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1.
Radiol Phys Technol ; 17(3): 679-696, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38874896

RESUMEN

During the radiographic examination of the chest and bones in hospitals, communicating and maintaining posture is difficult for some patients, and movement before or during X-ray irradiation may necessitate re-exposure owing to body wobbling movements or breathing movements. To prevent the need for re-exposure during radiography and to determine the exposure timing, a body movement detection system that considers breathing movements was developed in this study. The posture of a patient was monitored using an RGB camera. The acquired video data was analyzed to detect body movement using either an inter-frame difference method or an optical flow estimation method. The performance of the system was evaluated by detecting the body and breathing movements during positioning. Consequently, the inter-frame difference method detected 179.8-1222.2 pixels during body movements, and the optical flow estimation method confirmed that the feature points moved by 5.5-26.6 mm (4.2-20.3 pixels). When detecting breathing movements, 82-585 pixels were detected by the inter-frame difference method, and the optical flow estimation method showed that the feature points moved by 5.2 mm (2-4 pixels). Therefore, the proposed method can detect body movements during radiography to prevent re-exposure due to body wobble and breathing movements. For healthcare providers, it will lead to reduce not only concerns about patient exposure but also unnecessary radiographic workload.


Asunto(s)
Movimiento , Humanos , Radiografía/instrumentación , Radiografía/métodos , Respiración , Postura , Exposición a la Radiación/prevención & control , Exposición a la Radiación/análisis
3.
Gan To Kagaku Ryoho ; 49(1): 47-52, 2022 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-35046361

RESUMEN

INTRODUCTION: Several studies reported that skeletal muscle mass affects the clinical response and quality of life of cancer patients during chemotherapy. Here we examined the adverse events and effects of anticancer drugs on the skeletal muscle mass of patients with esophageal cancer who received biweekly docetaxel, cisplatin, and 5-fluorouracil(DCF)neoadjuvant chemotherapy in our department. SUBJECTS AND METHODS: We retrospectively analyzed 105 patients with esophageal cancer who received biweekly-DCF neoadjuvant chemotherapy in 2009-2019. The cross-sectional area of the psoas muscle at the level of the third lumbar vertebra on computed tomography was assessed to calculate the psoas muscle index(PMI). Patients were divided into the high PMI group(high-group)and low PMI group(low-group)by cut-off value(male: 6.36 cm2/m2; female: 3.92 cm2/m2). Hematological toxicity, non-hematological toxicity, and therapeutic effect were retrospectively examined. RESULTS: Male in the high-group had significantly less ≥Grade 3 hematological toxicity than those in the low-group. Univariate and multivariate analyses showed that PMI(odds ratio: 1, p<0.05)was significantly related to decreased hematological toxicity. CONCLUSION: In preoperative chemotherapy for esophageal cancer, the incidence of hematological toxicity was significantly higher in patients with low skeletal muscle mass. Thus, skeletal muscle mass may be a marker for determining optimal anticancer drug dosage.


Asunto(s)
Neoplasias Esofágicas , Terapia Neoadyuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/uso terapéutico , Neoplasias Esofágicas/tratamiento farmacológico , Femenino , Fluorouracilo/uso terapéutico , Humanos , Masculino , Músculo Esquelético , Músculos Psoas , Calidad de Vida , Estudios Retrospectivos
4.
Surg Today ; 52(8): 1212-1217, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35091847

RESUMEN

PURPOSE: To analyze the effectiveness of incorporating virtual reality (VR) in lectures on esophageal and mediastinal anatomy and surgical procedures for medical students at Gifu University during clinical training. METHODS: We divided medical students participating in clinical training, randomly, into two groups of 30 students each: those who received a lecture using 3D images (3D group) and those who received a lecture using VR images (VR group). Four days after the lecture, the students completed a written test to allow us to evaluate their comprehension, and a questionnaire on their opinion of the lectures. RESULTS: Based on the results of the written test, the VR group achieved better understanding of computed tomography (CT) images (p = 0.0001) and better interpretation of surgical images (p = 0.0163). However, there was no difference in the scores for spatial recognition and general problems. The questionnaire revealed that the VR group became more interested in mediastinal anatomy (p = 0.0165) and surgery (p = 0.0135). CONCLUSIONS: Our findings suggest that VR enhances the learning process. The lecture incorporating the VR experience was more effective than the traditional lecture for promoting an understanding of CT images and interpretation of surgical images; thus, it enhances the learning experience for medical students studying surgery.


