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1.
Oncol Lett ; 28(3): 445, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39099584

RESUMEN

Microsatellite instability (MSI) status is a prognostic biomarker for immunotherapy in certain types of cancers, such as colorectal cancers (CRCs) and endometrial cancers (ECs). Tumors that are categorized as having high MSI (MSI-H) express high levels of neoantigens for immune recognition. The typical MSI test measures the length of short mononucleotide repeats (SMR) poly(A) 21-27; however, a limitation of this test is the difficulty in determining the shift size, particularly in endometrial cancer. To investigate an MSI detection assay with improved performance, the present study analyzed the use of poly(A) 40-44 mononucleotide repeats to detect the MSI status of 100 patients with either CRC (n=50) or EC (n=50). Capillary electrophoresis was used to evaluate five long mononucleotide repeat (LMR) markers, including poly(A) 40-A, 40-B, 40-C, 40-D and 44. The concordance rate of the LMR-MSI assay compared with an immunohistochemistry MSI detection assay was 96.0 and 95.1% for CRCs and ECs respectively, with the detection limit of the LMR-MSI assay demonstrated to be 2.5% MSI-H in HCT116 colorectal carcinoma cell lines. The LMR-MSI assay yielded a 95.1% concordance rate in ECs compared with that in the SMR-MSI test (87.8%). The LMR-MSI test identified a significantly higher mean shift size (13 bp) in MSI-H tumors compared with the SMR-MSI test (10 bp), in both EC and CRC tissue samples. Together, the present study suggested that the LMR-MSI test could potentially be a sensitive and practical technology for molecular laboratory testing, particularly in the use of immunotherapy for patients with CRCs and ECs.

2.
Oncol Rep ; 51(3)2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38240107

RESUMEN

Various types of human cancer may develop aberrant trophoblastic differentiation, including histological changes and altered expression of ß­human chorionic gonadotropin (ß­hCG). Aberrant trophoblastic differentiation in epithelial cancer is usually associated with poor differentiation, tumor metastasis, unfavorable prognosis and treatment resistance. Since ß­hCG­targeting vaccines have failed in an early phase II trial, it is crucial to obtain a better understanding of the molecular pathogenesis of trophoblastic differentiation in human cancer. The present review summarizes the clinical and translational research on this topic with the aim of accelerating the development of an effective targeted therapy. Ectopic expression of ß­hCG promotes proliferation, migration, invasion, vasculogenesis and epithelial­mesenchymal transition (EMT) in vitro, and enhances metastatic and tumorigenic capabilities in vivo. Signaling cascades modulated by ß­hCG include the TGF­ß receptor pathway, EMT­related pathways, the c­MET receptor tyrosine kinase and mitogen­activated protein kinase/ERK pathways, and the SMAD2/4 pathway. Taken together, these findings indicated that TGF­ß receptors, c­MET and ERK1/2 are potential therapeutic targets. Nevertheless, further investigation on the molecular basis of aberrant trophoblastic differentiation is mandatory to improve the design of precision therapy for this aggressive type of human cancer.


Asunto(s)
Gonadotropina Coriónica Humana de Subunidad beta , Neoplasias , Humanos , Transducción de Señal , Pronóstico , Sistema de Señalización de MAP Quinasas , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Transición Epitelial-Mesenquimal , Movimiento Celular , Línea Celular Tumoral
3.
Oncol Lett ; 26(6): 539, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38020305

RESUMEN

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line regimen for the treatment of non-small cell lung cancer (NSCLC) patients with EGFR mutations. However, false-negative results are occasionally observed, even with FDA-approved molecular tests. Such examples in have been reported in our pilot study showing a slightly upward-shifted amplification curve using commercial reverse transcription-quantitative (RT-q)PCR. Verification using peptide nucleic acid (PNA) clamping-sequencing, which has a sensitivity of ~0.1%, may allow better prediction of which patients will benefit from EGFR-TKI therapy. To confirm this hypothesis, samples were prospectively collected from 1,783 lung cancer cases diagnosed in National Cheng Kung University Hospital between 2012-2018. An independent lung cancer cohort of 1,944 cases was also recruited from other hospitals. The clinical significance of mutant-enriched PCR with PNA-sequencing was analyzed and patient outcomes were followed. A total of 17 of 34 cases (50%) were found to harbor EGFR mutations by PNA-sequencing. A total of 22 cases were discovered in the independent lung cancer cohort, and 14 of these (63.6%) cases had EGFR mutations. TKIs were administered to 14 of the 17 mutation-positive patients, and a partial response was observed in 4 cases and stable disease in 10 cases. Patients with EGFR mutations receiving a TKI regimen had a longer overall survival (OS) (median: 40.0 vs. 10.0 months) compared with those without treatment. The difference in OS was not significant. Based on the results of the present study, combining RT-qPCR with PNA-sequencing may be a practical supplementary technology in a clinical molecular laboratory for a subset of lung cancer patients in selection of EGFR TKI therapy.

