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INTRODUCTION: Urothelial carcinoma (UC) is a common type of malignant disease, but little is known about the diagnostic and prognostic markers of upper urinary tract urothelial cancer (UTUC) because of its rarity. To clarify the significance of ANXA10 in UTUC, we studied ANXA10 expression with immunohistochemistry (IHC). METHODS: The expression of ANXA10 was analyzed in the upper and lower urinary tract of UC by IHC in combination with The Cancer Genome Atlas (TCGA) data analysis. The association between ANXA10 expression and representative cancer-related molecules was also evaluated. RESULTS: ANXA10 expression was weak in normal upper tract urothelium but was positive in 39/117 (33%) UTUCs. ANXA10 was more frequently positive in tumors with pure UC (36%, p < 0.05), papillary morphology (50%, p < 0.01), low grade (G1/2: 57%, p < 0.01), and pTa/is/1 stage (55%, p < 0.01) than in those with histological variants (0%), nodular morphology (9%), G3 (16%), and pT2/3/4 (13%), respectively. ANXA10-positive patients showed better cancer-specific survival and progression-free survival than ANXA10-negative patients (p < 0.05). IHC showed that ANXA10 positivity was detected more in cases with the low expression of TP53 (p < 0.01) and Ki-67 labeling index <20% (p < 0.01). In TCGA dataset of muscle-invasive bladder cancer, higher ANXA10 expression correlated with papillary morphology, lower grade/stage, luminal papillary subtype, wild-type TP53, and FGFR3 gene mutation. CONCLUSION: We revealed that ANXA10 expression was increased during carcinogenesis and was observed more frequently in papillary UC of lower grade and stage. However, its expression decreased as cancer progressed. Therefore, the ANXA10 expression in UTUC might be clinically useful for decision-making.
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Carcinoma de Células Transicionales , Neoplasias Renales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/genética , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/patología , Neoplasias Renales/genética , Neoplasias Ureterales/genética , Neoplasias Ureterales/metabolismo , Neoplasias Ureterales/patología , Urotelio/metabolismo , Urotelio/patología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Anexinas/genética , Anexinas/metabolismoRESUMEN
Renal cell carcinoma (RCC) is one of the most common human cancers. We previously reported that claspin is a key regulator in the progression of gastric cancer, and it likely plays an important role in cancer stem cells of gastric cancer. However, the significance of claspin in RCC has not been examined. First, we analyzed the expression and distribution of claspin in 95 RCC cases by immunohistochemistry. In the nonneoplastic kidney, the staining of claspin was either weak or absent, whereas RCC tissue showed nuclear staining. In total, claspin expression was detected in 45 (47%) of 95 RCC cases. The claspin staining appeared relatively stronger in high nuclear grade RCC than in low nuclear grade RCC. Claspin-positive RCC cases were associated with higher T grade, tumor stage, nuclear grade, vein invasion, and poorer prognosis. CLSPN siRNA treatment decreased RCC cell proliferation. The levels of phosphorylated Erk and Akt were lower in CLSPN siRNA-transfected RCC cells than in control cells. In addition, claspin was coexpressed with CD44, epidermal growth factor receptor, p53, and programmed death ligand-1. These results suggest that claspin plays an important role in tumor progression in RCC and might be a prognostic marker and novel therapeutic target molecule.
