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1.
Pharmacol Res ; : 107302, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39004242

RESUMO

Bladder cancer stands as a prevalent global malignancy, exhibiting notable sex-based variations in both incidence and prognosis. Despite substantial strides in therapeutic approaches, the formidable challenge of drug resistance persists. The genomic landscape of bladder cancer, characterized by intricate clonal heterogeneity, emerges as a pivotal determinant in fostering this resistance. Clonal evolution, encapsulating the dynamic transformations within subpopulations of tumor cells over time, is implicated in the emergence of drug-resistant traits. Within this review, we illuminate contemporary insights into the role of clonal evolution in bladder cancer, elucidating its influence as a driver in tumor initiation, disease progression, and the formidable obstacle of therapy resistance.

2.
Chin J Cancer Res ; 36(3): 341-350, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38988484

RESUMO

Aging and circadian rhythms have been connected for decades, but their molecular interaction has remained unknown, especially for cancers. In this situation, we summarized the current research actuality and problems in this field using the bibliometric analysis. Publications in the PubMed and Web of Science databases were retrieved. Overall, there is a rising trend in the publication volume regarding aging and circadian rhythms in the field of cancer. Researchers from USA, Germany, Italy, China and England have greater studies than others. Top three publication institutions are University of California System, UDICE-French Research Universities and University of Texas System. Current research hotspots include oxidative stress, breast cancer, melatonin, cell cycle, calorie restriction, prostate cancer and NF-KB. In conclusion, results generated by bibliometric analysis indicate that many approaches involve in the complex interactions between aging and circadian rhythm in cancer. These established and emerging research directions guide our exploration of the regulatory mechanisms of aging and circadian rhythms in cancer and provide a reference for developing new research avenues.

3.
Prostate ; 83(7): 722-728, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36891865

RESUMO

PURPOSE: The objective of this study is to analyze characteristics of recurrent acute urinary retention (AUR) in patients with benign prostatic hyperplasia (BPH), utilizing a population based data set. Also, we sought to report on how AUR was treated, specifically regarding the need and length of catheterization and types of procedures utilized for mitigation. MATERIALS & METHODS: A retrospective observational cohort study was performed using Optum's deidentified Clinformatics® Data Mart Database. We compared two groups, BPH patients with AUR (n = 180,737) and BPH patients without AUR (n = 1,139,760) from January 1, 2003 to December 31, 2017. Also, we analyzed the factors affecting the development of multiple episodes of AUR through age-adjusted multivariate analysis. RESULTS: In contrast to the 47.7% of patients who had a single AUR episode, 33.5% of AUR patients developed 3 or more subsequent episodes of retention. For age matched patients, the risks of additional episodes of retention increase significantly with older age, Caucasian race, diabetes, neurologic conditions, or low income. Overall, the rate of BPH surgery in AUR patients over the study period decreased and the most common procedure was transurethral resection of the prostate. CONCLUSIONS: Risk factors for multiple episodes of AUR included age (60 and older), Caucasian race, lower income socioeconomic status, diabetes, and neurological disorders. Patients with a high probability of developing recurrent episodes of AUR are recommended to receive preemptive BPH medication before such AUR occurrences. Also, more expeditious surgical treatment should be considered rather than temporary catheterization when AUR occurs.


Assuntos
Hiperplasia Prostática , Ressecção Transuretral da Próstata , Retenção Urinária , Masculino , Humanos , Estados Unidos/epidemiologia , Hiperplasia Prostática/complicações , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/tratamento farmacológico , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Estudos Retrospectivos , Ressecção Transuretral da Próstata/efeitos adversos , Fatores de Risco , Doença Aguda
4.
Curr Issues Mol Biol ; 44(10): 4921-4929, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36286049

RESUMO

Pathways such as VEGF, EGF and mTOR are known to be one of the major mechanisms of tumorigenesis including kidney cancer. To identify potential signaling pathway proteins, we performed differential/correlation analyses of mTOR-associated genes from three public datasets. AKT1 protein, one of the PI3K/AKT/mTOR pathways, turned out to be the potential by showing a consistent discrepancy between ccRCC-associated conditions as well as strong correlation with other mTOR-associated genes across the datasets. Then, we analyzed how AKT1 alteration affects clear cell renal cell carcinoma. The pathology of 58 kidney cancer patients was constructed to analyze the relationship between the expression level of AKT1 through immunohistochemical staining and their clinicopathological data. Gender, age and TNM stage did not show significant results. AKT1 is a known oncogene. However, in this study, high expression of AKT1 showed a slight correlation with lower WHO/ISUP grade, longer recurrence-free and progression-free survival rates.