4.
Cell Commun Signal ; 21(1): 172, 2023 07 10.
Artículo en Inglés | MEDLINE | ID: mdl-37430297

RESUMEN

BACKGROUND: Protein phosphatase 2A (PP2A) is one of the major protein phosphatases in eukaryotic cells and is essential for cellular homeostasis. PP2A is a heterotrimer comprising the dimeric AC core enzyme and a highly variable regulatory B subunit. Distinct B subunits help the core enzyme gain full activity toward specific substrates and contribute to diverse cellular roles of PP2A. PP2A has been thought to play a tumor suppressor and the B56γ3 regulatory subunit was shown to play a key tumor suppressor regulatory subunit of PP2A. Nevertheless, we uncovered a molecular mechanism of how B56γ3 may act as an oncogene in colorectal cancer (CRC). METHODS: Polyclonal pools of CRC cells with stable B56γ3 overexpression or knockdown were generated by retroviral or lentiviral infection and subsequent drug selection. Co-immunoprecipitation(co-IP) and in vitro pull-down analysis were applied to analyze the protein-protein interaction. Transwell migration and invasion assays were applied to investigate the role of B56γ3 in affecting motility and invasive capability of CRC cells. The sensitivity of CRC cells to 5-fluorouracil (5-FU) was analyzed using the PrestoBlue reagent assay for cell viability. Immunohistochemistry (IHC) was applied to investigate the expression levels of phospho-AKT and B56γ3 in paired tumor and normal tissue specimens of CRC. DataSets of TCGA and GEO were analyzed to investigate the correlation of B56γ3 expression with overall survival rates of CRC patients. RESULTS: We showed that B56γ3 promoted epithelial-mesenchymal transition (EMT) and reduced the sensitivity of CRC cells to 5-FU through upregulating AKT activity. Mechanistically, B56γ3 upregulates AKT activity by targeting PP2A to attenuate the p70S6K-mediated negative feedback loop regulation on PI3K/AKT activation. B56γ3 was highly expressed and positively correlated with the level of phospho-AKT in tumor tissues of CRC. Moreover, high B56γ3 expression is associated with poor prognosis of a subset of patients with CRC. CONCLUSIONS: Our finding reveals that the B56γ3 regulatory subunit-containing PP2A plays an oncogenic role in CRC cells by sustaining AKT activation through suppressing p70S6K activity and suggests that the interaction between B56γ3 and p70S6K may serve as a therapeutic target for CRC. Video Abstract.


Asunto(s)
Neoplasias Colorrectales , Transición Epitelial-Mesenquimal , Humanos , Proteína Fosfatasa 2 , Proteínas Proto-Oncogénicas c-akt , Retroalimentación , Proteínas Quinasas S6 Ribosómicas 70-kDa , Fosfatidilinositol 3-Quinasas , Fluorouracilo
5.
Clin Genitourin Cancer ; 21(4): 508.e1-508.e10, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37183125

RESUMEN

Introduction/Background To determine the clinical significance of micropapillary urothelial carcinoma (MPUC) of the upper urinary tract (UTUC) and a potential therapeutic strategy. Patients and Methods A retrospective cohort study was conducted to examine the incidence of micropapillary UTUC from 2010 to 2018 and its clinicopathological characteristics. Clinical outcomes and cancer-specific survival (CSS) were compared between MPUC and conventional UTUC matched by stage within a 6-month variation of receiving surgery. Results A total of 24 MPUC cases were identified out of 901 cases (2.7%) of urothelial carcinoma (UC) of the renal pelvis and ureter. MPUC was significantly smaller (<3 cm) and associated with nodal metastasis compared with conventional UTUC (P = .017 & 0.021, respectively); however, no significant difference was observed for lymphovascular invasion, distant metastasis, or CSS (P > 0.50, respectively) compared with match controls. Six MPUC patients (25%) developed metastasis to the liver, lymph nodes, and lung during follow-up. Patients with HER2-positive MPUC (3 of 4) had a significantly higher risk of metastasis compared with HER2-negative MPUC (3 of 20; P = 0.035). Conclusions MPUC is an aggressive variant of UTUC and usually presents as a small locally advanced disease. HER2 immunohistochemistry may identify the subset of patients with micropapillary UTUC that are candidates for targeted therapy.


