FOXK2 suppresses the malignant phenotype and induces apoptosis through inhibition of EGFR in clear-cell renal cell carcinoma

Abstract

Forkhead box K2 (FOXK2) belongs to the forkhead box transcription factor family. Recent studies have revealed that FOXK2 plays essential roles in cancer cell proliferation and survival. However, the biological function of FOXK2 in renal cell carcinoma remains unexplored. In this study, we demonstrated that FOXK2 mRNA and protein levels were decreased in clear-cell renal cell carcinoma (ccRCC) tissues compared with that in corresponding non-tumor renal tissues, and decreased FOXK2 levels were associated with poor prognosis in ccRCC patients after nephrectomy. FOXK2 suppressed proliferation, migration, and invasion capabilities of ccRCC cells and induced cellular apoptosis in vitro. Moreover, we found that FOXK2 overexpression inhibited xenograft tumor growth and promoted apoptosis in vivo. Genome-wide transcriptome profiling using FOXK2 overexpressed 769-P cells revealed that the epidermal growth factor receptor (EGFR) was a potential downstream gene of FOXK2. Overexpression of EGFR is able to rescue the inhibited proliferation capacity and the enhanced apoptosis capacity due to the overexpression of FOXK2 in 769-P cells. Collectively, our results indicate that FOXK2 inhibits the malignant phenotype of ccRCC and acts as a tumor suppressor possibly through the inhibition of EGFR. This article is protected by copyright. All rights reserved.

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Head and Neck Cancers Associated with Exposure to the September 11, 2001 World Trade Center Terrorist Attacks

Abstract

Exposure at the World Trade Center (WTC) terrorist collapse site on September 11, 2001 has been associated with increased cancer risk, though observational studies have identified very few cases of head and neck cancer (HNC) in exposed individuals. Eighty seven patients were identified who presented to our institution with HNC diagnosed from 2002-2017 who reported WTC exposure. The annual number and proportion of WTC-exposed HNC patients has been steadily increasing since 2002, with most cancers developing >10 years following the event. Furthermore, WTC-exposed patients with human papillomavirus (HPV)-positive OPC experienced significantly inferior outcomes compared to non-WTC exposed patients with HPV+ OPC (disease free survival 80.1% vs 65.6% at 4 years, p=0.04). This single institution study cannot establish evidence of exposure-mediated causation but higher recurrence rates in the WTC-exposed HPV+ OPC population suggest a treatment refractory tumor biology and possible exposure synergism with HPV-mediated oncogenesis. This article is protected by copyright. All rights reserved.

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NK/T Cell Lymphoma: Updates in Therapy

Abstract

Purpose of Review

Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly aggressive lymphoma which used to show a poor clinical outcome. Expression of P-glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness to conventional chemotherapy containing anthracycline. However, recent innovative approaches have improved the outcome and prognosis of ENKL. The purpose of this review is to summarize the proceedings of treatment.

Recent Findings

Concurrent chemoradiotherapy containing platinum and several drugs including L-asparaginase, methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL. SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) or other L-asparaginase-containing therapy is promising for advanced-stage ENKL, followed by either autologous or allogeneic hematopoietic stem cell transplantation. Anti-PD-1 or other immunological checkpoint inhibitors are recently reported to be effective for relapsed/refractory ENKL thought to be due to EBV-driven upregulation of PD-L1 expression.

Summary

The prognosis of ENKL is therefore improving by the introduction of these strategies. The 5-year overall survival (OS) rate of limited stage was 63.2% [95% confidence interval (CI), 55.3 to 70.0%] before 2010, but was 79.4% (95% CI, 66.9 to 87.6%) in 2010 or after. However, there still exists a room for improvement, particularly for advanced-stage patients. The 2-year OS of advanced ENKL was 30.3% (95% CI, 19.5 to 41.7%) before 2010, but was 40.5% (95% CI, 24.8 to 55.8%) in 2010 or after. Optimal treatment scheme should further be explored.

