John F. Greene

Bio: John F. Greene is an academic researcher from Scott & White Hospital. The author has contributed to research in topics: Cholestasis & Biliary hyperplasia. The author has an hindex of 15, co-authored 26 publications receiving 923 citations. Previous affiliations of John F. Greene include Texas A&M University & Texas A&M Health Science Center College of Medicine.

Nephrogenic systemic fibrosis : A review of 6 cases temporally related to gadodiamide injection (omniscan)

Abstract: Objectives: Nephrogenic systemic fibrosis (NSF) is a rare acquired disorder that was first recognized in 1997. Presented is a retrospective review of 6 cases of NSF diagnosed by skin biopsy in our institution during the past 4 years and their relationship to gadodiamide exposure. Methods and Results: Patient age ranged from 23 to 71 years. The onset of symptoms consistent with NSF was between 19 days and 2 months after gadodiamide exposure. Five patients had severe renal impairment and started dialysis around the period of gadodiamide exposure (1 day before the 37 days after contrast administration). The sixth patient had a clotted access at the time of a contrast-enhanced magnetic resonancne venogram and was hence not being adequately dialyzed. The dose of gadodiamide ranged from 16 to 40 mL (0.11 to 0.36 mmol/kg). Despite having normal serum bicarbonate, 5 of the 6 patients had an elevated anion gap metabolic acidosis. Conclusions: In our 6 patients, all had either failing native or transplant kidneys at the time of gadodiamide exposure. The development of NSF was temporally related to gadodiamide injection, suggesting as the etiology dechelation of the agent and thus emphasizing the need for change in clinical practice.

Inhibition of histidine decarboxylase ablates the autocrine tumorigenic effects of histamine in human cholangiocarcinoma

Abstract: Background In several tumours the endogenous activity of histidine decarboxylase (HDC), the enzyme stimulating histamine synthesis, sustains the autocrine trophic effect of histamine on cancer progression. Cholangiocarcinoma is a biliary cancer with limited treatment options. Histamine interacts with four G-protein coupled receptors, H1–H4 histamine receptors (HRs). Objective To determine the effects of histamine stimulation and inhibition of histamine synthesis (by modulation of HDC) on cholangiocarcinoma growth. Methods In vitro studies were performed using multiple human cholangiocarcinoma lines. The expression levels of the histamine synthetic machinery and HRs were evaluated along with the effects of histamine stimulation and inhibition on cholangiocarcinoma proliferation. A xenograft tumour model was used to measure tumour volume after treatment with histamine or inhibition of histamine synthesis by manipulation of HDC. Vascular endothelial growth factor (VEGF) expression was measured in cholangiocarcinoma cells concomitant with the evaluation of the expression of CD31 in endothelial cells in the tumour microenvironment. Results Cholangiocarcinoma cells display (1) enhanced HDC and decreased monoamine oxidase B expression resulting in increased histamine secretion; and (2) increased expression of H1–H4 HRs. Inhibition of HDC and antagonising H1HR decreased histamine secretion in Mz-ChA-1 cells. Long-term treatment with histamine increased proliferation and VEGF expression in cholangiocarcinoma that was blocked by HDC inhibitor and the H1HR antagonist. In nude mice, histamine increased tumour growth (up to 25%) and VEGF expression whereas inhibition of histamine synthesis (by reduction of HDC) ablated the autocrine stimulation of histamine on tumour growth (∼80%) and VEGF expression. No changes in angiogenesis (evaluated by changes in CD31 immunoreactivity) were detected in the in vivo treatment groups. Conclusion The novel concept that an autocrine loop (consisting of enhanced histamine synthesis by HDC) sustains cholangiocarcinoma growth is proposed. Drug targeting of HDC may be important for treatment of patients with cholangiocarcinoma.

Quantification of gadolinium in nephrogenic systemic fibrosis: re-examination of a reported cohort with analysis of clinical factors.