Asunto(s)
Terapia Molecular Dirigida , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/fisiopatología , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/tratamiento farmacológico , Carcinoma Papilar/fisiopatología , Genes erbB-2/genética , Estudios de Casos y Controles , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Regulación Neoplásica de la Expresión Génica , Invasividad Neoplásica/genética , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo
6.
PLoS One ; 18(4): e0284227, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37098015

RESUMEN

Microsatellite instability (MSI) is the primary predictive biomarker for therapeutic efficacies of cancer immunotherapies. Establishment of the MSI detection methods with high sensitivity and accessibility is important. Because MSI is mainly caused by defects in DNA mismatch repair (MMR), immunohistochemical (IHC) staining for the MMR proteins has been widely employed to predict the responses to immunotherapies. Thus, due to the high sensitivity of PCR, the MSI-PCR analysis has also been recommended as the primary approach as MMR IHC. This study aimed to develop a sensitive and convenient platform for daily MSI-PCR services. The routine workflow used a non-labeling QIAxcel capillary electrophoresis system which did not need the fluorescence labeling of the DNA products or usage of a multi-color fluorescence reader. Furthermore, the 15 and 1000 bp size alignment markers were used to precisely detect the size of the DNA product. A cohort of 336 CRC cases was examined by MSI-PCR on the five mononucleotide MSI markers recommended by ESMO. The PCR products were analyzed in the screening gels, followed by high-resolution gel electrophoresis for confirmation if needed. In the MSI-PCR tests, 90.1% (303/336) cases showed clear major shift patterns in the screening gels, and only 33 cases had to be re-examined using the high-resolution gels. The cohort was also analyzed by MMR IHC is, which revealed 98.5% (331/336) concordance with MSI-PCR. In the five discordant cases, 4 (3 MSI-L and 1 MSS) showed MSH6 loss. Besides, one case exhibited MSI-H but no loss in the MMR IHC. Further NGS analysis, in this case, found that missense and frameshift mutations in the PMS2 and MSH6 genes occurred, respectively. In conclusion, the non-labeling MSI-PCR capillary electrophoresis revealed high concordance with the MMR IHC analysis and is cost- and time-effective. Therefore, it shall be highly applicable in clinical laboratories.


Asunto(s)
Neoplasias Colorrectales , Inestabilidad de Microsatélites , Humanos , Reparación de la Incompatibilidad de ADN/genética , Flujo de Trabajo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Repeticiones de Microsatélite/genética , Proteínas de Unión al ADN/genética , Electroforesis Capilar , Homólogo 1 de la Proteína MutL/genética
7.
Mol Carcinog ; 62(7): 951-962, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37014154

RESUMEN

Sprouty2 (SPRY2) is known to inhibit the RAS/MAPK/ERK pathway, and is a potential study target for cancer. The effect of SPRY2 in colorectal cancer (CRC) and whether it is influenced by KRAS mutation are not known. We manipulated SPRY2 gene expression and used an activating KRAS-mutant plasmid to determine its effect on CRC cell function in vitro and/or in vivo. We performed SPRY2 immunohistochemical staining in 143 CRC specimens and analyzed the staining results with various clinicopathological characteristics in relation to KRAS mutation status. SPRY2 knockdown in Caco-2 cells carrying the wild-type (WT) KRAS gene upregulated phosphorylated ERK (p-ERK) levels and increased cell proliferation in vitro, but inhibited cell invasion. However, SPRY2 knockdown in SW480 cells (activating KRAS mutant) or Caco-2 cells transfected with KRAS-mutant plasmid did not significantly alter p-ERK levels, cell proliferation, or invasion. The xenografts of SPRY2-knockdown Caco-2 cells were larger with less deep muscle invasion than those of control cells. The clinical cohort study revealed a positive association of SPRY2 protein expression with pT status, lymphovascular invasion, and perineural invasion in KRAS-WT CRCs. However, the associations were not observed in KRAS-mutant CRCs. Interestingly, high SPRY2 expression was related to shorter cancer-specific survival in both KRAS-WT and KRAS-mutant CRC patients. Our study demonstrated the dual role of SPRY2 as an inhibitor of RAS/ERK-driven proliferation and as a promoter of cancer invasion in KRAS-WT CRC. SPRY2 may promote the invasion and progression of KRAS-WT CRC, and might also enhance KRAS-mutant CRC progression through pathways other than invasion.


