ABSTRACT
OBJECTIVE: Intraoperative hypotension remains a serious adverse event of photodynamic diagnosis-assisted transurethral resection of bladder tumor with oral administration of 5-aminolevulinic acid. We conducted a re-analysis of perioperative hypotension in photodynamic diagnosis-assisted transurethral resection of the bladder tumor with oral 5-aminolevulinic acid to ascertain its safety. METHODS: A total of 407 cases who underwent transurethral resection of bladder tumors in our institution were reviewed (274 cases for the PDD group with photodynamic diagnosis and 133 for the white light (WL) group without). A classification of hypotension severity was devised to identify risk factors for clinically troublesome hypotension. The distribution of hypotension severity in each of the PDD and WL groups was compared. Additionally, the patient background and perioperative data by hypotension severity were compared only in the PDD group. RESULTS: More patients with moderate and severe hypotension were noted in the PDD group. The renal function was lower with increasing hypotension severity in the PDD group. More patients on general anesthesia were included in the mild and moderate hypotension group, whereas more patients on spinal anesthesia were included in the severe hypotension group. Furthermore, the frequency of side effects other than hypotension tended to increase with hypotension severity. CONCLUSIONS: Renal function impairment and the other adverse effects of 5-aminolevulinic acid may be risk factors for severe hypotension. Mild or moderate hypotension may be caused by general anesthesia and severe hypotension may be caused by spinal anesthesia. To elucidate specific risk factors, further case-control studies are warranted.
Subject(s)
Aminolevulinic Acid , Hypotension , Photosensitizing Agents , Transurethral Resection of Bladder , Urinary Bladder Neoplasms , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Aminolevulinic Acid/administration & dosage , Aminolevulinic Acid/adverse effects , Cystectomy/adverse effects , Hypotension/etiology , Hypotension/diagnosis , Intraoperative Complications/etiology , Intraoperative Complications/diagnosis , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/adverse effects , Retrospective Studies , Risk Factors , Severity of Illness Index , Transurethral Resection of Bladder/adverse effects , Urinary Bladder Neoplasms/surgeryABSTRACT
Since 2020, the coronavirus disease 2019 pandemic has led to the widespread practice of hand hygiene and wearing face masks, not only among medical personnel, but also among the general population. Thus, the impact of the coronavirus disease 2019 pandemic on the incidence of febrile neutropenia should be verified. This study aimed to examine the incidence of febrile neutropenia in hospitalized patients receiving chemotherapy at Kanazawa University Hospital. Among inpatients at the Department of Urology receiving chemotherapy, we compared the incidence of febrile neutropenia between 317 cases in 2018-2019 and 276 cases in 2020. We retrospectively analyzed the factors of febrile neutropenia via binomial logistic regression analysis based on patient characteristics and the characteristics of primary diseases, with statistical significance set at p < 0.05. Febrile neutropenia occurred in 20/317 cases in 2018-2019 and 1/276 cases in 2020, with a significant decrease in the latter (p = 0.005). In a multivariate analysis, we identified the following independent risk factors for febrile neutropenia: non-coronavirus disease 2019 era (p = 0.005), first course of therapy (p = 0.005), malnutrition (p = 0.032), and past history of febrile neutropenia (p = 0.018). Due to the coronavirus disease 2019 pandemic, hygiene policies for medical personnel and quarantine measures for patients were thoroughly implemented. Therefore, the incidence of febrile neutropenia in 2020 decreased to 1/15 of the previous incidence. Thus, the hygiene for medical personnel and patients during the expected period of chemotherapy-induced neutropenia is important for febrile neutropenia prevention.
