Targeted receptor tyrosine kinase inhibitor (TKI) is a standard treatment in advanced renal cell carcinoma (RCC). However, the role of PTEN in TKI resistance remains poorly understood. We aimed to ...determine the functional role of PTEN knockout and analyse the predictive significance of PTEN expression for TKI treatment in RCC.
We developed PTEN knockout cells in RCC cell lines using the CRISPR-Cas9 system and analysed the effect of PTEN knockout on spheroid formation and resistance to sunitinib and sorafenib.
PTEN knockout promoted spheroid formation and decreased sunitinib/sorafenib sensitivity in RCC cell lines. PTEN immunohistochemistry in 74 metastatic RCCs treated with sunitinib and sorafenib revealed negative PTEN expression in 23% of samples. Kaplan-Meier analysis showed a significant association of negative PTEN expression with poor progression-free survival in metastatic RCC treated with sunitinib and sorafenib (p=0.024) or sunitinib alone (p=0.009).
PTEN may be a biomarker and therapeutic target in patients with metastatic RCC.
Tryptophan metabolism has been shown to be involved in tumor development. Two main tryptophan-degrading enzymes, tryptophan 2,3-dioxygenase (TDO2) and indoleamine 2,3-dioxygenase 1 (IDO1), may ...potently promote cancer cell survival and distant metastasis in diverse types of cancer, such as lung and breast cancer. IDO1 overexpression is an independent prognosticator in gastric cancer (GC). This work aimed to uncover the expression of TDO2 and its clinicopathologic significance in GC.
TDO2 expression was evaluated in public data of The Cancer Genome Atlas cohort STAD and in two different GC cohorts. Correlation between TDO2 and immune cell infiltrates as well as PD-L1 tumor staining was investigated. The biofunction of TDO2 was examined with MTT, colony formation, and spheroid formation assays by RNA interference.
TDO2 expression was correlated with both progressive disease and clinical outcome, and its expression was an independent predictor of prognosis in GC. TDO2 expression was correlated with infiltration of immune cells and tumor expression of PD-L1. Inhibition of TDO2 expression suppressed cell proliferation, colony formation, and cell invasion of GC cells. Additionally, suppression of TDO2 expression inhibited spheroid body-formation and viability of GC organoids.
Our data show that TDO2 might be a crucial marker for predicting prognosis and targeted therapy in GC.
The prognostic value and the best method of testing of topoisomerase II alpha (TOP2A) status have not been established in modern tailored therapy based on breast cancer subtype.
The frequencies of ...TOP2A overexpression and
amplified were 55.8% and 9.5%, respectively. TOP2A overexpression correlated strongly with non-luminal A subtype (χ
-test,
0.001). TOP2A overexpression was significantly associated with relapse-free survival in luminal B breast cancer (
= 316; log rank test,
0.001) but not in other breast cancer subtypes. Cox regression analysis showed that TOP2A overexpression is a significant prognostic factor in luminal B breast cancer (hazard ratio (HR) 4.00, 95% confidence interval (CI) 1.65-9.54,
= 0.002).
amplified was recognized in HER2 positive breast cancer (
0.001). In HER2 positive breast cancer,
amplified (HR 0.30, 95% CI 0.085-1.07,
= 0.063) appeared to be a better prognostic factor.
In modern tailored therapy, TOP2A overexpression can be a poor prognostic factor in luminal B breast cancer. In contrast,
amplified could be a better prognostic factor in HER2 positive breast cancer.
Between May 2005 and April 2015, a total of 643 consecutive non-metastatic invasive breast cancers were evaluated for
amplified using fluorescence
hybridization analysis (FISH) and for TOP2A overexpression using the immunohistochemistry assay. FISH ratios of 2 or higher were designated as
amplified, and TOP2A staining >10% was defined as TOP2A overexpression. The prognostic values of
amplified and TOP2A overexpression were retrospectively evaluated.
Esophageal cancer is the sixth leading cause of cancer-related death worldwide. However, molecular targeted therapy and novel therapeutic targets are needed for esophageal squamous cell cancer ...(ESCC). In a previous study, we reported that protocadherin (PCDH) B9 plays an important role in several cancers. Therefore, in this study, we examined the clinical significance of PCDHB9 expression in ESCC.
PCDHB9 expression was examined using immunohistochemistry in 128 cases and using quantitative reverse transcription-polymerase chain reaction in 16 cases of ESCC. PCDHB9 function in ESCC cells was examined using RNA interference.
High PCDHB9 expression was identified in 5 of 16 (31.3%). In total, 51 (40%) ESCC cases showed strong PCDHB9 expression, whereas nonneoplastic mucosa rarely showed its expression. High PCDHB9 expression was significantly associated with T classification, N grade, and stage in ESCC. In ESCC cell lines, PCDHB9 knockdown affected cell growth, migration, and adhesion. Further, the expression of integrin (ITG) A3, ITGA4, ITGA5, ITGB1, ITGB6, vimentin, snail family transcriptional repressor 1, and cadherin 2 (NCAD) was significantly reduced and cadherin 1 was significantly increased in PCDHB9 knockdown ESCC cells.
These results suggest that PCDHB9 plays a tumor-promoting role and is a potential biomarker and therapeutic target in ESCC.
