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Oncology Research 2024Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate.... (Review)
Review
Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm with intermediate malignancy characterized by a propensity for recurrence but a low metastatic rate. Diagnostic challenges arise from the diverse pathological presentation, variable symptomatology, and lack of different imaging features. However, IMT is identified by the fusion of the anaplastic lymphoma kinase (ALK) gene, which is present in approximately 70% of cases, with various fusion partners, including ran-binding protein 2 (RANBP2), which allows confirmation of the diagnosis. While surgery is the preferred approach for localized tumors, the optimal long-term treatment for advanced or metastatic disease is difficult to define. Targeted therapies are crucial for achieving sustained response to treatment within the context of genetic alteration in IMT. Crizotinib, an ALK tyrosine kinase inhibitor (TKI), was officially approved by the US Food and Drug Administration (FDA) in 2020 to treat IMT with ALK rearrangement. However, most patients face resistance and disease progression, requiring consideration of sequential treatments. Combining radiotherapy with targeted therapy appears to be beneficial in this indication. Early promising results have also been achieved with immunotherapy, indicating potential for combined therapy approaches. However, defined recommendations are still lacking. This review analyzes the available research on IMT, including genetic disorders and their impact on the course of the disease, data on the latest targeted therapy regimens and the possibility of developing immunotherapy in this indication, as well as summarizing general knowledge about prognostic and predictive factors, also in terms of resistance to systemic therapy.
PubMed: 38948020
DOI: 10.32604/or.2024.050350 -
Nature Cardiovascular Research Oct 2023Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on...
Among the diverse populations of myeloid cells that reside within the healthy and diseased heart, C-C chemokine receptor 2 (CCR2) is specifically expressed on inflammatory populations of monocytes and macrophages that contribute to the development and progression of heart failure. Here, we evaluated a peptide-based imaging probe (Cu-DOTA-ECL1i) that specifically recognizes CCR2 monocytes and macrophages for human cardiac imaging. Compared to healthy controls, Cu-DOTA-ECL1i heart uptake was increased in subjects following acute myocardial infarction, predominately localized within the infarct area, and was associated with impaired myocardial wall motion. These findings establish the feasibility of molecular imaging of CCR2 expression to visualize inflammatory monocytes and macrophages in the injured human heart.
PubMed: 38947883
DOI: No ID Found -
Cancer Innovation Jun 2024Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and...
Integrative genomic and transcriptomic profiling of pulmonary sarcomatoid carcinoma identifies molecular subtypes associated with distinct immune features and clinical outcomes.
BACKGROUND
Pulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive subtype of non-small cell lung cancer (NSCLC), characterized by the presence of epithelial and sarcoma-like components. The molecular and immune landscape of PSC has not been well defined.
METHODS
Multiomics profiling of 21 pairs of PSCs with matched normal lung tissues was performed through targeted high-depth DNA panel, whole-exome, and RNA sequencing. We describe molecular and immune features that define subgroups of PSC with disparate genomic and immunogenic features as well as distinct clinical outcomes.
RESULTS
In total, 27 canonical cancer gene mutations were identified, with the most frequently mutated gene, followed by . Interestingly, most and KRAS mutations were earlier genomic events mapped to the trunks of the tumors, suggesting branching evolution in most PSC tumors. We identified two distinct molecular subtypes of PSC, driven primarily by immune infiltration and signaling. The Immune High (IM-H) subtype was associated with superior survival, highlighting the impact of immune infiltration on the biological and clinical features of localized PSCs.
CONCLUSIONS
We provided detailed insight into the mutational landscape of PSC and identified two molecular subtypes associated with prognosis. IM-H tumors were associated with favorable recurrence-free survival and overall survival, highlighting the importance of tumor immune infiltration in the biological and clinical features of PSCs.
PubMed: 38947760
DOI: 10.1002/cai2.112 -
Cancer Innovation Jun 2024Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and,...
BACKGROUND
Immune checkpoint inhibitors (ICI) are increasingly used in the first-line treatment of malignant tumors. There is increasing recognition of their cardiotoxicity and, in particular, their potential to lead to myocarditis. Cardiovascular magnetic resonance (CMR) can quantify pathological changes, such as myocardial edema and fibrosis. The purpose of this systematic review and meta-analysis was to examine the evidence for the roles of CMR in predicting prognosis in ICI-associated myocarditis.
METHODS
PubMed, Cochrane Library, and Web of Science databases were searched until October 2023 for published works investigating the relationship between CMR parameters and adverse events in patients with ICI-associated myocarditis. The analysis included studies reporting the incidence of late gadolinium enhancement (LGE), T1 values, T2 values, and CMR-derived left ventricular ejection fraction (LVEF). Odds ratios (OR) and weighted mean differences (WMD) were combined for binary and continuous data, respectively. Newcastle-Ottawa Scale was used to assess the methodological quality of the included studies.