Subject(s)
COVID-19 , Febrile Neutropenia , Urologic Neoplasms , Humans , Retrospective Studies , Inpatients , Pandemics , COVID-19/epidemiology , Urologic Neoplasms/drug therapyABSTRACT
The suppression of androgen receptor (AR) expression exacerbates the migration potential of prostate cancer. This study identified a previously unrecognized regulation of the AR-controlled pathway that promotes migration potential in prostate cancer cells. Prostate cancer cells that pass through a transwell membrane (mig cells) have a higher migration potential with a decreased AR expression than parental cells. In this study, we aimed to elucidate the mechanism of migration enhancement associated with the suppression of AR signaling. Expression of C-C motif ligand 20 (CCL20) is upregulated in mig cells, unlike in the parental cells. Knockdown of AR with small interfering RNA (siAR) in LNCaP and C4-2B cells increased CCL20 secretion and enhanced the migration of cancer cells. Mig cells, CCL20-treated cells, and siAR cells promoted cell migration with an enhancement of AKT phosphorylation and Snail expression, while the addition of a C-C chemokine receptor 6 (CCR6, the specific receptor of CCL20) inhibitor, anti-CCL20 antibody, and AKT inhibitor suppressed the activation of AKT and Snail. With 59 samples of prostate cancer tissue, CCL20 secretion was profuse in metastatic cases despite low AR expression levels. Snail expression was associated with the expression of CCL20 and CCR6. A xenograft study showed that the anti-CCL20 antibody significantly inhibited Snail expression, thereby suggesting a new therapeutic approach for castration-resistant prostate cancer with the inhibition of the axis between CCL20 and CCR6.
Subject(s)
Prostatic Neoplasms , Proto-Oncogene Proteins c-akt , Male , Humans , Proto-Oncogene Proteins c-akt/metabolism , Receptors, Androgen , Signal Transduction , Chemokine CCL20/genetics , Chemokine CCL20/metabolism , Cell Line, Tumor , Receptors, CCR6/genetics , Cell ProliferationABSTRACT
AIM: Although many reports have shown that Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) is effective for postoperative urinary continence, the postoperative voiding status and sexual function associated with this technique have not yet been adequately compared with those associated with conventional RARP (C-RARP). In this study, the lower urinary tract function, erectile function, and cancer control after C-RARP and RS-RARP were compared chronologically. MATERIALS AND METHODS: We selected 50 cases of C-RARP and RS-RARP each by propensity score matching and evaluated them over time using various questionnaires. Urinary continence recovery rates and biochemical recurrence (BCR)-free survival rates were calculated using the Kaplan-Meier method and compared between the two groups using the log-rank test. RESULTS: When urinary continence was defined as 0 pads per day, 0 pads per day + 1 security linear, or ≤1 pad per day, the postoperative improvement in urinary continence was better with RS-RARP over the course of up to 1 year for all definitions. The International Consultation on Incontinence Questionnaire-Short Form total scores and the Overactive Bladder Symptom Scores were better in the postoperative RS-RARP group. There were no significant differences in the International Prostate Symptom Score total score, QOL score, and erectile hardness score between the two groups during the observation period. The BCR-free survival did not differ significantly between the two groups CONCLUSIONS: Postoperative urinary continence was better in the RS-RARP group than in the C-RARP group; however, the voiding function, erectile function, and cancer control did not differ significantly.
