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1.
Int J Biol Macromol ; 276(Pt 1): 133758, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992550

ABSTRACT

In this study, a one-step extrusion method is proposed to prepare blended polylactic acid (PLA)/thermoplastic starch (TPS) using a novel plant-derived compatibilizer, pyrogallic acid (PGA), to enhance the PLA/TPS compatibility. The effects of PGA on the mechanical behavior, fractured cross-section morphology, thermal and dynamic mechanical performance, and water resistance of PLA/TPS blends were systematically studied. Results demonstrate that the addition of PGA effectively improves the compatibility between TPS and PLA, resulting in enhanced tensile strength, crystallinity, elongation at break, thermal stability, and hydrophobicity of the blends. Specifically, incorporating 1.5 phr of PGA into the blend system yields the highest values for tensile strength (23.38 MPa) and elongation at break (16.96 %), which are 24.7 % and 233.2 %, respectively, higher than those observed for pure PLA/TPS blends. Furthermore, other properties exhibit obvious improvements upon incorporation of PGA into the blends. This approach provides a promising strategy for enhancing the performance of PLA/TPS blends and expanding their applications in food packaging, agricultural film, etc.

2.
Neuropharmacology ; 257: 110032, 2024 Jun 08.
Article in English | MEDLINE | ID: mdl-38852839

ABSTRACT

The full mechanism of action of propofol, a commonly administered intravenous anesthetic drug in clinical practice, remains elusive. The focus of this study was the role of GABAergic neurons which are the main neuron group in the ventral pallidum (VP) closely associated with anesthetic effects in propofol anesthesia. The activity of VP GABAergic neurons following propofol anesthesia in Vgat-Cre mice was observed via detecting c-Fos immunoreactivity by immunofluorescence and western blotting. Subsequently, chemogenetic techniques were employed in Vgat-Cre mice to regulate the activity of VP GABAergic neurons. The role of VP GABAergic neurons in generating the effects of general anesthesia induced by intravenous propofol was further explored through behavioral tests of the righting reflex. The results revealed that c-Fos expression in VP GABAergic neurons in Vgat-Cre mice dramatically decreased after propofol injection. Further studies demonstrated that chemogenetic activation of VP GABAergic neurons during propofol anesthesia shortened the duration of anesthesia and promoted wakefulness. Conversely, the inhibition of VP GABAergic neurons extended the duration of anesthesia and facilitated the effects of anesthesia. The results obtained in this study suggested that regulating the activity of GABAergic neurons in the ventral pallidum altered the effect of propofol on general anesthesia.

3.
Cell Mol Biol Lett ; 29(1): 79, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38783169

ABSTRACT

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a common complication after anesthesia/surgery, especially among elderly patients, and poses a significant threat to their postoperative quality of life and overall well-being. While it is widely accepted that elderly patients may experience POCD following anesthesia/surgery, the exact mechanism behind this phenomenon remains unclear. Several studies have indicated that the interaction between silent mating type information regulation 2 homologue 1 (SIRT1) and brain-derived neurotrophic factor (BDNF) is crucial in controlling cognitive function and is strongly linked to neurodegenerative disorders. Hence, this research aims to explore how SIRT1/BDNF impacts cognitive decline caused by anesthesia/surgery in aged mice. METHODS: Open field test (OFT) was used to determine whether anesthesia/surgery affected the motor ability of mice, while the postoperative cognitive function of 18 months old mice was evaluated with Novel object recognition test (NORT), Object location test (OLT) and Fear condition test (FC). The expressions of SIRT1 and other molecules were analyzed by western blot and immunofluorescence staining. The hippocampal synaptic plasticity was detected by Golgi staining and Long-term potentiation (LTP). The effects of SIRT1 and BDNF overexpression as well as chemogenetic activation of glutamatergic neurons in hippocampal CA1 region of 18 months old vesicular glutamate transporter 1 (VGLUT1) mice on POCD were further investigated. RESULTS: The research results revealed that older mice exhibited cognitive impairment following intramedullary fixation of tibial fracture. Additionally, a notable decrease in the expression of SIRT1/BDNF and neuronal excitability in hippocampal CA1 glutamatergic neurons was observed. By increasing levels of SIRT1/BDNF or enhancing glutamatergic neuron excitability in the CA1 region, it was possible to effectively mitigate synaptic plasticity impairment and ameliorate postoperative cognitive dysfunction. CONCLUSIONS: The decline in SIRT1/BDNF levels leading to changes in synaptic plasticity and neuronal excitability in older mice could be a significant factor contributing to cognitive impairment after anesthesia/surgery.


