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1.
Neurosurg Rev ; 47(1): 259, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38844722

RESUMO

raumatic brain injury (TBI) is a significant global health concern, particularly affecting young individuals, and is a leading cause of mortality and morbidity worldwide. Despite improvements in treatment infrastructure, many TBI patients choose discharge against medical advice (DAMA), often declining necessary surgical interventions. We aimed to investigate the factors that can be associated with DAMA in TBI patients that were recommended to have surgical treatment. This study was conducted at single tertiary university center (2008-2018), by retrospectively reviewing 1510 TBI patients whom visited the emergency room. We analyzed 219 TBI surgical candidates, including 50 declining surgery (refused group) and the others whom agreed and underwent decompressive surgery. Retrospective analysis covered demographic characteristics, medical history, insurance types, laboratory results, CT scan findings, and GCS scores. Statistical analyses identified factors influencing DAMA. Among surgical candidates, 169 underwent surgery, while 50 declined. Age (60.8 ± 17.5 vs. 70.5 ± 13.8 years; p < 0.001), use of anticoagulating medication (p = 0.015), and initial GCS scores (9.0 ± 4.3 vs. 5.3 ± 3.2; p < 0.001) appeared to be associated with refusal of decompressive surgery. Based on our analysis, factors influencing DAMA for decompressive surgery included age, anticoagulant use, and initial GCS scores. Contrary to general expectations and some previous studies, our analysis revealed that the patients' medical conditions had a larger impact than socioeconomic status under the Korean insurance system, which fully covers treatment for TBI. This finding provides new insights into the factors affecting DAMA and could be valuable for future administrative plans involving national insurance.


Assuntos
Lesões Encefálicas Traumáticas , Alta do Paciente , Humanos , Lesões Encefálicas Traumáticas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Craniectomia Descompressiva , Recusa do Paciente ao Tratamento , Descompressão Cirúrgica , Escala de Coma de Glasgow
2.
Ann Surg Treat Res ; 106(5): 263-273, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38725802

RESUMO

Purpose: The cytotoxic T-lymphocyte-associated protein 4 (CTLA4) is involved in the progression of various cancers, but its biological roles in breast cancer (BRCA) remain unclear. Therefore, we performed a systematic multiomic analysis to expound on the prognostic value and underlying mechanism of CTLA4 in BRCA. Methods: We assessed the effect of CTLA4 expression on BRCA using a variety of bioinformatics platforms, including Oncomine, GEPIA, UALCAN, PrognoScan database, Kaplan-Meier plotter, and R2: Kaplan-Meier scanner. Results: CTLA4 was highly expressed in BRCA tumor tissue compared to normal tissue (P < 0.01). The CTLA4 messenger RNA levels in BRCA based on BRCA subtypes of Luminal, human epidermal growth factor receptor 2, and triple-negative BRCA were considerably higher than in normal tissues (P < 0.001). However, the overexpression of CTLA4 was associated with a better prognosis in BRCA (P < 0.001) and was correlated with clinicopathological characteristics including age, T stage, estrogen receptors, progesterone receptors, and prediction analysis of microarray 50 (P < 0.01). The infiltration of multiple immune cells was associated with increased CTLA4 expression in BRCA (P < 0.001). CTLA4 was highly enriched in antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. Conclusion: This study provides suggestive evidence of the prognostic role of CTLA4 in BRCA, which may be a therapeutic target for BRCA. Furthermore, CTLA4 may influence BRCA prognosis through antigen binding, immunoglobulin complexes, lymphocyte-mediated immunity, and cytokine-cytokine receptor interaction. These findings help us understand how CTLA4 plays a role in BRCA and set the stage for more research.

3.
Can Vet J ; 65(4): 371-374, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38562972

RESUMO

An 8-year-old neutered male shih tzu dog underwent laparotomy for cystolithectomy. Ten days later, multiple various-sized cystic nodules were observed on the suture line and surrounding abdominal skin, although the surgical incision had healed well. Microscopically, various-sized cysts lined with thin walls of stratified squamous epithelium in the dermis were dilated and filled with keratin. Adnexal differentiation from the wall was not seen. Thus, the abdominal lesions were diagnosed as comedones and epidermal cysts. Herein, we describe the case of a dog with comedones and epidermal cysts on the abdominal skin after a laparotomy. Key clinical message: Multiple various-sized cystic lesions of the follicles are described. The implantation of epidermal fragments into the dermis by surgery may induce epidermal cysts and comedones in the skin of hyperadrenocorticism-affected dogs.