Subject(s)
Erectile Dysfunction , Prostatic Neoplasms , Robotic Surgical Procedures , Robotics , Male , Humans , Prostate , Erectile Dysfunction/etiology , Erectile Dysfunction/prevention & control , Propensity Score , Quality of Life , Prostatic Neoplasms/surgery , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Prostatectomy/adverse effects , Prostatectomy/methods , Treatment OutcomeABSTRACT
AIMS: This study aimed to investigate the postoperative urinary continence rate and incontinence types compared over time between conventional robot-assisted radical prostatectomy (C-RARP) and Retzius-sparing RARP (RS-RARP). METHODS: All 61 cases were selected from the C-RARP and RS-RARP by propensity score matching, and the pad scale, 24-h pad weight test, and International consultation on incontinence questionnaire-short form (ICIQ-SF) were followed-up over time up to 12 months. RESULTS: The probability of urinary continence per pad scale evaluation differed according to how it was defined: the continence rate 12 months after C-RARP and RS-RARP were 94% and 95% for 1 pad/day, 85% and 92% for 1 security pad/day, 61% and 85% for no pad use, respectively, which were all significantly better with RS-RARP. The results of the 24-h pad weight test were significantly better with RS-RARP at both 3 and 12 months, with median C-RARP versus RS-RARP values of 5 versus 1 g and 2 versus 0 g, respectively. In terms of types of urinary incontinence, the rates of postoperative stress urinary incontinence (SUI) increased in both procedures but to a lesser extent in RS-RARP. Other types of urinary incontinence, such as urge incontinence and terminal dribbling, did not differ significantly before and after surgery and between the two procedures. CONCLUSIONS: Postoperative urinary continence was better with RS-RARP than with C-RARP per all follow-up parameters until 12 months postoperatively. Postoperative SUI was significantly lower with RS-RARP than with C-RARP, which was considered the main reason for better postoperative urinary continence with RS-RARP.
Subject(s)
Robotic Surgical Procedures , Robotics , Urinary Incontinence, Stress , Urinary Incontinence , Male , Humans , Urinary Incontinence/epidemiology , Urinary Incontinence/etiology , Urinary Incontinence/surgery , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Prostate/surgery , Prostatectomy/adverse effects , Prostatectomy/methods , Urinary Incontinence, Stress/surgery , Treatment OutcomeABSTRACT
OBJECTIVE: Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100 ng/mL and chemokine (CC motif) ligand 2 ≥ 320 pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. METHODS: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. RESULTS: Patients with chemokine (CC motif) ligand 2 ≥ 320 pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2 < 320 pg/mL. Multivariate analysis was performed to determine whether chemokine (CC motif) ligand 2 was a useful prognostic factor. Independent significant predictors of worse overall survival were prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8 and chemokine (CC motif) ligand 2 ≥ 320 pg/dL. Prognostic predictors of prostate cancer-specific survival or cancer-free survival in multivariate analysis were prostate-specific antigen ≥ 100 ng/mL and Gleason score ≥ 8. A novel risk classification system was created to predict overall survival in patients based on the number of risk factors present (chemokine (CC motif) ligand 2 ≥ 320 pg/mL, prostate-specific antigen ≥ 100 ng/mL, Gleason score ≥ 8). Scores 2 or 3, 1 and 0 indicated Poor, Intermediate and Good risk groups, respectively. CONCLUSIONS: This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.
Subject(s)
Chemokine CCL2 , Prostate-Specific Antigen , Prostatic Neoplasms , Humans , Male , Biomarkers , Chemokine CCL2/blood , Follow-Up Studies , Prognosis , Prostate/pathology , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Retrospective StudiesABSTRACT
BACKGROUND: Visceral metastasis (VM), an important poor prognostic factor of prostate cancer (PC), is not commonly observed in castration sensitive status but is often observed after castration-resistant progression. However, the site, timing of emergence, and incidence of VM in castration-resistant patients have not yet been fully elucidated. METHODS: Demographic, surgical, pathological, and follow-up data of PC patients treated at Kanazawa University Hospital between January 2000 and December 2016 were retrospectively analyzed using their medical charts. From this data, risk factors of VM and survival of patients with VM were elucidated. RESULTS: Of 1364 patients, 21 (1.5%) had VM at diagnosis. Of 179 (13.1%) castration-resistant patients, 55 experienced emergence of new VM during treatment course. Incidence of new VM, especially nonlung, such as liver and adrenal metastases, increased significantly in proportion with the number of prescribed treatments. Multivariate analysis revealed that T stage, M stage, age, and treatment history with androgen receptor (AR) signaling-targeted agents and/or taxanes significantly increased the risk of VM. Compared with the group with VM at diagnosis, survival after diagnosis of VM following treatment was significantly shorter. CONCLUSION: Although sequential use of new AR signaling-targeted agents and taxanes for castration-resistant PC (CRPC) is a standard treatment strategy, it often results in development of VM. Elucidating the mechanisms of VM are essential to improve survival in patients with CRPC.
