ABSTRACT
Introduction: Myeloid-derived suppressor cell (MDSC) exhibits immunosuppressive functions and affects cancer progression, but its relationship with prostate cancer remains unclear. We elucidated the association of polymorphonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC) levels of the total peripheral blood mononuclear cells (PBMCs) with prostate cancer progression and evaluated their roles as prognostic indicators. Methods: We enrolled 115 patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC, n = 62), metastatic hormone-sensitive prostate cancer (mHSPC, n = 23), and metastatic castration-resistant prostate cancer (mCRPC, n = 30). Subsequently, the proportions of MDSCs in each disease progression were compared. Log-rank tests and multivariate Cox regression analyses were performed to ascertain the associations of overall survival. Results: The patients with mCRPC had significantly higher PMN-MDSC percentage than those with nmHSPC and mHSPC (P = 7.73 × 10-5 and 0.0014). Significantly elevated M-MDSC levels were observed in mCRPC patients aged <70 years (P = 0.016) and with a body mass index (BMI) <25 kg/m2 (P = 0.043). The high PMN-MDSC group had notably shorter median survival duration (159 days) than the low PMN-MDSC group (768 days, log-rank P = 0.018). In the multivariate analysis including age, BMI, and MDSC subset, PMN-MDSC was significantly associated with prognosis (hazard ratios, 3.48; 95% confidence interval: 1.05-11.56, P = 0.042). Discussion: PMN-MDSC levels are significantly associated with mCRPC prognosis. Additionally, we highlight the remarkable associations of age and BMI with M-MDSC levels in mCRPC, offering novel insights into MDSC dynamics in prostate cancer progression.
Subject(s)
Myeloid-Derived Suppressor Cells , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Myeloid-Derived Suppressor Cells/immunology , Myeloid-Derived Suppressor Cells/metabolism , Prostatic Neoplasms, Castration-Resistant/immunology , Prostatic Neoplasms, Castration-Resistant/pathology , Prostatic Neoplasms, Castration-Resistant/mortality , Prostatic Neoplasms, Castration-Resistant/blood , Aged , Prognosis , Middle Aged , Neutrophils/immunology , Disease Progression , Aged, 80 and over , Neoplasm MetastasisABSTRACT
Low testosterone levels in men have been linked to decreased physical and mental function, as well as a reduced quality of life. Previous prospective observational studies have suggested an association between testosterone and sleep traits, but the causality of this relationship remains unclear. We aimed to explore the potential causal link between genetically determined sleep traits and testosterone levels in men using Mendelian randomization (MR) analysis from the UK Biobank dataset. Our exposures were genetic variants associated with sleep traits (chronotype and sleep duration), whereas our outcomes were traits of sex steroid hormones (total testosterone, TT; bioavailable testosterone, BAT; and sex hormone-binding globulin, SHBG). We employed inverse variance weighted (IVW) and weighted median (WM) methods to assess the causal associations. The IVW method offers a robust estimate of causality, whereas the WM method provides reliable results even when some genetic variants are invalid instruments. Our main analysis involving sex steroid hormones and chronotype identified 155 chronotype-related variants. The primary findings from the analysis, which used chronotype as the exposure and sex steroid hormones as the outcomes, showed that a genetically predicted chronotype score was significantly associated with an increased levels of TT (association coefficient ß, 0.08; 95% confidence interval [CI], 0.02-0.14; P = 0.008) and BAT (ß, 0.08; 95% CI, 0.02-0.14; P = 0.007), whereas there was no significant association with SHBG (ß, 0.01; 95% CI, -0.02-0.03; P = 0.64). Meanwhile, MR analysis of sex steroid hormones and sleep duration was performed, and 69 variants associated with sleep duration were extracted. There were no significant association between sleep duration and sex steroid hormones (TT, P = 0.91; BAT, P = 0.82; and SHBG, P = 0.95). Our data support a causal association between chronotype and circulating testosterone levels in men. These findings underscore a potential causal relationship between chronotype and testosterone levels in men, suggesting that lifestyle adjustments are crucial for men's health. Recognizing factors that influence testosterone is essential. One limitation of this study is the use of one-sample MR, which can introduce potential bias due to non-independence of genetic associations for exposure and outcome. In conclusion, our findings indicate that a morning preference is correlated with circulating testosterone levels, emphasizing the potential impact of lifestyle habits on testosterone levels in men.
