Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 162
Filtrar
1.
BMC Med Genomics ; 14(1): 245, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627261

RESUMO

BACKGROUND: Ductal adenocarcinoma and neuroendocrine cancer are rare subtypes of prostate cancer with poor prognosis and limited therapeutic options. We present the first case of ductal adenocarcinoma having a neuroendocrine phenotype. CASE PRESENTATION: A 63-year-old man presented with gross hematuria and urinary retention, and his serum prostate-specific antigen level was 4.58 ng/mL. We performed transurethral resection of the prostate, and the diagnosis was ductal adenocarcinoma with a Gleason score of 5 + 4 for acinar adenocarcinoma. Magnetic resonance imaging showed local invasion of left lobe of the prostate and bone metastasis of the left trochanteric section of the femur. Multidisciplinary treatments such as androgen deprivation therapy, chemoradiation therapy, and surgery for metastatic lesions have led to long-term survival. Since next-generation sequencing revealed PTEN and RB1 co-loss and TP53 mutations, we re-evaluated the immunohistochemistry and he was found to be positive for synaptophysin. CONCLUSIONS: This is the first Japanese case of ductal adenocarcinoma with a neuroendocrine phenotype. Genetic analysis may help not only guide the therapeutic strategies, but also sometimes with the diagnosis.

2.
Br J Cancer ; 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611307

RESUMO

BACKGROUND: Cabozantinib is an oral tyrosine kinase inhibitor in renal cell carcinoma (RCC), whose targets include oncogenic AXL and unique ligand GAS6. Critical gaps in basic knowledge need to be addressed to devise an exclusive biomarker and candidate when targeting the AXL/GAS6 axis. METHODS: To clarify the effects of the AXL/GAS6 axis on RCC, we herein performed a large-scale immunogenomic analysis and single-cell counts including various metastatic organs and histological subtypes of RCC. We further applied genome-wide mutation analyses and methylation arrays. RESULTS: Varying patterns of AXL and GAS6 expression were observed throughout primary RCC tumours and metastases. Scoring individual AXL/GAS6 levels in the tumour centre and invasive margin, namely, the AXL/GAS6 score, showed a good ability to predict the prognosis of clear cell RCC. Metastasis- and histological subtype-specific differences in the AXL/GAS6 score existed since lung metastasis and the papillary subtype were weakly related to the AXL/GAS6 axis. Cell-by-cell immunohistological assessments clarified an immunosuppressive environment in tumours with high AXL/GAS6 scores. Genomic alterations in the PI3K-mTOR pathway and DNA methylation profiling revealed distinct differences with the AXL/GAS6 score in ccRCC. CONCLUSION: The AXL/GAS6 scoring system could predict the outcome of prognosis and work as a robust biomarker for the immunogenomic state in RCC.

3.
Nat Commun ; 12(1): 5547, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34545095

RESUMO

A cutting edge therapy for future immuno-oncology is targeting a new series of inhibitory receptors (IRs): LAG-3, TIM-3, and TIGIT. Both immunogenomic analyses and diagnostic platforms to distinguish candidates and predict good responders to these IR-related agents are vital in clinical pathology. By applying an automated single-cell count for immunolabelled LAG-3, TIM-3, and TIGIT, we reveal that individual IR levels with exclusive domination in each tumour can serve as valid biomarkers for profiling human renal cell carcinoma (RCC). We uncover the immunogenomic landscape associated with individual IR levels in human RCC tumours with metastases in various organs and histological subtypes. We then externally validate our results and devise a workflow with optimal biomarker cut-offs for discriminating the LAG-3, TIM-3, and TIGIT tumour profiles. The discrimination of LAG-3, TIM-3, and TIGIT profiles in tumours may have a broad impact on investigations of immunotherapy responses after targeting a new series of IRs.