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Proteínas Adaptadoras Transductoras de Señales/genética , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Expresión Génica/genética , Neoplasias Renales/genética , Neoplasias Renales/patología , Biomarcadores de Tumor/genética , Progresión de la Enfermedad , Receptores ErbB/genética , Femenino , Humanos , Riñón/patología , Masculino , Persona de Mediana Edad , Células Madre Neoplásicas/patología , PronósticoRESUMEN
Background Prostate cancer (PCa) is a common malignancy worldwide and is the second leading cause of cancer death in men. The standard therapy for advanced PCa is androgen deprivation therapy (ADT). Although ADT, including bicalutamide treatment, is initially effective, resistance to bicalutamide frequently occurs and leads to the development of castration-resistant PCa. Thus, clarifying the mechanisms of bicalutamide resistance is urgently needed. We designed this study to assess the expression and function of PCDHB9, which encodes the protocadherin B9 protein. Methods The expression of PCDHB9 was determined using immunohistochemistry and a qRT-PCR. The effects of the overexpression or knockdown of PCDHB9 on cell growth, migration, adhesion were evaluated. To evaluate the PCDHB9-mediated effects in PCa, we performed a gene expression analysis using DU145 transfected with PCDHB9. We examined the effects of PCDHB9 inhibition on bicalutamide resistance. Results The qRT-PCR revealed that the expression of PCDHB9 was much higher in PCa than that in non-neoplastic prostate tissues. In 152 clinically localized PCa cases immunohistochemistry showed that 59% of PCa cases were positive for protocadherin B9. A Kaplan-Meier analysis showed that the high expression of protocadherin B9 was associated with PSA recurrence after radical prostatectomy. A functional analysis showed that PCDHB9 modulated cell migration and adhesion. We also found that PCDHB9 induced the expression of ITGB6 based on a gene expression analysis. The effect of PCDHB9 inhibition on bicalutamide sensitivity was examined using MTT assays. The IC50 value of PCDHB9 siRNA-transfected PCa cells was significantly lower than that of negative control siRNA-transfected cells. Furthermore, immunohistochemical staining of protocadherin B9 in 74 PCa patients who were treated with androgen depletion therapy, including bicalutamide treatment, demonstrated that the high expression of protocadherin B9 was significantly associated with poor overall survival. Conclusions PCDHB9 plays an important role in the progression of PCa and bicalutamide resistance. Collectively, our results suggest that PCDHB9 targeted therapy may be more effective than bicalutamide alone.
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Anilidas/farmacología , Cadherinas/biosíntesis , Nitrilos/farmacología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Compuestos de Tosilo/farmacología , Anciano , Antineoplásicos/farmacología , Cadherinas/genética , Adhesión Celular/fisiología , Movimiento Celular/fisiología , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Neoplasias de la Próstata/genética , Receptores Androgénicos/metabolismo , Estudios RetrospectivosRESUMEN
OBJECTIVES: Bladder cancer (BC) is a common malignancy worldwide. Signal peptidase complex 18 (SPC18) protein, which is encoded by the SEC11A gene, is one of the subunits of the signal peptidase complex and induces transforming growth factor-α secretion. In the present study, we analyzed the expression and function of SPC18 protein in human BC. METHODS: Expression of SPC18 was analyzed by immunohistochemistry. RNA interference was used to inhibit SEC11A expression in BC cell lines. For constitutive expression of the SEC11A gene, a SEC11A expression vector was transfected into BC cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Modified Boyden chamber assays were used to examine cell invasiveness. RESULTS: SPC18 was upregulated in 54% of 81 BC cases. SPC18 expression served as an independent prognostic classifier of patients with BC. SPC18-positive BC cases frequently expressed cytokeratin 5/6, a marker of basal-like BC. Cell growth and invasiveness were inhibited by SEC11A knockdown and enhanced by forced expression of SEC11A. CONCLUSION: These results indicate that SPC18 plays an important role in the progression of BC. Specific inhibitors of SPC18 may be promising anticancer drugs for patients with basal-like BC.
