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1.
BMC Nephrol ; 25(1): 123, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580974

RESUMO

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease that sometimes recurs in patients after kidney transplantation (KT) and increases the risk of graft loss. Proteinuria is a common early sign of recurrent FSGS, but an abrupt decrease in urine volume is rare. Herein, we report a patient with early recurrence of FSGS with anuria following KT. CASE PRESENTATION: A 55-year-old man with end-stage kidney disease caused by primary FSGS experienced anuria on postoperative day 2 following deceased donor KT. Laboratory results revealed that serum tacrolimus trough levels were consistently elevated at the time of anuria. At first, we considered acute calcineurin inhibitor (CNI) nephrotoxicity based on graft biopsy on light microscopy, laboratory findings, and clinical courses. However, the allograft function did not recover even after discontinuation of CNI, and recurrent FSGS was diagnosed 2 weeks later on electron microscopy. A total of 13 sessions of plasmapheresis and two administrations of rituximab (375 mg/m2) were required to treat recurrent FSGS. The patient achieved a partial response, and the spot urine protein-to-creatinine ratio decreased from 15.5 g/g creatinine to 5.2 g/g creatinine. At 5 months following KT, the serum creatinine level was stable at 1.15 mg/dL. CONCLUSIONS: These findings highlight that anuria can occur in cases of early recurrence of FSGS combined with acute CNI nephrotoxicity.


Assuntos
Anuria , Glomerulosclerose Segmentar e Focal , Nefropatias , Transplante de Rim , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores de Calcineurina/toxicidade , Creatinina , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/etiologia , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Recidiva
2.
J Clin Med ; 13(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38256628

RESUMO

Chronic myelomonocytic leukemia (CMML) is a rare hematologic disorder that infrequently causes acute kidney injury (AKI). CMML can transform into acute myeloid leukemia (AML), which can be accompanied by a deterioration in kidney function. However, severe AKI due to extramedullary manifestations of AML is rare. Herein, we present the case of a 67-year-old male patient with CMML that transformed into AML with severe AKI necessitating hemodialysis. The cause of the AKI was the AML transformation. The patient, with stable kidney function after chemotherapy for CMML, presented with a sudden decline in kidney function. Hemodialysis was initiated because of severe AKI, and histopathologic evaluation of the kidney biopsy specimen revealed severe, diffuse mixed inflammatory cell infiltrates in the interstitium and c-kit-immunopositive myeloblast-like cells. A bone marrow biopsy was performed because of the kidney biopsy findings suggesting that leukemic infiltration led to the diagnosis of AML. The patient received chemotherapy for AML, and his kidney function recovered. As illustrated in this case, severe AKI can develop as an early extramedullary manifestation during transformation from CMML to AML. Therefore, in patients with CMML and rapidly declining renal function, transformation into AML should be considered and histopathologically confirmed by kidney biopsy.

3.
Theranostics ; 14(2): 460-479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38169528

RESUMO

Rationale: Platinum-based chemotherapy is commonly used for treating solid tumors, but drug resistance often limits its effectiveness. Cancer-associated fibroblast (CAF)-derived extracellular vesicle (EV), which carry various miRNAs, have been implicated in chemotherapy resistance. However, the molecular mechanism through which CAFs modulate cisplatin resistance in oral squamous cell carcinoma (OSCC) is not well understood. We employed two distinct primary CAF types with differential impacts on cancer progression: CAF-P, representing a more aggressive cancer-promoting category, and CAF-D, characterized by properties that moderately delay cancer progression. Consequently, we sought to investigate whether the two CAF types differentially affect cisplatin sensitivity and the underlying molecular mechanism. Methods: The secretion profile was examined by utilizing an antibody microarray with conditioned medium obtained from the co-culture of OSCC cells and two types of primary CAFs. The effect of CAF-dependent factors on cisplatin resistance was investigated by utilizing conditioned media (CM) and extracellular vesicle (EVs) derived from CAFs. The impacts of candidate genes were confirmed using gain- and loss-of-function analyses in spheroids and organoids, and a mouse xenograft. Lastly, we compared the expression pattern of the candidate genes in tissues from OSCC patients exhibiting different responses to cisplatin. Results: When OSCC cells were cultured with conditioned media (CM) from the two different CAF groups, cisplatin resistance increased only under CAF-P CM. OSCC cells specifically expressed insulin-like growth factor binding protein 3 (IGFBP3) after co-culture with CAF-D. Meanwhile, IGFBP3-knockdown OSCC cells acquired cisplatin resistance in CAF-D CM. IGFBP3 expression was promoted by GATA-binding protein 1 (GATA1), a transcription factor targeted by miR-876-3p, which was enriched only in CAF-P-derived EV. Treatment with CAF-P EV carrying miR-876-3p antagomir decreased cisplatin resistance compared to control miRNA-carrying CAF-P EV. On comparing the staining intensity between cisplatin-sensitive and -insensitive tissues from OSCC patients, there was a positive correlation between IGFBP3 and GATA1 expression and cisplatin sensitivity in OSCC tissues from patients. Conclusion: These results provide insights for overcoming cisplatin resistance, especially concerning EVs within the tumor microenvironment. Furthermore, it is anticipated that the expression levels of GATA1 and miR-876-3p, along with IGFBP3, could aid in the prediction of cisplatin resistance.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma de Células Escamosas , Vesículas Extracelulares , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Humanos , Animais , Camundongos , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Meios de Cultivo Condicionados/farmacologia , Meios de Cultivo Condicionados/metabolismo , Proliferação de Células , MicroRNAs/metabolismo , Vesículas Extracelulares/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Linhagem Celular Tumoral , Microambiente Tumoral/genética
4.
J Surg Case Rep ; 2023(7): rjad429, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37525746