Subject(s)
Brain-Derived Neurotrophic Factor , CA1 Region, Hippocampal , Down-Regulation , Neuronal Plasticity , Neurons , Postoperative Cognitive Complications , Sirtuin 1 , Animals , Sirtuin 1/metabolism , Sirtuin 1/genetics , Brain-Derived Neurotrophic Factor/metabolism , Brain-Derived Neurotrophic Factor/genetics , Mice , Neurons/metabolism , Postoperative Cognitive Complications/metabolism , Postoperative Cognitive Complications/etiology , CA1 Region, Hippocampal/metabolism , Male , Mice, Inbred C57BL , Long-Term Potentiation , Glutamic Acid/metabolism , Cognitive Dysfunction/etiology , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/physiopathology
4.
Front Med (Lausanne) ; 11: 1353822, 2024.
Article in English | MEDLINE | ID: mdl-38741768

ABSTRACT

Background: Retroperitoneal fibrosis, a condition of uncertain origin, is rarely linked to 8% of malignant cases, including breast, lung, gastrointestinal, genitourinary, thyroid, and carcinoid. The mechanism leading to peritoneal fibrosis induced by tumors is not well understood, possibly encompassing direct infiltration of neoplastic cells or the initiation of inflammatory responses prompted by cytokines released by tumor cells. We report a case of breast cancer with renal metastasis and retroperitoneal fibrosis detected using 18F-FDG PET/CT, providing help for clinical diagnosis and treatment. Case report: A 49-year-old woman was referred to the hospital with elevated creatinine and oliguria for over a month. Abdominal computer tomography (CT) and magnetic resonance imaging (MRI) showed a retroperitoneal fibrosis-induced acute kidney injury (AKI) was suspected. However, a percutaneous biopsy of the kidney lesion confirmed metastasis from breast cancer. The physical examination revealed inverted nipples and an orange peel appearance on the skin of both breasts. Ultrasonography revealed bilateral hyperplasia (BIRADS 4a) of the mammary glands and bilateral neck and axillary lymphadenopathy. Subsequently, 18F-deoxyglucose positron emission tomography/computer tomography (18F-FDG PET/CT) detected abnormally high uptake (SUVmax) in the bilateral mammary glands and axillary lymph nodes, suggesting bilateral breast cancer. Furthermore, abnormal 18F-FDG uptake was detected in the kidney, suggesting renal metastasis. In addition, abnormal 18F-FDG uptake was observed in the vertebrae, accompanied by an elevation in inhomogeneous bone mineral density, raising suspicion of bone metastases. However, the possibility of myelodysplasia cannot be dismissed, and further investigations will be conducted during close follow-ups. There was significant 18F-FDG uptake in the retroperitoneal position indicating a potential association between retroperitoneal fibrosis and breast cancer. The final pathological diagnosis of the breast tissue confirmed bilateral invasive ductal carcinoma. The patient had been treated with 11 cycles of albumin-bound (nab)-paclitaxel (0.3 mg) and had no significant adverse reaction. Conclusion: In this case, neither the bilateral breast cancer nor the kidney metastatic lesion showed typical nodules or masses, so breast ultrasound, abdominal CT, and MRI did not suggest malignant lesions. PET/CT played an important role in detecting occult metastases and primary lesions, thereby contributing to more accurate staging, monitoring treatment responses, and prediction of prognosis in breast cancer.

6.
Front Med (Lausanne) ; 11: 1373773, 2024.
Article in English | MEDLINE | ID: mdl-38576712

ABSTRACT

Background: One of the exceptionally rare forms of non-Hodgkin's lymphoma (NHL) is primary cardiac lymphoma (PCL). The principal clinical manifestation in patients with PCL involves cardiac symptoms resulting from myocardial infiltration by lymphoma, including arrhythmias, heart failure, and chest pain. 18F-FDG PET/CT serves as a reliable and indispensable imaging modality for assessing clinically staging NHL. Case report: We present a rare case involving a 72-year-old woman diagnosed with primary intracardiac diffuse large B-cell lymphoma. For further staging, the patient underwent 18F-FDG PET/CT, revealing multiple nodular soft tissue density lesions in the heart and pericardium exhibiting increased FDG metabolism (SUVmax = 12.1). The supradiaphragmatic and infradiaphragmatic segments of the inferior vena cava exhibited irregular morphology with localized nodular changes and increased FDG metabolism in the surrounding area (SUVmax = 9.7). Additionally, multiple enlarged lymph nodes were identified in the left axilla, mediastinum, and adjacent to the abdominal aorta, displaying heterogeneous FDG uptake with an SUVmax of 9.3, indicating lymphoma involvement. The above imaging findings suggested that the mass was a PCL. Hence, the patient underwent a combination of chemotherapy and immunotherapy using R-CDOP (rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone). Following two courses of treatment within a span of 2 months, there was a partial remission observed in the cardiac lymphoma and the enlarged lymph nodes. Conclusion: The case elucidated in this report contributes to an enhanced understanding of the disease for clinicians, with 18F-FDG PET/CT providing comprehensive insights into the extent of cardiac involvement, as well as the engagement of extracardiac organs and pathologic lymph nodes. The 18F-FDG PET/CT examination not only visually delineates the lesion's location and extent but also serves as a cornerstone for clinical tumor staging, offering valuable support for treatment monitoring and subsequent follow-up.