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Péptido Hidrolasas/genética , Neoplasias de la Vejiga Urinaria/genética , Adulto , Anciano , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Femenino , Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/fisiopatologíaRESUMEN
OBJECTIVE: Esophageal cancer is one of the deadliest cancers in the world, and the main subtype is esophageal squamous cell carcinoma (ESCC), which comprises 90% of cases. Expression of tryptophan 2,3-dioxygenase (TDO2), an enzyme involved in tryptophan catabolism, has been linked with tumor survival and poor prognosis of brain and breast cancer. However, no studies have investigated the potential role of TDO2 in esophageal cancer. Here we explored the expression and biological significance of TDO2 in ESCC. METHODS: TDO2 protein expression was evaluated in 90 ESCC tissue samples by immunohistochemistry. TDO2 function in ESCC cell lines and spheroid colony formation were evaluated by RNA interference (RNAi). RESULTS: TDO2 overexpression was associated with tumor stage, recurrence status, and the CD44 cancer stem cell marker in ESCC. TDO2 overexpression was correlated with poor outcome of ESCC patients. Inhibition of TDO2 expression by RNAi in TE-10 and TE-11 cell lines reduced both the number and the size of spheroid colonies as well as cell proliferation. Knockdown of TDO2 expression also induced inactivation of the epidermal growth factor receptor signaling pathway. CONCLUSION: Our results imply that TDO2 could play an important role in the progression of ESCC. Furthermore, TDO2 may be a potential therapeutic target in ESCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/enzimología , Neoplasias Esofágicas/enzimología , Células Madre Neoplásicas/enzimología , Triptófano Oxigenasa/metabolismo , Anciano , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Línea Celular Tumoral , Proliferación Celular , Quimioterapia Adyuvante , Progresión de la Enfermedad , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Esofagectomía , Femenino , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Receptores de Hialuranos/metabolismo , Inmunohistoquímica , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Células Madre Neoplásicas/patología , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Triptófano Oxigenasa/genética , Regulación hacia ArribaRESUMEN
BACKGROUND: The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis in some cancers. However, the expression and biological role of T-UCRs in renal cell carcinoma (RCC) remain poorly understood. This study aimed to examine the expression and functional role of Uc.416 + A and analyze the association between Uc.416 + A and epithelial-to-mesenchymal transition in RCC. METHODS: Expression of Uc.416 + A in 35 RCC tissues, corresponding normal kidney tissues and 13 types of normal tissue samples was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We performed a cell growth and migration assay in RCC cell line 786-O transfected with negative control and siRNA for Uc.416 + A. We evaluated the relation between Uc.416 + A and miR-153, which has a complimentary site of Uc.416 + A. RESULTS: qRT-PCR analysis revealed that the expression of Uc.416 + A was higher in RCC tissues than that in corresponding normal kidney tissues. Inhibition of Uc.416 + A reduced cell growth and cell migration activity. There was an inverse correlation between Uc.416 + A and miR-153. Western blot analysis showed Uc.416 + A modulated E-cadherin, vimentin and snail. The expression of Uc.416 + A was positively associated with the expression of SNAI1, VIM and inversely associated with the expression of CDH1. CONCLUSIONS: The expression of Uc.416 + A was upregulated in RCC and especially in RCC tissues with sarcomatoid change. Uc.416 + A promoted epithelial-to-mesenchymal transition through miR-153. These results suggest that Uc.416 + A may be a promising therapeutic target.
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Carcinoma de Células Renales/metabolismo , Transición Epitelial-Mesenquimal/genética , Neoplasias Renales/metabolismo , MicroARNs/fisiología , ARN no Traducido/metabolismo , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Humanos , ARN no Traducido/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: We aimed to assess the usefulness of 3-T 4-dimensional (4D) arterial spin-labeling (ASL)-based magnetic resonance angiography (MRA) with color-coded time-of-arrival (TOA) maps for the evaluation of cerebral arteriovenous malformations (AVMs). METHODS: Our study included 6 patients with cerebral AVMs. They underwent 4D-ASL MRA at 3T and digital subtraction angiography. A pseudocontinuous arterial spin labeling protocol with look-locker sampling was used for spin labeling. Two independent readers reviewed the 4D-ASL MRA images with color-coded TOA maps for the nidus size, arterial feeders, and venous drainage. Two other readers consensually reviewed the digital subtraction angiography images. RESULTS: The cerebral AVMs were demonstrated on all 4D-ASL MRA images. In 5 high-flow AVMs, the color-coded TOA maps were especially useful for identifying the feeder/drainer. Intermodality agreement was excellent for the nidus size (κ = 1.0), very good for arterial feeders (κ = 0.88), and good for venous drainage (κ = 0.80). CONCLUSIONS: The 4D-ASL 3-T MRA with color-coded TOA maps is useful for assessing the gross angiographic characteristics of intracranial AVMs.