RESUMO

Although intratumoral hemorrhage is common in patients with malignant brain tumors, reports on its clinical course are scarce. This report presents a rare case of a patient with intratumoral hemorrhage with gliosarcoma invading the venus sinus. This invasion and a small draining vein were observed at diagnosis. Magnetic resonance imaging performed 1 week later showed new-onset venous ectasia, which caused intratumoral hemorrhage. This case provides insight into the mechanisms underlying intratumoral hemorrhage and highlights the emergence of new intratumoral vasculature as a potential warning sign for hemorrhage.

5.
J Korean Med Sci ; 38(33): e258, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37605497

RESUMO

BACKGROUND: This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific co-stimulatory and co-inhibitory factors were investigated. METHODS: The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed. Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations. RESULTS: The mean follow-up duration was 27.5 months (range, 4.1-43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3-20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = -1.746) and those of PD-L1 and EZH1 (R2 linear = -2.118); these relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival. CONCLUSION: These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.


Assuntos
Glioblastoma , Histonas , Humanos , Antígeno CTLA-4/genética , Antígeno B7-H1 , Lisina , Prognóstico , Antígenos CD28 , Glioblastoma/diagnóstico , Glioblastoma/genética , Epigênese Genética , Estudos Retrospectivos , Linfócitos T
6.
Medicina (Kaunas) ; 59(7)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37512118

RESUMO

C3 glomerulonephritis (C3GN) is a rare cause of end-stage kidney disease and frequently recurrent in allografts following kidney transplantation (KT). Herein, we describe the case of a kidney transplant recipient who developed recurrent C3GN along with BK-virus-associated nephropathy (BKVAN) following KT. A 33-year-old man diagnosed with membranoproliferative glomerulonephritis 17 years ago underwent preemptive KT with a donor kidney from his aunt. Proteinuria gradually increased after 3 months following KT, and graft biopsy was performed 30 months after KT. Histopathological examination revealed recurrent C3GN. The dosages of triple immunosuppressive maintenance therapy agents were increased. Subsequently, serum C3 levels recovered to normal levels. However, at 33 months following KT, the BK viral load increased and graft function gradually deteriorated; a second graft biopsy was performed at 46 months following KT, which revealed BKVAN and decreased C3GN activity. The dosages of immunosuppressive agents were decreased; subsequently, BKVAN improved and graft function was maintained with normal serum C3 levels at 49 months following KT. This case indicates that C3GN is highly prone to recurrence following KT and that immunosuppressive therapy for C3GN increases the risk of BKVAN.


