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1.
Asian J Androl ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38657119

ABSTRACT

Tumor metabolic reprogramming is a hallmark of cancer development, and targeting metabolic vulnerabilities has been proven to be an effective approach for castration-resistant prostate cancer (CRPC) treatment. Nevertheless, treatment failure inevitably occurs, largely due to cellular heterogeneity, which cannot be deciphered by traditional bulk sequencing techniques. By employing computational pipelines for single-cell RNA sequencing, we demonstrated that epithelial cells within the prostate are more metabolically active and plastic than stromal cells. Moreover, we identified that neuroendocrine (NE) cells tend to have high metabolic rates, which might explain the high demand for nutrients and energy exhibited by neuroendocrine prostate cancer (NEPC), one of the most lethal variants of prostate cancer (PCa). Additionally, we demonstrated through computational and experimental approaches that variation in mitochondrial activity is the greatest contributor to metabolic heterogeneity among both tumor cells and nontumor cells. These results establish a detailed metabolic landscape of PCa, highlight a potential mechanism of disease progression, and emphasize the importance of future studies on tumor heterogeneity and the tumor microenvironment from a metabolic perspective.

2.
Asian J Androl ; 25(2): 192-197, 2023.
Article in English | MEDLINE | ID: mdl-36629158

ABSTRACT

Reprogramming of metabolism is a hallmark of tumors, which has been explored for therapeutic purposes. Prostate cancer (PCa), particularly advanced and therapy-resistant PCa, displays unique metabolic properties. Targeting metabolic vulnerabilities in PCa may benefit patients who have exhausted currently available treatment options and improve clinical outcomes. Among the many nutrients, glutamine has been shown to play a central role in the metabolic reprogramming of advanced PCa. In addition to amino acid metabolism, glutamine is also widely involved in the synthesis of other macromolecules and biomasses. Targeting glutamine metabolic network by maximally inhibiting glutamine utilization in tumor cells may significantly add to treatment options for many patients. This review summarizes the metabolic landscape of PCa, with a particular focus on recent studies of how glutamine metabolism alterations affect therapeutic resistance and disease progression of PCa, and suggests novel therapeutic strategies.


Subject(s)
Glutamine , Prostatic Neoplasms, Castration-Resistant , Male , Humans , Glutamine/metabolism , Glutamine/therapeutic use , Prostatic Neoplasms, Castration-Resistant/drug therapy
3.
Asian J Androl ; 23(4): 400-408, 2021.
Article in English | MEDLINE | ID: mdl-33586698

ABSTRACT

Although localized prostate cancer (PCa) can be cured by prostatectomy and radiotherapy, the development of effective therapeutic approaches for advanced prostate cancer, including castration-resistant PCa (CRPC) and neuroendocrine PCa (NEPC), is lagging far behind. Identifying a novel prognostic and diagnostic biomarker for early diagnosis and intervention is an urgent clinical need. Here, we report that apolipoprotein A-I (ApoA-I), the major component of high-density lipoprotein (HDL), is upregulated in PCa based on both bioinformatics and experimental evidence. The fact that advanced PCa shows strong ApoA-I expression reflects its potential role in driving therapeutic resistance and disease progression by reprogramming the lipid metabolic network of tumor cells. Molecularly, ApoA-I is regulated by MYC, a frequently amplified oncogene in late-stage PCa. Altogether, our findings have revealed a novel indicator to predict prognosis and recurrence, which would benefit patients who are prone to progress to metastasis or even NEPC, which is the lethal subtype of PCa.


Subject(s)
Apolipoprotein A-I/metabolism , Prostatic Neoplasms/metabolism , Analysis of Variance , Cell Line/metabolism , Cell Line/physiology , Disease Progression , Humans , Lipoproteins, HDL/analysis , Lipoproteins, HDL/pharmacology , Male , Prognosis , Prostate/pathology , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology
4.
Medicine (Baltimore) ; 94(42): e1706, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26496281

ABSTRACT

Inflammatory myofibroblastic tumor (IMT) rarely arises in genitourinary tract especially beyond collecting system, which determines the unspecific clinic symptoms and sometimes can mimic malignancy. Therefore, IMT's diagnosis may usually be a pitfall. This case report characterizes a 35-year-old woman with a history of lower quadrant lasting pain followed by fever. Furthermore, radiologic examinations revealed that there were 2 lesions located in left adrenal area and left renalis. Owing to the anatomic complexity, the surgical resection was not complete. The pathologic diagnosis of the lesions was IMT. Adjuvant nonsteroids anti-inflammatory drugs were administrated after the operation. The symptoms were controlled finally and no further growing lesion was observed during a 1-year follow-up.Inflammatory myofibroblastic tumor is rare in genitourinary tract beyond the collecting system. Diagnosis should be based on histopathology. Presently, the authors report this rare case with the aim to share the experience regarding differential diagnosis and therapy.


Subject(s)
Granuloma, Plasma Cell , Urogenital Neoplasms , Adult , Female , Granuloma, Plasma Cell/diagnosis , Granuloma, Plasma Cell/surgery , Humans , Urogenital Neoplasms/diagnosis , Urogenital Neoplasms/surgery
5.
Asian J Androl ; 16(5): 778-81, 2014.
Article in English | MEDLINE | ID: mdl-24875823

ABSTRACT

This case-controlled study was designed to evaluate the association between various baseline parental factors and the risk of hypospadias in China. Patients were selected from tertiary referral hospitals in Anhui, a province in mid-eastern China. A questionnaire was given to the parents of each patient. The final database included 193 cases and 835 controls. The incidence of additional coexistent anomalies was 13.0%, primarily cryptorchidism (9.8%). Ten patients (5.1%) were from families with genital anomaly, including five families (2.6%) with hypospadias. The risks of hypospadias was higher for children of mothers > 35 (odds ratio [OR] =1.47) and < 18 (OR = 2.95) years of age, and in mothers who had consumed alcohol (OR = 2.67), used drugs (OR = 1.53) and had an infection (OR = 1.87) during pregnancy. The risk of hypospadias was also higher when mothers (OR = 1.68) and fathers (OR = 1.74) were engaged in agriculture. Other factors assessed were not associated with the risk of hypospadias.


Subject(s)
Agriculture/statistics & numerical data , Alcohol Drinking/epidemiology , Hypospadias/epidemiology , Maternal Exposure/statistics & numerical data , Occupational Exposure/statistics & numerical data , Paternal Exposure/statistics & numerical data , Pregnancy Complications, Infectious/epidemiology , Substance-Related Disorders/epidemiology , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , China/epidemiology , Comorbidity , Cryptorchidism/epidemiology , Female , Genetic Predisposition to Disease , Humans , Hypospadias/genetics , Male , Maternal Age , Pregnancy , Retrospective Studies , Risk Factors , Young Adult
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