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Imagenología Tridimensional/métodos , Malformaciones Arteriovenosas Intracraneales/patología , Angiografía por Resonancia Magnética/métodos , Marcadores de Spin , Adolescente , Adulto , Anciano , Angiografía de Substracción Digital , Mapeo Encefálico/métodos , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
AIM: To evaluate whether 3-T four-dimensional (4D) arterial spin-labelling (ASL) -based magnetic resonance angiography (MRA) is useful for assessing the collateral circulation via the circle of Willis in patients with carotid artery steno-occlusive disease. MATERIALS AND METHODS: Institutional review board approval and prior written informed consent from all patients were obtained. The inclusion criteria were fulfilled by 13 patients with carotid artery steno-occlusive disease. All underwent 4D-ASL MRA at 3 T and digital subtraction angiography (DSA). The flow-sensitive alternating inversion recovery (FAIR) preparation scheme with look-locker sampling was used for spin labeling. At 300-ms intervals seven dynamic scans were obtained with a spatial resolution of 0.5×0.5×0.6 mm(3). The collateral flow via the circle of Willis was read on 4D-ASL MRA and DSA images by two sets of two independent readers each. κ statistics were used to assess interobserver and intermodality agreement. RESULTS: On DSA, collateral flow via the anterior communicating artery (AcomA) was observed in six patients, via the posterior communicating artery (PcomA) in four patients, and via both the AcomA and PcomA in three patients. With respect to the qualitative evaluation of 4D-ASL MRA images, interobserver agreement was excellent for all items (κ=1). 4D-ASL MRA and DSA consensus readings agreed on the type of collateral flow pattern in 10 of the 13 patients (77%). Intermodality agreement was good (κ=0.606; 95% confidence interval (CI): 0.215-0.997). CONCLUSION: 3 T 4D-ASL MRA may be a useful tool for the evaluation of the collateral circulation in patients with carotid artery steno-occlusive disease.
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Estenosis Carotídea/diagnóstico , Círculo Arterial Cerebral , Circulación Colateral , Angiografía por Resonancia Magnética/métodos , Anciano , Anciano de 80 o más Años , Angiografía de Substracción Digital , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Marcadores de SpinRESUMEN
PURPOSE: To evaluate whether 3-T four-dimensional (4D) arterial spin-labeling (ASL)-based magnetic resonance (MR) angiography is useful for the evaluation of shunt lesions in patients with intracranial dural arteriovenous fistulas (AVFs). MATERIALS AND METHODS: Institutional review board approval and prior written informed consent from all patients were obtained. Nine patients with intracranial dural AVF (seven men, two women; age range, 52-77 years; mean age, 63 years) underwent 4D ASL MR angiography at 3 T and digital subtraction angiography (DSA). Spin tagging was with flow-sensitive alternating inversion recovery with Look-Locker sampling. At 300-millisecond intervals, seven dynamic images with a spatial resolution of 0.5 × 0.5 × 0.6 mm(3) were obtained. The 4D ASL MR angiographic and DSA images were read by two sets of two independent readers each. Interobserver and intermodality agreement was assessed with the κ statistic. RESULTS: On all 4D ASL MR angiographic images, the major intracranial arteries were demonstrated at a temporal resolution of 300 milliseconds. Interobserver agreement was excellent for the fistula site (κ = 1.00; 95% confidence interval [CI]: 1.00, 1.00), moderate for the main arterial feeders (κ = 0.53; 95% CI: 0.08, 0.98), and good for venous drainage (κ = 0.77; 95% CI: 0.35, 1.00). Intermodality agreement was excellent for the fistula site and venous drainage (κ = 1.00; 95% CI: 1.00, 1.00) and good for the main arterial feeders (κ = 0.80; 95% CI: 0.58, 1.00). CONCLUSION: The good-to-excellent agreement between 3-T 4D ASL MR angiographic and DSA findings suggests that 3-T 4D ASL MR angiography is a useful tool for the evaluation of intracranial dural AVFs.