Assuntos
Antígenos CD/metabolismo , Carcinoma de Células Renais/metabolismo , Receptor Celular 2 do Vírus da Hepatite A/metabolismo , Neoplasias Renais/metabolismo , Receptores Imunológicos/metabolismo , Idoso , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/genética , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Fenótipo , Reprodutibilidade dos Testes
4.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360727

RESUMO

Hereditary leiomyomatosis and renal cell carcinoma (HL (RCC)) entails cutaneous and uterine leiomyomatosis with aggressive type 2 papillary RCC-like histology. HLRCC is caused by pathogenic variants in the FH gene, which encodes fumarate hydratase (FH). Here, we describe an episode of young-onset RCC caused by a genomic FH deletion that was diagnosed via clinical sequencing. A 35-year-old woman was diagnosed with RCC and multiple metastases: histopathological analyses supported a diagnosis of FH-deficient RCC. Although the patient had neither skin tumors nor a family history of HLRCC, an aggressive clinical course at her age and pathological diagnosis of FH-deficient RCC suggested a germline FH variant. After counseling, the patient provided written informed consent for germline genetic testing. She was simultaneously subjected to paired tumor profiling tests targeting the exome to identify a therapeutic target. Although conventional germline sequencing did not detect FH variants, exome sequencing revealed a heterozygous germline FH deletion. As such, paired tumor profiling, not conventional sequencing, was required to identify this genetic deletion. RCC caused by a germline FH deletion has hitherto not been described in Japan, and the FH deletion detected in this patient was presumed to be of maternal European origin. Although the genotype-phenotype correlation in HLRCC-related tumors is unclear, the patient's family was advised to undergo genetic counseling to consider additional RCC screening.


Assuntos
Fumarato Hidratase/deficiência , Deleção de Genes , Mutação em Linhagem Germinativa , Leiomiomatose/genética , Erros Inatos do Metabolismo/genética , Hipotonia Muscular/genética , Síndromes Neoplásicas Hereditárias/genética , Transtornos Psicomotores/genética , Neoplasias Cutâneas/genética , Neoplasias Uterinas/genética , Adulto , Feminino , Fumarato Hidratase/genética , Testes Genéticos , Humanos
5.
Cancer Immunol Immunother ; 70(10): 3001-3013, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34259900

RESUMO

Despite the high sensitivity of renal cell carcinoma (RCC) to immunotherapy, RCC has been recognized as an unusual disease in which CD8+ T-cell infiltration into the tumor beds is related to a poor prognosis. To approach the inner landscape of immunobiology of RCC, we performed multiplexed seven-color immunohistochemistry (CD8, CD39, PD-1, Foxp3, PD-L1, and pan-cytokeratin AE1/AE3 with DAPI), which revealed the automated single-cell counts and calculations of individual cell-to-cell distances. In total, 186 subjects were included, in which CD39 was used as a marker for distinguishing tumor-specific (CD39+) and bystander (CD39-) T-cells. Our clear cell RCC cohort also revealed a poor prognosis if the tumor showed increased CD8+ T-cell infiltration. Intratumoral CD8+CD39+ T-cells as well as their exhausted CD8+CD39+PD-1+ T-cells in the central tumor areas enabled the subgrouping of patients according to malignancy. Analysis using specimens post-antiangiogenic treatment revealed a dramatic increase in proliferative Treg fraction Foxp3+PD-1+ cells, suggesting a potential mechanism of hyperprogressive disease after uses of anti-PD-1 antibody. Our cell-by-cell study platform provided spatial information on tumors, where bystander CD8+CD39- T-cells were dominant in the invasive margin areas. We uncovered a potential interaction between CD8+CD39+PD-1+ T-cells and Foxp3+PD-1+ Treg cells due to cell-to-cell proximity, forming a spatial niche more specialized in immunosuppression under PD-1 blockade. A paradigm shift to the immunosuppressive environment was more obvious in metastatic lesions; rather the infiltration of Foxp3+ and Foxp3+PD-1+ Treg cells was more pronounced. With this multiplexed single-cell pathology technique, we revealed further insight into the immunobiological standing of RCC.


Assuntos
Linfócitos T CD8-Positivos/metabolismo , Carcinoma de Células Renais/genética , Imunoterapia/métodos , Neoplasias Renais/genética , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/patologia , Prognóstico , Resultado do Tratamento
6.
Int J Clin Oncol ; 2021 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-34101038