8.
Mol Pharm ; 21(5): 2544-2554, 2024 May 06.
Article in English | MEDLINE | ID: mdl-38588328

ABSTRACT

Vascular endothelial growth factor (VEGF) targeted therapy serves as an important therapeutic approach for renal cancer, but its clinical effectiveness is unsatisfactory. Moreover, there is a lack of reliable biomarkers for preoperative assessment of tumor VEGF expression. This study aimed to explore the potential for further applications of 177Lu/89Zr-labeled aflibercept (Abe), a VEGF-binding agent, in imaging visualization of VEGF expression and therapy for renal cancer. To determine specificity uptake in renal cancer, BALB/c mice with VEGF-expressing Renca tumor were intravenously injected with [89Zr]Zr-Abe, [177Lu]Lu-Abe, or Cy5.5-Abe and the blocking group was designed as a control group. PET, SPECT, and fluorescence images were acquired, and the biodistribution of [89Zr]Zr-Abe and [177Lu]Lu-Abe was performed. Additionally, the [177Lu]Lu-Abe, [177Lu]Lu-Abe-block, 177Lu only, Abe only, and PBS groups were compared for evaluation of the therapeutic effect. To assess the safety, we monitored and evaluated the body weight, blood biochemistry analysis, and whole blood analysis and major organs were stained with hematoxylin and eosin after [177Lu]Lu-Abe treatment. DOTA-Abe was successfully labeled with 177Lu and Df-Abe with 89Zr in our study. The uptake in tumor of [89Zr]Zr-Abe was significantly higher than that of [89Zr]Zr-Abe-block (P < 0.05) and provided excellent tumor contrast in PET images. [177Lu]Lu-Abe demonstrated promising tumor-specific targeting capability with a high and persistent tumor uptake. The standardized tumor volume of [177Lu]Lu-Abe was significantly smaller than those of other treatment groups (P < 0.05). [177Lu]Lu-Abe also had smaller tumor volumes and reduced expression of VEGF and CD31 compared to those of the control groups. Fluorescence images demonstrate higher tumor uptake in the Cy5.5-Abe group compared to the Cy5.5-Abe-block group (P < 0.05). In conclusion, [89Zr]Zr-Abe enables noninvasive analysis of VEGF expression, serving as a valuable tool for assessing the VEGF-targeted therapy effect. Additionally, all of the findings support the enhanced therapeutic efficacy and safety of [177Lu]Lu-Abe, making it a viable option for clinical practice in renal cancer.


Subject(s)
Kidney Neoplasms , Lutetium , Mice, Inbred BALB C , Radioisotopes , Receptors, Vascular Endothelial Growth Factor , Recombinant Fusion Proteins , Zirconium , Animals , Receptors, Vascular Endothelial Growth Factor/metabolism , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/pharmacokinetics , Zirconium/chemistry , Mice , Kidney Neoplasms/drug therapy , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/metabolism , Tissue Distribution , Humans , Cell Line, Tumor , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Radiopharmaceuticals/pharmacokinetics , Radiopharmaceuticals/chemistry , Theranostic Nanomedicine/methods , Female , Positron-Emission Tomography/methods , Xenograft Model Antitumor Assays
9.
CNS Neurosci Ther ; 30(2): e14604, 2024 02.
Article in English | MEDLINE | ID: mdl-38332635