Subject(s)
Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/metabolism , Receptors, Androgen/metabolism , Aged , Aged, 80 and over , Androstenes/therapeutic use , Benzamides , Docetaxel/therapeutic use , Humans , Incidence , Lung Neoplasms/secondary , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Nitriles , Phenylthiohydantoin/analogs & derivatives , Phenylthiohydantoin/therapeutic use , Prostatic Neoplasms, Castration-Resistant/epidemiology , Prostatic Neoplasms, Castration-Resistant/pathology , Retrospective Studies , Risk Factors , Signal Transduction/drug effects , Taxoids/therapeutic useABSTRACT
BACKGROUND: Our previous report has shown that the flavonoid 2'-hydroxyflavanone (2'-HF) showed inhibition of androgen receptor (AR) activity against androgen-sensitive prostate cancer (PCa) cells, LNCaP, and exhibited antitumor effects against androgen-insensitive PCa cells, PC-3, and DU145. In the present study, we prepared a derivative of 2'-HF, 16MS7F1924, and confirmed the effects of this derivative on PCa cells. METHODS: The antiproliferation effects of 16MS7F1924 were investigated in PCa cells using LNCaP, PC-3, DU145 and docetaxel-resistant and cabazitaxel-resistant cell lines of PC-3-TxR/CxR and DU145-TxR/CxR. Prostate-specific antigen (PSA) and AR expression level in whole cells and the nucleus were confirmed in LNCaP by reverse transcriptase polymerase chain reaction and Western blot analysis. AR activity in LNCaP cells was confirmed by luciferase assay using PSA promoter-driven reporter. To analyze the antiproliferative effects, cell-based assays using flow cytometry, immunocytochemistry, and TUNEL assay as well as Western blot analysis were employed. Furthermore, PC-3, DU145 and each chemoresistant strain of human PCa cells were subcutaneously xenografted. The antitumor effects of 16MS7F1924 were evaluated in vivo. RESULTS: 16MS7F1924 showed antitumor effect on all PCa cells in a dose-dependent manner. 16MS7F1924 reduced the expression of PSA messenger RNA (mRNA) and protein and inhibited AR activity in a dose-dependent manner, while expression of AR protein and mRNA was reduced by 16MS7F1924. 16MS7F1924 induced mitotic catastrophe and apoptosis. Apoptotic cells were increased in a dose-dependent manner, and the apoptosis was mediated through the Akt pathway. Tumor growth was safely and significantly inhibited by both intraperitoneal and oral administration of 16MS7F1924 in vivo. CONCLUSION: 16MS7F1924 had sufficient antitumor activity against androgen-sensitive and cabazitaxel-resistant PCa cells and may be useful as a novel therapeutic agent overcoming hormone- and chemoresistant PCas.
Subject(s)
Androgen Receptor Antagonists/therapeutic use , Antineoplastic Agents/therapeutic use , Flavanones/chemistry , Flavanones/therapeutic use , Prostatic Neoplasms/drug therapy , Taxoids , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Humans , Male , Mice , Mice, SCID , Molecular Structure , PC-3 Cells , Prostatic Neoplasms/pathology , Xenograft Model Antitumor AssaysABSTRACT
OBJECTIVES: To evaluate the safety and efficacy of transvaginal mesh surgery using a polytetrafluoroethylene mesh to treat pelvic organ prolapse. METHODS: This prospective observational study included women undergoing transvaginal mesh surgery for pelvic organ prolapse that used new polytetrafluoroethylene mesh cut into a shape similar to that of Elevate. We evaluated the subjective and objective outcomes at 3 and 12 months, as well as postoperative complication rates. RESULTS: This study included 55 patients. The pelvic organ prolapse quantification scores improved significantly at 3 and 12 months after surgery compared with scores before surgery. In four patients (7.3%), a pelvic examination showed stage 2 objective recurrence without subjective symptoms. Clavien-Dindo grades 2 and 3 perioperative complications were observed in 9.1% and 1.8% of the patients, respectively. Vaginal mesh exposure occurred in one patient (1.8%) at the time of the 3-month follow-up evaluation. The mesh was exposed at the proximal midline of the anterior vaginal wall. CONCLUSIONS: These findings show the safe and effective use of the polytetrafluoroethylene mesh for transvaginal mesh surgery.