Comédons et kystes épidermiques sur la peau abdominale d'un chien survenant après une laparotomie. Un chien shih tzu mâle castré de 8 ans a subi une laparotomie pour cystolithectomie. Dix jours plus tard, de multiples nodules kystiques de différentes tailles ont été observés sur la ligne de suture et sur la peau abdominale environnante, bien que l'incision chirurgicale ait bien cicatrisé. Au microscope, des kystes de différentes tailles bordés de fines parois d'épithélium pavimenteux stratifié dans le derme étaient dilatés et remplis de kératine. Aucune différenciation annexielle par rapport à la paroi n'a été observée. Ainsi, les lésions abdominales ont été diagnostiquées comme des comédons et des kystes épidermiques. Nous décrivons ici le cas d'un chien présentant des comédons et des kystes épidermiques sur la peau abdominale après une laparotomie.Message clinique clé:De multiples lésions kystiques des follicules, de différentes tailles, sont décrites. L'implantation chirurgicale de fragments d'épiderme dans le derme peut provoquer des kystes épidermiques et des comédons dans la peau des chiens atteints d'hypercorticisme.(Traduit par Dr Serge Messier).


Assuntos
Doenças do Cão , Cisto Epidérmico , Cães , Masculino , Animais , Cisto Epidérmico/cirurgia , Cisto Epidérmico/veterinária , Cisto Epidérmico/patologia , Laparotomia/veterinária , Doenças do Cão/cirurgia , Doenças do Cão/patologia
4.
Parasitol Res ; 123(4): 192, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38652173

RESUMO

The pathogenic free-living amoebae, Naegleria fowleri and Acanthamoeba polyphaga, are found in freshwater, soil, and unchlorinated or minimally chlorinated swimming pools. N. fowleri and A. polyphaga are becoming problematic as water leisure activities and drinking water are sources of infection. Chlorine dioxide (ClO2) gas is a potent disinfectant that is relatively harmless to humans at the concentration used for disinfection. In this study, we examined the amoebicidal effects of ClO2 gas on N. fowleri and A. polyphaga. These amoebae were exposed to ClO2 gas from a ready-to-use product (0.36 ppmv/h) for 12, 24, 36, and 48 h. Microscopic examination showed that the viability of N. fowleri and A. polyphaga was effectively inhibited by treatment with ClO2 gas in a time-dependent manner. The growth of N. fowleri and A. polyphaga exposed to ClO2 gas for 36 h was completely inhibited. In both cases, the mRNA levels of their respective actin genes were significantly reduced following treatment with ClO2 gas. ClO2 gas has an amoebicidal effect on N. fowleri and A. polyphaga. Therefore, ClO2 gas has been proposed as an effective agent for the prevention and control of pathogenic free-living amoeba contamination.


Assuntos
Acanthamoeba , Compostos Clorados , Desinfetantes , Naegleria fowleri , Óxidos , Compostos Clorados/farmacologia , Naegleria fowleri/efeitos dos fármacos , Acanthamoeba/efeitos dos fármacos , Óxidos/farmacologia , Desinfetantes/farmacologia , Fatores de Tempo , Análise de Sobrevida , Amebicidas/farmacologia
5.
J Wildl Dis ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38688514

RESUMO

A free-living female Korean water deer (Hydropotes inermis argyropus) was found with swelling in the left femur. Radiographic and histopathologic examination confirmed distal femoral osteosarcoma with metastases to the inguinal lymph node and the lungs; there are no previous reports of osteosarcoma in water deer.