Asunto(s)
Educación de Pregrado en Medicina , Estudiantes de Medicina , Realidad Virtual , Educación de Pregrado en Medicina/métodos , Humanos , Imagenología Tridimensional , Aprendizaje
5.
BMC Gastroenterol ; 21(1): 467, 2021 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-34906075

RESUMEN

BACKGROUND: The development of esophago-bronchial fistula after esophagectomy and reconstruction using a posterior mediastinal gastric tube remains a rare complication associated with a high rate of mortality. CASE PRESENTATION: A 63-year-old man with esophageal cancer underwent a thoracoscopic esophagectomy with two-field lymph node dissection and reconstruction via a gastric tube through the posterior mediastinal route. Postoperatively, the patient developed extensive pyothorax in the right lung due to port site bleeding and hematoma infection. Four months after surgery, he developed an esophago-left bronchial fistula due to ischemia of the cervical esophagus and severe reflux esophagitis at the site of the anastomosis. Because of respiratory failure due to the esophago-bronchial fistula and the history of extensive right pyothorax, right thoracotomy and left one-lung ventilation were thought to be impossible, so we decided to perform the surgery in three-step systematically. First, we inserted a decompression catheter and feeding tube into the gastric tube as a gastrostomy and expected neovascularization to develop from the wall of the gastric tube through the anastomosis after this procedure. Second, 14 months after esophagectomy, we constructed an esophagostomy after confirming blood flow in the distal side of the cervical esophagus via gastric tube using intraoperative indocyanine green-guided blood flow evaluation. In the final step, we closed the esophagostomy and performed a cervical esophago-jejunal anastomosis to restore esophageal continuity using a pedicle jejunum in a Roux-en-Y anastomosis via a subcutaneous route. CONCLUSION: This three-step operation can be an effective procedure for patients with esophago-left bronchial fistula after esophagectomy, especially those with respiratory failure and difficulty in undergoing right thoracotomy with left one-lung ventilation.


Asunto(s)
Fístula Bronquial , Neoplasias Esofágicas , Insuficiencia Respiratoria , Fístula Bronquial/etiología , Fístula Bronquial/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Respiratoria/etiología
6.
BMC Surg ; 21(1): 217, 2021 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-33906625

RESUMEN

BACKGROUND: Variation of the vertebral artery bifurcation is rare. This branching abnormality can cause unexpected vertebral artery damage and bleeding during thoracoscopic esophagectomy. There are few reports of abnormal branching of the vertebral artery associated with neurosurgery but none related to esophagectomy. We report the case together with the results of the evaluation of vertebral artery bifurcation and length in 50 patients with esophageal cancer in our hospital. CASE PRESENTATION: Thoracoscopic esophagectomy was performed on a 70-year-old patient with esophageal cancer. During lymph node dissection around the right reccurent laryngeal nerve, an unusual blood vessel was found running along the right subclavian artery. We determined this blood vessel to be the right vertebral artery branching far more centrally than usual. Because this anatomical abnormality was clarified, we could then recognize that the right reccurent laryngeal nerve coursed around the right vertebral artery and the right subclavian artery and thus was running in a larger arch than usual. CONCLUSION: Long right vertebral artery may appear in the surgical field of the thoracoscopic esophagectomy. Knowledge of such anatomical variation is important to prevent iatrogenic injury of the right vertebral artery and the right reccurent laryngeal nerve.