5.
J Korean Med Sci ; 36(46): e293, 2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845871

RESUMO

OBJECTIVES: To investigate the prevalence of bladder pain syndrome (BPS)-like symptoms in the general population of South Korea. METHODS: Between April 16, 2016 and April 29, 2016, we conducted an online survey and computer-assisted personal interviews with adults aged 40-79 years in Korea using structured questionnaires. The sample size was 3,000 (95% confidence level standard error ± 1.79%), and the sampling method was simple randomization according to sex, age, and residential area in proportion to the resident registration demographics of the Korean Ministry of Interior and Safety as of March 2016. All participants were surveyed using the Korean version of the Pelvic Pain and Urgency/Frequency (PUF) Patient Symptom Scale and Geriatric Depression Scale (GDS). The primary outcome was the prevalence of BPS-like symptoms, defined as a total PUF score of ≥ 12. RESULTS: Overall, the prevalence of BPS-like symptoms was 16.4% (483 of 3,000 participants). Women (21.4%) had a significantly higher prevalence of BPS-like symptoms than men (10.7%) (P < 0.01). The prevalence by age was significantly higher in the 70s group than in the other age groups (P < 0.01), and increased significantly with the increasing severity of depression on the GDS (P < 0.01). The prevalence of BPS-like symptoms according to the marital status was significantly different, that is, the prevalence among divorced/bereaved individuals was higher than those of married or unmarried individuals (P < 0.01). CONCLUSION: Our large, representative population-based study showed that BPS-like symptoms are widespread among the general population of South Korea. BPS is considered a disease that deserves greater attention as it is far more common than previously thought and can negatively affect many people's quality of life.


Assuntos
Cistite Intersticial/epidemiologia , Adulto , Idoso , Cistite Intersticial/complicações , Depressão/complicações , Depressão/patologia , Feminino , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Prevalência , República da Coreia/epidemiologia , Índice de Gravidade de Doença , Fatores Sexuais , Inquéritos e Questionários
6.
Medicina (Kaunas) ; 57(6)2021 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-34073208

RESUMO

Background and objectives: To investigate the risk factors for emphysematous cystitis (EC) compared to those of acute cystitis (AC) to increase clinicians awareness of the possibility for the aggravation of patient status. Materials and methods: We retrospectively reviewed a total of 54 patients who were hospitalized with a diagnosis of EC by abdominal computed tomography (CT) scan from 2006 to 2020. The control group included 92 patients who were hospitalized for the treatment of AC in the same period. We sought to identify the clinical features and predisposing diseases, such as age, sex, diabetes mellitus (DM), hypertension (HTN), cerebrovascular accident (CVA), chronic kidney disease (CKD), neurogenic bladder (NB), history of urinary tract infection (UTI), and emphysematous pyelonephritis (EPN), that were associated with the development of EC. Results: The median (interquartile range (IQR)) age of the patients with EC was older than that of the patients with AC (78.5 (15.3) years (range: 52-100) vs. 70.0 (26.5) years (range: 28-97 years)). Sepsis and mortality occurred only in the EC group (48.1% and 11.1%, respectively). The univariate analysis of predisposing factors revealed that age, DM, HTN, CVA, CKD, and NB were significantly associated with EC. In the multivariate analysis, DM (OR, 6.251; 95% CI, 2.254-17.250; p < 0.001), CKD (OR, 18.439; 95% CI, 3.421-99.404; p = 0.001), NB (OR, 7.374; 95% CI, 1.993-27.285; p = 0.003) were associated with EC. Conclusions: The results of this study revealed that DM, CKD, and NB were significant risk factors for EC. The tendency toward sepsis and high mortality underscore the need for careful observation while treating patients with EC with the risk noted above.