ABSTRACT

AIM: Repeated exposure to ketamine during the neonatal period in mice leads to cognitive impairments in adulthood. These impairments are likely caused by synaptic plasticity and excitability damage. We investigated the precise role of brain-derived neurotrophic factor (BDNF) in the cognitive impairments induced by repeated ketamine exposure during the neonatal period. METHODS: We evaluated the cognitive function of mice using the Morris water maze test and novel object recognition test. Western blotting and immunofluorescence were used to detect the protein levels of BDNF. Western blotting, Golgi-Cox staining, transmission electron microscopy, and long-term potentiation (LTP) recordings were used to assess synaptic plasticity in the hippocampus. The excitability of neurons was evaluated using c-Fos. In the intervention experiment, pAdeno-CaMKIIα-BDNF-mNeuronGreen was injected into the hippocampal CA1 region of mice to increase the level of BDNF. The excitability of neurons was enhanced using a chemogenetic approach. RESULTS: Our findings suggest that cognitive impairments in mice repeatedly exposed to ketamine during the neonatal period are associated with downregulated BDNF protein level, synaptic plasticity damage, and decreased excitability of glutamatergic neurons in the hippocampal CA1 region. Furthermore, the specific upregulation of BDNF in glutamatergic neurons of the hippocampal CA1 region and the enhancement of excitability can improve impaired synaptic plasticity and cognitive function in mice. CONCLUSION: BDNF downregulation mediates synaptic plasticity and excitability damage, leading to cognitive impairments in adulthood following repeated ketamine exposure during the neonatal period.


Subject(s)
Cognitive Dysfunction , Ketamine , Mice , Animals , Brain-Derived Neurotrophic Factor/metabolism , Ketamine/toxicity , Down-Regulation , Neuronal Plasticity/physiology , Hippocampus/metabolism , Neurons/metabolism , Cognitive Dysfunction/metabolism
10.
Front Med (Lausanne) ; 11: 1172746, 2024.
Article in English | MEDLINE | ID: mdl-38362535

ABSTRACT

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of soft tissue sarcoma that often involves the deep soft tissue of the extremities and trunk in young and middle-aged adults. It is uncommon in the elderly. Here we discuss a case of LGFMS in an elderly patient who had recurrence and metastasis within 2 years of resection of the primary tumor. Case report: A 71-year-old LGFMS patient was presented with a mass in the left forearm accompanied by pain and numbness from the left upper arm to fingers. The patient subsequently underwent 3 surgical resections, although she had 3 recurrences within 6 months after the initial diagnosis. Considering the malignant biological behavior of the tumor, an amputation at 5 cm above the elbow was eventually performed. However, recurrence in the extremity of the stump and chest wall metastasis were observed 2 years after amputation. Then resection of the metastases, radiotherapy and particle implantation therapy were performed. The patient is currently undergoing follow-up and has no evidence of recurrence. Conclusion: In our case, multiple early postoperative recurrences may be associated with a positive margin at initial operation. The patient underwent a total of 5 operations including local resection of the primary tumor, twice wide resections, amputation and metastatic surgery with 4 early postoperative recurrences and metastases within 4 years, suggesting that LGFMS may have highly invasive biological behavior. Our case demonstrated that early aggressive surgical treatment is recommended for LGFMS patients with a positive margin at initial operation and patients who had recurrence even after wide resection rather than local resection. Further research is needed to develop more effective treatment options for rapidly progress and highly aggressive LGFMS.

11.
J Environ Manage ; 353: 120191, 2024 Feb 27.
Article in English | MEDLINE | ID: mdl-38325286

ABSTRACT

The daily discharge of rural sewage in China occupies 30 % of the national wastewater discharge, and developing an energy-efficient, easy to operate, and decentralized rural sewage treatment technology becomes an important task. In this work, a novel rural sewage treatment technology, Electrocoagulation enhanced Gravity-Driven Membrane Bioreactor (EC-GDMBR) was exploited for the rural sewage treatment under long-term operation (160 days). Two EC-GDMBRs with various module structures of ceramic membrane (horizontal module and side module) not only displayed the desirable effluent quality, but also sustained the stable flux (8-13 LMH). The electrocoagulation, electrooxidation, biodegradation, and separation in EC-GDMBRs were able to synergistically remove the particle matter, organic (CODCr effluent <11.6 ± 1.2 mg/L) and nutrients (NH3-N effluent <0.1 mg/L, TN effluent <8.5 mg/L, TP effluent <0.05 mg/L). Besides, the high permeability of ceramic membrane and large porosity of biofilm on its surface improved the sustainability of stable flux during the long-term operation. Moreover, by analyzing bacterial abundance, Extracellular Polymeric Substances, Adenosine Tri-Phosphate and Confocal Laser Scanning Microscopy, a large number of microorganisms grew and accumulated on the carrier, as well as formed the biofilm (23.46-659.9 µm), while Nitrobacteria (1.6-4.1 %) and Nitrate (0.01-0.06 %) exited in the carrier biofilms, promoting the nitrogen removal. Compared with EC-GDMBR with side module of ceramic membrane, EC-GDMBR with horizontal module of ceramic membrane has advantages in flux behavior, organic/nutrient removal, microbial abundance/activity, abundance of nitrogen removal functional bacteria and water permeability of biofilm, because the ceramic membrane of horizontal module can promote the uniform growth of biofilm and improve the uniformity of flow penetration distribution. In general, the findings of this work verify the reliability of EC-GDMBR for the sustainable operation of wastewater treatment and improve its application value of rural sewage treatment.