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Malformaciones Vasculares del Sistema Nervioso Central/diagnóstico por imagen , Angiografía por Resonancia Magnética/métodos , Anciano , Angiografía de Substracción Digital , Medios de Contraste , Femenino , Humanos , Yopamidol , Masculino , Persona de Mediana Edad , Marcadores de SpinRESUMEN
OBJECTIVE: The purpose of this study was to determine how the gray-to-white matter contrast in healthy subjects changes on high-b-value diffusion-weighted imaging (DWI) acquired at 3 T and evaluate whether high-b-value DWI at 3 T is useful for the detection of cortical lesions in inflammatory brain diseases. METHODS: Ten healthy volunteers underwent DWI at b = 1000, 2000, 3000, 4000, and 5000 s/mm(2) on a 3-T MRI unit. On DW images, 1 radiologist performed region-of-interest measurements of the signal intensity of 8 gray matter structures. The gray-to-white matter contrast ratio (GWCR) was calculated. Ten patients with inflammatory cortical lesions were also included. All patients underwent conventional MRI and DWI at b = 1000 and 3000 s/mm(2). Using a 4-point grading system, 2 radiologists independently assessed the presence of additional information on DW images compared with fluid-attenuated inversion recovery images. Interobserver agreement was assessed by κ statistics. RESULTS: In the healthy subjects, the b value increased as the GWCR decreased in all evaluated gray matter structures. On DW images acquired at b = 3000 s/mm(2), mean GWCR was less than 1.0 in 7 of 8 structures. For both reviewers, DWI at b = 3000 s/mm(2) yielded significantly more additional information than did DWI at b = 1000 s/mm(2) (P < 0.05). Interobserver agreement for DWI at b = 1000 s/mm(2) and b = 3000 s/mm(2) was fair (κ = 0.35) and excellent (κ = 1.0), respectively. CONCLUSIONS: At 3-T DWI, the gray-to-white matter contrast in most gray matter structures reverses at b = 3000 s/mm. In the evaluation of cortical lesions in patients with inflammatory brain diseases, 3-T DWI at b = 3000 s/mm was more useful than b = 1000 s/mm(2).
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Encefalopatías/diagnóstico , Encéfalo/anatomía & histología , Imagen de Difusión por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inflamación/diagnóstico , Masculino , Persona de Mediana Edad , Valores de Referencia , Estadísticas no ParamétricasRESUMEN
Introduction: Apalutamide is a new second-generation anti-androgen agent approved in 2019 for the treatment of metastatic, castration-sensitive, and non-metastatic, castration-resistant prostate cancer. We herein report a case of apalutamide-induced interstitial lung disease. Case presentation: A 74-year-old Japanese male patient with non-metastatic, castration-resistant prostate cancer commenced hormonal therapy with apalutamide (240 mg/day orally) after 46 months of maximal androgen blockade therapy with bicalutamide and leuprorelin. Thirty-five days following therapy initiation with apalutamide, he was hospitalized because of dyspnea. Chest computed tomography showed diffuse bilateral interstitial infiltrates and ground-glass opacities in the upper and lower lobes of the lungs. Following a diagnosis of drug-induced interstitial lung disease resulting from apalutamide treatment, the treatment with apalutamide was stopped. Steroid therapy was initiated, and the dyspnea resolved. Conclusion: Clinicians should be aware that apalutamide, and other drugs in general, can cause drug-induced interstitial lung disease within 3 months.