Subject(s)
Mendelian Randomization Analysis , Sleep , Testosterone , Humans , Male , Testosterone/blood , Sleep/genetics , Sleep/physiology , Sex Hormone-Binding Globulin/genetics , Sex Hormone-Binding Globulin/metabolism , Middle Aged , Circadian Rhythm/genetics , Polymorphism, Single Nucleotide , Aged , ChronotypeABSTRACT
BACKGROUND: Leukocyte telomere length (LTL) and myeloid-derived suppressor cells (MDSC) are associated with aging and the development and progression of cancer. However, the exact nature of this relationship remains unclear. Our study aimed to investigate the potential of LTL and MDSC as diagnostic biomarkers for prostate cancer while also seeking to deepen our understanding of the relationship of these potential biomarkers to each other. METHODS: Our study involved patients undergoing a prostate biopsy. We analyzed the relative LTL in genomic DNA obtained from peripheral blood leukocytes as well as the percentage of MDSC and their subtypes in peripheral blood mononuclear cells (PBMC). Our evaluation focused on examining the relationship between LTL and MDSC and pathological diagnoses as well as investigating the correlation between LTL and MDSC levels. RESULTS: In our study of 102 participants, 56 were pathologically diagnosed with localized prostate cancer (cancer group), while 46 tested negative (control group). The cancer group exhibited significantly shorter LTL in comparison to the control group (p = 0.024). Additionally, the cancer group showed a tendency towards a higher percentage of monocytic MDSC (M-MDSC), although this difference did not reach statistical significance (p = 0.056). Our multivariate logistic regression analysis revealed that patients with shorter LTL and higher percentages of M-MDSC had a 2.98-fold (95% CI = 1.001-8.869, p = 0.049) and 3.03-fold (95% CI = 1.152-7.977, p = 0.025) increased risk of prostate cancer diagnosis, respectively. There was also a significant negative correlation between LTL and M-MDSC. (r = -0.347, p < 0.001). CONCLUSIONS: Our research has established a correlation between LTL and MDSC in patients undergoing biopsy for prostate cancer. Notably, we observed that individuals with localized prostate cancer tend to have shorter LTL and a higher percentage of M-MDSC prior to their diagnosis. These findings suggest that LTL and M-MDSC could potentially serve as adjunctive biomarkers for the early diagnosis of prostate cancer.
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Enzalutamide is a second-generation androgen receptor inhibitor that increases overall survival (OS) rates in patients with metastatic castration-resistant prostate cancer (mCRPC). This study evaluates the efficacy of circulating tumor cell (CTC) status as a prognostic biomarker following enzalutamide administration. A retrospective subgroup analysis and prognostic survey were conducted on 43 patients with mCRPC and bone metastases treated in Juntendo University-affiliated hospitals from 2015 to 2022. Patients were treated with 160 mg enzalutamide daily. CTC analyses on blood samples were performed regularly before and every three months after treatment. The relationship between the patients' clinical factors and the OS rate was analyzed using the log-rank test; the median OS was 37 months. Patients with no detected CTCs at baseline showed significantly longer OS than those with detectable CTCs at baseline. Furthermore, patients demonstrating negative reversion of CTCs during enzalutamide treatment had significantly longer OS than patients with CTC-positivity. Two biomarkers-higher hemoglobin at baseline and achieving negative reversion of CTCs-were significantly associated with prolonged OS. This study suggests that patients achieving CTC-negative reversion during treatment for mCRPC with bone metastases exhibit improved long-term OS. Chronological measurement of CTC status might be clinically useful in the treatment of mCRPC.
ABSTRACT
Testosterone is crucial in regulating several body functions in men, including metabolic, sexual, and cardiovascular functions, bone and muscle mass, and mental health. Therefore, optimizing testosterone levels in men is an important step to maintaining a healthy body and mind, especially as we age. However, traditional testosterone replacement therapy has been shown to lead to male infertility, caused by negative feedback in the hypothalamic-pituitary-gonadal (HPG) axis. Recent advances in research have led to the discovery of many new methods of administration, which can have more or less suppressive effects on the HPG axis. Also, the usage of ancillary medications instead of or after testosterone administration might help maintain fertility in hypogonadal patients. The goal of this narrative review is to summarize the newest methods for optimizing fertility parameters in patients undergoing treatment for hypogonadism and to provide the necessary information for healthcare providers to make the right treatment choices.