Subject(s)
Sewage , Waste Disposal, Fluid , Sewage/chemistry , Reproducibility of Results , Membranes, Artificial , Bioreactors , Nitrogen/metabolism , Bacteria/metabolism
12.
Mol Neurobiol ; 61(8): 5459-5480, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38200350

ABSTRACT

The mechanism of ketamine-induced neurotoxicity development remains elusive. Mitochondrial fusion/fission dynamics play a critical role in regulating neurogenesis. Therefore, this study was aimed to evaluate whether mitochondrial dynamics were involved in ketamine-induced impairment of neurogenesis in neonatal rats and long-term synaptic plasticity dysfunction. In the in vivo study, postnatal day 7 (PND-7) rats received intraperitoneal (i.p.) injection of 40 mg/kg ketamine for four consecutive times at 1 h intervals. The present findings revealed that ketamine induced mitochondrial fusion dysfunction in hippocampal neural stem cells (NSCs) by downregulating Mitofusin 2 (Mfn2) expression. In the in vitro study, ketamine treatment at 100 µM for 6 h significantly decreased the Mfn2 expression, and increased ROS generation, decreased mitochondrial membrane potential and ATP levels in cultured hippocampal NSCs. For the interventional study, lentivirus (LV) overexpressing Mfn2 (LV-Mfn2) or control LV vehicle was microinjected into the hippocampal dentate gyrus (DG) 4 days before ketamine administration. Targeted Mfn2 overexpression in the DG region could restore mitochondrial fusion in NSCs and reverse the inhibitory effect of ketamine on NSC proliferation and its faciliatory effect on neuronal differentiation. In addition, synaptic plasticity was evaluated by transmission electron microscopy, Golgi-Cox staining and long-term potentiation (LTP) recordings at 24 h after the end of the behavioral test. Preconditioning with LV-Mfn2 improved long-term cognitive dysfunction after repeated neonatal ketamine exposure by reversing the inhibitory effect of ketamine on synaptic plasticity in the hippocampal DG. The present findings demonstrated that Mfn2-mediated mitochondrial fusion dysfunction plays a critical role in the impairment of long-term neurocognitive function and synaptic plasticity caused by repeated neonatal ketamine exposure by interfering with hippocampal neurogenesis. Thus, Mfn2 might be a novel therapeutic target for the prevention of the developmental neurotoxicity of ketamine.


Subject(s)
Animals, Newborn , Cognition , GTP Phosphohydrolases , Hippocampus , Ketamine , Mitochondrial Dynamics , Neural Stem Cells , Neurogenesis , Rats, Sprague-Dawley , Animals , Ketamine/pharmacology , Ketamine/toxicity , Ketamine/administration & dosage , Neurogenesis/drug effects , Neural Stem Cells/drug effects , Neural Stem Cells/metabolism , Mitochondrial Dynamics/drug effects , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , GTP Phosphohydrolases/metabolism , Cognition/drug effects , Male , Neuronal Plasticity/drug effects , Anesthesia/adverse effects , Rats , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondrial Proteins
14.
CNS Neurosci Ther ; 30(2): e14410, 2024 02.
Article in English | MEDLINE | ID: mdl-37592394

ABSTRACT

AIMS: Cognitive dysfunction associated with chronic pain may be caused by impaired synaptic plasticity. Considering the impact of silent information regulator 1 (SIRT1) on synaptic plasticity, we explored the exact role of SIRT1 in cognitive impairment caused by chronic pain. METHODS: We evaluated the memory ability of mice with the fear conditioning test (FCT) after spared nerve injury (SNI) model. Western blotting and immunofluorescence were used to analyze the expression levels of SIRT1. Hippocampal synaptic plasticity was detected with Golgi staining, transmission electron microscopy, and long-term potentiation (LTP). In the intervention study, AAV9-CaMKIIα-Cre-EGFP was injected to SIRT1flox/flox mice to knockdown the expression levels of SIRT1. Besides, SNI mice were injected with AAV2/9-CaMKIIα-SIRT1-3*Flag-GFP or SRT1720 to increase the expression levels or enzymatic activity of SIRT1. RESULTS: Our current results indicated that cognitive function in SNI mice was impaired, SIRT1 expression in glutaminergic neurons in the hippocampal CA1 area was downregulated, and synaptic plasticity was altered. Selective knockdown of SIRT1 in hippocampus damaged synaptic plasticity and cognitive function of healthy mice. In addition, the impaired synaptic plasticity and cognitive dysfunction of SNI mice could be improved by the upregulation of SIRT1 expression or enzyme activity. CONCLUSIONS: Reduced SIRT1 expression in hippocampus of SNI mice may induce cognitive impairment associated with chronic pain by mediating the impaired synaptic plasticity.