Assuntos
Cistite , Enfisema , Idoso , Idoso de 80 Anos ou mais , Cistite/complicações , Cistite/epidemiologia , Enfisema/complicações , Enfisema/diagnóstico por imagem , Enfisema/epidemiologia , Análise Fatorial , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
7.
Medicina (Kaunas) ; 57(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34577793

RESUMO

Giant multilocular prostatic cystadenoma is a rare benign tumor of the prostate gland that presents as a large retroperitoneal pelvic mass. The mass is usually located between the urinary bladder and rectum, and results in obstructive voiding symptoms and a change in bowel habits. Complete surgical excision is the treatment of choice. We present a case of rapid recurrent giant multilocular prostatic cystadenoma after laparoscopic excision for primary case. A previously healthy 54-year-old man presented with acute urinary retention. Prostate MRI showed a large cystic mass approximately 13 cm in size, multiple septa and lobulation in the prostate, and no visible solid lesions. Laparoscopic marsupialization of giant multilocular prostatic cystadenoma cysts was performed. One year later, the patient presented with local recurrence. Repeated laparoscopic complete resection was performed without any complications and further recurrence. Giant multilocular prostatic cystadenoma has the risk of recurrence in case of incomplete resection. Surgical treatment should be performed with the goal of complete removal following the same principles as cancer surgery.


Assuntos
Cistadenoma , Laparoscopia , Neoplasias da Próstata , Cistadenoma/diagnóstico por imagem , Cistadenoma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia
8.
Medicina (Kaunas) ; 57(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34206139

RESUMO

Background and objectives: The aim of our study was to evaluate the role of diabetes mellitus (DM) as a significant factor affecting spontaneous stone expulsion, as suggested by previous research. Materials and methods: We investigated the influence of DM on the ureter using a murine model. The mouse-model arm of this study used 20 15 -week-old mice, including 10 normal (control) mice and 10 DM mice. We measured the proximal, middle and distal ureteral smooth muscle thickness in each mouse and the differences among ureteral sections were analyzed. Mouse ureteral specimens were also analyzed via western blotting to detect relative protein expression of phosphor-extracellular signal regulated kinases (P-ERK), phosphor-C-Jun N-terminal kinase (P-JNK), vascular endothelial growth factor (VEGF), and protein kinase C (PKC), which are representative factors involved in cell regulation. Results: We observed significant hyperproliferation of ureteral smooth muscle in DM mice compared to normal mice, which may provoke reduced peristalsis. The ureteral smooth muscle of DM mice was significantly thicker than that of normal mice in all ureteral tissues: proximal (p = 0.040), mid (p = 0.010), and distal (p = 0.028). The relative protein expression of P-ERK (p = 0.005) and P-JNK (p = 0.001) was higher in the diabetic group compared to the normal group. Additionally, protein expression of VEGF (p = 0.002) and PKC (p = 0.001) were remarkably up-regulated in DM mice. Conclusions: Hyperproliferation of ureteral smooth muscle was observed in DM mice, but not in normal mice. The pathways mediated by P-ERK, P-JNK, VEGF, and PKC may play an important role in pathological ureteral conditions.


Assuntos
Diabetes Mellitus , MAP Quinases Reguladas por Sinal Extracelular , Animais , Proliferação de Células , Camundongos , Músculo Liso/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
9.
Medicina (Kaunas) ; 57(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34357008

RESUMO

Background and Objectives: Retroperitoneal schwannoma is a very rare case of schwannoma which commonly occurs in the other part of the body. However, it is difficult to distinguish schwannoma from other tumors before pathological examination because they do not show specific characteristics on imaging study such as ultrasound, computed tomography (CT), and magnetic resonance image (MRI). Case summary: A 60-year-old male showed a retroperitoneal cystic tumor which is found incidentally during evaluation of coexisted bladder tumor. Neurogenic tumor was suspicious for the retroperitoneal tumor through pre-operative imaging study. Finally, a schwannoma was diagnosed by immunohistochemical examination after complete surgical excision laparoscopically. Conclusion: As imaging technology is developed, there may be more chances to differentiate schwannoma from other neoplasm. However, still surgical resection and histopathological examination is feasible for diagnosis of schwannoma.


