- The supraorbital approach to the basal frontal lobe for resection of brain metastasis. [Journal Article]
- WNWorld Neurosurg 2019 Jun 14
- This video illustrates the use of the supraorbital craniotomy via an eyebrow incision for access to the basal frontal lobe. This approach is particularly useful for removal of lesions in the dominant…
This video illustrates the use of the supraorbital craniotomy via an eyebrow incision for access to the basal frontal lobe. This approach is particularly useful for removal of lesions in the dominant hemisphere where a transcortical approach could place speech centers at risk. The case is that of a 57-year-old woman who presented after a mental status change who was noted to have a large left frontal mass. The patient had a history of melanoma, and pathological analysis of the intracranial lesion was consistent with metastatic melanoma. The patient underwent an uneventful gross-total lesion resection. The step-by-step techniques for performing this operation are illustrated. Although not used in this case because we had an excellent view of the lesion, removal of the orbital rim allows the surgeon to obtain a better inferior-to-superior trajectory without using retraction. Of utmost importance to satisfactory cosmetic outcome are meticulous layer-by-layer closure of the eyebrow incision and maintaining pressure on the wound at the time of extubation. This pressure prevents accumulation of hematoma or cerebrospinal fluid, which places the wound under tension, impedes healing, and detrimentally affects cosmetic outcome. Additional adjuncts in this procedure may include hyperextending the head to bring the tumor into more direct view and drilling the skull base flush to expand the operative corridor. Minimally invasive approaches are excellent for the removal of metastasis because they are smaller incisions that remain well vascularized and heal quickly, allowing the patient to initiate adjuvant therapy sooner. The patient's family provided consent for publication.
- Post-translational inhibition of YAP oncogene expression by 4-hydroxynonenal in bladder cancer cells. [Journal Article]
- FRFree Radic Biol Med 2019 Jun 14
- The transcriptional regulator YAP plays an important role in cancer progression and is negatively controlled by the Hippo pathway. YAP is frequently overexpressed in human cancers, including bladder …
The transcriptional regulator YAP plays an important role in cancer progression and is negatively controlled by the Hippo pathway. YAP is frequently overexpressed in human cancers, including bladder cancer. Interestingly, YAP expression and activity can be inhibited by pro-oxidant conditions; moreover, YAP itself can also affect the cellular redox status through multiple mechanisms. 4-Hydroxynonenal (HNE), the most intensively studied end product of lipid peroxidation, is a pro-oxidant agent able to deplete GSH and has an anti-tumoral effect by affecting multiple signal pathways, including the down-regulation of oncogene expressions. These observations prompted us to investigate the effect of HNE on YAP expression and activity. We demonstrated that HNE inhibited YAP expression and its target genes in bladder cancer cells through a redox-dependent mechanism. Moreover, the YAP down-regulation was accompanied by an inhibition of proliferation, migration, invasion, and angiogenesis, as well as by an accumulation of cells in the G2/M phase of cell cycle and by an induction of apoptosis. We also established the YAP role in inhibiting cell viability and inducing apoptosis in HNE-treated cells by using an expression vector for YAP. Furthermore, we identified a post-translational mechanism for the HNE-induced YAP expression inhibition, involving an increase of YAP phosphorylation and ubiquitination, leading to proteasomal degradation. Our data established that HNE can post-translationally down-regulate YAP through a redox-dependent mechanism and that this modulation can contribute to determining the specific anti-cancer effects of HNE.
- CX-F9, a Novel RSK2 Inhibitor, suppresses Cutaneous Melanoma Cells Proliferation and Metastasis through regulating Autophagy. [Journal Article]
- BPBiochem Pharmacol 2019 Jun 14
- Approximately 60% of melanoma have BRAF mutation which leads to the abnormal activation of MAPK signaling pathway. Therefore, targeting these signaling pathways is particularly important for melanoma…
Approximately 60% of melanoma have BRAF mutation which leads to the abnormal activation of MAPK signaling pathway. Therefore, targeting these signaling pathways is particularly important for melanoma therapy. Ribosomal S6 Kinase 2 (RSK2) is a downstream target of ERK1/2 in MAPK/ERK pathway and inhibition of RSK2 suppresses the tumorigenesis and metastasis of neoplasm. We investigated whether CX-F9, a novel RSK2 inhibitor predicted by computer, inhibits the malignant phenotype of melanoma cells. In this study, we found knockdown of RSK2 expression in melanoma cells induces autophagy and inhibits its proliferation, migration and invasion. CX-F9 directly binds to RSK2 and inhibits the kinase activity. CX-F9 significantly suppressed cell proliferation, induced autophagy, apoptosis and cycle arrest, as well as inhibited migration and invasion in SK-MEL-5 and SK-MEL-28 cells. Western blotting revealed that CX-F9 declined the activation of p-CREB. Moreover, CX-F9 inhibited tumor formation and metastasis in vivo. Furthermore, CX-F9 suppressed cell proliferation, migration, invasion in BRAF inhibitor resistant melanoma cells. These findings reveal a new RSK2 inhibitor CX-F9 could significantly suppressed malignant phenotype of melanoma in vitro and in vivo, which provide a novel strategy for melanoma treatment in clinic.
