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PloS One 2024The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising...
BACKGROUND
The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising therapeutic strategy. Forsythoside B (FB) is a phenylethanoid glycoside isolated from Forsythiae fructus, which has been reported to have anti-inflammatory effects. However, the mechanism of the neuroprotective effect of FB on CIRI remains unclear.
METHODS
Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R.
RESULTS
FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation.
CONCLUSION
FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI.
Topics: Animals; Sirtuin 1; NLR Family, Pyrin Domain-Containing 3 Protein; Reperfusion Injury; Male; Rats, Sprague-Dawley; Inflammasomes; Rats; Infarction, Middle Cerebral Artery; Neuroprotective Agents; Brain Ischemia; Caffeic Acids; Glucosides
PubMed: 38885233
DOI: 10.1371/journal.pone.0305541 -
Radiation Oncology (London, England) Jun 2024Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates,...
Stereotactic body radiation therapy is beneficial for a subgroup of patients with urothelial cancer and solitary metastatic disease: a single institution real-world experience.
BACKGROUND
Standard treatment options for patients with metastatic urothelial cancer (mUC) include systemic platinum-based chemotherapy, immunotherapy, antibody-drug-conjugates, and targeted therapy. Oligometastatic disease (OMD) may be an intermediate state between localized and generalized cancer. The best treatment strategy for OMD and oligoprogressive (OPD) disease is poorly studied in mUC but local stereotactic body radiation therapy (SBRT) could be an option to avoid or delay systemic treatment. The aim of this study was to assess the efficacy and feasibility of SBRT given in a real-world patient population.
METHODS
All patients with mUC treated with SBRT at Karolinska University Hospital, Stockholm, Sweden between 2009 and 2022 were included in this study. Baseline clinical characteristics, treatment data, SBRT dosimetry data and treatment outcome were collected retrospectively. The study endpoints were local control rate (LCR), progression-free-survival (PFS), overall survival (OS) and feasibility of SBRT.
RESULTS
In total 39 patients were treated with SBRT. The median follow-up was 25.6 months. The LCR was 82%. PFS and OS were 4.1 and 26.2 months, respectively. Treatment was well tolerated; all patients but one (treatment related pain) completed the planned SBRT. Number of metastases irradiated with SBRT was significantly associated with outcome; patients with only one irradiated lesion had more favourable PFS compared to individuals with 2 or more metastases (HR 4.12, 95% CI: 1.81-9.38, p = 0.001). A subgroup of patients (15%) achieved a sustained long-term survival benefit and never required systemic treatments after SBRT.
CONCLUSIONS
SBRT was well tolerated and associated with high LCR. A subpopulation of patients with single metastatic lesion achieved long-term OS and never required subsequent systemic treatment after SBRT. Prospective randomized studies are warranted to discover treatment predictive biomarkers and to investigate the role of SBRT in oligometastatic UC.
Topics: Humans; Radiosurgery; Male; Female; Aged; Middle Aged; Retrospective Studies; Aged, 80 and over; Survival Rate; Urologic Neoplasms; Neoplasm Metastasis; Adult; Urinary Bladder Neoplasms
PubMed: 38880908
DOI: 10.1186/s13014-024-02465-y -
Cureus May 2024Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in...
Choroidal metastasis originating from renal cell carcinomas (RCCs) is rare. To the best of our knowledge, 31 cases of choroidal metastasis from RCC have been reported in the English literature as of January 31, 2024. Nevertheless, physicians need to be vigilant in recognizing this condition, as its progression impacts the quality of life (QOL) of affected patients. In Case 1, a 60-year-old male with a medical history of papillary RCC experienced a deterioration in visual acuity (VA) and was diagnosed with solitary choroidal metastasis. Subsequently, multiple metastases were identified, prompting the initiation of a combination therapy regimen consisting of pembrolizumab plus axitinib. Despite treatment, progression of choroidal metastasis and a further decline in VA were observed. The patient underwent stereotactic radiotherapy and experienced complete resolution of the choroidal metastasis, accompanied by a slight improvement in VA. In Case 2, a 76-year-old man presented with a renal tumor accompanied by lung metastases. He underwent nephrectomy, and the histological diagnosis was papillary RCC. We initiated combination therapy consisting of nivolumab plus cabozantinib. The patient experienced a decrease in VA during treatment. We identified extensive fine metastases scattered throughout the bilateral choroid. We administered axitinib, but the patient experienced bilateral blindness. Given the absence of established therapy for choroidal metastasis, it is crucial to maintain flexibility in treatment selection. Local or systemic approaches should be used as deemed appropriate for each individual case.
PubMed: 38868281
DOI: 10.7759/cureus.60191 -
Clinical Case Reports Jun 2024Intracranial RDD is rare medical event mimicking different diagnoses. Although the surgical resection is the best treatment option, but radiation therapy can also...
KEY CLINICAL MESSAGE
Intracranial RDD is rare medical event mimicking different diagnoses. Although the surgical resection is the best treatment option, but radiation therapy can also achieves long-term suboptimal outcomes.