Asunto(s)
Neoplasias Esofágicas , Esofagectomía , Anciano , Neoplasias Esofágicas/cirugía , Humanos , Escisión del Ganglio Linfático , Arteria Vertebral/diagnóstico por imagen
7.
Front Oncol ; 11: 769068, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34993133

RESUMEN

This study aimed to compare the effects of abiraterone acetate plus prednisone (AAP) with androgen deprivation therapy (ADT) with those of combined androgen blockade (CAB) therapy in patients with high-risk metastatic hormone-sensitive prostate cancer (mHSPC). This study retrospectively identified 163 patients with high-risk mHSPC at Kindai University and affiliated hospitals between January 2014 and December 2020. Kaplan-Meier analysis was used to summarize progression-free survival (PFS) and overall survival (OS). Multivariate Cox proportional hazard modeling was used to identify the prognostic factors in the overall cohort. Propensity score matching was used to adjust the clinical characteristics, and log-rank test was applied to these propensity score-matched cohorts. Seventy-four patients who received AAP with ADT and 89 patients who received CAB were included in this study. The median follow-up duration was 27 months (range, 2-89 months). The median PFS and OS were not reached by the AAP+ADT group and 15 and 79 months, respectively, in the CAB group. The Eastern Cooperative Oncology Group (ECOG) performance status (PS) score and AAP+ADT were significant prognostic factors for PFS, whereas ECOG PS score, visceral metastasis, and AAP+ADT were significant prognostic factors for OS. The 2-year PFS was 76.1% in the AAP+ADT group and 38.6% in the CAB group (P < 0.0001), and the 2-year OS was 90.2% in the AAP+ADT group and 84.8% in the CAB group (P = 0.015). In conclusion, AAP+ADT had better PFS and OS than CAB in patients with high-risk mHSPC.

8.
Ann Gastroenterol Surg ; 4(4): 422-432, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32724886

RESUMEN

Aim: The objective of this retrospective, single-institution study was to assess the safety and feasibility of reconstruction using subtotal stomach (SS) with esophagectomy for patients with esophageal cancer (EC). Although several different gastric-tube-making and anastomotic methods have been reported, the incidence rate of anastomotic leakage with EC surgery is generally reported over 10%. Complications should be avoided, and patient quality of life (QOL) should be maintained postoperatively. We have used SS reconstruction and hand-sutured cervical esophagus-subtotal gastric anastomosis at the neck wound in EC surgery. Short- and long-term outcomes in cases using SS are not well known. Methods: Between January 2008 and September 2019, 300 patients underwent esophagectomy for EC and reconstruction using SS. The primary endpoint was the rate of anastomotic leakage. Secondary endpoints were postoperative morbidities, QOL, and changes in patients' body weight and skeletal muscle weight. Results: Anastomotic leakage was observed in two patients (0.67%), and pneumonia was observed in nine patients (3.0%). Fifteen patients (5.0%) had an anastomotic stenosis requiring a bougie. Nausea occurred in 11 patients (3.7%), and dumping syndrome occurred in seven patients (2.3%). Dysphagia and early feeling of abdominal fullness scores tended to be high after surgery but gradually decreased after 6 months. Good results were obtained for reflux feeling scores. Body weight changed with an average decrease of -2 ± 3.71 kg (P = .071) over 5 years. Conclusion: Reconstruction using SS resulted in an extremely low rate of anastomotic leakage and good QOL postoperatively in patients with EC.

9.
Esophagus ; 17(4): 508-511, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32246296

RESUMEN

BACKGROUND: With the recent improvement of medical image analysis technology, three-dimensional (3D) holograms technology is beginning to be used as intraoperative image support. CASE PRESENTATION: We used a wearable holographic computer during thoracoscopic esophagectomy in a 70-year-old man with esophageal cancer. During lymph node dissection around the right recurrent laryngeal nerve, abnormal blood vessels were observed beside the right subclavian artery (RSA). As a result of confirming the anatomical variation of the right vertebral artery (RVA) using the 3D holograms, it was possible to understand that the RVA branched from a low position on the RSA. CONCLUSIONS: Holographic image-guided thoracoscopic esophagectomy using wearable holographic computer provided better spatial recognition of vascular variation and safe lymph node dissection.