Subject(s)
Hypogonadism , Infertility, Male , Humans , Male , Testosterone/adverse effects , Hypogonadism/complications , Hypogonadism/drug therapy , Hypogonadism/chemically induced , Infertility, Male/drug therapy , Fertility , Hormone Replacement TherapyABSTRACT
The aim of this study is to examine the correlation between aging, serum total testosterone and biomarkers of multiple organ functions in men. The participants consisted of 12,547 outpatients, whose serum testosterone level was measured. A multiple regression analysis was conducted to determine whether biomarkers including hemoglobin (Hb), hematocrit (Hct), luteinizing hormone (LH), follicle stimulating hormone (FSH), alkaline phosphatase (ALP), albumin (ALB), creatinine (Cre), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glucose (Glu), C-reactive protein (CRP), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) values were associated with serum total testosterone concentration. Significant correlations (p < 0.05) were found between total testosterone and Hb, Hct, LH, FSH, ALP, ALB, TG, HDL-C, AST, ALT, Glu, and CRP. In addition, significant correlations (p < 0.05) were found between Hb, Hct, LH, FSH, ALP, ALB, TG and HDL-C associated with [age × testosterone]. This large-scale study provided new insights into correlations between serum testosterone and biomarkers associated with age-related diseases, suggesting that testosterone is especially important for maintaining homeostasis in aging males. Thus, hypogonadism in elderly patients may be associated with multiple organ dysfunctions.
Subject(s)
Follicle Stimulating Hormone , Luteinizing Hormone , Male , Humans , Aged , Testosterone , Triglycerides , Cholesterol, HDL , BiomarkersABSTRACT
Background: Testosterone is an essential sex hormone that plays a vital role in the overall health and development of males. It is well known that obesity decreases testosterone levels, but it is difficult to determine the causal relationship between body composition and testosterone. Methods: To investigate potential causal associations between body composition and testosterone levels by a first time application of Mendelian randomization methods. Exposure variables in men included body composition (fat mass, fat-free mass, and body mass index). In addition to whole body fat and fat-free mass, we examined fat and fat-free mass for each body part (e.g., trunk, left arm, right arm, left leg and right leg) as exposures. Instrumental variables were defined using genome-wide association study data from the UK Biobank. Outcome variables in men included testosterone levels (total testosterone [TT], bioavailable testosterone [BT], and sex hormone-binding globulin [SHBG]). A one-sample Mendelian randomization analysis of inverse-variance weighted and weighted median was performed. Results: The number of genetic instruments for the 13 exposure traits related to body composition ranged from 156 to 540. Genetically predicted whole body fat mass was negatively associated with TT (ß=-0.24, P=5.2×10-33), BT (ß=-0.18, P=5.8×10-20) and SHBG (ß=-0.06, P=8.0×10-9). Genetically predicted whole body fat-free mass was negatively associated with BT (ß=-0.04, P=2.1×10-4), but not with TT and SHBG, after multiple testing corrections. When comparing the causal effect on testosterone levels, there was a consistent trend that the effect of fat mass was more potent than that of fat-free mass. There were no differences between body parts. Conclusion: These results show that reducing fat mass may increase testosterone levels.
Subject(s)
Mendelian Randomization Analysis , Testosterone , Male , Humans , Genome-Wide Association Study , Body Composition/genetics , Gonadal Steroid HormonesABSTRACT
Introduction: In this study, we aimed to evaluate the feasibility, utility, and potential effects of LQ-M/D App, a smartphone application developed by Life Quest Inc., Tokyo, Japan, for patients with mild cognitive impairment (MCI) and mild dementia. The app incorporates cognitive and physical exercise training, lifestyle habit acquisition features, and a continuity improvement feature added in the post-update version to enhance user engagement. The continuity improvement feature includes the optimization of training content, and disease education, and enables family monitoring via a family app. Methods: A retrospective analysis was conducted on app usage, cognitive and exercise training implementation and interruptions, questionnaire response rates, and cognitive assessments in a single institution. A total of 20 patients used the app, with 10 patients using the pre-update version without the continuity improvement feature, and the other 10 patients using the post-update version with the continuity improvement feature. Results and Conclusion: The results demonstrated that the LQ-M/D App could be effectively used by the study population, and the continuity improvement feature positively influenced app usage in several aspects. Although a potential association between app usage and cognitive ability was suggested, the scatter in the data points warrants cautious interpretation. Limitations of the study included a small sample size, a single institution setting, and the retrospective nature of the study. In the future, a randomized controlled trial design using a larger sample size and multiple institutions to further evaluate the effectiveness of LQ-M/D App in managing MCI and mild dementia should be performed.