ABSTRACT
An 83-year-old male with a history of tension-type headaches was evaluated. He was conscious with no focal neurological deficits. His brain MRI revealed an enhancable bifrontal tumor originating from falx cerebri and superior sagittal sinus dura. Due to the patient's preference and decline for gross total resection, she underwent a stereotactic biopsy. The pathology was positive for Rosai-Dorfman diseases. He received definitive targeted radiation with a total dose of 4500 cGy administered in 200 cGy daily fractions. His 4-year follow-up showed regional tumor control with excellent neurological outcome.
PubMed: 38868118
DOI: 10.1002/ccr3.9053 -
Technology in Cancer Research &... 2024Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for...
Recurrence after stage III lung cancer treatment usually appears with a poor prognosis, and salvage therapy for these patients is challenging, with limited data for reirradiation. Fifteen patients with recurrent stage III lung cancer treated with stereotactic body radiotherapy (SABR) between October 2013 and December 2017 were retrospectively evaluated for local control as a first endpoint; overall survival, disease-free survival, and treatment-related toxicity were secondary endpoints. The median age was 68 (IQR: 50-71) years, and the median tumor size was 3.3 cm (IQR: 3.0-4.5). The radiation field was all within the previous radiation (previous 80%-90% isodose line), and the median dose was 66 Gy/(2 Gy × 33 ) For SABR, the median biologically effective dose at an α/β ratio of 10 (BED) was 60.0 Gy (IQR: 39.38-85.0) and given in 3 to 5 fractions. Three patients experienced grade 3 or 4 toxicity but none experienced grade 5. The median follow-up period was 14 (IQR: 10-23) months. The local control rate was found as 86.7% in the first year, 80% in the second year, and 80% in the third year. The median disease-free survival was 8 (IQR: 6-20) months and the median overall survival was 14 (IQR: 10-23) months. The rate of overall survival was 66.6% for the first year and 33.3% for the second and third years. The disease-free survival rate was 46.6% for the first year and 40% for the second and third years. Nine patients who received doses of BED ≥ 50 Gy developed no local recurrence ( = .044). In local local-regional recurrence of lung cancer, radiosurgery as reirradiation can be used at doses of BED ≥ 50 Gy and above to provide local control for radical or palliative purposes. SABR is an important and relatively safe treatment option in such recurrences.
Topics: Humans; Radiosurgery; Middle Aged; Lung Neoplasms; Aged; Male; Female; Neoplasm Recurrence, Local; Re-Irradiation; Retrospective Studies; Neoplasm Staging; Treatment Outcome; Radiotherapy Dosage; Dose Fractionation, Radiation
PubMed: 38860536
DOI: 10.1177/15330338231208616 -
Acta Neurochirurgica Jun 2024The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a... (Review)
Review
PURPOSE
The gold standard for diagnostics in primary central nervous system lymphoma (PCNSL) is histopathological diagnosis after stereotactic biopsy. Yet, PCNSL has a multidisciplinary diagnostic work up, which associated with diagnostic delay and could result in treatment delay. This article offers recommendations to neurosurgeons involved in clinical decision-making regarding (novel) diagnostics and care for patients with PCNSL with the aim to improve uniformity and timeliness of the diagnostic process for patients with PCNSL.
METHODS
We present a mini review to discuss the role of stereotactic biopsy in the context of novel developments in diagnostics for PCNSL, as well as the role for cytoreductive surgery.
RESULTS
Cerebrospinal fluid-based diagnostics are supplementary and cannot replace stereotactic biopsy-based diagnostics.
CONCLUSION
Histopathological diagnosis after stereotactic biopsy of the brain remains the gold standard for diagnosis. Additional diagnostics should not be a cause of diagnostic delay. There is currently no sufficient evidence supporting cytoreductive surgery in PCNSL, with recent studies showing contradictive data and suboptimal study designs.
Topics: Humans; Central Nervous System Neoplasms; Lymphoma; Time-to-Treatment; Delayed Diagnosis; Neurosurgeons; Biopsy; Stereotaxic Techniques; Cytoreduction Surgical Procedures; Treatment Delay
PubMed: 38858236
DOI: 10.1007/s00701-024-06138-3 -
Translational Lung Cancer Research May 2024rearrangements are infrequently observed in non-small cell lung cancer (NSCLC). Advanced genomic detection techniques have unveiled such infrequent genomic variations,...
BACKGROUND
rearrangements are infrequently observed in non-small cell lung cancer (NSCLC). Advanced genomic detection techniques have unveiled such infrequent genomic variations, particularly fusions in approximately 0.5% of NSCLC patients. Tyrosine kinase inhibitors (TKIs) have revolutionized the standard of care in lung cancer and more recently a second generation MET TKI tepotinib received Food and Drug Administration (FDA) approval for MET exon 14 alterations in metastatic NSCLC. Despite this, the therapeutic landscape for -rearranged NSCLC patients remains significantly unexplored. The aim of our report is to detail a unique case of a patient with metastatic lung adenocarcinoma with a novel fusion detected by next-generation sequencing (NGS) following previous treatment resistance.