Subject(s)
Gynecologic Surgical Procedures/methods , Pelvic Organ Prolapse/surgery , Polytetrafluoroethylene/therapeutic use , Surgical Mesh/adverse effects , Aged , Aged, 80 and over , Female , Humans , Postoperative Complications , Treatment Outcome , Vagina/surgeryABSTRACT
Chemokines are a small family of cytokines that were first discovered as chemotactic factors in leukocytes during inflammation, and reports on the relationship between chemokines and cancer progression have recently been increasing. The CCL2-CCR2 axis is one of the major chemokine signaling pathways, and has various functions in tumor progression, such as increasing tumor cell proliferation and invasiveness, and creating a tumor microenvironment through increased angiogenesis and recruitment of immunosuppressive cells. This review discusses the roles of the CCL2-CCR2 axis and the tumor microenvironment in cancer progression and their future roles in cancer therapy.
Subject(s)
Cell Proliferation , Chemokine CCL2/immunology , Neoplasm Proteins/immunology , Receptors, CCR2/immunology , Signal Transduction/immunology , Tumor Microenvironment/immunology , Animals , HumansABSTRACT
Macrophages are present in most human tissues and have very diverse functions. Activated macrophages are usually divided into two phenotypes, M1 macrophages and M2 macrophages, which are altered by various factors such as microorganisms, tissue microenvironment, and cytokine signals. Macrophage polarity is very important for infections, inflammatory diseases, and malignancies; its management can be key in the prevention and treatment of diseases. In this review, we assess the current state of knowledge on macrophage polarity and report on its prospects as a therapeutic target.
Subject(s)
Cell Polarity/physiology , Macrophages/pathology , Animals , Cytokines/metabolism , Disease , Humans , Macrophages/metabolismABSTRACT
Chemokines, which are basic proteins that exert their effects via G protein-coupled receptors and a subset of the cytokine family, are mediators deeply involved in leukocyte migration during an inflammatory reaction. Chemokine (C-C motif) ligand 20 (CCL20), also known as macrophage inflammatory protein (MIP)-3α, liver activation regulated chemokine (LARC), and Exodus-1, is a small protein that is physiologically expressed in the liver, colon, and skin, is involved in tissue inflammation and homeostasis, and has a specific receptor C-C chemokine receptor 6 (CCR6). The CCL20-CCR6 axis has long been known to be involved in inflammatory and infectious diseases, such as rheumatoid arthritis and human immunodeficiency virus infections. Recently, however, reports have shown that the CCL20-CCR6 axis is associated with several cancers, including hepatocellular carcinoma, colorectal cancer, breast cancer, pancreatic cancer, cervical cancer, and kidney cancer. The CCL20-CCR6 axis promotes cancer progression directly by enhancing migration and proliferation of cancer cells and indirectly by remodeling the tumor microenvironment through immune cell control. The present article reviewed the role of the CCL20-CCR6 axis in cancer progression and its potential as a therapeutic target.