RESUMO

OBJECTIVE: The aim of this study was to evaluate the clinical significance of the on-treatment C-reactive protein (CRP) status during systemic treatment as the predictive marker for the response of subsequent nivolumab monotherapy in patients with refractory metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: A total of 73 mRCC patients treated with nivolumab were retrospectively reviewed. We evaluated the serum CRP levels before and after molecular-targeted treatments. Patients whose CRP did not exceed baseline value were defined as the CRP-control group and the others were defined as the CRP-progression group. The clinical impact of CRP-control on the efficacy of nivolumab was assessed. RESULTS: Twenty-four patients (33%) were categorized into the CRP-control group. The CRP-control group patients (median PFS not reached) had significantly longer PFS than the CRP-progression group (median PFS 11.9 months, 95% confidence interval, CI 4.1-19.8, p = 0.038). The CRP-control group had a tendency of longer OS from nivolumab initiation than the CRP-progression group (p = 0.071). By multivariate analysis, the on-treatment CRP-control was the independent predictive factor for PFS (hazard ratio HR 0.37, 95% CI 0.14-0.99, p = 0.047). CONCLUSION: The on-treatment CRP-control could be the predictive factor for the efficacy of nivolumab in refractory mRCC patients.

8.
Surg Case Rep ; 7(1): 80, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797633

RESUMO

BACKGROUND: In Japan, the prevalence of synchronous multiple intramucosal gastric carcinoma is reported to be 5-15%. Here is a case of a synchronous small gastric carcinoma fulfilling the definite indication and curative criteria for endoscopic submucosal dissection with multiple lymph node metastases. CASE PRESENTATION: A Japanese woman in her fifties with a history of endoscopic resection for mucosal poorly differentiated adenocarcinoma was evaluated, with the UICC TNM classification stage being cT1aN0M0 cStageIA. She had undergone total gastrectomy with D1 + lymph node dissection. Histopathological examination revealed 16 individual sporadic lesions in the gastric body, with maximum diameter 3 mm and localization in the lamina propria. Twenty-seven nodes were resected, and metastasis of the carcinoma was revealed in 24 nodes. CONCLUSIONS: Undifferentiated intramucosal gastric cancer has a relatively high probability of lymph node metastasis; however, synchronous early lesions are often overlooked. Frequent follow-up examinations may increase the detection of multiple gastric cancers.

9.
Rinsho Ketsueki ; 62(1): 25-29, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33551421

RESUMO

A 44-year-old woman was diagnosed with anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) with clinical stage IVA (nodal and bladder involvement). Complete response (CR) was achieved after the CHOP chemotherapy; however, 12 months after the last course of chemotherapy, ALCL relapsed in the form of skin lesions without nodal involvement. After achieving a second CR with chemotherapy, autologous stem cell transplantation was performed. Two months after transplantation, the disease again relapsed as multiple skin lesions. Electron beam irradiation was performed; however, other skin lesions appeared thereafter and spontaneously disappeared. At present, 3.4 years after the transplantation, the patient is free from disease. ALK-positive ALCL relapsing as skin lesions may behave differently from the nodal relapse. An accumulation of cases is required to elucidate ALCL characteristics relapsing as skin lesions.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Anaplásico de Células Grandes , Adulto , Quinase do Linfoma Anaplásico , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/terapia , Recidiva Local de Neoplasia , Receptores Proteína Tirosina Quinases , Remissão Espontânea , Transplante Autólogo
10.
Eur Radiol ; 31(2): 875-883, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32829418

RESUMO

OBJECTIVES: To investigate the clinical utility of the Vesical Imaging-Reporting and Data System (VI-RADS) by comparing its diagnostic performance for muscle-invasive bladder cancer (MIBC) between radiologists and urologists based on multiparametric MRI, including three-dimensional (3D) fast spin-echo (FSE) T2-weighted acquisitions. METHODS: This study included 66 treatment-naïve patients (60 men, 6 women; mean age 74.0 years) with pathologically proven bladder cancer who underwent multiparametric MRI, including 3D FSE T2-weighted imaging, before transurethral bladder tumour resection between January 2010 and November 2018. The MRI scans were categorised according to the five-point VI-RADS score by four independent readers (two board-certified radiologists and board-certified urologists each), blinded to the histopathological findings. The VI-RADS scores were compared with the postoperative histopathological diagnosis. Interobserver agreement was assessed using weighted kappa coefficients. ROC analysis and generalised estimating equations were used to evaluate the diagnostic performance. RESULTS: Forty-nine (74.2%) and 17 (25.8%) tumours were confirmed to be non-MIBC and MIBC, respectively, based on pathological examination. The interobserver agreement was good-to-excellent between all pairs of readers (range, 0.73-0.91). The urologists' sensitivity/specificity values for DCE-MRI VI-RADS scores were significantly lower than those of radiologists. No significant differences were observed for the overall VI-RADS score. The AUC for the overall VI-RADS score was 0.94, 0.92, 0.89, and 0.87 for radiologists 1 and 2 and urologists 1 and 2, respectively. CONCLUSIONS: The VI-RADS score, based on multiparametric MRI including 3D FSE T2-weighted acquisitions, can be useful for radiologists and urologists to determine the bladder cancer muscle invasion status preoperatively. KEY POINTS: • VI-RADS (using multiparametric MRI including 3D FSE T2-weighted acquisitions) achieves good to excellent interobserver agreement and has similar diagnostic performance for detecting muscle invasion by both radiologists and urologists. • The diagnostic performance of the overall VI-RADS score is high for both radiologists and urologists, particularly due to the dominant effect of diffusion-weighted imaging on the overall VI-RADS score. • The sensitivity and specificity values of the T2WI VI-RADS scores for four readers in our study (using 3D FSE T2-weighted acquisitions) were similar (with slightly higher specificity values) to previously published results (using 2D FSE T2-weighted acquisitions).