Asunto(s)
Neoplasias Esofágicas/cirugía , Holografía/instrumentación , Cirugía Asistida por Computador/instrumentación , Toracoscopía/métodos , Arteria Vertebral/anomalías , Anciano , Neoplasias Esofágicas/patología , Esofagectomía/métodos , Humanos , Imagenología Tridimensional/métodos , Escisión del Ganglio Linfático/métodos , Masculino , Estadificación de Neoplasias , Nervio Laríngeo Recurrente/cirugía , Arteria Subclavia/cirugía , Arteria Vertebral/diagnóstico por imagen , Arteria Vertebral/cirugía
10.
JCI Insight ; 4(17)2019 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-31484823

RESUMEN

Sustained therapeutic responses from traditional and next-generation antiandrogen therapies remain elusive in clinical practice due to inherent and/or acquired resistance resulting in persistent androgen receptor (AR) activity. Antisense oligonucleotides (ASO) have the ability to block target gene expression and associated protein products and provide an alternate treatment strategy for castration-resistant prostate cancer (CRPC). We demonstrate the efficacy and therapeutic potential of this approach with a Generation-2.5 ASO targeting the mouse AR in genetically engineered models of prostate cancer. Furthermore, reciprocal feedback between AR and PI3K/AKT signaling was circumvented using a combination approach of AR-ASO therapy with the potent pan-AKT inhibitor, AZD5363. This treatment strategy effectively improved treatment responses and prolonged survival in a clinically relevant mouse model of advanced CRPC. Thus, our data provide preclinical evidence to support a combination strategy of next-generation ASOs targeting AR in combination with AKT inhibition as a potentially beneficial treatment approach for CRPC.


Asunto(s)
Antineoplásicos/farmacología , Oligonucleótidos Antisentido/farmacología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Antineoplásicos/uso terapéutico , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Oligonucleótidos Antisentido/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/patología , Proteínas Proto-Oncogénicas c-akt/farmacología , Pirimidinas , Pirroles , Transcriptoma
11.
Hinyokika Kiyo ; 65(2): 45-47, 2019 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-31067842

RESUMEN

A 86-year-old man visited our hospital to undergo a careful examination for asymptomatic gross hematuria. First, we performed cystoscopy and found a tumor projecting from the right ureteral orifice. We therefore performed computed tomography, which revealed right ureteral cancer projecting into the lower ureter and severe megaureter on bothsides. To evaluate the left megaureter, we performed retrograde pyelography, but were unable to insert a guide-wire. We therefore performed magnetic resonance-urography, which revealed an expanded left lower ureter, but no findings of hydronephrosis or any tumor lesions. Based on the findings of these examinations, we diagnosed the patient with right ureteral cancer with megaureter. Right nephroureterectomy and partial cystectomy were performed in April 2017. The pathological findings resulted in a diagnosis of invasive urothelial carcinoma. The patient experienced recurrence in his bladder at 3 months follow-up cystoscopy and underwent transurethral resection of bladder tumor.


Asunto(s)
Carcinoma de Células Transicionales , Uréter , Neoplasias Ureterales , Anciano de 80 o más Años , Carcinoma de Células Transicionales/diagnóstico , Carcinoma de Células Transicionales/cirugía , Cistectomía , Humanos , Masculino , Recurrencia Local de Neoplasia , Uréter/patología , Neoplasias Ureterales/diagnóstico , Neoplasias Ureterales/cirugía
12.
Prostate ; 79(5): 554-563, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30614022