Subject(s)
Cell Movement/immunology , Cell Proliferation , Chemokines/metabolism , Macrophages/immunology , Neoplasms/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology , Tumor Microenvironment/immunology , Chemokine CCL20/metabolism , Disease Progression , Humans , Neoplasms/metabolism , Receptors, CCR6/metabolismABSTRACT
Understanding the mechanism of chemoresistance and disease progression in patients with prostate cancer is important for developing novel treatment strategies. In particular, developing resistance to cabazitaxel is a major challenge in patients with docetaxel-resistant and castration-resistant prostate cancer (CRPC) because cabazitaxel is often administered as a last resort. However, the mechanism by which cabazitaxel resistance develops is still unclear. C-C motif chemokine ligands (CCL) were shown to contribute to the castration resistance of prostate cancer cells via an autocrine mechanism. Therefore, we focused on CCL as key factors of chemoresistance in prostate cancer cells. We previously established a cabazitaxel-resistant cell line, DU145-TxR/CxR, from a previously established paclitaxel-resistant cell line, DU145-TxR. cDNA microarray analysis revealed that the expression of CCL2 was upregulated in both DU145-TxR and DU145-TxR/CxR cells compared with DU145 cells. The secreted CCL2 protein level in DU145-TxR and DU145-TxR/CxR cells was also higher than in parental DU145 cells. The stimulation of DU145 cells with CCL2 increased the proliferation rate under treatments with cabazitaxel, and a CCR2 (a specific receptor of CCL2) antagonist suppressed the proliferation of DU145-TxR and DU145-TxR/CxR cells under treatments of cabazitaxel. The CCL2-CCR2 axis decreased apoptosis through the inhibition of caspase-3 and poly(ADP-ribose) polymerase (PARP). CCL2 is apparently a key contributor to cabazitaxel resistance in prostate cancer cells. Inhibition of the CCL2-CCR2 axis may be a potential therapeutic strategy against chemoresistant CRPC in combination with cabazitaxel.
Subject(s)
Cell Proliferation/drug effects , Chemokine CCL2/pharmacology , Drug Resistance, Neoplasm/drug effects , Prostatic Neoplasms/drug therapy , Taxoids/pharmacology , Xenograft Model Antitumor Assays/methods , Animals , Cell Line, Tumor , Cell Proliferation/genetics , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Drug Resistance, Neoplasm/genetics , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/drug effects , Humans , Male , Mice, SCID , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Receptors, CCR2/genetics , Receptors, CCR2/metabolism , Tumor Burden/drug effects , Tumor Burden/geneticsABSTRACT
BACKGROUND: Coffee inhibits the progression of prostate cancer; however, the direct mechanism through which coffee acts on prostate cancer cells remains unclear. This study aimed to identify the key compounds of coffee that possess anti-cancer effects and to investigate their mechanisms of action. METHODS: The anti-proliferation and anti-migration effects of six potentially active types of coffee compounds, including kahweol acetate, cafestol, caffeine, caffeic acid, chlorogenic acid, and trigonelline hydrochloride, were evaluated using LNCaP, LNCaP-SF, PC-3, and DU145 human prostate cancer cells. The synergistic effects of these compounds were also investigated. Apoptosis-related and epithelial-mesenchymal transition-related proteins, androgen receptor in whole cell and in nucleus, and chemokines were assessed. A xenograft study of SCID mice was performed to examine the in vivo effect of coffee compounds. RESULTS: Among the evaluated compounds, only kahweol acetate and cafestol inhibited the proliferation and migration of prostate cancer cells in a dose-dependent manner. The combination treatment involving kahweol acetate and cafestol synergistically inhibited proliferation and migration (combination index <1) with the induction of apoptosis, the inhibition of epithelial-mesenchymal transition, and decrease in androgen receptor, resulting in the reduction of nuclear androgen receptor in androgen receptor-positive cells. Moreover, kahweol acetate and cafestol downregulated CCR2 and CCR5 without an increase in their ligands, CCL2 and CCL5. The xenograft study showed that oral administration of kahweol acetate and cafestol significantly inhibited tumor growth. CONCLUSION: Kahweol acetate and cafestol synergistically inhibit the progression of prostate cancer. These coffee compounds may be novel therapeutic candidates for prostate cancer.