7.
Nat Neurosci ; 27(1): 90-101, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38177337

RESUMO

Panic disorder is characterized by uncontrollable fear accompanied by somatic symptoms that distinguish it from other anxiety disorders. Neural mechanisms underlying these unique symptoms are not completely understood. Here, we report that the pituitary adenylate cyclase-activating polypeptide (PACAP)-expressing neurons in the lateral parabrachial nucleus projecting to the dorsal raphe are crucial for panic-like behavioral and physiological alterations. These neurons are activated by panicogenic stimuli but inhibited in conditioned fear and anxiogenic conditions. Activating these neurons elicits strong defensive behaviors and rapid cardiorespiratory increase without creating aversive memory, whereas inhibiting them attenuates panic-associated symptoms. Chemogenetic or pharmacological inhibition of downstream PACAP receptor-expressing dorsal raphe neurons abolishes panic-like symptoms. The pontomesencephalic PACAPergic pathway is therefore a likely mediator of panicogenesis, and may be a promising therapeutic target for treating panic disorder.


Assuntos
Ansiedade , Sintomas Inexplicáveis , Camundongos , Animais , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Medo , Comportamento Animal/fisiologia
8.
Biomed Pharmacother ; 170: 116010, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38128183

RESUMO

Triple-negative breast cancer (TNBC) is associated with metabolic heterogeneity and poor prognosis with limited treatment options. New treatment paradigms for TNBC remains an unmet need. Thus, therapeutics that target metabolism are particularly attractive approaches. We previously designed organometallic Au(III) compounds capable of modulating mitochondrial respiration by ligand tuning with high anticancer potency in vitro and in vivo. Here, we show that an efficacious Au(III) dithiocarbamate (AuDTC) compound induce mitochondrial dysfunction and oxidative damage in cancer cells. Efficacy of AuDTC in TNBC mouse models harboring mitochondrial oxidative phosphorylation (OXPHOS) dependence and metabolic heterogeneity establishes its therapeutic potential following systemic delivery. This provides evidence that AuDTC is an effective modulator of mitochondrial respiration worthy of clinical development in the context of TNBC. ONE SENTENCE SUMMARY: Metabolic-targeting of triple-negative breast cancer by gold anticancer agent may provide efficacious therapy.


Assuntos
Antineoplásicos , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Fosforilação Oxidativa , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo , Ouro/farmacologia , Ouro/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral
9.
Dev Cell ; 59(2): 211-227.e5, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38141609

RESUMO

Fetal bone development occurs through the conversion of avascular cartilage to vascularized bone at the growth plate. This requires coordinated mobilization of osteoblast precursors with blood vessels. In adult bone, vessel-adjacent osteoblast precursors are maintained by mechanical stimuli; however, the mechanisms by which these cells mobilize and respond to mechanical cues during embryonic development are unknown. Here, we show that the mechanoresponsive transcriptional regulators Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) spatially couple osteoblast precursor mobilization to angiogenesis, regulate vascular morphogenesis to control cartilage remodeling, and mediate mechanoregulation of embryonic murine osteogenesis. Mechanistically, YAP and TAZ regulate a subset of osteoblast-lineage cells, identified by single-cell RNA sequencing as vessel-associated osteoblast precursors, which regulate transcriptional programs that direct blood vessel invasion through collagen-integrin interactions and Cxcl12. Functionally, in 3D human cell co-culture, CXCL12 treatment rescues angiogenesis impaired by stromal cell YAP/TAZ depletion. Together, these data establish functions of the vessel-associated osteoblast precursors in bone development.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Transativadores , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Angiogênese , Desenvolvimento Ósseo , Morfogênese , Osteoblastos/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Sinalização YAP
10.
Neurosurg Rev ; 46(1): 314, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012480

RESUMO

The purpose of this study was to systematically review studies in the literature to assess the superiority between microsurgery and radiosurgery regarding the efficacy in improving petroclival meningioma (PCM)-related trigeminal neuralgia (TN). PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched from the inception until December 08, 2022. The overall proportion of patients with improved TN after treatment in all six included studies was 56% (95% confidence interval [CI], 35-76.9%). Higgins I2 statistics showed significant heterogeneity (I2 = 90%). Subgroup analysis showed that the proportion of improved TN was higher in the microsurgery group than that in the radiosurgery group (89%; 95% CI, 81-96.5% vs. 37%, 95% CI, 22-52.7%, respectively, p < 0.01). Subgroup analysis (for studies that documented the number of posttreatment Barrow Neurological Institute scores 1 and 2) revealed that the proportion of pain-free without medication after treatment was higher in the microsurgery group than that in the radiosurgery group (90.7%; 95% CI, 81-99.7% vs. 34.5%, 95% CI, 21.3-47.7.7%, respectively, p < 0.01). Based on the results of this meta-analysis, we concluded that microsurgery is superior to radiosurgery in controlling PCM-related TN.