RESUMEN

BACKGROUND: HOX genes encode transcription factors that play key roles in modulating normal tissue morphogenesis, differentiation and homeostasis. Disruption of normal HOX gene expression occurs frequently in human cancers and is associated with both tumor promoting and suppressing activities. Among these is, HOXA10, a pleiotropic gene that is critical for normal prostate development. In this study we characterized HOXA10 expression in human and mouse PCa to gain insights into its clinical significance. METHODS: A meta-analysis of HOXA10 mRNA expression was carried out across several publicly available data sets. Expression of HOXA10 protein expression was assessed by immunohistochemistry (IHC) using human radical prostatectomy (RP) cases. We correlated HOXA10 expression to clinicopathological features and investigated its relationship to biochemical recurrence (BCR) after RP by the Kaplan-Meier method. HOXA10 mRNA and IHC protein expression was also examined in a mouse model of Pten-null PCa. RESULTS: A meta-analysis of HOXA10 gene expression indicated dysregulated expression of HOXA10 in human PCa. IHC profiling of HOXA10 revealed inverse correlations between HOXA10 expression and Gleason pattern, Gleason score, and pathological stage (P < 0.01). Patients with low expression profiles of HOXA10 were associated with a higher risk of BCR, (OR, 3.54; 95%CI, 1.21-16.14; P = 0.049) whereas patients with high HOXA10 expression experienced longer times to BCR (P = 0.045). However, HOXA10 was not an independent predictor of BCR (OR, 1.52; 95%CI, 0.42-5.54; P = 0.52). Evaluation of expression patterns of HOXA10 in mouse prostate tumors mimicked that of humans. CONCLUSIONS: Our findings show that HOXA10 expression is inversely associated with tumor differentiation and high HOXA10 expression is associated with improved BCR-free survival. This study provides human and mouse evidence to suggest tumor suppressive roles for HOXA10 in the context of prostate cancer.


Asunto(s)
Proteínas Homeobox A10/genética , Neoplasias de la Próstata/genética , Anciano , Animales , Expresión Génica , Proteínas Homeobox A10/biosíntesis , Humanos , Inmunohistoquímica , Masculino , Ratones , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , ARN Mensajero/biosíntesis , ARN Mensajero/genética
13.
J Transl Med ; 13: 150, 2015 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-25953027

RESUMEN

BACKGROUND: Despite recent advances in the treatment for advanced prostate cancer, outcomes remain poor. This lack of efficacy has prompted the development of alternative treatment strategies. In the present study we investigate the effects of the multikinase inhibitor sorafenib in a genetically engineered mouse model of prostate cancer and explore the rational combination with the mTOR inhibitor everolimus. METHODS: Conditional prostate specific PTEN-deficient knockout mice were utilized to determine the pharmacodynamic and chemopreventive effects of sorafenib. This mouse model was also used to examine the therapeutic efficacy of sorafenib alone or in combination with everolimus. Preclinical efficacy was assessed by comparing the reduction of tumor burden, proliferation, angiogenesis and the induction of apoptosis. Molecular responses were assessed by immunohistochemical, TUNEL and western blot assays. RESULTS: Pharmacodynamic analysis revealed that a single dose of sorafenib decreased activation of the PI3K/AKT/mTOR signaling axis at doses of 30-60 mg/kg, but activated JAK/STAT3 signaling. Levels of cleaved casapase-3 increased in a dose dependent manner. Chemoprevention studies showed that chronic sorafenib administration was capable of inhibiting tumor progression through the reduction of cancer cell proliferation, angiogenesis and the induction of apoptosis. In intervention models of established castration-naïve and castration-resistant prostate cancer, treatment with sorafenib provided modest but statistically insignificant reduction in tumor burden. However, sorafenib significantly inhibited cancer cell proliferation and MVD but had minimal effects on the induction of apoptosis. Interestingly, the administration of sorafenib increased the expression levels of the androgen receptor, p-GSK3ß and p-ERK1/2 in castration-resistant prostate cancers. In both intervention models, combination therapy demonstrated a clear tendency of enhanced antitumor effects over monotherapy. Notably, the treatment combination of sorafenib and everolimus overcame therapeutic escape from single agent therapy in castration-resistant prostate cancers. CONCLUSIONS: In summary, we provide insights into the molecular responses of sorafenib therapy in a clinically relevant model of prostate cancer and present preclinical evidence for the development of targeted treatment strategies based on the use of multikinase inhibitors in combination with mTOR inhibitors for the treatment of advanced prostate cancer.


