Primary signet-ring cell carcinoma of the bladder treated with laparoscopic radical cystectomy: a case report.

Primary bladder adenocarcinomas comprise 0.5-2% of all epithelial bladder neoplasms. Of these, primary signet-ring cell carcinoma of the bladder is particularly rare, accounting for 0.24% of all bladder malignancies. This tumor is frequently diagnosed at an advanced stage and has a poor prognosis. No standard treatment has yet been established. We here report a patient in whom laparoscopic cystectomy following neoadjuvant chemotherapy was effective. Our patient was a 69-year-old man who had had microscopic hematuria, undergone transurethral resection of a mass in the bladder, and been diagnosed pathologically with a primary signet-ring cell carcinoma of the bladder. No metastases were detected on computed tomography. The patient was treated with a combination of paclitaxel, cisplatin, and gemcitabine prior to undergoing laparoscopic cystectomy. The histopathological diagnosis on this operative specimen was dysplasia and no metastases were detected in the dissected lymph nodes. Complete remission has now been maintained for 9 years.

[A Retrospective Study on the Malignancies after Renal Transplantation].

Detection of post-transplant malignant tumors and the analysis of the associated risk factors is important for monitoring the progress after renal transplantation. In this study, we retrospectively examined the medical records of 298 patients who underwent renal transplantation at two facilities in Nagasaki Prefecture (Nagasaki University Hospital and National Hospital Organization Nagasaki Medical Center). Of the 298 patients, 45 (15.1%) patients had developed malignant tumors with 50 lesions. The most common type of malignant tumor was skin cancer (eight patients; 17.8%), followed by renal cancer (six patients; 13.3%), and pancreatic cancer and colorectal cancer, (four patients; 9.0% each). Five patients (11.1%) had multiple cancers, four of whom had skin cancer. The cumulative incidence within 10 and 20 years after renal transplantation was 6.0 and 17.9%, respectively. Univariate analysis identified age at transplantation and administration of cyclosporine and rituximab as risk factors, while multivariate analysis identified age at transplantation and administration of rituximab as independent factors. The administration of rituximab was associated with the development of malignant tumors. However, further investigation is required to establish the association with post-transplant malignant neoplasms.

Pathological Significance and Prognostic Role of WWC1 in Upper Urinary Tract Urothelial Cancer.

BACKGROUND/AIM: WW and C2 domain-containing 1 (WWC1) protein is a suppressor of malignancies. However, there is no information on the pathological significance of WWC1 in upper urinary tract cancer (UTUC). PATIENTS AND METHODS: In this study, WWC1 immunoreactivity was investigated in 152 non-metastatic UTUC samples. The relationships between WWC1 expression and grade, pT stage, proliferative index (using an antibody to Ki-67), and the immunohistochemical expression of matrix metalloproteinase (MMP)-2 and -9 were evaluated. RESULTS: WWC1 expression was negatively associated with tumor grade and pT stage (p<0.001). Positive expression of WWC1 was a better predictor of the UTUC recurrence and subsequent metastasis, and the multivariate analysis showed that WWC1 expression was a significant predictor of subsequent metastasis (hazard ratio=0.29, p=0.020). WWC1 expression inversely correlated with the proliferative index (odds ratio=2.59, p=0.023) and expression of MMP9 (odds ratio=2.19, p=0.040) but not with MMP2 expression, by multivariate analyses. CONCLUSION: WWC1 expression was negatively associated with malignant aggressiveness via the suppression of cancer cell proliferation and MMP9 expression in patients with UTUC. This suggests WWC1 to be a useful predictor and novel therapeutic target in patients with UTUC.

Alternative Treatment with Every-Other-Day Dosing of Sunitinib for Metastatic Renal Cell Carcinoma: Extended Follow-Up.

INTRODUCTION: We investigated the efficacy and safety of every-other-day dosing of sunitinib for the treatment of metastatic renal cell carcinoma (mRCC) with extended follow-up and the impact of immune checkpoint inhibitor (ICI) drugs. METHODS: Thirty-two patients received standard dosing treatment (standard group), and 32 received every-other-day treatment (experimental group). Efficacy endpoints included progression-free survival (PFS), overall survival (OS), and objective response rate. We also analyzed the clinical course of patients treated with nivolumab after sunitinib. RESULTS: The minimum follow-up was 42 months. Median PFS and OS were significantly longer in the experimental group compared with the standard group (27.6 vs. 6.2 and 87.1 vs. 24.6 months, respectively). The incidence of dose interruption of sunitinib caused by adverse events was significantly lower in the experimental group than in the standard group (28.1% vs. 56.3%, p = 0.042). Multivariate analysis showed that every-other-day dosing was a significant independent prognostic factor (p = 0.038), although nivolumab use was not (p = 0.232). Twelve patients were treated with nivolumab after sunitinib, and patients who did not respond to nivolumab tended to respond to pretreatment sunitinib for a long period. DISCUSSION/CONCLUSION: Long-term follow-up confirmed the efficacy and safety of every-other-day dosing of sunitinib for mRCC patients in the ICI era.