Assuntos
Neurilemoma , Neoplasias Retroperitoneais , Neoplasias da Bexiga Urinária , Humanos , Linfonodos/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Neurilemoma/cirurgia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/cirurgia , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia
10.
J Korean Med Sci ; 35(43): e359, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169555

RESUMO

BACKGROUND: Complicated acute pyelonephritis (APN) is a life-threatening condition that requires immediate intervention. This study examined the characteristics of APN occurring as a complication of ureteral stone. METHODS: We retrospectively reviewed 85 patients diagnosed with APN complicated by ureteral stone between December 2006 and July 2017 at our institution. Patients with concomitant renal stone, multiple ureteral stones, ureteral strictures, ureteral cancer, and urogenital anomalies, including vesicoureteral reflux were excluded. Clinical characteristics including age, sex, underlying disease, medical history, stone characteristics, initial laboratory data, and the procedure used to correct urinary obstruction were summarized, and the risk factors associated with sepsis and septic shock were analyzed. RESULTS: Sepsis was diagnosed at initial presentation in 62 patients, 17 of whom suffered from septic shock. Disease-related death did not occur in any patient. Previous history of stone (P = 0.015), leukocytosis (P < 0.001), elevated C-reactive protein levels (P = 0.006), and low albumin (P = 0.038) were significant risk factors for progression to sepsis. The absence of hypertension (P = 0.047), thrombocytopenia (P = 0.006), decreased erythrocyte sedimentation rate (ESR) (P = 0.003), elevated blood urea nitrogen (P = 0.016), and positive blood culture (P = 0.018) were significant predictors for progression to septic shock. Multivariate analysis revealed that previous history of stone (P = 0.015) was an independent risk factor for sepsis, while the absence of hypertension (P = 0.047), thrombocytopenia (P = 0.013), and decreased ESR (P = 0.009) were risk factors for shock. CONCLUSION: The risk factors associated with the progression from APN to sepsis differed from those associated with the progression from sepsis to septic shock. Various factors should be considered while selecting treatment options based on the severity of APN associated with ureteral stone. It should be managed with aggressive treatment and close observation, especially in the presence of risk factors.


Assuntos
Sepse/complicações , Choque Séptico/complicações , Cálculos Ureterais/complicações , Obstrução Ureteral/etiologia , Urolitíase , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Obstrução Ureteral/cirurgia
11.
J Korean Med Sci ; 32(10): 1669-1673, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28875612

RESUMO

The objectives of this study were to investigate patients treated for scrotal trauma at our institute for the last three decades to describe our experience with an emphasis on the etiologies and ultrasonographic findings in these patients. We reviewed medical records of patients who underwent scrotal ultrasonography for evaluation of testicular trauma at our institutes from 1986 to 2015. Trends regarding the etiology of scrotal trauma were evaluated during each decade. The echo pattern and contour definition of the testicular parenchyma and the pattern of hematoma development were recorded to evaluate radiographic findings of testicular injury. The correlation between ultrasonographic and intraoperative findings was assessed. A total of 115 patients were analyzed. Most patients (92.2%) presented with blunt trauma. The most common etiology of testicular trauma was assault during the first and second decades, while injury related to a fall was most common during the third decade. Of the 77 patients (67.0%) who underwent urgent exploration, 46 patients (59.7%) had testicular rupture. Loss of contour definition, heterogeneous echo pattern of the testicular parenchyma, and testicular hematoma showed a moderate to strong degree of correlation with testicular rupture (Spearman correlation co-efficient: 0.5-0.8). Over the past 30 years, the etiology of testicular injury changed from assault to falls or athletic injury and the severity of injury has decreased. Our findings demonstrate the importance of ultrasonography for determining an appropriate management strategy in scrotal trauma. Surgical exploration should be considered in patients with abnormal ultrasonographic findings.


