?Ganon-Elazar Irit?Avivi Ron?Ram 《Annals of hematology》2017,96(2):271-278
We aimed to test the efficacy and toxicity of autologous hematopoietic cell transplant (HCT) in Multiple Myeloma (MM) patients aged ≥65 years compared to patients aged 60–64. Two hundred twenty consecutive patients (age ≥65, n = 87) with MM aged 60 and above, who underwent HCT as part of an upfront MM treatment, at four Israeli centers between 2000 and 2014 were included. A melphalan dose of 200 mg/m2 was more frequent in the 60–64 age group vs. the ≥65 age group (77 vs. 57%, p = 0.002). There were no differences between groups in median day of neutrophil engraftment, incidence of infections, grades 3–4 mucositis, cardiovascular events, or non-relapse mortality at 100 days post HCT (4.7, vs. 5%, p = 0.9). A similar rate of improvement in response level was observed (36, vs. 35%, p = 0.87). At 3 years post HCT progression-free survival (PFS) was higher in the 60–64 age group (42 vs. 29%, p = 0.04); however, it was no longer so after adjustment for disease status prior to HCT (p = 0.49). In a Multivariate analysis, melphalan doses and age did not predict PFS. There was no difference in overall survival (OS) between age groups (p = 0.2). We conclude that toxicity profile, response, PFS, and OS of HCT in aged ≥65 patients with myeloma is similar to patients aged 60–64. 相似文献
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Barash H Gross E Edrei Y Pappo O Spira G Vlodavsky I Galun E Matot I Abramovitch R 《Hepatology (Baltimore, Md.)》2008,48(4):1232-1241
Liver diseases and regeneration are associated with hemodynamic changes denoting pathological alterations. Determining and monitoring physiological and pathological liver changes is essential for diagnostic and therapeutic objectives. Our aim was to determine the feasibility of functional magnetic resonance imaging (fMRI) during hypercapnia and hyperoxia for monitoring liver pathology. Liver fMRI images were acquired in rodents following acute bleeding, partial hepatectomy, and fibrosis. Results were quantitated and confirmed by histology. Changes induced by hyperoxia and hypercapnia following hemorrhage significantly correlated with the percentage of blood loss, reflecting lower liver perfusion and diminished vessel responsiveness to gas saturation. Hepatectomy resulted in an early decline in signal intensity changes due to hyperoxia, suggesting a decrease in liver perfusion and blood content. Following hepatectomy, signal intensity changes due to hypercapnia increased, signifying a change in liver perfusion from a mainly portal to a more arterial source. Two weeks after induction of fibrosis, signal intensity changes due to hypercapnia became much lower and those due to hyperoxia were much higher than those in normal livers, reflecting the increased perfusion due to the inflammatory process as confirmed by histologic analysis. With fibrosis progression, signal intensity changes induced by hypercapnia and hyperoxia were gradually attenuated, indicating structural and functional alterations of the liver vasculature during fibrosis. CONCLUSION: In various liver pathologies, fMRI response to hypercapnia and hyperoxia is sensitive to changes in liver hemodynamic status involved in hepatic damage or recovery; thus, this technique may offer an additional noninvasive diagnostic tool for evaluation and follow-up of liver diseases by means of examining perfusion-related alterations. 相似文献
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George Pentheroudakis Yael Spector Dimitrios Krikelis Vassiliki Kotoula Eti Meiri Vassiliki Malamou-Mitsi George Fountzilas Mats Sanden Nicholas Pavlidis Hila Benjamin Ranit Aharonov 《Clinical & experimental metastasis》2013,30(4):431-439
No data exist on biologic differences between Cancer of unknown primary (CUP) and metastatic solid tumors of known primary site. We assigned a primary tissue of origin in 40 favorable CUP patients (A: serous peritoneal carcinomatosis n = 14, B: axillary adenocarcinoma n = 8, C: upper squamous cervical adenopathy n = 18) by means of a 64-microRNA assay. Subsequently, we profiled the expression of 733 microRNAs (miRs) in the CUP cases and compared results with metastases from 20 ovarian carcinomas, 10 breast adenocarcinomas, 20 squamous head neck or lung tumors. In the Peritoneal CUP versus Ovarian (Known Primary Metastases) KPM comparison, a total of 12 miR were significantly differentially expressed: higher than twofold expression difference in CUP was seen only for miR-513a-5p (3.7-fold upregulated) and miR-483-5p (2.5-fold upregulated), while miR-708 exhibited a twofold downregulation. In the Breast CUP versus Breast KPM comparison, only miR-29c that were downregulated in CUP by 2.7-fold satisfied the FDR threshold. miR-30e and miR-27b, downregulated in ovarian CUPs versus KPMs, were also non-significantly downregulated in breast CUP by 2.0- and 1.4-fold respectively. Six miRs, which belong to the 17–92 oncocluster showed a trend of upregulation in Breast CUP versus Breast KPM cases. A CUP signature remains elusive. 相似文献
10.