Asunto(s)
Neoplasias Colorrectales , Proteínas Proto-Oncogénicas p21(ras) , Humanos , Células CACO-2 , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Línea Celular Tumoral , Estudios de Cohortes , Neoplasias Colorrectales/patología , Proliferación Celular , Mutación , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Péptidos y Proteínas de Señalización Intracelular/genética , Péptidos y Proteínas de Señalización Intracelular/metabolismo
8.
Front Oncol ; 12: 1014132, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36568146

RESUMEN

Clonality assessment, which can detect neoplastic T cells by identifying the uniquely recombined T-cell receptor (TCR) genes, provides important support in the diagnosis of T-cell lymphoma (TCL). BIOMED-2 is the gold standard clonality assay and has proven to be effective in European TCL patients. However, we failed to prove its sensitivity in Taiwanese TCL patients, especially based on the TCRß gene. To explore potential impact of genetic background in the BIOMED-2 test, we analyzed TCRß sequences of 21 healthy individuals and two TCL patients. This analysis suggests that genetic variations in the BIOMED-2 primer sites could not explain the difference in sensitivity. The BIOMED-2 test results of the two TCL patients were positive and negative, respectively. Interestingly, a higher percentage (>81%) of non-recombined TCRß sequences was observed in the test-negative patient than those of the test-positive patient and all healthy individuals (13~66%). The result suggests a new TCR target for enhancing TCL diagnosis. To further explore the hypothesis, we proposed a cost-effective digital PCR assay that quantifies the relative abundance of non-recombined TCRß sequences containing a J2-2P~J2-3 segment. With the digital PCR assay, bone marrow specimens from TCL patients (n=9) showed a positive outcome (i.e., the relative abundance of the J2-2P~J2-3 sequences ≧5%), whereas non-TCL patients (n=6) gave a negative result. As five of nine TCL patients had a negative BIOMED-2 test result, the J2-2P~J2-3 sequences may improve TCL detection. This is the first report showing the capability of characterizing non-recombined TCR sequences as a supplementary strategy for the BIOMED-2 clonality test.

9.
Artif Intell Med ; 125: 102244, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35241257

RESUMEN

The detection of the most common type of liver tumor, that is, hepatocellular carcinoma (HCC), is one essential step to liver pathology image analysis. In liver tissue, common cell change phenomena such as apoptosis, necrosis, and steatosis are similar in tumor and benign tissue. Hence, the detection of HCC may fail when the patches covered only limited tissue region without enough neighboring cell structure information. To address this problem, a Feature Aligned Multi-Scale Convolutional Network (FA-MSCN) architecture is proposed in this paper for automatic liver tumor detection based on whole slide images (WSI). The proposed network integrates the features obtained at different magnification levels to improve the detection performance by referencing more neighboring information. The FA-MSCN consists of two parallel convolutional networks in which one would extract high-resolution features and the other would extract low-resolution features by atrous convolution. The low-resolution features then go through central cropping, upsampling, and concatenation with high-resolution features for final classification. The experimental results demonstrated that Multi-Scale Convolutional Network (MSCN) improves the detection performance compared to Single-Scale Convolutional Network (SSCN), and that the FA-MSCN is superior to both SSCN and MSCN, demonstrating on HCC detection.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico , Humanos , Procesamiento de Imagen Asistido por Computador , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Redes Neurales de la Computación
10.
Transplant Proc ; 54(6): 1575-1578, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-34702598

RESUMEN

We report a case of a heart transplant recipient who presented with a rapidly growing Epstein-Barr virus (EBV)-positive, diffuse large B-cell lymphoma 7 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Because of the atypical radiologic presentation, the initial tentative diagnosis was a mediastinal abscess. This observation indicates a potential risk of EBV reactivation after coronavirus disease 2019 (COVID-19) vaccination, which might lead to or aggravate the presentation of posttransplant lymphoproliferative disorder in transplantation patients. Transplant surgeons should be aware of the potential immunomodulatory effects of the COVID-19 vaccination.