Assuntos
Glomerulonefrite Membranoproliferativa , Glomerulonefrite , Transplante de Rim , Nefrite Intersticial , Masculino , Humanos , Adulto , Transplante de Rim/efeitos adversos , Glomerulonefrite/etiologia , Imunossupressores/efeitos adversos , Glomerulonefrite Membranoproliferativa/complicações
7.
Medicina (Kaunas) ; 59(5)2023 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-37241223

RESUMO

Monoclonal antibodies directed against immune checkpoint proteins have been widely used to treat various cancers and have resulted in favorable clinical outcomes. Despite these beneficial properties, immune checkpoint inhibitors (ICIs) can induce side effects called immune-related adverse events, including sarcoidosis-like reactions (SLR) across multiple organs. Here, we report a case of renal SLR after ICI treatment, and we review the related literature. A 66-year-old Korean patient with non-small cell lung cancer was referred to the nephrology clinic for renal failure after the 14th pembrolizumab treatment dose. A renal biopsy revealed multiple epithelioid cell granulomas, with several lymphoid aggregates in the renal interstitium and a moderate degree of inflammatory cell infiltration in the tubulointerstitium. A moderate dose of steroid therapy was initiated, and the serum creatinine level partially recovered after four weeks of treatment. Judicious monitoring of renal SLR is, therefore, required during ICI therapy, and a timely diagnosis by renal biopsy and appropriate treatment are important.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Sarcoidose , Humanos , Idoso , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/diagnóstico , Antineoplásicos Imunológicos/efeitos adversos , Sarcoidose/induzido quimicamente , Sarcoidose/tratamento farmacológico , Sarcoidose/patologia
8.
J Korean Med Sci ; 38(12): e89, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-36974398

RESUMO

As the global coronavirus disease 2019 (COVID-19) pandemic continues to sweep across the globe, reports of kidney involvement in adult patients infected with COVID-19 have been documented, and recently, cases in the pediatric population have also been reported. This report highlights the case of an 11-year-old boy who developed acute kidney injury presenting as gross hematuria, proteinuria, and hypertension immediately after a COVID-19 infection. A renal biopsy allowed us to diagnose the patient with post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis. Oral prednisolone and cyclophosphamide treatments were initiated after methylprednisolone pulse therapy administration. Currently, the patient is receiving medical treatment for five weeks, and his renal function is gradually recovering. Previous studies have suggested that, although quite rare, a variety of kidney complications can occur after COVID-19 infection or vaccination, and it is recommended to monitor renal function through evaluation. Herein, we report a pediatric case of post-COVID-19 infection-associated de novo crescentic immune-mediated glomerulonephritis consistent with rapidly progressive glomerulonephritis.


Assuntos
Injúria Renal Aguda , COVID-19 , Glomerulonefrite , Nefrite , Masculino , Adulto , Humanos , Criança , Glomerulonefrite/etiologia , Glomerulonefrite/complicações , COVID-19/complicações , COVID-19/patologia , Rim/patologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/patologia
9.
J Craniofac Surg ; 33(5): e537-e538, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35762626

RESUMO

ABSTRACT: Craniopharyngioma is rare epithelial tumor that develops along the craniopharyngeal duct, and most of these tumors occur in the sellar and suprasellar regions. Although it rarely occurs in the extracranial region, sphenoid solitary lesions were not reported in previous literature. In this study, we report a case of infrasellar craniopharyngioma within the sphenoid sinus without intracranial lesion. A patient with intermittent headache visited a private clinic and presented with sphenoid lesions based on the Magnetic resonance imaging scan results. The mass was completely removed using endoscopic endonasal transsphenoidal approach without any complications and showed characteristic pathologic findings, which lead to the diagnosis of craniopharyngioma.


Assuntos
Craniofaringioma , Neoplasias Hipofisárias , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Osso Esfenoide/patologia , Seio Esfenoidal/diagnóstico por imagem , Seio Esfenoidal/patologia , Seio Esfenoidal/cirurgia
10.
Vaccines (Basel) ; 10(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35214760

RESUMO

Various vaccines against COVID-19 have been developed and proven to be effective, but their side effects, especially on kidney function, are not yet known in detail. In this study, we report the clinical courses and histopathologic findings of new-onset kidney diseases after COVID-19 vaccination as confirmed via kidney biopsy. Five patients aged 42 to 77 years were included in this study, and baseline kidney function was normal in all patients. The biopsy-proven diagnosis indicated newly developed kidney diseases: (1) IgA nephropathy presenting with painless gross hematuria, (2) minimal change disease presenting with nephrotic syndrome, (3) thrombotic microangiopathy, and (4) two cases of acute tubulointerstitial nephritis presenting with acute kidney injury. Individualized treatment was applied as per disease severity and underlying pathology, and the treatment outcomes of all patients were improved. Since this is not a controlled study, the specific pathophysiologic link and causality between the incidence of kidney diseases and COVID-19 vaccination are difficult to confirm. However, clinicians need to consider the possibility that kidney diseases may be provoked by vaccines in patients who have renal symptoms.