Assuntos
Neoplasias Meníngeas , Meningioma , Radiocirurgia , Neoplasias da Base do Crânio , Neuralgia do Trigêmeo , Humanos , Neuralgia do Trigêmeo/cirurgia , Meningioma/radioterapia , Meningioma/cirurgia , Resultado do Tratamento , Radiocirurgia/métodos , Microcirurgia , Neoplasias da Base do Crânio/cirurgia , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Estudos Retrospectivos
11.
BMC Cancer ; 23(1): 690, 2023 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-37481516

RESUMO

Our previous work showed that KRAS activation in gastric cancer cells leads to activation of an epithelial-to-mesenchymal transition (EMT) program and generation of cancer stem-like cells (CSCs). Here we analyze how this KRAS activation in gastric CSCs promotes tumor angiogenesis and metastasis. Gastric cancer CSCs were found to secrete pro-angiogenic factors such as vascular endothelial growth factor A (VEGF-A), and inhibition of KRAS markedly reduced secretion of these factors. In a genetically engineered mouse model, gastric tumorigenesis was markedly attenuated when both KRAS and VEGF-A signaling were blocked. In orthotropic implant and experimental metastasis models, silencing of KRAS and VEGF-A using shRNA in gastric CSCs abrogated primary tumor formation, lymph node metastasis, and lung metastasis far greater than individual silencing of KRAS or VEGF-A. Analysis of gastric cancer patient samples using RNA sequencing revealed a clear association between high expression of the gastric CSC marker CD44 and expression of both KRAS and VEGF-A, and high CD44 and VEGF-A expression predicted worse overall survival. In conclusion, KRAS activation in gastric CSCs enhances secretion of pro-angiogenic factors and promotes tumor progression and metastasis.


Assuntos
Neoplasias Gástricas , Animais , Camundongos , Fator A de Crescimento do Endotélio Vascular , Proteínas Proto-Oncogênicas p21(ras) , Metástase Linfática
12.
Int J Mol Sci ; 24(11)2023 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-37298320

RESUMO

Efficient delivery of functional factors into target cells remains challenging. Although extracellular vesicles (EVs) are considered to be potential therapeutic delivery vehicles, a variety of efficient therapeutic delivery tools are still needed for cancer cells. Herein, we demonstrated a promising method to deliver EVs to refractory cancer cells via a small molecule-induced trafficking system. We generated an inducible interaction system between the FKBP12-rapamycin-binding protein (FRB) domain and FK506 binding protein (FKBP) to deliver specific cargo to EVs. CD9, an abundant protein in EVs, was fused to the FRB domain, and the specific cargo to be delivered was linked to FKBP. Rapamycin recruited validated cargo to EVs through protein-protein interactions (PPIs), such as the FKBP-FRB interaction system. The released EVs were functionally delivered to refractory cancer cells, triple negative breast cancer cells, non-small cell lung cancer cells, and pancreatic cancer cells. Therefore, the functional delivery system driven by reversible PPIs may provide new possibilities for a therapeutic cure against refractory cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Vesículas Extracelulares , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Vesículas Extracelulares/metabolismo , Sirolimo/farmacologia , Proteína 1A de Ligação a Tacrolimo , Proteínas de Ligação a Tacrolimo/metabolismo
13.
Clin Neurol Neurosurg ; 228: 107703, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37058770