[Renal Cell Carcinomas in Patients on Chronic Dialysis].

Patients on chronic dialysis for end-stage renal disease (ESRD) show an increased incidence of renal cell carcinoma (RCC). We investigated the clinicopathological characteristics and outcomes of 54 patients who underwent nephrectomy for RCC due to ESRD between 1992 and 2019. The patients consisted of 44 men and 10 women, with a median age of 62.9 years. The median duration of dialysis before surgery was 12.9 years. The clinical stage of the 54 RCCs was stage I in 44, stage II in 1, stage III in 1, and stage IV in 8. With a median follow-up of 5.1 years after surgery, the 5-year cancer-specific and overall survival rates were 84.3 and 61.8%, respectively. Patients with symptomatic RCC had a longer period of dialysis, presented with larger tumors of higher grade and stage, and had worse prognosis compared with those with incidentally discovered RCC. Cox proportional hazards analysis performed with clinicopathological features and symptomatic/incidental detection showed that older age and symptomatic RCC were independently associated with worse overall survival. Our data show that early detection is important for a good prognosis.

Oral administration of E-type prostanoid (EP) 1 receptor antagonist suppresses carcinogenesis and development of prostate cancer via upregulation of apoptosis in an animal model.

Prostaglandin E2 plays an important role in carcinogenesis and malignant potential of prostate cancer (PC) cells by binding to its specific receptors, E-type prostanoid (EP) receptors. However, anti-carcinogenic effects of the EP receptor antagonist are unclear. In this study, we used a mouse model of PC. The mice were provided standard feed (control) or feed containing the EP1 receptor antagonist and were sacrificed at 10, 15, 30, and 52 weeks of age. Apoptosis was evaluated by immunohistochemical analysis using a cleaved caspase-3 assay. The incidence of cancer in the experimental group was significantly lower than that in the control group at 15, 30, and 52 weeks of age. The percentage of poorly differentiated PC cells was significantly lower in the experimental group than in the control group at 30 and 52 weeks of age. The percentage of apoptotic cells in the experimental group was significantly higher than that in the control group at 15, 30, and 52 weeks of age. These findings indicate that feeding with the addition of EP1 receptor antagonist delayed PC progression via the upregulation of apoptosis. We suggest that the EP1 receptor antagonist may be a novel chemopreventive agent for PC.

Pathological significance and prognostic role of LATS2 in prostate cancer.

BACKGROUND: Large tumor suppressor 2 (LATS2) is an important regulator of the Hippo pathway and it plays crucial roles in cell survival and behaviors. Herein, we evaluated the pathological roles of LATS2 in prostate cancer (PC), for which very little information is available. METHODS: Cell proliferation, migration, and invasion in response to the siRNA-mediated knockdown (KD) LATS2 expression were evaluated in two PC cell lines (LNCaP and PC3). The expression of LATS2 in specimens from 204 PC patients was investigated immunohistochemically, and the relationships between its expression and clinicopathological features, proliferation index (PI; measured using an anti-KI-67 antibody), and biochemical recurrence (BCR) were investigated. RESULTS: KD of LATS2 increased the growth, migration, and invasion in LNCaP cells and only increased migration in PC3 cells. The expression of LATS2 was negatively associated with the grade group, T, N, M stage, and PI. In addition, the expression of LATS2 was a useful predictor of the histological effects of neoadjuvant hormonal therapy and BCR-free survival periods. A multivariate analysis model including clinicopathological features showed that negative expression of LATS2 had a significantly higher risk of BCR (odds ratio = 2.95, P < 0.001). CONCLUSIONS: LATS2 acts as a tumor suppressor in PC. LATS2 expression is a useful predictor for BCR. LATS2-related activities are possibly dependent on the androgen-dependency of PC cells. Therefore, we suggest that LATS2 could be a potential therapeutic target and a useful predictor for outcome in patients with PC.