We report a case of gamma knife surgery (GKS)-induced chronic encapsulated expanding hematoma with extensive literature review. A 17-year-old young man underwent GKS after embolization for ...arteriovenous malformation (AVM) in the right frontal lobe and the AVM completely disappeared. He developed a generalized convulsion 15 years after GKS. MRI showed a small oedematous change at the AVM site. His epileptic seizure was controlled with anticonvulsant. His epilepsy recurred after three years, and MRI revealed an intracerebral hematoma with extensive surrounding edema at the same lesion. He underwent cerebral angiography and a recurrence of AVM was prevented. The hematoma was surgically removed, and intraoperative finding confirmed an old hematoma with a capsule and capillary hyperplasia, without developing cavernous angioma. The final diagnosis was a secondary chronic encapsulated expanding hematoma after GKS. This is the first report to show the early-stage imaging findings of this late effect after GKS.
Informamos de un caso de hematoma encapsulado crónico expansivo inducido por una intervención quirúrgica con bisturí de rayos gamma (GKS) con una amplia revisión bibliográfica. Un joven de 17 años se sometió a una GKS después de una embolización por malformación arteriovenosa (MAV) en el lóbulo frontal derecho, y la MAV desapareció por completo. Desarrolló una convulsión generalizada 15 años después de la GKS. La resonancia magnética (RM) mostró un pequeño cambio edematoso en la ubicación de la MAV. Su ataque epiléptico se controló con un anticonvulsivo. Su epilepsia se repitió 3 años después, y la RM reveló un hematoma intracerebral con un edema circundante extenso en la misma lesión. Se sometió a una angiografía cerebral y se evitó la recidiva de la MAV. El hematoma se extirpó quirúrgicamente, y el hallazgo intraoperatorio confirmó un antiguo hematoma con una hiperplasia capsular y capilar, sin desarrollo de angioma cavernoso. El diagnóstico final fue un hematoma encapsulado crónico expansivo secundario después de la GKS. Este es el primer informe que muestra los hallazgos del diagnóstico por imagen en la fase temprana de este efecto tardío después de la GKS.
Mucinous urothelial carcinoma (UC) is a rare variant and only 18 cases of mucinous UC have been reported. In this article, we report a case of mucinous UC focusing on both cytological and ...histological findings. A 92‐year‐old female was referred to our hospital because of gross hematuria. Clinical computed tomography scan showed 2.2‐cm papillary lesion in the lower part of the left ureter. Urine cytology was performed, and cytopathological findings showed that there were a few atypical cells with pale to clear cytoplasm, and a low amount of mucin in the background was identified by periodic acid‐schiff (PAS) and alcian blue (AB) staining. Laparoscopic radical nephrectomy of left renal pelvis and ureter was performed. The gross examination revealed that a white‐gray, papillary‐sessile tumor was found in the lower part of the left ureter. Histologically, conventional high grade UC cells were seen in some areas, and tumor cells in other areas showed abundant clear cytoplasm with extracellular and intracytoplasmic mucin. Immunohistochemical analysis revealed that tumor cells were positive for CK7, CK20, p63, GATA3, MUC1, MUC2, and MUC5AC and negative for MUC6 and CDX2. Histopathological diagnosis was mucinous UC with clear cell component, and the pathological stage was pT1N0M0. The patient has remained well and disease‐free for 3 months after the operation. Familiarity and recognizing the characteristic pathological findings of mucinous UC are important because it represents a malignant neoplasm.
We report a case of gamma knife surgery (GKS)-induced chronic encapsulated expanding hematoma with extensive literature review. A 17-year-old young man underwent GKS after embolization for ...arteriovenous malformation (AVM) in the right frontal lobe and the AVM completely disappeared. He developed a generalized convulsion 15 years after GKS. MRI showed a small oedematous change at the AVM site. His epileptic seizure was controlled with anticonvulsant. His epilepsy recurred after three years, and MRI revealed an intracerebral hematoma with extensive surrounding edema at the same lesion. He underwent cerebral angiography and a recurrence of AVM was prevented. The hematoma was surgically removed, and intraoperative finding confirmed an old hematoma with a capsule and capillary hyperplasia, without developing cavernous angioma. The final diagnosis was a secondary chronic encapsulated expanding hematoma after GKS. This is the first report to show the early-stage imaging findings of this late effect after GKS.
Gastric cancer (GC) is one of the most common malignancies worldwide. Gremlin1 is an antagonist of bone morphogenetic proteins that plays a critical role in several biological processes including ...cancer biology.
We immunohistochemically examined the expression and distribution of Gremlin1 in non-neoplastic gastric mucosa in a series of 159 GC cases.
Among 159 GC primary tumors, 59 (37%) were positive for Gremlin1. Gremlin1-negative GC cases showed significantly more advanced clinicopathologic factors and a trend toward intestinal-type GC. Gremlin1 expression was also frequently observed in MUC5AC-positive and G-type GC cases. Gremlin1-negative GCs had a poorer survival rate than Gremlin1-positive GCs (p=0.002). Univariate and multivariate analyses revealed that Gremlin1 expression is an independent predictor of survival in GCs.
These results indicate that Gremlin1 could be involved in GC progression and may be a good marker of long-term survival in GC.
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