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Standard therapy for metastatic small cell carcinoma of the prostate (SCCP) remains undefined. We have effectively treated relapsed SCCP with amrubicin. A 72-year-old patient, diagnosed with T4N1M0 prostate cancer, started hormonal therapy in May 2012, elsewhere, and his prostate-specific antigen levels remained low. However, pulmonary and hepatic metastases occurred; high neuron-specific enolase levels suggested SCCP, which was confirmed by repeated biopsy at our institution. In October 2016, chemotherapy with irinotecan and cisplatin was initiated for metastases to the lung, liver, and left pelvic lymph nodes, and partial response (PR) was achieved. After six cycles, brain metastases occurred. After ten cycles, his pro-gastrin-releasing peptide levels increased suddenly, and brain and hepatic metastases enlarged. Amrubicin was started in December 2016 and seven cycles were safely completed, with PR and markedly reduced brain metastasis volume, until his pneumonitis-related death in June 2017. Amrubicin may be an effective second-line chemotherapy option for SCCP.
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Primary adenocarcinoma of the rete testis is an extremely rare tumor with a poor prognosis. Herein, we report a case of primary adenocarcinoma of the rete testis accompanied by elevated serum carbohydrate antigen 19-9 (CA19-9) antigen levels in a 44-year-old man who presented with left scrotal swelling. Para-aortic lymph node swelling was observed on the computed tomography scan. Germ cell tumor markers were within the normal range, but serum CA19-9 antigen levels were high. Radical orchiectomy was performed, and histological examination revealed primary adenocarcinoma of the rete testis with no evidence of other primary carcinomas. The patient underwent three lines of chemotherapy, although no reports suggest the use of gemcitabine and oxaliplatin (GEMOX) in a patient with adenocarcinoma of the rete testis. Unfortunately, he developed metastasis at multiple sites and passed away due to adenocarcinoma 13 months after undergoing orchiectomy. Some reports suggest that CA19-9 antigen levels are elevated in patients with adenocarcinoma of the rete testis, although it has not been clarified whether elevated CA19-9 antigen levels reflect the progression of adenocarcinoma of the rete testis. In this case, as CA19-9 antigen levels increased with progression, CA19-9 might be a marker for primary adenocarcinoma of the rete testis. GEMOX chemotherapy as a line of treatment in primary adenocarcinoma of the rete testis has not been reported. Therefore, further studies must evaluate the efficacy of the aforementioned chemotherapy regimen.
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Kinesin family member C1 (KIFC1) is a minus end-directed motor protein that plays an essential role in centrosome clustering. Previously, we reported that KIFC1 is involved in cancer progression in prostate cancer (PCa). We designed this study to assess the involvement of KIFC1 in docetaxel (DTX) resistance in PCa and examined the effect of KIFC1 on DTX resistance. We also analyzed the possible role of a KIFC1 inhibitor (CW069) in PCa. We used DTX-resistant PCa cell lines in DU145 and C4-2 cells to analyze the effect of KIFC1 on DTX resistance in PCa. Western blotting showed that KIFC1 expression was higher in the DTX-resistant cell lines than in the parental cell lines. Downregulation of KIFC1 re-sensitized the DTX-resistant cell lines to DTX treatment. CW069 treatment suppressed cell viability in both parental and DTX-resistant cell lines. DTX alone had little effect on cell viability in the DTX-resistant cells. However, the combination of DTX and CW069 significantly reduced cell viability in the DTX-resistant cells, indicating that CW069 re-sensitized the DTX-resistant cell lines to DTX treatment. These results suggest that a combination of CW069 and DTX could be a potential strategy to overcome DTX resistance.
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Cisplatin (CDDP)based combination chemotherapy is the standard for muscleinvasive bladder cancer (MIBC). However, nearly all patients undergoing CDDP chemotherapy become refractory due to the development of CDDP resistance. Therefore, clarification of the mechanisms of CDDP resistance is urgently needed. The transcribed ultraconserved regions (TUCRs) are a novel class of noncoding RNAs that are highly conserved across species and are associated with carcinogenesis and cancer progression. In addition, emerging evidence has shown the involvement of androgen receptor (AR) signals in urothelial carcinoma (UC) progression. The aim of the present study was to investigate the expression of transcribed ultraconserved region Uc.63+, and to analyze the effects of Uc.63+ on AR expression and CDDP resistance in UC. Quantitative reverse transcriptionpolymerase chain reaction (qRTPCR) revealed that the expression of Uc.63+ was higher in UC tissues than that in nonneoplastic bladder tissues and 15 types of normal tissue. An MTT assay revealed that Uc.63+ was involved in cell proliferation. Western blotting demonstrated that the expression of AR was disrupted by the overexpression or knockdown of Uc.63+ in ARpositive UMUC3 cells. Furthermore, knockdown of Uc.63+ increased sensitivity to CDDP in UMUC3 cells. Conversely, overexpression of Uc.63+ had no effect on CDDP sensitivity in ARnegative RT112 cells. Additionally, we observed that the expression of Uc.63+ was increased in CDDPresistant UMUC3 cells (UMUC3CR) in comparison with that in parental UMUC3 cells. Knockdown of Uc.63+ resensitized the UMUC3CR cells to CDDP. These results indicated that Uc.63+ may be a promising therapeutic target to overcome CDDP resistance in UC.