Pathological Roles of Prostaglandin E2-specific E-type Prostanoid Receptors in Hormone-sensitive and Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Prostaglandin (PG) E2 mediates malignant aggressiveness by binding to four specific E-type prostanoid receptors (EP1R - 4R). This study aimed to clarify the pathological significance of EPRs in hormone-sensitive prostate cancer (HSPC) and castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: EP1R - 4R expression was examined in 102 HSPC and 27 CRPC specimens. The relationships between their expression and proliferation index (PI), apoptotic index (AI), and vascular endothelial growth factor (VEGF)-A expression were analyzed. RESULTS: EP4R expression in CRPC was significantly higher compared to that in HSPC, even in advanced disease (T3/4, N1, and/or M1). EP4R expression was significantly correlated with PI, AI, and VEGF-A expression in CRPC. Such significant relationships were not detected between EP1R - 3R and CRPC. CONCLUSION: EP4R expression in CRPC was significantly higher than that in HSPC and was associated with cancer cell proliferation, apoptosis, and pro-angiogenetic potential.

Stage-specific Embryogenic Antigen-4 Expression in Castration-resistant Prostate Cancer and its Correlation With the Androgen Receptor.

BACKGROUND/AIM: Stage-specific embryonic antigen (SSEA)-4 plays important roles in the malignant aggressiveness of various cancers. The aim of this study was to investigate the pathological characteristics of SSEA-4 in castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: SSEA-4 expression and its pathological roles were evaluated in five prostate cancer (PC) cell lines and 27 CRPC tissues. The relationship between SSEA-4 and the androgen receptor (AR) was also examined. RESULTS: SSEA-4 expression was detected in AR-negative cells (PC3, DU145, and AICaP1) but was not detected in AR-positive cells (LNCaP and AICaP2). SSEA-4 expression in human CRPC tissues was significantly higher than that in locally advanced or metastatic hormone sensitive PC (HSPC) tissues. A negative correlation was also detected between SSEA-4 and AR in CRPC tissues but not in HSPC tissues. CONCLUSION: SSEA-4 was over-expressed in CRPC and the changes were mediated by complex mechanisms that related to the AR and hormonal therapy.

Ceruloplasmin Levels in Cancer Tissues and Urine Are Significant Biomarkers of Pathological Features and Outcome in Bladder Cancer.

BACKGROUND/AIM: A previous report showed that immune complex-ceruloplasmin (CP) in urine is associated with carcinogenesis and malignant behavior in bladder cancer (BC). We investigated the pathological significance and prognostic roles of urine and tissue levels of CP protein in BC patients. MATERIALS AND METHODS: Urine CP levels were measured using an enzyme-linked immunosorbent assay in 97 patients. CP expression in BC tissues was evaluated by immunohistochemical analysis in 176 patient samples. RESULTS: Urine CP levels were positively associated with tumor grade and pT stage in non-muscle invasive BC (NMIBC). CP expression in BC tissues was positively associated with tumor growth and progression. Multivariate analysis demonstrated that high urine CP levels was an independent predictor of recurrence in the urinary tract in NMIBC (hazard ratio=2.87, p=0.016). CONCLUSION: CP-related markers, especially urine CP levels, are useful biomarkers of malignant potential and prognosis in NMIBC.

Efficacy of propiverine hydrochloride for urinary incontinence after robot-assisted or laparoscopic radical prostatectomy.

INTRODUCTION: To clarify the efficacy and safety of propiverine hydrochloride for incontinence after robot-assisted laparoscopic prostatectomy (RALP)/laparoscopic radical prostatectomy (LRP), along with changes in the urethral pressure profile (UPP) and quality of life in patients treated with propiverine hydrochloride. MATERIALS AND METHODS: In this randomized, comparative study, 104 patients who were aware of urinary incontinence after RALP or LRP were assigned to receive propiverine hydrochloride (treatment group) or not (controls). Pad test results, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) scores, and UPP results [including maximum urethral closure pressure (MUCP) and functional urethral length (FUL)], were recorded immediately and at 6 months postoperatively. RESULTS: No serious intraoperative complications or adverse events were caused by propiverine hydrochloride. The pad-test negative rate was significantly greater in the treatment group than in controls (89.1% vs. 73.2%, p = 0.044). Changes in ICIQ-SF scores and MUCP were significantly greater in the treatment group than in controls [-6.5 vs. -4.5 points (p = 0.021), and +49.5 vs. +28.7 mmHg (p = 0.038), respectively]. FUL change did not significantly differ between groups [+4.5 vs. +3.8 mm (p = 0.091)]. In univariate logistic regression analyses, body mass index (BMI), MUCP, and treatment with propiverine hydrochloride were significantly associated with continence status. In multivariate analyses, BMI and MUCP were independently associated with continence status [odds ratio (OR), 1.266; 95% confidence interval (CI), 1.047-1.530 (p = 0.015), and OR, 0.986; 95% CI, 0.973-0.999 (p = 0.042), respectively]. CONCLUSIONS: Treatment with propiverine hydrochloride alleviated urinary incontinence while improving patient symptoms and quality of life after RALP or LRP.

Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer.

BACKGROUND/AIM: The pathological significance of thrombospondin (TSP)-1 and -2 in bladder cancer (BC) is well-known whereas that of TSP-3, 4 and 5 remains unclear. Our aim is to clarify the pathological significance and prognostic roles of TSP-3 to 5 expression in BC patients. PATIENTS AND METHODS: TSP-3 to 5 expression, proliferation index (PI), apoptotic index (AI) and microvessel density (MVD) were evaluated in 206 BC patients by immunohistochemical techniques. RESULTS: TSP-5 expression was positively associated with grade, T stage, metastasis, and worse prognosis. PI in TSP-5-positive tissues was significantly higher compared to negative tissues. In contrast, AI in TSP-5-positive tissues was significantly lower compared to negative tissues. Expressions of TSP-3 and 4 were not associated with any clinicopathological features, survival, PI, or AI. CONCLUSION: TSP-5 plays important roles in malignant behavior via cell survival regulation whereas the pathological significance of TSP-3 and TSP-4 in BC might be minimal.

Efficacy of salt reduction for managing overactive bladder symptoms: a prospective study in patients with excessive daily salt intake.

This study aimed to investigate the efficacy of salt intake restriction on overactive bladder (OAB) symptoms in patients with excessive salt intake. Patients received a brochure on nutritional guidance regarding salt intake reduction and received health education every 4 weeks for 12 weeks. Data from overactive bladder symptom score (OABSS) questionnaires and frequency volume charts (FVCs) were evaluated. The daily salt intake was estimated by determining the urinary sodium and creatinine concentrations using spot urine samples. Of the 98 patients included, 71 (72.4%) successfully restricted their daily salt intake after 12 weeks (salt restricted [R] group), while 27 (27.6%) did not (salt non-restricted [N-R] group). The scores to each OABSS question and the resulting total score improved significantly in the R group; however, the individual scores remained unchanged and the total score increased in the N-R group. The FVC data indicated improved voided volumes in the R group as compared to in the N-R group. Ultimately, 17 (23.9%) patients in the R group no longer fulfilled the OAB diagnostic criteria after salt intake reduction. Thus, salt intake reduction improved urinary symptoms in patients with OAB and may be a therapeutic option for OAB in patients with excessive daily salt intakes.

Presurgical bladder wall thickness is a useful marker to predict the postsurgical improvement of symptoms in patients with pelvic organ prolapse-related overactive bladder.

OBJECTIVES: Pelvic organ prolapse (POP) is a cause of overactive bladder (OAB), and transvaginal mesh (TVM) surgery can improve the symptoms. Bladder wall thickness (BWT) is a useful and safe marker to evaluate bladder function in urinary disorders. The main purpose of this study is to clarify the relationship between BWT and changes in the OAB symptom score (OABSS) after TVM operation in patients with POP. METHODS: BWT was measured by ultrasonography before and 6 months after surgery at three sites in the bladder: the anterior wall, trigone, and dome. Similarly, the OABSS was evaluated at the time of BWT measurement. Changes induced in BWT at each site and the mean BWT at all sites after TVM surgery were analyzed. Similarly, the relationship between presurgical BWT and the decrease in OABSS was investigated. RESULTS: TVM surgery improved OABSS in 30 patients (responders; 73.2%), while 11 patients were judged as nonresponders (26.8%). BWT at the anterior bladder wall and dome as well as the mean BWT at all three sites were significantly decreased by TVM surgery (P < .001). Similar trends were identified in OABSS responders; however, all markers showed no significant changes in OABSS nonresponders. All the BWT-related markers before surgery were significantly lower in OABSS responders than in OABSS nonresponders. CONCLUSIONS: BWT at the bladder anterior wall and dome, but not the trigone, were decreased by TVM surgery. We conclude that presurgical BWT may be a useful marker to predict the improvement in OAB symptoms by TVM surgery in patients with POP-related OAB.