Asunto(s)
COVID-19 , ChAdOx1 nCoV-19 , Infecciones por Virus de Epstein-Barr , Trasplante de Corazón , Trastornos Linfoproliferativos , Humanos , ChAdOx1 nCoV-19/efectos adversos , COVID-19/prevención & control , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/diagnóstico , Herpesvirus Humano 4 , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/diagnóstico
11.
Int J Mol Sci ; 22(20)2021 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-34681622

RESUMEN

Phosphatidylinositol 3-kinase catalytic subunit type 3 (PIK3C3), the mammalian ortholog of yeast vesicular protein sorting 34 (Vps34), belongs to the phosphoinositide 3-kinase (PI3K) family. PIK3C3 can phosphorylate phosphatidylinositol (PtdIns) to generate phosphatidylinositol 3-phosphate (PI3P), a phospholipid central to autophagy. Inhibition of PIK3C3 successfully inhibits autophagy. Autophagy maintains cell survival when modifications occur in the cellular environment and helps tumor cells resist metabolic stress and cancer treatment. In addition, PIK3C3 could induce oncogenic transformation and enhance tumor cell proliferation, growth, and invasion through mechanisms independent of autophagy. This review addresses the structural and functional features, tissue distribution, and expression pattern of PIK3C3 in a variety of human tumors and highlights the underlying mechanisms involved in carcinogenesis. The implications in cancer biology, patient prognosis prediction, and cancer therapy are discussed. Altogether, the discovery of pharmacological inhibitors of PIK3C3 could reveal novel strategies for improving treatment outcomes for PIK3C3-mediated human diseases.


Asunto(s)
Fosfatidilinositol 3-Quinasas Clase III/metabolismo , Neoplasias/patología , Autofagia , Proliferación Celular , Fosfatidilinositol 3-Quinasas Clase III/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasas Clase III/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias/metabolismo , Células Madre Neoplásicas/citología , Células Madre Neoplásicas/metabolismo , Dominios Proteicos
12.
PLoS One ; 16(9): e0257152, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34559836

RESUMEN

Approximately 5-7% of non-small cell lung cancer (NSCLC) cases harbor an anaplastic lymphoma kinase (ALK) fusion gene and may benefit from ALK inhibitor therapy. To detect ALK fusion genes, we developed a novel test using reverse transcription polymerase chain reaction (RT-PCR) for the ALK kinase domain (KD). Since ALK expression is mostly silenced in the adult with the exception of neuronal tissue, the normal lung tissue, mesothelial lining, and inflammatory cells are devoid of ALK transcript, making ALK KD RT-PCR an ideal surrogate test for ALK fusion transcripts in lung or pleural effusion. The test was designed with a short PCR product (197 bp) to work for both malignant pleural effusion (MPE) and formalin-fixed, paraffin-embedded (FFPE) NSCLC samples. Using ALK IHC as a reference, the sensitivity of the test was 100% for both MPE and FFPE. The specificity was 97.6% for MPE and 97.4% for FFPE. Two false positive cases were found. One was a metastatic brain lesion which should be avoided in the future due to intrinsic ALK expression in the neuronal tissue. The other one resulted from ALK gene amplification. Due to potential false positivity, subsequent confirmation tests such as fluorescence in situ hybridization or multiplex PCR would be preferable. Nevertheless, the test is simple and inexpensive with no false negativity, making it a desirable screening test. It also offers an advantage over multiplex RT-PCR with the capability to detect novel ALK fusions. Indeed through the screening test, we found a novel ALK fusion partner (sperm antigen with calponin homology and coiled-coil domains 1 like gene, SPECC1L) with increased sensitivity to crizotinib in vitro. In summary, a novel RNA-based ALK KD analysis was developed for ALK rearrangement screening in MPE and FFPE specimens of NSCLC. This simple inexpensive test can be implemented as routine diagnostics.


Asunto(s)
Quinasa de Linfoma Anaplásico/genética , Carcinoma de Pulmón de Células no Pequeñas/enzimología , Carcinoma de Pulmón de Células no Pequeñas/genética , Detección Precoz del Cáncer , Reordenamiento Génico , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/genética , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Proteínas de Ciclo Celular/genética , Proliferación Celular/efectos de los fármacos , Estudios de Cohortes , Crizotinib/farmacología , Crizotinib/uso terapéutico , ADN de Neoplasias/genética , Receptores ErbB/genética , Femenino , Formaldehído , Células HEK293 , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Proteínas Asociadas a Microtúbulos/genética , Persona de Mediana Edad , Adhesión en Parafina , Derrame Pleural Maligno/enzimología , Derrame Pleural Maligno/genética , Serina Endopeptidasas/genética , Fijación del Tejido
13.
J Med Ultrasound ; 29(2): 123-125, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34377645