ABSTRACT
BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) occurs in 1 in 500-4000 people worldwide. Genetic mutation is a biomarker for predicting renal dysfunction in patients with ADPKD. In this study, we performed a genetic analysis of Japanese patients with ADPKD to investigate the prognostic utility of genetic mutations in predicting renal function outcomes. METHODS: Patients clinically diagnosed with ADPKD underwent a panel genetic test for germline mutations in PKD1 and PKD2. This study was conducted with the approval of the Ethics Committee of Juntendo University (no. 2019107). RESULTS: Of 436 patients, 366 (83.9%) had genetic mutations. Notably, patients with PKD1 mutation had a significantly decreased ΔeGFR/year compared to patients with PKD2 mutation, indicating a progression of renal dysfunction (-3.50 vs. -2.04 mL/min/1.73 m2/year, p = 0.066). Furthermore, PKD1 truncated mutations had a significantly decreased ΔeGFR/year compared to PKD1 non-truncated mutations in the population aged over 65 years (-6.56 vs. -2.16 mL/min/1.73 m2/year, p = 0.049). Multivariate analysis showed that PKD1 mutation was a more significant risk factor than PKD2 mutation (odds ratio, 1.81; 95% confidence interval, 1.11-3.16; p = 0.020). CONCLUSIONS: The analysis of germline mutations can predict renal prognosis in Japanese patients with ADPKD, and PKD1 mutation is a biomarker of ADPKD.
Subject(s)
Polycystic Kidney, Autosomal Dominant , Humans , Aged , Polycystic Kidney, Autosomal Dominant/diagnosis , Polycystic Kidney, Autosomal Dominant/genetics , TRPP Cation Channels/genetics , Mutation , Germ-Line Mutation , BiomarkersABSTRACT
Testosterone plays a key role in the maintenance of physical and mental functions in men. Age-related testosterone decline is closely associated with sarcopenia and muscle deterioration, while testosterone decline is linked with the etiology and prevention of diseases such as angina pectoris, arteriosclerosis, obesity, metabolic syndrome, and dementia. Late-onset hypogonadism (LOH) is defined as a disease characterized by age-related testosterone decline and associated clinical symptoms. Testosterone replacement therapy improves health-related QOL in patients with LOH.
Subject(s)
Hypogonadism , Testosterone , Male , Humans , Testosterone/therapeutic use , Testosterone/metabolism , Men's Health , Quality of Life , Hypogonadism/drug therapy , Hypogonadism/etiology , Obesity/complications , Hormone Replacement Therapy/adverse effects , AgingABSTRACT
Testosterone plays an important role in maintaining both physical and mental function. Age-related testosterone depletion contributes to the development of angina, arteriosclerosis, obesity, metabolic syndrome, dementia, frailty, and a range of other conditions. A condition involving age-related testosterone depletion and the associated clinical symptoms is defined as late-onset hypogonadism (LOH). LOH is treated by testosterone replacement therapy. Indications for testosterone replacement therapy are determined by evaluating symptoms and signs.
Subject(s)
Hypogonadism , Metabolic Syndrome , Humans , Hypogonadism/diagnosis , Hypogonadism/drug therapy , Testosterone/therapeutic use , Obesity , Metabolic Syndrome/diagnosis , Hormone Replacement TherapyABSTRACT
BACKGROUND: The chronic abnormal production of testosterone (T) is associated with many disorders in men. Fingernail clippings might be more suited for the diagnosis and medium-to-long term therapeutic monitoring for the T-related chronic disorders than the blood-derived specimens. The objective of this study was to characterize a thumbnail clipping as the specimen for assessing the several months-old T status. METHODS: Thumbnail clippings from various subjects were analyzed by liquid chromatography/electrospray ionization-tandem mass spectrometry to evaluate the gender difference, and changes caused by aging and androgen deprivation therapy (ADT) in the thumbnail T concentration. RESULTS: There was an evident gender difference in the thumbnail T concentrations [male; 2.55 ± 0.85 ng/g and female; 0.48 ± 0.29 ng/g, mean ± SD (n = 25 each), Welch t-test]. The thumbnail T concentrations significantly decreased with age in men (n = 268, Scheffé F-test), which was similar to those of the free or bioavailable T in serum/plasma. The thumbnail T concentrations sharply decreased by a 6-months ADT (especially the effect of the luteinizing hormone-releasing hormone agonist/antagonist) for patients with prostate cancer (n = 10). CONCLUSIONS: The thumbnail clipping can be a specimen to retrospectively assess the average T production.