Assuntos
Testículo/lesões , Adolescente , Adulto , Hematoma/etiologia , Humanos , Masculino , República da Coreia , Escroto/patologia , Testículo/diagnóstico por imagem , Testículo/patologia , Ultrassonografia , Adulto Jovem
12.
Exp Cell Res ; 336(1): 119-29, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26112218

RESUMO

Despite its wide use as a first-line therapeutic agent, gemcitabine has shown limited efficacy in advanced pancreatic cancer due to chemoresistance by as yet unidentified mechanisms. Our goal here was to identify molecular features involved in gemcitabine chemoresistance. Pyruvate kinase M2 (PKM2), a key enzyme of aerobic glycolysis, has recently emerged as an important therapeutic target for cancer treatment. It is involved in the metabolic reprogramming of cancer cells and has previously unexpected non-metabolic functions that are heavily involved in tumor growth and survival. Herein, we report that the chemoresistance of pancreatic cancer to gemcitabine was dependent on PKM2 expression and its non-metabolic function. Knocking-down of PKM2 significantly enhanced gemcitabine-induced cell apoptosis through the activation of caspase 3/7 and PARP cleavage, and this inhibitory activity was associated with p38-mediated activation of p53 phosphorylation at serine 46. Our findings support the potential of PKM2 as a novel target for gemcitabine chemoresistance and suggest the feasibility of combining gemcitabine and PKM2 inhibition for the improved chemotherapy of pancreatic cancer.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Proteínas de Transporte/metabolismo , Desoxicitidina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Hormônios Tireóideos/metabolismo , Apoptose , Western Blotting , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Proliferação de Células , Desoxicitidina/farmacologia , Humanos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Neoplasias Pancreáticas/enzimologia , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Hormônios Tireóideos/genética , Células Tumorais Cultivadas , Gencitabina , Proteínas de Ligação a Hormônio da Tireoide
13.
J Korean Med Sci ; 31(11): 1808-1813, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27709861

RESUMO

The objectives of this study were to investigate risk factors and the incidence of ciprofloxacin resistance and extended-spectrum beta-lactamases (ESBL) in patients with acute bacterial prostatitis (ABP). We reviewed the medical records of 307 patients who were diagnosed with ABP between January 2006 and December 2015. The etiologic pathogens and risk factors for ciprofloxacin-resistant E. coli and ESBL-producing microbes, susceptibility to ciprofloxacin, and the incidence of ESBL in patients with ABP were described. History of prior urologic manipulation was an independent risk factor for ciprofloxacin-resistant (P = 0.005) and ESBL-producing microbes (P = 0.005). Advanced age (over 60 years) was an independent risk factor for ciprofloxacin-resistant microbes (P = 0.022). The ciprofloxacin susceptibility for Escherichia coli in groups without prior manipulation was documented 85.7%. For groups with prior manipulation, the susceptibility was 10.0%. Incidence of ESBL-producing microbes by pathogen was 3.8% for E. coli and 1.0% for Klebsiella pneumonia in the absence of manipulation group, and 20% and 33.3% in the presence of manipulation group, respectively. Initial treatment of ABP must consider patient's age and the possibility of prior manipulation to optimize patient treatment. With the high rate of resistance to fluoroquinolone, cephalosporins with amikacin, or carbapenems, or extended-spectrum penicillin with beta lactamase inhibitor should be considered as the preferred empirical ABP treatment in the patients with history of prior urologic manipulation.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Ciprofloxacina/uso terapêutico , Farmacorresistência Bacteriana , Prostatite/diagnóstico , beta-Lactamases/metabolismo , Doença Aguda , Adulto , Fatores Etários , Idoso , Amicacina/farmacologia , Antibacterianos/farmacologia , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Cefalosporinas/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/isolamento & purificação , Humanos , Imipenem/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/enzimologia , Klebsiella pneumoniae/isolamento & purificação , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prostatite/tratamento farmacológico , Prostatite/microbiologia , República da Coreia , Estudos Retrospectivos , Fatores de Risco
14.
J Korean Med Sci ; 29(12): 1684-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25469070

RESUMO

Testicular torsion is a surgical emergency in the field of urology. Knowledge of the epidemiology and pathophysiology is significant to an urologist. However, the epidemiology of testicular torsion in Korea has not been studied. We performed a nationwide epidemiological study to improve knowledge of the epidemiology of testicular torsion. From 2006-2011, the Korean Urologic Association began the patient registry service. The annual number of patients with testicular torsion from 2006 to 2011 were 225, 250, 271, 277, 345, and 210, respectively. The overall incidence of testicular torsion in males was 1.1 per 100,000; However, the incidence in men less than 25 yr old was 2.9 per 100,000. Adolescents showed the highest incidence. Total testicular salvage rate was 75.7% in this survey. There was no geographic difference of testicular salvage rate. Minimizing the possibility of orchiectomy for testicular torsion is important to improve public awareness to expedite presentation and provider education to improve diagnosis and surgery.