RESUMEN

Schwannomas, namely neurilemmomas, are benign nerve sheath tumors and comprise the myelin sheaths around the peripheral nerves. Schwannomas commonly occur in the head and neck, or extremities, less found in the mediastinum and retroperitoneum, and rarely in the pelvis. We report a 40-year-old male presenting with an 18-month history of nocturia and urinary frequency. Transrectal ultrasound revealed a well-defined, 2.81 cm × 3.77 cm in size, homogeneous, hypoechoic mass in the tail of the left seminal vesicle, compatible with the finding of a well-demarcated mass at the left seminal vesicle with homogeneous contrast enhancement on computed tomography. He underwent laparoscopic excision of the mass via da Vinci robotic surgical system. Intraoperative sonography showed that the mass exhibited the majority of hypoechoic density with some hyperechoic spots inside. Pathology reveals schwannoma. Both of erectile and ejaculatory functions were claimed postoperatively. Our case report highlights the potential of either intraoperative or preoperative sonography in the assessment of the seminal vesicle schwannoma.

14.
Transl Oncol ; 14(10): 101175, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34243015

RESUMEN

BACKGROUND: Renal cell carcinoma with rhabdoid features (RCC-RF) is an aggressive histologic variant in the adults and is usually unresponsive to standard chemotherapy. METHODS: Expression of SMARCB1/INI1 was examined in primary RCC-RF (n = 5). Stable INI1 with/without prostaglandin E2 receptor 1 (EP1) knockdown cell lines were created in the ACHN and 786-O RCC cell lines and measured for epidermal growth factor receptor (EGFR)-related signaling pathways. Chemosensitivity to targeted drugs in vitro was tested after knocking down of INI1 in both cell lines. The outcome of co-targeting of INI1 and EP1 in RCC was examined using a tumorigenicity assay. RESULTS: Expression of INI1 was markedly reduced at both transcriptional and translational levels in primary RCC-RF. Immunohistochemical expression of INI1 protein was lost in the nuclei of rhabdoid cells compared with conventional RCC (n = 8). Using two cell lines with different genetic background, we showed that knocking down of INI1 activates the EGFR signaling with up-regulated AKT and ERK pathways and sensitizes cancer cells to Erlotinib treatment in vitro. However, cell-line dependent effects were also demonstrated with reference to impact of INI1 or EP1 on cell growth, migration and response to Gefitinib or Everolimus treatment in vitro. CONCLUSION: Inactivation of INI1 may play a role in the pathogenesis of RCC-RF. Erlotinib is recommended in the management of patients with INI1-related RCC.

15.
Urol Oncol ; 39(10): 732.e17-732.e23, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-33773916

RESUMEN

PURPOSE: To investigate the clinical implications of identifying urothelial carcinoma (UC) with trophoblastic differentiation (UCTD). MATERIALS AND METHODS: A prospective cohort study was performed from 2010 to 2016 to examine the incidence of UCTD in urinary tract cancer and association with clinicopathological indicators and patient outcome. RESULTS: UCTD was detected in 47 of 859 (5.5%) cases of UC of the bladder and 65 of 635 (10.2%) cases in the upper urinary tract. UCTD of the bladder was significantly associated with non-papillary, multiple, larger size ( > 3 cm), muscle invasion, and nodal metastasis (P ≤ 0.0001, respectively). A higher risk of recurrence (P = 0.005), progression (P < 0.0001), and patient death (P < 0.0001) was observed for UCTD than those with traditional, high-grade UC of the bladder. Among four patterns of expression, focal expression of ß-human chorionic gonadotropin was frequently detected in papillary tumor (P < 0.005) and UCs of smaller than 3 cm (P = 0.03). Significant indicators in predicting poor disease-specific overall survival in multivariate statistical model were tumor staging (P = 0.001), followed by non-focal ß-hCG expression (P = 0.049). CONCLUSION: UCTD is more often identified in the upper urinary tract than in the bladder. UCTD of the bladder was significantly associated with higher risk of recurrence, progression, and patient death. Expression of ß-hCG in non-focal patterns predicts a worse prognosis for patients with UCTD and deserves an individualized treatment planning.