Subject(s)
Nails , Testosterone , Humans , Male , Androgen Antagonists/therapeutic use , Nails/chemistry , Retrospective Studies , Testosterone/analysisABSTRACT
Recent studies have demonstrated that epigenetic modifications are deeply involved in neurogenesis; however, the precise mechanisms remain largely unknown. To determine the role of UTX (also known as KDM6A), a demethylase of histone H3K27, in neural development, we generated Utx-deficient mice in neural stem/progenitor cells (NSPCs). Since Utx is an X chromosome-specific gene, the genotypes are sex-dependent; female mice lose both Utx alleles (UtxΔ/Δ ), and male mice lose one Utx allele yet retain one Uty allele, the counterpart of Utx on the Y chromosome (UtxΔ/Uty ). We found that UtxΔ/Δ mice exhibited fetal ventriculomegaly and died soon after birth. Immunofluorescence staining and EdU labeling revealed a significant increase in NSPCs and a significant decrease in intermediate-progenitor and differentiated neural cells. Molecular analyses revealed the downregulation of pathways related to DNA replication and increased H3K27me3 levels around the transcription start sites in UtxΔ/Δ NSPCs. These results indicate that UTX globally regulates the expression of genes required for proper neural development in NSPCs, and UTX deficiency leads to impaired cell cycle exit, reduced differentiation, and neonatal death. Interestingly, although UtxΔ/Uty mice survived the postnatal period, most died of hydrocephalus, a clinical feature of Kabuki syndrome, a congenital anomaly involving UTX mutations. Our findings provide novel insights into the role of histone modifiers in neural development and suggest that UtxΔ/Uty mice are a potential disease model for Kabuki syndrome.
Subject(s)
Histones , Hydrocephalus , Animals , Female , Male , Mice , Fetal Development , Histone Demethylases/genetics , Hydrocephalus/genetics , Neurogenesis , Stem Cells , Neural Stem CellsABSTRACT
This study aimed to assess outcomes of microdissection testicular sperm extraction (MD-TESE) and identify predictors for sperm retrieval (SR) in patients with non-mosaic Klinefelter syndrome (NM-KFS). We retrospectively evaluated 37 patients with NM-KFS who underwent MD-TESE. Data of age at operation, body mass index (BMI), testicular volume, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), preoperative and postoperative testosterone levels with reduction ratio between the two values, and FSH/preoperative testosterone ratio were analysed. These patients were divided into two groups according to success or failure of SR: the successful and failure groups. Factors related to SR were evaluated by statistical analyses using the Mann-Whitney U test and logistic regression modelling. Regarding these factors, the cut-off level was specified using the receiver operating characteristics (ROC) curve. Moreover, the percentage of SR at that level was assessed. A simple scoring model was developed based on the multivariate analysis. Fourteen patients underwent successful SR, whereas 23 experienced failure SR. Statistical analysis found preoperative testosterone and FSH levels to be significant factors associated with SR. On the ROC curve, the cut-off levels for preoperative testosterone and FSH were 2.34 ng/ml and 33.2 mIU/ml respectively. A new scoring model was developed, consisting of preoperative testosterone (≥2.34 ng/ml) and FSH (≤33.2 mIU/ml). The sperm retrieval rates (SRRs) were clearly discriminated by stratification according to the scoring model. The SRR of the cases of scores of 2, 1 and 0 were 87.5%, 31.6% and 10% respectively. At our hospital, the SRR of MD-TESE in patients with NM-KFS was 37.8%. The patients with high testosterone and low FSH levels tended to demonstrate successful SR.