Assuntos
Orquiectomia/estatística & dados numéricos , Torção do Cordão Espermático/epidemiologia , Torção do Cordão Espermático/cirurgia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Humanos , Incidência , Lactente , Recém-Nascido , Coreia (Geográfico)/epidemiologia , Masculino , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Torção do Cordão Espermático/diagnóstico , Resultado do Tratamento , Adulto Jovem
15.
Toxicol Lett ; 399: 9-18, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971455

RESUMO

Fine particulate matter (PM2.5) is a risk factor for pulmonary diseases and lung cancer, and inhaled PM2.5 is mainly deposited in the bronchial epithelium. In this study, we investigated the effect of long-term exposure to low-dose PM2.5 on BEAS-2B cells derived from the normal bronchial epithelium. BEAS-2B cells chronically exposed to a concentration of 5 µg/ml PM2.5 for 30 passages displayed the phenotype promoting epithelial-mesenchymal transition (EMT) and cell invasion. Cellular internalization of exosomes (designated PM2.5 Exo) extracted from BEAS-2B cells chronically exposed to low-dose PM2.5 promoted cell invasion in vitro and metastatic potential in vivo. Hence, to identify the key players driving phenotypic alterations, we analyzed microRNA (miRNA) expression profiles in PM2.5 Exo. Five miRNAs with altered expression were selected: miRNA-196b-5p, miR-135a-2-5p, miR-3117-3p, miR-218-5p, and miR-497-5p. miR-196b-5p was the most upregulated in both BEAS-2B cells and isolated exosomes after PM2.5 exposure. In a functional validation study, genetically modified exosomes overexpressing a miR-196b-5p mimic induced an enhanced invasive phenotype in BEAS-2B cells. Conversely, miR-196b-5p inhibition diminished the PM2.5-enhanced EMT and cell invasion. These findings indicate that exosomal miR-196b-5p may be a candidate biomarker for predicting the malignant behavior of the bronchial epithelium and a therapeutic target for inhibiting PM2.5-triggered pathogenesis.

16.
Phytomedicine ; 127: 155503, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38490077

RESUMO

BACKGROUND: Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE: This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN: systematic review METHODS: PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION: These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.


Assuntos
Produtos Biológicos , Carcinoma de Células de Transição , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Neoplasias da Bexiga Urinária , Masculino , Humanos , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Testiculares/tratamento farmacológico , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Transdução de Sinais , Microambiente Tumoral
17.
J Cancer Res Clin Oncol ; 150(3): 123, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38472489

RESUMO

BACKGROUND: There is currently a limited number of studies on transglutaminase type 1 (TGM1) in tumors. The objective of this study is to perform a comprehensive analysis across various types of cancer to determine the prognostic significance of TGM1 in tumors and investigate its role in the immune environment. METHOD: Pan-cancer and mutational data were retrieved from the TCGA database and analyzed using R (version 3.6.4) and its associated software package. The expression difference and prognosis of TGM1 were examined, along with its correlation with tumor heterogeneity, stemness, mutation landscape, and RNA modification. Additionally, the relationship between TGM1 expression and tumor immunity was investigated using the TIMER method. RESULTS: TGM1 is expressed differently in various tumors and normal samples and is associated with the overall survival and progression-free time of KIRC, ACC, SKCM, LIHC, and STES. In LICH, we found a negative correlation between TGM1 expression and 6 indicators of tumor stemness. The mutation frequencies of BLCA, LIHC, and KIRC were 1.7%, 0.3%, and 0.3% respectively. In BLCA and BRCA, there was a significant correlation between TGM1 expression and the infiltration of CD4 + T cells, CD8 + T cells, neutrophils, and dendritic cells. CONCLUSION: TGM1 has the potential to serve as both a prognostic marker and a drug target.