Subject(s)
Chronic Pain , Cognitive Dysfunction , Animals , Mice , Cognitive Dysfunction/genetics , Cognitive Dysfunction/metabolism , Down-Regulation , Hippocampus/metabolism , Neuronal Plasticity/physiology , Sirtuin 1/genetics , Sirtuin 1/metabolism
15.
Eur J Nucl Med Mol Imaging ; 51(5): 1246-1260, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38135849

ABSTRACT

PURPOSE: Triple-negative breast cancer (TNBC) has a poor prognosis due to the absence of effective therapeutic targets. Vascular endothelial growth factor (VEGF) family are expressed in 30-60% of TNBC, therefore providing potential therapeutic targets for TNBC. Aflibercept (Abe), a humanized recombinant fusion protein specifically bound to VEGF-A, B and placental growth factor (PIGF), has proven to be effective in the treatment in some cancers. Therefore, 89Zr/177Lu-labeled Abe was investigated for its theranostic role in TNBC. METHODS: Abe was radiolabeled with 89Zr and 177Lu via the conjugation of chelators. Flow cytometry and cell immunofluorescent staining were performed to evaluate the binding affinity of Abe. Sequential PET imaging and fluorescent imaging were conducted in TNBC tumor bearing mice following the injection of 89Zr-labeled Abe and Cy5.5-labeled Abe. Treatment study was performed after the administration of 177Lu-labeled Abe. Tumor volume and survival were monitored and SPECT imaging and biodistribution studies were conducted. Safety evaluation was performed including body weight, blood cell measurement, and hematoxylin-eosin (H&E) staining of major organs. Expression of VEGF and CD31 was tested by immunohistochemical staining. Dosimetry was estimated using the OLINDA software. RESULTS: FITC-labeled Abe showed a strong binding affinity to VEGF in TNBC 4T1 cells and HUVECs by flow cytometry and cell immunofluorescence. Tumor uptake of 89Zr-labeled Abe peaked at 120 h (SUVmax = 3.2 ± 0.64) and persisted before 168 h (SUVmax = 2.54 ± 0.42). The fluorescence intensity of the Cy5.5-labeled Abe group surpassed that of the Cy5.5-labeled IgG group, implying that Cy5.5-labeled Abe is a viable candidate monitoring in vivo tumor targeting and localization. 177Lu-labeled Abe (11.1 MBq) served well as the therapeutic component to suppress tumor growth with standardized tumor volume at 16 days, significantly smaller than PBS group (about 815.66 ± 3.58% vs 3646.52 ± 11.10%, n = 5, P < 0.01). Moreover, SPECT images confirmed high contrast between tumors and normal organs, indicating selective tumor uptake of 177Lu-labeled Abe. No discernible abnormalities in blood cells, and no evident histopathological abnormality observed in liver, spleen, and kidney. Immunohistochemical staining showed that 177Lu-labeled Abe effectively inhibited the expression of VEGF and CD31 of tumor, suggesting that angiogenesis may be suppressed by 177Lu-labeled Abe. The whole-body effective dose for an adult human was estimated to be 0.16 mSv/MBq. CONCLUSION: 89Zr/177Lu-labeled Abe could be a TNBC-specific marker with diagnostic value and provide insights into targeted therapy in the treatment of TNBC. Further clinical evaluation and translation may be of high significance for TNBC.