Asunto(s)
Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/genética , Niacinamida/análogos & derivados , Fosfohidrolasa PTEN/metabolismo , Compuestos de Fenilurea/administración & dosificación , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Apoptosis , Proliferación Celular , Modelos Animales de Enfermedad , Everolimus/administración & dosificación , Ingeniería Genética/métodos , Homocigoto , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Masculino , Ratones , Ratones Noqueados , Neovascularización Patológica , Niacinamida/administración & dosificación , Fosfohidrolasa PTEN/genética , Transducción de Señal , Sorafenib
14.
Asian Pac J Cancer Prev ; 16(5): 1827-31, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25773832

RESUMEN

BACKGROUND: We generated a mouse model of prostate cancer based on the adult-prostate-specific inactivation of phosphatase and tensin homolog (PTEN) using the Cre-loxP system. The potential of our mice as a useful animal model was examined by evaluating the chemopreventive efficacy of the anti-androgen, chlormadinone acetate (CMA). MATERIALS AND METHODS: Six-week-old mice were treated subcutaneously with 50 µg/g of CMA three times a week for 9 or 14 weeks and sacrificed at weeks 15 and 20. Macroscopic change of the entire genitourinary tract (GUT) and histologically evident prostate gland tumor development were evaluated. Proliferation and apoptosis status in the prostate were examined by immunohistochemistry. RESULTS: CMA triggered significant shrinkage of not only the GUT but also prostate glands at 15 weeks compared to the control (p=0.017 and p=0.010, respectively), and the trend became more marked after a further five-weeks of treatment. The onset of prostate adenocarcinoma was not prevented but the proliferation of cancer cells was inhibited by CMA, which suggested the androgen axis is critical for cancer growth in these mice. CONCLUSIONS: Conditional PTEN-deficient mice are useful as a preclinical model for chemoprevention studies and serve as a valuable tool for the future screening of potential chemopreventive agents.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antagonistas de Andrógenos/uso terapéutico , Acetato de Clormadinona/uso terapéutico , Fosfohidrolasa PTEN/genética , Neoplasias de la Próstata/tratamiento farmacológico , Adenocarcinoma/patología , Adenocarcinoma/prevención & control , Animales , Anticarcinógenos/uso terapéutico , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quimioprevención , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/prevención & control , Sistema Urogenital/citología , Sistema Urogenital/patología
15.
Carcinogenesis ; 35(9): 2142-53, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-24986896

RESUMEN

Castration-resistant prostate cancer is an incurable heterogeneous disease that is characterized by a complex multistep process involving different cellular and biochemical changes brought on by genetic and epigenetic alterations. These changes lead to the activation or overexpression of key survival pathways that also serve as potential therapeutic targets. Despite promising preclinical results, molecular targeted therapies aimed at such signaling pathways have so far been dismal. In the present study, we used a PTEN-deficient mouse model of prostate cancer to show that plasticity in castration-resistant tumors promotes therapeutic escape. Unlike castration-naïve tumors which depend on androgen receptor and PI3K/AKT signal activation for growth and survival, castration-resistant tumors undergo phenotypic plasticity leading to increased intratumoral heterogeneity. These tumors attain highly heterogeneous phenotypes that are characterized by cancer cells relying on alternate signal transduction pathways for growth and survival, such as mitogen-activated protein kinase and janus kinase/signal transducer and activator of transcription, and losing their dependence on PI3K signaling. These features thus enabled castration-resistant tumors to become insensitive to the therapeutic effects of PI3K/AKT targeted therapy. Overall, our findings provide evidence that androgen deprivation drives phenotypic plasticity in prostate cancer cells and implicate it as a crucial contributor to therapeutic resistance in castration-resistant prostate cancer. Therefore, incorporating intratumoral heterogeneity in a dynamic tumor model as a part of preclinical efficacy determination could improve prediction for response and provide better rationale for the development of more effective therapies.