Subject(s)
Azoospermia , Klinefelter Syndrome , Humans , Male , Sperm Retrieval , Microdissection , Klinefelter Syndrome/surgery , Klinefelter Syndrome/complications , Testosterone , Retrospective Studies , Semen , Testis/surgery , Spermatozoa , Follicle Stimulating HormoneABSTRACT
The elder population has increased, introducing the profound medical and social challenge of maintaining health in aging seniors and the need for a medical approach to sustaining physical and mental health. The relationship between diseases and lifestyle-related factors such as diet and exercise are important. A health-conscious lifestyle improves one's health condition from a medical perspective, as indicated by new wellness monitoring using health devices and recent research into the efficacy of functional lunches incorporating utilitarian agricultural, forestry, and fishery products and foods. For a period of 3 months, and solely at lunchtime, 21 participants consumed the contents of a bento (Japanese box lunch), which incorporated functional (healthy) foods. A variety of factors were analyzed, including: weight, weight fluctuation rate, abdominal girth, triglycerides, total cholesterol value, and 8-OHdG (8-hydroxy-2'-deoxyguanosine). The bento comprising functional foods resulted in a reduction in both weight and abdominal girth without calorie restrictions. A reduction over time was observed in 8-OHdG, an oxidative stress marker, as compared to values prior to initiation of the study. Usage of a health device, exercise/dietary advice from a physician and nutritionist, and the availability of meals incorporating functional agricultural products might help prevent lifestyle disease and lead to improved health management.
Subject(s)
Functional Food , Lunch , Aged , Diet , Humans , Japan , Male , Oxidative Stress , Pilot Projects , PropanolaminesABSTRACT
BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) instillation is a standard treatment for non-muscle-invasive bladder cancer (NMIBC); however, not all patients benefit from BCG therapy. Currently, no surrogate marker exists to predict BCG efficacy, and thereby, identify patients who will benefit from this treatment. OBJECTIVE: To evaluate the utility of urine Mycobacterium tuberculosis complex polymerase chain reaction (MTC-PCR) assay as a predictive marker for recurrence and progression following BCG therapy. DESIGN SETTING AND PARTICIPANTS: A prospective analysis was carried out for of intermediate- or high-risk NMIBC patients who received BCG instillation for the first time. Urine samples, for MTC-PCR assay, were collected at baseline and annually for up to 10 yr after the last BCG instillation, including induction and maintenance therapy. The first postoperative sample for MTC-PCR was taken at 1 yr from the last instillation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis was performed using the Kaplan-Meier method, and risk factors for recurrence and progression after BCG treatment were assessed using Cox regression analysis. RESULTS AND LIMITATIONS: During follow-up (median: 57 mo), 468/521 samples (89.8%) were MTC-PCR positive, and 108/123 patients (87.8%) exhibited MTC-PCR positivity at least once. Five-year recurrence- and progression-free survival in patients who were not MTC-PCR positive was significantly lower than in patients who were MTC-PCR positive at least once (p < 0.001). Using multivariable Cox regression analysis, MTC-PCR positivity at least once was a significant prognostic factor for recurrence (hazard ratio [HR]: 36.782, p < 0.001) and progression (HR: 47.209, p < 0.001). CONCLUSIONS: Patients who were not MTC-PCR positive, even once after BCG therapy, were extremely likely to exhibit recurrence and progression. Urine MTC-PCR may be an extremely useful, noninvasive surrogate marker to predict recurrence and progression following BCG therapy. PATIENT SUMMARY: Urine Mycobacterium tuberculosis complex polymerase chain reaction may be a novel biomarker capable of identifying patients at risk of recurrence and progression after bacillus Calmette-Guérin (BCG) immunotherapy.
ABSTRACT
BACKGROUND/AIM: Curcumin is a natural compound of turmeric, which inhibits prostate cancer cell proliferation. This study examined whether treatment of LNCaP prostate cancer cells with the combination of curcumin and dutasteride, a 5-alpha reductase inhibitor, affect proliferation and the amount of testosterone and dihydrotestosterone. MATERIALS AND METHODS: LNCaP Cells were incubated with curcumin or the combination of curcumin and dutasteride and cell proliferation was measured at 72 h. LC-MS/MS was used to determine testosterone and dihydrotestosterone concentrations in prostate cancer cells. RESULTS: Curcumin combined with dutasteride suppressed proliferation and affected apoptosis of LNCaP cells. The combination of curcumin and dutasteride also reduced the amount of testosterone and dihydrotestosterone in LNCaP cells. The secretion of prostate-specific antigen was inhibited by the combination treatment in a dose-dependent manner. CONCLUSION: Treatment with the combination of curcumin and dutasteride may interfere with the intra-tumoral androgen activity.