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Cancers, Vol. 10, Pages 31: Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Cancers, Vol. 10, Pages 31: Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Cancers doi: 10.3390/cancers10020031

Authors: Viviana Vergaro Monica Civallero Cinzia Citti Maria Cosenza Francesca Baldassarre Giuseppe Cannazza Samantha Pozzi Stefano Sacchi Francesco Fanizzi Giuseppe Ciccarella

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration.

http://ift.tt/2DGchGo

NK/T Cell Lymphoma: Updates in Therapy

Abstract

Purpose of Review

Extranodal NK/T cell lymphoma (ENKL), nasal type, is a highly aggressive lymphoma which used to show a poor clinical outcome. Expression of P-glycoprotein on lymphoma cells of ENKL is a major reason for the refractoriness to conventional chemotherapy containing anthracycline. However, recent innovative approaches have improved the outcome and prognosis of ENKL. The purpose of this review is to summarize the proceedings of treatment.

Recent Findings

Concurrent chemoradiotherapy containing platinum and several drugs including L-asparaginase, methotrexate, and alkylators shows excellent outcomes for the limited-stage ENKL. SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) or other L-asparaginase-containing therapy is promising for advanced-stage ENKL, followed by either autologous or allogeneic hematopoietic stem cell transplantation. Anti-PD-1 or other immunological checkpoint inhibitors are recently reported to be effective for relapsed/refractory ENKL thought to be due to EBV-driven upregulation of PD-L1 expression.

Summary

The prognosis of ENKL is therefore improving by the introduction of these strategies. The 5-year overall survival (OS) rate of limited stage was 63.2% [95% confidence interval (CI), 55.3 to 70.0%] before 2010, but was 79.4% (95% CI, 66.9 to 87.6%) in 2010 or after. However, there still exists a room for improvement, particularly for advanced-stage patients. The 2-year OS of advanced ENKL was 30.3% (95% CI, 19.5 to 41.7%) before 2010, but was 40.5% (95% CI, 24.8 to 55.8%) in 2010 or after. Optimal treatment scheme should further be explored.

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Cancers, Vol. 10, Pages 31: Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Cancers, Vol. 10, Pages 31: Cell-Penetrating CaCO3 Nanocrystals for Improved Transport of NVP-BEZ235 across Membrane Barrier in T-Cell Lymphoma

Cancers doi: 10.3390/cancers10020031

Authors: Viviana Vergaro Monica Civallero Cinzia Citti Maria Cosenza Francesca Baldassarre Giuseppe Cannazza Samantha Pozzi Stefano Sacchi Francesco Fanizzi Giuseppe Ciccarella

Owing to their nano-sized porous structure, CaCO3 nanocrystals (CaCO3NCs) hold the promise to be utilized as desired materials for encapsulating molecules which demonstrate wide promise in drug delivery. We evaluate the possibility to encapsulate and release NVP-BEZ235, a novel and potent dual PI3K/mTOR inhibitor that is currently in phase I/II clinical trials for advanced solid tumors, from the CaCO3NCs. Its chemical nature shows some intrinsic limitations which induce to administer high doses leading to toxicity; to overcome these problems, here we proposed a strategy to enhance its intracellular penetration and its biological activity. Pristine CaCO3 NCs biocompatibility, cell interactions and internalization in in vitro experiments on T-cell lymphoma line, were studied. Confocal microscopy was used to monitor NCs-cell interactions and cellular uptake. We have further investigated the interaction nature and release mechanism of drug loaded/released within/from the NCs using an alternative approach based on liquid chromatography coupled to mass spectrometry. Our approach provides a good loading efficiency, therefore this drug delivery system was validated for biological activity in T-cell lymphoma: the anti-proliferative test and western blot results are very interesting because the proposed nano-formulation has an efficiency higher than free drug at the same nominal concentration.

from Cancer via ola Kala on Inoreader http://ift.tt/2DGchGo
via IFTTT

JNA Journal Club

No abstract available

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