Assuntos
Neoplasias , Humanos , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Transglutaminases
18.
Redox Biol ; 73: 103208, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851002

RESUMO

BACKGROUND: Recently, numerous studies have reported the interaction between senescence and oxidative stress in cancer. However, there is a lack of a comprehensive understanding of the precise mechanisms involved. AIM: Therefore, our review aims to summarize the current findings and elucidate by presenting specific mechanisms that encompass functional pathways, target genes, and related aspects. METHODS: Pubmed and Web of Science databases were retrieved to search studies about the interaction between senescence and oxidative stress in cancer. Relevant publications in the reference list of enrolled studies were also checked. RESULTS: In carcinogenesis, oxidative stress-induced cellular senescence acts as a barrier against the transformation of stimulated cells into cancer cells. However, the senescence-associated secretory phenotype (SASP) is positively linked to tumorigenesis. In the cancer progression stage, targeting specific genes or pathways that promote oxidative stress-induced cellular senescence can suppress cancer progression. In terms of treatment, many current clinical therapies combine with novel drugs to overcome resistance and reduce side effects by attenuating oxidative stress-induced senescence. Notably, emerging drugs control cancer development by enhancing oxidative stress-induced senescence. These studies highlight the complacted effects of the interplay between oxidative stress and senescence at different cancer stages and among distinct cell populations. Future research should focus on characterizing the roles of distinct senescent cell types in various tumor stages and identifying the specific components of SASP. CONCLUDSION: We've summarized the mechanisms of senescence and oxidative stress in cancer and provided illustrative figures to guide future research in this area.


Assuntos
Senescência Celular , Neoplasias , Estresse Oxidativo , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Neoplasias/genética , Neoplasias/tratamento farmacológico , Animais , Fenótipo Secretor Associado à Senescência , Transdução de Sinais
19.
Oncol Res ; 32(3): 503-515, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361753

RESUMO

The increasing interest in RNA modifications has significantly advanced epigenomic and epitranscriptomic technologies. This study focuses on the immuno-oncological impact of ALYREF in human cancer through a pan-cancer analysis, enhancing understanding of this gene's role in cancer. We observed differential ALYREF expression between tumor and normal samples, correlating strongly with prognosis in various cancers, particularly kidney renal papillary cell carcinoma (KIRP) and liver hepatocellular carcinoma (LIHC). ALYREF showed a negative correlation with most tumor-infiltrating cells in lung squamous cell carcinoma (LUSC) and lymphoid neoplasm diffuse large B-cell lymphoma (DLBC), while positive correlations were noted in LIHC, kidney chromophobe (KICH), mesothelioma (MESO), KIRP, pheochromocytoma and paraganglioma (PARD), and glioma (GBMLGG). Additionally, ALYREF expression was closely associated with tumor heterogeneity, stemness indices, and a high mutation rate in TP53 across these cancers. In conclusion, ALYREF may serve as an oncogenic biomarker in numerous cancers, meriting further research attention.


Assuntos
Neoplasias , Proteínas Nucleares , Proteínas de Ligação a RNA , Fatores de Transcrição , Humanos , 5-Metilcitosina , Neoplasias/metabolismo
20.
Int J Surg ; 110(4): 2323-2337, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38241327

RESUMO

Spindle and kinetochore-associated complex subunit 3 (SKA3) is a microtubule-binding subcomplex of the outer kinetochore, which plays a vital role in proper chromosomal segregation and cell division. Recently, SKA3 have been demonstrated its oncogenic role of tumorigenesis and development in cancers. In this review, the authors comprehensively deciphered SKA3 in human cancer from various aspects, including bibliometrics, pan-cancer analysis, and narrative summary. The authors also provided the top 10 predicted drugs targeting SKA3. The authors proposed that SKA3 was a potential target and brought new therapeutic opportunities for cancer patients.


Assuntos
Proteínas de Ciclo Celular , Neoplasias , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/cirurgia , Terapia de Alvo Molecular/métodos , Medicina de Precisão/métodos , Proteínas Associadas aos Microtúbulos/metabolismo
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