Asunto(s)
Inmunohistoquímica/métodos , Neoplasias Trofoblásticas/patología , Neoplasias de la Vejiga Urinaria/patología , Anciano , Diferenciación Celular , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos
16.
Pathol Res Pract ; 217: 153288, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33276219

RESUMEN

Microsatellite instability (MSI) is reflective of a deficient mismatch repair (dMMR) system, which is mostly associated with the methylation of mismatch repair (MMR) genes and BRAF mutations in sporadic colorectal cancers (CRCs). We performed a retrospective study to analyze the clinicopathological features of dMMR CRCs and their association with the BRAF V600E mutation. The incidence of dMMR CRCs in our cohort was 7.4 % (118/1603). Immunohistochemistry (IHC) revealed four common dMMR IHC patterns in 116 dMMR CRCs from 110 patients. dMMR type 1 (MLH1-/PMS2-) CRCs were the most frequent pattern, usually showing typical proximal location and MSI histology. The BRAF V600E mutation was almost exclusively observed in dMMR type 1 (32 of 72) and dMMR type 2 (PMS- only, 7 of 18) CRCs (p = 0.001). Patients with dMMR type 3 (MSH2-/MSH6-) CRCs were usually diagnosed at younger ages (p < 0.001) and had the strongest family history of Lynch syndrome-associated tumors (p = 0.002). dMMR type 3 CRCs frequently presented at advanced stages (p = 0.005) with perineural invasion (p = 0.021). We also found a significant positive association of dMMR type 1 and type 3 with advanced stages of CRC, whereas dMMR types 2 and 4 (MSH6- only) were usually diagnosed at early stages of CRC (p < 0.001). In conclusion, BRAF V600E mutations almost exclusively occurred in dMMR type 1 and 2 CRCs. Patterns of MMR protein expression display distinct associations with tumor staging and age at diagnosis.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Colorrectales/enzimología , Reparación de la Incompatibilidad de ADN , Enzimas Reparadoras del ADN/análisis , Inestabilidad de Microsatélites , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mutación , Estadificación de Neoplasias , Fenotipo , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos
17.
Front Oncol ; 9: 631, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31380273

RESUMEN

Third-generation tyrosine kinase inhibitors (TKIs) were developed to overcome T790M-mediated resistance to earlier generations of epidermal growth factor receptor (EGFR)-targeted TKIs. We compared four well-established and one in-house method for the analysis of the EGFR T790M mutation in plasma cell-free DNA (cfDNA), in hope to find a better way to select non-small cell lung cancer (NSCLC) patients appropriate for 3rd-generation TKI therapy. For sensitivity levels of each method, plasmid DNA with EGFR T790M mutations was serially diluted with cfDNA from healthy controls with wild type EGFR. The clinical performance was analyzed in a clinical cohort of EGFR mutation-positive NSCLC patients with acquired EGFR TKI resistance (n = 40). All methods except the therascreen kit (Qiagen) had a sensitivity level of 10 copies of T790M plasmid DNA in the spiked specimen. The detection rates of the EGFR T790M mutation in plasma cfDNA from the clinical cohort were 42.5, 35, 32.5, 22.5, and 17.5% for the in-house ARMS method, Bio-Rad droplet digital PCR, PANAMutyper, Therascreen EGFR Plasma RGQ PCR Kit and Cobas EGFR Mutation kit (with suboptimal template amounts), respectively. Osimertinib was given to 17 of 20 patients with EGFR T790M mutations. The best treatment responses, based on the RECIST criteria, included 6 partial responses (PR) and 7 stable diseases (SD). The PANAMutyper and the Bio-Rad droplet digital PCR were comparable, the Cobas EGFR Mutation kit required significantly more template for testing. The best combination would be the in-house ARMS method plus the PANAMutyper or Bio-Rad droplet digital PCR, which would have a detection rate of 50% (20/40) and a disease control rate of 76% (13/17).

18.
EBioMedicine ; 43: 270-281, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-30982765

RESUMEN

BACKGROUND: In our preliminary screening, expression of miR-338-5p was found to be higher in primary colorectal cancer (CRC) with metastasis. The autophagy related gene- phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3) appeared to be targeted by miR-338-5p. Here, we provide solid evidence in support of PIK3C3 involved in miR-338-5p related metastasis of CRC in vitro and in vivo. METHODS: The potential clinical relevance of miR-338-5p and its target gene was analysed on benign colorectal polyps and primary CRCs by QPCR. Mouse spleen xenograft experiment was performed to examine the importance of miR-338-5p for metastasis. FINDINGS: PIK3C3 was one of target genes of miR-338-5p. In primary CRCs, expression of miR-338-5p is positively related to tumour staging, distant metastasis and poor patient survival. Patients with higher ratios of miR-338-5p/PIK3C3 also had significantly poor overall survival, supporting their significance in the progression of CRC. Over-expression of miR-338-5p promotes CRC metastasis to the liver and lung in vivo, in which PIK3C3 was down-regulated in the metastatic tumours. In contrast, overexpression of PIK3C3 in miR-338-5p stable cells inhibited the growth of metastatic tumours. Both migration and invasion of CRC in vitro induced by miR-338-5p are mediated by suppression of PIK3C3. Using forward and reverse approaches, autophagy was proved to involve in CRC migration and invasion induced by miR-338-5p. INTERPRETATION: MiR-338-5p induces migration, invasion and metastasis of CRC in part through PIK3C3-related autophagy pathway. The miR-338-5p/PIK3C3 ratio may become a prognostic biomarker for CRC patients. FUND: NCKU Hospital, Taiwan, Ministry of Science and Technology, Taiwan.