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Bexiga Urinária , Idoso , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Músculos , Radiologistas , Sensibilidade e Especificidade , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Urologistas
11.
Int Urol Nephrol ; 53(3): 465-469, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33025406

RESUMO

PURPOSE: Intravesical bacillus Calmette-Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy. METHODS: We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6-8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens. RESULTS: According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p = 0.116, and p < 0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%. CONCLUSION: RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

12.
Cancer Sci ; 112(3): 1084-1094, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33368857

RESUMO

This study aimed to clarify the clinical characteristics and oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) who developed muscle-invasive bladder cancer (MIBC) after radical nephroureterectomy (RNU). We identified 966 pTa-4N0-2M0 patients with UTUC who underwent RNU and clarified the risk factors for MIBC progression after initial intravesical recurrence (IVR). We also identified 318 patients with primary pT2-4N0-2M0 MIBC to compare the oncological outcomes with those of patients with UTUC who developed or progressed to MIBC. Furthermore, immunohistochemical examination of p53 and FGFR3 expression in tumor specimens was performed to compare UTUC of MIBC origin with primary MIBC. In total, 392 (40.6%) patients developed IVR after RNU and 46 (4.8%) developed MIBC at initial IVR or thereafter. As a result, pT1 stage on the initial IVR specimen, concomitant carcinoma in situ on the initial IVR specimen, and no intravesical adjuvant therapy after IVR were independent factors for MIBC progression. After propensity score matching adjustment, primary UTUC was a favorable indicator for cancer-specific death compared with primary MIBC. Subgroup molecular analysis revealed high FGFR3 expression in non-MIBC and MIBC specimens from primary UTUC, whereas low FGFR3 but high p53 expression was observed in specimens from primary MIBC tissue. In conclusion, our study demonstrated that patients with UTUC who develop MIBC recurrence after RNU exhibited the clinical characteristics of subsequent IVR more than those of primary UTUC. Of note, MIBC subsequent to UTUC may have favorable outcomes, probably due to the different molecular biological background compared with primary MIBC.


Assuntos
Carcinoma de Células de Transição/mortalidade , Neoplasias Renais/patologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias Ureterais/patologia , Neoplasias da Bexiga Urinária/mortalidade , Administração Intravesical , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/terapia , Quimioterapia Adjuvante , Cistectomia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Músculo Liso/patologia , Músculo Liso/cirurgia , Terapia Neoadjuvante , Recidiva Local de Neoplasia/patologia , Nefroureterectomia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Neoplasias Ureterais/mortalidade , Neoplasias Ureterais/terapia , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/secundário , Neoplasias da Bexiga Urinária/terapia
13.
Jpn J Clin Oncol ; 50(11): 1313-1320, 2020 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-33089867