11.
Diagnostics (Basel) ; 12(2)2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35204360

RESUMO

Renal allograft biopsy is the gold standard procedure for diagnosis of kidney rejection via specific pathological changes. To provide a better assessment of immunologic events in acute T-cell-mediated rejection (acute TCMR) and BK virus-associated nephropathy (BKVAN) cases, we used multiplex immunofluorescence staining to identify infiltrating mononuclear cell subsets in the cortex area of transplanted kidneys. Antibodies to CD4, CD8, CD20, CD68, Foxp3, and cytokeratin were used. In cortical interstitium, CD8+ cells were significantly more prevalent in acute TCMR than BKVAN cases (34% vs. 22.8%, p = 0.034). In medulla, CD20+ cells were significantly more prevalent in BKVAN than acute TCMR cases (51.9% vs. 11.3%, p = 0.028).

12.
J Korean Med Sci ; 36(30): e218, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34342187

RESUMO

Various coronavirus disease 2019 (COVID-19) vaccines are being developed, which show practical preventive effects. Here, we report a 51-year-old healthy man with nephrotic syndrome secondary to minimal change disease (MCD) after Ad26.COV.2 (Janssen) vaccination. He had no comorbid disease and received Ad26.COV.2 on April 13, 2021. Seven days after vaccination, he developed edema and foamy urine. Edema rapidly aggravated with decreased urine volume. He was admitted to the hospital 28 days after vaccination, and his body weight increased by 21 kg after vaccination. His serum creatinine level was 1.54 mg/dL, and 24-h urinary protein excretion was 8.6 g/day. Kidney biopsy revealed no abnormality in the glomeruli and interstitium of the cortex and medulla under the light microscope. Electron microscopy revealed diffuse effacement of the podocyte foot processes, thus, he was diagnosed with MCD. High-dose steroid therapy was applied, and his kidney function improved three days after steroid therapy. Three weeks after steroid use, his serum creatinine decreased to 0.95 mg/dL, and spot urine protein-to-creatine decreased to 0.2 g/g. This case highlights the risk of new-onset nephrotic syndrome secondary to MCD after vectored COVID-19 vaccination. Although the pathogenesis is uncertain, clinicians need to be careful about adverse renal effects of COVID-19 vaccines.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Síndrome Nefrótica/etiologia , SARS-CoV-2/imunologia , Vacinação/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/etiologia
13.
J Pathol Transl Med ; 55(3): 225-229, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33677954

RESUMO

We present a rare case of spindle cell oncocytoma (SCO) of the sella turcica with malignant histologic features and rapid progression. A 42-year-old woman experienced bilateral blurred vision and was preoperatively misdiagnosed as having a pituitary macroadenoma on magnetic resonance imaging. After surgery, SCO was diagnosed by the histopathologic features of interlacing fascicles of spindle tumor cells with finely granular, eosinophilic cytoplasm. Focal anaplastic changes and necrosis were present. Immunohistochemically, the tumor cells were positive for vimentin, epithelial membrane antigen, S-100, galectin-3, and thyroid transcription factor 1. Four months later, the tumor had progressed, and second surgery with adjuvant radiotherapy was performed; the patients remains under observation. In this report, we proposed distinctive radiologic features for differential diagnosis between SCO and other pituitary tumors.

14.
Diagnostics (Basel) ; 10(5)2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-32370297

RESUMO

Indolamine-2,3-dioxygenase (IDO) is an intracellular enzyme that catalyzes amino acid tryptophan to L-kynurenine. IDO is overexpressed in various cancers and several IDO inhibitors have been assessed in multiple clinical trials. If an IDO inhibitor is to be commercialized, IDO immunohistochemistry will be an important method. In this study, 80% (28/35) of mature T- and natural killer (NK)-cell neoplasms showed positivity for IDO protein (score 1: five, score 2: one, score 3: seven, score 4: fifteen). In addition, 29.9% (23/77) of mature B-cell lymphomas showed positivity for IDO protein (score 1: three, score 2: tewelve, score 3: four, score 4: four). In mature B-cell lymphomas, 95.7% (22/23) of IDO positive cases were diffuse B-cell lymphomas. Our study includes various types of lymphoma that were previously unreported and shows various patterns of IDO stain according to the type. When the results are accumulated, IDO immunohistochemistry will be a useful tool to diagnose lymphomas and to predict their prognosis.

