Palliative radiation is often used to abate pain and prevent bone fractures in patients with metastatic cancer. Hypofractionation, meaning delivery of larger doses of radiation in each treatment ...session (fraction), has become the standard of care in most cases. It not only reduces the burden on the medical system and facilitates the relief of symptoms but also enables the maintenance of the continuity of systemic therapy. Radiation recall phenomenon (RRP) is an acute inflammatory reaction in previously irradiated tissues that is provoked by chemotherapeutic drug administration. The incidence, severity, and prognosis of RRP following hypofractionated radiation therapy have not been studied. The symptoms of RRP depend on the radiation field, with the greatest concern associated with mucosal and dermal damage, though other symptoms have also been reported. Here, we describe a case of a 41-year-old woman with metastatic breast cancer (hormone receptor-positive, HER2/neu negative), who received palliative radiation to four other fields along the course of her disease, before her presentation with isolated myonecrosis of the thigh muscles. This RRP occurred four months following the last of two fractions of 8 Gy radiation to this region, given three months apart, and after six courses of cisplatin + gemcitabine. The symptoms improved with cessation of gemcitabine and prolonged administration of non-steroidal anti-inflammatory medications.
The implementation of angiogenic gene therapy at clinics is hindered by the transience of the therapeutic effect. Recruiting vascular wall smooth muscle cells, a process termed 'maturation', can ...stabilize newly formed vessels.
To induce angiogenesis followed by vessel maturation in a murine ischemic limb model by endothelial cell-specific promoter regulated expression of vascular endothelial growth factor (VEGF) and platelet-derived growth factor-BB (PDGF-BB).
We constructed adenoviral vectors containing angiogenic factors VEGF and PDGF-B regulated by a modified preproendothelin-1 (PPE-1-3x) promoter and investigated their angiogenic effect in a murine ischemic limb model.
VEGF gene therapy increased perfusion and the vessel density in the limb shortly after expression with PPE-1-3x promoter or cytomegalovirus (CMV) promoter vectors, but only PPE-1-3xVEGF treatment exhibited a sustained effect. Expression of PDGF-B by PPE-1-3x promoter resulted in morphological maturation of the vasculature and further increased the perfusion, while nonspecific expression of PDGF-B with CMV promoter had no therapeutic effect. Regulation of dual therapy with VEGF and PDGF-B by PPE-1-3x promoter resulted in an early-onset, sustained angiogenic effect accompanied by vessel maturation.
Systemic gene therapy with the angiogenic factors VEGF and PDGF-B under angiogenic- endothelial cell-specific regulation was effective in inducing functionally and morphologically mature vasculature.
Cancer is a complex disease that involves aberrant gene expression regulation. Discriminating the modified expression patterns driving tumor biology from the many that have no or little contribution ...is important for understanding cancer molecular basis. Recurrent deregulation patterns observed in multiple cancer types are enriched for such driver events. Here, we studied splicing alterations in hundreds of matched tumor and normal RNA-seq samples of eight solid cancer types. We found hundreds of cassette exons for which splicing was altered in multiple cancer types and identified a set of highly frequent altered splicing events. Specific splicing regulators, including RBFOX2, MBNL1/2 and QKI, appear to account for many splicing alteration events in multiple cancer types. Together, our results provide a first global analysis of regulated splicing alterations in cancer and identify common events with a potential causative role in solid tumor development.
Erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor is a standard post chemotherapy advanced treatment line for metastatic urothelial carcinoma harboring FGFR2/3 genomic alterations. It ...was approved based on a phase 2 clinical trial, revealing a 40% response rate, and 13.8 months overall survival. These FGFR genomic alterations are uncommon. Thus, real-world data on erdafitinb use is scant. We herein describe erdafitinib treatment outcome in a real world patient cohort.
We retrospectively reviewed the data of patients treated with erdafitinib from 9 Israeli medical centers.
Twenty-five patients with metastatic urothelial carcinoma (median age 73, 64% male, 80% with visceral metastases) were treated with erdafitinib between January 2020 to October 2022. A clinical benefit (complete response 12%, partial response 32%, stable disease 12%) was seen in 56%. Median progression-free survival was 2.7 months, and median overall survival 6.73 months. Treatment related toxicity ≥ grade 3 occurred in 52%, and 32% discontinued therapy due to adverse events.
Erdafitinib therapy is associated with a clinical benefit in the real world setting, and associated with similar toxicity as reported in prospective clinical trials.
Light intensities that limit electron flow induce rapid degradation of the photosystem II (PSII) reaction center D1 protein. The mechanism of this phenomenon is not known. We propose that at low ...excitation rates back electron flow and charge recombination between the QB radical or QA radical semiquinone acceptors and the oxidized S2,3 states of the PSII donor side may cause oxidative damage via generation of active oxygen species. Therefore, damage per photochemical event should increase with decreasing rates of PSII excitation. To test this hypothesis, the effect of the dark interval between single turnover flashes on the inactivation of water oxidation, charge separation and recombination, and the degradation of D1 protein were determined in spinach thylakoids. PSII inactivation per flash increases as the dark interval between the flashes increases, and a plateau is reached at dark intervals, allowing complete charge recombination of the QB radical/S2,3 or QA radical/S2 states (about 200 and 40 s, respectively). At these excitation rates: (i) 0.7% and 0.4% of PSII is inactivated and 0.4% and 0.2% of the D1 protein is degraded per flash, respectively, and (ii) the damage per flash is about 2 orders of magnitude higher than that induced by equal amount of energy delivered by excess continuous light. No PSII damage occurs if flashes are given in anaerobic conditions. These results demonstrate that charge recombination in active PSII is promoted by low rates of excitation and may account for a the high quantum efficiency of the rapid turnover of the D1 protein induced by limiting light
The compression of extended, coded sequences allows for laser ranging measurements with low peak power levels. Previous realizations of this approach were restricted by additive noise of direct, ...incoherent detection. In this work we bring together pulse sequence coding and optical coherent detection to achieve very high sensitivity. Collected sequences with an overall energy equivalent to only 800 photons are successfully compressed. The observed sensitivity agrees with analytic predictions. Compared with incoherent detection, measurement durations are reduced by four orders of magnitude. The protocol is suitable for laser ranging over tens of kilometers, depending on atmospheric conditions.
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