- Enhancing lentiviral transduction to generate melanoma-specific human T cells for cancer immunotherapy. [Journal Article]
- JIJ Immunol Methods 2019 Jun 14
- Introduction of a tumor antigen-specific T cell receptor (TCR) into patient-derived lymphocytes has already exhibited promising results for the treatment of melanoma and other malignancies in clinica…
Introduction of a tumor antigen-specific T cell receptor (TCR) into patient-derived lymphocytes has already exhibited promising results for the treatment of melanoma and other malignancies in clinical trials. However, insufficient or unsuccessful ex vivo manufacturing of engineered T cells due to low expansion and/or transduction rate can still be observed in some patients. Thus, we isolated human CD8+ T cells from healthy donors and equipped them with a gp100-specific TCR using a lentiviral construct in combination with a novel chemical lentiviral transduction enhancer (Lentiboost) to increase the rate of transduced cells. Following experiments to determine the ideal multiplicity of infection (MOI) and to analyze the efficacy of the transduction enhancer using a GFP-encoding lentivirus, we analyzed in the next step the transduction rate, cell count, and functionality of gp100 TCR-transduced T cells, i.e. antigen-specific cytokine secretion and lytic capacity. In order to increase the number of transduced cells, antigen-specific stimulation was performed, either once for 1 week (1st activation) or twice for another week (2nd activation). In general, each cycle of antigen-specific stimulation resulted in expansion of TCR-positive cells, while no further significant increase of transduced cells was observed after 2nd activation. Cytokine production pattern of transduced cells after antigen encounter, however, revealed significant antigen-specific secretion of TNF and IFNγ after the 1st as well as the 2nd activation. Furthermore, TCR T cells, either activated once or twice, showed significant cytotoxicity towards antigen-positive tumor cells. Taken together, these results show that it is feasible to transduce human T cells using a lentiviral construct in combination with this novel lentiviral transduction enhancer, which shows potential in the growing field of cancer immunotherapy.
- Prognosis and cure of long-term cancer survivors: A population-based estimation. [Journal Article]
- CMCancer Med 2019 Jun 17
- CONCLUSIONS: The study findings confirmed that several cancer types are curable. Became aware of the possibility of cancer cure has relevant clinical and social impacts.
- microRNA-374 inhibits proliferation and promotes apoptosis of mouse melanoma cells by inactivating the Wnt signalling pathway through its effect on tyrosinase. [Journal Article]
- JCJ Cell Mol Med 2019 Jun 17
- Melanoma is one of the most malignant skin tumours with constantly increasing incidence worldwide. Previous studies have demonstrated that microRNA-374 (miR-374) is a novel biomarker for cancer thera…
Melanoma is one of the most malignant skin tumours with constantly increasing incidence worldwide. Previous studies have demonstrated that microRNA-374 (miR-374) is a novel biomarker for cancer therapy. Therefore, this study explores whether miR-374 targeting tyrosinase (TYR) affects melanoma and its underlying mechanism. We constructed subcutaneous melanoma models to carry out the following experiments. The cells were transfected with a series of miR-374 mimics, miR-374 inhibitors or siRNA against TYR. Dual luciferase reporter gene assay was used for the verification of the targeting relationship between miR-374 and TYR. Reverse transcription quantitative polymerase chain reaction and western blot analysis were conducted to determine the expression of miR-374, TYR, β-catenin, B-cell leukaemia 2 (Bcl-2), Bcl-2 associated X protein (Bax), Low-density lipoprotein receptor-related protein 6 (LRP6), Leucine-rich repeat G protein-coupled receptor 5 (LGR5) and CyclinD1. Cell proliferation, migration, invasion, cell cycle distribution and apoptosis were evaluated using cell counting kit-8 assay, scratch test, transwell assay and flow cytometry respectively. TYR was proved as a putative target of miR-374 as the evidenced by the result. It was observed that up-regulated miR-374 or down-regulated TYR increased expression of Bax and decreased expressions of TYR, β-catenin, LRP6, Bcl-2, CyclinD1 and LGR5, along with diminished cell proliferation, migration, invasion and enhanced apoptosis. Meanwhile, cells with miR-374 inhibitors showed an opposite trend. These findings indicated that up-regulated miR-374 could inhibit the expression of TYR to suppress cell proliferation, migration, invasion and promote cell apoptosis in melanoma cells by inhibiting the Wnt signalling pathway.