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Antineoplásicos/farmacología , Carcinoma de Células Transicionales/genética , Cisplatino/farmacología , Resistencia a Antineoplásicos/genética , ARN no Traducido/metabolismo , Receptores Androgénicos/metabolismo , Neoplasias de la Vejiga Urinaria/genética , Anciano , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/patología , Línea Celular Tumoral , Proliferación Celular/genética , Cisplatino/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Masculino , Persona de Mediana Edad , Interferencia de ARN , ARN no Traducido/genética , Transducción de Señal/genética , Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Hyperplastic anomaly of the anterior choroidal artery (hyperplastic AchA) and posterior communicating artery of duplicate origin (duplicated Pcom) are rare vessel anomalies. With some literature review, we here report three cases of hyperplastic AchA, one of which was considered a new type of hyperplastic AchA. This case was not categorized into Takahashi classification.
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Arterias Cerebrales/anomalías , Arterias Cerebrales/diagnóstico por imagen , Plexo Coroideo/anomalías , Plexo Coroideo/diagnóstico por imagen , Arteria Carótida Interna/diagnóstico por imagen , Arteria Carótida Interna/patología , Arterias Cerebrales/patología , Plexo Coroideo/irrigación sanguínea , Círculo Arterial Cerebral/anomalías , Círculo Arterial Cerebral/diagnóstico por imagen , Círculo Arterial Cerebral/patología , Humanos , Hiperplasia/diagnóstico por imagen , Hiperplasia/patologíaRESUMEN
OBJECTIVES: Prostate cancer (PCa) is a common malignancy worldwide. Docetaxel has been an important treatment option for patients with metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients with CRPC treated with docetaxel eventually become refractory. In the present study, we analyzed the expression and distribution of kinesin family member C1 (KIFC1) in human PCa by immunohistochemistry and examined the effect of inhibiting KIFC1 expression on docetaxel resistance. METHODS: Expression of KIFC1 was determined using immunohistochemistry. RNA interference was used to inhibit KIFC1 expression in PCa cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. CONCLUSIONS: These results indicate that KIFC1 plays an important role in PCa progression. Immunohistochemical analysis of KIFC1 would facilitate identification of patients with poor prognoses after radical prostatectomy, as well as patients with poor therapeutic outcomes after docetaxel-based chemotherapy.