RESULTS
Five cohort studies were included (average age 65-68 years; 25.4% female). Of these, four studies were included in the meta-analysis of LGE-related findings. Patients with major adverse cardiovascular events (MACE) had a higher incidence of LGE compared with patients without MACE (OR = 4.18, 95% CI: 1.72-10.19, = 0.002). A meta-analysis, incorporating data from two studies, showed that patients who developed MACE exhibited significantly higher T1 value (WMD = 36.16 ms, 95% CI: 21.43-50.89, < 0.001) and lower LVEF (WMD = - 8.00%, 95% CI: -13.60 to -2.40, = 0.005). Notably, T2 value (WMD = -0.23 ms, 95% CI: -1.86 to -1.39, = 0.779) was not associated with MACE in patients with ICI-related myocarditis.
CONCLUSIONS
LGE, T1 value, and LVEF measured by CMR imaging have potential prognostic value for long-term adverse events in patients with ICI-related myocarditis.
PubMed: 38947756
DOI: 10.1002/cai2.109 -
Endoscopic Ultrasound 2024Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to...
BACKGROUND AND OBJECTIVES
Pancreatic cancer (PC) is the third cause of cancer-related deaths. Early detection and interception of premalignant pancreatic lesions represent a promising strategy to improve outcomes. We evaluated risk factors of focal pancreatic lesions (FPLs) in asymptomatic individuals at hereditary high risk for PC.
METHODS
This is an observational single-institution cohort study conducted over a period of 5 years. Surveillance was performed through imaging studies (EUS or magnetic resonance imaging/magnetic resonance cholangiopancreatography) and serum biomarkers. We collected demographic characteristics and used univariate and multivariate logistic regression models to evaluate associations between potential risk factors and odd ratios (ORs) for FPL development.
RESULTS
A total of 205 patients completed baseline screening. Patients were followed up to 53 months. We detected FPL in 37 patients (18%) at baseline; 2 patients had lesions progression during follow-up period, 1 of them to PC. Furthermore, 13 patients developed new FPLs during the follow-up period. Univariate and multivariate analyses revealed that new-onset diabetes (NOD) is strongly associated with the presence of FPL (OR, 10.94 [95% confidence interval, 3.01-51.79; < 0.001]; OR, 9.98 [95% confidence interval, 2.15-46.33; = 0.003]). Follow-up data analysis revealed that NOD is also predictive of lesions progression or development of new lesions during screening (26.7% 2.6%; = 0.005).
CONCLUSIONS
In a PC high-risk cohort, NOD is significantly associated with presence of FPL at baseline and predictive of lesions progression or new lesions during surveillance.
PubMed: 38947744
DOI: 10.1097/eus.0000000000000057 -
IScience Jun 2024Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat...
Ischemic stroke can cause depolarized brain waves, termed peri-infarct depolarization (PID). Here, we evaluated whether topiramate, a neuroprotective drug used to treat epilepsy and alleviate migraine, has the potential to reduce PID. We employed a rat model of photothrombotic ischemia that can reliably and reproducibly induce PID and developed a combined electrocorticography-laser speckle contrast imaging (ECoG-LSCI) platform to monitor neuronal activity and cerebral blood flow (CBF) simultaneously. Topiramate administration after photothrombotic ischemia did not rescue CBF but significantly restored somatosensory evoked potentials in the forelimb area of the primary somatosensory cortex. Moreover, infarct volume was investigated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and neuronal survival was evaluated by Nissl staining. Mechanistically, the levels of inflammatory markers, such as ED1 (CD68), Iba-1, and GFAP, decreased significantly after topiramate administration, as did BDNF expression, while the expression of NeuN and Bcl-2/Bax increased, which is indicative of reduced inflammation and improved neuroprotection.
PubMed: 38947531
DOI: 10.1016/j.isci.2024.110033 -
IScience Jun 2024Retinal ganglion cells (RGCs) summate inputs and forward a spike train code to the brain in the form of either maintained spiking (sustained) or a quickly decaying brief...
Retinal ganglion cells (RGCs) summate inputs and forward a spike train code to the brain in the form of either maintained spiking (sustained) or a quickly decaying brief spike burst (transient). We report diverse response transience values across the RGC population and, contrary to the conventional transient/sustained scheme, responses with intermediary characteristics are the most abundant. Pharmacological tests showed that besides GABAergic inhibition, gap junction (GJ)-mediated excitation also plays a pivotal role in shaping response transience and thus visual coding. More precisely GJs connecting RGCs to nearby amacrine and RGCs play a defining role in the process. These GJs equalize kinetic features, including the response transience of transient OFF alpha (tOFFα) RGCs across a coupled array. We propose that GJs in other coupled neuron ensembles in the brain are also critical in the harmonization of response kinetics to enhance the population code and suit a corresponding task.