Subject(s)
Carbocyanines , Receptors, Vascular Endothelial Growth Factor , Triple Negative Breast Neoplasms , Vascular Endothelial Growth Factor A , Female , Humans , Animals , Mice , Vascular Endothelial Growth Factor A/metabolism , Triple Negative Breast Neoplasms/diagnostic imaging , Triple Negative Breast Neoplasms/drug therapy , Precision Medicine , Tissue Distribution , Cell Line, Tumor , Placenta Growth Factor/metabolism , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/metabolism
16.
Quant Imaging Med Surg ; 13(12): 8571-8586, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38106313

ABSTRACT

Background: Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is a rare occurrence, has a very poor prognosis, and is marked by a high risk of relapse. Accurate prediction of patient prognosis before treatment initiation, along with timely adjustment of the treatment plan, holds paramount importance. 2-Deoxy-2-[fluorine-18]-fluoro-D-glucose (18F-FDG) positron emission tomography combined with computed tomography (PET/CT) imaging techniques are conventionally performed prior to treatment initiation in DLBCL patients, offering indispensable functional and metabolic insights into lymphoma lesions. Methods: We conducted a retrospective case-control study using data collected from January 2014 to December 2022, including 24 patients diagnosed with PA-DLBCL. Clinical information of patients was collected based on inpatient medical records, including age, gender, B symptoms, adrenocorticotropic hormone (ATCH), lactate dehydrogenase (LDH), ß2-microglobulin, albumin (Alb), ferritin (Fe), blood calcium, Eastern Cooperative Oncology Group performance status (ECOG-PS), International Prognostic Index, Ann Arbor staging, number of involved organs, and Hans' algorithm. Prior to treatment, all patients underwent baseline 18F-FDG PET/CT, and the metabolic parameters of the tumor were calculated using a threshold of 41% of maximum standardized uptake value (SUVmax), including metabolic tumor volume (MTV) and total lesion glycolysis (TLG). Prognostic analysis of overall survival (OS) was performed using Kaplan-Meier survival analysis, as well as univariate and multifactor Cox proportional hazards regression models. Results: The 24 enrolled patients comprised 16 men and 8 women (median age 65 years, range 51-90 years). The median follow-up period was 17.5 months (range, 1-107 months). In univariate analysis, Ann Arbor stage, ß2-microglobulin, ATCH, number of involved organs, regions of lymph node involvement, treatment, chemotherapy cycles, SUVmax, MTV, and TLG showed association with OS (P<0.1). In multivariate analysis, Ann Arbor stage, ß2-microglobulin, ATCH, number of involved organs, and treatment were shown to be independent prognostic factors for OS. We found that SUVmax, MTV, and TLG correlated with Ann Arbor staging (P<0.05), mean standardized uptake value (SUVmean) and TLG correlated with the number of involved organs (P<0.05). Conclusions: PA-DLBCL is characterized by a low incidence and a poor prognosis. Baseline 18F-FDG PET/CT quantization parameters showed correlations with Ann Arbor staging and number of involved organs. Increasing the sample size or prolonging the follow-up period may reveal the predictive value of PET/CT quantization parameters.

17.
Rev. esp. enferm. dig ; 115(12): 742-744, Dic. 2023. ilus
Article in English | IBECS | ID: ibc-228733

ABSTRACT

We present a case of a 67-year-old male presenting with severe abdominal pain, laboratory tests revealed IgG levels of 63.5 g/L, IgG4 levels of 63.7 g/L, and negative results for ANCA (Anti-Neutrophil Cytoplasmic Antibodies), Hematuria immunofixation electrophoresis, as well as Cold globulin qualitative test. 18F-FDG PET/CT revealed multiple lesions with increased metabolism in the submaxillary saliva gland, intrahepatic bile ducts, prostate, seminal vesicle glands, and the body of the pancreas. Additionally, a circular cystic-solid lesion with metabolic heterogeneity was observed in the head of the pancreas, accompanied by visible dilatation of the pancreatic duct. The diagnostic imaging suggested IgG4-related disease (IgG4-RD), while pancreatic malignancy could not be definitively ruled out. The patient underwent fine-needle aspiration (FNA) biopsies of lung nodules and the prostate gland, all of which were consistent with the diagnosis of IgG4-RD. Additionally, FNA biopsy of a pancreatic lesion is consistent with the diagnosis of pancreatic ductal adenocarcinoma.(AU)


Subject(s)
Humans , Female , Aged , Electrophoresis , Pancreatic Neoplasms , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Immunoglobulin G4-Related Disease
18.
Front Med (Lausanne) ; 10: 1266630, 2023.
Article in English | MEDLINE | ID: mdl-37795411