RESUMO

OBJECTIVE: Many neurosurgeons routinely perform postoperative intensive care unit (ICU) management after clipping of unruptured intracranial aneurysms (UIAs). However, whether routine postoperative ICU care is necessary remains a clinical question. Therefore, we investigated which factors acted as risk factors that actually required ICU care after microsurgical clipping of unruptured aneurysms. METHODS: We included a total of 532 patients who underwent clipping surgery for UIA between January 2020 and December 2020. The patients were divided into two groups: those who really required ICU care (41 patients, 7.7%) and those who did not (491 patients, 92.3%). A backward stepwise logistic regression model was used to identify factors that were independently associated with ICU care requirement. RESULTS: The mean hospital stay duration and the operation time were significantly longer in the ICU requirement group than in the no ICU requirement group (9.9 ± 10.7 vs. 6.3 ± 3.7 days, p = 0.041), (259.9 ± 128.4 vs. 210.5 ± 46.1 min, p = 0.019). The transfusion rate was significantly higher (p = 0.024) in the ICU requirement group. Multivariable logistic regression analysis identified male sex (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.15-4.76; p = 0.0195), operation time (OR, 1.01; 95% CI, 1.00-1.01; p = 0.0022), and transfusion (OR, 2.35; 95% CI, 1.00-5.51; p = 0.0500) as independent risk factors for requiring ICU care after clipping. CONCLUSIONS: Postoperative ICU management may not be mandatory after clipping surgery for UIAs. Our results suggest that postoperative ICU management may be more required in the male sex, patients with longer operation times, and those who received a transfusion.


Assuntos
Aneurisma Intracraniano , Humanos , Masculino , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/etiologia , Procedimentos Neurocirúrgicos/efeitos adversos , Procedimentos Neurocirúrgicos/métodos , Tempo de Internação , Instrumentos Cirúrgicos , Fatores de Risco , Estudos Retrospectivos , Resultado do Tratamento
14.
World Neurosurg ; 174: e82-e91, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36894007

RESUMO

BACKGROUND: The regimen of prophylactic antibiotic for endoscopic endonasal skull base surgery (EE-SBS) varies considerably depending on surgeons and their institutes. The purpose of the present meta-analysis is to assess the effect of antibiotic regimens on EE-SBS surgery for anterior skull base tumor. METHODS: The PubMed, Embase, Web of Science, and Cochrane clinical trial databases were systematically searched through October 15, 2022. RESULTS: The 20 included studies were all retrospective. The studies included a total of 10,735 patients who underwent EE-SBS for skull base tumor. The proportion of patients with postoperative intracranial infection across all 20 studies was 0.9% (95% confidence interval [CI] 0.5%-1.3%). The proportion of postoperative intracranial infection in the multiple antibiotics group did not show statistically significant difference to that of the single antibiotic agent group (proportion: 0.6%, 95% CI 0%-1.4% vs. proportion: 1%, 95% CI 0.6%-1.5%, respectively, P = 0.39). The ultra-short duration maintenance group showed lower incidence of postoperative intracranial infection, although it did not reach statistical significance (ultra-short group: 0.7%, 95% CI 0.5%-0.9%; short duration: 1.8%, 95% CI 0.5%-3%; and long duration: 1%, 95% CI 0.2%-1.9%, P = 0.22) The combination of the multiple antibiotics group did not show meaningful low incidence of postoperative intracranial infection (antibiotics combination group: 0.6%, 95% CI 0%-1.4%; cefazolin single group: 0.8%, 95% CI 0%-1.6%; and single antibiotics other than cefazolin: 1.2%, 95% CI 0.7%-1.7%, P = 0.22). CONCLUSIONS: Multiple antibiotics did not show superiority compared with single antibiotic agent. Also, long maintenance duration of antibiotics did not reduce the incidence of postoperative intracranial infection.


Assuntos
Cefazolina , Neoplasias da Base do Crânio , Humanos , Antibacterianos/uso terapêutico , Antibioticoprofilaxia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/tratamento farmacológico , Estudos Retrospectivos , Base do Crânio/cirurgia , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Base do Crânio/tratamento farmacológico
15.
Pathogens ; 12(2)2023 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-36839446