Itai Spector Yael Zilberstein Adi Lavy Olga Genin Hila Barzilai-Tutsch Ana Bodanovsky Orna Halevy Mark Pines 《The American journal of pathology》2013,182(3):905-916
Apolipoprotein E4 (APOE4) genotype is the strongest genetic risk factor for late-onset Alzheimer disease and confers a proinflammatory, neurotoxic phenotype to microglia. Here, we tested the hypothesis that bone marrow cell APOE genotype modulates pathological progression in experimental Alzheimer disease. We performed bone marrow transplants (BMT) from green fluorescent protein–expressing human APOE3/3 or APOE4/4 donor mice into lethally irradiated 5-month-old APPswe/PS1ΔE9 mice. Eight months later, APOE4/4 BMT–recipient APPswe/PS1ΔE9 mice had significantly impaired spatial working memory and increased detergent-soluble and plaque Aβ compared with APOE3/3 BMT–recipient APPswe/PS1ΔE9 mice. BMT-derived microglia engraftment was significantly reduced in APOE4/4 recipients, who also had correspondingly less cerebral apoE. Gene expression analysis in cerebral cortex of APOE3/3 BMT recipients showed reduced expression of tumor necrosis factor-α and macrophage migration inhibitory factor (both neurotoxic cytokines) and elevated immunomodulatory IL-10 expression in APOE3/3 recipients compared with those that received APOE4/4 bone marrow. This was not due to detectable APOE-specific differences in expression of microglial major histocompatibility complex class II, C-C chemokine receptor (CCR) type 1, CCR2, CX3C chemokine receptor 1 (CX3CR1), or C5a anaphylatoxin chemotactic receptor (C5aR). Together, these findings suggest that BMT-derived APOE3-expressing cells are superior to those that express APOE4 in their ability to mitigate the behavioral and neuropathological changes in experimental Alzheimer disease.Humans uniquely have three different apolipoprotein E (APOE) alleles (ɛ2, ɛ3, and ɛ4). APOE4 is the single greatest genetic risk factor for late-onset Alzheimer disease (AD), and there is a gene dosage effect.1 However, genetic association does not inform function/pathogenesis. Multiple mechanisms have been postulated that predominantly focus on production, metabolism, or clearance of amyloid-β (Aβ) and that are variably supported by multiple observations, including: i) APOE genotype is strongly related to Aβ levels in brain and cerebrospinal fluid of AD patients2,3; ii) modulation of apolipoprotein E (apoE) protein levels in brain results in alterations of Aβ burden4,5; iii) Aβ degradation is at least partially apoE dependent6,7; and iv) Aβ clearance is differentially modulated by apoE isoforms, with APOE4 mice exhibiting reduced central and peripheral Aβ clearance compared with APOE3 mice.8–10 Aβ degradation and clearance is at least partially dependent on microglia, the innate immune effector cells of the brain. Microglia have migratory and phagocytic capacity, are increased in the vicinity of Aβ plaques, and phagocytose Aβ.11–13
APOE genotype modulates central nervous system innate immune function in culture,14 including astrocyte and microglia elaboration of cytokines and chemokines,15,16 microglia production of reactive oxygen species,17 microglia-mediated paracrine neurotoxicity,18 microglia migration,19 and other functions.20 However, the specific contribution of microglial APOE genotype to AD pathophysiology in vivo is largely unknown.To address this critical question and to test a potential therapeutic application, we used the fact that bone marrow transplantation (BMT) results in the gradual replacement of endogenous (host) microglia (to the near exclusion of other cell types) with microglia derived from donor marrow, in both wild-type mice and transgenic mouse models of AD.21–24 We used targeted-replacement (TR) APOE mice homozygous for either the APOE3 or APOE4 gene inserted into the mouse APOE regulatory elements25,26 that coexpressed green fluorescent protein (GFP). We transplanted whole bone marrow (BM) isolated from TR APOE3/3;GFP or TR APOE4/4;GFP mice into lethally irradiated APPswe/PS1ΔE9 mice to determine the specific role of microglial APOE genotype in the pathological progression of AD. 相似文献