Determination of optimal planning target volume margins in patients with gynecological cancer

PurposeTo define optimal planning target volume (PTV) margins for intensity modulated radiotherapy (IMRT) ± knee-heel support (KHS) in patients treated with adjuvant radiotherapy.MethodsComputed tomography (CT) scans ± KHS of 10 patients were taken before and at 3rd and 5th week of treatment, fused and compared with initial IMRT plans.ResultsA PTV margin of 15 mm in anteroposterior (AP) and superoinferior (SI) directions and 5 mm in lateral directions were found to be adequate without any difference between ± KHS except for the SI shifts in CTV-primary at the 3rd week. Five mm margin for iliac CTV was found to be inadequate in 10–20% of patients in SI directions however when 7 mm margin was given for iliac PTV, it was found to be adequate. For presacral CTV, it was found that the most striking shift of the target volume was in the direction of AP. KHS caused significantly less volume of rectum and bladder in the treated volume.ConclusionsPTV margin of 15 mm in SI and AP, and 5 mm in lateral directions for CTV-primary were found to be adequate. A minimum of 7 mm PTV margin should be given to iliac CTV. The remarkable shifting in presacral CTV was believed to be due to the unforeseen hip malposition of obese patients. The KHS seems not to provide additional beneficial effect in decreasing the shifts both in CTV-primary and lymphatic, however it may have a beneficial effect of decreasing the OAR volume in PTV margins.     

LncRNA NEAT1 promotes docetaxel resistance in prostate cancer by regulating ACSL4 via sponging miR-34a-5p and miR-204-5p

Docetaxel resistance remains one of the main problems in clinical treatment of metastatic prostate cancer (PCa). Previous studies identified differently expressed lncRNAs in docetaxel-resistant PCa cell lines, while the potential mechanisms were still unknown. In the present study, we found NEAT1 was expressed at high levels in docetaxel-resistant PCa clinical samples and related cell lines. When knockdown NEAT1, cell proliferation and invasion in docetaxel-resistant PCa cells in vitro and in vivo were downregulated. Our further researches explained that NEAT1 exerts oncogenic function in PCa by competitively ‘sponging’ both miR-34a-5p and miR-204-5p. Inhibition of miR-34a-5p or miR-204-5p expression mimics the docetaxel-resistant activity of NEAT1, whereas ectopic expression of miR-34a-5p or miR-204-5p attenuates the anti-drug function of NEAT1 in PCa cells. Besides, we also found ACSL4 is a target of both miR-34a-5p and miR-204-5p, and ACSL4 was also inhibited by miR-34a-5p and miR-204-5p. Moreover, suppression of miR-34a-5p or/and miR-204-5p greatly restrained the expression of ACSL4 upon NEAT1 overexpression. Joint expression of miR-34a-5p and miR-204a-5p synergistically decreased the expression of ASCL4, indicating miR-34a-5p and miR-204a-5p collaboratively inhibit the expression of ACSL4. Innovatively, we concluded that NEAT1 contributes to the docetaxel resistance by increasing ACSL4 via sponging miR-34a-5p and miR-204-5p in PCa cells.     

Allosteric interference in oncogenic FLI1 and ERG transactions by mithramycins

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Tampering with cancer chemoresistance by targeting the TGM2-IL6-autophagy regulatory network

Macroautophagy/autophagy is a well-established process involved in maintaining cellular homeostasis, but its role in cancer is complex and even controversial. Many studies have reported a correlative relationship between increased autophagy and evolving cancer cells under stress conditions such as nutrient or oxygen deprivation; however, there has been a lack of a plausible mechanistic link to properly target the autophagy process in the context of this microenvironment. We recently unveiled a positive regulatory loop involving TGM2 (transglutaminase 2)-NFKB/NF-κB signaling, IL6 and autophagy in cancer using mantle cell lymphoma (MCL) as a model system. These pathways are functionally connected to each other, thereby promoting malignant B cell survival and leading to enhanced lymphoma progression both in mice and in patients. Disruption of this network could provide an opportunity to increase the efficacies of current therapies and to reduce MCL drug resistance.     

Autofluorescence imaging for recurrence detection in skin cancer postoperative scars

This clinical study is a first attempt to use autofluorescence for recurrence diagnosis of skin cancer in postoperative scars. The proposed diagnostic parameter is based on a reduction in scar autofluorescence, evaluated in the green spectral channel. The validity of the method has been tested on 110 postoperative scars from 56 patients suspected of non‐melanoma skin cancer, with eight patients (13 scars) available for the repeated examination. The recurrence diagnosis within a scar has been made after two subsequent autofluorescence check‐ups, representing the temporal difference between the scar autofluorescence amplitudes as a vector. The recognition of recurrence has been discussed to represent the significant deviations from the value of vector angle θ. This new autofluorescence‐based method can be easily integrated into the postoperative monitoring of surgical scars and can help diagnose the recurrence of skin cancer from the early stage of scar development.     

Localization of vanadium-containing particles in the lungs of uranium/vanadium miners

Several geological formations of the Utah-Colorado mining region mined for uranium ore during and after World War II had been mined earlier for vanadium. Therefore, most miners and millers from that region were exposed to those metals’ ores or tailings at one time or another. Preliminary investigation to determine uranium and vanadium retained in the lungs of a former uranium miner and miller from this region, who died of lung cancer (mesothelioma), showed a high nonuniform distribution of vanadium. This observation led to the hypothesis that the vanadium content in the lungs could be associated with inhaled particles. Further examination of spectra of characteristic X-rays obtained by scanning particle-induced X-ray emission (microPIXE) of an autopsy sample of this lung indicated that vanadium was indeed present in localized sites within the 20-μm spatial resolution of the proton beam. This work points out that the microPIXE-RBS (Rutherford backscattering) test for vanadium can be used for site localization of inhaled particles retained in the lungs. Further studies are in progress to: (i) locate uranium-bearing particles in lung tissues of former uranium miners and millers; and (ii) evaluate the local doses of alpha radiation received from these particles.