RESUMO

Naegleria fowleri is a pathogenic free-living amoeba, commonly found around the world in warm, fresh water and soil. N. fowleri trophozoites can infect humans by entering the brain through the nose and causing usually fatal primary amebic meningoencephalitis (PAM). Trophozoites can encyst to survive under unfavorable conditions such as cold temperature, starvation, and desiccation. Recent technological advances in genomics and bioinformatics have provided unique opportunities for the identification and pre-validation of pathogen-related and environmental resistance through improved understanding of the biology of pathogenic N. fowleri trophozoites and cysts at a molecular level. However, genomic and transcriptomic data on differential expression genes (DEGs) between trophozoites and cysts of N. fowleri are very limited. Here, we report transcriptome Illumina RNA sequencing (RNA-seq) for N. fowleri trophozoites and cysts and de novo transcriptome assembly. RNA-seq libraries were generated from RNA extracted from N. fowleri sampled from cysts, and a reference transcriptome was generated through the assembly of trophozoite data. In the database, the assembly procedure resulted in 42,220 contigs with a mean length of 11,254 nucleotides and a C+G content of 37.21%. RNA sequencing showed that 146 genes in cysts of N. fowleri indicated 2-fold upregulation in comparison with trophozoites of N. fowleri, and 163 genes were downregulated; these genes were found to participate in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The KEGG pathway included metabolic (131 sequences) and genetic information processing (66 sequences), cellular processing (43 sequences), environmental information processing (22 sequences), and organismal system (20 sequences) pathways. On the other hand, an analysis of 11,254 sequences via the Gene Ontology database showed that their annotations contained 1069 biological processes including the cellular process (228 sequences) and metabolic process (214 sequences); 923 cellular components including cells (240 sequences) and cell parts (225 sequences); and 415 molecular functions including catalytic activities (195 sequences) and binding processes (186 sequences). Differential expression levels increased in cysts of N. fowleri compared to trophozoites of N. fowleri, which were mainly categorized as serine/threonine protease, kinase, and lipid metabolism-related proteins. These results may provide new insights into pathogen-related genes or environment-resistant genes in the pathogenesis of N. fowleri.

16.
Chem Sci ; 14(3): 557-565, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36741517

RESUMO

The anti-breast cancer stem cell (CSC) properties of a series of gold(i) complexes comprising various non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine 1-8 are reported. The most effective gold(i)-NSAID complex 1, containing indomethacin, exhibits greater potency for breast CSCs than bulk breast cancer cells (up to 80-fold). Furthermore, 1 reduces mammosphere viability to a better extent than a panel of clinically used breast cancer drugs and salinomycin, an established anti-breast CSC agent. Mechanistic studies suggest 1-induced breast CSC death results from breast CSC entry, cytoplasm localisation, an increase in intracellular reactive oxygen species levels, cyclooxygenase-2 downregulation and inhibition, and apoptosis. Remarkably, 1 also significantly inhibits tumour growth in a murine metastatic triple-negative breast cancer model. To the best of our knowledge, 1 is the first gold complex of any geometry or oxidation state to demonstrate anti-breast CSC properties.

17.
Brain Tumor Res Treat ; 11(1): 1-7, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36762802

RESUMO

Brain metastasis (BM) is the most common type of brain tumor in adults. The contemporary management of BM remains challenging. Advancements in systemic cancer treatment have increased the survival of patients with cancer. Although the treatment of BM is still complicated, advances in radiotherapy, including stereotactic radiosurgery and chemotherapy, have improved treatment outcomes. Surgical resection is the traditional treatment for BM and its role in the surgical resection of BM has been well established. However, refinement of the surgical resection technique and strategy for BM is needed. Herein, we discuss the evolving role of surgery in patients with BM and the future of BM treatment.