Pharmacological Effects and Potential Clinical Usefulness of Polyphenols in Benign Prostatic Hyperplasia.

Benign prostatic hyperplasia (BPH) is arguably the most common benign disease among men. This disease is often associated with lower urinary tract symptoms (LUTS) in men and significantly decreases the quality of life. Polyphenol consumption reportedly plays an important role in the prevention of many diseases, including BPH. In recent years, in addition to disease prevention, many studies have reported the efficacy and safety of polyphenol treatment against various pathological conditions in vivo and in vitro. Furthermore, numerous studies have also revealed the molecular mechanisms of the antioxidant and anti-inflammatory effects of polyphenols. We believe that an improved understanding of the detailed pharmacological roles of polyphenol-induced activities at a molecular level is important for the prevention and treatment of BPH. Polyphenols are composed of many members, and their biological roles differ. In this review, we first provide information regarding the pathological roles of oxidative stress and inflammation in BPH. Next, the antioxidant and anti-inflammatory effects of polyphenols, including those of flavonoids and non-flavonoids, are discussed. Finally, we talk about the results and limitations of previous clinical trials that have used polyphenols in BPH, with particular focus on their molecular mechanisms of action.

Excessive accumulation of visceral fat is associated with lower urinary symptoms including overactive bladder in female patients.

OBJECTIVE: To assess the relationship between visceral fat accumulation and lower urinary tract symptoms in female patients. METHODS: In this single-center study, we enrolled all women who underwent screening abdominal computed tomography 3 months before the study, irrespective of whether they experienced lower urinary tract symptoms. The Overactive Bladder Symptom Score was used to assess subjective symptoms. Uroflowmetry and ultrasound assessment of post-void residual urine were carried out to assess objective signs. We analyzed the relationship between lower urinary tract symptoms and various body fat accumulation parameters, including visceral fat area, visceral fat volume and total abdominal fat volume, assessed using computed tomography scans. RESULTS: A total of 182 patients were divided into the overactive bladder (n = 71, 39.0%) and the non-overactive bladder (n = 111, 61.0%) groups. The visceral fat area, visceral fat volume and visceral fat volume/total abdominal fat volume values were all significantly higher in the overactive bladder group than in the non-overactive bladder group (P < 0.001). Of these parameters, the visceral fat volume/total abdominal fat volume ratio showed the strongest correlation with the total Overactive Bladder Symptom Score (r = 0.394, P < 0.001). The maximum urine flow rate correlated negatively with the visceral fat volume/total abdominal fat volume value (visceral fat volume/total abdominal fat volume r = -0.289, P < 0.001). Subsequent multivariate analysis showed that a high visceral fat volume/total abdominal fat volume value, age and metabolic syndrome-related diseases were independent risk factors for the presence of overactive bladder. CONCLUSIONS: Excessive accumulation of visceral fat is independently associated with overactive bladder in females.

Present Status, Limitations and Future Directions of Treatment Strategies Using Fucoidan-Based Therapies in Bladder Cancer.

Bladder cancer (BC) is a common urological cancer, with poor prognosis for advanced/metastatic stages. Various intensive treatments, including radical cystectomy, chemotherapy, immune therapy, and radiotherapy are commonly used for these patients. However, these treatments often cause complications and adverse events. Therefore, researchers are exploring the efficacy of natural product-based treatment strategies in BC patients. Fucoidan, derived from marine brown algae, is recognized as a multi-functional and safe substrate, and has been reported to have anti-cancer effects in various types of malignancies. Additionally, in vivo and in vitro studies have reported the protective effects of fucoidan against cancer-related cachexia and chemotherapeutic agent-induced adverse events. In this review, we have introduced the anti-cancer effects of fucoidan extracts in BC and highlighted its molecular mechanisms. We have also shown the anti-cancer effects of fucoidan therapy with conventional chemotherapeutic agents and new treatment strategies using fucoidan-based nanoparticles in various malignancies. Moreover, apart from the improvement of anti-cancer effects by fucoidan, its protective effects against cancer-related disorders and cisplatin-induced toxicities have been introduced. However, the available information is insufficient to conclude the clinical usefulness of fucoidan-based treatments in BC patients. Therefore, we have indicated the aspects that need to be considered regarding fucoidan-based treatments and future directions for the treatment of BC.

Pathological and Pharmacological Roles of Mitochondrial Reactive Oxygen Species in Malignant Neoplasms: Therapies Involving Chemical Compounds, Natural Products, and Photosensitizers.