Abstract: Background Nephrogenic systemic fibrosis (NSF) has been associated with exposure to gadolinium-based contrast agent (GdCA) used in medical imaging Objective We sought to quantify levels of gadolinium in affected skin of patients with NSF and correlate the levels to clinical and laboratory parameters Methods Skin biopsy specimens were analyzed using inductively coupled plasma mass spectroscopy (ICP-MS) and the micrograms of gadolinium per gram (μg/g) of dry tissue were determined Clinical and laboratory data were obtained through retrospective chart review Pearson correlation coefficients were used to correlate tissue gadolinium levels with various parameters Results Six patients from a prior cohort were analyzed for gadolinium in affected skin The mean amount of gadolinium in affected skin of NSF patients was 3201 μg/g No gadolinium was found in limited control tissue from patients unexposed to GdCA or in patients exposed to such agents, but without disease Higher levels of gadolinium in skin correlated with younger age, lower body weight, lower corrected serum calcium levels, and lower erythropoietin dosing Limitations The study was limited by the small number of cases and by the retrospective nature of the data and skin samples Conclusion Gadolinium is present in substantial amounts within the skin of patients with NSF Quantification of gadolinium in tissue using ICP-MS may facilitate our understanding of the disease

The NCI60 human tumour cell line anticancer drug screen

Abstract: The US National Cancer Institute (NCI) 60 human tumour cell line anticancer drug screen (NCI60) was developed in the late 1980s as an in vitro drug-discovery tool intended to supplant the use of transplantable animal tumours in anticancer drug screening. This screening model was rapidly recognized as a rich source of information about the mechanisms of growth inhibition and tumour-cell kill. Recently, its role has changed to that of a service screen supporting the cancer research community. Here I review the development, use and productivity of the screen, highlighting several outcomes that have contributed to advances in cancer chemotherapy.

Cell Cycle Proteins as Promising Targets in Cancer Therapy

Abstract: Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.

Cyclin-dependent kinase pathways as targets for cancer treatment.

Abstract: Cyclin-dependent kinases (cdks) are critical regulators of cell cycle progression and RNA transcription. A variety of genetic and epigenetic events cause universal overactivity of the cell cycle cdks in human cancer, and their inhibition can lead to both cell cycle arrest and apoptosis. However, built-in redundancy may limit the effects of highly selective cdk inhibition. Cdk4/6 inhibition has been shown to induce potent G1 arrest in vitro and tumor regression in vivo; cdk2/1 inhibition has the most potent effects during the S and G2 phases and induces E2F transcription factor-dependent cell death. Modulation of cdk2 and cdk1 activities also affects survival checkpoint responses after exposure to DNA-damaging and microtubule-stabilizing agents. The transcriptional cdks phosphorylate the carboxy-terminal domain of RNA polymerase II, facilitating efficient transcriptional initiation and elongation. Inhibition of these cdks primarily affects the accumulation of transcripts with short half-lives, including those encoding antiapoptosis family members, cell cycle regulators, as well as p53 and nuclear factor-kappa B-responsive gene targets. These effects may account for apoptosis induced by cdk9 inhibitors, especially in malignant hematopoietic cells, and may also potentiate cytotoxicity mediated by disruption of a variety of pathways in many transformed cell types. Current work is focusing on overcoming pharmacokinetic barriers that hindered development of flavopiridol, a pan-cdk inhibitor, as well as assessing novel classes of compounds potently targeting groups of cell cycle cdks (cdk4/6 or cdk2/1) with variable effects on the transcriptional cdks 7 and 9. These efforts will establish whether the strategy of cdk inhibition is able to produce therapeutic benefit in the majority of human tumors.

Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Abstract: Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.

ACR Guidance Document for Safe MR Practices: 2007

Abstract: E. Kanal is a consultant for, is a member of the speakers bureau of, and provides research support for Bracco Diagnostics and GE Healthcare; is a member of the speakers bureau of and provides research support for Siemens Medical Solutions; and provides research support for Berlex and Medtronic. T. Gilk is a consultant for Mednovus, Inc. J. R. Gimbel provides research support for St. Jude Medical, Medtronic, and Biotronik. J. Nyenhuis is a consultant for and provides research support to Medtronics. J. Weinreb is a consultant and member of the speakers bureau for GE Healthcare.