Subject(s)
Curcumin , Prostatic Neoplasms , 5-alpha Reductase Inhibitors/pharmacology , Azasteroids/pharmacology , Cell Line, Tumor , Chromatography, Liquid , Curcumin/pharmacology , Dihydrotestosterone/pharmacology , Dutasteride/pharmacology , Humans , Male , Prostatic Neoplasms/drug therapy , Tandem Mass SpectrometryABSTRACT
The risk of a gonadal tumor is high in testicular disorder of sexual development (DSD) with the Y chromosome, but cases of DSD without the Y chromosome are extremely rare. We reported a gonadal tumor in a phenotypically male individual with 46, XX testicular DSD. A testicular tumor was incidentally found in a 32-year-old phenotypic male who was presented to the hospital with male infertility. A diagnosis of 46, XX testicular DSD was made by the presentation of karyotype analysis of 46, XX with the sex-determining region of the Y chromosome (SRY) positive and gonadal tissue without female gonads. Surgery was performed due to a gradually growing tumor. The partial orchidectomy was performed with the diagnosis of a benign Leydig cell tumor in frozen biopsy.
Subject(s)
Chromosomes, Human, Y/genetics , Infertility, Male/etiology , Leydig Cell Tumor/genetics , Sex-Determining Region Y Protein/genetics , Testicular Neoplasms/genetics , Testis/abnormalities , Adult , Biopsy , Female , Humans , Incidental Findings , Leydig Cell Tumor/pathology , Leydig Cell Tumor/surgery , Male , Orchiectomy , Sex-Determining Region Y Protein/metabolism , Sexual Development/genetics , Testicular Neoplasms/pathology , Testicular Neoplasms/surgeryABSTRACT
PURPOSE: Cryptorchidism is one of the most common causes of non-obstructive azoospermia (NOA) in adulthood. Even if early orchidopexy is performed to preserve fertility potential, some patients still suffer from azoospermia. Fertility potential is significantly lower in bilateral than unilateral cryptorchidism. The aims of this study were to identify clinical parameters that predict the likely success of sperm recovery by microscopic testicular sperm extraction (micro-TESE) and also the likely outcome of intracytoplasmic sperm injection using sperm from NOA patients who submitted to bilateral orchidopexy. METHODS: Fifty-two NOA patients with a history of bilateral cryptorchidism underwent micro-TESE. The following clinical parameters were evaluated as predictive factors for successful sperm recovery: age at micro-TESE; age at orchidopexy; period from orchidopexy to micro-TESE; luteinizing hormone (LH); follicle-stimulating hormone (FSH); testosterone; average testicular volume; and body mass index. RESULTS: In the successful sperm retrieval group, average testicular volume was significantly greater, while serum LH and FSH, and body mass index were significantly lower. In a multivariate analysis, average testicular volume was positively correlated with successful sperm recovery. CONCLUSION: Our results indicate that testicular volume in NOA patients with bilateral cryptorchidism is a predictor for successful sperm recovery.
ABSTRACT
As testicular torsion is a medical emergency, it requires quick diagnosis and treatment. Color Doppler ultrasound (CDUS) is useful for the diagnosis of testicular torsion. An accurate diagnosis can be difficult when CDUS indicates the preservation of blood flow in the testis. We examined the accuracy of testicular torsion diagnosis in patients with acute scrotum made by doctors on duty using CDUS. The subjects included 26 patients who visited our department between January 2016 and June 2018 presenting with acute scrotal pain. Patients were placed into one of three groups based on testicular blood flow evaluated by CDUS. The first group had no testicular blood flow, the second had diminished blood flow, and the last group had normal or increased blood flow. Patients were also diagnosed through scrotal exploration. Finally, patients were further divided into two groups identified by CDUS frequency utilized during diagnosis (12 MHz groups and ≤8 MHz groups), and the diagnostic accuracy of the two groups was compared. Characterizing torsion by either the absence of or diminished, testicular blood flow in the CDUS evaluation, the sensitivity and specificity of the CDUS performed by doctors on duty accounted for 69.2% and 53.8%, respectively. No improvement in diagnostic accuracy was evident despite the usage of a 12-MHz ultrasonic transducer. In this study, the sensitivity of CDUS performed by doctors on duty was about 70%, suggesting that scrotal exploration should be performed promptly even if testicular blood flow is observed and testicular torsion is suspected from medical history and body findings.