RESUMO

OBJECTIVES: In our multicenter study evaluating metastatic papillary renal cell carcinoma (PRCC), 29% of tumors diagnosed as PRCC in collaborative institutes were finally diagnosed as other RCCs under central review. In those tumors, mucinous tubular and spindle cell carcinoma (MTSCC) was the leading histology, followed by unclassified RCC (ucRCC). We focused on those patients with MTSCC or ucRCC. METHODS: We reviewed the processes for the pathological diagnoses of nine tumors and reviewed their clinical features. RESULTS: All of the MTSCCs and ucRCCs were positive for AMACR, which is frequently positive in PRCC. Mucin was demonstrated in 80% of the MTSCCs, and its presence is important for their diagnoses. One MTSCC was diagnosed as a mucin-poor variant. The presence of spindle cells with low-grade nuclei was suggestive of MTSCC, but the diagnosis of high-grade MTSCC was difficult. Four tumors were diagnosed as ucRCC by histological and immunohistochemical findings. Three of the four tumors were suspicious of ucRCC in the initial review due to atypical findings as PRCC. Sunitinib and interferon-α were effective for one MTSCC patient who survived for >5 years. Two MTSCC patients who were Memorial Sloan-Kettering Cancer Center poor risk had unfavorable prognoses. One patient with mucin-poor MTSCC had an indolent clinical course. Two of four ucRCC patients showed durable stable disease with targeted agents (TAs) and survived >3 years. CONCLUSION: Some MTSCC metastases progressed very slowly and poor-risk tumors progressed rapidly. Systemic therapies including TAs showed some efficacies. Some patients who have metastatic ucRCC with microscopic papillary architecture can benefit from TAs.


Assuntos
Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Diagnóstico Diferencial , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade
14.
Cancer Sci ; 111(12): 4652-4655, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33038052

RESUMO

Cyclin-dependent kinase 12 (CDK12), one of the key factors associated with DNA damage response pathways, is located on chromosome 17 proximal to Erb-B2 receptor tyrosine kinase 2 (ERBB2). In this report, CDK12 and ERBB2 coamplification was detected by targeted next-generation sequencing in two urothelial carcinomas. The staining intensity of the CDK12 and human epidermal growth factor receptor-2 proteins was associated with the prognosis of each urothelial carcinoma case. Our results suggest that CDK12 coamplification with ERBB2 might be associated with tumor aggressiveness and contribution to cancer pathogenesis. Therapies targeting CDK12 should be developed for these patients.


Assuntos
Quinases Ciclina-Dependentes/genética , Amplificação de Genes , Genes erbB-2 , Neoplasias Renais/genética , Neoplasias da Bexiga Urinária/genética , Adenocarcinoma/genética , Adenocarcinoma/terapia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/genética , Carcinoma de Células de Transição/terapia , Progressão da Doença , Evolução Fatal , Genes p53 , Humanos , Neoplasias Renais/terapia , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
15.
IJU Case Rep ; 3(2): 69-71, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32743474

RESUMO

Introduction: Cellular angiofibroma is a benign mesenchymal tumor that is rare and has a good prognosis. However, preoperative distinction of cellular angiofibroma from malignant tumors is difficult. Case presentation: A 77-year-old man complained of a left inguinal mass, which was a solid, painless, mobile tumor measuring approximately 40 mm and contacted with the left spermatic cord. Based on his age, the location and imaging findings, a preoperative diagnosis of myxoid liposarcoma was made. The patient underwent left high inguinal orchiectomy with complete resection of the tumor. Histologically and immunohistochemically, the tumor had no feature of malignancy. A postoperative diagnosis of cellular angiofibroma was made. The patient remains free of disease recurrence 12 months after surgery. Conclusion: Cellular angiofibroma is a benign but rare tumor, which is sometimes difficult to distinguish from malignant neoplasms. Further studies are needed to accurately preoperatively diagnose this tumor.

16.
Diagn Pathol ; 15(1): 102, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32758244

RESUMO

BACKGROUND: Ductal carcinoma of the prostate is a histological subtype with a higher mortality than acinar adenocarcinoma. The number of cases is small and there are no treatment guidelines. We believe that this is the first report of ductal carcinoma of the prostate with an adenomatosis polyposis coli (APC) gene mutation in Japan. CASE PRESENTATION: An 85-year-old man presented with gross hematuria, and a papillary tumor in the prostatic urethra that was diagnosed as ductal carcinoma of the prostate following transurethral resection. Genetic analysis found an APC mutation with loss of heterozygosity. Immunostaining revealed focal nuclear translocation of ß-catenin. APC mutations associated with loss of ß-catenin degradation in the Wnt signaling pathway and result in over accumulation of ß-catenin are thought to increase mortality. In this patient, ß-catenin migrated into tumor cell nuclei. CONCLUSION: To the best of our knowledge, this is the first report of ductal carcinoma of the prostate with an APC mutation in Japan. The development of a therapeutic Wnt inhibitor is discussed.