15.
Artigo em Inglês | MEDLINE | ID: mdl-32155755

RESUMO

(1) Background: Cervical cancer is one of the most common cancers in Korean women. This study was performed to discover the utility of HPV (Human Papillomavirus) testing in screening of cervical lesions and to provide the prevalence of HPV and the genotype distribution in a single center of Korea. (2) Methods: A total of 15,141 women who underwent both HPV testing and cervical cytology were enrolled in this retrospective medical record review study. (3) Results: HPV testing showed higher sensitivity than cytology for the detection of histological high-grade squamous lesions. Furthermore, the sensitivity and specificity of HPV testing varied depending on the method used. The BD Onclarity™ HPV assay had higher sensitivity (90%) than the MyHPV CHIP™ kit (all types of HPV: 82%; high-risk HPV: 76%) for high-grade squamous lesions. A combination of MyHPV CHIP™ and cytology detected 90.9% (30/33) of histological high-grade squamous lesions. A combination of BD Onclarity™ HPV assay and cytology detected 96.55% (84/87) of histological high-grade squamous lesions. In addition, HPV prevalence and genotype distribution were different depending on the HPV testing method used. (4) Conclusion: HPV testing showed higher sensitivity than cytology, but the sensitivity and specificity of HPV testing had variation depending on the method used.


Assuntos
Papillomaviridae , Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Adulto , Idoso , Detecção Precoce de Câncer , Feminino , Humanos , Programas de Rastreamento , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/diagnóstico , República da Coreia , Estudos Retrospectivos , Displasia do Colo do Útero/diagnóstico , Displasia do Colo do Útero/virologia
16.
Brain Tumor Res Treat ; 7(1): 39-43, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31062530

RESUMO

Meningeal dissemination (MDS) of glioblastoma is rare, although its incidence might have been underestimated. MDS of glioblastoma has a fatal course. Thus, rapid and precise diagnosis of MDS is important for further palliative treatment. Unfortunately, MDS of glioblastoma could be diagnosed at a delayed time, causing failure to treat patient optimally. Herein, we present a case of a 56-year-old male with MDS of glioblastoma mimicking chronic subdural hemorrhage (CSDH) after head trauma due to slip down. During treatment for CSDH, MDS of glioblastoma was not controlled appropriately. The patient succumbed to MDS of glioblastoma at 9 weeks after the date of diagnosis of CSDH which could be an MDS.

17.
Int J Clin Exp Pathol ; 12(3): 978-986, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31933908

RESUMO

Heat shock protein 90 (HSP90), a molecular chaperone, plays critical roles in cellular protection against various stressful stimuli and in the regulation of cellular growth and apoptosis. HSP90 has four human isoforms; HSP90α, HSP90ß, glucose related protein 94 (GRP94), and tumor necrosis factor (TNF) receptor-associated protein 1 (TRAP1). We evaluated the differential expression of these HSP90 isoforms in colorectal cancer (CRC) and correlated their expression levels with clinicopathological factors and patient survival rates. We performed immunohistochemical staining for HSP90α, HSP90ß, GRP94, and TRAP1 in 129 CRC tumor samples and found that HSP90α expression was significantly associated with advanced pT stage (P = 0.011) and shorter recurrence-free survival (RFS) (P = 0.010), whereas GRP94 expression was correlated with low grade (P = 0.029) and better RFS (P < 0.001). HSP90ß and TRAP1 had no prognostic impact, although HSP90ß expression was positively correlated with tumor size (P = 0.008). Based on our results, HSP90α and GRP94 are potential prognostic biomarkers of CRC. In addition, the differences in expression and functional activities among four HSP90 isoforms imply that isoform selectivity should be seriously considered when HSP90 inhibitors are studied or adopted for the treatment of CRC.