PubMed: 38947503
DOI: 10.1016/j.isci.2024.110099 -
International Journal of Nanomedicine 2024To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the...
PURPOSE
To address the problem of suboptimal reactive oxygen species (ROS) production in Radiation therapy (RT) which was resulted from exacerbated tumor hypoxia and the heterogeneous distribution of radiation sensitizers.
MATERIALS AND METHODS
In this work, a novel nanomedicine, designated as PLGA@IR780-Bi-DTPA (PIBD), was engineered by loading the radiation sensitizer Bi-DTPA and the photothermal agent IR780 onto poly(lactic-co-glycolic acid) (PLGA). This design leverages the tumor-targeting ability of IR780 to ensure selective accumulation of the nanoparticles in tumor cells, particularly within the mitochondria. The effect of the photothermal therapy-enhanced radiation therapy was also examined to assess the alleviation of hypoxia and the enhancement of radiation sensitivity.
RESULTS
The PIBD nanoparticles exhibited strong capacity in mitochondrial targeting and selective tumor accumulation. Upon activation by 808 nm laser irradiation, the nanoparticles effectively alleviated local hypoxia by photothermal effect enhanced blood supplying to improve oxygen content, thereby enhancing the ROS production for effective RT. Comparative studies revealed that PIBD-induced RT significantly outperformed conventional RT in treating hypoxic tumors.
CONCLUSION
This design of tumor-targeting photothermal therapy-enhanced radiation therapy nanomedicine would advance the development of targeted drug delivery system for effective RT regardless of hypoxic microenvironment.
Topics: Animals; Photothermal Therapy; Reactive Oxygen Species; Nanoparticles; Cell Line, Tumor; Humans; Polylactic Acid-Polyglycolic Acid Copolymer; Mice; Indoles; Tumor Hypoxia; Radiation-Sensitizing Agents; Mice, Inbred BALB C; Mitochondria; Neoplasms; Nanomedicine
PubMed: 38946887
DOI: 10.2147/IJN.S450124 -
The Journal of Physical Chemistry. A Jul 2024Under irradiation of a vacuum ultraviolet (VUV) photon, methane dissociates and yields multiple fragments. This photochemical behavior is not only of fundamental...
Under irradiation of a vacuum ultraviolet (VUV) photon, methane dissociates and yields multiple fragments. This photochemical behavior is not only of fundamental importance but also with wide-ranging implications in several branches of science. Despite that and numerous previous investigations, the product channel branching is still under debate, and the underlying dissociation mechanisms remain elusive. In this study, the photofragment imaging technique was exploited for the first time to map out the momentum and anisotropy parameter distributions of the CH, CH, and CH fragments at the 118 nm photolysis wavelength (10.48 eV photon energy). In conjunction with previously reported results of the H atom fragment at 121.6 nm (10.2 eV), a complete set of product channel branching in both two-body and three-body fragmentations is accurately determined. We concluded that extensive nonadiabatic transitions partake in the processes with two-body fragmentations accounting for more than 90% of overall photodissociation, for which the channel branching values for CH + H and CH + H are about 0.66 and 0.25, respectively. Careful kinematic analysis enables us to untangle the intertwined triple fragmentations into the CH( and ) + H + H and CH(Π) + H + H channels and to evidence their underlying sequential (or stepwise) mechanisms. With the aid of electronic correlation and prior theoretical calculations of the potential energy surfaces, the most probable or dominant dissociation pathways are elucidated. Comparisons with fragmentary reports in the literature on various photochemical aspects are also documented, and discrepancies are clarified. This comprehensive study benchmarks the VUV photochemistry of methane and advances our understanding of this important process.
PubMed: 38946501
DOI: 10.1021/acs.jpca.4c01914 -
Chemical Communications (Cambridge,... Jul 2024By employing an aptamer as the bridge and combining catalytic hairpin assembly with the Au aggregation amplification effect, a lateral flow assay (LFA) is designed for...
By employing an aptamer as the bridge and combining catalytic hairpin assembly with the Au aggregation amplification effect, a lateral flow assay (LFA) is designed for simultaneous detection of liver cancer-associated miRNA and exosomes. The LFA can differentiate between liver cancer patients and healthy individuals with simple operation and high accuracy.
PubMed: 38946429
DOI: 10.1039/d4cc02559h