Asunto(s)
Autofagia/genética , Fosfatidilinositol 3-Quinasa Clase I/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Interferencia de ARN , Regiones no Traducidas 3' , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Humanos , Ratones , Metástasis de la Neoplasia , Estadificación de Neoplasias , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
19.
Microsc Res Tech ; 82(6): 709-719, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30741460

RESUMEN

Tuberculosis (TB) remains the leading cause of morbidity and mortality from infectious disease in developing countries. The sputum smear microscopy remains the primary diagnostic laboratory test. However, microscopic examination is always time-consuming and tedious. Therefore, an effective computer-aided image identification system is needed to provide timely assistance in diagnosis. The current identification system usually suffers from complex color variations of the images, resulting in plentiful of false object detection. To overcome the dilemma, we propose a two-stage Mycobacterium tuberculosis identification system, consisting of candidate detection and classification using convolution neural networks (CNNs). The refined Faster region-based CNN was used to distinguish candidates of M. tuberculosis and the actual ones were classified by utilizing CNN-based classifier. We first compared three different CNNs, including ensemble CNN, single-member CNN, and deep CNN. The experimental results showed that both ensemble and deep CNNs were on par with similar identification performance when analyzing more than 19,000 images. A much better recall value was achieved by using our proposed system in comparison with conventional pixel-based support vector machine method for M. tuberculosis bacilli detection.


Asunto(s)
Procesamiento de Imagen Asistido por Computador/métodos , Microscopía/métodos , Mycobacterium tuberculosis/aislamiento & purificación , Redes Neurales de la Computación , Esputo/microbiología , Tuberculosis Pulmonar/diagnóstico , Humanos , Mycobacterium tuberculosis/citología
20.
World J Gastroenterol ; 24(10): 1152-1166, 2018 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-29563759

RESUMEN

AIM: To investigate the clinicopathological significance of progesterone receptor membrane component 1 (PGRMC1) and PGRMC2 in hepatocellular carcinoma (HCC). METHODS: We performed immunohistochemical staining to evaluate the estrogen receptor (ER), progesterone receptor (PR), PGRMC1, and PGRMC2 in a clinical cohort consisting of 89 paired HCC and non-tumor liver samples. We also analyzed HCC data (n = 373) from The Cancer Genome Atlas (TCGA). We correlated the expression status of PGRMC1 and PGRMC2 with clinicopathological indicators and the clinical outcomes of the HCC patients. We knocked down or overexpressed PGRMC1 in HCC cell lines to evaluate its biological significance in HCC cell proliferation, differentiation, migration, and invasion. RESULTS: We found that few HCC cases expressed ER (5.6%) and PR (4.5%). In contrast, most HCC cases expressed PGRMC1 (89.9%) and PGRMC2 (100%). PGRMC1 and PGRMC2 exhibited significantly lower expression in tumor tissue than in non-tumor tissue (P < 0.001). Lower PGRMC1 expression in HCC was significantly associated with higher serum alpha-fetoprotein expression (P = 0.004), poorer tumor differentiation (P = 0.045) and liver capsule penetration (P = 0.038). Low PGRMC1 expression was an independent predictor for worse disease-free survival (P = 0.002, HR = 2.384, CI: 1.377-4.128) in our cases, as well as in the TCGA cohort (P < 0.001, HR = 2.857, CI: 1.781-4.584). The expression of PGRMC2 did not relate to patient outcome. PGRMC1 knockdown promoted a poorly differentiated phenotype and proliferation of HCC cells in vitro, while PGRMC1 overexpression caused the opposite effects. CONCLUSION: PGRMC1 is a non-classical hormonal receptor that negatively regulates hepatocarcinogenesis. PGRMC1 down-regulation is associated with progression of HCC and is a poor prognostic indicator.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Proteínas de la Membrana/metabolismo , Receptores de Progesterona/metabolismo , Carcinogénesis/patología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Diferenciación Celular , Movimiento Celular , Proliferación Celular , Supervivencia sin Enfermedad , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células Hep G2 , Humanos , Hígado/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Pronóstico , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética
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