Differentiation of tumour and inflammation: characterisation of [methyl-3H]methionine (MET) and O-(2-[18F]fluoroethyl)-L-tyrosine (FET) uptake in human tumour and inflammatory cells

Purpose

Previous studies suggest that radiolabelled amino acids could be superior to FDG in differentiating tumour and inflammation. Therefore the aim of this study was to investigate the uptake of FET and MET in human tumour and inflammatory cells and to investigate their uptake kinetics.

Methods

For uptake studies, cells were incubated with 370 kBq FET or 3.7 kBq MET for 15 min. Kinetic studies were performed at variable concentrations of FET and MET. Competitive inhibition studies were done with BCH, MeAIB and L-serine.

Results

All inflammatory cells incorporated more MET than the tumour cells. The uptake of FET, in contrast, was significantly lower in all inflammatory cells than in the tumour cells. In tumour cells the uptake of MET was about five times the uptake of FET. The competitive inhibitors reduced uptake of both tracers to 20–40% in tumour cells and to 70% in inflammatory cells. Kinetic studies showed that MET and FET transport was saturable in all cells except macrophages and followed a Michaelis-Menten kinetic. Highest capacity (V _max) and affinity (K _m) for the uptake of MET was observed in granulocytes. Capacity and affinity for FET uptake were highest in the DHL-4 cells.

Conclusion

In contrast to MET, FET accumulated to a significantly greater extent in tumour cells than in inflammatory cells. The marked differences between tumour and inflammatory cells concerning FET and MET uptake suggest that FET and MET are substrates of different subtypes of the L system.     

Clinical features and diagnosis of the MM2 cortical subtype of sporadic Creutzfeldt-Jakob disease

OBJECTIVE: To describe clinical features and diagnostic tests of the MM2 cortical subtype in sporadic Creutzfeldt-Jakob disease. METHODS: Clinical symptoms, magnetic resonance imaging studies, electroencephalograms, and cerebrospinal fluid markers were studied in 12 patients with genetically and neuropathologically verified sporadic Creutzfeldt-Jakob disease. Histological findings were semiquantitatively evaluated. RESULTS: Compared with classical sporadic Creutzfeldt-Jakob disease, the disease duration was prolonged (median, 14 months). All patients had dementia and early and prominent neuropsychological signs such as spatial disorientation, aphasia, or apraxia. Alzheimer disease was the most frequent initial diagnosis (33%). Increased S100B protein in the cerebrospinal fluid was found in 100%; the 14-3-3 protein test was positive in 91%. Electroencephalograms revealed periodic sharp wave complexes in 42%. T2-weighted magnetic resonance imaging showed basal ganglia hyperintensities in only 1 patient, and cortical hyperintensities were not necessarily present. Severe cortical damage was the most prominent histological feature. CONCLUSIONS: The S100B (100%) and 14-3-3 (91%) protein investigations were the most sensitive diagnostic tests. Prolonged disease duration, dementia as the only typical Creutzfeldt-Jakob disease symptom for a longer time, and low sensitivity of magnetic resonance imaging studies and electroencephalograms make the diagnosis in the MM2 cortical subtype difficult. Therefore, detailed clinical investigation is especially important in this sporadic Creutzfeldt-Jakob disease subtype. We suggest that rapidly progressive dementia with early and prominent neuropsychological deficits in older patients should lead to suspicion of the MM2 cortical subtype even if other neurological deficits are absent. At least some cases of MM2 cortical sporadic Creutzfeldt-Jakob disease may be misdiagnosed as rapidly progressive Alzheimer disease.     

PET/MRI in head and neck cancer: initial experience

Purpose

To evaluate the feasibility of PET/MRI (positron emission tomography/magnetic resonance imaging) with FDG (¹⁸F-fluorodeoxyglucose) for initial staging of head and neck cancer.

Methods

The study group comprised 20 patients (16 men, 4 women) aged between 52 and 81?years (median 64?years) with histologically proven squamous cell carcinoma of the head and neck region. The patients underwent a PET scan on a conventional scanner and a subsequent PET/MRI examination on a whole-body hybrid system. FDG was administered intravenously prior to the conventional PET scan (267?C395?MBq FDG, 348?MBq on average). The maximum standardized uptake values (SUV_max) of the tumour and of both cerebellar hemispheres were determined for both PET datasets. The numbers of lymph nodes with increased FDG uptake were compared between the two PET datasets.