Asunto(s)
Adenocarcinoma/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fosfohidrolasa PTEN/deficiencia , Neoplasias de la Próstata Resistentes a la Castración/terapia , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Butadienos/administración & dosificación , Carcinogénesis/genética , Proliferación Celular , Terapia Combinada , Modelos Animales de Enfermedad , Resistencia a Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Everolimus , Humanos , Masculino , Ratones , Ratones Transgénicos , Terapia Molecular Dirigida , Nitrilos/administración & dosificación , Orquiectomía , Fosfohidrolasa PTEN/genética , Fenotipo , Próstata/metabolismo , Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Receptores Androgénicos/metabolismo , Sirolimus/administración & dosificación , Sirolimus/análogos & derivados
16.
BJU Int ; 110(6 Pt B): E228-34, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22332735

RESUMEN

UNLABELLED: What's known on the subject? and What does the study add? Targeted agents with a similar or different target molecule are often used sequentially in the treatment of metastatic RCC. Two tyrosine kinase inhibitors, sorafenib and sunitinib, have been reported to show little cross-resistance, when used sequentially. In addition, a recent report showed that sunitinib rechallenge could potentially benefit selected patients. This case series shows that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment. Outcomes of the sorafenib rechallenge were not significantly affected by the response to the initial sorafenib treatment or by the duration of intervening treatments between first sorafenib and rechallenge. OBJECTIVE: To investigate clinical outcomes of sorafenib rechallenge during sequential therapy for patients with metastatic renal cell carcinoma (RCC). PATIENTS AND METHODS: Patients with metastatic RCC who received sorafenib rechallenge after failed treatment first with sorafenib and subsequently with other agents, were retrospectively reviewed for patient characteristics, best response, progression-free survival (PFS), and adverse events (AEs). RESULTS: Of the 14 patients who received sorafenib rechallenge, 12 were evaluable for response. Eleven patients had previously undergone nephrectomy, and 10 had previously received systemic therapy, mostly interferon-α (nine patients) and interleukin-2 (six patients), with a median duration of 9 months. The best responses after the first sorafenib therapy were partial response (PR) in two patients, stable disease (SD) in seven, and progressive disease (PD) in two. The median PFS was 5.7 months. Initial sorafenib therapy was discontinued because of PD in eight patients and AEs in four patients. Rechallenge with sorafenib was undertaken after a 7.6 month median interval from the initial sorafenib challenge. Eight patients achieved SD on sorafenib rechallenge and median PFS was 5.4 (95% confidence interval, 3.8-7.0) months. The outcome of the sorafenib rechallenge was not significantly affected by the response to the initial sorafenib treatment or by the duration of treatments received between first sorafenib and rechallenge. No severe AE was newly observed on the rechallenge. CONCLUSION: In the systemic treatment of advanced RCC, it was suggested that patients once refractory to sorafenib could regain disease control on rechallenge with sorafenib during sequential treatment.


Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/secundario , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/patología , Piridinas/uso terapéutico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Retratamiento , Estudios Retrospectivos , Sorafenib
17.
Hinyokika Kiyo ; 58(1): 7-11, 2012 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-22343736

RESUMEN

The prognostic factor was retrospectively analyzed in 52 castration-resistant prostate cancer treated with docetaxel (DTX) in our institutions from April, 2006 to August, 2009. The treatment outcomes were decided with prostate specific antigen (PSA) progression-free survival and overall survival. These were calculated by Kaplan-Meier methods and tested with Log-rank test. Median PSA progression-free survival was 8.8 months and median overall survival was 24.1 months. Prognostic factors on PSA progression were PSA value before DTX treatment and rate of PSA decrement after DTX treatment. Prognostic factors on overall survival were Gleason score (GS), PSA value before DTX treatment, rate of PSA decrement after DTX treatment and positive of bone metastasis in Log-rank test. Odds ratio of PSA ≧20 ng/ml before DTX treatment was 2.99 and PSA decreasing rate < 30% was 3.65. These were statistically significant (p < 0.001) risk factors in the overall survival.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/mortalidad , Taxoides/uso terapéutico , Anciano , Anciano de 80 o más Años , Castración , Supervivencia sin Enfermedad , Docetaxel , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos
18.
Hinyokika Kiyo ; 54(11): 745-7, 2008 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-19068731

RESUMEN

Urinary stone formation after orthotopic neobladder construction is a delayed complication. A giant bladder stone was found in a 67-year-old man who had undergone radical cystectomy and orthotopic neobladder substitution (Hautmann method) in 1998. The stone was removed by cystolithotripsy and weighed 108 g.