18.
J Gastrointest Surg ; 27(4): 666-676, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36627466

RESUMO

BACKGROUND: Patients (pts) with locally advanced gastric adenocarcinoma (LAGA) often receive neoadjuvant chemotherapy. A minority of patients do not respond to chemotherapy and thus may benefit from upfront surgery. Patient-derived organoids (PDOs) are an in vitro model that may mimic the chemotherapy response of the original tumors. METHODS: PDOs were generated from endoscopic biopsies of LAGAs prior to the initiation of chemotherapy and treated with the two chemotherapy regimens: FLOT and FOLFOX. Cell proliferation was assayed after 3-6 days. Following chemotherapy, pts underwent surgical resection, and percent pathological necrosis was determined. RESULTS: Successful PDOs were obtained from 13 of 24 (54%) LAGAs. Failure to generate PDOs were due to contamination (n = 3, 13%), early senescence (n = 3, 13%), and late senescence (n = 5, 21%). By H&E staining, there were significant similarities in tumor morphology and high concordance in immunohistochemical expression of 6 markers between tumors and derived PDOs. Four of 13 pts with successful PDOs did not undergo chemotherapy and surgery. For the remaining 9 pts, percent necrosis in resected tumors was ≤ 50% in 2 pts. The corresponding PDOs from these 2 pts were clearly chemoresistant outliers. The Pearson correlation coefficient between chemosensitivity of PDOs to FOLFOX (n = 2) or FLOT (n = 7) and percent tumor necrosis in resected tumors was 0.87 (p = 0.003). CONCLUSIONS: PDOs from pts with LAGAs in many respects mimic the original tumors from which they are derived and may be used to predict resistance to neoadjuvant chemotherapy. SYNOPSIS: Patient-derived organoids (PDOs) can serve as personalized in vitro models of patient tumors. In this study, PDOs from locally advanced gastric cancers were able to reliably predict resistance to neoadjuvant chemotherapy.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Terapia Neoadjuvante , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/metabolismo , Organoides/metabolismo , Organoides/patologia , Necrose
19.
World Neurosurg ; 171: e605-e610, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36535554

RESUMO

BACKGROUND: Brain metastasis from thyroid cancer (TCBM) is extremely rare; thus, despite a good treatment outcome for thyroid cancer, TCBM has shown poor clinical outcomes. Considering the short survival and poor general condition of patients with TCBM, stereotactic radiosurgery may be preferred to achieve local control. METHODS: A total of 25 patients with TCBM who underwent Gamma Knife radiosurgery (GKS) were initially included in this study; however, 3 patients were excluded because of a lack of data. RESULTS: There were 7 men (31.8%) and 15 women (68.2%) and the mean age was 63.7 years. The most common type of thyroid cancer histology was papillary carcinoma. Fourteen patients (63.6%) harbored single brain metastatic tumor and 8 (36.3%) had multiple brain metastatic tumors. The mean duration from thyroid cancer diagnosis to detection of brain metastasis was 7.7 years (range, 0-23 years). The median dose of radiation of GKS was 22 Gy (range, 18-25 Gy). There was no radiation-induced complication after GKS. The median overall survival (OS) was 15 months and the 1-year OS of patients with TCBM was 63%, the 2-year OS was 38%, and the 5-year OS was 28%. The 6-month progression-free survival (PFS) for local recurrence of TCBM was 90.4%, the 1-year PFS was 84%, and the 3-year PFS was 84%. CONCLUSIONS: GKS showed favorable local control for TCBM. However, the rate of distant brain metastasis was high and median survival of patients with TCBM was only 15 months.


Assuntos
Neoplasias Encefálicas , Radiocirurgia , Neoplasias da Glândula Tireoide , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias Encefálicas/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Seguimentos
20.
Arch Dermatol Res ; 315(5): 1233-1239, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36512072

RESUMO

An individual's first impression can be influenced by a number of esthetic factors, one of which is a natural hairline. The anterior hairline can be affected by various factors, such as race, age, forehead shape, and hair loss progression, similar to androgenetic alopecia. Information on the shape, hairline location on the forehead, and race are required to classify the anterior hairline. According to previous studies, the shape of the anterior hairline can be classified as round, M-shaped, rectangular, bell-shaped, or triangular. This study aimed to analyze the type of anterior hairline in Asian males without androgenetic alopecia. The subjects consisted of 461 males in China, Japan, Kazakhstan, Mongolia, the Philippines, South Korea, and Taiwan. We classified the shape of the anterior hairline into four types: M-shaped (M), rectangular (R), round (O), and wave-shaped (W). We classified the location of the anterior hairline into three types: high (H), middle (M) and low (L), according to the subjects' forehead ratio. Finally, we combined the shape and location types to devise a novel classification system for the anterior hairline type. The most common hairline types in our newly developed classification were MM (23.94%), RM (18.00%) and ML (11.04%). The least common types were OL (0.58%), OH (2.34%) and WH (2.74%). Our results will set standards for hairline shapes and locations, which will be helpful for evaluating hair loss treatment, establishing criteria and designs for reconstructive surgery, and developing camouflage makeups for the forehead hairline.


Assuntos
Testa , Cabelo , Humanos , Masculino , Alopecia , Povo Asiático
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