17.
Cancer Sci ; 111(10): 3639-3652, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32677159

RESUMO

Mucin 1 C-terminal subunit (MUC1-C) has been introduced as a key regulator for acquiring drug resistance in various cancers, but the functional role of MUC1-C in urothelial carcinoma (UC) cells remains unknown. We aimed to elucidate the molecular mechanisms underlying the acquisition of cisplatin (CDDP) resistance through MUC1-C oncoprotein in UC cells. MUC1-C expression was examined immunohistochemically in tumor specimens of 159 UC patients who received CDDP-based perioperative chemotherapy. As a result, moderate to high MUC1-C expression was independently associated with poor survival in UC patients. Using human bladder cancer cell lines and CDDP-resistant (CR) cell lines, we compared the expression levels of MUC1-C, multiple drug resistance 1 (MDR1), the PI3K-AKT-mTOR pathway, and x-cystine/glutamate transporter (xCT) to elucidate the biological mechanisms contributing to the acquisition of chemoresistance. MUC1-C was strongly expressed in CR cell lines, followed with MDR1 expression via activation of the PI3K-AKT-mTOR pathway. MUC1-C also stabilized the expression of xCT, which enhanced antioxidant defenses by increasing intracellular glutathione (GSH) levels. MUC1 down-regulation showed MDR1 inhibition along with PI3K-AKT-mTOR pathway suppression. Moreover, it inhibited xCT stabilization and resulted in significant decreases in intracellular GSH levels and increased reactive oxygen species (ROS) generation. The MUC1-C inhibitor restored sensitivity to CDDP in CR cells and UC murine xenograft models. In conclusion, we found that MUC1-C plays a pivotal role in the acquisition of CDDP resistance in UC cells, and therefore the combined treatment of CDDP with a MUC1-C inhibitor may become a novel therapeutic option in CR UC patients.


Assuntos
Carcinoma/tratamento farmacológico , Carcinoma/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Mucina-1/genética , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/genética , Animais , Carcinoma/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias Urológicas/metabolismo
18.
Pathol Int ; 70(10): 712-723, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32652869

RESUMO

The development of systemic therapies, including vascular endothelial growth factor-tyrosine kinase inhibitors (VEGF-TKI) and mammalian target of rapamycin (mTOR) inhibitors, represents a major breakthrough in the treatment of patients with renal cell carcinoma (RCC). However, inherent resistance is observed in some patients and acquired resistance commonly develops in many patients within several months of the initiation of systemic therapies. Since these treatments rarely cure patients, their aim is to suppress tumor progression and prolong survival. Therefore, the establishment of dependable criteria that predict responses and resistance to systemic therapies is clinically important, and the underlying molecular mechanisms also need to be elucidated for the future development of more effective therapies. We herein review recent advances in research on the molecular mechanisms underlying resistance, with a focus on morphological characteristics, tumor angiogenesis, and the tumor immune microenvironment in RCC and their relationships with VEGF-TKI treatments. Recent therapies using immune checkpoint inhibitors (ICI) and newly developed VEGF-TKI also appear to be effective for advanced RCC, with stable and durable responses to ICI being observed in some RCC patients. These new drugs and their outcomes have been briefly described.

19.
Spinal Cord Ser Cases ; 6(1): 37, 2020 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404920

RESUMO

INTRODUCTION: Spinal intramedullary endodermal cyst is a rare spinal cord tumour. In particular, an endodermal cyst that includes glial tissues is extremely rare. Herein, we present the case of an individual with a thoracic spinal cord intramedullary endodermal cyst, which includes glial tissues that achieved gross total resection by surgery. CASE PRESENTATION: A 59-year-old man presented with a 10-month history of right thigh pain and numbness. Magnetic resonance imaging (MRI) revealed a well-marginated 15-mm cystic lesion at the T7-T8 level. We performed cystectomy and achieved gross total resection. Pathological findings revealed an endodermal cyst, with the presence of glial tissues. No recurrence of cysts was observed upon MRI 2 years after the surgery. DISCUSSION: Endodermal cyst is defined by pathological findings of a cyst lined by columnar epithelium of presumed endodermal derivation. To date, only 104 reported cases of intramedullary endodermal cysts have been reported; our report was the third case that showed the presence of glial cells in the cyst during pathological examination. Intramedullary cysts are generally difficult to completely resect, with many recurrences. Although we achieved gross total resection, careful follow-up is necessary in the future.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...