Results

No MRI-induced artefacts where observed in the PET images. The tumour was detected by PET/MRI in 17 of the 20 patients, by PET in 16 and by MRI in 14. The PET/MRI examination yielded significantly higher SUV_max than the conventional PET scanner for both the tumour (p?<?0.0001) and the cerebellum (p?=?0.0009). The number of lymph nodes with increased FDG uptake detected using the PET dataset from the PET/MRI system was significantly higher the number detected by the stand-alone PET system (64 vs. 39, p?=?0.001).

Conclusion

The current study demonstrated that PET/MRI of the whole head and neck region is feasible with a whole-body PET/MRI system without impairment of PET or MR image quality.     

Vertigo during the Epley maneuver and success rate in patients with BPPV

To investigate whether reported vertigo during the Epley maneuver predicts therapeutic success in patients with benign paroxysmal positioning vertigo of the posterior semicircular canal (pc-BPPV). Fifty consecutive adult patients with pc-BPPV, based on a positive Dix–Hallpike test (DHT), were treated with the Epley maneuver and retested after 2 days. Patients were asked to report the presence of vertigo upon assuming each of the four positions of the maneuver. Thirty seven patients (74 %) were treated successfully in one session. Twenty out of 23 patients who reported vertigo at turning the head to the opposite side (2nd position) had a negative DHT on follow-up. These patients had a higher chance of a successful outcome compared to patients who did not report vertigo in the 2nd position (Odds ratio 5.3, 95 % CI: 1.3–22.2, p = 0.022). Report of vertigo at the other positions was not associated with the outcome. Report of vertigo at the second position of a single modified Epley maneuver is associated with therapeutic success.     

‘Part of the job’: male-to-male sexual experiences and abuse of young men working as ‘truck cleaners’ along the highways of Pakistan

As part of a study on the sexual health and social protection needs of men who have sex with men in Pakistan, 11 young men employed as assistants to truckers (‘truck cleaners’) who acknowledged having had sexual experiences with men, were interviewed and their social background and sexual initiation and their subsequent sexual lives were explored. For most truck cleaners, the first instance of sexual contact between the truck cleaner and the driver was forced and happened at an early age. Sex with other men, as well as with women (including sex workers) was widely reported. Drug and alcohol use was common. There is strong potential for HIV and STIs to spread through these sexual networks. Measures to prevent young men from entering into a career as truck helpers should be considered, as well as interventions to improve the health and social situation of those already employed.     

RhoB modifies estrogen responses in breast cancer cells by influencing expression of the estrogen receptor

Introduction

RhoB has been reported to exert positive and negative effects on cancer pathophysiology but an understanding of its role in breast cancer remains incomplete. Analysis of data from the Oncomine database showed a positive correlation between RhoB expression and positivity for both estrogen receptor alpha (ERα) and progesterone receptor (PR).

Methods

This finding was validated by our analysis of a tissue microarray constructed from a cohort of 113 patients and then investigated in human cell models.

Results

We found that RhoB expression in tissue was strongly correlated with ERα and PR expression and inversely correlated with tumor grade, tumor size and count of mitosis. In human breast cancer cell lines, RhoB attenuation was associated with reduced expression of both ERα and PR, whereas elevation of RhoB was found to be associated with ERα overexpression. Mechanistic investigations suggested that RhoB modulates ERα expression, controlling both its protein and mRNA levels, and that RhoB modulates PR expression by accentuating the recruitment of ERα and other major co-regulators to the promoter of PR gene. A major consequence of RhoB modulation was that RhoB differentially regulated the proliferation of breast cancer cell lines. Interestingly, we documented crosstalk between RhoB and ERα, with estrogen treatment leading to RhoB activation.

Conclusion

Taken together, our findings offer evidence that in human breast cancer RhoB acts as a positive function to promote expression of ERα and PR in a manner correlated with cell proliferation.