Asunto(s)
Complicaciones Posoperatorias , Cálculos de la Vejiga Urinaria/terapia , Derivación Urinaria , Anciano , Cistectomía , Humanos , Litotricia , Masculino , Factores de Tiempo , Cálculos de la Vejiga Urinaria/química , Cálculos de la Vejiga Urinaria/diagnóstico , Cálculos de la Vejiga Urinaria/patología , Derivación Urinaria/métodos
19.
Comput Methods Programs Biomed ; 92(3): 238-48, 2008 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18514362

RESUMEN

The aim of this paper is to describe three emerging computer-aided diagnosis (CAD) systems induced by Japanese health care needs. CAD has been developing fast in the last two decades. The idea of using a computer to help in medical image diagnosis is not new. Some pioneer studies are dated back to the 1960s. In 1998, the first U.S. FDA (Food and Drug Administration) approved commercial CAD system, a film-digitized mammography system, was launched by R2 Technologies, Inc. The success was quickly repeated by a number of companies. The approval of Medicare CAD reimbursement in the U.S. in 2001 further boosted the industry. Today, CAD has its significance in the economy of the medical industry. FDA approved CAD products in the field of breast imaging (mammography, ultrasonography and breast MRI) and chest imaging (radiography and CT) can be seen. In Japan, as part of the "Knowledge Cluster Initiative" of the government, three computer-aided diagnosis (CAD) projects are hosted at the Gifu University since 2004. These projects are regarding the development of CAD systems for the early detection of (1) cerebrovascular diseases using brain MRI and MRA images by detecting lacunar infarcts, unruptured aneurysms, and arterial occlusions; (2) ocular diseases such as glaucoma, diabetic retinopathy, and hypertensive retinopathy using retinal fundus images; and (3) breast cancers using ultrasound 3-D volumetric whole breast data by detecting the breast masses. The projects are entering their final development stage. Preliminary results are presented in this paper. Clinical examinations will be started soon, and commercialized CAD systems for the above subjects will appear by the completion of this project.


Asunto(s)
Diagnóstico por Computador/métodos , Necesidades y Demandas de Servicios de Salud , Encéfalo/diagnóstico por imagen , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/diagnóstico por imagen , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/radioterapia , Fondo de Ojo , Humanos , Japón , Imagen por Resonancia Magnética , Radiografía
20.
Nihon Hoshasen Gijutsu Gakkai Zasshi ; 58(3): 375-82, 2002 Mar.
Artículo en Japonés | MEDLINE | ID: mdl-12522345

RESUMEN

We have been developing automated detection algorithms for masses and clustered microcalcifications in a mammography computer-aided diagnosis (CAD) system. In this study, we investigated the potential of our CAD system by comparing 579 physicians' interpretation results with that of the CAD system's cancer detection for 100 mammograms (21 malignant and 29 benign cases) employed in a physicians' self-learning course. As a result, our CAD system detected 7 out of 8 malignant lesions whose physicians' averaged sensitivity was less than 60%. Although the average of physicians' sensitivities were 76% (about 16 cases), the CAD system's detection rate was 90% (19 cases). Sensitivity was raised up to 97% if the physicians' interpretation and the CAD system's detection result were treated in a matter of logical OR. Thus, it was raised the possibility that even the less-experienced physicians would diagnose with a higher sensitivity by using the computer output as a guide effectively.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Diagnóstico por Computador , Mamografía , Médicos , Competencia Clínica , Femenino , Humanos , Variaciones Dependientes del Observador , Sensibilidad y Especificidad
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