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Diterpenes/pharmacology , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Animals , Apoptosis/drug effects , Cell Line, Tumor , Cell Movement/drug effects , Cell Proliferation/drug effects , Coffee/chemistry , Diterpenes/administration & dosage , Drug Synergism , Epithelial-Mesenchymal Transition/drug effects , Humans , Male , Mice , Mice, SCID , PC-3 Cells , Random Allocation , Xenograft Model Antitumor AssaysABSTRACT
Understanding the mechanism of lymph node metastasis, a poor prognostic sign for prostate cancer, and the further dissemination of the disease is important to develop novel treatment strategies. Recent studies have reported that C-C chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in lymph node metastasis and promotes cancer progression. Tumor necrosis factor-α (TNF-α) is chronically produced at low levels within the tumor microenvironment. The aim of this study was to determine whether TNF-α promotes prostate cancer dissemination from metastatic lymph nodes through activation of the CCL21/CCR7 axis. First, human prostate cancer cells were determined to express both TNF-α and CCR7. Second, low concentrations of TNF-α were confirmed to induce CCR7 in prostate cancer cells through phosphorylation of ERK. Finally, CCL21 was found to promote the migration of prostate cancer cells through phosphorylation of the protein kinase p38. Our results suggest that TNF-α leads to the induction of CCR7 expression and that the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis.
Subject(s)
Prostatic Neoplasms/pathology , Receptors, CCR7/physiology , Tumor Necrosis Factor-alpha/pharmacology , Cell Line, Tumor , Cell Movement , Chemokine CCL21/physiology , Humans , Lymphatic Metastasis , MAP Kinase Signaling System/physiology , Male , Receptors, CCR7/genetics , Up-Regulation , p38 Mitogen-Activated Protein Kinases/physiologyABSTRACT
Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling.
Subject(s)
Bone Neoplasms/metabolism , Bone Neoplasms/secondary , Chemokine CCL5/metabolism , Prostatic Neoplasms/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Coculture Techniques , Gene Expression Regulation, Neoplastic , Humans , Male , Protein Array Analysis , Stromal Cells/cytology , Stromal Cells/metabolism , Tumor Microenvironment , Up-RegulationABSTRACT
AIMS: To examine which preoperative factors, including urodynamic evaluations, and operative procedures could predict continence status after robot-assisted radical prostatectomy (RARP) in this study. MATERIALS AND METHODS: Univariate and multivariate logistic regression analyses of preoperative factors such as age, body mass index, prostate-specific antigen level before biopsy, prostate size before surgery, membranous urethral length measured using magnetic resonance imaging (MRI), bladder compliance and maximum urethral closure pressure (MUCP) measured by urodynamic study (UDS), and nerve-sparing (NS) status predicting 24-hr pad test >2 g/day at 1 year after RARP were examined in 111 patients enrolled in this study. RESULTS: The number of patients with incontinence at 1 year after RARP was 39 (35.1%). The only predictive factor for urinary continence was NS grades. To investigate the contribution of NS to urinary continence, 84 patients underwent UDS three times; before, immediately after, and 1 year after RARP. Chronological UDS revealed that recovery patterns of storage and voiding functions were the same among non-NS, unilateral-NS, and bilateral-NS groups, and that higher degrees of NS contributed to lesser decreases in MUCP and longer functional urethral length (FUL) after RARP. CONCLUSION: Preoperative factors, including the results of UDS, could not predict continence 1 year after RARP. The NS procedure contributed to continence status. NS favorably affected MUCP and FUL; however, it did not affect bladder function after RARP. Neurourol. Urodynam. 35:1034-1039, 2016. © 2015 Wiley Periodicals, Inc.