Asunto(s)
Antineoplásicos/farmacología , Resistencia a Antineoplásicos/genética , Cinesinas/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Taxoides/farmacología , Anciano , Antineoplásicos/uso terapéutico , Vasos Sanguíneos/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Supervivencia sin Enfermedad , Docetaxel , Técnicas de Silenciamiento del Gen , Humanos , Receptores de Hialuranos/metabolismo , Cinesinas/genética , Masculino , Clasificación del Tumor , Invasividad Neoplásica , Células Madre Neoplásicas/metabolismo , Próstata/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , ARN Mensajero/metabolismo , ARN Interferente Pequeño , Estudios Retrospectivos , Esferoides Celulares/efectos de los fármacos , Taxoides/uso terapéuticoRESUMEN
Bladder cancer, the majority of which is urothelial carcinoma (UC), is a common malignancy worldwide. Genes encoding transmembrane/secretory proteins expressed specifically in certain cancers may be ideal biomarkers for cancer diagnosis and may represent therapeutic targets. In the present study, the expression and function of the bone marrow stromal cell antigen 2 (BST2) gene was analyzed in UC. Reverse transcription-quantitative polymerase chain reaction demonstrated that expression of BST2 in normal tissue samples was the highest in liver tissue. However, expression of BST2 in UC tissue samples was higher than in normal liver. Immunohistochemical analysis revealed weak or no staining of BST-2 in non-neoplastic mucosa, whereas UC tissue exhibited stronger and more extensive staining compared with non-neoplastic mucosa. BST-2 staining was observed mainly on UC cell membranes. In total, 28 (41%) of 69 UC cases were positive for BST-2. UC cases positive for BST-2 were more frequently T2/3/4 cases [so-called muscle-invasive bladder cancer (MIBC)] than Ta/is/1 cases (P=0.0001). However, Kaplan-Meier analysis demonstrated no association between BST-2 expression and survival. BST2 small interfering RNA (siRNA)-transfected T24 cells exhibited significantly reduced cell growth relative to negative control siRNA-transfected T24 cells. The levels of phosphorylated Akt and extracellular signal-regulated kinase were lower in BST2 siRNA-transfected T24 cells than in control cells. These results suggest the involvement of BST-2 in the pathogenesis of UC. Since BST-2 is expressed on the cell membrane, BST-2 may be a good therapeutic target for MIBC.
RESUMEN
BACKGROUND: Renal cell carcinoma (RCC) is one of the most common types of cancer in developed countries. Bone marrow stromal cell antigen 2 (BST2) gene, which encodes BST2 transmembrane glycoprotein, is overexpressed in several cancer types. In the present study, we analyzed the expression and function of BST2 in RCC. MATERIALS AND METHODS: BST2 expression was analyzed by immunohistochemistry in 123 RCC cases. RNA interference was used to inhibit BST2 expression in a RCC cell line. RESULTS: Immunohistochemical analysis showed that 32% of the 123 RCC cases were positive for BST2. BST2 expression was positively associated with tumour stage. Furthermore, BST2 expression was an independent predictor of survival in patients with RCC. BST2 siRNA-transfected Caki-1 cells displayed significantly reduced cell growth and invasive activity relative to negative control siRNA-transfected cells. CONCLUSION: These results suggest that BST2 plays an important role in the progression of RCC. Because BST2 is expressed on the cell membrane, BST2 is a good therapeutic target for RCC.
Asunto(s)
Antígenos CD/metabolismo , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Anciano , Antígenos CD/genética , Carcinoma de Células Renales/genética , Línea Celular Tumoral , Membrana Celular/metabolismo , Movimiento Celular , Proliferación Celular , Femenino , Proteínas Ligadas a GPI/genética , Proteínas Ligadas a GPI/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/genética , Masculino , Interferencia de ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genéticaRESUMEN
Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC. Quantitative real-time polymerase chain reaction analysis revealed that the expression of T-UCR Uc.63+ was increased in PC tissues. MTT assay and wound healing assay revealed that Uc.63+ was involved in cell growth and cell migration. miR-130b was predicted to have binding sites within the Uc.63+ sequence. The expression of miR-130b was significantly disturbed by the overexpression or knockdown of Uc.63+. We also showed that Uc.63+ regulated the expression of MMP2 via miR-130b regulation. Furthermore, overexpression of Uc.63+ increased the expression of AR and its downstream molecule PSA and promoted resistance to docetaxel through AR regulation. In patients treated with docetaxel, the expression of serum Uc.63+ in the docetaxel-resistant patients was higher than that in the docetaxel-sensitive patients (P = 0.011). Moreover, Kaplan-Meier analysis showed that the high expression of serum Uc.63+ correlated with a worse prognosis (P = 0.020). These results substantially support the important role that Uc.63+ plays in PC progression by interacting with miR-130b and indicate that Uc.63+ could potentially be a promising serum marker for deciding the best treatment for patients with CRPC.