CASE DESCRIPTION
A 73-year-old female was initially started on carboplatin, pemetrexed and pembrolizumab with maintenance, but eventually had progression in the left upper lobe (LUL). Upon progression she was enrolled in a clinical trial of a monoclonal antibody with or without a PD-1 inhibitor, but brain metastasis progression was eventually detected by magnetic resonance imaging (MRI) requiring stereotactic radiosurgery (SRS) and a craniotomy. The trial drug was eventually discontinued due to progression and toxicity and NGS on bronchoscopy tissue revealed fusion. The patient was initiated on tepotinib and continues with clinical and radiological stable disease for over 12 months. The patient's response to a MET inhibitor, tepotinib, underscores the potential efficacy of selective MET inhibitors for individuals with previously unexplored fusions.
CONCLUSIONS
The positive response to tepotinib of a patient with NSCLC harboring a novel -Fusion underscores the importance of the use of comprehensive next-generational sequencing-based panels and highlights the necessity for additional research and clinical exploration of selective MET inhibitors for managing NSCLC with rearrangements.
PubMed: 38854944
DOI: 10.21037/tlcr-24-34 -
Frontiers in Oncology 2024The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older...
Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group.
The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.
PubMed: 38854736
DOI: 10.3389/fonc.2024.1391464 -
Frontiers in Oncology 2024Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel...
PURPOSE
Bulky tumor remains as a challenge to surgery, chemotherapy and conventional radiation therapy. Hence, in efforts to overcome this challenge, we designed a novel therapeutic paradigm via strategy of Stereotactic Central/Core Ablative Radiation Therapy (SCART).), which is based on the principles of SBRT (stereotactic body radiation therapy and spatially fractionated radiation therapy (SFRT). We intend to safely deliver an ablative dose to the core of the tumor and with a low dose at tumor edge. The purpose of the phase 1 study was to determine dose-limiting toxicities (DLT)s and the Maximum Tolerated Dose (MTD) of SCART.
METHODS AND MATERIALS
We defined a SCART-plan volume inside the tumor, which is proportional to the dimension of tumor. VMAT/Cyberknife technique was adopted. In the current clinical trial; Patients with biopsy proven recurrent or metastatic bulky cancers were enrolled. The five dose levels were 15 Gy X1, 15Gy X3, 18GyX3, 21GyX3 and 24GyX3, while keeping the whole tumor GTV's border dose at 5Gy each fraction. There was no restriction on concurrent systemic chemotherapy agents.
RESULTS
21 patients were enrolled and underwent SCART. All 21 patients have eligible data for study follow-up. Radiotherapy was well tolerated with all treatment completed as scheduled. The dose was escalated for two patients to 24GyX3. No grade 3 or higher toxicity was observed in any of the enrolled patients. The average age of patients was 66 years (range: 1485) and 13 (62%) patients were male. The median SCART dose was 18Gy (range: 15 - 24). Six out of the 18 patients with data for overall survival (OS) died, and the median time to death was 16.3 months (range: 1 - 25.6). The mean percent change for tumor shrinkage between first visit volumes and post-SCART volumes was 49.5% (SD: 40.89, p-value:0.009).
CONCLUSION
SCART was safely escalated to 24 GyX 3 fractions, which is the maximum Tolerated Dose (MTD) for SCART. This regimen will be used in future phase II trials.
PubMed: 38854732
DOI: 10.3389/fonc.2024.1364627 -
Frontiers in Oncology 2024The detection rate of ground glass nodules (GGNs) has increased in recent years because of their malignant potential but relatively indolent biological behavior; thus,... (Review)
Review
The detection rate of ground glass nodules (GGNs) has increased in recent years because of their malignant potential but relatively indolent biological behavior; thus, correct GGN recognition and management has become a research focus. Many scholars have explored the underlying mechanism of the indolent progression of GGNs from several perspectives, such as pathological type, genomic mutational characteristics, and immune microenvironment. GGNs have different major mutated genes at different stages of development; mutation is the most common mutation in GGNs, and mutation is the most abundant mutation in the invasive stage of GGNs. Pure GGNs have fewer genomic alterations and a simpler genomic profile and exhibit a gradually evolving genomic mutation profile as the pathology progresses. Compared to advanced lung adenocarcinoma, GGN lung adenocarcinoma has a higher immune cell percentage, is under immune surveillance, and has less immune escape. However, as the pathological progression and solid component increase, negative immune regulation and immune escape increase gradually, and a suppressive immune environment is established gradually. Currently, regular computer tomography monitoring and surgery are the main treatment strategies for persistent GGNs. Stereotactic body radiotherapy and radiofrequency ablation are two local therapeutic alternatives, and systemic therapy has been progressively studied for lung cancer with GGNs. In the present review, we discuss the characterization of the multidimensional molecular evolution of GGNs that could facilitate more precise differentiation of such highly heterogeneous lesions, laying a foundation for the development of more effective individualized treatment plans.
PubMed: 38841161
DOI: 10.3389/fonc.2024.1380527