Subject(s)
Postoperative Complications/prevention & control , Prostatectomy/adverse effects , Prostatectomy/methods , Robotic Surgical Procedures/adverse effects , Robotic Surgical Procedures/methods , Urinary Incontinence/etiology , Urinary Incontinence/prevention & control , Urodynamics , Age Factors , Aged , Body Mass Index , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neoplasm Grading , Prostate-Specific Antigen/analysis , Prostatic Neoplasms/complications , Prostatic Neoplasms/surgery , Urinary Bladder/physiopathologyABSTRACT
We examined the efficacy of recombinant thrombomodulin (rTM) for treatment of patients with disseminated intravascular coagulation (DIC) caused by urinary tract infections. Thirteen DIC patients treated with rTM (rTM group) and 11 not receiving rTM (non-rTM group) were enrolled in this study. Blood data including coagulation markers collected before and after the treatment,a hospitalized term,and period of antibiotic treatment were compared. There were no significant differences in baseline characteristics between the two groups. Both groups showed significant improvement in all parameters such as blood biochemical data,coagulation markers,and DIC score 5-7 days after treatment. However, changes in platelet and DIC score from baseline to early phase (day 1-3) were significantly greater in the rTM group than in the non-rTM group (pï¼0.05). In addition,changes in FDP value showed slight but not significant improvement in rTM group compared to the non-rTM group in the early treatment phase (pï¼ 0.084). The period of antibiotic usage was significantly shorter in the rTM group,whereas the hospitalized term showed no significant difference between the groups. Definite adverse effects were not present in the rTM group. In conclusion,administration of rTM may have a beneficial effect in patients with DIC induced by urinary tract infections,compared with conventional treatment.
Subject(s)
Disseminated Intravascular Coagulation/drug therapy , Disseminated Intravascular Coagulation/etiology , Thrombomodulin/administration & dosage , Urinary Tract Infections/complications , Aged , Aged, 80 and over , Anticoagulants/administration & dosage , Benzamidines , Female , Guanidines/administration & dosage , Heparin/administration & dosage , Humans , Male , Middle Aged , Recombinant Proteins/administration & dosage , Retrospective Studies , Treatment OutcomeABSTRACT
Introduction: Low-dose-rate brachytherapy is performed for localized prostate cancer. We report the first case of a bladder stone encompassing the seed migrated into the bladder in a patient treated with low-dose-rate brachytherapy. Case presentation: A man was diagnosed with prostate cancer and underwent low-dose-rate brachytherapy. After 2 months, dysuria occurred, and ultrasonography revealed a needle-shaped high-intensity protruding from the prostate into the bladder. Cystoscopy examination found a seed link connector. With the possibility of natural dissolution of the seed link, careful observation was chosen. However, 16 months later, hematuria occurred, and an X-ray revealed a bladder stone encompassing the seed. Compared with the X-ray right after seeding, the seed located near the right bladder neck had fallen. The seed was removed by transurethral bladder lithotripsy. Conclusion: Seeds should be carefully located within the prostate, otherwise a bladder stone may be formed encompassing the seed.
ABSTRACT
Several markers that reflect inflammation and nutritional status have been associated with oncological outcomes in many tumors. This study aimed to describe the impact of pretreatment inflammatory and nutritional indices on the oncological outcomes in nonmetastatic renal cell carcinoma (RCC). A total of 213 Japanese patients with nonmetastatic RCC at Kanazawa University Hospital between October 2007 and December 2018 were included. The inflammatory and nutritional indices, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein-to-albumin ratio (CAR), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI), were retrospectively analyzed. The optimal cutoffs for NLR, PLR, CAR, PNI, and GNRI were 2.18, 153.7, 0.025, 48.4, and 98, respectively. According to Kaplan-Meier curves, elevated NLR, PLR, CAR, and GNRI correlated with increased metastasis, while NLR and PNI correlated with worse overall survival (OS). In multivariate analysis, high CAR was an independent poor risk factor for metastasis (hazard ratio (HR), 3.08; 95% confidence interval (CI), 1.24-7.67; p = 0.016). Furthermore, high NLR showed an independent prognostic factor for worse OS (HR, 3.96; 95% CI, 1.01-15.59; p = 0.049). The pretreatment inflammatory and nutritional indices such as NLR and CAR might be promising prognostic factors for nonmetastatic RCC.