18.
J Med Case Rep ; 12(1): 241, 2018 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-30126443

RESUMO

BACKGROUND: Amyloidosis is a very rare disease that is difficult to diagnose because of the unspecific early clinical manifestations of the disease. Accurate and early diagnosis is extremely important because the effect of treatment is dependent on the extent of disease progression. Sicca syndrome and nail dystrophy are very rare symptoms of amyloidosis. We report here a case of sicca syndrome and nail dystrophy with renal dysfunction in a 52-year-old Korean woman who was diagnosed as having systemic amyloidosis. CASE PRESENTATION: We present the case of a 52-year-old Korean woman complaining of dry mouth and nail dystrophy for 4 months as an initial symptom. A slit lamp examination revealed superficial keratoconjunctival erosion in both eyes. A laboratory test showed anemia, azotemia, and proteinuria. Urine protein electrophoresis showed increased gamma globulin excretion. Serum free light chain of kappa and lambda were increased. Histopathological studies of biopsy specimens of minor salivary glands and kidney revealed deposits of amyloid fibrils. A bone marrow aspiration biopsy showed hypercellular marrow with 5% plasma cells. She was diagnosed as having primary systemic amyloidosis then started on chemotherapy. CONCLUSION: Such atypical mucocutaneous manifestations of amyloidosis can serve as important early diagnostic signs with less invasive biopsy confirmation in patients with systemic amyloidosis.


Assuntos
Amiloidose/patologia , Nefropatias/patologia , Rim/patologia , Lábio/patologia , Dermatopatias/patologia , Amiloide/imunologia , Amiloidose/imunologia , Biópsia , Feminino , Humanos , Rim/imunologia , Nefropatias/imunologia , Masculino , Pessoa de Meia-Idade , Dermatopatias/imunologia
19.
Pathol Res Pract ; 214(3): 350-355, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29496312

RESUMO

MicroRNA-200c (miR-200c) is known to play a pivotal role in the regulation of epithelial-to-mesenchymal and mesenchymal-to-epithelial transition processes. However, the biological function of miR-200c in human carcinogenesis remains controversial. We examined the association of miR-200c expression with various clinicopathological factors, including KRAS mutation status and survival, in patients with colorectal cancer (CRC). The expression level of miR-200c was evaluated in 109 paired CRC and normal tissue samples using quantitative reverse transcription polymerase chain reaction. The KRAS mutation status of the CRC samples was determined using the PNAClamp™ KRAS Mutation Detection kit. Compared with the normal tissue group, miR-200c expression was significantly upregulated in the CRCs (P < .001). The expression of miR-200c was increased in CRCs with higher grade (P = .009), advanced stage (P = .042), and lymphovascular invasion (P = .003). Thirty-one CRCs (28.4%) had KRAS mutations in codon 12 or 13. CRCs with KRAS mutations had significantly higher miR-200c expression than CRCs with wild-type KRAS (P = .003). In survival analysis, high miR-200c expression was correlated with worse overall survival (P = .017) and recurrence-free survival (P = .048). Our results indicate that miR-200c is involved in tumor progression and aggressiveness in CRCs, and this oncogenic role of miR-200c may be triggered by activation of the KRAS signaling pathway.


Assuntos
Carcinogênese/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , Biomarcadores Tumorais/análise , Neoplasias do Colo/genética , Neoplasias Colorretais/patologia , Humanos , Mutação/genética
20.
Int J Clin Exp Pathol ; 11(3): 1554-1561, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31938253

RESUMO

The proteins p110α and p110ß are isoforms of the catalytic subunit of class I phosphoinositide 3-kinases (PI3Ks). Class I PI3Ks are involved in the regulation of cell survival, growth, proliferation, and migration, and their aberrant activation contributes to the oncogenesis of various human cancers. In this study, we assessed expression of p110α and p110ß in non-small cell lung cancer (NSCLC) and their association with clinicopathological factors and patient survival. Seventy-six NSCLC cases were analyzed by immunohistochemical staining for p110α and p110ß. Of the 76 tumors, 18 (23.7%) and 43 (56.6%) were classified in the high p110α and p110ß expression groups, respectively. Expression of p110α was higher in smokers compared with non-smokers (P = 0.042). No other clinicopathological factors showed significant association with p110α or p110ß expression. In univariate and multivariate survival analyses, high p110ß expression was associated with worse overall survival (OS) in stage I NSCLCs (P < 0.001), whereas the high p110α expression group had shorter OS in stage II to IV NSCLCs (P = 0.005). Our results suggest that p110α and p110ß play different roles depending on tumor stage, and that both p110α and p110ß have potential as independent prognostic biomarkers of NSCLC.

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