- MITF controls the TCA cycle to modulate the melanoma hypoxia response. [Journal Article]
- PCPigment Cell Melanoma Res 2019 Jun 17
- In response to the dynamic intra-tumor microenvironment, melanoma cells adopt distinct phenotypic states associated with differential expression of the microphthalmia-associated transcription factor …
In response to the dynamic intra-tumor microenvironment, melanoma cells adopt distinct phenotypic states associated with differential expression of the microphthalmia-associated transcription factor (MITF). The response to hypoxia is driven by hypoxia-inducible transcription factors (HIFs) that reprogram metabolism and promote pro-angiogenisis. HIF1α indirectly represses MITF that can activate HIF1α expression. Although HIF and MITF share a highly related DNA-binding specificity, it is unclear whether they co-regulate subset of target genes. Moreover, the genome-wide impact of hypoxia on melanoma and whether melanoma cell lines representing different phenotypic states exhibit distinct hypoxic responses is unknown. Here we show, that three different melanoma cell lines exhibit widely different hypoxia responses with only a core 23 genes regulated in common after 12 h in hypoxia. Surprisingly, under hypoxia MITF is transiently up-regulated by HIF1α and co-regulates a subset of HIF targets including VEGFA. Significantly, we also show that MITF represses itself and also regulates SDHB to control the TCA cycle and suppress pseudo-hypoxia. Our results reveal a previously unsuspected role for MITF in metabolism and the network of factors underpinning the hypoxic response in melanoma. This article is protected by copyright. All rights reserved.
- Certain and uncertain malignant potential in melanocytic skin neoplasms. [Journal Article]
- JCJ Cutan Pathol 2019 Jun 17
- In a recent article, Lee et al. investigated the reactivity for 5-hydroxymethylcytosine (5-hmC) in 54 heavily pigmented melanocytic tumors . This article is protected by copyright. All rights rese…
In a recent article, Lee et al. investigated the reactivity for 5-hydroxymethylcytosine (5-hmC) in 54 heavily pigmented melanocytic tumors . This article is protected by copyright. All rights reserved.
- Powering a prospective melanoma chemoprevention trial in high-risk cohorts. [Letter]
- IJInt J Dermatol 2019 Jun 17
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- Combination Nivolumab/Ipilimumab Immunotherapy For Melanoma With Subsequent Unexpected Cardiac Arrest: A Case Report and Review of Literature. [Journal Article]
- JIJ Immunother 2019 Jun 14
- The success of immunotherapy in the treatment of patients with advanced melanoma has paved the way for unprecedented successes in the treatment of many other malignancies. We present a case of extens…
The success of immunotherapy in the treatment of patients with advanced melanoma has paved the way for unprecedented successes in the treatment of many other malignancies. We present a case of extensively metastatic oral mucosal melanoma that responded successfully to combined immune checkpoint blockade with ipilimumab and nivolumab but developed multiple immune-related adverse events, including myocarditis, a rare event associated with immunotherapy of elderly melanoma patients. Though the acute myocarditis was managed successfully, the patient succumbed to sudden cardiac death. This case highlights the fact, that autoimmune carditis must be considered when working up the sudden onset of shortness of breath in patients on immune checkpoint blockade. After controlling the acute myocarditis with high-dose steroids, which should be tapered over 6 weeks, further cardiology care is needed, and a defibrillator might have to be implanted. Understanding the pathophysiology of immune-related adverse events could make cancer immunotherapy both more effective and safer.