Oxidative stress plays an important role in cellular processes. Consequently, oxidative stress also affects etiology, progression, and response to therapeutics in various pathological conditions including malignant tumors. Oxidative stress and associated outcomes are often brought about by excessive generation of reactive oxygen species (ROS). Accumulation of ROS occurs due to dysregulation of homeostasis in an otherwise strictly controlled physiological condition. In fact, intracellular ROS levels are closely associated with the pathological status and outcome of numerous diseases. Notably, mitochondria are recognized as the critical regulator and primary source of ROS. Damage to mitochondria increases mitochondrial ROS (mROS) production, which leads to an increased level of total intracellular ROS. However, intracellular ROS level may not always reflect mROS levels, as ROS is not only produced by mitochondria but also by other organelles such as endoplasmic reticulum and peroxisomes. Thus, an evaluation of mROS would help us to recognize the biological and pathological characteristics and predictive markers of malignant tumors and develop efficient treatment strategies. In this review, we describe the pathological significance of mROS in malignant neoplasms. In particular, we show the association of mROS-related signaling in the molecular mechanisms of chemically synthesized and natural chemotherapeutic agents and photodynamic therapy.

Mechanisms Underlying the Inhibition of Tyrosine Kinase Inhibitor-Induced Anorexia and Fatigue by Royal Jelly in Renal Cell Carcinoma Patients and the Correlation between Macrophage Colony Stimulating Factor and Inflammatory Mediators.

Inflammation is a common adverse event of anti-cancer therapy. Royal jelly (RJ) modulates inflammation by regulating the levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, and interleukin (IL)-6 produced by macrophages. Macrophage colony stimulating factor (M-CSF) is a crucial regulator of macrophage activities, and we hypothesized that RJ alters M-CSF levels. In this randomized controlled trial, we investigated the association between M-CSF and adverse events in renal cell carcinoma patients treated with tyrosine kinase inhibitors (TKIs) after an oral intake of RJ (n = 16) or placebo (n = 17). The serum levels of M-CSF, TNF-α, TGF-ß, and IL-6 were measured by an enzyme-linked immunosorbent assay, and their temporal changes and correlation between such changes were analyzed. The post-/pretreatment ratio of M-CSF levels was associated with anorexia after 2 weeks and fatigue after 2, 4, and 12 weeks. The M-CSF level in the RJ group was higher than that in the placebo group at the same timepoints. The TNF-α level in the RJ group was lower than that in the placebo group between 6 and 12 weeks, and the TGF-ß level in the RJ group was higher than that in the placebo group; however, contrasting findings were detected after 12 weeks. Additionally, the M-CSF level was significantly correlated with the TGF-ß level after 4 weeks and IL-6 level after 8 and 10 weeks. Among TNF-α, TGF-ß, and IL-6, the post-/pretreatment ratio of TGF-ß after 12 weeks was associated with TKI-induced anorexia, and the ratios after 10 and 12 weeks were associated with fatigue. Our results demonstrated that an oral intake of RJ suppressed anorexia and fatigue via complex mechanisms associated with inflammation-related factors, such as M-CSF and TGF-ß in renal cell carcinoma patients treated with TKIs. In addition, we newly found that such RJ-related effects were dependent on the treatment duration.

Relationship Between Stage-specific Embryonic Antigen-4 and Anti-cancer Effects of Neoadjuvant Hormonal Therapy in Prostate Cancer.

BACKGROUND/AIM: Stage-specific embryonic antigen-4 (SSEA-4) expression is associated with malignant aggressiveness and is useful as a marker for identifying cancer stem cells. Our aim was to assess the relationship between hormonal therapy and SSEA-4 expression in prostate cancer (PC). MATERIALS AND METHODS: SSEA-4 expression in paired specimens from PC patients who underwent neoadjuvant hormonal therapy (NHT) and radical prostatectomy (60 pre-NHT specimens and 60 post-NHT specimens) was evaluated using immunohistochemistry. Proliferation index (PI) and apoptotic index (AI) were also evaluated. RESULTS: Post-NHT tissues had significantly elevated SSEA-4 expression whereas anti-tumor effects of NHT were inversely correlated with SSEA-4 expression level. SSEA-4 expression in post-NHT tissues was significantly associated with biochemical recurrence-free survival. SSEA-4 expression in the post-NHT tissues was positively associated with PI and negatively done with AI. CONCLUSION: SSEA-4 is a potential therapeutic target for limiting the malignant potential in hormone-naïve PC when considering the use of NHT.