ABSTRACT

Background: Xp11.2 translocation/TFE3 gene fusion associated with renal cell carcinoma (Xp11.2 RCC) exhibits unique biological characteristics and is associated with an increased incidence of tumor thrombosis, lymph node metastasis, and advanced disease stages. Multimodality imaging, including US, contrast-enhanced CT, multi-parametric MRI, and 18F-FDG PET/CT plays a crucial role in the preoperative diagnosis and differentiation of renal tumors. Case report: A 15-year-old female presented with lumbar pain worsened, and developed persistent painless hematuria. The CT attenuation values of the scan without contrast, corticomedullary phase, nephrographic phase, and delayed phases were 35 HU, 83 HU, 82 HU, and 75 HU, respectively. The solid component of the mass displayed heterogeneous marked enhancement. Furthermore, MRU indicated that the lesion involved the cortical medulla and infringed on the renal sinus fat. The lesion appeared isosignal in T1WI, slightly low signal in T2WI, and slightly high signal in DWI. The degree of enhancement in the three phases of enhancement scan was lower than that in the renal parenchyma, and hemorrhage and necrosis were observed within the internal part of the lesion. To further clarify the staging, the patient underwent 18F-FDG PET/CT. PET/CT images showed multiple irregular occupancies in the right kidney with unclear borders, showing a heterogeneous increase in 18F-FDG uptake, with SUVmax values ranging from 2.3 to 5.2 in the routine imaging phase (60 min post-injection), compared to SUVmax values ranging from 2.8 to 6.9 in the delayed imaging phase (160 min post-injection). Additionally, multiple enlarged and fused lymph nodes were observed in the medial part of the right kidney and the retroperitoneum, exhibiting a heterogeneous increase in 18F-FDG uptake, with SUVmax values ranging from 4.1 to 8.7 in the routine imaging phase, compared to SUVmax values ranging from 4.4 to 9.1 in the delayed imaging phase. The postoperative pathology, immunohistochemistry, and molecular analysis of histiocytes were consistent with a diagnosis of Xp11.2 RCC. One month after surgery, enhanced-CT examination of the patient revealed lung metastasis, peritoneal metastasis, and multiple lymph node metastases throughout the body, with an overall survival of 16 months. Conclusion: Xp11.2 RCC exhibits unique biological characteristics and is associated with an increased incidence of tumor thrombosis, lymph node metastasis, and advanced disease stages. Long-term follow-up is essential to monitor the likelihood of recurrence and metastasis. 18F-FDG PET/CT examination can comprehensively visualize the lesion's location and extent, providing a basis for clinical tumor staging and aiding in treatment monitoring and follow-up. To address the limitations of FDG, the utilization of specific tracers designed for RCC or tracers that are not excreted via the urinary system would be ideal. Further advancements in molecular imaging technologies and the development of novel tracers hold great promise in advancing the diagnosis and management of RCC, ultimately contributing to better patient outcomes and overall disease management.

19.
Clin Nucl Med ; 48(11): 953-955, 2023 11 01.
Article in English | MEDLINE | ID: mdl-37703458

ABSTRACT

ABSTRACT: Primary small cell carcinoma of the ureter is an extremely rare malignancy with a poor prognosis. We present rare interesting 18 F-FDG PET/CT images of primary small cell carcinoma of the ureter in a 37-year-old man with early recurrence and multiple metastases 2 months after laparoscopic left nephroureterectomy and pelvic tumor resection. PET/CT showed high FDG-avid lesions in the pelvis, peritoneum, the left posterior wall of the bladder, and in the right lung, providing important value in the detection of recurrence and systemic metastases.


Subject(s)
Carcinoma, Small Cell , Lung Neoplasms , Small Cell Lung Carcinoma , Ureter , Male , Humans , Adult , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18
20.
Front Med (Lausanne) ; 10: 1269587, 2023.
Article in English | MEDLINE | ID: mdl-37731724

ABSTRACT

Postpubertal testicular teratoma exhibits malignant biological behavior and has metastatic potential. We report a case of a 17-year-old patient diagnosed with postpubertal testicular teratoma with massive retroperitoneal metastasis. The pathological examination revealed a mature teratoma without any other components. However, the patient had a significantly increased level of AFP, and 18F-FDG PET/CT showed the retroperitoneal metastasis had increased FDG uptake, with a SUVmax of 15.6, suggesting the coexistence of other germ cell tumor components, and the patient might have a poor prognosis. After resection of the retroperitoneal tumor, PET/CT further revealed multiple abdominal and pelvic metastases, with a SUVmax of 22.5. Therefore, the patient received a cycle of chemotherapy and follow-up PET/CT imaging showed the achievement of complete metabolic response after the treatment. In this case, PET/CT played a crucial role in detecting metastasis, compensating for the limitations of pathological sampling, thus establishing a definitive diagnosis and predicting prognosis. And it was evident that PET/CT also has the advantage of evaluating therapeutic efficacy.

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